2001/2002 - Swiss TPH

Transcription

15.11.2002
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Swiss Tropical
Institute Basel
Biennial R e p o r t
Swiss Tropical Institute
Institut Tropical Suisse
Schweizerisches Tropeninstitut
UG 1+4
Socinstrasse 57 Postfach
CH-4002 Basel Switzerland
UG 2+3
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11:10 Uhr
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LIST OF ABBREVIATIONS: Projects and Organisations
COST
European Cooperation in the field of Scientific and
Technical Research
CSRS
Centre Suisse de Recherches Scientifiques,
Abidjan, Côte d’Ivoire
CSSI/ITS
Centre de Support en Santé International,
N’Djaména, Chad
DFID
Department for International Development, UK
DUHP
Dar es Salaam Urban Health Project,
Dar es Salaam, Tanzania
ETH
Swiss Federal Institute of Technology
GTZ
Deutsche Gesellschaft für technische Zusammenarbeit, Germany
IHRDC
Ifakara Health Research and Development Centre,
Tanzania
IDRC
International Development Research Centre,
Ottawa, Canada
LSHTM
London School of Hygiene and Tropical
Medicine, UK
MIH
Master of International Health (MSc degree)
MMV
Medicines for Malaria Venture
NCCR
National Centre of Competence in Research
NIH
National Institute of Health, USA
NGO
Non Governmental Organisation
PNGIMR
Papua New Guinea Institute of Medical Research,
Goroka
RGS
R. Geigy Foundation
SANW
Swiss Academy of Sciences
SCIH
Swiss Centre for International Health
SDC
Swiss Agency for Development and Cooperation
SNSF
Swiss National Science Foundation
UNDP
United Nations Development Programme
USAID
United States Agency for International
Development
WEHI
Walter and Eliza Hall Institute of Medical Research,
Melbourne, Australia
WHO/TDR UNDP/ World Bank/ WHO Special Programme for
Research and Training in Tropical Diseases
01_Inhalt
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Swiss Tropical
Institute Basel
Biennial Report
2001– 2002
Outline of contents
Overview of the STI
Foreword
Financial Statement
Research in the STI
1. Molecular Parasitology and Molecular Epidemiology
2. Molecular Diagnostics
3. Molecular Immunology
4. Parasite Chemotherapy
5. Biostatistics and Basic Epidemiology
6. Clinical and Intervention Epidemiology
7. Environment, Society and Health Systems
8. Cultural Epidemiology
Teaching and Training
Lists of students
Medical and Diagnostic Services (MEDDIA)
The Swiss Centre for International Health (SCIH)
STI Services and STI Foundations
Rudolf Geigy and the founding of the STI
Further Activities and Networks
Lists of Staff and Research Groups
02-03_Table of Contents
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Table of Contents
Table of abbreviations
Inside front cover
Overview of the STI
4
Foreword
5
Editorial Note
9
Financial Statement
10
SECTION 4 Parasite Chemotherapy
4.1
Drug discovery and evaluation of new antiprotozoal
compounds (ParaScreen Screening Centre)
25
26
Orally-available diamidines · Pharmacokinetics of diamidines ·
Testing of new compounds against other parasites · dUTPase ·
Medicinal plants
4.2
4.3
4.4
Medicines for Malaria Venture (MMV)
Use of OZ compounds against schistosomiasis
Trypanosomosis in eastern Africa and the activities
of the EANETT network
27
28
28
Research activities
SECTION 1 Molecular Parasitology and Molecular
Epidemiology
12
1.1
var-gene expression in naturally infected samples,
var-gene regulation, and DNA binding proteins
13
1.2
Stage-specifically regulated genes in P. falciparum
13
1.3
Immunological and functional importance of the
structural domains of the Plasmodium falciparum
merozoite surface protein 2
14
Effect of vaccination with the malaria vaccine
Combination B on the parasite population
15
1.4
1.5
A molecular biological study of infection dynamics in
Navrongo, Ghana
1.6
Development of a parallel micro array-based technique for the analysis of point mutations in genes of
P. falciparum associated with drug resistance
1.7
4.5
5.1
5.2
5.3
5.4
15
2.2
2.3
5.5
Development of a “Tool box” for molecular monitoring
in malaria intervention trials
16
5.6
5.8
17
Cloning and expression of recombinant antigens for
serological diagnosis
17
SECTION 3 Molecular Immunology
3.1
17
Development and evaluation of a PCR genotyping
system for Leishmania species
Identification of L. infantum antigens as potential
vaccine candidates and for use in early diagnosis
Development of subunit vaccines against malaria
Search for new malaria vaccine candidate antigens
3.4
3.5
2
Analysis of immune responses of the Aotus monkey,
an experimental infection model for Plasmodium
falciparum malaria
17
19
34
Epidemiological studies of concomitant immunity
in malaria
Epidemiology of the spatial distribution of human
parasitoses
Clinical epidemiology of meningococcal meningitis
in Northern Ghana
Other statistical support
34
34
35
35
Interventions against malaria; vaccine development
and clinical trials
38
Combination B and vaccines against asexual blood stages ·
Pre-erythrocytic and asexual blood-stage Malaria Vaccine
Programme; LSP vaccine candidates
6.2
Interventions against malaria; chemotherapy
38
Intermittent treatment of malaria · COTRIFAZID against resistant
malaria in semi-immune subjects: study of efficacy and tolerance
19
6.3
Interventions against malaria; insecticide-treated nets
(ITNs)
39
The KINET project: operational aspects · KINET: health impact of ITNs ·
Beyond KINET: implications for malaria control · Nets with a longlasting insecticide treatment (NELLIT)
20
6.4
Treatment of African trypanosomiasis
41
Treatment of African trypanosomiasis with melarsoprol: IMPAMEL
Program · Development of new trypanocidal drugs
6.5
23
Schistosomiasis; new developments in chemotherapy
and control
42
Field trial of artemether in the control of S. haematobium infection ·
In-depth study of artemisinin derivatives · Optimising chemotherapeutic interventions against S. haematobium
22
Conjugate vaccines against epidemic meningococcal
meningitis in Africa
22
Mycobacterium ulcerans infections: prospects for
vaccine development and serodiagnosis
34
SECTION 6 Clinical and Intervention Epidemiology 37
6.1
Cell biology of the malaria parasite · Identification and characterisation of a conserved, stage specific gene product of P. falciparum
that induces antibodies that inhibit parasite growth · The involvement
of glyceraldehyde-3-phosphate dehydrogenase(GAPDH) in the
secretory pathway of P. falciparum
3.3
32
33
Clinical Trials · Other statistical support
New strategies for the design of epitope-focussed vaccines ·
Development of improved adjuvants and antigen delivery systems ·
Identification of synthetic mimotopes of P. falciparum protein antigen
surface loops
3.2
Measuring malaria transmission intensity and its
effects on morbidity and mortality
Statistical methodology for the analysis of spatial data
Statistical methods for estimating prevalences from
data with diagnostic error or uncertainty
Dynamics of malaria infection in areas of high transmission
Incidence and duration of infection in malaria · Sequestered malaria
parasites
5.7
2.1
30
SECTION 5 Biostatistics and Basic Epidemiology 32
15
SECTION 2 Molecular Diagnostics
Tsetse fly transmission studies
Surface proteins at different stages in the life-cycle · Immune
responses in insect vectors · Transmissibility of drug-resistant
trypanosomes
6.6
Schistosomiasis epidemiology
44
Questionnaires for rapid schistosomiasis screening · Co-infection
with S. haematobium and HIV-1 in rural Zambia · Morbidity due to
S. mekongi in Northeastern Cambodia · Standardisation of ultrasound findings on schistosomiasis morbidity
Swiss Tropical Institute Report 2001– 2002
02-03_Table of Contents
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Table of Contents
6.7
Parasite associations and multiparasitism in
Côte d’Ivoire
45
Effect of praziquantel against hookworm
6.8
Interventions against water-related pathogens
SECTION 9 Teaching and Training
70
9.1
70
Teaching at the University of Basel
The post-graduate programme, “Urban Health in Developing
Countries” · Centre for African Studies, Basel · Master in International
Health – a joint European programme · tropEd partner institutions
45
Amoebiasis · Pure water from sunlight: The SODIS health impact
study · Water-borne pathogens in Switzerland
Students awarded degrees from Sept. 2000 – Aug. 2002 72
Students currently working on research projects
73
SECTION 7 Environment, Society and Health
Systems
49
7A. Urban Health and Health Systems
50
9.2
7A.1 Health impact and management of wastewater use
in small-scale agriculture in urban Sahelian settings:
risks and potential intervention strategies
50
7A.2 Inhabitants of a deprived urban area manage their
own environment
51
7A.3 Health and well-being in urban West Africa
51
Abidjan; social networks and illness
7A.4 Health and Health Services in Dar es Salaam, Tanzania 51
Private – public interactions and quality of care · Care for diabetic
patients · Hypertension – a public health problem
STI Diploma Courses
74
Health Care and Management in Tropical Countries (HCMTC) · Short
courses · General Tropical Course · Health Systems Management
9.3
E-Learning
75
9.4
Teaching in universities other than Basel
75
9.5
Other teaching and training activities
76
SECTION 10 Medical and diagnostic services
(MEDDIA)
77
10.1 Medical Services
77
Travel clinic · Outpatient department
7A.5 Health and elderly people in urban Indonesia
53
7B. Human and Animal Health; Health of Nomadic
Populations
54
7B.1 The interface of human and animal health among
nomadic pastoralists in Chad: zoonoses and health
services
54
7B.2 Zoonotic disease: risks and control measures
55
10.2 Diagnostic Services
78
Reference Centre for Tropical and Travel Medicine and
Parasitological Diagnosis · Molecular Diagnostics Unit · Institut
Tropical Rhénan (ITR) in France
10.3 Vector Control Centre
78
10.4 Operational research on travel medicine
79
Imported malaria in travellers from Kenya · Hepatitis A vaccination in
travellers
Tuberculosis in Chad · Healthy milk for the Sahel: milk hygiene in Mali ·
Dog rabies in an urban area: Incidence and scope for control, Chad
7B.3 Health of livestock
57
Calf mortality and parasites of livestock in traditional livestock
production in Côte d’Ivoire
7C. Efficient Provision of Health Services
57
7C.1 Health Services in Chad
57
Constraints on scaling-up health related interventions · Prevention
of HIV/AIDS
11.1 Health Systems Support Unit
81
Tanzania: Needs assessment and policy for clinical training ·
Managed care pharmacy in Switzerland · Health Technology
83
Clinical Trial of a new trypanocidal agent (DB 289)
58
7C.3 Drug donations to Tanzania
58
7C.4 Costs and benefits of water and sanitation interventions 58
7C.5 ECOZOO: a model to assess the economic
advantages of control of zoonotic disease
59
7C.6 Resource allocation in the Swiss health care system
59
7C.7 Female Genital Mutilation in the context of migration:
care of migrant women in the Swiss health care system 60
8.1
80
11.2 Pharmaceutical Medicine Unit (PMU)
7C.2 Burkina Faso; strengthening maternity services
SECTION 8 Cultural Epidemiology
SECTION 11 The Swiss Centre for International
Health (SCIH)
Outlook of the SCIH
84
Table: Short-term assignments of the SCIH 2000 – 2002
Table: Long-term projects of the SCIH 1996 – 2002
85
86
SECTION 12 STI Services
88
DICEL (Documentation, Information, Communication and
E-learning) · Biostatistics Unit · Central Laboratory · Life
Sciences Training Facility · Technical Services
88
The STI Foundations
89
89
92
62
Cultural research for rural mental health in
the Sundarban region of West Bengal, India
64
8.2
Cultural research for urban mental health in Mumbai
65
8.3
Cultural study of fatigue and weakness in Pune, India 66
8.4
Cultural study of schizophrenia and psychosis in
South India
67
8.5
Gender and tuberculosis
67
Staff and doctoral students of the STI
94
8.6
Tuberculosis treatment trial in Metro Manila,
Philippines
68
Africa Day in the STI
96
3
04_Overview
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The Swiss Tropical Institute (STI) Overview
The Swiss Tropical Institute (STI)
The Swiss Tropical Institute was founded in 1943 as a public organisation. It is supported by the Swiss Federal Government and the
Canton of Basel-Stadt (total 22%). The greater part of the funding is from competitively-acquired project funds and the earnings of the
Service Departments.
The mandate of the STI is:
To contribute to the improvement of the health of populations internationally and nationally
through excellence in research, services, and teaching and training.
BOARD of G OVERNORS
(Kuratoriu m)
10 m em b ers
D irecto rate
Director: M.Tan ner
Deputy Director: N.A. Weiss
4 H ead s o f D ep artm en ts
A d m in istratio n an d co n tro llin g
D o cu m en tatio n , In fo rm atio n , e-learn in g (D IC E L )
N.A. W eiss
IT and Network: S. Roelly
Docu mentation and Information: H. Imml er
U. Wasse r
T each in g an d T rain in g
A. Hoffman n
M ed ical P arasito lo g y
& In fectio n B io lo g y
N.A. Weiss
Pu b lic H ealth
& E p id em io lo g y
M.G . Weiss
S w iss C en tre fo r
In tern atio n al H ealth
N. Loren z
M ed ical an d D iag n o stic
S ervices an d R esearch
C. Hatz
M o l. E p id em io lo g y &
M o l. P arasito lo g y
H.-P. Bec k
B io statistics an d
B asic E p id em io lo g y
T. Smit h
P h arm aceu tical M ed ical U n it
(P M U )
C. Bu rri
M ed ical S ervices
T ravel C lin ic
C.Hat z
M o lecu lar
D iag n o stics
I. Felg er
C lin ical an d In terven tio n
Ep id em io lo g y
B. Genton , C. Lengel er
H ealth System s
S u p p o rt U n it (H S S U )
N. Loren z
D iag n o stic Services
M o lecu lar
Im m u n o lo g y
G. Pl uschk e
En viro n m en t, S o ciety,
H ealth S ystem s
M.Tann er, K.Wyss, J. Zin sstag
C en tre d e S u p p o rt en
S an té In tern atio n al (C h ad )
D.M. Daug la
P arasite
C h em o th erap y
R. Brun
C u ltu ral E p id em io lo g y
H.-P. Mart i
Vector Control Centre
W. Rudin
M.G . W eiss
Directorate
Administration (Financial Statement, p. 10); Teaching and Training (Section 9, p. 70)
Documentation, Information, e-learning (DICEL) (Section 12, p. 88)
Service Departments
Medicine and Diagnostics (Section 10, p. 77)
Support Centre for International Health (Sec. 11, p. 80)
The Department is a centre of competence in travel and tropical
medicine. It provides parasitological and diagnostic services.
The Travel Clinic offers advice for travellers to tropical and subtropical countries, vaccination services and a 24-hour emergency service.
Provides assistance in the implementation of health projects,
acts as executing and support agency for health development
and offers short- and long-term consultancies and expertise in
all aspects of health services management, planning, risk analysis and evaluation.
Research Departments: Sections 1– 8
Medical Parasitology and the Biology of Infection
Public Health and Epidemiology
Studies host-parasite relationships and determinants of infection and morbidity at the molecular, cellular, clinical and population levels.
Explores new approaches in epidemiology; assesses interventions for disease control; studies determinants of health seeking
and the organisation and planning of health systems in Africa,
Asia & Europe.
Full lists of the staff of all Departments and Research Groups will be found on pages 94 – 95
4
Swiss Tropical Institute Report 2001–2002
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Foreword
FOREWORD
Two years have again passed,
and it is once more my great
pleasure to introduce our new
Biennial Report to all of you:
staff members, collaborators,
colleagues, friends of the STI,
and the wider interested public
in Switzerland and abroad. We
are very happy and proud to
present our activities in the first
years of the new millennium. All
of them could only be undertaken thanks to your support
and collaboration.
The goal of our Institute has
Prof. Marcel Tanner, STI Director
(Source: R. Dürr)
not changed. We remain committed to contributing to development in the field of health at local, national and international
levels. In the space of this report we can only present a summary of our key activities and achievements in the period
2001– 2002, but we hope it will demonstrate how we are pursuing our aims, and stimulate your interest and support. Our project leaders and staff members are always happy to provide
further information, and you can also refer to our web site
(www.sti.ch) and our publications. We hope that reading the
Report will stimulate further contacts and a very fruitful dialogue
with all of you.
Main Developments and Highlights
The main body of the report describes the activities of the Institute in research, teaching and the provision of services in more
detail. In this foreword I want to highlight some of the things that
enable the STI to thrive and develop.
Our last report, for the years 1999 – 2000, was an important
benchmark. It showed how the STI had developed from a Tropi-
cal Institute into an Institute of International Health, stepping out
into the new millennium supported by an effective network of
national and international collaboration. This Report is appearing at the moment when we celebrate the centenary of the birth
of the founder and first director of our Institute, the late Professor
Rudolf Geigy. The STI has grown and developed since its foundation in 1943, but we are still guided by Rudolf Geigy’s vision in
the field of medical parasitology, his profound understanding of
combining field and laboratory research, and his pioneering
work towards research partnership between North and South. A
scientific symposium and a short celebration will mark the centenary on December 5 – 6, 2002. A short brochure has been written summarising Rudolf Geigy’s life and achievements, as well
as his important contributions to biology, medicine and development co-operation (see page 89).
To honour and remember our founder’s significant contribution to biomedical sciences and research partnership, the
R. Geigy Foundation has created an award for excellence in
research, the aim of which is to help and encourage younger
scientists who will go on to contribute to scientific progress in
their chosen field. The first R. Geigy Award was presented in
2001 to Professor Fred Binka, a Ghanaian physician and epidemiologist with a PhD from the University of Basel. He has
made outstanding contributions to malaria research and control
in Africa. After working for the Roll Back Malaria campaign of
WHO, he has returned to teach in the School of Public Health in
the University of Ghana. The second award will be presented at
the R. Geigy Jubilee Symposium in December 2002 to Dr. Lea
Knopf, a Swiss veterinarian. Working under difficult field conditions in Côte d’Ivoire, she generated important data on the link
between parasitic disease burden and the health of cattle. She
is now extending her work in the direction of molecular biological studies of parasitic organisms.
Within the STI, the last two years have been a time of consolidation. The established structure, with two research departments and two service departments, has continued to provide
an efficient basis for us to pursue our goals in the fields of
Members of the Board of Governors (Kuratorium) Status June 2002
Mme. A-C. Clottu Vogel
Commission for Research Partnerships with Developing
Countries (KFPE), Berne, Switzerland
Prof. F. Gutzwiller Chairman
Institute for Social & Preventive Medicine, Zürich,
Switzerland
Prof. J. Louis
WHO and University of Lausanne, Switzerland
Prof. J.-L. Maurer
Graduate Institute of Development Studies (IUED) Geneva,
Switzerland
Prof. U. Meyer
Biocentre, University of Basel
Prof. C. Nissen Druey
Faculty of Medicine, University of Basel
Mr. J. Rüegger
Cantonal Department of Education, Basel
Dr. B. Sottas
Swiss Science Council, Berne, Switzerland
Mr. J.H. Schwarzenbach Vice-Chairman
Prof. W. Zimmerli
University of Basel Teaching Hospital, Liestal
Prof. M. Tanner: Director STI, ex officio
Mr. U. Wasser: Secretary to the Board
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Foreword
research, teaching and training, and direct services to individuals and communities as well as to governmental and non-governmental organisations. We have moved towards yet more
coherence in the organisation of research activities, which are
now driven by eight research teams, each with a clearly defined
profile and a strategic plan. The focussing of our work and the
streamlining of our management processes would not have
been possible without the competent guidance and advice provided by the Board of Governors (p. 5) and the international
External Research Review Team (p. 7). We are extremely grateful to them for their critical assessments, fruitful contributions
and far-sighted recommendations. These stimuli have significantly assisted the development of the STI.
The overall budget of the STI remained unchanged, at a level
of 17 million CHF (excluding the two million for internal management). Only 22 – 25% of the budget is covered by subsidies from
the local government (Canton Basel-Stadt, 12%) and the Office
of Education & Science of the Swiss Federal Government
(10%), but this support is vital. Hardly any donors or funding
agencies are prepared to invest in core functions, such as the
work of the STI as a key reference centre, the salaries of longterm staff, and maintenance of the infrastructure. The foundations associated with the STI, the Jubilee Foundation and the
R. Geigy Foundation (p. 89). have provided additional support
for research projects, and the R. Geigy Foundation has also
enabled us to carry out essential renovation and modernisation
of our second lecture theatre and of the heating and security
systems of the Institute.
The current funding periods will finish at the end of 2003 and
2004, and the STI has already prepared proposals to apply for
further support until the end of 2007. We have applied for a
higher core contribution, i.e. 25% of the total budget, as the
present level of 22% is no longer sufficient to maintain our competence at the highest level of quality as well as to allow investments in core structures. Decisions about future funding of the
STI are expected by the end of 2002 from Canton Basel-Stadt,
and in 2003 from the National Government, and they will be crucial for the further development of the STI along the lines presented in this report. However, we remain optimistic about the
future, since all the external evaluations carried out during the
reporting period underlined the STI’s competence and effectiveness in all domains of research, teaching and training, and services.
These achievements have been reflected in our success in
competing for third-party funds. We have obtained substantial
funding from the Swiss National Science Foundation (SNSF),
private Foundations (including the Bill & Melinda Gates Foundation) and bi- and multilateral donors. The funding volume from
the SNSF was doubled from July 2000 onwards to approximately 1.6 million CHF per year with our participation in one of
the new National Centres of Excellence in Research (NCCRs).
The STI was involved from the planning stage in the NCCR
North-South; mitigating syndromes of global change, and is
responsible for one of its eight Integrated Projects (IP4), entitled
Health and well-being. The project has two main foci; on urban
health and on the health of nomadic populations.
Countries in which the STI has major collaborative projects and mandates (excluding scientific collaborations and networks in Europe, N. America and Australia).
6
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Foreword
Through its Swiss Centre for International Health (SCIH), the
STI has been able to broaden and consolidate its considerable
portfolio of projects in consultancy, project support and backstopping. These include a considerable number of long-term
mandates to plan and execute collaborative projects and programmes – despite the fact that prevailing strategies of development co-operation favour short-term assistance and consultancies. Besides projects in countries where we have worked for
many years, we have established interesting service and support links with Eastern Europe and Central Asia, which will also
lead to scientific collaboration in the near future. The SCIH is
now a well established consultancy and backstopping unit, and
it also contributes significantly to global research and discussion on health development issues such as health financing and
health sector reforms. The new Pharmaceutical Medical Unit
(PMU) within the SCIH offers specialist services for the design,
implementation and monitoring of clinical trials. The staff of the
SCIH also share their expertise and knowledge by teaching in
university and other courses in Switzerland and elsewhere, and
in the STI’s postgraduate courses for health professionals.
The reporting period was also marked by an excellent performance of the Clinical and Diagnostic Services. The benefits from the Travel Clinic and Vaccination Centre, and from the
diagnostic services, have continued to support the new applied
research group Molecular Diagnostics, working on the application of molecular biology to create novel and improved diagnostic methods. The Medical and Diagnostic Services have established a leading position in Switzerland and developed important collaborative links with the units of travel and tropical
medicine at other Swiss universities, particularly Zurich, Berne
and Lausanne. Besides providing reference services in parasitology and tropical medicine, the staff of the Medical & Diagnostic Services have contributed to clinical studies of novel
therapeutic approaches and new vaccines, and contributed
their clinical expertise to many of the research projects carried
out in the STI, for example trials of improved treatments for tropical diseases such as trypanosomiasis.
Research in the STI still covers a very broad spectrum, but
the overall goal of contributing to health development provides
coherence and consistency. The research profile is further
shaped by three key principles: i) the iterative process between
the populations concerned (the “field”) and the laboratory,
ii) interdisciplinary approaches to health and well-being, and
iii) a research process undertaken in partnership with colleagues in the South. It is possible that our concern that our
research should be relevant to the daily lives of people, especially in the South, reduces our “academic freedom” – in the
sense that we cannot always pursue to the end all the basic and
theoretical questions that might arouse our scientific curiosity.
But there is really no lack of opportunity to carry out intellectually
satisfying basic research that is also consistent with remaining
true to our mandate.
We have been able to achieve a constantly high level of scientific productivity, which has received international recognition.
At the same time, there has been increasing interest in Switzerland in the expertise that the STI can offer in research on health
systems and health economics.
Research activities are based on eight research teams,
divided between the departments of Medical Parasitology &
Biology of Infection, and Public Health & Epidemiology. The
members of the teams are listed on page 95. The lists demonstrate that though the structure of research in the STI has been
clarified, it is by no means rigid, and continues to support a truly
interdisciplinary approach. As the lists of collaborators following
the individual sections of the report show, many projects involve
contributions from members of several research groups and
departments, and from the Medical Department and the SCIH.
In our internal Research Committee, scientists of the STI
meet regularly to discuss research and evaluate new proposals.
This serves to ensure coherence, and also to maintain contact
between the research teams and ensure that opportunities to
exploit the many potential synergies between the departments
are used to the full. In addition, the External Research Review
Team provides decisive and valuable guidance every year.
The research of the last two years is described in detail in the
first eight sections of this report. It continues to be varied, as a
Members of the External Research Review Team,
2001 and 2002
Dr. Michael Alpers (2001, 2002)
Papua New Guinea Institute for Medical Research
Prof. Thomas Bickle (2001, 2002)
Biozentrum, Basel
Prof. Fred Binka (2002)
School of Pulbic Health, University of Ghana
Prof. David Bradley (2001, 2002) Chairman
London School of Hygiene and Tropical Medicine
(LSHTM), UK
Prof. Ulrich Certa (2001, 2002)
F. Hoffmann-La Roche Ltd, Basel
Prof. Nicholas Fasel (2001, 2002)
Institute of Biochemistry, University of Lausanne,
Switzerland
Dr Jane Kengeya-Kayondo (2001, 2002)
TDR/TDF/WHO, Geneva, Switzerland
Dr Eric Lüdin (2001)
Hoffmann-La Roche, Basel
Prof. Anne Mills (2001, 2002)
LSHTM, London, UK
Dr Odile Puijalon-Mercereau (2001, 2002)
Pasteur Institute, Paris, France
Dr Jayashree Ramakrishna (2002)
National Institute of Mental Health, Bangalore, India
Dr Hans-Rudolf Roth (2002)
Statistics Institute, Swiss Federal Institute of Technology
(ETH), Zürich
Representatives of the Board of Governors
Prof. R. Gisler (2001)
Basel Institute for Immunology, Basel
Prof. Jacques Louis (2001, 2001)
WHO and University of Lausanne, Switzerland
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Foreword
Commission of the Canton of
glance at the Table of Contents
Basel continue to support
on page 2 will show. Work on
students from the South to do
communicable diseases ranges
postgraduate courses here.
from vaccine development and
Apart from participants in short
trials, and the development of
courses, about 20 students
new drugs, to innovative contricome every year from Africa,
butions to spatial statistics and
Asia and South America to do
basic immunology and epidemidiploma courses, and nearly 30
ology. Further achievements inare currently registered for MIH
clude authoritative analyses in
or PhD degrees, or completed
cultural epidemiology and mental
degrees during the reporting
health, a first validation of strateperiod.
gies to combine human and vetWe all enjoy the undergraduerinary medicine to serve nomaate and postgraduate courses
dic populations effectively, and
at the STI. They are a great
new insights into health planning
opportunity to share experience
under resource constraints in
Africa and in Switzerland. Some In 2001 the STI opened its doors to the public, presenting its activities to about across cultures, and we feel that
it is a privilege and a unique
projects have been completed or 1200 visitors. (Source: R. Dürr)
opportunity to participate in a
are being phased out, and new
process of mutual learning for change. Our contacts do not end
ones have started – adhering to the principles on which our
when the courses are over, but contribute to strengthening the
research is based, and building on the firm basis of what has
worldwide network of individuals and institutions that is so
already been accomplished.
important for our work. We are proud of the fact that former students of the STI have gone back to key positions in their own
Teaching and training has been a cornerstone of the STI’s
countries’ health services, and that past and present Directors
activities since its foundation in 1943 (see page 89). Besides
of two of our partner-institutes in the South have studied for a
offering its own courses, the STI has always been closely linked
Basel PhD degree in the STI: Andrew Kitua and Hassan
with the University of Basel, with members of the STI’s senior
Mshinda of the Ifakara Health Research and Development Censtaff holding teaching appointments in the University. In the last
tre in Tanzania, and Fred Binka and Abraham Hodgson of the
two years, the STI has consolidated its role as an Associated
Navrongo Health Research Centre in Ghana.
Institute of the University of Basel – an achievement that is
Besides students who come to do formal courses, there are
reflected in the appointment of the Director as Dean of the
trainees who come to the STI from projects and partner-instituFaculty of Science from 2002 onwards.
tions in the South, to acquire specific skills and experience in
The STI has contributed significantly to the development of
the laboratories, the computer services or the administration. All
the new curriculum in biology in the University by designing and
these exchanges add up to a substantial contribution to the
developing a new course in The Biology of Infection and Epibuilding of research and management capacity in the South.
demiology. This course reflects the expertise and experience of
the STI, and will contribute to the further strengthening of
Basel’s excellence in the area of Life Sciences. The STI is also
Outlook
contributing its international and public health experience to the
reformed curriculum in medicine, and is a founding member of
The present Report shows the current profile of the STI in the
the new inter-faculty Centre for African Studies at the University
areas of research, teaching and training, and service provision.
of Basel. We have also started to develop new initiatives to
These very diverse but interlinked activities are all aimed at purdevelop modern web-based teaching approaches that can be
suing our overall goal: to contribute to health development
used for “distance-learning” and can also complement classical
locally, nationally and internationally. Provided that we do obtain
course work, particularly in the fields of parasitology, biology of
enough support for our core activities from the local and
infection, tropical medicine, epidemiology and public health.
national governments, we are confident that we shall continue to
These innovative projects are funded by the national initiative
fulfil our mandate.
Swiss Virtual Campus as well as by private foundations, and we
Looking towards the future, we hope that by 2007 (the end of
are also greatly indebted to retired professors of the University
the next funding period), the STI will have fulfilled the aims
of Basel who work voluntarily with the project to give us the benshown in the box on the next page. The mid-term strategic plans
efit of their expertise in the field of e-learning.
of each department culminate in these ambitious, overarching
The postgraduate courses offered by the STI are now fully
aims. We are ready to accept the challenge and hope that the
accredited by the University of Basel, and these, as well as the
pursuit of our aims will bring STI into a position among the top
interfaculty doctoral programme in epidemiology, bring stuten institutes of International Health worldwide.
dents from all parts of the world to the Institute. The STI is a
Finally, it is also my pleasure and my wish to stress that none
founding member and a co-ordinating centre of tropEd, a netof the achievements described in this report would have been
work of European institutions which offer a joint course leading
possible without the most fruitful partnership and collaboration
to the degree of Master of International Health (MIH). The first
with national and international institutions and the generous,
three students to complete this course in the STI graduated this
unconditional support granted by all our many donors menyear. We are happy that the Swiss Government and the Stipend
tioned in this report. We are deeply indebted to them. My warm
8
05-09_Foreword
15.11.2002
11:15 Uhr
Seite 9
Foreword
Outlook
We hope that by 2007 the STI will have:
• been involved in at least two more phase I– III malaria vaccine trials;
• substantially developed its links with the European Community and the research opportunities it offers, particularly the
6th Framework and the European Developing Countries Clinical Trial Network;
• developed micro-array-technologies for resistance monitoring in malaria and possibly TB;
• participated in the discovery and development of at least
one lead compound as an antimalarial and one as an antitrypanosomal drug;
• developed and led at least one integrated malaria control
program in a highly endemic area;
• validated the concept of “one medicine” (the combination of
human and animal health services) for nomadic populations
in the Sahelian belt;
• combined the resources of cultural epidemiology with epidemiology and health systems research to provide basic
knowledge about people’s experience of, and attitudes to,
health and illness, that can support informed decision-making in health planning;
• established and validated concrete strategies to reduce
poverty through health interventions in urban and rural areas;
• obtained further recognition for coherent pursuit of research
partnerships;
• continued to play a leading role in the European network of
tropical institutes and within the European and global efforts
to assist health development;
• further integrated its expertise and experience in the Swiss
research community through participation in a second
NCCR;
• fostered its position as an Associated Institute of the University of Basel by strengthening strategic priority areas of
the University of Basel, such as Life Sciences and African
Studies;
• realised technical and didactic contributions for modern
teaching/training at university level;
• established its reference role in travel and tropical medicine
in Switzerland;
• introduced its experience and expertise in International
Health into the Swiss networks of both Public Health and
Development Co-operation.
personal thanks go to Jennifer Jenkins who again planned,
compiled and edited this report. Her excellence, commitment
and stamina rendered all possible. Finally I should also like to
express my deepest appreciation for the great commitment of
all 150 of the STI’s scientific, technical and administrative staff
and students, and all of its collaborating institutions – locally,
nationally and internationally – to reaching the achievements
described, that will certainly also contribute to world-wide health
development. I wish you a stimulating and informative reading
of this report and look forward to your reactions and comments.
Marcel Tanner
Director
Editorial Note
The first time I edited an STI report I added a small Editorial Note, and this has become a tradition. Its purpose is
twofold. First and foremost, it gives me an opportunity to thank all the people who helped in the task of preparing
this report. These include the leaders of research groups and Heads of Departments who took responsibility for the
contents of their own sections, and the many other people who were involved in writing, correcting, rewriting,
checking bibliographies and lists of names, and providing photographs – or simply gave me their moral support
and encouragement. In particular, I want to thank Marcel Tanner, with whom I have now worked on four Biennial
Reports. He has always made time in his more-than-busy day to discuss the decisions we had to make.
The second purpose of the Editorial Note is to draw attention to features that may require some explanation. One is that we always list
the people who have worked on a project alphabetically, because many projects involve scientists with different specialities, each
equally responsible for part of the work. Another result of the collaboration across groups and departments is that there is some duplication of references – not because we want to inflate our bibliography, but because we want to provide a complete list of publications
for each section.
Finally, I should like to follow Marcel Tanner’s example and look into the future – in this case, the future of the STI Report. One thing
that is relatively certain is that the next report will have a new editor, as I shall be retiring soon. It has been an interesting task, though
often a stressful one, and I have learnt a great deal in the process – not least from the staff of the Kreis printing works, who have not only
provided a consistently high quality of printing and production, but been very helpful in matters of design and layout.
My other prediction is that the Biennial Report will become longer. The first one in the present format, in 1989, had 26 pages (and two
blank ones “for notes”). This year we have 96, and if the trend continues, future editors will need to have a firm hand on the “delete” key
if they are to keep the publication within reasonable bounds. Naturally, the length of an institution’s report reflects editorial policy as well
as the amount of activity – but the growth of the STI report clearly does also reflect a real expansion in all aspects of the Institute’s work.
Looking at the Institute’s long-term prospects and well-founded hopes for the future, there is every reason to expect that in 2004 there
will be still more to write about.
Jennifer Jenkins
9
10-11_Financial Statement
18.11.2002
15:48 Uhr
Seite 10
Financial Statement
ANNUAL ACCOUNTS
2001
2000
in 1,000 CHF
in 1,000 CHF
14,692
1,875
2,270
18,837
0
18,837
12,690
1,875
2,249
16,814
0
16,814
12,949
5,069
493
18,511
326
18,837
12,197
4,104
421
16,722
92
16,814
1,213
2,295
818
5,341
9,667
1,698
1,973
893
5,300
9,864
1,639
2,034
4,821
21
900
252
9,667
2,270
1,915
4,812
10
900
–43
9,864
Profit and loss account
Income
Self managed income
Contribution of the Swiss national government
Contribution of the Basel local government
Total income
Loss
Expenditure
Staff expenditure
Material expenditure
Investments
Total expenditure
Profit
Balance sheet
Assets
Liquid funds
Debtors
Prepaid expenses
Fixed assets
Liabilities
Creditors
Accrued liabilities
Mortgage
General provision
Provision for VAT
Reserve
10
10-11_Financial Statement
21.11.2002
11:08 Uhr
Seite 11
Financial Statement
Profit and loss account by main activities including internal accounted services
2001
in %
Research:
– in Medical Parasitology and
Infection Biology
– in Public Health and Epidemiology
Total research
31%
11%
Service Centres:
– Clinical and Diagnostic Services
– Swiss Centre for International Health
Total services
34%
Central Functions
Infrastructure
Income
in 1,000 CHF
2000
Expenditure
in 1,000 CHF
Balance
in 1,000 CHF
in %
Income
in 1,000 CHF
Expenditure
in 1,000 CHF
Balance
in 1,000 CHF
29%
4,186
1,995
6,181
4,403
2,132
6,535
–217
–137
–354
2,122
2,253
–131
4,305
2,532
6,837
3,457
2,585
6,042
848
–53
795
18%
3,638
3,622
16
8%
102%
1,703
20,481
1,703
20,155
0
326
3,476
2,146
5,622
3,781
2,231
6,012
–305
–85
–390
2,084
1,977
107
3,790
4,119
7,909
3,328
4,206
7,534
462
–87
375
11%
2,114
2,114
0
8%
100%
1,607
19,336
1,607
19,244
0
92
11%
41%
FUNDING OF THE STI 2001–2002
Overall Funding
Total Budget = 19.2 million CHF
STI Foundations
5.2%
Local
Government
11.4%
National
Government
9.5%
Teaching
7.7%
Funding of Research
Total = 6.3 million CHF
SNSF 2.2%
Other External
Funds 15.9%
Medical and
Diagnostic Services
20.2%
STI Foundations: R. Geigy & Jubilee Foundations
SNSF: Swiss National Science Foundation
SCIH: Swiss Centre for International Health
(mandates, project implementation, other services)
SCIH and
Mandates 27.9%
STI Foundations
8.2%
Local
Government
20.8%
SNSF 7.6%
Other External
Funds 32.6%
National
Government
30.8%
Local Government: Canton of Basel City
Other External Funds: Funding competitively acquired
from national and international organisations (see list
below)
External funding: Berna Biotech, Bill and Melinda Gates Foundation (BMGF); Bundesamt für Veterinärwesen; Commission for Research Partnerships with Developing Countires (KFPE); Commission for Technology & Innovation (CTI); Education Dept. Basel City; EQUAM Stiftung; Fondation Hélvétique (Mada); Freie Akademische Gesellschaft;
Glaxo Smith Kline; Guggenheim-Schnurr Foundation; Leprahilfe Berne (ALES); Lotteriefonds Baselland; Medicines for Malaria Venture (MMV); Meningitis Research Foundation; Novartis Foundation; Optimus Foundation; Pevion Biotech; Roche Research Foundation; Stanley Thomas Johnson Foundation; Swiss Academy of Sciences; Swiss
Agency for Development and Co-operation (SDC), Swiss Federal Institute for Environmental Science & Technology (EAWAG); World Health Organisation (WHO).
11
12-16_Section_01
15.11.2002
11:17 Uhr
Seite 12
SECTION 1
Molecular Parasitology and Molecular Epidemiology
Introduction
The Molecular Parasitology-Epidemiology Group and the Molecular Diagnostics Group (Section 2) are closely interwoven
research teams, with shared staff, laboratories, and research
projects. Both groups are also strongly linked to other groups at
STI, especially Biometrics and Epidemiology (Section 5), Clinical and Intervention Epidemiology (Section 6) and the Medical
and Diagnostic services (Section 10).
The main focus of work in Molecular Parasitology-Epidemiology is the malaria parasite Plasmodium falciparum, with an
emphasis on:
• Basic molecular biology of Plasmodium falciparum.
• Molecular epidemiology of malaria in endemic areas.
Our mission and vision is to learn to understand this parasite
and its interaction with the human host, by studying the molecular biology which supports the parasite’s survival, and the epidemiology of infection on a molecular level. With this knowledge
we hope to be able to improve current interventions to control
the parasite, for example with new drugs or vaccines, or to identify innovative ways of controlling the devastating disease of
malaria.
In our studies of the basic molecular biology of Plasmodium
falciparum, the main emphasis is on gene regulation and
expression, including the analysis of the regulation of cytoadherence-conferring var genes in naturally infected individuals
and the ex vivo expression of these antigenically variable var
genes (1.1). We have also continued our analysis of stagespecifically regulated genes (1.2), and our studies of the
functional and immunological properties of one of the major
merozoite surface proteins, MSP2, (1.3), which is one of the
components of the recently-tested combination vaccine ComB.
One of the most important aims of malaria research is to protect small children –
like this one in Papua New Guinea – who are most vulnerable to severe disease.
(Source: H.-P. Beck)
Linking molecular approaches to epidemiological studies
enables us to analyse malaria infection and transmission in
great detail. For example, genotyping makes it possible to
analyse the dynamics of infection and generate data on multiplicity of infection. This means that we can monitor interventions
such as vaccine trials to a much finer degree than can be done
using conventional methods to identify parasites in blood. The
application of molecular biological methods to a trial of the vaccine ComB is described in section 1.4. In a longitudinal study in
Navrongo, Ghana, genotyping has enabled us to build up a
detailed picture of the dynamics of infection in this area (1.5).
12
Molecular biological methods can contribute many important
new insights into processes of infection and transmission. An
additional application is the monitoring of point mutations in
Plasmodium genes associated with resistance to antimalarials.
Information about the development and spread of resistance is
vital for policy decisions about control and treatment guidelines.
However, the amount of information that can be obtained has
been limited by the currently used PCR-RFLP procedures, so
that the number of samples that can be handled is limited.
Together with the Molecular Diagnostics group (Section 2) we
The research team of Molecular Parasitology-Epidemiology and Molecular Diagnostics. (Source: H.-P. Beck)
are working on developing new tools for large-scale research
and intervention studies. This involves developing semi-automated methods that can be used to handle large series of samples. To achieve this aim we are developing a micro arraybased technique for the parallel analysis of point mutations in
Plasmodium falciparum genes (1.6.). Eventually, we hope to
establish automated genotyping systems not only for studies on
drug resistance but also for investigations of polymorphic antigens or vaccine candidates.
During the past five years, the “STI Malaria Molecular Epidemiology Team” has built up considerable experience in the
application of molecular epidemiology in intervention trials. We
are now in the process of creating a “molecular tool box” that
can be used in a variety of intervention trials. The various techniques we are developing, such as quantitative PCR assays for
use in epidemiological studies, are described in section 1.7.
Once they are available we shall promote their use both in control trials and in programme-based evaluations of malaria control. Wherever possible, these tools will be transferred to laboratories in endemic areas.
Several major scientific developments are planned for the
near future. We will use our new micro array system for SNP
analysis to establish a genetic resistance index to antimalarials
in several malaria endemic areas over time. At present, such
data is only available for a few areas, and is often incomplete. In
the field of basic molecular biology of the malaria parasite, we
have now initiated a study using our information about var
genes to focus on the development of candidate vaccines
against malaria, using a rational and molecular-epidemiological
approach.
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Seite 13
SECTION 1 Molecular Parasitology and Molecular Epidemiology
1.1
var-gene expression in naturally infected samples,
var-gene regulation, and DNA binding proteins
We previously reported (STI 1999 – 2000) that var genes, coding
for the cytoadherence-conferring protein PfEMP1, are flanked
by two distinct and conserved types of 5’ sequences (var17type and 5B1-type). The majority of var genes are subtelomerically located and flanked by a var17-type 5’ upstream region. In
contrast, var genes located at internal chromosome positions all
have the 5B1-type 5’ upstream sequence. We also reported that
transient transfection assays of P. falciparum parasites revealed
that a fragment of about 2.5 kb of each type of var gene 5’
upstream sequences promotes transcription of the cat reporter
gene, suggesting that at least the minimal regulatory sequences
required for transcription of var genes are contained within both
types of 5’ upstream sequences.
In order to obtain more detailed information on these
upstream regions, we have generated clones in which the cat
reporter gene is controlled by partially deleted var gene
upstream regions for transient expression studies. Recently, we
replaced the cat reporter gene with the luciferase gene, and
could show in tightly-synchronised time-course experiments
that partial deletion affects transcription. Meanwhile, it has been
shown by Kirk Deitsch and his group that the regulation of var
genes is more complex than had been thought, e.g. it involves
an intron sequence. To elucidate this question we initiated a collaboration with his laboratory, and obtained their clones containing various intron sequences. These clones are being used to
generate constructs controlling the luciferase reporter gene
under the control of our upstream region (full length and deletions) containing the intron sequences.
We also subcloned restriction fragments (50bp to 350bp in
length) derived from the subtelomeric 4A3 var-gene upstream
segment (-2313 to -569 from the ATG-Start-codon), and from the
central 5B1 var-gene upstream segment (-2022 to -421 from the
ATG-codon) for studies on DNA binding proteins. These fragments were subsequently analysed for DNA binding properties,
using gel retardation assays with parasite nuclear extracts.
Three distinct and specific DNA-protein interactions were
revealed, and were termed CPE1 (central promoter element),
and SPE (subtelomeric promoter element) 1 and 2. Using
nuclear extracts from highly synchronised cultures we showed
that complexes SPE1 and CPE1 occur exactly at the time when
the respective var gene mRNA is turned off. These complexes
are observed at different time points, which clearly shows that
transcriptional control of the two var gene subfamilies is distinctively different, and that CPE1 and SPE1 are involved in var
gene transcription. We now also have preliminary evidence that
deletion of CPE1 results in a 2.5 fold increase of luciferase activity in transient transfection experiments, indicating that CPE1 is
indeed a functional repressor element. SPE2 has been shown to
be strictly confined to late stage parasites (older than 32 hours)
and might play a role in var gene silencing. We plan to analyse
the functions of SPE1 and 2 and CPE1 further, in particular
their involvement in regulation in concert with downstream
sequences such as the intron.
We have also started to analyse chromatin involvement and
changes during var gene switching, by selecting parasites on
the 3D7 background for var genes binding to CSA, CD36, and
ICAM1. As yet, we have been unable to select for adherence to
CSA, and have therefore concentrated on the analysis of ICAM1
and CD36 binders.
The finding of the apparent dimorphism of the two var gene
upstream regions is intriguing, and we are interested in its biological significance. We therefore started to study var gene
expression and cytoadherence ex vivo (i.e. directly in blood
samples taken from naturally infected individuals). At present,
little is known about the hierarchy and programme of var gene
expression within a given parasite isolate due to technical difficulties in undertaking such studies in endemic areas. We have
developed a robust RT-PCR technique, and have initiated two
studies in Papua New Guinea on ex vivo var gene expression.
To assess the correlation of expressed genes with age and
stage of immunity of the individual, we collected finger prick
blood samples in a cross-sectional study from 6 children aged
0 – 3 years, 21 children aged 4 –10 years, and 15 adults, all
infected with P. falciparum. To assess the dynamics of var gene
expression and switching in chronically infected individuals, we
carried out a longitudinal study, collecting finger prick or venous
blood samples from 20 children aged 7– 9 years every 2 weeks
for 4 months, and from 10 children aged 7– 9 years every
5th day for 1 month.
The number of P. falciparum strains in each blood sample
was determined by msp2 PCR-RFLP analysis. From the 15 samples with a parasitaemia higher than 0.5%, aliquots were cultured until the trophozoite stage to perform static cytoadherence assays using CHO cells (which naturally express CSA)
and with transfected CHO cells which expressed either CD36 or
ICAM1. var mRNA was isolated from total RNA using magnetic
beads tagged with an anti-ATS oligonucleotide. After reverse
transcription, PCR reactions were carried out amplifying both 5’
up stream regions, as well as the DBL1, CIDR, and DBL2
domains. All PCR products were cloned and at least 20 – 30
clones were picked and sequenced on an automated
sequencer (in collaboration with Hoffmann-La Roche).
Preliminary data revealed that 1– 5 different var sequences
(mostly 1– 3) are transcribed per domain and blood sample. In
one case, the same var gene (5’ UTR 5B1-DBL1) was detected
in samples taken 2 weeks after the initial sample from the same
individual. Another (CIDR) was detected 4 weeks after the initial
sample, and a third (DBL2) even after 10 weeks. Specific
primers will be designed to link different domains (e.g. DBL1
and CIDR) to test for any recombination events. In addition, specific PCR analyses on cDNA will be carried out to follow those
var genes which were expressed after 2 or more weeks, to find
out in how many follow-up samples they reappear. A casecontrol study on var gene expression in Papua New Guinea is
planned for the near future.
Scientist:
H.-P. Beck
Students:
M. Kästli, T. Voss (PhD); S. Bopp, A. Lüscher (MSc)
Collaboration:
WEHI, Australia (A. Cowman); PNGIMR (J. Reeder, A. Cortés);
Cornell University, Ithaca, USA (K. Deitsch)
Funding:
SNSF; Boehringer Ingelheim Fonds
1.2
Stage-specifically regulated genes in P. falciparum
During the last years we have generated and analysed a gene
library containing stage-specifically expressed genes, and
within the library specific for ring stages we identified several
13
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Seite 14
Location of ETRAMP2 in the parasitophorous vacuole (PVM), shown by immunogold transmission electron-micrograph of permeabilised parasites stained with
anti-ETRAMP2 serum and visualised with 5 nm gold particles.
(Source: D. Ferguson, Oxford University, UK)
genes belonging to a completely new gene family, etramps,
coding for proteins we termed “early transcribed membrane
proteins”. This family contains 13 members, all except three
expressed during the erythrocytic stages. Six ETRAMPs are
present at early stages, whereas others are tightly regulated
throughout the later part of the cycle. Only one ETRAMP seems
to be constitutively expressed during the whole erythrocytic
cycle. For four ETRAMPs we prepared recombinant proteins to
raise antisera in mice. Location studies were carried out with
these sera and we can show that ETRAMPs are located in
the parasitophorous vacuole membrane (PVM). Interestingly,
and showed that the open reading frame (ORF) is interrupted by
a central intron in both genes, and both ORFs code for relatively
small proteins of 244 and 138 amino acids. Interestingly, one
protein contains histidine-rich repeats at its C-terminus, whilst
the other contains a histidine-rich domain at its N-terminus.
Mouse sera were obtained against both histidine-rich
domains, and we carried out localisation studies. The proteins
locate in Maurer’s clefts (shown by co-localisation with antiSec31), and they have been named MAHRP1 and MAHRP2
(membrane-associated histidine rich protein). We were able to
show that MAHRP1 binds 6 haematin molecules and enhances
the breakdown of H2O2. This might indicate that one function of
the proteins is to protect such important structures as Maurer’s
clefts from oxidative stress and destruction. Further studies on
structural function, trafficking and the biochemical function of
both proteins are currently being done. Interestingly, the only
polymorphism of MAHRP1 has been identified as a variation in
the number of histidine-rich repeats. The importance of this is
under investigation.
During our studies on var gene promoter binding proteins we
also identified replication protein A of P. falciparum by mass
spectrometry. This is a protein with major binding activity for single-stranded DNA in parasite nuclear extracts, only present in
trophozoites and older parasites, but not in ring stages. The
complete mRNA contained an ORF of approximately 6 kb, with
the predicted pfrpa sequence just spanning half of the
sequence. Since such a long uninterrupted upstream region is
unusual, we attempted to clone and express 3 fragments from
this region to raise antibodies against the recombinant proteins.
We were able to obtain recombinant proteins, but the antibodies
gave ambiguous results, and we decided not to pursue this
project.
Scientist:
H.-P. Beck
Students:
T. Spielmann, T. Voss (PhD); E. Kump, C. Spycher (MSc)
Collaboration:
University of Marburg, Germany (K. Lingelbach); La Trobe University, Melbourne, Australia (L. Tilley), University of Oxford, UK
(D. Ferguson); Biozentrum Basel (P. Jenoe)
1.3
Immunological and functional importance of the
structural domains of the Plasmodium falciparum
merozoite surface protein 2
Staining of two different proteins, both located on the PVM. Left, anti-ETRAMP
serum. Centre; anti-exp 1. Right; the two pictures overlaid. Top and bottom rows;
different ETRAMPS.
ETRAMPs form distinct patterns within the PVM, distinguishable
from the location of another PVM protein, EXP1. We have compiled detailed location patterns and stage-specific expression
data, on both RNA and protein levels.
We also identified two other genes that are exclusively transcribed in early ring stage parasites, whose predicted amino
acid sequences revealed a similar structure to each other, comprising a transmembrane domain, and a histidine-rich region of
approximately 80 and 50 amino acids. The complete coding
sequence was obtained from the Malaria Sequencing Project
14
Merozoite Protein 2 (MSP2) continues to be an important subject of our research on the molecular biology of the malaria parasite. Current projects aim to generate plasmid constructs for
the transfection of P. falciparum cultures in vitro, in order to
achieve allelic replacement of the endogenous MSP2 by an
MSP2 with deleted repeats. With this approach we are able to
assess cross-reactivity between different MSP2 variants, and to
analyse the anti-MSP2 response after vaccination with ComB
(Combination B), which contains the 3D7-form of MSP2.
After the 3D7 form of MSP2 had been used successfully as
one of three subunits of the Combination B malaria vaccine, this
allele was chosen for a detailed study of the biological function
of the central region containing the intragenic repeats. A transfection construct has been cloned, with the aim of generating a
parasite line with a 3D7 genetic background, but with the
repeats deleted. To elucidate the role of antibodies against vari-
12-16_Section_01
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Scientist:
I. Felger
Technologist:
S. Steiger
PhD students:
C. Flück, A. Irion
Collaboration:
WEHI, Australia (A. Cowman)
Funding:
SNSF
1500
4
1000
2
500
0
The msp2 locus of P. falciparum was genotyped in all samples
from the vaccine trial of Combination B (ComB) in Papua New
Guinea (6.1). The results revealed that the vaccine had had a
selective effect, in favour of alternative allelic variants which
were not present in the vaccine.
Molecular analysis could also be used for assessing vaccine
efficacy. For example, assessment of parasite prevalence in the
different trial groups by PCR gave a more precise result than
microscopy. New molecular outcome measures were explored,
such as the rate of infection by new clones, which can be determined by PCR-RFLP even though other clones may already be
present. The efficacy of vaccination was estimated to be 53%
against new 3D7 type infections, whereas no effect was seen
against infection by FC27-type alleles.
A sequencing project is being undertaken to analyse the
nucleotide sequences of all 3D7-type breakthrough infections,
characterising the msp2 alleles of the 3D7 allelic family from all
parasite clones that appeared in the group of vaccinated children after vaccination. These alleles were compared to those
from placebo recipients. The aim was to test the hypothesis that
“escape variants” of 3D7-type infections occurring in vaccinated children represent a distinct subgroup of alleles.
Scientists:
H.-P. Beck, I. Felger, B. Genton, T. Smith
PhD student:
C. Flück
Collaboration:
PNGIMR (M. Alpers)
Funding:
SNSF
1.5
A molecular biological study of infection dynamics in
Navrongo, Ghana
A major molecular epidemiological field study consisting of six
2-monthly cross-sectional surveys with 349 individuals of all
ages was performed in Northern Ghana, where transmission of
malaria shows seasonal variation. Molecular typing was performed by PCR-RFLP, discriminating 38 3D7-type alleles and
36 FC27-type alleles. One of the aims was to analyse the relationship of multiplicity of infection to age and seasonality. The
mean multiplicity of infection was 4.8 concurrent infections per
person in the wet season, and 3.9 in the dry season. This result
60+
40 to 59
20 to 39
10 to 19
5 To 9
3 to 4
1 to 2
<1
0
1.4
Effect of vaccination with the malaria vaccine
Combination B on the parasite population
Mean Multiplicity
6
2000
GMPD
ous parts of MSP2 we will perform invasion inhibition assays
using cultured lines and our transfection constructs together
with human hyperimmune sera, polyclonal antisera from mice
immunised with the different recombinant MSP2 domains, and
affinity purified MSP2 antibodies. Further constructs will carry
FC27 and 3D7-type alleles with various parts deleted. Knowledge about the functional importance of the variable or repetitive parts of MSP2 will greatly help in the formulation of a next
generation of MSP2 vaccines.
Age groups in years
Changes in parasite density and multiplicity of infection with age.
GMPD = General Mean Parasite Density
Multiplicity
for the wet season is comparable to the situation in areas of
perennial transmission. Multiplicity was dependent on age. The
peak was reached at 10 –19 years of age, later than that found
in other studies in areas of holoendemic and perennial transmission (see also 5.4).
The consecutive blood samples of each individual were further analysed to study the infection dynamics of the individual
parasite clones in the course of the year. The data set of PCRRFLP genotypes was used to determine rates of acquisition and
loss of parasite clones, as well as the duration of each infection
in all age groups and in different seasons. These longitudinal
study results revealed major differences between the allelic
families with respect to turnover rates, clearance, and acquisition of individual infections. The persistence of clones seemed
to be unaffected by the change in season, but both gains and
losses of parasite clones were reduced during the dry season.
The longitudinal genotyping data will be further analysed to
examine infection and clearance rates (allowing for imperfect
detection; see 5.3).
Scientists:
I. Felger, T. Smith
PhD students:
S. Owusu, W. Sama
MSc/ATA students: B. Glinz (ATA), A. Tiaden (MSc)
Collaboration:
Navrongo Health Research Centre, Ghana
Funding:
WHO/TDR
1.6
Development of a parallel micro array-based
technique for the analysis of point mutations in
genes of P. falciparum associated with drug
resistance
Point mutations (SNPs) in a number of genes in P. falciparum
have been associated with resistance to antimalarials. Analysis
of the prevalence of particular SPNs in parasites isolated from
the blood of malaria patients, or better, from parasites circulating in the community, can provide information about the level of
drug resistance in a given area.
The identification of point mutations in genes associated with
drug resistance by manual analysis of SNPs is time-consuming,
and there are limits to the number of samples it is feasible to
examine. We have now developed an innovative parallel SNP
15
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analysis system based on micro arrays to test for point mutations associated with drug resistance in P. falciparum. We were
able to obtain a complete micro array spotter and scanner line,
and we have already used this technology to analyse SNPs in
the following genes: pfmdr, pfcrt, pfdhfr, pfdhps, which are
linked with resistance to sulphadoxine-pyrimethamine and
chloroquine. We have successfully compared our array-based
analysis system not only with the commonly used RFLP system,
but also with a MALDI-TOF SNP analysis system (in collaboration with Hoffmann-La Roche). Currently, we are establishing
standard protocols, and continuing to optimise the system. In
particular, we want to improve the multiplex system to minimise
the number of PCR reactions needed, and to reduce working
time as far as possible, to make it feasible to process large
numbers of samples. The ability to process large numbers of
samples will open up possibilities for carrying out studies on a
much larger scale than at present. A patent for the technology
has been applied for.
We are already conducting epidemiological studies on SNPs
associated with drug resistance, aiming to establish the relationship between SNP prevalence in an area and clinical failure
rates at the health facilities. Until now, it has not been possible to
show an association between treatment outcome and the presence of mutant parasites that could enable treatment failure in
individual patients to be predicted. Projects in Tanzania and
Papua New Guinea have started to investigate the relationship
i) The use of PCR and real-time PCR for diagnosing parasites
gives more accurate estimates for parasite presence and
density (in particular in low grade infections) than microscopy.
ii) The analysis of parasite dynamics can be used as an outcome measure for interventions. It provides detailed information on many parameters, such as the duration of an infection, the incidence of individual parasite clones, clearance
rates, and multiplicity of infection. All this information can be
obtained by using PCR amplification of a polymorphic
marker gene and genotyping all the individual parasite
clones from consecutive blood samples from the same
patient.
iii) In trials of malaria vaccines genotyping is of particular importance if the vaccines contain a polymorphic antigen. Selective effects of such vaccines can only be assessed by molecular means.
iv) In drug resistance studies or in trials of new drugs, genotyping can be used to distinguish between new infections and
recrudescences. This application is already well established.
The results obtained through genotyping are valuable, but the
work is time-consuming. We are therefore aiming at establishing
new semi-high-throughput technologies for genotyping various
marker genes. Once the techniques are available we shall promote their use both in controlled trials and in program-based
evaluations of malaria control. Currently we are developing the
following new tools:
• quantitative real time PCR for increase in sensitivity
• a “DNA-chip” for SNP detection
• semi-automated msp2 genotyping for the analysis of parasite dynamics.
Scientists:
H.-P. Beck, I. Felger, B. Genton, T. Smith, M. Tanner
Small prototype micro array for SNP analysis of genes in P. falciparum associated
with drug resistance.
Publications:
between parasitological and clinical outcomes in in vivo studies,
and the distribution of several molecular markers among
asymptomatic individuals, in areas with different levels of
malaria endemicity and drug resistance.
Scientists:
As the Molecular Epidemiology and Molecular Diagnostics
groups work closely together, the publications for both are collected at the end of Section 2, page 18.
H.-P. Beck, A. Crameri, I. Felger, B. Genton
Students:
J. Marfurt, K. Mugittu (PhD); R. Burki, A. Regös (MSc)
Collaboration:
Policlinique Universitaire Lausanne, Switzerland; PNGIMR;
WEHI, Melbourne, Australia; IHRDC, Ifakara, Tanzania
Funding:
SNSF; Roche Research Foundation, Basel; Freie Akademische
Gesellschaft, Basel.
1.7
Development of a “Tool box” for molecular monitoring
in malaria intervention trials
During the past 5 years our team has built up considerable
experience in the application of molecular epidemiology in the
frame of intervention trials. We have collected genotyping data
in several studies described elsewhere in this report: bednet
use (6.3), trials of the new drug Co-artemether, and of iron supplementation (STI 1999 – 2000), and in trials of two vaccines,
SPf66 and Combination B (6.1). Based on this experience we
have developed the rationale and the methodology for molecular monitoring in malaria field trials. The key issues are:
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SECTION 2
Molecular Diagnostics
Introduction
the certification of tests. The unit is closely integrated in the
The Molecular Diagnostics Unit, nested within the Molecular
planning and carrying out of many research projects in the
Parasitology and Molecular Epidemiology Group, was estabSTI. Molecular diagnostic methods are important in many
lished in June 2000, and conducts research to generate and
descriptive and intervention studoptimise methods and protocols
ies, such as trials of vaccines or
for the diagnosis of parasitic
drugs. A number of these are
infections in individuals and in
described elsewhere in this report
community samples, using mole(Sections 1, 6, 10).
cular biological techniques.
Molecular diagnostic services
Our aims are to provide supcurrently being routinely offered
port and services, and to carry
are the detection and differentiaout applied research. We provide
tion of Entamoeba species, Plassupport for the routine molecular
modium species and Leishmania
tests carried out in the Medical
species by PCR. Recombinant
Diagnostics department (MEDantigens for serological diagnosis
DIA), offering technical advice,
candidates have been cloned
trouble-shooting and quality conand expressed. For Leishmania, a
trol. We carry out genotyping
diagnostic PCR system has been
commissioned by third parties Laboratory work in the STI, Basel. (Source: H.-P. Beck)
developed, and antigens for the
(companies or research groups).
early diagnosis of L. infantum have been identified. Some of
A large part of our work, however, is the development or
these are not only valuable for diagnosis but are potential canadaptation of new molecular assays for diagnosis in individuals
didates for a vaccine against this parasite.
or on an epidemiological scale. We also design and supervise
small field studies to evaluate new PCR assays and to prepare
2.1
Development and evaluation of a PCR genotyping
system for Leishmania species
The aim is to standardize a PCR-based genotyping assay for
Leishmania species. Our Leishmania PCR-RFLP assay, based
on the repetitive mini-exon gene, was originally established
using DNA from isolates cultured in vitro. We are now working
on a test in which DNA is isolated directly from biopsy samples.
Since this eliminates the culture stage, the time until a result
becomes available is considerably reduced. The test has been
evaluated by isolating DNA directly from 50 biopsies. In parallel,
positivity was determined by culture, serology and a second,
alternative PCR assay (leg PCR). Sensitivity was established by
limiting dilution experiments, and inhibition effects of increasing
amounts of human genomic DNA were assessed. A plasmid
was generated as a positive internal control, containing both
PCR primers and an unrelated Leishmania sequence which is
not digested by the diagnostic restriction enzymes.
There is an increasing demand for species differentiation by
PCR, so in order to reduce “hands-on” time, all steps were optimized to define efficient standard operating procedures.
Scientist:
I. Felger
MSc students:
D. Makia, J. Marfurt
Funding:
Nationalversicherung, Switzerland
2.2
Cloning and expression of recombinant antigens
for serological diagnosis
The preparation of high-quality antigen material for serological
tests can be a very time-consuming task in a diagnostic laboratory. Particularly in the diagnosis of helminth infections, serological cross-reactivity is a concern when using whole parasite
extract. In response to the need of the STI MEDDIA department
for diagnostic antigens specific for individual helminth infections, we have started to produce and evaluate recombinant
antigens using molecular biological approaches.
To develop a suitable diagnostic antigen for Strongyloides
stercoralis, a monomer, a dimer and a tetramer of an artificial
gene fragment representing a sequence specific for S. stercoralis were cloned and expressed in E. coli. The sensitivity and
specificity of diagnosis using these recombinant peptides were
established using a panel of sera specific for various parasite
infections, in particular for other helminths. ELISAs and Western
blots were performed to assess the use of the recombinant peptides for routine serology. The dimer clone showed a promising
potential for developing a confirmation test for S. stercoralis
infections.
A Toxocara canis specific antigen has also been cloned,
expressed and taken further for evaluation by ELISA and Western blots.
Scientists:
J. Burckhardt, I. Felger
Technologist:
S. Steiger
MSc student:
M. Annaheim
2.3
Identification of L. infantum antigens as potential
vaccine candidates and for use in early diagnosis
In order to identify potential vaccine candidates against Leishmania infantum, we compared the mRNA population from noninfective (log phase) parasites with the mRNA population from
infective stages (stationary parasites) by differential cDNA
preparation. Thus, we expected to identify antigens involved in
invasion, which might represent important vaccine candidates.
Up to date, we have obtained twelve differentially expressed
sequences. Six of them have no known homologue in GenbankTM.
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Seite 18
Publications in Molecular Epidemiology, Molecular Parasitology and
Molecular Diagnostics
To elucidate their potential use as vaccine candidates, further
sequence analysis and localization studies will be performed to
decide which antigens are most promising.
Antigens expressed on the cell surface might provide a useful diagnostic tool, though they are probably not good vaccine
candidates. In our quest for early diagnostic markers, we identified 4 clones from a L. infantum expression library recognized
by sera from naturally and artificially infected dogs. All antigens
have been produced as recombinant proteins and have been
tested on dogs in L. infantum endemic areas for their usefulness
in an early detection system. Two of the antigens have been
identified as being recognized early during the course of infection, and trials are now being carried out in collaboration with an
industial partner.
Scientist:
H.-P. Beck
Technologist:
J. Marfurt
PhD student:
I. Niederwieser
Collaboration:
Hebrew University, Jerusalem, Israel (Charles Jaffe); University
of Madrid, Spain (José Maria Alunda); University of Barcelona,
Spain (Montserrat Portus); University of Besançon, France
(Renauld Piarroux)
Publications in Molecular Epidemiology, Molecular Parasitology and Molecular Diagnostics
Brahimi K, Spielmann T, Ward G, Quevillon E, Barale J-C, Jaureguiberry G, Jambou R & Langsley G (submitted) The Plasmodium falciparum intermediate compartment-specific GTPases Rab1A and Rab1B. J Biol Chem.
Beck H-P (2002) Restriction fragment length polymorphism (RFLP) analysis. In:
Malaria Methods and Protocols, Ed: Doolan DL, Totowa NJ, Humana Press,
205 – 212.
Färnert A, Arez AP, Babiker HA, Beck H-P, Benito A, Björkman A, Bruce MC, Conway D, Day KP, Henning L, Mercereau-Puijalon O, Ranford-Cartwright LC, Rubio
JM, Snounou G, Zwetyenga J & do Rosaria VE (2000) Genotyping of Plasmodium
falciparum infections by PCR: a comparative multicentre study. Trans R Soc Trop
Med Hyg 95, 225 –232.
Beck H-P (2001) Screen test: topics in international health: Malaria, 2nd edition.
(CD review) Trends Parasitol 17, 301– 301.
Felger I, Genton B, Smith T, Tanner M & Beck H-P (in press) Molecular monitoring
in malaria vaccine trials. Trends Parasitol.
Spielmann T (2002) Southern blotting of parasite DNA. In: Malaria Methods and
Protocols, Ed: Doolan DL, Totowa NJ, Humana Press, 165 –176.
Genton B, Betuela I, Felger I, Al-Yaman F, Anders R, Saul A, Rare L, Baisor M,
Lorry K, Brown GV, Pye D, Irving DO, Smith TA, Beck H-P & Alpers MP (2002) A
recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase I/IIb trial in
Papua New Guinea. J Infect Dis 185, 820 – 827.
Voss T (2002) Extraction and purification of Plasmodium total RNA. In: Malaria
Methods and Protocols, Ed: Doolan DL, Totowa NJ, Humana Press151–158.
Heckendorn F, N’Goran EK, Felger I, Vounatsou P, Yapi A, Oettli A, Marti H, Dobler
M, Traoré M, Lohourignon KL & Lengeler C (in press) Species-specific field testing
of Entamoeba sp. in an area of high endemicity. Trans R Soc Trop Med Hyg.
Irion A, Beck H-P & Smith T (2002) Assessment of positivity in immuno-assays with
variability in background measurements: a new approach applied to the antibody
response to Plasmodium falciparum MSP2. J Immunol Methods 259, 111–118.
Niederwieser I, Felger I & Beck H-P (2000) Limited polymorphism in Plasmodium
falciparum sexual stage antigens. Am J Trop Med Hyg 95, 163 –169.
Mack SJ, Bugawan TL, Moonsamy PV, Erlich JA, Trachtenberg EA, Paik YK,
Bogovich A, Stoneking M, Saha M, Beck H-P & Erlich HA (2000) Evolution of
pacific/asian populations inferred from HLA class II allele frequency distributions.
Tissue Antigens 55, 383 – 400.
Müller DA, Charlwood JD, Felger I, Ferreira C, do Rosario V & Smith T (2001)
Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium
falciparum in Sao Tome. Acta Trop 78, 155 –162.
Owusu-Agyei S, Smith T, Beck H-P, Amenga-Etego L & Felger I (2002) Molecular
epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana. Trop Med Int Health 7,
421– 428.
Schneider AG, Felger I, Smith T, Abdullah S, Beck H-P & Mshinda H (2001) A point
mutation in codon 76 of pfcrt of Plasmodium falciparum is positively selected for
by chloroquine treatment in Tanzania. Infection Genetics and Evolution 18, 1–7.
Spielmann T & Beck H-P (2000) Analysis of stage-specific transcription in Plasmodium falciparum reveals a set of genes exclusively transcribed in ring stage
parasites. Mol Biochem Parasitol 111, 453 – 458.
Spielmann T, Ferguson DJ & Beck H-P (in press) Plasmodium falciparum possesses a family of small charged membrane proteins located in the parasitophorous vacuole which are tightly regulated during all erythrocytic stages. Mol
Biol Cell.
Voss TS, Mini T, Jenoe P & Beck H-P (2002) Plasmodium falciparum possesses a
cell cycle-regulated short type replication protein a large subunit encoded by an
unusual transcript. J Biol Chem 17,17493 –17501.
Reviews, editorials, book chapters, and non-peer reviewed articles
Beck H-P (2002) Extraction and purification of Plasmodium parasite DNA. In:
Malaria Methods and Protocols, Ed: Doolan DL, Totowa NJ, Humana Press,
159 –164.
18
Felger I & Beck H-P (2002) Genotyping of Plasmodium falciparum in the host (ii)
PCR-RFLP analysis. In: Malaria Methods and Protocols, Ed: Doolan DL, Totowa
NJ, Humana Press, 117–130.
Warhurst DC, Adagu IS, Beck H-P, Duraisingh MT, Kirby GC, von Seidlein L &
Wright CW (2000) Mode of action of Artemether/lumefantrine (CoartemR: the sole,
fixed, oral ADDC) and its role in combatting multidrug-resistance. In: Treatment
guidelines in endemic falciparum malaria, Novartis Consensus Meeting, Cartagena 20 –25 August 2000, 5 –7.
SELECTED ABBREVIATIONS: Molecular Biology of
Parasites
ATS
acidic terminal sequence
CAT
chloramphenical-acetyl transferase
CD36
cluster of differentiation 36
CIDR
cysteine-rich interdomain region
CPE
central promoter element
CSA
chondroiting sulphate A
CSP
circumsporozoite protein
3D7
name of a P. falciparum strain
DBL1, 2
var gene products
ETRAMPs early transcribed membrane proteins
EXP1
exported protein 1
GAPDH
glyceraldehyde-3-phosphate dehydrogenase
GFP
green fluorescent protein
GPI
glycosylphosphatidylinositol
ICAM1
intracellular adhesion molecule 1
MAHRP
membrane-associated histidine rich protein
MHC
major histocompatibility complex
MSP
merozoite surface protein of P. falciparum
ORF
open reading frame
PCR-RFLP PCR-restriction fragment length polymorphism
PfEMP1
P. falciparum erythrocyte membrane protein
PFRPA
P. falciparum replication protein A
PVM
parasitophorous vacuole membrane
Sec31
protein of coat protein II complex
SNP
single nucleotide polymorphism
SPE
subtelomeric promoter element
TCR
T cell receptor
TRGV
T cell receptor variable gene
var
variable genes encoding PfEMP1
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SECTION 3
Molecular Immunology
Introduction
in other vaccines as safe and effective antigen delivery systems. We are also developing tools and technologies to study
immune responses of the Aotus monkey, an experimental infection model for Plasmodium falciparum malaria that is suitable for
the preclinical evaluation of blood-stage candidate vaccines.
The bacterial meningitis project involves a longitudinal study
of the molecular epidemiology of the carriage of meningococci
as well as outbreaks of disease. The
study is being carried out in northern
Ghana, where meningitis epidemics
occur every few years. The results will
Malaria due to Plasmodium falciparum
provide important background infor(3.1– 3.3).
mation for the evaluation and introEpidemic bacterial meningitis caused
duction of new conjugate vaccines
by Neisseria meningitidis (3.4).
against meningococcal infections in
Buruli ulcer caused by MycobacAfrica.
terium ulcerans (3.5).
Buruli ulcers, like leprosy and
tuberculosis, are caused by a
In the field of malaria research, goals
Mycobacterium, in this case M. ulcerinclude the evaluation of immune
ans. The disease, which can be
effector functions, the search for new
severely crippling, is becoming more
vaccine candidate antigens, and the Child with meningitis in northern Ghana. (Source: S. Gagneux)
development and evaluation of new Studies of menigitis also include an investigation of risk-factors and and more prevalent, particularly in a
long-term sequelae. (Section 5.7)
number of West African countries. Our
types of vaccine formulation which
studies in Ghana, in collaboration with the District Health Sercould improve the immunogenicity/effectiveness of peptide vacvices, are focussed on the evaluation of prospects for the
cines. One approach is to present mimotopes of P. falciparum
design of a vaccine and the development of a serological diagprotein surface loops by attaching them to reconstituted
nostic test for early disease.
influenza virosomes (IRIV), which have been successfully used
Since it started in 1995 the Molecular Immunology unit has
steadily developed a focus on vaccinology. This area of
research complements activities of other units of the Institute.
Technology platforms have been developed for the analysis of
the specificity and effector functions of host immune responses
(with a focus on the human immune system), and of the antigenic diversity of parasites. To make full use of this research
capacity, projects in three disease
systems have been initiated and are
now well established. These are:
3.1
Development of subunit vaccines against malaria
New strategies for the design of epitope-focussed vaccines
As a starting point for the development of new strategies for the
design of a synthetic malaria vaccine we have performed
detailed analyses of the immune response against the peptide
vaccine candidate SPf66 in humans. These investigations, and
additional studies with selected peptide epitopes in animal
models, have revealed that:
i) Only antibody responses against particular “critical epitopes” of the parasite cell surface proteins seem to inhibit
parasite growth. Therefore we consider that the most promising approach to developing a vaccine against malaria is to
design one which targets the immune response towards
such “critical epitopes”. Such a targeted vaccine should produce fewer useless “smokescreen” immune responses, and
potentially contra-productive or harmful ones.
ii) The ideal malaria vaccine should cover all the variant strains
in a given setting. Such a vaccine should be based on functionally important conserved sequences of P. falciparum.
However, such structures are often not very immunogenic, so
they have to be delivered in a highly immunogenic form.
Semiconserved parasite sequences are abundant and easier to identify. However, while antibody responses show considerable cross-reactivity, cellular immune responses to
P. falciparum have been shown by clonal analyses with
human T cells to be absolutely variant-specific. In a mixed
infection, cohabiting parasite strains may actually facilitate
each other’s survival by down-regulating cellular immune
responses via altered peptide ligand inhibition mechanisms.
There is a danger that a vaccine incorporating a semiconserved sequence could have a similar effect.
iii) Due to their inherent flexibility, short linear peptide epitope
sequences often do not elicit antibody responses that crossreact with the target antigens in the native form. The coupling
of several individual epitopes to a continuous surrogate protein sequence is one strategy suggested to overcome this
problem, but it may not be a suitable one as it generates too
many neoantigenic sites.
iv) Development of improved adjuvants and antigen delivery
systems is a prerequisite for the development of a successful
subunit malaria vaccine.
Development of improved adjuvants and antigen delivery
systems
In our analyses of the saponin adjuvant QS-21, it turned out to
be a far more potent adjuvant than the commonly-used alum in
inducing adaptive immune responses (including cytotoxic T
cells) against the SPf66 peptide. However, clinical use of effective new adjuvant formulations is often compromised by the
development of severe side effects, and further investigation will
be needed.
Another line of investigation is into using immunopotentiating
reconstituted influenza virosomes (IRIV) as a safe antigen delivery system for subunit vaccines. Our starting point was to investigate the possibility of associating peptide or protein antigens
19
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Seite 20
in a defined fashion with IRIV. These are spherical, unilammelar
vesicles, prepared by detergent removal from a mixture of natural and synthetic phospholipids and influenza surface glycoproteins. They have been shown to be a highly effective means of
enhancing the immune response to a variety of antigens.
The haemagglutinin membrane glycoprotein of the influenza
virus plays a key role in the activity of IRIV. This major antigen of
influenza virus is a fusion-inducing component, which facilitates
antigen delivery to immunocompetent cells. In the hepatitis A
vaccine Epaxal-BernaTM, the first licensed vaccine in which IRIV
are used as a delivery system for a non-influenza antigen, the
hepatitis A antigen spontaneously binds to the IRIV.
In collaboration with BernaBiotech/Pevion (R. Glück, R. Zurbriggen) we have developed and evaluated a method to “hook”
antigens on to phosphatidylethanolamine and to integrate the
phospolipid-antigen conjugates into the virosomal membrane
during the virosome reconstitution process. As a first model
antigen we used the peptide unit of SPf66 and investigated the
immunological properties of the SPf66-loaded virosomes in
mice. In these experiments, the presentation of multiple copies
of the antigen on the virosome surface induced strong antibody
responses.
Identification of synthetic mimotopes of P. falciparum protein
antigen surface loops
The next step was to hook mimotopes (structures that mimic the
immunogenic properties of epitopes) of malaria antigen surface
loops to the surface of the virosomes. Due to their inherent flexibility, linear peptides often elicit antibodies that bind to denatured proteins, but fail to recognise the same sequences in
native protein structures. This is one problem that has so far hindered the application of synthetic peptides in vaccine design.
Others are that peptides in serum have only a limited stability
against proteolysis, and that their immunogenicity when administered as conjugates in human-compatible adjuvants is often
weak. We have now shown that these problems may be alleviated by using conformationally defined peptidomimetics coupled to virosomes. In collaboration with the Chemistry Department of the University of Zürich (J. Robinson) we have identified
and optimised conformationally restricted cyclic peptide structures that mimic surface loops of three key malaria vaccine candidate antigens; the NPNA repeat region of circumsporozoite
protein (CSP), apical membrane antigen 1 (AMA-1), and the
19KD fragment of merozoite surface protein 1 (MSP-1).
Starting with a small cyclic peptide containing portions of the
NPNA-repeat region of CSP we have identified and profiled an
optimised mimotope which very efficiently elicits antibodies that
also cross-react with P. falciparum sporozoites and inhibit
sporozoite invasion of human liver cells (collaboration with D.
Mazier and O. Silvie, INSERM). These results demonstrated that
it is possible to start from a lead structure and design a compound with optimal immunological properties in a stepwise
process.
With AMA-1, we used two alternative approaches to identify a
lead structure for mimotope development. The first approach,
immunological studies with a library of synthetic templatebound cyclic 12-mer peptidomimetics, turned out to be less
successful than a second strategy in which a larger synthetic
peptide structure was used as a starting point. Some of the
monoclonal antibodies (mAbs) generated against this structure
had growth-inhibitory activity against blood stage parasites in
20
vitro. Epitopes recognised by these mAbs were characterised,
and smaller sequence stretches are now serving as lead structure(s) for the design of an improved second generation AMA-1
mimotope.
In the case of MSP-1, a first generation mimotope has been
identified that elicits parasite-binding antibodies. The immunological properties of this lead structure are currently being
investigated in detail.
We compared a mimotope-virosome formulation with the
same mimotope presented as a multiple antigenic peptide
(MAP) construct, in which several copies of the mimotope are
adsorbed to alum as an adjuvant. Both formulations elicited
comparable levels of anti-mimotope antibody responses in
mice. However, only the antibodies against the virosomal formulation bound to Plasmodium. This indicated that phosphatidylethanolamine-coupled antigens were located on the surface of
the virosomes without their conformation being disturbed,
whereas adsorption to alum dramatically changed it.
A clinical trial is envisioned in the near future. Experience
with (non-malaria) virosomal vaccine formulations in other laboratories has shown that responses in humans are often far
stronger (without severe adverse side effects) than those
observed in pre-clinical studies in mice. The stronger response
is attributed to natural anti-influenza pre-immunity in humans.
Scientists:
C. Daubenberger, M. Müller, G. Pluschke
Technologists:
M. Naegeli, F. Pöltl-Frank
PhD students:
M. Bastian, R. Moreno, B. Nickel, S. Okitsu
MSc students:
B. Hübner (ATA), S. Krattiger, E. Peduzzi, F. Schwager,
S. Siegrist, D. Vogel
Collaboration:
Pevion/Berna Biotech Ltd, Bern, Switzerland (R. Glück, R. Zurbriggen); Institute for Organic Chemistry, University of Zürich,
Switzerland (J. Robinson); Fundación Instituto de Inmunología
de Colombia (FIDIC), Universidad Nacional de Colombia,
Bogotà (E. Lioy, J. Lozano, M. E. Patarroyo); INSERM, Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires,
Paris, France (D. Mazier, O. Silvie); Hoffmann-La Roche, Basel
(H. Matile)
Funding:
Kommission für Technologie und Innovation, BBT, Berne,
Switzerland; Roche Research Foundation, Basel, Switzerland
3.2
Search for new malaria vaccine candidate antigens
Cell biology of the malaria parasite
The description of the complete P. falciparum genome will soon
become available, and cell biological approaches will be needed that can make full use of this new information resource.
Although methods for searching for conserved features in coding regions of genes have improved, more than 60% of P. falciparum genes do not yet have identifiable paralogs or orthologs
in genome databases. Furthermore, the analysis of N-terminal
signal sequences of predicted P. falciparum gene products with
available computer programs does not allow any prediction of
their actual sub-cellular localisation. One major aim of our project is to investigate at the molecular level the interaction of proteins involved in the vesicular transport which plays a part in the
secretory pathway, and to identify transported proteins. Results
will lead to a better understanding of the cell biology of the parasite, and to the identification of novel proteins located at the
interface between host and parasite, which could be prime candidate targets for vaccine development.
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Seite 21
For the identification of novel secreted and trans-membrane
proteins of P. falciparum we have developed a functional
screening system based on transformation of the yeast
Hansenula polymorpha with constructs coding for fusion proteins. These constructs consist of about 100 amino acids of the
N-terminal sequences of putative open reading frames (ORF)
derived from the P. falciparum genome project, and the reporter
protein GFP (green fluorescent protein). We found that P. falciparum sequences representing functional signal peptides could
be recognised by the secretory apparatus of the yeast and this
could then guide the fusion proteins to different sub-cellular
compartment(s) detectable under the microscope.
Validation experiments with sequences from well characterised malaria proteins demonstrated that H. polymorpha tolerates the A-T rich codon usage of P. falciparum, and that the
expressed fusion proteins encompassing known signal
sequences of P. falciparum and GFP appeared to be recognised by the secretory apparatus of the yeast. We have now
started to analyse fusion proteins containing N-terminal
sequences encoded by newly-predicted P. falciparum ORF. We
concentrated at this stage on ORFs that in silico (i.e. based on
predictions using sequence analysis with special computer
software) showed signal sequences in at least one of the three
signal prediction algorithms currently available. About ten fusion
proteins tested were found to be located in vesicular structures
in the transformants. A first ORF has been expressed in E. coli,
and mAbs have been raised against the recombinant protein for
the determination of the sub-cellular localisation and stage specific expression of the predicted protein.
Identification and characterisation of a conserved, stage
specific gene product of P. falciparum that induces antibodies
that inhibit parasite growth
We have identified a novel conserved protein, designated D13,
which is expressed in asexual blood-stages of Plasmodium falciparum. The predicted ORF D13 contains 863 amino acids with
a calculated molecular mass of 99.7 kDa. When the D13 amino
acid sequence of P. falciparum was compared to that of close
protein counterparts (orthologs) from P. knowlesi and P. yoelii,
sequence identities were 38% and 41%, respectively. The alignment of deduced amino acid sequences revealed that a repeat
region with twelve consecutive repeats of the pentamer motif
K/RN/SD/ENI/M/T exists in D13 of P. falciparum, but not in D13
of other Plasmodium species. A stretch of 139 amino acids from
the N-terminal end was expressed in E. coli, and the purified
protein was used to generate anti-D13 mAbs. These recognised
one band of about100 kDa in Western blot analysis of total parasite lysates.
Western and Northern blot analyses of lysates of synchronised blood stage parasites showed that D13 is highly
expressed at both mRNA and protein levels during schizogony,
declines rapidly in early ring stages, and is undetectable in the
trophozoite. An immunofluorescence assay using con-focal
microscopy showed that the protein was highly expressed during schizogony, and was detectable in a distinct area in individual merozoites. Inclusion of anti-D13 mAb in in vitro blood stage
cultures of P. falciparum reduced parasite growth by about 45%.
A search of the PlasmoDB database and of sequences of the
parasites Theileria annulata and Theileria parva which, like Plasmodium, have apical complexes, revealed that a domain
encompassing the N-terminal 156 amino acids of D13 is highly
conserved between P. vivax, P. knowlesi, P. yoeli, P. falciparum,
T. parva and T. annulata. Hence, D13 might represent a member
of a protein family functional in several apicomplexan parasites.
The N-terminal domain of D13 includes ten strictly-conserved
cysteine residues, which are indicative of a complex domain
structure.
The involvement of glyceraldehyde-3-phosphate dehydrogenase
(GAPDH) in the secretory pathway of P. falciparum
An in vitro transcription-translation-translocation assay suggested that GAPDH of P. falciparum is associated with the cell
membrane. We have cloned and recombinantly expressed this
protein. When mAbs were raised against the recombinant protein they showed no cross-reactivity with human GAPDH.
Spatial and temporal changes in the distribution of both
GAPDH and another glycolytic enzyme, aldolase, were
observed in liver and asexual blood-stages of P. falciparum by
indirect immunofluorescence microscopy. Aldolase and GAPDH
co-localised in the cytosol during the ring and trophozoite
stages, whereas during schizogony only GAPDH was enriched
in the periphery of the parasite. In merozoites it was strongly
polarised towards the apical pole. The mechanism associated
with this change in distribution was investigated using a quantitative binding assay that measures recruitment of GAPDH to
HeLa cell microsomal membranes in the presence of the small
GTPase Rab2. Microsomal membranes treated with Rab2
showed a 5-fold increase in the level of membrane-associated
parasite GAPDH, indicating that the Rab2-dependent recruitment of cytosolic components to membranes is conserved in
evolution. Two overlapping fragments of GAPDH (residues
1–192 and 133 – 337) were evaluated in the microsomal binding
assay. We found that the N’-terminal 133 amino acids of GAPDH
competitively inhibited Rab2-stimulated GAPDH recruitment to
the membrane and, more importantly, contained the domain
required for membrane-binding.
These combined results suggest that GAPDH has non-glycolytic functions in P. falciparum, including roles in vesicular
transport and in the biogenesis of apical organelles. These nonglycolytic functions as well as the potential of GAPDH as a drug
target are currently being investigated.
Immunofluorescent staining of P. falciparum parasites by mABs specific for
GAPDH (a) and RAP-1 (b). The distribution of the two proteins in the parasite cell
is shown clearly by (c), in which the first two images are overlaid.
(Source: C. Daubenberger)
Scientists:
C. Daubenberger, M. Müller, G. Pluschke
Technologists:
M. Curcic, J.-P. Dangy
Students:
D. Diaz (PhD), N. Pfeiffer (MSc)
Collaboration:
RheinBiotech, Düsseldorf, Germany (U. Dahlems); Vienna
International Research Cooperation Center, Austria (J. Lipp);
Wayne State University, Detroit, USA (E. Tisdale); INSERM,
Immunobiologie Cellulaire et Moléculaire des Infections Parasitaires, Paris, France (O. Silvie, D. Mazier); Hoffmann-La
Roche, Basel (B. Bohrmann, U. Certa, H. Matile)
Funding:
SNSF
21
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3.3
Analysis of immune responses of the Aotus monkey,
an experimental infection model for Plasmodium
falciparum malaria
The New World monkey genus Aotus is recommended by WHO
as an experimental model for P. falciparum blood stage infections, and is used for the evaluation of candidate malaria vaccines. We are characterising elements of the Aotus immune
system to facilitate detailed analyses of induced immune
responses. In addition to TCR, MHC and Ig genes, we have
recently characterised Aotus T cells. These T cells are
thought to play crucial roles during early immune responses to
pathogens. A subset of human T cells carrying the V9V2
TCR recognise small, phosphorylated non-peptidic antigens.
However, the precise role of these cells in human immune
responses against pathogens, and the role of the ligands they
recognise, remain unclear because of the lack of suitable animal models (similar reactivities have not been found in mice).
We have analysed the reactivity of spleen cells of the New
World monkey Aotus nancymaae against isopentenyl pyrophosphate (IPP), a phosphorylated microbial metabolite that selectively activates V9V2 T cells. Spleen cells were stimulated by
IPP, and the expanding cell population expressed the V9 TCR.
TRGV-J and TRDV-D-J rearrangements. These were similar in
Aotus and human T cells with respect to TCR gene segment
usage, the diversity of the CDR3 regions, and a high degree of
germ line sequence homology of the TCR gene segments
employed. Phylogenetic analysis of gene segments from
human, Pan troglodytes and Aotus nancymaae TRGV showed
that the inter-species differences are smaller than the intraspecies differences. The TRGV9 gene segments are located on
a distinct clade of the phylogenetic tree. The structural and
functional conservation of V9V2 T cells in Aotus nancymaae
and humans implies a functionally important and evolutionarily
conserved mechanism for recognition for phosphorylated microbial metabolites.
Scientists:
C. Daubenberger, G. Pluschke
Students:
D. Diaz (PhD), B. Hübner (ATA), M. Salomon (MSc)
Collaboration:
Fundación Instituto de Inmunología de Colombia (FIDIC),
Universidad Nacional de Colombia, Bogotà, Colombia,
(R. Rodriquez, M. E. Patarroyo, W. Vecino)
3.4
Conjugate vaccines against epidemic meningococcal
meningitis in Africa
The highest number of cases and the highest burden of
meningococcal disease in the world are in sub-Saharan Africa,
in an area that is referred to as the meningitis belt. Thirteen different serogroups of meningococci have been identified, each
expressing a different capsule polysaccharide. Bacteria of serogroup A have historically been the main cause of epidemic
meningococcal disease. Within the meningitis belt, meningococcal disease occurs in epidemic cycles that last between
8 and 15 years. Epidemics start in the dry season and decline
rapidly with the arrival of the rainy season. The mechanisms that
cause the epidemic cycles are not well understood.
In 1998, we started to analyse the dynamics of carriage of
Neisseria meningitidis and N. lactamica in the KassenaNankana District in northern Ghana. In a continuing field survey,
37 dwelling-compounds randomly selected from a complete list
22
The bacteriology laboratory of the
Navrongo Health Research Centre,
Ghana. (Source: G. Pluschke)
of the district population (Navrongo Demographic Surveillance
System) are visited 6-monthly (once in the dry season and once
in the wet season of each year), and all the people present in
these compounds at the time of the visit are monitored for Neisseria carriage (total about 300). The studies have provided
information on longitudinal patterns of colonisation with multiple
types of N. meningitidis and N. lactamica, and spatio-temporal
patterns of colonisation and disease during and before a potential new epidemic. The purpose of the studies is to determine
whether patterns of carriage during inter-epidemic and pre-epidemic periods can help to elucidate the precipitating factors of
major epidemics of meningococcal meningitis, and to provide
background information to underpin envisioned clinical trials in
Africa of a meningococcal vaccine in which a capsule polysaccharide is conjugated with a carrier protein.
Our data indicate that in contrast to Europe and the USA, carriage of non-encapsulated meningococci and other non-pathogenic meningococci is infrequent in Africa. Carriage of such
non-serogroupable meningococci may protect against meningococcal disease, by eliciting cross-reactive immunity against
pathogenic strains. The low levels of carriage in Africa may thus
increase people’s susceptibility to epidemics.
After an epidemic of N. meningitidis serogroup A in the
Kassena-Nankana District in 1997, carriage of serogroup A
decreased. For a period of about two years no serogroup A
meningococci were isolated, either from cases or from carriers.
However, a new serogroup A outbreak is now being observed.
Since only four years have passed, this indicates that the
decline in “herd immunity” may not be the crucial factor determining the time intervals between epidemics. Molecular typing
revealed that the current outbreak is caused by a different
serogroup A clone from that causing the previous epidemic.
This clone, with sequence type 7, was observed for the first time
in Africa in 1995. The previous outbreak was caused by a clone
with sequence type 5, which first caused an epidemic in Mecca
in 1987, and subsequently spread through the meningitis belt of
Africa.
Between the two outbreaks, a fulminating increase in the
number of carriers of serogroup X meningococci was observed,
coinciding with a number of cases of meningitis caused by
meningococci of this serogroup, which until now have been
regarded as largely apathogenic. Multilocus sequence typing
and pulsed-field gel electrophoresis of the serogroup X organisms indicated a close relationships with other strains isolated in
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Africa during recent decades, but detailed genetic analysis
shows that further microevolution had occurred after they
arrived in the district. Meningococci of group X are pathogenic,
but it is not clear whether they have the potential to cause epidemics. (W135 meningococci, which had not previously been
associated with epidemics, were the cause of a recent epidemic in Burkina Faso with an unusually high mortality rate.)
The recent increase in outbreaks caused by meningococci of
serogroups other than A and C may reflect a replacement of
these serogroups with others as a result of mass vaccination
with serogroup A/C carbohydrate vaccine. One of the aims of
our surveys is to investigate whether vaccination could be leading to the replacement of one serogroup by another, as has
already been observed for pneumococci. If this is happening, it
has major implications for the development of meningococcal
conjugate vaccines for Africa.
Because the currently available unconjugated serogroup A
capsule polysaccharide vaccine is not very satisfactory, as it
does not induce long-lasting immunological memory and is not
sufficiently immunogenic in young children, a vaccine is being
developed in which the capsule polysaccharide is conjugated
to a carrier protein. This vaccine is expected to be more effective. However, experience with conjugate vaccines against
Haemophilus and pneumococci indicates that a vaccine of this
type would probably have a far more profound effect on
serogroup A colonisation than the unconjugated vaccine. Its
introduction must, therefore, be accompanied by investigations
that can detect potential serogroup replacements.
Plans for the clinical evaluation of meningococcal conjugate
vaccines in northern Ghana are currently being pursued,
together with the Meningitis Vaccine Project (MVP), a partnership between the WHO and the Program for Appropriate Technology in Health (PATH). Our studies are providing essential
baseline information for these trials.
Scientists:
B. Genton, G. Pluschke, T. Smith
Technologists:
J.-P. Dangy, M. Naegeli
PhD students:
S. Gagneux, A. Hodgson, J. Leimkugel
MSc students:
E. Arnold, C. Flierl
Collaboration:
Navrongo Health Research Centre, Navrongo, Ghana;
Max-Planck-Institut für Molekulare Genetik, (M. Achtman); University of Würzburg, Germany (I. Ehrhard)
Funding:
Meningitis Research Foundation, Bristol, UK; Stanley
Thomas Johnson Foundation, Berne, Switzerland;
Dept. of Education, Canton Basel-Stadt (scholarship)
3.5
Mycobacterium ulcerans infections: prospects for
vaccine development and serodiagnosis
In Ghana and many other regions of West Africa the incidence
of Mycobacterium ulcerans infections (Buruli ulcer) is increasing. This emerging infectious disease of the skin and subcutaneous tissues affects mainly poor people living in rural areas,
mostly children under 15. The disease starts as painless
swellings in the skin which later break down into ulcers. In the
absence of early surgical intervention, the disease often ends in
crippling deformities, loss of organs such as the eye, disability
or death. The socio-economic impact of Buruli ulcer on rural
economies is substantial, and the disease has been recognised
by the World Health Organisation as one of the diseases of
poverty.
The mode of transmission and the risk factors for infection
are uncertain, although globally the disease has been found to
be associated with riverine and wetland environments. There is
no known primary preventive measure to control the disease.
Further, there is no effective drug treatment; the only currently
accepted treatment is “wide” surgical excision of the lesions, to
remove all infected tissue.
Surgical treatment of Buruli ulcer by “wide excision”. (Source: G. Pluschke)
Even after ulcers have healed, permanent handicaps remain.
(Source: E. Mensah-Quainoo)
In accordance with the research priorities of WHO, the goals of
our research are i) to understand the transmission of M. ulcerans better, ii) to evaluate possibilities of developing methods for
early diagnosis, and iii) to investigate prospects for vaccine
development.
For microepidemiological analyses we are developing
molecular-biological tools which should allow us to differentiate
between closely related M. ulcerans isolates coming from the
same area. These tools should allow us to map the spreading of
genetic variants in time and space, and to identify environmental reservoirs relevant for infection.
There is a broad antigenic overlap between mycobacterial
species. This complicates the analysis of adaptive immune
responses to M. ulcerans, and also hampers the development
of specific serodiagnostic tests for M. ulcerans that would be
suitable for areas where TB is also endemic. However, the
immunological cross-reactivity may be advantageous to people
exposed to M. ulcerans, as there is evidence of an association
between BCG vaccination and a lower incidence of M. ulcerans
disease. This has raised interest in the nature of the cross-reactive immune responses.
23
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Seite 24
In spite of a profound T cell anergy to mycobacterial antigens, patients with M. ulcerans infection seem to be able to
raise antibody responses against a broad range of M. ulcerans
antigens. Our Western blot analyses demonstrated heterogeneous antibody responses in sera from M. ulcerans patients
from the Ga district in southern Ghana. Comparisons of reaction
patterns of these patient sera with lysates of M. ulcerans, M.
tuberculosis, M. marinum and BCG indicate that a small proportion of antibodies recognised non-cross-reactive M. ulcerans
antigens. However, the complexity of the reaction patterns complicates the identification of these M. ulcerans specific antigens.
To dissect the humoral immune response, we have started to
generate panels of monoclonal antibodies (mAbs) against M.
ulcerans antigens. We observed that the nature of humoral
immune responses of mice to M. ulcerans antigens strongly
depends on the procedure used. This facilitates the generation
of mAbs against a broad range of antigens. Some immunisation schedules predominantly induced broad cross-reactive
humoral immune responses, and in other cases, antibodies
reacted either with both M. ulcerans and M. marinum, or only
with M. ulcerans. Among the first mAbs isolated, both crossreactive and non-cross-reactive specificities were observed.
Antibodies with the same specificities can also be identified in
patient sera.
The description of the complete M. ulcerans genome will
soon be available and will facilitate identification of the antigens
recognised by these mAbs. Characterisation of antigenic structures unique for M. ulcerans will contribute to an understanding
of host-pathogen interaction and help to investigate the feasibility of developing an assay for early diagnosis of M. ulcerans disease which can be used in the field. In the long run, these studies may also support development of a M. ulcerans vaccine.
Factors which speak for the feasibility of a vaccine include i) the
largely extracellular nature of the infection, ii) the contribution
of an immunosuppressive toxin to pathogenesis (offering
the prospect of breaking immune suppression with a vaccine),
iii) evidence for a (limited) protective effect of BCG vaccination
against Buruli ulcer, and iv) evidence for occasional spontaneous healing, which may be associated with adaptive immunity.
Scientist:
G. Pluschke
Technologist:
J.-P. Dangy
Students:
V. Christen (MSc), D. Diaz (PhD), S. Rondini (PhD)
Collaboration:
Ga District Health Management Team, Ghana MOH (E. Mensah-Quainoo); School of Public Health, University of Ghana,
Accra (F. Binka); Noguchi Memorial Institute for Medical
Research, Accra, Ghana (D. Yeboah-Manu); Institute for Infectious Diseases, University of Berne, Switzerland (T. Bodmer)
Funding:
24
Stanley Thomas Johnson Foundation, Berne, Switzerland;
Department of Education, Canton Basel-Stadt (scholarship)
Publications:
Daubenberger C, Nickel B, Hübner B, Siegler U, Meinl E & Pluschke G (2001)
Herpesvirus saimiri transformed T cells and peripheral blood mononuclear cells
restimulate identical antigen-specific human T cell clones. J Immunol Methods
254, 99 –108.
Daubenberger CA, Nickel B, Ciatto C, Grütter M, Pöltl-Frank F, Rossi L, Siegler U,
Robinson J, Kashala O, Patarroyo ME & Pluschke G (in press) Amino acid dimorphism and parasite immune evasion: cellular immune responses to a promiscuous
epitope of Plasmodium falciparum Merozoite Surface Protein-1 displaying dimorphic amino acid polymorphisms are highly constrained. Eur. J. Immunol
Daubenberger CA, Salomon M, Vecino W, Hübner B, Troll H, Rodriquez R, Patarroyo ME & Pluschke G (2001) Functional and structural conservation of V9V2
T cells in Aotus nancymaae, a primate infection model for Plasmodium falciparum
malaria. J Immunol 167, 6421– 6430.
Diaz D, Daubenberger CA, Zalac T, Rodriguez R & Patarroyo ME (2002) Sequence
and expression of MHC-DPB1 molecules of the new world monkey Aotus
nancymaae, a primate model for Plasmodium falciparum. Immunogenetics, 54,
251– 259.
Gagneux S, Hodgson A, Smith T, Wirth T, Ehrhard I, Morelli G, Genton B, Binka F,
Achtman M & Pluschke G (2002) Prospective study of a serogroup X Neisseria
meningitidis outbreak in northern Ghana. J Infect Dis 185, 618 – 626.
Gagneux S, Hodgson A, Wirth T, Ehrhard I, Morelli G, Kriz P, Genton B, Smith T,
Binka F, Pluschke G & Achtman M (2002) Clonal groupings in serogroup X Neisseria meningitidis. Emerg Infec Dis 8, 462 – 466.
Hodgson A, Smith T, Gagneux S, Adjuik M, Pluschke G, Mensah NK, Binka F &
Genton B (2001) Risk factors for meningococcal meningitis in northern Ghana.
Trans R Soc Med Hyg 95, 477– 480.
Hodgson A, Smith T, Gagneux S, Akum ah I, Adjuik M, Pluschke G, Binka F & Genton B (2001) Survival and sequelae of meningococcal meningitis in Ghana. Int J
Epidemiol 30, 1440 –1446.
Kashala O, Amador R, Valero V, Moreno A, Barbosa A, Nickel B, Daubenberger
CA, Guzman F, Pluschke G & Patarroyo ME (2002) Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide
vaccine SPf66 combined with the immunological adjuvant QS-21. Vaccine 20,
2263 –2277.
Lioy E, Suarez J, Guzman F, Siegrist S, Pluschke G & Patarroyo ME (2001) Synthesis biological and immunological properties of cyclic peptides from Plasmodium
falciparum Merozoite Surface Protein-1. Angew Chem Int Ed Engl 40, 2631– 2635.
Moreno R, Jiang L, Moehle K, Zurbriggen R, Glück R, Robinson JA & Pluschke G
(2001) Exploiting conformationally constrained peptidomimetics and an efficient
human-compatible delivery system in synthetic vaccine design. Chembiochem 2,
838 – 843.
Moreno R, Pöltl-Frank F, Stüber D, Matile H, Mutz M, Weiss N & Pluschke G (2001)
A rhoptry-associated protein 1-binding monoclonal antibody raised against a heterologous peptide sequence inhibits Plasmodium falciparum growth in vitro. Infect
Immun 69, 2558 –2568.
Pfeiffer B, Moreno R, Moehle K, Zurbriggen R, Glück R, Pluschke G & Robinson
JA (2001) Application of protein epitope mimetics in vaccine design. Chimia 55,
334 – 339.
Zhu P, van der Ende A, Falush D, Brieske N, Morelli G, Linz B, Popovic T, Schuurman IG, Adegbola RA, Zurth K, Gagneux S, Platonov AE, Riou JY, Caugant DA,
Nicolas P & Achtman M (2001) Fit genotypes and escape variants of subgroup III
Neisseria meningitidis during three pandemics of epidemic meningitis. Proc Natl
Acad Sci USA 98, 5234 – 5239.
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SECTION 4
Parasite Chemotherapy
Introduction
passed phase I clinical trials successfully, and is now undergoThe research area Parasite Chemotherapy comprises activities
ing a phase II trial in sleeping sickness patients in the Democrain drug discovery and development of drugs. The main area of
tic Republic of Congo.
concentration is on chemotherapeutic agents against protozoan
The Eastern Africa Network for Trypanosomosis (EANETT),
parasites, but studies have also been carried out on the
which comprises national institutes from Uganda, Kenya, Tanzachemotherapy of schistosomiasis. Besides working on new
nia and Sudan, with the STI as a backup institution, started its
drugs, the group is also maintaining the long tradition of work on
activities at the beginning of 2001, with funding from the Swiss
trypanosomosis in the STI with a variety of activities, often in colDirectorate for Development and Co-operation (SDC). Many of
laboration with partners in Switzerland or in Africa. These
the problems associated with the spread of sleeping sickness in
include laboratory studies of the molecular biology of parasite
eastern Africa can best be tackled by an international group
development in the tsetse fly and the transmission of parasites,
working together. For example,
and initiating and supporting a
there is a need to know more
network of African partners to
Gates Found.
WHO
about the spread of resistance
carry out collaborative projects
and of the risk of the two forms of
in sleeping sickness research
EU
Companies
SDC
human disease, caused by Tryand control.
panosoma brucei gambiense
Activities in drug discovery
DRUG DISCOVERY
EANETT
and T.b.rhodesiense, spreading
have been intensified during the
Screening
Collaboration with African
partners
Lead optimisation
and
overlapping. Apart from
last two years by adding new
Isolation of T. b. gambiense
Preclinical evaluation
research, the aims of the network
projects to the portfolio of
Melarsoprol resistance
Basic research
WHO stabilate bank
include increasing research
ParaScreen, the STI Screening
capacity by training and technolCentre. A new project called
Uni Basel students
Uni Strasbourg
ogy transfer in field and laboradUTPase as a drug target for the
tory methodologies, and assistcontrol of protozoal and bacterial
MMV
TSETSE TRANSMISSION
ing young scientists to obtain
infections emerged from the
Uni Bern
Screening
Procyclins
higher degrees. EANETT has
European COST B9 action, and
Lead optimisation
GPI-anchor
been given international recogniis now receiving financial supPreclinical evaluation
Defense peptides
Mode of action
Drug resistance
tion by WHO, the International
port from the EU framework proUni Osaka
Scientific Council for Trypanosogramme. A consortium including
miasis Research and Control
the STI and the Universities of Project overview.
(ISCTRC) and the Programme
North Carolina and Georgia,
against African Trypanosomiasis (PAAT). As a young network it
supported by the Gates Foundation, is carrying out a project
still has to prove that it is functional and viable. An important
to develop novel drugs against sleeping sickness. In addition
step will be the acquisition of additional funds to maintain its
to these projects, screening of drugs from various sources
research and training activities. New institutions from neighhas continued. Collaboration with TDR/WHO Drug Discovery
bouring countries are expected to join as full or co-opted memResearch was consolidated, and contacts with private industry
bers.
could be improved.
Fundamental research on tsetse fly transmission of tryThe Medicines for Malaria Venture (MMV) Foundation is suppanosomes has continued. In a fruitful collaboration with the
porting the project Synthetic peroxides, which has made
Institute of Molecular Biology of the University of Berne, genetitremendous progress during the last two years. In our last report
cally modified trypanosomes have been used to elucidate the
(STI 1999 –2000) we described work on promising trioxolane
biological role of different parasite surface proteins in the estabcompounds of the OZ series. We have now been able to
lishment of the parasite in the vector. A similar collaboration was
improve their oral bioavailability as well as their metabolic stabilcontinued with Osaka University, Japan, on the anchoring of
ity and pharmacokinetic properties. These compounds now
surface proteins, using a similar approach (knockouts and overhave an in vivo efficacy higher than that of the semi-synthetic
expression). A project with the Institute of Molecular and Celluartemisinins. Early in 2003 the consortium with partners from
lar Biology in Strasbourg, France, investigated host defence
Nebraska University, Omaha, USA; Monash University, Victoria,
molecules produced by insects in response to infection with
Australia, and STI and Hoffmann-La Roche in Basel, will select
protozoan parasites.
three compounds for clinical studies.
Our tsetse facility is one of the very few laboratories in Europe,
The search for new chemotherapeutic agents against tryand the only one in Switzerland, where transmission experiments
panosomosis continues to be of great importance. The drugs
with African trypanosomes in their natural vector can be peravailable are old and ineffective, and the number of treatment
formed, and we want to ensure that we maintain a “critical mass”
failures with melarsoprol, still the major first line treatment, is
of personnel with the expertise to carry out this work. Alongside
increasing. The project supported by the Gates Foundation has
our projects on drug development, and our collaborative studies,
already made rapid progress in developing a promising new
we plan to develop our own programme of research in the area
group of drugs, the diamidines. Guided by analysis of structureof vector-parasite interactions, which will not only add to our
activity relationships, diamidines could be identified which are
understanding of the basic biology of infection, but offer a
highly active both in vitro and in rodent models. The lead comchance to find new molecules with antiprotozoal activity.
pound DB 289 is an orally available prodrug which has already
25
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4.1
Drug discovery and evaluation of new antiprotozoal
compounds (ParaScreen Screening Centre)
The ParaScreen Screening Centre was consolidated during the
last two years by involvement in major drug discovery and
development consortia: the MMV project Synthetic Peroxides
(4.2); the Gates Foundation supported project Diamidines as
new drugs for sleeping sickness, and the EU-funded project
dUTPase as a drug target for the control of protozoal and bacterial infections. Interesting links could be established to pharmaceutical industries. The integrated in vitro drug screening in
96-well microtiter plates with end-point determinations based on
photometric or fluorometric reading or liquid scintillation counting was further improved and additional animal models were
introduced.
For all assays and animal models, Standard Operational Procedures (SOPs) have been established and data for reference
drugs are available. For the African trypanosomes and Plasmodium spp. flow sheets describe the sequence of assays/tests
and the exclusion criteria. For data management, EXCEL sheets
were developed for internal use and for reporting to the various
consortia and suppliers of compounds. TDR/WHO maintains a
data bank where the results from our screening centre as well as
those of other screening centres are compiled.
Compounds for our general screening were obtained from
different sources: through TDR/WHO Drug Discovery Research,
from collaborating chemists/phytochemists/pharmacists in the
frame of the European COST B9 Action, Antiparasitic
Chemotherapy, and from various pharmaceutical companies.
We screened about 1000 compounds annually in vitro, most of
them against the 4 protozoan parasites, and tested them on
mammalian cells for cytotoxicity. Compounds which fulfilled the
given criteria were tested in the corresponding animal model
except for substances active against T. cruzi and L. donovani
which were sent to another screening centre for in vivo evaluation.
In vitro screening assays
Trypanosoma b. rhodesiense/T. b. gambiense
T. b. brucei multi-drug resistant strain
Trypanosoma cruzi
Leishmania donovani
Plasmodium falciparum (various strains)
human and animal cell lines
The animal models
acute T. b. rhodesiense (STIB 900), T. b. brucei (STIB 795)
chronic CNS model T. b. brucei (GVR35)
T. b. gambiense model (STIB 754) in SCID mice
P. berghei model (ANKA strain)
Schistosoma spp. models
Orally-available diamidines
Only a very limited number of drugs is available for treatment of
sleeping sickness and none of them are applicable by the oral
route. An international consortium was funded by the Bill &
Melinda Gates Foundation to carry out research on di-cationic
compounds active against trypanosomes and Leishmania, and
26
to bring a selected compound to registration. The new molecules are synthesised at the universities of North Carolina and
Georgia, and their biological activity is investigated in the STI
and at the London School of Hygiene and Tropical Medicine
(LSHTM). Preclinical and clinical studies are managed by
Immtech International (Chicago) in collaboration with the Pharmaceutical Medicine Unit (PMU) in the STI.
R2
R1
O
Y1
Y2
General structure of diphenyl furans.
In the last 18 months we screened over 300 compounds in
vitro. Activity against African trypanosomes was excellent and
could constantly be improved to IC50 values below 1 ng/ml.
Compounds with activity against T.b.rhodesiense were tested in
the acute STIB 900 mouse model using a 4-day intraperitoneal
treatment with the highest tolerated dose. We found that STIB
900 is very hard to cure, despite the fact that the trypanosomes
are susceptible to all known drugs. After disappearance of parasitaemia the treated mice relapsed at times up to 30 days after
treatment. The untreated controls died around day 7 post-infection. We then evaluated several T.b.brucei strains to find a
model which could be cured more easily. STIB 795 (= S427)
could be cured by all those compounds which in the STIB 900
model had only extended survival. Based on these findings we
changed our flow chart, introducing STIB 795 for primary in vivo
screening and the more stringent STIB 900 for secondary
screening. Up to now, we have identified 7 compounds which
gave 100% cure of mice infected with T.b.rhodesiense STIB
900. A further 9 compounds resulted in cure of 3 out of 4 mice.
Some of the compounds are prodrugs which can be given orally
since they are well absorbed by this route. In the blood, the prodrugs are metabolised to active metabolites. Such orallyabsorbed prodrugs also have the potential to cross the bloodbrain barrier, a prerequisite for a drug for second stage disease.
One compound of this series, DB 289, a diaminophenylfuran, is a lead compound which had already reached the stage
of clinical trials in Africa. It is a prodrug with oral bioavailability
which could cure acute infections of T.b.rhodesiense in mice
and African green monkeys. The monkey experiments were carried out at the Primate Unit of KETRI, Nairobi, in collaboration
with our laboratory, the University of N. Carolina and Immtech,
Chicago. DB 289 has now successfully undergone preclinical
testing, including confirmation of efficacy in monkey experiments, and phase I trials in healthy volunteers, and the Pharmaceutical Medical Unit of the STI is now carrying out phase II clinical trials in 1st stage sleeping sickness patients (11.2).
Subsequent in vitro and in vivo screening has revealed several compounds which are even more effective than DB 289.
The chemists are now trying to produce prodrugs of those molecules to facilitate oral bioavailability. The mode of action of the
compounds is also being studied, especially the interaction with
DNA which might cause toxicity problems.
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Pharmacokinetics of diamidines
Within the “Diamidine project” a Ph D project (S. Bernhard) was
initiated to establish the pharmacokinetics of selected lead
compounds in the mouse model and to elucidate the phenomenon of relapse after treatment. It was observed that mice
infected with STIB 900 and treated with these novel diamidines
relapsed 2– 3 weeks after treatment, a situation which is comparable to the situation in human patients after melarsoprol treatment. The project also aims at identifying the tissue compartments where the trypanosomes are “hiding” during treatment.
Prime candidates are the CNS and other deep tissues where the
parasites are not easily accessible to the drugs. These studies
could lead to a better understanding of the distribution of trypanosomes and of drugs during infection and treatment.
Testing of new compounds against other parasites
One of the major pathogens of livestock is Trypanosoma evansi,
which causes the disease surra in horses, camels, water buffaloes and cattle in different parts of the world. Therefore we
also tested some of the active compounds against T. evansi,
both in vitro and in a mouse model. Infected mice could be
cured with a total dose <1 mg/kg given over 4 days.
The 300 compounds tested against trypanosomes were also
tested against the other protozoan parasites included in our routine test panel. Fewer compounds were active against T. cruzi
and L. donovani than against the African trypanosomes, and the
IC50 values were not as low. The most promising compounds
were tested in mouse models at the LSHTM. Many of the compounds also proved to have excellent in vitro activity against
P. falciparum. We are currently testing the most active ones in
the P. berghei mouse model in the STI and in the P. chabaudi
model in the UK.
sites, which can be developed into new drugs for diseases
caused by trypanosomes, leishmanias and plasmodia.
Medicinal plants
In the frame of a PhD project (M. Senn) medicinal plants from
Tanzania were collected and crude extracts prepared with solvents of different polarities. This is a collaboration between the
STI, the Institute of Organic Chemistry of the University of Basel,
and the University of Dar es Salaam, Tanzania. The plants were
selected on the basis of ethnopharmacological information and
previous phytochemical work performed in our group. The aim
is the identification of novel antiprotozoal lead compounds
which can be exploited in lead optimisation programmes.
Other collaborations with phytochemists in Europe, Africa,
Asia and South America aimed at isolating pure compounds
with antiparasitic activity from medicinal and other plants. Collaboration with the University of Barcelona on alkaloids and with
the University of Würzburg, Germany on naphthylisoquinoline
alkaloids from tropical lianas proved to be productive and led to
the discovery of novel molecules with promising antimalarial
and antileishmanial activities. The phytochemical approach
offers interesting possibilities of discovering new active molecules which can be taken as starting point for analogue synthesis with the aim of improving the efficacy and pharmacological
properties of the molecule.
Scientists:
R. Brun, M. Kaiser
Technologists:
J. Easterbrook, E. Gobright, G. Riccio, C. Scheurer
PhD students:
S. Bernhard, M. Senn
Collaborations:
LSHTM, London, UK (S. L. Croft); Freie Universität Berlin, Germany (O. Kayser); University of North Carolina, Chapel Hill,
USA (R. Tidwell & J. Ed. Hall); Georgia State University, USA
(D. Boykin); University of Washington, Seattle, USA (F. Buckner); Murdoch University, Perth, Australia (S. Reid); Philadelphia University, Amman, Jordan (S. Khalid); Department of Natural Products, University of Barcelona, Spain (C. Codina &
J. Bastida); Institute of Organic Chemistry, Würzburg, Germany
(G. Bringmann); Universidad Nacional de Cordoba, Argentina
(N. Sperandeo); Institute for Chemistry and Biochemistry,
Prague, Czech Republic (A. Holy); Palacky University, Olomouc, Czech Republic (P. Hradil); University of Hamburg,
Germany (C. Kunick); Madurai Kamaraj University, India
(J. Muthukrishnan); University of Wales, Cardiff, UK (I. Gilbert);
University of Basel (U. Séquin); ETH Zürich (J. Heilmann &
S. Mayr); Kenya Trypanosomiasis Research Institute, Kikuyu,
Kenya; Dr. D. Diallo, Bamako, Mali; TDR/WHO; Actelion,
Allschwil, Switzerland; Glaxo Smith Kline, Madrid, Spain, and
various other companies in Europe and USA.
Funding:
TDR Drug Discovery Research; Government of Switzerland
(participation in COST B9); Bill and Melinda Gates Foundation;
contract work for private customers
dUTPase
The EU-sponsored project dUTPase as a drug target for the
control of protozoal and bacterial infections was initiated at the
beginning of 2002. This is a collaboration between Cardiff University (chemistry), University of York (protein crystallisation),
Instituto de Parasitologia y Biomedicina (cloning of enzymes),
the Swedish pharmaceutical company Medivir, and the STI (biological evaluation of inhibitors). The aim is to identify effective
inhibitors of dUTPase, an essential enzyme in protozoan para-
4.2
PARASCREEN screening laboratory. (Source: M. Kaiser)
The consortium Synthetic peroxides started its MMV project in
mid-2000. The goal is to identify an achiral orally active and
non-toxic compound that is more potent than the semi-synthetic
artemisinins, with a treatment duration of a maximum of three
days and a price below one US$ per course of treatment. The
consortium includes the University of Nebraska, where compounds are synthesised, and Monash University in Melbourne,
where metabolic and pharmacokinetic studies are being done.
Toxicological studies are contributed by Hoffmann-La Roche.
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The role of the STI is the screening and evaluation of compounds in culture and in mouse malaria models.
A total of 297 trioxolanes of the series named OZ were
received for screening from J. Vennerstrom, and during the
last 2 years, 252 compounds were tested in vitro for activity
against Plasmodium falciparum. Most showed good activity,
and 184 compounds had an IC50 value < 5 ng/ml. Of these,
73 had a value < 1 ng/ml. These activities are comparable to
those of the semi-synthetic artemisinins. The 184 compounds
were further tested in the P. berghei ANKA strain mouse model
at 10 mg/kg given by oral and subcutaneous routes in Tween/
ethanol.
New compounds were synthesised in series of 9. The results
of our screening were reported back to the chemists as quickly
as possible. Structure activity relationship (SAR) analysis
enabled the chemists to optimise the molecule to improve activity, oral absorption and pharmacokinetic behaviour. Selection
could also be done to reduce toxicity or to avoid rapid metabolism. As a result of these procedures, the in vivo efficacy of new
series of compounds could be increased constantly. Therefore
a decreased dose of 3 mg/kg given orally could be used.
For secondary in vitro screening a panel of 12 additional
P. falciparum strains was used. The strains originate from different continents and they express chloroquine and/or
pyrimethamine resistance. We determined IC50 values for
selected OZ compounds in three independent assays. The
range of the IC50 values of a given OZ compound for the panel
of strains was between 2 and 6 (mean 4). Two artemisinin
derivatives were used for comparison, and their range was
4.8. This indicated that none of the P. falciparum strains in our
panel of strains had innate resistance to OZ compounds.
Secondary tests for prophylactic activity were performed in
mice. They were treated 1, 2 or 3 days prior to infection and the
blood was examined daily for parasites. The OZ compounds
showed prophylactic activity for up to 72 hours, whereas
artemisinins were protective for less than one day. An “onset
and recrudescence” test was also performed. The onset of drug
action was determined after a single fixed dose at day + 3 postinfection. The reduction of parasitaemia was monitored 6h and
12h after treatment, and the time of recrudescence was
100
80
control
artesunate
OZ 05
Parasitemia (%)
chloroquine
40
OZ 27
mefloquine
20
OZ 209
0
5
10
15
20
25
Time post infection (days)
Infection
Treatment (100 mg/kg orally)
Onset and recrudescence of parasitaemia in mice infected with P. berghei treated
with OZ compounds compared with chloroquine and artesunate.
28
Scientists:
R. Brun, B. Scorneaux, S. Wittlin
Technologists:
J. Chollet, J. Santo Tomas, C. Scheurer, M. Vogel
Collaborations:
University of Nebraska Medical Centre, Omaha, USA (J. Vennerstrom); Monash University, Victoria, Australia (S. & W. Charman); Hoffmann-La Roche, Basel (H. Matile); MMV Headquarters, Geneva.
Funding:
4.3
Use of OZ compounds against schistosomiasis
Schistosomiasis is a very widespread tropical disease, for
which new drugs are also needed. Studies of the effects of
artemether derivatives on schistosomes, described in the last
STI report, have been continued and extended to field trials
(see Section 6.5) The different synthetic peroxides made available through the MMV project were also systematically
screened for their effects on juvenile and adult schistosomes.
The first results are promising. OZ compounds showed a highly
effective schistosomicidal effect against both juvenile and adult
worms, often irrespective of their anti-malarial effect. These
observations offer promising avenues of future research into
new leads for antischistosomal drugs. In contrast to those
tested earlier, the new derivatives of the OZ compounds
showed effects that were different from the effects observed
with artemether. The in vitro schistosomicidal effects, unlike
those of artemether, were not haemin-dependent.
Scientists:
B. Scorneaux, M. Tanner, S. Wittlin
Guest Scientist:
S. H. Xiao
Collaboration:
Office of Population Research, Princeton University, USA
(J. Utzinger); Institute of Parasitic Diseases, Chinese Academy
of Preventive Medicine, Shanghai, PR China (S.H. Xiao);
WHO/TDR (R. Bergquist, R. Ridley)
Funding:
WHO/TDR
OZ 177
60
0
assessed by daily blood smears for 14 days. Administration of
OZ compounds resulted in the disappearance of parasitaemia
within 24 hours. With artemether, in contrast, the mice stayed
aparasitaemic for 3 – 4 days, but then become positive and
died. Mice treated with OZ 27 showed an onset of recrudescence on day 14, comparable to that seen with the standard
drug mefloquine. With OZ 209 the mice stayed aparasitaemic
during the 60-day observation period. We compared treatment
for 3 days with10 mg/kg with treatment on a single day with
30 mg/kg. Giving the same amount distributed over 3 days gave
a higher efficacy than giving it as a single dose.
4.4
Trypanosomosis in eastern Africa and the activities
of the EANETT network
Until the late 1970s there was effective collaboration between
East African countries for research into and control of sleeping
sickness. However, today collaboration on a national level
hardly exists, although many problems really need to be tackled
by an organisation stretching across national boundaries. Collaboration does exist between Kenya and Uganda to control
sleeping sickness along their common border by Lake Victoria,
but there is no co-operation on a national level between Uganda
and Sudan, although these countries share epidemic areas of
T.b.gambiense sleeping sickness, where there are tens of thou-
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sands of patients. In the South of Sudan there is still civil war,
and the only medical services for sleeping sickness patients are
provided by Médecins sans Frontières (MSF) from France and
Switzerland. In Tanzania the number of cases is increasing
especially in the Kigoma area. Population movements could
play a crucial role in the spread of the disease.
One cause of concern is the alarming increase in cases of
relapse after melarsoprol treatment observed in NW Uganda
and S Sudan. For the first 40 years after the introduction of
melarsoprol in 1949 the relapse rate was constant at 2– 5%.
Since the mid 1990s, relapse rates increased in NW Uganda
and S Sudan to over 20%. Similar observations were made in
NW Angola and in certain areas of DR Congo. In relapsed
patients the infection tends to be resistant to further melarsoprol
treatment. For the advanced stage of sleeping sickness the only
drug available besides melarsoprol (Arsobal®) is eflornithine
(Ornidyl®). Eflornithine is not effective against T.b.rhodesiense
and is very expensive. For years it was not available, but now
Aventis is giving the drug (and also melarsoprol and pentamidine) free to WHO. Eflornithine or a combinations of eflornithine
with melarsoprol or nifurtimox (a drug registered for Chagas disease) can normally cure relapsed patients.
In the absence of large-scale international collaboration
between the countries where trypanosomosis is a growing problem, institutions in four East African countries, together with the
STI with its widely-accepted expertise in research in trypanosomosis and tsetse fly transmission, came together to found
the Eastern Africa Network for Trypanosomosis (EANETT) in
November 2000. The STI already had an excellent and longstanding relationship with the Kenya Trypanosomiasis Research
Institute (KETRI), Kikuyu, Kenya, and the Livestock Health
Research Institute (LIRI), Tororo, Uganda. Contacts with scientists working on trypanosomosis in Tanzania and in Khartoum,
Sudan have now been established as well.
Meeting of EANETT members. (Source: EANETT)
EANETT has been awarded core funding for 3 years by the
Swiss Agency for Development and Co-operation (SDC). A
Memorandum of Understanding was signed by all member
institutions. In all member institutions the facilities for communication and information have been improved. An administrative
basis has been established. The network operates a web-site.
EANETT has become a member organisation of the WHO
Steering Committee Treatment and Drug Resistance Network for
Sleeping Sickness, of the International Scientific Council for Trypanosomiasis Research and Control (ISCTRC), and of the Programme Against African Trypanosomiasis (PAAT). Financial
support from WHO was received for surveillance in southern
Sudan, for a sleeping sickness diagnostic training course in
Kinshasa (DRC) and for a Geographical Information System
(GIS) training course in Yaounde (Cameroon). EANETT presented its activities at the 26th ISCTRC Conference in October
2001 in Ouagadougou, and encouraged discussions about the
foundation of a West African Network for Trypanosomosis.
One of the main aims of the network is training and capacity
building. In 2001, two training courses were held at KETRI with
participants from all the network countries. One was a two-week
GIS training course, organised by KETRI staff with additional
tutors from a local company and from WHO, and the other was a
two-week course in Molecular Biology and Entomology. A first
PhD programme as a collaboration between KETRI and STI was
started in June 2002, on melarsoprol resistance in T.b. gambiense from South Sudan. Proposals for further MSc and PhD programmes were submitted to the Board of Management at the
last meeting in Khartoum in June 2002.
Research activities
Some research activities have already started. In all countries
active and passive surveillance of patients has been undertaken. In the last 18 months more than 7000 people were screened,
and villages where sleeping sickness was found were geo-referenced to create a data base which can be used to develop a
risk map. In NW Uganda, blood samples and cerebrospinal
fluid samples from parasitologically confirmed T.b.gambiense
sleeping sickness cases were inoculated in Mastomys natalensis. By this procedure, ten new isolates were obtained and
cryopreserved in liquid nitrogen for subsequent propagation in
tissue culture for molecular characterisation. The isolates will
also be used for drug sensitivity determinations.
Another project is the establishment of a monkey model for
T.b.gambiense, which is not yet available. At the Primate Unit of
KETRI six monkeys (2 vervet, 2 highland and 2 lowland sykes)
have now undergone a quarantine period and are ready for
infection with a T.b.gambiense isolate from Uganda. Two other
new in vivo models for T.b.gambiense have already been established. One uses Grammomys surdaster, a Central African tree
rat. There are some problems with this model. Breeding of the
rats is difficult because of the small litter size, and maintenance
and handling are difficult because they are aggressive and do
not like disturbance. In addition, parasitaemia fluctuated greatly,
from 108/ml to undetectable. The infected rats survived up to 60
days. Another model, which is now recommended, uses SCID
mice, an immuno-deficient breed. The mice show a stable parasitaemia for 7 days post-infection and survive up to 30 days.
Scientists:
R. Brun, M. Kaiser
Technologists:
K. Honegger, M. Oberle, C. Schmid
Collaborations:
Livestock Health Research Institute, Tororo, Uganda; Kenya
Trypanosomiasis Research Institute, Kikuyu, Kenya; Tropical
Medicine Research Institute, Khartoum, Sudan; National Institute for Medical Research, Tabora Station, Tanzania; Tsetse
and Trypanosomiasis Research Institute, Tanga, Tanzania;
Médecins sans Frontières, France and Switzerland (operating
in NW Uganda and S Sudan)
Funding
SDC
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4.5
Tsetse fly transmission studies
The molecular-biological studies of the surface proteins of trypanosomes and their role at different stages in the life-cycle
described in our last report (STI 1999 –2000) have continued,
some in collaboration with other institutions: the University of
Berne, in Switzerland, Osaka University in Japan, and the Institute of Molecular and Cellular Biology in Strasbourg, France.
The aim is not only to obtain a deeper understanding of the parasite and its life-cycle, but also to identify possible new drug targets.
Surface proteins at different stages in the life-cycle
Bloodstream form trypanosomes of T. brucei spp. express variant surface glycoproteins (VSG) on their surface. The procyclic
midgut forms have procyclins as their major surface proteins.
Six genes encode proteins with glutamic acid-proline repeats
(coded EP), and two genes encode proteins with a pentapeptide repeat (coded GPEET). A study showed that different procyclin gene products are expressed in an orderly manner. By
day 3, GPEET2 was the only procyclin detected. By day 7, however, GPEET2 had disappeared and was replaced by several
isoforms of glycosylated EP. Unexpectedly, it was discovered
that the N-terminal domains of all procyclins were quantitatively
removed by proteolysis in the fly, but not in culture. These findings suggest that one function of the protease-resistant C-terminal domain is to protect the parasite surface from digestive
enzymes in the tsetse fly gut. Long slender bloodstream forms
are highly susceptible to the proteases, but not stumpy forms.
Surface proteins are anchored by glycosylphosphatidylinositol (GPI), which is essential for parasite survival. In T. congolense, procyclic forms express a glutamic acid/alanine-rich
protein (GARP) on their surface, which is bound to the membrane by a GPI anchor. Two other molecules are present, also
anchored by GPI. One, a 24 – 34 kDa protein, is a proteaseresistant surface molecule (PRS). The expression of GARP and
the other surface molecules depends on the morphological
form of the trypanosome and the duration of the infection in
the fly. Unexpectedly, 14 days post-infection, procyclic organisms are frequently negative for both GARP and PRS, suggesting that they express another surface antigen at this point in the
life cycle.
The infection rates and the kinetics of procyclin expression of
T. brucei AnTat 1.1 in five different tsetse fly species were
compared (M. Oberle). In the 3 species of the morsitans group
(G.m.morsitans, G. pallidipes and G. austeni) more heavy
midgut infections developed than in the species from the palpalis group (G. palpalis palpalis and G. fuscipes fuscipes).
There was also a difference in the expression of the two types of
procyclins, EP and GPEET: the species of the morsitans group
down-regulated GPEET expression much faster than those of
the palpalis group (day 8 vs. day 12 post-infection). The age of
the flies also influenced the expression pattern, with a longer
expression of both EP and GPEET in older flies compared to
teneral flies.
Immune responses in insect vectors
In collaboration with the Institute of Molecular and Cellular
Biology in Strasbourg, France (N. Boulanger) the immune
responses of Drosophila melanogaster to infection with Crithidia
spp., and of Glossina morsitans to infection with Trypanosoma
b.brucei, were studied. In Drosophila, an oral infection triggered
the synthesis of several antimicrobial peptides. One molecule
was specifically induced in the hemolymph after infection with
Crithidia but not with bacteria, suggesting that the Drosophila
immune system can discriminate between pathogens. In
Glossina morsitans three antimicrobial peptides could be identified: a cecropin, an attacin and a defensin. These peptides
were induced after oral infection or after injection of trypanosomes into the hemolymph.
Transmissibility of drug-resistant trypanosomes
Very little is known about the transmissibility of drug-resistant
trypanosomes. In a pilot experiment we attempted to transmit a
drug-resistant procyclic trypanosome population. 100 tsetse
flies were infected with procyclic forms of T.b. brucei STIB 247
which were made resistant to 1mg/ml suramin, and 100 were
infected with the original (wild) strain. At 15 days post-infection
and then twice a week until day 29 a saliva sample from each
fly was examined for metacyclic forms. Only one fly infected
with the wild type had metacyclic forms in the saliva, and
none that were infected with the resistant type. At day
22 post-infection 3 flies infected with the drug-resistant strain
were dissected. Procyclic trypanosomes could be isolated from
the midgut. These were found still to be drug-resistant. It was
not clear why transmission failed. One reason could have been
that the trypanosomes had lost their infectivity for the vector
because the procyclic forms had been kept for a long period in
culture. For further studies we need trypanosome strains
(including drug-resistant populations) which show a high transmission rate (> 20 % salivary gland infections) in the tsetse fly.
Scientists:
R. Brun, M. Kaiser
Technologist:
C. Kunz Renggli
MSc student:
M. Oberle
Collaborations:
Institute for General Microbiology, University of Bern, Switzerland (I. Roditi, E. Vassella); Osaka University, Japan
(T. Kinoshita); CNRS, Strasbourg, France (N. Boulanger).
Funding:
SNSF (I. Roditi)
A tsetse fly deposits a larva (Stage III). The outer cuticle of the larva hardens and becomes darker. After metamorphosis the adult fly emerges. (Source: STI library, W. Patana)
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Publications:
Abegaz BM, Bezabuh M, Msuta T, Brun R, Menche D, Mühlbacher J & Bringmann
G (2002) Gaboroquinones A and B and 4’-O-Demethylknipholone-4’-O--D-glucopyranoside, Phenylanthraquinones from the roots of Bulbina frutescens. J Nat
Prod 65, 1117–1121
Acosta-Serrano A, Vassella E, Liniger M, Kunz Renggli C, Brun R, Roditi I &
Englund PT (2001) The surface coat of procyclic Trypanosoma brucei: Programmed expression and proteolytic cleavage of procyclin in the tsetse fly. Proc
Natl Acad Sci USA 98, 1513 –1518.
Ankli A, Heinrich M, Bork P, Wolfram L, Bauerfeind P, Brun R, Schmid C, Weiss C,
Bruggisser R, Gertsch J, Wasescha M & Sticher O (2002) Yucatec Mayan medicinal plants: evaluation based on indigenous uses. J Ethnopharmacol 79, 43 – 52.
Boulanger N, Ehret-Sabatier L, Brun R, Zachary D, Bulet P & Imler J-L (2001)
Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp. Insect Biochem Mol Biol 31, 129 –137.
Boulanger N, Brun R, Ehret-Sabatier L Kunz C & Bulet P (2002) Immunopeptides
in the immune reactions of Glossina morsitans to bacterial and Trypanosoma brucei brucei infections. Insect Biochem Mol Biol 32, 369 –375.
Bringmann G, Günther C, Saeb W, Mies J, Wickramasinghe A, Mudodo V & Brun
R (2000) Ancistrolikokines A-C: new 5,8’-coupled naphthylisoquinoline alkaloids
from Ancitrocladus likoko. J Nat Prod 63, 1333 –1337.
Bringmann G, Hamm A, Günther C, Michel M, Brun R & Mudodo V (2000)
Ancistroealaines A and B, two new bioactive naphthylisoquinolines, and related
naphthoic acids from Ancitrocladus ealaensis. J Nat Prod 63, 1465 –1470.
Bringmann G, Wael S, Mies J, Messer K, Wohlfahrt M & Brun R (2000) One-step
oxidative dimerization of genuine, unprotected naphthylisoquinolines alkaloids to
give Michellamines and other bioactive quateraryls. Synthesis 13, 1843 –1847.
Bringmann G, Messer K, Wolf K, Mühlbacher J, Grüne M, Brun R & Louis AM
(2002) Dioncophylline E from Dioncophyllum tholonnii, the first 7,3’-coupled dioncophyllaceous naphthylisoquinoline alkaloid. Phytochemistry 60, 389 –397.
Bringmann G, Menche D, Kraus J, Mühlbacher J, Peters K, Peters E-M, Brun R,
Bezabih M & Abegaz BM (2002) Atropo-enantioselective total synthesis of
knipholone and related antiplasmodial phenylanthraquinones. J Org Chem 67,
5595 – 5610.
Bringmann G, Menche D, Brun R, Msuta T & Abegaz BM (2002) Bulbineknipholone, a new axially chiral phenylanthraquinone from Bulbine abyssinica
(Asphodelaceae): Isolation, structural elucidation, atropo-enantioselective synthesis, and antiplasmodial activity. Eur J Org Chem 1107–1111.
Bringmann G, Messer K, Brun R & Mudogo V (2002) Ancistrocongolines A–D, new
naphthylisoquinoline alkaloids from Ancistrocladus congolensis. J Nat Prod 65,
1096 –101.
Heilmann J, Mayr S, Brun R, Rali T & Sticher O (2000) Antiprotozoal activity and
cytotoxicity of novel 1,7-Dioxadispiro[5.1.5.2]pentadeca-9,12-dien-11-one derivatives from Amomum aculeatum. Helv Chim Acta 83, 2939 –2945.
Herrera MR, Machocho AK, Nair JJ, Campbell WE, Brun R. Viladomat F, Codina C
& Bastida J (2001) Alkaloids from Cyrtanthus elatus. Fitoterapia 72, 444 – 448.
Herrera MR, Machocho AK, Brun R, Viladomat F, Codina C & Bastida J (2001)
Criane and lycorane type alkaloids from Zephyranthes citrina. Planta Med 67,
191–193.
Hofer A, Steverding D, Chabes A, Brun R & Thelander L (2001) Trypanosoma brucei CTP synthetase – a new target for the treatment of African sleeping sickness.
PNAS 98, 6412– 6416.
Kayser O, Kiderlen AF & Brun R (2001) In vitro activity of aurones against Plasmodium falciparum strains K1 and NF54. Planta Med 67, 718 –721.
Klenke B, Stewart M, Barrett MP, Brun R & Gilbert I (2001) Synthesis and biological evaluation of s-triazine substituted polyamines as potential new anti-trypanosomal drugs. J Med Chem 44, 3440 –3452.
Labrana J, Machocho AK, Kricsfalusy V, Brun R, Codina C, Viladomat F & Bastida
J. Alkaloids from Narcissus angustifolius subsp. Transcarpathicus (Amaryllidaceae). Phytochemistry 60, 847– 52.
Mäser P, Grether-Bühler Y, Kaminsky R & Brun R (2002) An anti-contamination
cocktail for the in vitro isolation and cultivation of parasitic protozoa. Parasitol Res
88, 172 –174.
Mäser P, Vogel D, Schmid C, Raez B & Kaminsky R (2001) Identification and characterization of trypanocides by functional expression of an adenosine transporter
from Trypanosoma brucei in yeast. J Mol Med 79, 121–127.
Matovu E, Enyaru JCK, Legros D, Schmid C, Seebeck T & Kaminsky R (2001)
Melarsoprol refractory T.b. gambiense from Omugo, North Western Uganda. Trop
Med Int Health 6, 407–11.
Nair JJ, Machocho AK, Campbell WE, Brun R, Viladomat F, Codina C & Bastida J
(2000) Alkaloids from Crinum macowanii. Phytochemistry 54, 945 – 50.
Schmidt TJ, Brun R, Willuhn G & Khalid SA (2002) Antitrypanosomal activity of
Helenalin and some structurally related sesquiterpene lactones. Planta Med. 68,
750 –751
Schwarz O, Brun R, Bats JW & Schmalz H-G (2002) Synthesis and biological evaluation of new antimalarial isonitriles related to marine diterpenoids. Tetrahedron L
43, 1009 –1013.
Zuccotto F, Zvelebil M, Brun R, Chowdhury SF, di Lucrezia R, Leal I, Maes L, RuizPerez LM, Pacanowska DG & Gilbert I (2001) Novel inhibitors of Trypanosoma
cruzi dihydrofolate reductase. Eur J Med Chem 36, 395 – 405.
Bringmann G, Wohlfarth M, Rischer H, Schlauer J & Brun R (2002) Extract screening by HPLC coupled to MS-MS, NMR, and CD: a dimeric and three monomeric
naphthylisoquinoline alkaloids from Ancistrocladus griffithii. Phytochemistry 61,
195.
Brun R, Burri C & Gichuki CW (2001) The story of CGP 40215: studies on its efficacy and pharmacokinetics in African green monkey infected with Trypanosoma
brucei rhodesiense. Trop Med Int Health 6, 362 –368.
Brun R, Schumacher R, Schmid C, Kunz C & Burri C (2001) The phenomenon of
treatment failures in human African trypanosomiasis. Trop Med Int Health 6,
906 – 914.
Bütikofer P, Vassella E, Boschung M, Kunz Renggli C, Brun R, Pearson TW &
Roditi I (2002) Glycosylphosphatidylinositol-anchored surface molecules of Trypanosoma congolense insect forms are developmentally regulated in the tsetse
fly. Mol Biochem Parasitol 119, 7–16.
Chowdhury SF, Di Lucrezia R, Guerrero RH, Brun R, Goodman J, Ruiz-Perez LM,
Gonzalez Pacanowsca D & Gilbert IH (2001) Novel inhibitors of leishmanial dihydrofolate reductase. Bioorg Med Chem Lett 11, 977– 80.
Gong KW, Kunz S, Zoraghi R, Kunz Renggli C, Brun R & Seebeck T (2001)
cAMP-specific phosphodiesterase TbPDE1 is not essential in Trypanosoma brucei
in culture or during midgut infection of tsetse flies. Mol Biochem Parasitol 116,
229 –32.
Heilman J, Brun R, Mayr S, Rali T & Sticher O (2001) Minor cytotoxic and antibacterial compounds from the rhizomes of Amomum aculeatum. Phytochemistry 57,
1281–1285
Examining a cage containing tsetse flies during an EANETT workshop in KETRI,
Kenya. (Source: EANETT)
31
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SECTION 5
Biostatistics and Basic Epidemiology
Introduction
The biostatistics unit research program both addresses topical
problems in the epidemiology of tropical diseases and develops
new statistical methodology for these problems.
Most of the epidemiological studies relate to either malaria or
helminths (including schistosomes). We collaborate in projects
to produce disease maps for these parasites, and also study
within-host dynamics and transmission.
Diagnostic techniques for parasitic diseases are often insensitive (infections can be overlooked) and one focus of our
methodological research is therefore on spatial statistics and
longitudinal data analysis, including the development of
methodologies that allow for effects of imperfect diagnosis. Projects on the molecular epidemiology of malaria are carried out
collaboratively with the Molecular Epidemiology Group. We also
work closely with the Clinical Epidemiology and Interventions
researchers, providing the data analysis expertise for clinical
trials, and we provide statistical support to the other research
groups in STI, including statistical input for clinical trials.
The group has collaborated in many epidemiological field
studies in Africa and Papua New Guinea, and is using the databases from these studies in novel analyses of risk factors for
morbidity and mortality and to evaluate models of parasite
dynamics. To support further development of malaria models
we have also recovered the original data files from the Garki
project (a major survey carried out in 1971-6 in Nigeria) and
hope to be able to use these data to evaluate new dynamic
models of malaria transmission.
We will be continuing our empirical studies of the effects
of malaria transmission intensity and infection on morbidity
and mortality, including the work on the dynamics of malaria
parasites in areas of high transmission, and the development
of spatial statistical methods for modelling point-referenced
data in malaria epidemiology. Many other projects in STI
involve analysis of spatial data, and modelling these data will
require further methodological developments, especially in the
field of modelling spatially misaligned data. This will feed
into work on the empirical mapping of malaria as part of the
international Mapping Malaria Risk in Africa collaboration
(MARA). The other main area which we are developing is in
fitting dynamic models of malaria transmission to human parasitaemia data. We envisage that the current projects on estimating the duration of malaria infections will lead to improvements
in dynamic models of malaria and hence increase understanding of the long term effects of interventions which disrupt
malaria transmission. Similar analyses are planned for studies
of schistosomiasis.
The virtuous cycle induced by mosquito nets
5.1
Measuring malaria transmission intensity and its
effects on morbidity and mortality
32
Reduced vector survival
Reduced
sporozoite
rate
Area
(mass)
effect
Reduced reservoir
of infectious humans
Reduced prevalence
in humans
Slow (rate limiting)
step
Reduced
incidence
of infection
in humans
Change in parasite prevalence with time in children in
Michenga village, Tanzania.
1
0.9
Parasite rate
Collaboration in studies of the epidemiological effects of malaria control involved contributions to the design of field studies of
the effects of malaria transmission intensity and of the epidemiological effects of insecticide-treated nets (ITNs) (6.3). ITNs
have both immediate and long-term effects on malaria transmission, and our analyses aim to estimate long-term effects that
have been overlooked, owing to unavoidable limitations in the
design of randomised controlled trials.
One of our other innovations in this field has been to fit
dynamic models of malaria immunity to age-prevalence curves.
In a study of effects of mosquito net coverage on age-prevalence patterns in Papua New Guinea we found that net use
resulted in a shift in the age-prevalence curve, so that the protective effect of the nets appeared to be concentrated in
younger individuals. This effect could be neatly modeled using
a dynamic model due to Aron & May.
More recently we have used a different model (that of the
Garki project) to estimate vectorial capacity and entomological
inoculation rates from field data. This offers a way of allowing for
heterogeneity in age-groups and season of survey in malaria
mapping, within the MARA collaboration. We have used the
same models to estimate the long-term effects of mosquito net
use on transmission, allowing for the transmission effects.
An important recent controversy relates to whether young
children exposed less to malaria, for example by using ITNs,
may be more susceptible later in life. We have carried out a
meta-analysis of literature data, and we also have data from the
long-term follow-up of the Navrongo ITN trial in Ghana, and
observational data from Papua New Guinea. None of these
gave evidence of a delayed risk.
ITN use
0.8
0.7
Intervention
0.6
0.5
0
6
12
18
24
30
36
42
48
54
Study Month
At the time marked “intervention” the villagers were provided with mosquito nets.
Following the intervention, the parasite prevalence in children declined considerably. The decline was not observed immediately, and probably resulted from longterm reductions in malaria transmission. The study also showed that there was
little difference between groups assigned impregnated or non-impregnated nets.
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SECTIONand
5 Biostatistics
Basic Epidemiology
and Basic Epidemiology
1.0
Cumulative Survival
0.9
0.9
A
B
C
D
0.8
1.0
0.9
0.9
0.8
0
2
4
6
8 0
2
4
6
8
Years since start of trial
Kaplan-Meier figures of cumulative survival in the ITN trial in Navrongo, Ghana.
Thick lines: control group. Thin lines: ITN group. Arrows indicate the date when
ITNs were given to the control group.
Age-groups at the start of the trial: A < 6 months; B 6 –11 months; C 1 year;
D 2–4 years.
Further understanding of delayed risk needs new analyses of
the shapes of age-prevalence and age-incidence curves and
how these relate to exposure. We are using the Garki dataset to
test methods for summarising age-prevalence curves. To understand how age-patterns of incidence are related to transmission
intensity we are analysing Demographic and Health Survey
(DHS) data in relation to malaria transmission indices derived
from the Mapping Malaria Risk in Africa (MARA) database.
Scientists:
B. Genton, C. Lengeler, T. Smith, P. Vounatsou
PhD student:
A. Gemperli
Collaboration:
PNGIMR (I. Müller); MARA network
Funding:
SNSF
5.2
Statistical methodology for the analysis of spatial
data
An important component of the statistical work is in the area
of mapping of parasitic diseases. This includes work on the
mapping of malaria in Africa in collaboration with the MARA
project.
For some time we have been using Bayesian models for
spatial analysis of data assigned to areas, for example in the
assessment of effects of environmental, socio-economic and
dietary covariates on nutritional indicators in the 1982–3
National Nutrition Survey of PNG (see STI 1999 –2000 and list of
publications below), and more recently we used similar models
for studying space-time patterns in malaria in South Africa. An
innovation was to develop Bayesian hierarchical models for
areal multinomial data with latent categories. These were
applied in spatial analysis of class I HLA haplotype frequencies
in Papua New Guinea (where some alleles are untypable) to
assess environmental and linguistic effects.
Like most Bayesian models for area data, these methods
used univariate conditional autoregressive (CAR) models for the
spatially structured random effects. We have now extended
these models to multivariate analogues and applied them to
spatial modelling of children’s weights and heights in PNG. All
these specifications lead to improper posterior distributions.
However, we have extended this work by developing rich, flexible classes of multivariate CAR models with proper posterior
distributions.
CAR models are adequate for modelling data with neighbourhood structure but most of our data are point-referenced
(geostatistical), and the appropriate statistical models involve
specifying spatial correlation by parameterising the variancecovariance matrix of the outcome (variogram modeling). This
can be extremely computationally intensive because it involves
repeatedly inverting large matrices. We are currently investigating ways of avoiding or speeding up matrix inversions within
a Monte Carlo Markov chain sampling framework, for example
we have used adaptive importance sampling-resampling to
analyse DHS data from Mali.
Analyses of the relation between infant mortality and malaria
transmission also employ data from misaligned databases (e.g.
the DHS and MARA databases) where data are collected from
different geographical locations. We have developed an accelerated failure time Bayesian spatial model with measurement
error which takes into account the misalignment.
Infant Mortality
Deaths per 1000 Infants
Observed Malaria Risk
150 to 170
0.5 to 0.75
130 to150
0.25 to 0.5
110 to 130
0 to 0.25
<110
Map of southern Mali, showing the proportion of children found positive for malaria
in the locations surveyed.
>170
0.75 to 1
Map of southern Mali, showing the estimated infant mortality over the whole area,
adjusted for malaria risk and for socio-economic factors.
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Basic Epidemiology
and Basic Epidemiology
We are also working on a spatial bivariate survival MarshallOlkin type model to investigate competing risks of clinical
malaria and severe anaemia in infants. This will allow us to
assess whether the hazard of one event is modified by the
occurrence of the other.
Scientists:
T. Smith, P. Vounatsou
PhD students:
A. Gemperli, I. Kleinschmidt
Collaboration:
University of Connecticut, USA (A. Gelfand); MARA network
Funding:
SNSF
5.3
Statistical methods for estimating prevalences from
data with diagnostic error or uncertainty
One of the problems encountered in the analysis of schistosomiasis data is the low sensitivity of the test used to detect the
infection. Estimating infection by counting eggs in urine or stool
samples is further complicated by day-to-day variation in egg
excretion. To reduce underestimation of the infection prevalence
and intensity, urine or stool samples need to be collected over a
number of consecutive days and, in the case of stool examinations, multiple stool specimens from the same sample must be
tested. We developed a Bayesian latent class logistic model
which parameterises the sensitivity of the test, and estimates
the prevalence of infection taking into account the diagnostic
error. We applied this model to assess the effect of praziquantel
treatment on the prevalence and intensity of hookworm infection, allowing for the infections that had been overlooked. We
extended the model to estimate the prevalence of co-infection
with S. mansoni and hookworm in the presence of diagnostic
error, and to assess the effect of sampling effort on the estimating co-infection prevalence, assuming that the latent and the
observed data arose from multinomial distributions with the following categories: no infection, hookworm infection, S. mansoni
infection and coinfection respectively (see also 6.7).
Scientist:
P. Vounatsou
Collaboration:
University of Princeton, USA (J. Utzinger); University of Cambridge, UK (M. Booth)
Sequestered malaria parasites
A second issue in the dynamics of malaria parasites is the estimation of the numbers of sequestered parasites in patients. In
collaboration with researchers in Kenya we are carrying out
longitudinal biochemical analyses of putative markers of the
sequestered load in patients in Kilifi, Kenya. Laboratory support
for this project in Basel is provided within the Molecular
Immunology group. The data from the studies in Kilifi will be
analysed using a Bayesian model of parasite dynamics, with
the objective of validating the proposed marker(s). If suitable
marker(s) of sequestered parasite loads are found these will
open up new areas of malaria epidemiology.
Scientist:
T. Smith
PhD students:
L. Ochola, W. Sama
Collaboration:
KEMRI/Wellcome Trust Laboratories, Kilifi, Kenya (K. Marsh);
Institut für medizinische Biometrie, University of Tübingen, Germany (K. Dietz)
Funding:
Canton of Basel-Stadt (scholarship); SNSF
5.5
Epidemiological studies of concomitant immunity in
malaria
We carried out several studies to test whether existing malaria
infections protect against the clinical effects of superinfection.
Observational data from Papua New Guinea suggested that
asymptomatic P. malariae infections protect against fever,
whether caused by P. falciparum or not. A study in São Tomé
also found apparent protection by P. falciparum infections
against non-malaria fevers, as great as that against clinical
malaria. Analysis of similar data from Tanzania and from the
Garki project is in progress.
Ideally this question would be addressed by comparing the
incidence of clinical attacks in individuals previously treated
with anti-malarials with that in controls. Such a study was carried
out by one of our PhD students, S. Owusu-Agyei, who indeed
found that there were more symptoms of clinical malaria in
adults in northern Ghana whose parasites had previously been
cleared, than in controls who had not been so treated.
Scientists:
B. Genton, T. Smith
5.4
Dynamics of malaria infection in areas of high
transmission
PhD student:
S. Owusu-Agyei
Collaboration:
IHRDC, Ifakara, Tanzania; Navrongo Health Research Centre;
PNGIMR
Incidence and duration of infection in malaria
Funding:
SNSF
Many malaria infections are sub-patent, and this severely
biases analyses of rates of acquisition and persistence of infections, which do not take this into account. To address this we
have developed a hierarchical hidden Markov model to estimate clearance and infection rates of malaria infections, allowing for the fact that the sensitivity of the diagnostic test is not
100%. We fitted this model to a dataset of molecular typing of
monthly samples from Tanzanian children, and propose to use
this, as well as related approaches (e.g. immigration-death
models) to analyse comprehensively the relationships between
age, exposure, and the acquisition and clearance of malaria
parasites in a large study from Ghana in which much of the parasite typing has already been completed by the Molecular Epidemiology group (1.5).
34
5.6
Epidemiology of the spatial distribution of human
parasitoses
We are studying the basic biological, demographical, ecological and socio-economic mechanisms responsible for the transmission and frequency of single-species and multiple-species
parasitic infections in the region of Man in Côte d’Ivoire. The
research programme is investigating a wide range of human
parasitoses such as malaria, schistosomiasis, geohelminthiases, amoebiasis and giardiasis. We are aiming to identify risk
factors influencing disease distribution at individual, village and
regional levels, and to develop a predictive model for human
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SECTION 5 Biostatistics and Basic Epidemiology
parasitoses based on climatic factors. Remote sensing technologies are being employed for the assessment of environmental and climatic features, and questionnaires for the
appraisal of socio-economic factors. A comprehensive geographic information system (GIS) has been established, and
Bayesian spatial models have been developed for the purposes
of mapping and prediction. The risk maps will be used for the
planning of intervention strategies and this will contribute to an
effective and integrated disease control approach for human
parasitoses that can readily be adapted to the local epidemiological settings. We are also engaged in similar analyses of data
from Nigeria.
Scientists:
5.8
Clinical Trials
The group provided the statistical input to the Phase IIb trial of
the Combination-B malaria vaccine in Papua New Guinea, and
both data management and statistical input to the Randomised
Controlled Trial of the treatment schedule for melarsoprol
(IMPAMEL 1), and the IMPAMEL 2 project (6.4). Currently the
protocol is being finalised for a Phase I trial of CS02, a long synthetic peptide vaccine candidate (6.1). The group will provide
statistical support for this trial.
M. Tanner, P. Vounatsou
Research Assistant: B. Matthys
PhD student:
G. Raso
Collaboration:
University of Princeton, USA (J. Utzinger); Nigerian Institute
of Medical Research, (M. Mafe); CSRS, Côte d’lvoire
5.7
Clinical epidemiology of meningococcal meningitis in
Northern Ghana
The group provides statistical and epidemiological input to
studies of Neisseria meningitidis in Navrongo, northern Ghana,
which are closely integrated with the molecular typing studies
discussed in Section 3.4. A case-control study of survivors of
the 1996 – 97 epidemic indicated that important risk factors were
exposure to cooking smoke, and sharing a bedroom with
another case. Careful analysis of the epidemic curve and of
spatio-temporal patterns of the epidemic suggested, however,
that much of the transmission probably occurs before epidemics of invasive disease. Audiometry of survivors indicated a
high frequency of hearing problems, and that these may be the
main long term sequelae of meningococcal meningitis in the
African meningitis belt.
Scientists:
B. Genton, T. Smith
PhD students:
S. Gagneux, A. Hodgson
Collaboration:
Navrongo Health Research Centre, Ghana; Ministry of Health,
Ghana
Funding:
Canton of Basel-Stadt (scholarship); Meningitis Research
Foundation, Bristol, UK
Statistical support for other projects within STI ranges from informal advice to co-supervision of students. Major areas of involvement have been:
• Support in data management and analysis of the projects of
the Cultural Epidemiology group, especially on determinants
of stigma and definition of stigma scores. (Section 8).
• Support for studies of zoonoses and human and animal health
in Chad included capture-mark-recapture analyses in a
canine rabies project in N’Djaména, analysis of serum retinol
in Chadian pastoralists, and analysis of nematode egg counts
in N’dama cattle (7B.3).
• Analysis of data collected from a prospective cohort study
conducted in two villages in Zambia, to compare the efficacy
of praziquantel in the treatment of schistosomiasis haematobium in people with and without concomitant HIV infection
(6.6).
• Differential diagnosis of Entamoeba in stool samples (6.8).
• Effects of rice irrigation on helminth prevalence in Côte
d’Ivoire.
Publications:
Abdulla S, Armstrong Schellenberg J, Nathan R, Mukasa O, Marchant T, Smith T,
Tanner M & Lengeler C (2001) Impact of an insecticide treated net programme on
the prevalence of parasitaemia and anaemia in children under two years of age in
the Kilombero Valley, Tanzania. BMJ 322, 270 – 273.
Binka FN, Hodgson A, Adjuik M & Smith T (in press) Mortality in a seven-and-a-half
year follow-up of a trial of inseticide-treated nets in Ghana. Trans R Soc Trop Med
Hyg.
Charlwood JD, Qassim M, Elnsur EI, Donnelly M, Petrarca V, Billingsley PF, Pinto J
& Smith T (2001) The impact of indoor residual spraying with malathion on malaria
in refugee camps in eastern Sudan. Acta Trop 80,1– 8.
Gagneux S, Hodgson A, Smith T, Wirth T, Ehrhard I, Morelli G, Genton B, Binka FN,
Achtman M & Pluschke G (2002) Prospective study of a serogroup X Neisseria
meningitidis outbreak in northern Ghana. J Infect Dis 185, 618 – 26.
Gagneux S, Wirth T, Hodgson A, Ehrhard I, Morelli G, Kriz P, Genton B, Smith T,
Binka FN & Pluschke G, Achtman M (2002) Clonal groupings in serogroup X Neisseria meningitidis. Emerg Infec Dis 8, 462 – 466.
Gelfand A & Vounatsou P (in press) Proper multivariate conditional autoregressive
models for spatial data analysis. Biostatistics.
Biostatistics Group members evaluate a statistical model. (Source: N.A. Weiss)
Genton B, Betuela I, Felger I, Al-Yaman F, Anders R, Saul A, Rare L, Baisor M,
Lorry K, Brown GV, Pye D, Irving DO, Smith T, Beck HP & Alpers MP (2000) A
recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase I/IIb trial in
Papua New Guinea. J Infect Dis 185, 820 –7.
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Heckendorn F, N’Goran EK, Felger I, Vounatsou P, Yapi A, Oettli A, Marti HP, Dobler
M, Traore M, Lohourignon KL & Lengeler C (in press) Species-specific field testing
of Entamoeba sp. in an area of high endemicity. Trans R Soc Trop Med Hyg.
Schneider AG, Premji Z, Felger I, Smith T, Abdulla S, Beck H-P & Mshinda HA (in
press) Point mutation in codon 76 of pfcrt of P. falciparum is positively selected for
by Chloroquine treatment in Tanzania. Infection Genetics and Evolution.
Hii JLK, Smith T, Vounatsou P, Alexander N, Mai A, Ibam I & Alpers MP (2001) Area
effects of bed net use in a malaria endemic area in Papua New Guinea. Trans R
Soc Trop Med Hyg 95, 7–13.
Smith T, Genton B, Baea K, Gibson N, Narara A & Alpers M (2001) Prospective risk
of morbidity in relation to malaria infection in an area of high endemicity of multiple
species of Plasmodium. Am J Trop Med Hyg 64, 262 – 267.
Hodgson A, Smith T, Gagneux S, Adjuik M, Pluschke G, Mensah NK, Binka F &
Genton B (2001) Risk factors for meningococcal meningitis In northern Ghana.
Trans R Soc Trop Med Hyg 95, 477– 80.
Smith T, Genton B, Betuela I, Rare L & Alpers MP (2002) Mosquito nets for the
elderly? Trans R Soc Trop Med Hyg 96, 37– 38.
Hodgson A, Smith T, Gagneux S, Akumah I, Adjuik M, Pluschke G, Binka F & Genton B (2001) Survival and sequelae of meningococcal meningitis in Ghana. Int J
Epidemiol 30, 1440 –1446.
Irion A, Beck H-P & Smith T (2002) Assessment of positivity in immuno-assays with
variability in background measurements: a new approach applied to the antibody
response to Plasmodium falciparum MSP2. J Immunol Methods 259, 111– 8.
Kleinschmidt I, Sharp B, Mueller I & Vounatsou P (2002) Rise in malaria incidence
rates in South Africa: a small area spatial analysis in variation in time trends. Am J
Epidemiol 155, 257– 264.
Müller DA, Charlwood JD, Felger I, Ferreira C, do Rosario V & Smith T (2001)
Prospective risk of morbidity in relation to multiplicity of infection with Plasmodium
falciparum in São Tomé. Acta Trop 78, 155 –162.
Matthies F, Vounatsou P, Fraser-Hurt N, Mshinda H & Tanner M (in press) The therapeutic efficacy and perceived treatment success of herbal antimalarials in
patients – an observational study at a traditional clinic in rural Tanzania. Am J Epidemiol.
Müller I, Vounatsou P, Allen BJ & Smith T (2001) Spatial patterns of child growth in
Papua New Guinea and their relation to environment, diet, socio-economic status
and subsistence activities. Ann Hum Biol 28, 263 –280.
Müller I, Vounatsou P, Smith T & Allen BJ (2001) Subsistence agriculture and child
growth in Papua New Guinea. Ecol Food Nutr 40, 367– 395.
Owusu-Agyei S, Binka F, Koram K, Anto F, Adjuik M, Nkrumah F & Smith T (in
press) Does radical cure place individuals at increased risk of recurrent symptomatic malaria? Trop Med Int Health.
Owusu-Agyei S, Smith T, Beck H-P, Amenga-Etego L & Felger I (2002) Molecular
epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana. Trop Med Int Health 7,
421– 428.
36
Smith T, Hii JLK, Genton B, Müller I, Booth M, Gibson N, Narara A & Alpers MP
(2001) Associations of peak shifts in age-prevalence for human malarias with bed
net coverage. Trans R Soc Trop Med Hyg 95, 1– 6.
Smith T, Leuenberger R & Lengeler C (2001) Child mortality and malaria transmission in Africa. Trends Parasitol 17, 145 –149.
Smith T (2001) Book Review: An introduction to randomized controlled clinical
trials by JNS Matthews. Trans R Soc Trop Med Hyg 95, 238.
Smith T (2001) Book Review: Design and analysis of cluster randomization trials in
health research by A Donner & N. Klar. Trans R Soc Trop Med Hyg 95, 238.
Smith T (2002) Imperfect vaccines and imperfect models. Trends Ecol Evol 17,
154 –156.
Smith T & Vounatsou P (in press) Bayesian modelling of a hidden Markov process
for estimating infection rates for highly polymorphic parasites when detectability is
imperfect. Stat Med.
Utzinger J, Vounatsou P, N’Goran EK, Tanner M & Booth M (2002) Reduction in the
prevalence and intensity of hookworm infections after praziquantel treatment for
schistosomiasis infection. Int J Parasitol. 32, 759 –765.
Vounatsou P, Smith T & Gelfand A (in press) Spatial modeling of gene frequencies
in the presence of undetectable alleles. J Appl Stat.
Weiss MG, Jadhav S, Raguram R, Vounatsou P & Littlewood R (2001) Psychiatric
stigma across cultures: local validation in Bangalore and London. Anthropology
and Medicine 8, 71– 87.
Zinsstag J, Schelling E, Daoud S, Schierle J, Hofmann P, Diguimbaye C, Daugla
DM, Ndoutamia G, Knopf L, Vounatsou P & Tanner M (2002) Serum retinol of chadian nomadic pastoralist women in relation to their livestocks’ milk retinol and
beta-carotene content. Int J Vitam Nutr Res. 72, 221– 228
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SECTION 6
Clinical and Intervention Epidemiology
Introduction
malarious settings, and tackled the issue of the effects of the
Intervention epidemiology, covering the spectrum from product
reduction of malaria transmission on child survival, within a
development to measuring the efficacy and effectiveness of
long-term cohort study. In the framework of the KINET project,
interventions against communicable diseases, is an important
malaria prevention with ITNs has been studied with unique thorcomponent of the STI research portfolio. Health interventions
oughness over a 4-year period. The experience gained in this
and their systematic study make a major contribution to the STI’s
study has contributed greatly to the rapid uptake of this intermission to improve the health of populations internationally.
vention in Tanzania and the rest of sub-Saharan Africa.
The range of diseases and research topics covered by interThe use of ITNs is one of the two main interventions that are
vention epidemiology is wide, although there has been a particthe mainstay of malaria control in highly endemic areas at presular focus on malaria in recent years. Many developments in this
ent. The other is the diagnosis and treatment of all clinical
area have been in support of the global Roll Back Malaria partepisodes. Intervention research on malaria at the STI currently
nership initiated in 1998. The STI has been an active member of
includes work on this strategy as well. The development of new
the partnership in many ways and participated in many projdrugs as a result of the rapid
ects. Other important tropical
spread of resistance against
diseases have not been negexisting drugs is paramount. The
lected. African sleeping sickSTI is involved in this through its
ness – a concern of the STI since
drug discovery programme (Secits foundation – remains an
tion 4.2), and conducted a test of
important research and intervenCotrifazid in Papua New Guinea
tion topic. Schistosomiasis also
(6.2). Work on drug resistance
continues to be a major research
markers and their measurement
interest. In recent years further
in the field is complementary to
developments have taken place,
this effort (1.6). An important
some of which are described
recent extension of the therapeuelsewhere in this report, for
tic use of antimalarials is intermitexample on the epidemiology of
meningococcal meningitis and Introductory meeting of study coordinators from many countries, IMPAMEL project. tent treatment given to children.
Yaounde, Cameroon, June 2000. (Source: C. Burri)
This potentially very important
Buruli ulcer (Section 3). Amoebidevelopment was tested for the first time in Tanzania by a large
asis and other diseases due to water-related pathogens have
team including the STI, and proved to be very successful (6.2).
been the subject of epidemiological studies and developments
Finally, current efforts to develop and test a malaria vaccine will
in diagnostic methods (Section 2).
help to further tackle the malaria problem in the medium-term,
The concept of intervention epidemiology highlights the
and substantial STI resources are going into this venture, which
close link between work on specific interventions and work
includes not only the developing and testing of new vaccines but
aimed at furthering our fundamental understanding of the epialso in-depth work in human immunology (Section 3).
demiology of diseases. Both applied and more basic research
Intervention studies could not be carried out without a sharing
are combined within projects and/or within research groups.
of expertise between the STI and partners in the South. ImporThis is well illustrated in the field of malaria vaccines by the
tant partnerships for the STI include the Ifakara Health Research
many links existing between the work on testing malaria vacand Development Centre (IHRDC) in Tanzania; the Centre
cines described below, and work described in the sections on
Suisse de Recherches Scientifiques (CSRS) and the University
Molecular Epidemiology and Molecular Immunology (Sections 1
of Cocody in Abidjan, Côte d’Ivoire, and the Navrongo Health
and 3). A further illustration is the applied work on schistosomiResearch Centre in Ghana. The STI’s office in N’Djaména, Chad
asis questionnaires, which was complemented by more basic
provides a base for work on the health of nomads and different
epidemiological work on multiparasitism.
zoonoses (Section 7B). In India, work on mental health is being
Another defining characteristic of intervention epidemiology
carried out in collaboration with a number of Indian institutions
at the STI is the close interaction between programme imple(Section 8). Work on trypanosomiasis has opened up a commentation and research. Through its long-standing experience
pletely new network of collaborating institutions, many located in
in project implementation and management, the STI has develareas where there are complex emergency situations.
oped the ability to deliver complex interventions, often under
Many of these partnerships are based on long-term co-operdifficult operational circumstances, while at the same time
ation – more than 50 years in the case of Ifakara. The range of
carrying out an associated research programme. Such proprojects in partnership is very wide, and they systematically
grammes require large trans-disciplinary teams working
include a strong component of research capacity building in the
together in a highly integrated fashion.
South. For example, four PhD degrees and one MSc were
The large KINET project in Tanzania illustrates this well.
awarded to African students working in the KINET project.
Expertise in epidemiology, statistics, demography, anthropolThe points discussed above all contribute to giving intervenogy, health economics and marketing was integrated in the
tion epidemiology at the STI its particular flavour and profile.
delivery and evaluation of this project, aiming at the provision of
Intervention epidemiology has made the STI highly visible in the
insecticide-treated nets (ITNs) on a large scale. In addition to a
international scene, and the large number of international expert
thorough evaluation of the process of implementing ITN use,
groups which include STI staff members (pages 92 – 93) are a
and its health impact, more basic work was done. This contestimony to the success of this philosophy.
firmed the importance of malaria in the first year of life in highly
37
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SECTION 6 Clinical and Intervention Epidemiology
6.1
Interventions against malaria; vaccine development
and clinical trials
Scientists:
H.-P. Beck, I. Felger, B. Genton, T.A. Smith, M. Tanner
Collaboration:
Institute of Biochemistry, University of Lausanne (Prof. G. Corradin); Centre Hospitalier Universitaire Vaudois (CHUV) (Prof.
F. Spertini); Policlinique Médicale Universitaire, Lausanne; Dictagene, Lausanne; PNGIMR (Prof. J. Reeder); La Trobe University, Melbourne, Australia; Queensland Institute of Medical
Research and the Cooperative Research Centre for Vaccine
Technology, Brisbane, Australia (Prof. R. Anders); WEHI, Melbourne, Australia
Funding:
Malaria Vaccine Initiative of the Bill and Melinda Gates Foundation; Dictagene
Combination B and vaccines against asexual blood stages
One of the strengths of research in the STI is the close collaboration between work in the field and in the laboratory. Work on
malaria vaccines is a good example of this. The trial of the vaccine Combination B in Papua New Guinea was described in our
last report (STI 1999 –2000). Since then, research has concentrated on detailed molecular biological analysis of samples from
the trial (Section 1.4).
Further documentation of the specific efficacy of the MSP2
vaccine component in reducing homologous infections justifies
the current approach, which is to favour the production and testing of this component of Combination B. Because of the selective pressure exerted by the 3D7 allelic type of MSP2 which was
included in the ComB vaccine, the next generation vaccine will
be composed of the two main allelic types of MSP2; 3D7 and
FC27. These will be tested as single antigens (FC27 alone) or
combined.
An important task last year was participation in working on a
concept and preparing a proposal for further development of
candidate vaccines against the asexual blood stage: AMA1,
MSP1 & 2, RESA and RAP2. This has been submitted to the
Malaria Vaccine Initiative (MVI) of the Bill and Melinda Gates
Foundation as a joint project of the STI with the Papua New
Guinea Institute of Medical Research (PNGIMR) and three institutions in Australia; the Walter and Eliza Hall Institute (WEHI) in
Melbourne, and the Queensland Institute of Medical Research,
and the Centre for Vaccine Technology, both in Brisbane.
Pre-erythrocytic and asexual blood-stage Malaria Vaccine
Programme; LSP vaccine candidates
An important initiative in research on malaria vaccines is to create a centre of excellence for malaria vaccine testing in Switzerland, using the acknowledged competence of four institutions:
the STI in Basel, and the Institute of Biochemistry, the University
Hospital (CHUV) and the Policlinique Médicale Universitaire, all
in Lausanne. Close and efficient collaboration among these
partners, each providing different expertise, should accelerate
the design and testing of candidate vaccines against malaria
and other diseases. It should also solve the problem of the
scarcity of challenge sites in Europe.
Concrete aims at present are: i) to develop a P. falciparum
challenge system in Lausanne, using the expertise of scientists
at the STI, ii) to conduct collaborative Phase I/IIa trials, using the
expertise of STI clinicians and malariologists, to assess the
safety, immunogenicity and protective capacity of the Long Synthetic Peptide (LSP) vaccine candidates, and iii) to conduct
Phase III trials in Tanzania and/or Papua New Guinea of candidates that have shown some efficacy in challenge studies.
The LSP vaccine candidates were developed as the result of
an innovative approach in the Institute of Biochemistry in Lausanne (Prof. G. Corradin), and are being produced by Dictagene, a new GMP biotechnology company in Lausanne. The
LSPs, with 100 or more amino acids, are derived from pre-erythrocytic and erythrocytic stage proteins. Two of them (200 –
300 amino acids) have already been successfully tested in a
Phase I clinical trial in the CHUV (Prof. F. Spertini).
38
6.2
Interventions against malaria; chemotherapy
Intermittent treatment of malaria
Antimalarial chemoprophylaxis given to children in endemic
areas has clearly been shown to reduce malaria morbidity,
school absenteeism, and all-cause mortality. Chemoprophylaxis
has been routinely recommended for children of all ages in
some African countries, but the practice has now been
stopped. The main reasons were economic and logistic ones,
but fears of the development of parasite resistance and of the
possible loss or delay in the acquisition of immunity to malaria
have also led to doubts about the promotion of malaria chemoprophylaxis for children and infants.
With the objective of maximising the protective effect of
chemoprophylaxis without compromising the development of
malaria immunity, the use of intermittent malaria treatment in the
first year of life was explored in a study in 701 Tanzanian infants
in Ifakara, Tanzania. Sulphadoxine-pyrimethamine (SP) was
administered in a randomised, placebo-controlled double-blind
study, alongside routine EPI vaccinations at the ages of 2, 3 and
9 months. The intermittent malaria treatment was associated
with 59% (95% CI: 41–72) and 50% (95% CI: 8 –73) reductions
in the incidence of clinical malaria and severe anaemia, respectively. The incidence of all-cause hospital admissions was
reduced by 30%. Serological responses to EPI vaccines were
not affected by the intervention and no drug-attributable side
effects were recorded.
When the intervention was discontinued there was no evidence of a rebound effect in malaria episodes, suggesting that
malaria-specific immunity had not been impaired or delayed.
On the basis of these findings the research teams involved are
currently planning a large-scale effectiveness trial in at least
four Tanzanian districts as well as a further efficacy study in
Manhica, Mozambique. These trials will be part of an international initiative (Barcelona, London, Copenhagen, Tübingen,
Basel) to carry the concept of intermittent treatment from efficacy to effectiveness, and thus into public health practice. WHO is
providing an umbrella for this initiative, and collaboration with
UNICEF is well established in all intervention countries (Gabon,
Ghana, Mozambique, Tanzania).
Scientist:
M. Tanner
Collaborations:
Hospital Clinic Barcelona (P. Alonso, C. Menendez, D. Schellenberg); IHRDC, Ifakara, Tanzania (H. Mshinda, E. Kahigwa);
Centro de Investigaçao em Saude da Manhiça (CISM), Manhiça, Mozambique (P. Alonso, C. Menendez, J. Aponte)
Funding:
WHO/TDR, Spanish Development Agency, SDC
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COTRIFAZID against resistant malaria in semi-immune
subjects: study of efficacy and tolerance
Cotrifazid (a combination of rifampicin, co-trimoxazole and isoniazid) has been proposed as an alternative to quinine plus
Fansidar (QF) which is the standard treatment given to semiimmune patients with chloroquine- or amodiaquine-resistant
malaria in Papua New Guinea. A study was carried out to show
that the efficacy of Cotrifazid is not inferior to the standard treatment (QF) or mefloquine, and assess tolerance to it. The trial
was conducted from April 2000 to April 2002 in two health centres in Madang and two in the East Sepik province of PNG. 382
patients were recruited, and the results for 314 of them could be
evaluated (108 Cotrifazid, 102 QF, 104 mefloquine). Safety data
showed that Cotrifazid is better tolerated than the other two regimens. Preliminary results on efficacy showed that the rate of
clinical failure (primary outcome: fever or history of fever + parasitaemia) was similar for the three regimens (over 95%), but
that the parasitological clearance with Cotrifazid was slightly
inferior to that with the other regimens at days 7 and 14.
Because of these results, a complementary one-arm study is
underway in 80 patients to assess the safety and efficacy of an
increased dose of Cotrifazid given over 5 days, using parasitological clearance as a primary outcome. Ancillary studies are
assessing the diagnostic performance of the rapid antigen test
(Optimal) in the follow-up of the patients under treatment, and
analysing the molecular markers of chloroquine- and Fansidarresistance in the samples at days 0 and 7 or 14 (the latter in collaboration with Dr A. Cowman’s group at WEHI, Australia).
Scientist:
B. Genton
Collaboration:
PNGIMR (I. Müller, J. Reeder); WEHI, Melbourne, Australia
(A. Cowman)
Funding:
Fatol GmbH, Germany
6.3
Interventions against malaria; insecticide-treated
nets (ITNs)
The KINET project: operational aspects
KINET was a large-scale programme for the social marketing of
insecticide-treated nets for malaria control in two rural districts
in Southern Tanzania, which ran from July 1996 to June 2000. It
consisted of three major components: i) programme implementation, ii) research and evaluation, and iii) capacity building.
Extensive formative research and in-depth social science work
were conducted prior to the start of marketing activities. The
findings showed that there were several local illness concepts,
one of which was “maleria”. This referred to mild malaria, and it
overlapped with the biomedical concept of malaria. Most
respondents linked “maleria” to mosquitoes (76%), and many
(52%) already used mosquito nets. However, local understanding of severe malaria (for example when it causes convulsions in
children) differed from the biomedical concept, and was not
linked to mosquitoes or malaria. A social marketing strategy to
promote ITNs was developed that incorporated insights from
these findings.
A total of 65,000 nets and 25,000 treatments were sold by the
project between May 1997 and June 2000. A strong evaluation
component allowed the monitoring of a number of important
aspects of the project. Firstly, detailed sales records were kept
The three key components of the KINET programme: Malaria control, evaluation
and training.
in order to be able to follow the development of the sales network. A detailed cost analysis was also performed in order to
allow a distribution cost analysis and a cost-effectiveness
assessment. The social marketing approach to ITN distribution
was estimated to cost $1560 per death averted and $57 per
DALY (disability adjusted life year) averted. When the costs and
the benefits of using untreated nets were included these costs
fell to $1018/death averted and $37/DALY averted.
Coverage figures were very encouraging, with 63% of children under five years in the Kilombero district and 31% in
Ulanga using a net by mid-1999. By 2000, over 20% of children
under five were protected by a treated net. Coverage was
higher in areas which had had longer access to the sociallymarketed treated nets: over 50% of infants in the 25 villages
where the social marketing was started in 1997 were using a
treated net. However, re-treatment rates were low (less than
one-third of ITN owners had re-treated their nets during the preceding 6 months).
One of the most innovative components of the KINET project
was the introduction and testing of a system designed to make
it easier for pregnant women to obtain nets. This was done
through a system of vouchers given to women attending antenatal clinics for the first time. The voucher was worth TSh 500
(approx. US$ 0.6 in 1999), and could be used to reduce the
price of a treated net at any retailer. The voucher return rate was
originally extremely high at 97% (7,720/8,000). However, two
years after the start of the scheme, awareness of the scheme in
the target group was only 43% (45/104), and only 12% of
women (12/103; 95% CI 4 – 48%) had used a voucher towards
the cost of a net. This was due to a low level of awareness of the
scheme among the women, and to the fact that the voucher was
not offered to them systematically by clinic staff. Discount
vouchers are a feasible system for targeted subsidies, but a
substantial amount of time and effort may be needed to achieve
high levels of awareness and uptake. The vouchers have two
important additional functions: strengthening the role of public
health services in the context of a social marketing program,
and providing an IEC tool to emphasise that the targeted group
is one which has a high risk of severe malaria. The KINET
voucher system is now being implemented on a large scale in a
number of countries.
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KINET: health impact of ITNs
The short-term and long-term effects of treated nets on child
survival were assessed with the help of a demographic surveillance system in a total population of 65,000. Treated nets were
associated with a 27% (95% CI 3 – 45%) improvement in child
survival in children aged 1 month to 4 years, while untreated
nets reduced the risk of dying by 19% (95% CI –9 – 40%). Combined with coverage figures, these results suggest that treated
and untreated nets in Kilombero and Ulanga prevented over
200 child deaths per year. Half the deaths in this area occurred
at home and three-quarters of the children had received treatment from a health facility before their death – a worrying finding, since it suggests an inadequate quality of care. Four independent risk factors for death were identified which were each
associated with more than 5% of total child mortality: not being
carried on the back while the mother cooked (odds ratio (OR)
1.6: 95% CI 1.3 –2.0), poor maternal education (OR 1.4: 95% CI
1.0 –1.9), lack of exclusive breastfeeding in the first 3 months of
life (OR 1.4: 1.1–1.8), and low socio-economic status (OR 1.3:
1.0 –1.6).
A major impact of the use of ITNs on malaria morbidity was
measured in young children, with a 62% reduction in parasitaemia and a 63% reduction in anaemia. Overall, the prevalence of anaemia decreased from 49% to 26% in all children.
The ITNs were rather homogeneously distributed throughout the
study villages at an average density of about 118 ITNs per thousand people. The distribution of parasitaemia and anaemia
cases did not have any significant spatial structure, and no
short-distance protective effects of the ITNs (i.e. protection of
neighbouring households) were detected for any of the morbidity parameters examined.
against mild anaemia and a protective efficacy of 38% (95%
CI 4 – 60) against severe anaemia (Hb <8 g/dl). Furthermore,
there was a trend for the children of non-anaemic women to
have better survival rates than children born to anaemic women
(RR 2.9, 95% CI 1.1–7.6).
Beyond KINET: implications for malaria control
A substantial amount of time and resources were devoted to a
full feedback on the KINET experience at local, national and
international levels. A highlight of this process was the presentation of the KINET experience by Dr. S. Abdulla at the UN Special Session on Children (UNGASS) in New York in May 2002.
Experience from the KINET project has been used extensively in formulating national and international policies for ITN
implementation. In Tanzania the KINET experience made it possible to obtain resources from the Swiss Agency for Development and Cooperation (SDC) to support an ITN unit within the
National Malaria Control Programme. Together with the recent
allocation of US$ 20 million for ITN work in Tanzania by the
Global Fund to fight AIDS, TB and malaria, a uniquely favourable situation has been created to achieve national coverage of
ITNs by the year 2005.
An important new ITN study was initiated in 2000 in Ifakara as
a follow-up of the KINET project. Using the existing demographic surveillance system combined with large-scale entomological field work, the spatial effects of ITNs on child mortality
will be examined in detail. This development is of great practical
importance, since it is possible that due to the mass killing of
mosquitoes through ITNs (the so called “mass effect”) the full
benefit of ITNs might be reached at less than 100% coverage.
As a result, even poor households unable to afford an ITN might
benefit from their neighbours’ nets.
Additional analysis of data on ITNs is reported in Section 5.1.
The extended analysis of a large data set from PNG highlights
the impact of nets in a highly endemic area. Re-analysis of mortality data from a trial in 1992 –1996 in Ghana made it possible to
explore the issue of long-term impact of ITNs. Together with a
similar analysis done in Burkina Faso and our recent review on
the relationship between overall child mortality and malaria
transmission, a sound scientific basis has been laid to dismiss
earlier concerns that reducing malaria transmission might only
lead to transient survival benefits.
Nets with long-lasting insecticide treatment (NELLIT)
Measuring the health impact of ITNs
in infants: weighing and measuring
children. (Source: S. Abdulla)
The positive impact of ITNs among pregnant women was
also substantial. Overall, 53% of them used ITNs. Use was
lowest among women aged 15 –19, primigravidae, unmarried
women, and those with no access to cash. Fewer ITN users
were positive for malaria than non-users (25 vs. 33%: P=0.06),
and the protective efficacy (PE) for parasitaemia was 23%
(CI 2– 41). Multiparous ITN users had a twofold decrease in
parasite density compared with multiparous non-ITN users
(625 parasites/µl vs. 1173 parasites/µl:P=0.01). Fewer ITN
users were anaemic (Hb < 11 g/dl) than non-users (72 vs. 82%:
P=0.01). ITNs had a protective efficacy of 12% (95% CI 2–21)
40
The major issue facing every ITN programme is that of re-treatment, and most programmes (including KINET) have clearly
failed to achieve sufficient re-treatment rates. A technological
solution to this issue is offered by nets with a long-lasting insecticide treatment (NELLIT), which are treated at the factory and
do not need any further re-treatment.
We have collaborated with a French company, Athanor SA, to
adapt a treatment process that was used for the insecticide
treatment of army uniforms, so that it could be used for polyester mosquito netting. The process was optimised, and extensive laboratory testing showed that even after being washed
50 times, the nets still killed more than 80% of mosquitoes in
a standard WHO bioassay. NELLIT have now been placed in
15 households in Ifakara in order to study how well the insecticide activity persists over a long term under real-life conditions.
Work was also done on the field validation of a simple test
37-48_Section_06
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Seite 41
Collecting mosquitoes from a
cage in the IHDRC, Ifakara.
Insects bred in the laboratory
are used to test whether the new
nets with long-lasting treatment
retain their ability to kill mosquitoes under conditions of normal
use. (Source: C. Lengeler)
(developed at the Liverpool School of Tropical Medicine) for
measuring insecticide on netting.
Scientists:
J. Armstrong Schellenberg, H. Grundmann, C. Lengeler,
B. Obrist, W. Rudin, T. Smith, A. Tami, M. Tanner
PhD students:
S. Abdulla, N. Kikumbih, T. Marchant, H. Minja, R. Nathan
MSc students:
T. Erlanger, O. Mukasa
Collaboration:
IHRDC, Ifakara, Tanzania; Liverpool School of Tropical Medicine, UK; LSHTM, UK; Navrongo Health Research Centre,
Ghana; Tanzanian National Malaria Control Programme; Tanzanian Essential Health Interventions Programme (TEHIP)
Funding:
Athanor SA; SDC; SNSF; Government of Tanzania; RGS, Basel;
WHO/TDR
injection of 2.2 mg/kg body weight for ten consecutive days,
and the control group followed the 26-day standard Angolan
schedule of 3 series of 4 daily injections of melarsoprol
(Arsobal®) with a 7-day interval between series. The new concise schedule proved to be equivalent to the standard one in
terms of safety and efficacy. The recommended 24 months follow up has recently been completed and there is strong evidence that the new treatment schedule is equally efficient in
comparison with the standard treatment.
In the light of the economic and practical advantages of the
new treatment, it was considered worthwhile to carry out a more
extensive trial. A follow-up program, IMPAMEL II, became operational in June 2000. The objective was to monitor the outcome of
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Côte
d'Ivoire
CAR
30
E.Guinea
12
219
R.Congo
South
Sudan
DR
Congo
569
6.4
Treatment of African trypanosomiasis
Angola
553
Treatment of African trypanosomiasis with melarsoprol:
IMPAMEL Program
Human African trypanosomiasis (sleeping sickness), caused by
the protozoan parasites Trypanosoma brucei gambiense (West
African form of the disease) and T. brucei rhodesiense (East
African form of the disease), affects 36 African countries. Some
60 million people are at risk of contracting the disease, but no
more than 3 – 4 million are under adequate surveillance. WHO
estimates that at least 300,000 – 500,000 individuals are
infected. Sleeping sickness due to T. b. gambiense is characterized by a chronic progressive course, which may last from
months to several years before death occurs. The form of disease caused by T. b. rhodesiense is usually acute and death
occurs within weeks or months after infection.
Only a few drugs are available for treatment, and melarsoprol
(Arsobal®) still remains the first line drug for late stage treatment, despite considerable efforts during the last decade to
find better alternatives. Until recently there was only a little pharmacological or pharmacokinetic information on melarsoprol.
Treatment schedules were long and complicated (3 – 4 series of
3 – 4 injections spaced by 24 hours with intervening rest periods
of 7–10 days), and had been devised empirically. No comparative studies with appropriate power had been carried out to test
different schedules. The hospitalisation period of 25 to 36 days
imposed an immense burden on the accompanying families
and limited hospital capacity.
In 1993, we proposed a treatment schedule for melarsoprol
with an abridged duration of only 10 days and 30% less total
drug. The schedule was based on pharmacokinetic investigations, which gave evidence that the interruptions between the
treatment series could be omitted. The first trial of the safety
and efficacy of this new, abridged treatment schedule, IMPAMEL I,
was described in detail in the previous report (STI 1999 –
2000). In an open, randomised equivalence trial in 500 patients
in Kwanza Norte, Angola, the study group was treated with an
Map of coutries taking part in the IMPAMEL II programme. Numbers show patients
enrolled in each country.
treatment according to the new protocol under field conditions
in selected centres in different endemic countries with a wide
variety of populations and settings and different baseline conditions (e.g. ethnic groups, nutritional status, HIV prevalence,
concomitant parasitic infections, relapse rates).
The study was a multinational, multicentre study. Eight countries agreed to participate, and suggested the involvement of,
21 centres. The study was officially launched at a coordinators’
meeting held jointly with WHO in June 2000. Eventually, data
were collected in 15 centres in seven countries, the first starting
enrolment in June 2000 and the last in January 2001. The participating countries were: Angola (Dondo, Viana, Uíge), Central
African Republic (Batangafo), Republic of Congo (Brazzaville,
Mossaka), Democratic Republic of Congo (Kinshasa, Kionzo,
Maluku), Côte d’Ivoire (Daloa), Equatorial Guinea (Mbini, Kogo)
and South Sudan (Kajo Keji, LiRangu, Tambura).
To reduce complexity, and because of the very difficult field
situations in some centres, and the lack of trained staff in some
places, the study was designed without randomisation or a control group. A total of 2,000 patients treated was set as a goal, to
achieve significant power for analysis despite the expected
large inter-centre variations. The enrolment period was set to
one year for each centre, with a follow up of 24 months. Recruitment most often took place under difficult circumstances.
The results of the study will be compared with any retrospective data available from the same centre, with existing literature
reports, and between centres. The outcome measures are
defined as follows. Primary efficacy outcome: parasitological
cure 24 hours after treatment. Secondary efficacy outcome:
relapse rate during follow up. Primary safety outcomes: rates of
41
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Development of new trypanocidal drugs
The Parasite Chemotherapy group at the STI is working on the
discovery and development of new drugs against trypanosomes (Section 4.1). One of these, an orally-available
diamidine, has reached the stage of a clinical trial, which is
being carried out by the Pharmaceutical Medicine Unit of the
SCIH (Section 11.2).
Scientists:
J. Blum, R. Brun, C. Burri, T. Smith, P. Vounatsou
PhD. Students:
C. Schmid, J. Seixas
MSc Student:
I. Küpfer
Collaboration:
Instituto de Combate e de Controlo das Tripanossomíases,
Luanda, Angola (Dr. T. Josenando); Programme National de
lutte contre la Trypanosomiase, Brazzaville, République du
Congo (Dr. C. Manthelot); Projet de Recherches Cliniques sur
la Trypanosomiase, Daloa, Côte d’Ivoire (Dr. F. Doua); Bureau
Central de la Trypanosomiase, Kinshasa, République Démocratique du Congo (Dr. M.B. Miaka); Programo Nacional de
Control de Tripanosomiasis, Bata, Guinea Equatorial (Dr P.
Ndongo Asumu, Dr. P. Simarro); Programme National de Lutte
contre la Trypanosomiase Humaine Africaine, Bangui, Central
African Republic (Dr. A. Nangouma); International Medical
Corps (Dr. M. Richer); MSF Switzerland (Dr. F. Chappuis, Dr. F.
Pittet); WHO, Department of Communicable Disease Surveillance and Response (Dr. J. Jannin); Swiss Humanitarian Aid,
Luanda, Angola (J.M. Jordan)
Data and Safety S. Bennett (LSHTM), P. Cattand (retired, ex WHO), B. GentonMonitoring Board: (STI), M. Odiit, (LIRI, Uganda), and L. Rombo (Mälar Hospital,
Eskilstuna Sweden)
Funding:
42
SDC
6.5
Schistosomiasis; new developments in
chemotherapy and control
Among the world’s parasitic diseases, schistosomiasis continues to rank in the second position after malaria in terms of the
extent of the endemic areas and the number of infected people.
There is no vaccine available, and the current mainstay of control is chemotherapy, with praziquantel as the drug of choice. In
view of concerns about the development of tolerance and/or
resistance to praziquantel, there is a need for research into and
development of new drugs for the prevention and cure of schistosomiasis. The work of the Parasite Chemotherapy group in the
STI on new drugs for the treatment of schistosomiasis is
described in Section 4.3. In this section we report on the continuation of the studies on the potential of artemether and other
artemisinin compounds in the control of schistosomiasis that we
described in our last report (STI 1999 –2000).
The interesting observation was made two decades ago by
Chinese scientists that derivatives of artemisinin, used in the
treatment of malaria, also have antischistosomal properties.
Artemether, the methyl ether derivative of dihydroartemisinin, is
now widely used in the treatment of malaria. In collaborative
studies between the STI, the Institute for Parasitic Diseases of
the Chinese Academy of Preventive Medicine, the CSRS and
the University of Cocody in Côte d’Ivoire, the potential of
artemether for the control of schistosomiasis has been explored
through detailed laboratory and field studies on S. japonicum,
S. mansoni and S. haematobium from 1998 onwards. The first
phase of this successful collaboration was summarised in our
last report (STI 1999 –2000). The in-depth laboratory studies on
Reduction in worm burden (%)
encephalopathic syndromes and frequency of death during
treatment. Secondary safety outcome: other severe adverse
reactions (i.e. skin reactions and neuropathies).
More than 2500 case report forms have been received so far.
The data have been double-entered in a database, all inconsistencies have been resolved, and missing data retrieved by
queries to the investigators. All cases of adverse drug reactions
were independently reviewed by two medical doctors, and if
necessary, additional information on the cases was requested
from the field. This process was recently finalised, the database
was audited and locked by an independent statistician, and the
analysis initiated. A preliminary assessment based on the
incoming bi-monthly country reports reveals the expected, significant inter-centre variation for the rates of encephalopathic
syndromes and death during treatment. However, the rates are
within the expected range when compared to the previous
experience in the same centres. A 24-month follow-up will be
terminated in autumn 2003.
Although the final data analysis has not been carried out,
there are enough results to show that the new schedule does
not lead to more adverse effects than the longer one, and is as
effective. This has already led a number of national programs to
decide to use the new treatment schedule in additional centres.
Those added so far are Obo (Central African Republic), Gamboma (Republic of Congo), Bulwem, Dipumba, Kakenge
(Democratic Republic of Congo). The following centres which
took part in the trial are continuing to use the concise treatment
schedule until the final results are published and a recommendation is made: Daloa (Côte d’Ivoire); CNPP Kinshasa, Kionzo,
Maluku (Democratic Republic of Congo); Batangafo (Central
African Republic); Brazzaville, Mossaka (Republic of Congo);
Kogo and Mbini (Equatorial Guinea).
100
80
60
40
20
0
0
7
14
21
28
35
42
Age of Schistosoma mansoni (days)
Susceptibility of Schistosoma mansoni parasites of different ages, harboured in
mice, to praziquantel (●
● ) and artemether (■). The grey bar shows the developmental period to reach oviposition.
the efficacy, mode of action and toxicity of artemisinin derivatives have been continued. In addition, the first field trial of
artemether as a protective agent against S. haematobium infection was carried out in Taabo, Côte d’Ivoire. The trial is
described below.
On the basis of our studies we conclude that artemether certainly has a role to play in schistosomiasis control, and it is now
time to translate the accumulated evidence into public health
policies and actions. Artemether, and perhaps other related
compounds (Section 4.3) open new perspectives for the control
of schistosomiasis. Artemether could well complement existing
control strategies, mainly through combination chemotherapy
strategies, and it has the potential to become an important com-
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ponent of integrated schistosomiasis control in many parts of
the world.
Artemether should not be recommended for schistosomiasis
control where malaria is also endemic, as there is some fear that
a treatment regimen aimed at schistosomiasis prevention might
select for drug-resistant malaria parasites. This is an important
concern, since artemisinins are often the only remaining effective antimalarials in an area. Nevertheless, there are many areas
where schistosomiasis is endemic but malaria is not, for example large parts of Brazil, China, Egypt and South Africa. In such
areas artemether treatment can be safely recommended for the
prevention of acute cases and the reduction of the incidence of
infection.
Besides developing the evidence-base for the application of
artemether in schistosomiasis control, work surrounding the
design and validation of schistosomiasis control strategies for
S. japonicum continued in a collaborative set-up with the
Queensland Institute for Medical Research, the University of
Queensland, and the Chinese authorities. Cost-effectiveness
studies demonstrated the feasibility of interventions, and indepth immunological studies helped to define new markers for
schistosome-related morbidity.
Field trial of artemether in the control of S. haematobium
infection
The first randomized, double-blind, placebo-controlled trial of
artemether against S. haematobium was undertaken in the village of Taabo, in a highly endemic area of Côte d’Ivoire. Urine
specimens from 440 schoolchildren were examined over 4 consecutive days, and they were then given 2 praziquantel treatments 4 weeks apart. Children who were then S. haematobiumnegative were randomized to receive 6 mg/kg artemether (n =
161) or placebo (n =161). Medication was administered orally
6 times, once every 4 weeks. Adverse events 72 hours after
medication, perceived illness episodes throughout the study
period, incidence and intensity of S. haematobium infections,
and micro- and macrohaematuria were assessed 3 weeks after
the final dose. We also monitored malaria parasitaemia and
treated positive cases with sulfadoxine-pyrimethamine.
Oral artemether was well tolerated. The incidence of patent
S. haematobium infections in artemether recipients was significantly lower than in placebo recipients (49% versus 65%, protective efficacy: 0.25, 95% CI: 0.08 – 0.38, P= 0.007). The geometric mean infection intensity in the artemether group was less
than half compared to placebo recipients (3.4 versus 7.4
eggs/10 ml urine, P < 0.001). Heavy S. haematobium infections,
micro- and macrohaematuria, and the incidence of malaria parasitaemia were all significantly lower in artemether recipients. In
conclusion, previous findings of the efficacy of artemether
against S. japonicum and S. mansoni could be confirmed for
S. haematobium, although the protective efficacy was considerably lower.
In-depth study of artemisinin derivatives
Laboratory studies on the antischistosomal properties of
artemisinin derivatives were continued. The activities of
artemether and artesunate, at present the two derivatives used
most widely in the treatment of malaria, were tested against different developmental stages of schistosome parasites. It is also
important to find out what effect the 7-day monotherapy regi-
mens which are being increasingly used to treat malaria have
on schistosomiasis, since in many areas malaria patients are
also likely to be exposed to schistosomiasis. This was investigated in the same series of experiments.
Mice infected with juvenile or adult S. mansoni were treated
with artemether or artesunate at various doses and regimens
including the ones currently used for monotherapy of malaria.
Three doses of artemether, at concentrations of 150 or 300 mg/
kg, administered to juvenile S. mansoni, resulted in worm reduction rates of 88 – 97%, which were significantly higher than the
67–77% obtained with artesunate (P< 0.05). 600 or 800 mg/kg
artemether, administered for 2– 4 consecutive days to mice with
adult S. mansoni, reduced the worm burden by 46 – 51%
(P< 0.05). The reduction of the worm burden with artesunate
was considerably lower, 24 – 33%, and not significant when
compared with untreated control mice. Seven-day monotherapy
regimens against adult S. mansoni showed total worm reduction
rates of 53 – 61% with artemether and 34 – 49% with artesunate.
We concluded that artemether and artesunate are both efficacious antischistosomals, but artemether displayed consistently
higher activities. In an investigation of the long-term toxicity of
oral artemether, SD strain rats were treated orally with 80 mg/kg
or 400 mg/kg once every 15 days for a total of 10 doses. The
results indicated that for rats, oral artemether at the dosages
given was safe.
International collaboration; Jürg Utzinger (STI) and Eliezer N‘Goran (University of
Cocody, Côte d’Ivoire), who were awarded the Lombard-Odier prize of the CSRS
for research in partnership in 2001, for their work on schistosomiasis in Côte
d’Ivoire. (Source: N.A. Weiss)
Optimising chemotherapeutic interventions against
S. haematobium
Praziquantel is still the most widely used drug against schistosomiasis, and it is important to find the optimum pattern of treatment and re-treatment to reduce reinfection and potential lasting damage from the disease. Four villages in south-central
Côte d’Ivoire where the prevalence of S. haematobium was high
were selected for a comparison of reinfection patterns 6 –24
months after systematic treatment of schoolchildren. At baseline, S. haematobium prevalence was 88 – 94% in Taabo, located beside a large man-made lake, and in Batera and Bodo,
where there were small dams. In Assinzé, a village without manmade environmental alterations, the baseline prevalence was
lower at 67%. Six months after praziquantel treatment prevalence and intensity of infections were significantly reduced in all
villages. The patterns of reinfection were different. In Taabo,
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prevalence of infection had returned almost to baseline level by
12 months after treatment. Prevalence and intensity of infection
increased gradually in Bodo and markedly during the second
year of the follow-up in Assinzé; and remained almost constant
from 6 –24 months post-treatment in Batera. This study confirmed that reinfection patterns vary widely, so that treatment
strategies should be well adapted to the characteristics of each
specific setting.
In a further study in Taabo, where unexpectedly fast reinfection was observed, all schoolchildren were treated twice with
praziquantel (40 mg/kg orally) 4 weeks apart. We found very high
cure and egg reduction rates of 93.0% and 96.6%, respectively,
which suggests that two doses of praziquantel within a few weeks
could be very efficacious in areas of high infection intensity.
Scientists:
B. Scorneaux, M. Tanner, S. Wittlin, P. Vounatsou
Guest Scientist:
S.H. Xiao
Collaboration:
Office of Population Research, Princeton University, USA
(J. Utzinger, J. Keiser); Institute of Parasitic Diseases, Chinese
Academy of Preventive Medicine, Shanghai, PR China (S.H.
Xiao); Hunan Institute for Parasitic Diseases, Yueyang PR
China (Y. Li); Queensland Institute for Medical Research, Brisbane, Australia (D. McManus); CSRS and Université de
Cocody, Abidjan, Côte d’Ivoire (E.K. N’Goran); WHO/TDR
(R. Bergquist)
Funding:
WHO/TDR, Swiss Academy of Sciences
6.6
Schistosomiasis epidemiology
Questionnaires for rapid schistosomiasis screening
An important epidemiological feature of schistosomiasis is its
focal spatial distribution. Rapid assessment procedures for the
identification of individuals and communities at highest risk of
morbidity enable interventions to be targeted cost-effectively.
More than a decade ago, the STI developed a powerful tool; the
use of questionnaires distributed through schools. Asking children about the presence of blood in urine proved to be highly
effective for community screening for S. haematobium. This
method was introduced and validated in rural Tanzania, and has
since been successfully extended to numerous other countries
in sub-Saharan Africa. This work was recently reviewed: in
10 countries, 133,880 children have been interviewed in 1,282
schools, and 54,996 children examined for S. haematobium. It
was consistently found that questionnaires were well accepted,
reliable and highly cost-effective for screening, despite a great
variability in cultural, ecological and epidemiological settings.
More recently, the questionnaire approach was also adapted
for intestinal schistosomiasis caused by S. mansoni. Evidence
from 48,258 children interviewed in 545 schools indicated that
reported “blood in stool” and reported “bloody diarrhoea” are
valuable indicators for community diagnosis. However, the diagnostic performance of the questionnaires for S. mansoni is
weaker than for S. haematobium, and although the results are
encouraging, there is a need for additional validation before this
approach can be used in a given setting. More recently, the use
of questionnaires was extended from community to individual
diagnosis and showed considerable promise.
WHO is recommending the use of questionnaires because of
their great potential as a first step to identify the communities at
highest risk of the disease, so that limited resources for control
can be optimally used.
44
Co-infection with S. haematobium and HIV-1 in rural Zambia
A prospective cohort study was conducted in two villages in
Zambia, to compare the efficacy of praziquantel in the treatment
of schistosomiasis haematobium in people with and without
concomitant HIV infection. 507 individuals with S. haematobium
infection were enrolled and followed up for 12 months after
treatment with a single dose of praziquantel. 73 of them were
co-infected with HIV. The study demonstrated that praziquantel
is still very effective in the treatment and control of
S. haematobium even when there is co-infection with HIV (without symptoms and signs of AIDS/HIV disease). Resistance to
S. haematobium reinfection was not altered in subjects coinfected with HIV. Individuals with co-infection excreted fewer
eggs and complained less of haematuria than those without HIV
infection, and the sensitivity and positive predictive value of
reported haematuria as an indication of heavy infection were
lower in the group co-infected with HIV. This observation may
have implications for the use of haematuria as an indicator for
rapid diagnosis of schistosomiasis in areas where HIV is highly
prevalent.
Morbidity due to S. mekongi in Northeastern Cambodia
A study of the effect of damage to internal organs due to S.
mekongi infection, and its reduction after treatment, was carried
out in the Northeastern Province of Stung Treng, in Cambodia.
In a baseline survey, parasitological and ultrasound examination
data were collected among 219 individuals from Sdau, a village
on one of the tributaries of the Mekong. Children less than 15
years of age were significantly more often infected and had significantly more heavy infections (> 400 eggs per gram of stool)
than older children. Other geohelminths detected in the study
population included hookworm (76%), Ascaris lumbricoides
(27%) and Trichuris trichiura (3%). Schistosomiasis infection
was significantly associated with hookworm infection (OR=2.77,
95% CI: 1.41– 5.44).
Pathology was found among 83% of all subjects (mean age:
16.4 years; range 3 – 69) and its prevalence was similar in all
age groups. Periportal thickening was detected more often in
younger than older groups (p < 0.05). Portal vein enlargement
was found more often among older subjects, but this difference
was not significant. Few cases of severe pathological lesions
were recorded.
Survey of infection with S. mekongi in Cambodia; children in Cambodia with stool
samples. (Source: S. Biays Odermatt)
Two groups were treated with praziquantel. In Group I, 49
people were only treated at baseline while in Group II, 44 people were treated at least once at 6 or 12 months after the initial
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baseline treatment. The 93 individuals were re-examined at
24 months after treatment with praziquantel. Both groups had
similar levels of pathology (around 78%) at baseline. At 24
months there was a statistically significant reduction in the
prevalence of infection (Group I: 28% and Group II: 15%) but no
significant change was observed in the prevalence of pathology, and after adjusting for age there were no statistically significant differences in the prevalence of infection and pathology
between the two groups. In conclusion, there is substantial morbidity due to S. mekongi in the remaining foci of endemicity in
S. E. Asia and multiple treatments may be necessary to reduce
pathological lesions. Furthermore, there is an association
between S. mekongi and hookworm infections.
Standardisation of ultrasound findings on schistosomiasis
morbidity
A revised practical guide to the standardised use of ultrasonography for the assessment of morbidity due to S. mansoni and
S. haematobium was published by WHO in 2000. Recommendations for S. japonicum and S. mekongi, which will be included
in a WHO publication covering all four Schistosoma species,
were discussed at a meeting initiated by WHO which was
prepared and organised by STI staff and held during the
3rd Regional Network meeting on Asian Schistosomiasis (RNAS)
in Phnom Penh in May 2002.
Scientists:
C. Hatz, C. Lengeler, P. Odermatt, M. Tanner, P. Vounatsou
PhD student:
V. Mwanakasale (coinfection study)
Collaboration:
CSRS and Université de Cocody, Abidjan, Côte d’Ivoire
(E.K. N’Goran, A. Yapi, N.A. N’Guessan, S.D. Kigbafori,
C. Acka Adjoua); Office of Population Research, Princeton
University, Princeton, USA (J. Utzinger, J. Keiser, B.H. Singer);
Imperial College, Division of Biomedical Sciences, London, UK
(E.C. Holmes, M.E. Bollard, J. Nicholson); University of Toronto,
Faculty of Medicine, Toronto, Canada (I. Bogoch); Médecins
sans Frontières-Switzerland, Cambodia; WHO, Hanoi, Vietnam;
WHO/TDR; University of Düsseldorf, Germany
Funding:
population being infected with at least three parasites, and only
8 individuals (3%) exhibiting no infection. In this community too,
we found a statistically significant positive association between
S. mansoni and hookworm infections with an adjusted odds
ratio of 2.09 (95% CI: 1.19 – 3.66, P= 0.01). Our findings call for
integrated approaches, employing chemotherapy in combination with health education and adequate water supplies and
sanitation for successful and sustainable control of multiple parasitic infections.
A large-scale epidemiological study that started in 2001 in
57 villages in the region of Man is screening children from each
primary school for schistosomes, geohelminths, intestinal protozoa and malaria parasites. The data will be coupled with a geographical information system (GIS) and used to produce risk
maps for single and multiple species parasitic infections. The
project is described in more detail in Section 5.5.
Effect of praziquantel against hookworm
Praziquantel is efficacious against all human schistosome parasites and has become the cornerstone of schistosomiasis control. Thus far, its anthelminthic properties have not been documented. We examined stool samples from 96 schoolchildren
from an area highly endemic for both S. mansoni and hookworm
infections before and 4 weeks after systematic praziquantel
treatment. We found a significant reduction in the prevalence of
hookworm infection, from 75.0% to 40.6% (OR = 0.21; 95% CI:
0.16 – 0.28). Infection intensities, expressed by geometric mean
egg counts of all children, were also reduced significantly
from 10.7 to 2.0 eggs per gram of stool (paired t-test =7.78,
P< 0.001). If these findings are confirmed, they indicate that the
use of praziquantel on a large scale for schistosomiasis control
could also help to reduce the burden of hookworm.
Scientists:
C. Lengeler, M. Tanner, P. Vounatsou
PhD student:
G. Raso
Collaboration:
CSRS and Université de Cocody, Abidjan, Côte d’Ivoire
(E.K. N’Goran, A. Yapi, N.A. N’Guessan, S.D. Kigbafori,
C. Acka Adjoua); Office of Population Research, Princeton
University, Princeton, USA (J. Utzinger, J. Keiser, B.H. Singer);
Department of Pathology, University of Cambridge, UK
(M. Booth); Institute for Infectious Diseases (A. Luginbühl,
K. Schopfer) and Institute of Geography (D. Wastl-Walter), University of Berne, Switzerland
Funding:
Centre for Health and Wellbeing at Princeton University, USA;
SNSF; Favre-Sturzenegger Foundation, Switzerland
MSF; WHO; Claire Sturzenegger-Jean Favre Foundation;
SNSF; Centre for Health and Wellbeing, Princeton University,
USA.
6.7
Parasite associations and multiparasitism
in Côte d’Ivoire
Multiple parasitic infections seem to be the rule rather than the
exception in many parts of the developing world, but most studies up to now have been in single organism-single host models.
We therefore carried out two studies in rural areas of western
Côte d’Ivoire. In the first, we explored possible parasite associations and assessed the extent of multiparasitism among
325 schoolchildren, aged 6 –14 years. Stool samples were
screened over several days to assess the prevalence of S. mansoni, geohelminths and intestinal protozoa. Multiparasitism was
extremely common with > 60% of the children harbouring three
or more parasites. We found a highly significant positive association between S. mansoni and hookworm infections with an
adjusted odds ratio of 2.25 (95% CI: 1.31– 9.85, P < 0.01). The
higher the intensity of S. mansoni infections the more likely the
children were to have a concurrent hookworm infection. In the
second study, on 260 people aged from 1 month to 69 years,
multiparasitism was again highly prevalent, with two thirds of the
6.8
Interventions against water-related pathogens
Amoebiasis
Amoebiasis, caused by Entamoeba histolytica, is one of the
most common intestinal parasitic infections world-wide. The disease is believed to affect about 480 million people, and leads to
40,000 –100,000 deaths per year. E. histolytica has been redescribed in recent years as a complex of two species that are
morphologically identical: the apathogenic E. dispar and the
pathogenic E. histolytica. It is the latter which causes the wellknown amoebiasis pathology, colitis and liver abscesses. Laboratory tests are now available that allow discrimination between
the two species, but as yet they have not been tested for field
use in epidemiological studies. Furthemore, few studies have
45
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Recording stool samples in the laboratory of the CSRS, Côte d‘Ivoire. (Source:
C. Lengeler)
been performed using a species-specific diagnosis at community level in endemic areas, especially in sub-Saharan Africa.
We conducted a repeated cross-sectional study in 967
schoolchildren in central Côte d’Ivoire (West Africa) in order to
compare and evaluate several diagnostic methods, and also to
assess the proportion of infections due to each species. Methods compared were light microscopy, two different antigen
detection assays, and one PCR assay. At the start of the study
(T0) all the children were screened by microscopy and an
unspecific ELISA test for “Entamoeba spp.” A single microscopic examination gave the prevalence of the E. histolytica/
E. dispar species complex as 18.8%, but using the unspecific
ELISA test it was 31.4%. About 2 months after the initial screening, new stool specimens were collected on two consecutive
days (T1 and T2), from all the 182 children who were found to be
positive by microscopy at T0, and from 155 randomly selected
children who were negative at the primary screening. The samples were examined microscopically and also tested with a second ELISA antigen detection test specific for E. histolytica
(n = 238), and with a species-specific PCR assay (n =193).
The cumulative microscopic prevalence for T1 and T2 was
27.7% for E. histolytica/E. dispar. The overall prevalence of
E. histolytica as found by species-specific ELISA antigen detection was 0.83%. When microscopically positive samples were
tested using a specific PCR assay the ratio of E. histolytica:
E. dispar was 1:46. These results suggest that the vast majority
of Entamoeba infections in this setting are apathogenic. This
might help to explain the observation that although high infection rates have been found in Africa using microscopic assays,
the rate of hepatic amoebic disease is low. Both species-specific tests performed well, but the ELISA test was found to be a
lot easier to use for large-scale field screening.
Scientists:
G. Bordmann I. Felger, C. Lengeler, HP Marti
Technologist:
A. Oettli
MSc Student:
F. Heckendorn
Collaboration:
CSRS, Abidjan, Côte d’Ivoire; Techlab Ltd, Baltimore, USA
Funding:
Techlab Ltd
Pure water from sunlight: the SODIS health impact study
More than one third of the people in rural and peri-urban areas
of developing countries have no access to sufficient clean
drinking water free of pathogens. Waterborne gastro-enteritis
remains a public health problem. SODIS (solar water disinfection) is a simple low-cost water purification method that uses
46
sunlight to kill water-borne pathogens in contaminated drinking
water by irradiation and increased temperature. The efficacy of
the method is well established, but it is now urgent to assess its
effectiveness under real life conditions. STI recently assessed
the social acceptability of SODIS in Bangladesh, and found
specific criteria for its implementation and use there.
A study in Bolivia is now in progress to assess the health
impact of the SODIS technology. In Bolivia, a nationwide SODIS
programme is operational to disseminate and promote SODIS
widely through interested local NGOs. This provides the ideal
framework for a comprehensive effectiveness study. A pilot
study confirmed that diarrhoeal illnesses are frequent (about
3 – 4 episodes per child per year), defined appropriate social
and cultural approaches, established valid study instruments
and selected a study team. A case-control study designed on
the basis of this preliminary work is now being carried out in 15
villages of the district of Mizque, department of Cochabamba, in
South-Western Bolivia, to assess the impact of the SODIS intervention on childhood diarrhoea in rural areas.
Scientists:
S. Indergand, D. Mäusezahl, T. Smith, M. Tanner
PhD Student:
M. Hobbins
Collaborations:
EAWAG/SANDEC, Dübendorf, Switzerland (M. Wegelin);
UNICEF, Bolivia; SODIS Foundation Latin America; CASA,
Cochabamba, Bolivia; University of Berkeley, California, USA
Funding:
Nestlé Corporation; Coca-Cola Corporation; NIH, USA
Water-borne pathogens in Switzerland
Collaboration has continued with the Cantonal Laboratories of
Baselland and Solothurn in north-western Switzerland, in projects aimed at improving understanding of the epidemiology of
water-borne agents that can cause diarrhoeal diseases and
gastroenteritis. In recent years, much attention has been paid to
“Norwalk-like viruses” (NLVs), which belong to the Caliciviridae.
NLVs are transmitted by the faecal-oral and aerosol routes, and
are one of the most common causes of outbreaks of nonbacterial gastroenteritis. In the United States, NLVs are thought to be
responsible for 96% of nonbacterial gastroenteritis and 67% of
all illnesses caused by known food-borne pathogens.
An outbreak investigation in the German-speaking area of
Switzerland made the first attempt to assess and describe the
epidemic potential of NLVs in this country. In co-operation with a
number of Cantonal Laboratories and public health specialists,
a total of 7 NLV-suspicious outbreaks during 2001 were
recorded, analysed and classified. In five of the seven outbreaks the NLV agent was demonstrated by RT-PCR in stool
samples (in one sample the PCR product could not be
sequenced, and in another no samples were provided). The
clinical symptoms fitted the case definition of NLV-infections.
Four of the outbreaks were in different schools and scout camps
(158 patients), one was a municipal outbreak (number of
patients estimated at a few hundred), one occurred in a health
resort (approximately 40 patients) and one was in a group of
25 friends and relations. The municipal outbreak was thought to
be water-borne, but the others were considered to demonstrate
the importance of person-to-person transmission of the NLVagent.
The outbreak investigations are being complemented by a
study on mixed infections and a case-control study to assess
the risk factors involved in NLV infections. More than 400 presumptive NLV cases from Switzerland have been screened so
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far, and around 14% proved to be NLV positive as established
by RT-PCR. This corresponds to the frequencies of NLV in other
countries such as the USA, the UK and the Netherlands. The
case-control study involves the cantonal medical services, private practitioners, and public and private diagnostic laboratories, and it will be the first of this kind and dimensions.
As a follow-up of earlier studies on cryptosporidiosis in Switzerland (see previous STI Reports), stool samples from patients
found to be positive for Cryptosporidium spp. were used for
genotyping. Nine out of 12 samples could be successfully
genotyped, and were all found to belong to the bovine genotype. In one stool sample, two strains of Cryptosporidium were
demonstrated, suggesting a mixed infection. One of the strains
showed a full sequence identity with reference strains from
calves, and the other a similarity of 97.5%. The fact that only
bovine genotypes were detected strongly suggests that sporadic cryptosporidiosis might primarily be a zoonotic disease in
Switzerland.
Scientist:
M. Tanner
Students:
A. Christen (MSc), R. Fretz (PhD)
Collaborations:
Cantonal Laboratory Baselland (P. Svoboda, T. Jaeggi); Cantonal Laboratory Solothurn (P. Kohler, T. Lüthi); Cantonal Medical Officers of Baselland (D. Schorr), Basel (B. Bucheli) and
Solothurn (H. Binz); Swiss Federal Office of Health (BAG)
(P. Baumgartner)
Funding:
Swiss Federal Office of Health (BAG); Canton of Baselland
Genton B (2001) Malaria vaccines: development of new technologies for immunization (invited review). CPD Inf 2, 102 –109.
Genton B & Loutan L (2001) Vaccinations: choix individuel ou responsabilité communautaire? Méd Hyg 59, 1163 –1164.
Genton B, Betuela I, Felger I, Al-Yaman F, Anders RF, Saul A , Rare L, Baisor M,
Lorry K, Brown GW, Pye D, Irving DO, Beck H-P, Smith TA & Alpers MP (2002) A
blood-stage malaria vaccine (MSP1, MSP2, RESA) reduces Plasmodium falciparum density and exerts a selective pressure on parasite populations in a Phase
I/IIb trial in Papua New Guinea. J Inf Dis 185, 820 – 827.
Genton B & Corradin G (2002) Malaria vaccines: from the laboratory to the field
(invited review). Curr Drug Targets – Immune, Endocrine & Metabolic Disorders 2,
255 –267.
Genton B (in press) Vaccins contre la pauvreté? Rev Méd Suisse Romande.
Hatz C (2001) The use of ultrasound in schistosomiasis. Adv Parasitol 48, 225-284.
Heckendorn F, N’Goran E.K, Felger I, Vounatsou P, Yapi A, Oettli A, Marti HP,
Dobler M, Traoré M, Lohourignon KL, Lengeler C (in press) Species-specific field
testing of Entamoeba sp. in an area of high endemicity. Trans. R. Soc.Trop. Med.
Hyg.
Hobbins M, Svoboda P, Tanner M & Lüthi T (2001) Nachweis von Norwalk-likeViren-Sequenzen in Umweltproben. Gwa 7, 473 – 479.
Jemaneh L. & Lengeler C (2001) The use of morbidity questionnaires to identify
communities with high prevalence of geohelminth infections in Gondar region,
Ethiopia. Ethiop Med J 39, 213 – 28.
Keiser J & Burri C (2001) Evaluation of quinolone derivatives for antitrypanosomal
activity. Trop Med Int Health 6, 369 – 389.
Keiser J, Stich G & Burri C (2001) New drugs for the treatment of Human African
Trypanosomiasis, an R&D perspective (Review). Trends Parasitol 17, 42 – 49.
Keiser J, N’Goran EK, Traoré M, Lohourignon KL, Singer BH, Lengeler C, Tanner M
& Utzinger J (2002) Polyparasitism with Schistosoma Mansoni, geohelminths, and
intestinal protozoa in rural Côte d’Ivoire. J Parasitol 88, 461– 466.
Publications:
Abdulla S, Armstrong Schellenberg JRM, Nathan R, Mukasa O, Marchant T, Smith
T, Tanner M & Lengeler C (2001) Impact of an insecticide treated net programme
on malaria morbidity in children under two years of age in Tanzania. BMJ 322,
270 – 273.
Abdulla S, Armstrong Schellenberg JRM, Mukasa O & Lengeler C (2002) Usefulness of a dispensary based case-control study for assessing morbidity impact of
a treated net programme. Int J Epidemiol 31, 175 –180.
Armstrong Schellenberg JR, Abdulla S, Nathan R, Mukasa O, Marchant T,
Kikumbih N, Mushi AK, Mponda H, Minja H, Mshinda H, Tanner M & Lengeler C
(2001) Effect of large-scale social marketing of insecticide-treated nets on child
survival in rural Tanzania. Lancet 357, 1241–7.
Armstrong Schellenberg JR, Nathan R, Abdulla S, Mukasa O, Marchant T, Tanner
M & Lengeler C (2002) Risk factors for child mortality in rural Tanzania. Trop Med
Int Health 7, 506 – 511.
Armstrong Schellenberg JR, Minja H, Mponda H, Kikumbih N, Mushi A, Nathan R,
Abdulla S, Mukasa O, Marchant T, Tanner M & Lengeler C (2002) Re-treatment of
mosquito nets with insecticide. Trans R Soc Trop Med Hyg. 96, 368 – 369.
Armstrong Schellenberg JRM, Mukasa O, Abdulla S, Marchant T, Lengeler C,
Kikumbih N, Mshinda H & Nathan R (2002) Ifakara Demographic Surveillance System (Ifakara DSS). INDEPTH Monograph 1, 159 –164.
Blum J, Nkunku S & Burri C (2001) Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol
treatment of Human African Trypanosomiasis. Trop Med Int Health 6, 390 – 400.
Blum J & Burri C (2002) Treatment of late stage sleeping sickness caused by T. b.
gambiense: a new approach to the use of an old drug. Swiss Med Wkly 132,
51– 56.
Burri C (2001) Are there new approaches to roll back trypanosomiasis (Editorial).
Trop Med Int Health 6, 327– 329.
Burri C & Keiser J (2001) Pharmacokinetic investigations on patients refractory to
melarsoprol treatment from northern Angola. Trop Med Int Health 6, 412 – 420.
Burri C & Brun R (in press) African trypanosomiasis – In: Mansons’s Tropical Diseases 21st Edition. Eds. Cook G, Zumla A. London: Harcourt Publishing.
Keiser J, N’Goran EK, Singer BH, Lengeler C, Tanner M & Utzinger J (in press).
Association between Schistosoma mansoni and hookworm infections among
schoolchildren in Côte d’Ivoire. Acta Trop.
Legros D, Ollivier G, Gastellu-Etchegorry C, Paquet C, Burri C, Jannin J & Büscher
P (2002) Treatment of human African trypanosomiasis – present situation and
needs for research and development. Lancet Infec.Dis. 2, 437– 40
Lengeler C (2000) Insecticide-treated bednets and curtains for preventing malaria.
Cochrane Database Syst Rev 2, CD000363.
Lengeler C, Utzinger J & Tanner M (2002) Questionnaires for rapid screening of
schistosomiasis in sub-saharan Africa. Bull World Health Org. 80, 235 – 242.
Lengeler C, Utzinger J & Tanner M (2002) Screening for schistosomiasis in subsaharan Africa. Trends Parasitol 18, 375 – 377.
Li Y, Sleigh AC, Ross AGP, Li Y, Zhang X, Williams GM, Yu X, Tanner M & McManus
DP (2001) Human susceptibily to Schistosoma japonicum in China correlates with
antibody isotypes to native antigens. Trans R Soc Trop Med Hyg 95, 441– 448.
Li YS, Sleigh AC, Tanner M, Dessein A, Williams GM & McManus DP (2002). Fiveyear impact of repeated praziquantel treatment on sub-clinical morbidity due to
Schistosoma japonicum in China. Trans R Soc Trop Med Hyg. 96, 438 – 443.
Marchant T, Armstrong Schellenberg J, Edgar T, Nathan R, Abdulla S, Mukasa O,
Mponda H & Lengeler C (2002) Socially-marketed insecticide-treated nets
improve malaria and anaemia in pregnancy in southern Tanzania. Trop Med Int
Health 7, 149 –158.
Marchant T, Armstrong Schellenberg J, Edgar T, Ronsmans C, Nathan R, Abdulla
S, Mukasa O, Urassa H & Lengeler C (2002) Anaemia during pregnancy in southern Tanzania. Ann. Trop. Med. Parasitol. 96, 477– 487.
Menendez C, Quinto LL, Kahigwa E, Alvarez L, Fernandez R, Gimenez N, Schnellenberg D, Aponte JJ, Tanner M & Alonso PL (2001) Effect of malaria on soluble
transferrin receptor levels in Tanzania infants. Am J Trop Med Hyg 65, 138 –142.
Minja H, Armstrong Schellenberg JA, Mukasa O, Nathan R, Abdulla S, Mponda H,
Tanner M, Lengeler C & Obrist van Eeuwijk B (2001) Introducing insecticidetreated nets in the Kilombero Valley, Tanzania: the relevance of local knowledge
and practice for an Information Education and Communication (IEC) campaign.
47
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N’Goran EK, Gnaka HK, Tanner M & Utzinger J (in press) Efficacy and side effects
of two praziquantel treatments against Schistosoma haematobium infections
among schoolchildren from Côte d’Ivoire. Ann Trop Med Parasitol.
Utzinger J, Chollet J, Zuwu T, Xiao S & Tanner M (2002) Comparative study of the
effects of artemether and artesunate on juvenile and adult Schistosoma mansoni
in experimentally infected mice. Trans R Soc Trop Med Hyg 96, 318 – 323.
N’Goran EK, Utzinger J, Guessan AN, Müller I, Zamblé K, Lohourignon KL, Traoré
M, Sosthène BA, Lengeler C & Tanner M (2001) Reinfection with Schistosoma
haematobium following school-based chemotherapy with praziquantel in four
highly endemic villages in Côte d’Ivoire. Trop Med Int Health 6, 817– 825.
Utzinger J, Vounatsou P, N’Goran EK, Tanner M & Booth M (2002) Reduction in the
prevalence and intensity of hookworm infections after praziquantel treatment for
schistosomiasis infection. Parasitol Int 32, 759 –765.
N’Goran EK, Utzinger J, Gnaka HN, Yapi A, N’Guessan NA, Kigbafori SD, Lengeler
C, Chollet J, Xiao S & Tanner M (in press) Randomized, double-blind, placebocontrolled trial of oral artemether for the prevention of patent Schistosoma haematobium infections. Am J Trop Med Hyg.
Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H
& Alonso P (2001) Intermittent treatment for malaria and anaemia control at time of
routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial.
Lancet 357,1471–7.
Smith T, Leuenberger R & Lengeler C (2001) Child mortality and malaria transmission intensity in Africa. Parasitol Today 17, 145 –149.
Svoboda P, Bissegger Ch, Campbell A & Tanner M (2001) Comparison of immunomagnetic separation and flocculation to isolate Cryptosporidium spp. Oocysts
from drinking water samples. Mitt Geb Lebensmittelunters Hyg 92, 168 –177.
Urbani C, Sinoun M, Socheat D, Pholsena K, Strandgaard H, Odermatt P & Hatz C
(2002) Epidemiology and control of mekongi schistosomiasis. Acta Trop 82,
157–168.
Utzinger J, N’Goran EK, N’Dri A, Lengeler C, Shuhua X & Tanner M (2000). Oral
artemether for prevention of Schistosoma mansoni infection: randomised controlled trial. Lancet 355 (9212), 1320– 5.
Utzinger J, N’Goran EK, Tanner M & Lengeler C (2000) Simple anamnestic questions and recalled water-contact patterns for self-diagnosis of Schistosoma mansoni infections among schoolchildren in western Côte d’Ivoire. Am J Trop Med Hyg
62, 649 – 655.
Utzinger J, N’Goran EK, N’Dri A, Lengeler C & Tanner M (2000). Efficacy of praziquantel against Schistosoma mansoni with particular consideration for intensity of
infection. Trop Med Int Health 5, 771–778.
Utzinger J, Booth M, N’Goran EK, Müller I, Tanner M & Lengeler C (2001) Relative
contribution of day-to-day and intra-specific variation in faecal egg counts of
Schistosoma mansoni before and after treatment with praziquantel. Parasitology
122, 537– 544.
Utzinger J, Chollet J, You JQ, Mei JY, Tanner M & Xiao SH (2001) Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and
S. mansoni in experimentally infected animals. Acta Trop 80, 9 –18.
Utzinger J, Xiao S, N’Goran EK, Bergquist R & Tanner M (2001) The potential of
artemether for the control of schistosomiasis. Int J Parasitol 31, 1549 –1562.
Utzinger J, Xiao S, Keiser J, Chen M, Zheng J & Tanner M (2001) Current progress
in the development and use of artemether for chemoprophylaxis of major human
schistosome parasites. Curr Med Chem 8, 1841–1859.
48
Xiao SH, Shen BG, Chollet J, Utzinger J & Tanner M (2000) Tegumental changes in
adult Schistosoma mansoni harboured in mice treated with artemether. J Parasitol
86, 1125 –1132.
Xiao SH, Utzinger J, Chollet J, Endriss Y, N’Goran EK & Tanner M (2000) Effect of
artemether against Schistosoma haematobium in experimentally infected hamsters. Int J Parasitol 30, 1001–1006.
Xiao SH, Chollet J, Utzinger J, Matile H, Mei JY & Tanner M (2001) Artemether
administered together with haemin damages schistosomes in vitro. Trans R Soc
Trop Med Hyg 95, 67–71.
Xiao SH, Shen BG, Chollet J, Utzinger J & Tanner M (2001) Tegumental alterations
in juvenile Schistosoma haematobium harboured in hamsters following artemether
treatment. Parasitol Int 50, 175 –183.
Xiao SH, Shen BG, Utzinger J, Chollet J & Tanner M (2002) Transmission electron
microscopic observations on ultrastructural damage in juvenile Schistosoma mansoni caused by artemether. Acta Trop 81, 53 – 61.
Xiao S, Tanner M, N’Goran EK, Utzinger J, Chollet J, Bergquist R, Chen M & Zheng
J (2002) Recent investigations of artemether, a novel agent for the prevention of
schistosomiasis japonica, mansoni and haematobia. Acta Trop 82, 175 –181.
Xiao S, Yang Y, You Q, Utzinger J, Guo H, Jiao P, Mei J, Guo J, Bergquist R & Tanner M (2002) Potential long-term toxicity of repeated orally administered doses of
artemether in rats. Am J Trop Med Hyg 66, 30 – 34.
Xiao S, Shen B, Utzinger J, Chollet J & Tanner M (in press) Ultrastructural alterations in adult Schistosoma mansoni caused by artemether. Mem Inst Oswaldo
Cruz.
Xiao S, Wu Y, Tanner M, Wu W, Utzinger J, Mei J, Scorneaux B, Chollet J & Zhai Z
(in press) Schistosoma japonicum: in vitro effects of artemether combined with
haemin depend on cultivation media, and appraisal of artemether adducts
appearing in the media. Parasitol Res.
Xiao S, You J, Gao H, Mai J, Jiao P, Chollet J, Tanner M & Utzinger J (in press)
Schistosoma japonicum: effect of artemether on glutathione S-transferase and
superoxide dismutase. Exp Parasitol.
Yang YQ, Xiao SH, Tanner M, Utzinger J, Chollet J, Wu JD & Guo J (2001)
Histopathological changes in juvenile Schistosoma haematobium harboured in
hamsters treated with artemether. Acta Trop 79, 135 –141.
Yu D, Sarol JN Jr., Hutton G, Tan D & Tanner M (2002) Cost effectiveness analysis
of the impacts on infection and morbidity attributable to three chemotherapy
schemes against Schistosoma japonicum in hyperendemic areas of the Dongting
Lake region, China. Southeast Asian J Trop Med Public Health.
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SECTION 7
Environment, Society and Health Systems
Introduction
• Assess and compare the frequency and distribution dynamics
The thematic umbrella “Environment, Society and Health Sysof the most relevant health problems and their estimated distems” is deliberately spanned very wide, and covers the activiease burden.
ties of several groups of researchers in the STI. Their interests
• Establish and map the key risk factors for ill-health, riskrange widely, but each of the projects undertaken within this
behaviour and risk groups.
framework attempts a systemic view, and places questions spe• Determine how low income city dwellers and nomadic populacific to disease and illness in the context of the society and the
tions perceive health problems, health risks and priorities in
health and social systems concerned.
relation to their actual health status.
The Swiss “research landscape” has been altered signifi• Analyse health- and help-seeking patterns and the factors that
cantly by the creation of fourteen National Centres of Comgovern the patterns.
petence in Research (NCCR) in 2000. These are long-term
• Determine the economic impact of health problems and illnational research programmes, each based at one university
ness burden at household/clan level.
but with a wide network of collaboration. The STI has been
• Review the concepts of “risk”
associated since the planning
and “vulnerability” in a transstage with the NCCR Northdisciplinary context and their
south; mitigating syndromes of
implication and applicability
global change, which is based
or health, environmental and
at the Centre for Development
social interventions.
and Environment in the Insti• Suggest, test and validate
tute of Geography, University of
adapted intervention strategies
Berne (Director, Prof. Hans
to improve health and wellHurni). The STI is responsible
being.
for Integrated Project 4 (IP4),
Health & Well-being. Starting
To achieve these objectives, epifrom July 2001, the NCCR funddemiological, anthropological,
ing provides some 800,000 CHF
demographic and economic
per year for an initial period of
approaches are being used, with
four years.
the support of a strong network
Project IP4 is concentrating
on projects in Africa, where The Centre Suisse de Recherches Scientifiques (CSRS) in Abidjan, Côte d’Ivoire; of collaboration with the other
regional co-ordinating centre for the NCCR project IP4. (Source: O. Girardin)
integrated projects of the NCCR
“syndromes of global change”
and the national and international partners of each of the IPs.
are highly prevalent. The continent is experiencing dramatic
IP4 has established the regional co-ordination centre for West
and interrelated demographic, social and economic changes
Africa, at the Centre Suisse de Recherches Scientifiques
that affect the health and well-being of many different popula(CSRS) in Abidjan, Côte d’Ivoire.
tion groups, often leading to marginalisation and poverty.
The expected outputs for the first four years of IP4 within the
National governments can barely meet the most urgent needs
NCCR are: i) an analysis of the burden of ill health and risk facfor health services. Consequently, increasing proportions of the
tors that govern the urban poor and nomadic populations; ii) an
population are excluded from health care both in urban and in
understanding of illness perception and how it governs healthrural areas. The great pressure on cultivable land is resulting in
seeking; iii) the designing and validation of adapted, accepted
unprecedented movements of people. The accelerated urbaniand feasible health care and promotion strategies; iv) the
sation process that is taking place is marked by important social
strengthening of national research capacity through training
transformations, and poor people in the rapidly-growing cities
and technology transfer, and v) achieving an overview of the key
are especially vulnerable. Among rural populations, nomadic
topic areas for possible mitigation strategies, focusing on the
groups in particular feel the impact of global changes. Tradivulnerability of the urban poor and the applicability of the “one
tional routes of migration may no longer be suitable owing to climedicine” concept for nomadic populations.
matic and environmental changes, and/or population pressure
It is evident that the STI’s role in the national and international
that brings resident populations into traditional areas of migranetwork of the NCCR will shape the research activities under the
tion. Apart from these new threats, nomadic populations have
umbrella, “Environment, Society and Health Systems” more and
always been largely excluded from health and education servmore in the coming years. The NCCR is not introducing comices, which have failed to develop structures adapted to their
pletely new interests into the research activities of the STI, but is
way of life.
a natural development, growing out of more than a decade of
The goal of IP4 is to generate a scientific basis for the
involvement in research on health systems and ways of improvdevelopment and validation of well-adapted, efficient and
ing health in urban environments, and many years of interest in
innovative strategies for health interventions and health planthe interface between human and animal health. Projects
ning options that will improve health and well-being for disrelated to these two main axes of the NCCR are described in
advantaged urban populations (the “urban poor”) and for
parts A and B of this section.
nomadic rural populations, with a particular emphasis on
The STI is also involved in a variety of other projects conwomen and children, by pursuing seven closely-interrelated
cerned with the efficient provision of health services, including
objectives:
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SECTION 7 Environment, Society and Health Systems
some which reflect the STI’s growing expertise in economic
analysis, and a continuing concern with studies in Switzerland
as well as internationally.
Research on health systems is a very wide area – indeed,
there are very few projects which do not in some way impinge
upon the delivery of health services. Intervention studies are
generally based on the local health facilities, and leave their
mark on staff training and infrastructure. Studies on diagnostic
methods, new drugs, or parasite resistance should eventually
be reflected in better health care. Finally, in the field of cultural
epidemiology the aim of many projects is to establish how
health services can be better adapted to fulfilling people’s perceived needs. A number of projects concerned in different ways
with provision of health services are described in Part 7C, in
addition to those elsewhere in this Report.
7A. Urban health and health systems
The explosive growth of cities in developing countries can have
dramatic effects on the health and well-being of people in urban
areas, and on their environment. The effects of urbanisation
have been an increasing concern since the 1980s, and many
activities of the STI in Africa have addressed questions of the
health and well-being of urban populations. From 1994 to 2001,
a number of aspects of urban agriculture were studied in Burkina Faso and Mauritania, especially the management and possible health risks of the use and re-use of wastewater for irrigation, and the economic impact of small-scale commercial homegardening. Another project, in Chad and in Senegal, using
participatory research methods, examined how people living in
deprived urban areas manage their environment. In East Africa,
research focussed on priority areas linked to the Dar es Salaam
Urban Health Project, which aimed at a structural and functional
rehabilitation of the public health services in this city of approximately 3 million inhabitants. During the reporting period, many
of these projects were gradually phased out, or were harmoniously integrated into project IP4 of the NCCR.
7A.1
Health impact and management of wastewater use
in small-scale agriculture in urban Sahelian settings:
risks and potential intervention strategies
Urban and peri-urban areas are very important sites for the production of vegetables and fruit by small-scale farmers and gardeners maintaining temporary or perennial home gardens.
Urban agriculture has substantial economic implications, both
for growers and consumers, but relatively few studies have
investigated the economics of urban agriculture in detail. Urban
agriculture helps to ensure a supply of fresh food in cities, and
can provide an income for people in the lower socio-economic
groups. On the other hand, it can create health risks for producers, food handlers and consumers owing to the fact that very
often wastewater is used and re-used for the irrigation of home
gardens. A project launched in 1994 investigated the complex
interactions involved in urban agriculture from epidemiological,
social, cultural and economic perspectives in two Sahelian
towns; Ouagadougou in Burkina Faso, and Nouakchott in Mauritania.
The first phases of the project included the identification of
health risks and the description of their distribution, the analysis
of the determinants of risk, and the identification and implementation of feasible intervention strategies. These activities were
described in the two preceding STI Biennial Reports. The main
activities during the third and last phase (2000 – 2001) were: i) to
assess the impact of home gardening on the household econ-
50
A “focus group” of home-gardeners in Ouagadougou talking about their lives and
problems. (Source: S. Gerstl)
omy through descriptive and analytical socio-economic studies;
ii) to support and follow up initiatives for demand-driven micro
projects identified during the second phase, by mobilising institutional actors (municipality, NGOs) and donors (co-operation
and multilateral agencies), and iii) to disseminate the research
results through workshops, conferences and publications.
Home gardeners represent an important but fragile population group in the urban social tissue. Home gardening is a major
income-generating activity that allows poorer, marginalised
people – often with limited access to education and no professional skills, and with limited access to resources – to cope in
the urban environment. However, households whose main earnings were from home gardening had lower monthly incomes
than comparable households with other activities, and these differences were specially marked in the rainy season. This was
one of the findings of sociological and participatory action
research, focussing on four communities of people living in the
area around home gardening sites, some of whom earned their
living from home gardens, and others who had other occupations. The survey provided information about social and economic conditions and also about the potential of the people to
improve their economic situation and the well-being of their
households, and their chances of doing so.
On the basis of these findings and the results from earlier
phases of research, and as a consequence of the participatory
action research, it was possible to launch concrete local interventions through partnerships between research groups and
municipal authorities, to ensure the sustainable and healthy
development of urban agriculture. In addition, the project also
contributed to the creation of regional networks and the organisation of meetings on urban agriculture in West Africa.
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Seite 51
Scientists:
G. Cissé, M. Tanner, K. Wyss
PhD student:
S. Gerstl
Collaboration:
CSRS, Abidjan, Côte d’Ivoire (O. Girardin); Ecole Inter-Etats
d’Ingénieurs de l’Equipement (EIER), Ouagadougou, Burkina
Faso (M. Kientga, S. Kenfack); WHO Office, Nouakchott, Mauritania (E. Benzerroug, L. Ould Baba, M. Ould Thaleb)
Funding:
SNSF, SDC
7A.2
Inhabitants of a deprived urban area manage their
own environment
The project aimed at fostering the translation of research results
into improvements in the living conditions of disadvantaged
populations in N’Djaména, Chad and Dakar, Senegal. In the last
phase of the project the objectives were to ensure exchange of
information, and to support and follow up initiatives identified
during the second phase, 1996 – 99, by the “action research”
capacity-building approach (STI Report 1999 – 2000). The study
activities were concentrated in N’Djaména, with parallel activities in Senegal. The approach was to empower all the actors
involved through regular scientific exchange, workshops, and a
wide dissemination of results which fostered the mobilisation of
institutional actors (municipal authorities, NGOs, etc.). The networking and sharing of experience between Chadian and Senegalese researchers was maintained by continuing scientific
exchange. At the end of the “phasing-out” period, communitybased organisations for better environmental management
have been empowered, and the activities of associations and
neighbourhood committees reinforced, so that they are able to
continue to carry out activities in the fields of sustainable waste
management, improved disease control, and social mobilisation
for street children. Collaboration between researchers and institutional actors (municipality, NGOs, multilateral agencies, etc.)
for sustainable urban environmental management has been
strengthened. Finally, networking and the sharing of experiences between different cities in the African region, and
between research groups, has been enhanced.
HIV/AIDS, malaria and diarrhoeal disease. In Abidjan a study of
social networks and illness, described below, is being followed
by further investigations of illness perception and coping strategies in a socio-economically very heterogeneous setting,
Yopougon Ward. Comparable studies have also been launched
in the other cities. Besides understanding the distribution of
health and disease and the underlying risk factors, these projects also aim to map urban health risks, and to relate biomedical and demographic findings to the inhabitants’ perceptions of
illness and of their environment.
Abidjan; social networks and illness
A project in Abidjan, Côte d’Ivoire (R. Bossart) examined social
networks and illness. The results showed that household members help each other in the identification of disease, in making
decisions about treatment, and with advice on health care
providers. The social network extending beyond the family is
quite wide when it comes to “moral support” – visits, comforting
words, and empathy – but is limited to a close circle of relatives
and friends when financial support is needed. Social networks
based on religion, both Christian and Moslem, play an important
role in terms of moral support and even in collecting money for
treatment. Only a few self-help groups, for instance rotating
credit associations, offer support to members in need. The main
conclusion is that the importance of social networks in illness
management is often idealised, and many individuals are left
alone in their struggle to find health care. This is particularly true
for people suffering from a stigmatised disease like HIV/AIDS.
They are afraid of speaking about their illness or asking for help,
even if they cannot afford to buy drugs.
Scientists:
G. Cissé, B. Obrist, N’D. Yémadji, M. Tanner, K. Wyss,
J. Zinsstag
Students:
R. Bossart (PhD), N. Othingué (PhD), M. Daigl (MSc)
Collaboration:
CSRS, Abidjan, Côte d’Ivoire (O. Girardin); Université de
Cocody (E. N’Goran) and Université de Abobo Adjamé, Abidjan, Côte d’Ivoire (P. Houenou); Ecole Inter-Etats d’Ingénieurs
de l’Equipement (EIER), Ouagadougou, Burkina Faso (M. Mampouya); CSSI-ITS , N’Djaména , Chad (M. Daugla); Ethnological Seminar, University of Basel; EPFL, Lausanne, Switzerland
(JC Bolay); EAWAG/SANDEC, Switzerland (R. Schertenleib,
D. Koné)
SNSF-NCCR, WHO/TDR, SDC, Swiss Academy of Sciences
(SANW)
Scientists:
N. Lorenz, M. Tanner, K. Wyss, N’D. Yémadji
Students:
D. Allassembaye (PhD), N. Othingué (MSc)
Collaboration:
CSSI-ITS, N’Djaména, Chad (M. Daugla); ENDA-GRAF, Dakar,
Senegal (M. Ndiaye); University of Avignon, France (P. Bachimon); University of Strasbourg, France (JL Piermay)
Funding:
Funding:
SNSF, SDC, WHO/TDR
7A.4
Health and Health Services in Dar es Salaam,
Tanzania
7A.3
Health and well-being in urban West Africa
One of the two main axes of research in project IP4 of the NCCR
(see Introduction above) concerns the improvement of the
health of people in urban areas, especially those in the most vulnerable groups. Studies are underway in three cities in three
countries; Abidjan in Côte d’Ivoire, Ouagadougou in Burkina
Faso, and N’Djaména in Chad. These are all places where the
STI has already worked and established networks of collaboration on which to base new projects. Studies are being carried
out on the prevalence of key health problems and their determinants, and on the relationship between highly vulnerable population groups, with particular emphasis on women and young
children, and important “diseases of poverty” such as
Private – public interactions and quality of care
Research within the EU-funded Concerted Action Improving
efficiency and quality of health networks in urban areas emphasised interactions between the public and private sectors. One
study compared the quality of public first-tier ante-natal care
(ANC) services with that of private ones in Dar es Salaam, Tanzania, on the basis of professionally-defined quality standards.
Structural, interpersonal and technical aspects of quality were
assessed for 16 randomly-selected providers, using checklists,
observation, and exit interviews with 166 women in the public
and 188 in the private sector. The results showed that both public and private providers were reasonably good in the structural
and interpersonal aspects of quality of care. However, both
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were poor in technical aspects of quality. For example, guidelines for dispensing prophylactic drugs against anaemia or
malaria were not respected, and diagnostic examinations for
the assessment of gestosis, anaemia, malaria or urine infection
were frequently not performed. Though neither public nor private providers were very good, private providers were significantly better in all aspects than public ones. The study concluded that approaches to improving quality of care should
emerge progressively as a result of regular quality assess-
Score for technical attributes of quality
40
30
20
10
0
public sector (n=166)
private sector (n=188)
Technical aspects of quality of care: comparison of scores between public and
private providers.
ments. Changes should be introduced by addressing a few
improvements at a time, always ensuring participation and ownership of every aspect of the strategy by the health personnel,
health planners and managers and also the community.
Scientists:
pation of the patients in sub-Saharan Africa. The aim was to
improve the quality of life and life expectancy of diabetes
patients in Dar es Salaam in a sustainable way, and to ensure
the availability and affordability of natural animal insulin. The
decision was made to decentralise the care of diabetics, which
had previously been based on the national referral hospital in
Muhimbili, by setting up clinics in three district hospitals. Initially, external funding supported the purchase of insulin.
Patients contributed 20% of the cost of treatment. At the time of
the evaluation this contribution had increased to 50%.
An evaluation of this cost-sharing project was carried out
by the SCIH/STI. The goal of the evaluation was to assess
i) whether the project’s main objectives, i.e. decentralisation by
setting up peripheral clinics, cost-sharing, and the constant
availability of natural animal insulin, had been achieved;
ii) whether the financial support from NDF had been invested as
planned, and iii) whether the project is sustainable, and valid for
other areas of Tanzania or other developing countries, and
whether there are lessons to be learnt for the improvement of
diabetes care.
The project was evaluated in terms of structure, process and
outcome. The main conclusion was that the project has
improved diabetes care in Dar es Salaam through better access
to care and availability of drugs, improved knowledge of diabetes among health facility staff, and improved diagnostic
methods. Patients have a better understanding of their disease
and are more satisfied with the care received. The workload at
the national referral hospital Muhimbili has been reduced. The
project has shown that the quality of life of diabetic patients can
be improved with relatively small investments. With decentralisation of care, cost-sharing and the purchase of natural insulin,
the financial burden to patients could be reduced.
G. Hutton, M. Tanner, K. Wyss
Students:
C. Boller (MD), S. Weiss (MSc)
Collaboration:
City Medical Office of Health, Dar es Salaam (D. Mtasiwa);
Gesellschaft für Technische Zusammenarbeit Germany
(R. Meyer); University of Brussels (B. Dujardin)
Funding:
Swiss Federal Office for Education and Science (BBW), SDC
Care for diabetic patients
Diabetes mellitus is one of the diseases whose prevalence
tends to increase as a result of “epidemiological transition”. It is
becoming an important cause of mortality, particularly in urban
areas. The overall prevalence of type 1 and type 2 diabetes in
African countries varies considerably. In Tanzania, it is estimated to be of the order of 0.01–1%. Life expectancy for a
newly diagnosed patient with type 1 (insulin dependent) diabetes in some parts of Africa may be as short as 1 year. Regular
provision of insulin significantly improves the outlook for these
patients, but insulin supply is at best intermittent, and insulin is
often not included in national essential drug lists. Even if insulin
is available, most patients cannot afford it. Diabetes care is not
usually integrated into primary health care facilities but is centralised in hospitals.
Based on an agreement with the Nutrition and Diabetes
Foundation (NDF), Bern, Switzerland, a diabetes project was
integrated into the Dar es Salaam Urban Health Project in 1994.
This was the first project for diabetes care with financial partici-
52
Diabetes clinic in Ilala, Dar es Salaam, Tanzania, showing the files kept on all
patients. (Source: Y. Brauchli)
Further projects concerned with diabetes care and insulin
supply have been started as diploma projects for Tanzanian students. One is assessing the availability and quality of services
for diabetic patients offered in private health facilities in Dar es
Salaam. These have mushroomed recently, and little data exists
about the services they offer. Another project plans to focus on
antidiabetic drugs, comparing sources, supply, availability,
quality and cost in the public and private sectors.
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Scientist:
K. Wiedenmayer
MSc students:
Y. Brauchli, T. Ewald, N. Ramadhani
Collaboration:
Nutrition and Diabetes Foundation (NDF), Bern, Switzerland
(A. Teuscher); Department of Pharmaceutics, MUCHS, Dar es
Salaam, Tanzania (M. Temu); City Medical Office of Health, Dar
es Salaam, Tanzania (D. Mtasiwa); Diabeteszentrum Lindenhof, Bern, Switzerland (A. Teuscher); Department of Pharmacy,
University of Basel (S. Krähenbühl)
Hypertension – a public health problem
Chronic diseases in general, and hypertension in particular, are
a rapidly expanding group of diseases that have been overlooked as public health problems in many developing countries
for a long period. Reports of a very high incidence of strokes in
elderly people in different parts of Tanzania have drawn attention to the scale of the problem.
A study in Dar es Salaam, a community in the early stages of
epidemiological transition, investigated how hypertension can
be diagnosed most efficiently in terms of the number and timing
of blood pressure measurements (screening of the general population with follow-up measurements in selected persons), the
associated risk factors (based on baseline data obtained by
questionnaire) and patterns of utilisation of health services (follow-up interviews at 6 months enquiring retrospectively about
use). A pilot study was conducted in the whole area of a district
of the city, with 17 enumerators who interviewed and examined
1769 adults in their homes. The mean age of the study group
was 36 years; 14% had no formal education, 71% had primary
school education and 2.6% had higher education. Initial results
based on a single visit indicated that 12% of adults had high
blood pressure. However, this proportion decreased to 5% after
several follow-up visits, which suggests that there is a considerable risk of false positives, and therefore efficient diagnostic
procedures must be designed to avoid this. However, despite
these diagnostic uncertainties, the number of people with
proven hypertension was clearly substantial, and there is a
need to implement appropriate control measures.
A further study examined local concepts concerning high
blood pressure, and illness behaviour associated with it, from
the perspective of medical anthropology. The study was carried
out in a low income neighbourhood near the centre of Dar es
Salaam. Local categories for the description of symptoms,
causes and healthcare-seeking were assessed in focus group
discussions and in-depth interviews, and then systematically
investigated in semi-structured interviews with 60 people suffering from “BP”.
People in Dar es Salaam do have concepts which centre
around the ideas of “BP/presha”, which is mainly seen as a
modern disease. The respondent’s answers regarding the inner
workings of the body regarding “blood” and “pressure”
remained vague. The answers were more elaborate with regard
to symptoms and causes. Symptoms centred around the heart,
particularly heart palpitations. Breathing problems, swollen
body parts, headaches and eye problems were also mentioned.
Stressful life situations were seen as explanations for the beginning of “BP/presha”. Causes included “thoughts”, “worries”,
“being shocked” and also wrong food, anger and family problems.
The illness is often treated at home with local remedies (a
cold bath, chewing garlic, drinking cold soda) or self-medication (with Panadol or Aspirin, sleeping pills or tranquillisers).
Local healers play a marginal role. Many people go to a hospital
for consultation and take drugs, but compliance regarding regular drug intake is low, especially once the troubling symptoms
have disappeared. It is also well known that one should take
care of one’s own body, control one’s weight, follow a diet, and
exercise, but few patients actually put this knowledge into practice. To conclude, people and especially women use this “modern disease” to draw attention to their difficult and burdensome
lives, turn to medicine to alleviate troubling symptoms, but know
very well that no medicine can actually change their suffering.
Scientists:
C. Lengeler, B. Obrist, M. Tanner
PhD student:
H. Strahl
Collaboration:
IUMSP (Institute for Social and Preventive Medicine) Lausanne,
Switzerland; AMMP (Adult Morbidity & Mortality Project), Dar es
Salaam, Tanzania; DUHP (Dar es Salaam Urban Health Project), Dar es Salaam, Tanzania; Institute of Anthropology,
University of Basel; Institute of Anthropology, University of
Freiburg, Germany
Funding:
SNSF
7A.5
Health and elderly people in urban Indonesia
The on-going process of health transition (i.e. demographic and
epidemiological change as well as changes in lifestyle) affects
elderly people in Indonesia especially in urban areas. Ageing in
cities of North Sulawesi is marked by three main concerns. One
is increased health risk. People suffer from non-communicable
diseases as well as communicable diseases as a result of a
changed lifestyle and altered socio-economic conditions. The
second is social insecurity because filial piety and the meeting
of kinship obligations are no longer guaranteed. The third is
economic uncertainty, because the material and financial support system is no longer reliable. This anthropological study
examines what growing old means under such conditions from
people’s own points of view in three medium-sized cities.
The emic definition of “being old” is not delimited by age in
years or biomedical diagnosis, but rather by the degree to
which an individual has control over body and mind. The physical and mental competence of ageing people can be assessed
by looking at their ability to perform the activities of daily life.
Chronic disabilities and illnesses are a heavy burden for the elderly and their caretakers. Senior citizens classify them in three
different categories: “illness that disturbs”; “illness that worries”,
and “illness that threatens”. Since these emic categories only
partially correspond with biomedical categories, the expectations of patients are often not met by health services, especially
in the alleviation of progressive ailments such as decreasing
eyesight and dental problems, and patients’ compliance is limited. In addition, although kinship obligations have a high cultural value, chronic illnesses and progressive ailments require
expensive and long term care, and take a heavy toll of family
members who are themselves struggling to make ends meet.
There are particular difficulties in families where members have
emigrated or are not willing to provide practical care.
Scientists:
P. van Eeuwijk, M. Tanner
Collaboration:
Faculty of Medicine, Institute of Public Health, Manado, North
Sulawesi, Indonesia; Faculty of Social and Political Sciences,
Institute of Anthropology, Manado, North Sulawesi, Indonesia;
Institute of Anthropology, University of Basel, Switzerland
Funding:
SNSF
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7B. Human and Animal Health; Health of
Nomadic Populations
International animal health is of growing interest in a world of
increasing global interaction. On the one hand, there is increasing public concern about zoonotic diseases that can be transferred from animals to humans. BSE, West Nile virus and, more
recently, bio-terrorism using Bacillus anthracis, are striking
examples. Recent public concern in industrialised countries has
generally been a result of dramatic events, but in many parts of
the world people are constantly exposed to zoonotic diseases.
Farmers and pastoralists live and work in close contact with
their animals. In many countries, people are exposed to infection through the animal products they consume because safety
regulations are not yet adequate. In many places, there is a
danger of rabies from dogs that have not been vaccinated.
Exposure to zoonotic disease is not the only link between the
health of people and animals. For people who depend on livestock for their livelihood, the health of their animals is a paramount concern, on which their own well-being depends. Projects to improve animal health have a direct economic impact
on human health. (See also 7 C 4, ECOZOO; a model to assess
the economic advantages of control of zoonotic disease.)
Among groups for whom human and animal health are inextricably linked, any attempt to improve health services for
humans has to consider the health of their animals at the same
time. That is why the research group Human and Animal Health
that was established in 1998 within the Department of Public
Health and Epidemiology has projects which extend far beyond
classical studies of zoonotic diseases and their transmission
between animals and humans, exploring broader considerations of disease control that consider the implications for the
health of both people and their animals. One major area of activity is among nomadic pastoralists in the Sahel zone – a group
which at present is poorly served by health systems designed
for a sedentary population. Here, the STI research team is investigating health systems caring for humans and those caring for
animals, and people’s perceptions of animal and human health,
in order to develop and promote novel synergistic and intersectorial approaches.
Since 2001, some of the projects in Human and Animal
Health are being carried out in the framework of project IP4,
“Health and Well-Being”, of the NCCR North-South, “Mitigating
Syndromes of Global Change”. Like the urban health projects in
IP4, the projects on the health of nomadic peoples and their animals are based on sites where the STI has already been working and has built up networks of collaboration over many years:
in Chad, Mali, Mauritania and Côte d’Ivoire.
Projects on zoonotic diseases and animal health have also
continued outside the NCCR framework, for example on milk
hygiene and tuberculosis in Mali, on rabies in Chad, and on parasites of livestock in Côte d’Ivoire. All the studies are undertaken in close partnership with numerous African institutions.
The scientific work is always linked with capacity building in the
collaborating countries, and in Switzerland it contributes to
capacity-building and training in international animal health.
7B.1
The interface of human and animal health among
nomadic pastoralists in Chad: zoonoses and health
services
A first series of field studies of the health of nomadic people in
Chad, some of which were described in the previous report (STI
1999 – 2000), provided the basis for the studies now being
undertaken as part of the IP4 of the NCCR. Surveys showed that
human illness among nomadic groups is dominated by infectious diseases. Nearly nine out of ten people reported that they
had been ill in the two weeks prior to the interview. The main
clinical symptoms were fever and respiratory and gastrointestiREPETITION DES VACCINATIONS
LA PREMIERE DOSE: LA FONDATION
LA DEUXIEME DOSE: LA CONSTRUCTION
LA TROISIEME DOSE: LA PROTECTION
Educational material used among nomadic groups in Chad, illustrating the need to
have three doses of vaccine for full protection – as a tent only gives full protection
when it has been built up in three stages, starting with a circle of holes in the
ground. (Source: watercolour pictures by Haroun Mahamet)
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nal affections, each accounting for about one fifth of all symptoms. Access to health services was often difficult. For example,
vaccination in the framework of the Expanded Programme on
Immunisation (EPI) was found to be only episodic, and no child
or woman was found among all nomadic groups investigated
who was fully covered by the full series of recommended vaccinations. Vitamin A levels were also low. Goat and cow milk are
the main source of vitamin A for these population groups, and
measurements of human serum retinol in women showed that
they were below recommended levels. The levels were correlated with the levels in the milk of their goats and cows, which
was their only source of the vitamin.
The very low vaccination coverage among women and children was striking. In contrast, the same surveys found that most
animals had been vaccinated at least once during the two years
before the survey. WHO and FAO have suggested that potential
synergies between public health and veterinary services, to
improve primary health care services, should be investigated.
Providing vaccination services for people and their livestock at
the same time and place would be convenient for nomadic
groups, and could reduce the cost for both sectors; public
health and livestock production. First results have demonstrated
the feasibility of running joint services, and grants have now
been secured for a full assessment of the performance and
cost-effectiveness of joint human and animal vaccination campaigns. The results are now leading to the formulation of a new
innovative intersectorial EPI policy, adapted to nomadic people
in Chad and in other Sahelian countries.
Pastoralists are particularly exposed to zoonotic disease. A
study was undertaken simultaneously in humans and animals to
investigate the spectrum of zoonotic diseases present. Brucellosis was found both in humans and livestock, but the prevalence was low. Two Brucella abortus strains were isolated from
cow’s milk. A high proportion of dromedaries (Camelus dromedarius) and small ruminants were found to be seropositive for Qfever. Seropositive humans were most often found among camel
breeders.
In parallel to the biomedical study of zoonoses, an anthropologist studied perceptions of ill-health and disease in a FulBe
pastoralist community, and their implications for health interventions and services in Chad. The FulBe pastoralists considered
only a few animal diseases to be transmissible to humans (e.g.
anthrax). In general, their perception of which health problems
should have priority correlated only to a limited extent with biomedical assessments. These observations, and the analysis of
health seeking and health service utilisation, should be interpreted carefully in the design of new health care concepts
adapted to these nomadic populations.
Scientists:
D. M. Daugla, M. Tanner, K. Wyss, J. Zinsstag
PhD students:
E. Schelling, N. Shani
Collaboration:
Institute of Veterinary Bacteriology, University of Berne,
Switzerland (J. Nicolet, P. Boerlin, J. Frey); Laboratoire
de Recherches Vétérinaires et Zootéchniques de Farcha,
N’Djaména, Chad (G. Ndoutamia); Sight and Life, HoffmannLa Roche, Basel; Ministry of Public Health, Chad; Faculty of
Geography, University of Freiburg, Germany
Funding:
SNSF-NCCR; Sight and Life Foundation; UNICEF; UBS Optimus Foundation, Zürich, Switzerland
7B.2
Zoonotic disease: risks and control measures
Tuberculosis in Chad
Tuberculosis is a growing public health problem in many parts
of the world, and livestock-keeping populations may be
exposed to both the human and animal infections. In Chad, up
to 17% of cattle investigated were tuberculin positive for
Mycobacterium bovis. A new mycobacteriological unit was set
up in the National Veterinary Laboratories in N’Djaména to
enable a detailed analysis to be made of mycobacterial infections. Of the 80 strains of mycobacteria isolated so far, most
were non-tuberculosis complex (NTM) strains. Of the 9 strains of
the tuberculosis complex characterised by spacer oligotyping,
6 were found to be M. tuberculosis of human origin and three
were M. bovis (1 from human sputum and 2 from cattle). This
was the first time that M. bovis was isolated from humans in
Chad, and the isolates are the first set of tuberculosis strains
from a well-defined transmission zone in Chad. Future work will
address key analytical questions such as: i) what is the proportion of M. bovis among the tuberculosis patients in Chad, and
what are the risk factors for M. bovis infections? ii) What is the
clinical significance of the large proportion of NTM strains isolated from TB suspects? iii) What are the cure rates for Directly
Observed Treatment Short Course (DOTS) for human tuberculosis in Chad, and how good is DOTS compliance? iv) What is the
situation regarding antibiotic resistance to first line tuberculosis
drugs in Chad, and how is it changing?
Milking in Mali. Vessels used for milking and transport are frequently a source of
contamination of milk by micro-organisms. (Source: J. Zinsstag)
Ultimately, we hope to describe the genotype flow of M. bovis
in relation to M. tuberculosis and the most important risk factors
for transmission among nomadic and sedentary populations,
and to model the transmission dynamics. In this context, further
collaboration is being set up with the Centre for Tropical Veterinary Medicine (CTVM) in Edinburgh and the tuberculosis knowledge programme at the Liverpool School of Tropical Medicine
(LSTM). These links will allow molecular epidemiological work
on tuberculosis to be developed.
Scientist:
J. Zinsstag
Students:
C. Diguimbaye (PhD), R. Ngandolo (MSc)
Collaboration:
Swiss National Centre for Mycobacteria (SNCM), University of
Zurich, Switzerland (G.Pfyffer); Laboratoire de Recherches
Vétérinaires et Zootéchniques de Farcha, N’Djaména, Chad
(G. Ndoutamia) ; Ministry of Public Health, Chad
Funding:
SNSF; Swiss Federal Commission for Scholarships for foreign
students
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(FAM); Institut du Sahel, Bamako, Mali (I. O. Alfaroukh); Laboratoire Central Vétérinaire, Bamako, Mali (C. F. Simbé); Institute
of Veterinary Bacteriology, University of Berne, Switzerland
(J. Nicolet, P. Boerlin, J. Frey)
Healthy milk for the Sahel: milk hygiene in Mali
Milk production is traditionally a prominent feature of the
economies of Sahelian countries in terms of income, employment, and resource utilisation. Milk is consumed raw, and also
used to make various fermented milk products. However production remains largely traditional, and little progress has been
made towards either improving productivity or the more efficient
use of the milk produced. The project “Healthy milk for the
Sahel” is specifically targeted to stimulating cattle and camel
milk production in Mali. Milk is an essential food source in the
Sahel, but ways are needed to improve its quality, to preserve its
nutritional value during processing and distribution, and to
reduce the potential health hazards associated with milk consumption. The objectives are: i) to describe and analyse traditional methods of processing and marketing of cow and camel
milk; ii) to conduct baseline risk analysis of raw milk and traditional milk products, with special emphasis on the presence of
organisms that may cause zoonotic diseases, such as
Mycobacterium bovis, Brucella abortus and Coxiella burnetii,
and iii) to develop improved procedures for the transformation
and conservation of milk to enhance its marketabilityand nutritional value, and to minimise risks for human health.
The project started in June 2000. A research partnership
agreement was signed between the Swiss Federal Institute of
Technology (ETHZ), the Swiss Tropical Institute (STI), the Institut
du Sahel (INSAH) and the Laboratoire Central Vétérinaire (LCV)
both in Bamako, Mali. Collaboration has also been established
with the Swiss Federal Research Station for Milk Technology
(FAM) for nutritional analyses. Field sampling and laboratory
analyses started in February 2001. In the second year of the
project, sampling of milk at selling points continued in greater
Bamako, and was extended to rural sites in Sikasso, Segou,
Mopti, Koulikoro and Timbuctoo.
Sampling of fresh milk showed that 22 – 25% of milk sold was
adulterated with water. Antibiotic residues were present in 6% of
the fresh milk samples. A very high proportion of milk samples
were positive for the Whiteside test (80% in rural and 74% in
urban areas), which confirmed the occurrence of subclinical
mastitis. The total contamination of fresh milk with micro-organisms is very high, reaching an average of 107 CFU/ml (colony
forming units/ml) in both urban and rural centres. Only 6% of the
samples would have complied with the standards used in
Kenya or in the European Union. These results indicate that
there is a high potential risk for humans of acquiring milk-borne
infections. Sources of contamination are the utensils used in
milking and transport. In the study samples, bacterial counts
rose continuously from an average total count of 1000 CFU/ml in
freshly-milked samples to 107 CFU/ml at the point of sale. Contaminating bacteria were mainly Enterobacteriaceae (faecal contamination), Enterococcus, Staphylococcus aureus (mastitis).
Yeasts and moulds were also present and the Abortus Bang
Ring-test (ABR) for brucellosis gave positive results for 31.5% of
the fresh milk samples. Samples of fermented milk products
were also tested with the direct milk ELISA test, after we had
established its reliability for use with fermented as well as fresh
samples. This confirmatory test gave positive results for 26.8%
of fresh and fermented milk samples.
Scientists:
B. Bonfoh, J. Zinsstag
MSc students:
A. Fané, M. Hetzel, P. Steinmann
Collaboration:
Laboratory for Dairy Science, ETH, Zürich, Switzerland (Z.
Farah); Swiss Federal Research Station for Milk Technology
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Funding:
SNSF, ETH Zürich
Dog rabies in an urban area: incidence and scope for control in
N’Djaména, Chad
This project started with a request from Chadian partners to
assist in the establishment in their laboratories of the standard
immunofluorescence method for rabies diagnosis. We used the
newly-introduced diagnostic method in a study on dog rabies in
urban N’Djaména. The incidence was approximately 7 cases
Vaccinating dogs in N’Djaména, Chad. (Source: J. Zinsstag)
per 10 000 dogs, based on an estimation of the total dog population of N’Djaména at about 23 000. These estimates were
obtained by a Chadian geography student who carried out a
study on dog demography, based on a household survey, and
an investigation of attitudes and current practices of people with
regard to their dogs. A pilot dog vaccination study was done in
three sectors of the city. The participation of the population was
high. Household and transect studies were carried out to
assess vaccination coverage by the proportion of dogs carrying
the collar mark given at vaccination. Analyses of survey data
using a Bayesian model revealed that 5% of dogs were ownerless, which is a surprisingly low proportion. Even when the ownerless dogs were taken into account, the achieved vaccination
coverage was above 70%, which is considered empirically as
the coverage threshold for the eradication of the disease.
Preliminary cost analyses suggest that 80 000 US$ should be
sufficient to vaccinate the whole dog population for one year.
We conclude that dog vaccination campaigns are a feasible
and cost-effective way to prevent animal and human rabies, and
repeated campaigns could lead to its eradication. This intervention could become sustainable without additional external funds
if dog owners contributed to the costs. This project is an example of “adaptive” operational research. In a next step the Chadian partners will develop a proposal for a mass campaign and
STI will contribute the evaluation and monitoring component.
The data collected will also be used to expand and validate our
transmission and economic models for zoonotic disease (see
Section 7C 5, ECOZOO).
Scientists:
N’D Yémadji, J. Zinsstag
Students:
U. Kayali (DVM), R. Mindekem (MSc)
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Collaboration:
Swiss Rabies Centre, Institute of Veterinary Virology, University
of Berne, Switzerland (E. Peterhans, R. Zanoni); Agence Canadienne de l’Inspection des Aliments, Canada (A. Wandeler)
Funding:
Swiss Federal Veterinary Office (BVET); MERIAL; BERNA
Biotech (Human rabies vaccine); EMDO Foundation; Zürcher
Hochschulverein; SDC
7B.3
Health of livestock
Calf mortality and parasites of livestock in traditional livestock
production in Côte d’Ivoire
In Côte d’Ivoire, national livestock production covers only a fraction of the domestic consumption of milk and meat. The country
therefore fosters livestock production to decrease dependence
on foreign imports and to cover local demand. One approach is
to improve local breeds by crossbreeding with exotic (European) animals. But crossbred animals are highly susceptible to
trypanosomes, ticks and worms and need expensive treatment
for protection. The local N’Dama breed is trypanotolerant, but
also has a lower productivity. One of the causes of low productivity is the high mortality of calves, about 20%. In the framework
of an existing research partnership with Ivorian institutions a
new project is investigating the causes of calf mortality. Its aim is
to define locally adapted strategies to reduce calf mortality and
ultimately to improve productivity.
Scientist:
J. Zinsstag
Students:
L. Achi (PhD), R. Taha (MSc), M. Wymann (PhD)
Collaboration:
Veterinary Faculty, University of Zürich, Switzerland (P.
Deplazes, H. Lutz); UFR Biosciences, University of Cocody,
Abidjan (E. A. N’Goran); Laboratoire National d’Appui au
Développement Agricole (C. Komoin)
Funding:
Guggenheim-Schnurr Foundation; Swiss Tropical Institute
Jubilee Foundation; SDC; Syngenta Foundation
7C. Efficient provision of Health Services
The provision of health services is expensive, and economic
evaluation is an essential part of the decision-making process. It
enables alternative health care options to be compared in terms
of their costs and their benefits, in order to show which are the
most efficient forms of health care delivery in terms of cost per
effect. Activities in the field of economic evaluation at the STI
cover both individual projects and the development of specific
themes or topics, both in Switzerland and in other countries.
Studies include analyses of the economic implications of vari-
ous methods to prevent HIV/AIDS in Chad, of measures to
improve maternal health services in Burkina Faso, and of the
use of insecticide-treated bednets to prevent malaria in Tanzania (see 6.3). Another study in Tanzania examines the process
of drug donation – a common way for “wealthy” nations to offer
support to countries with resource constraints – and its implications for the health system. On a global level, an analysis was
made of the economic effects of interventions to improve water
supply and sanitation. A study of brucellosis control in Mongolia
has provided data for developing a model to assess the costs
and benefits of controlling zoonotic disease from the points of
view of both human health services and the agricultural sector.
Even in industrialised countries, the allocation of resources for
health services is an important topic of public concern. A study
of resource allocation was carried out in two Swiss cantons.
Expenditure on health services is, of course, not the only
determinant of quality. Delivering appropriate services also
depends on studying the needs of both providers and users. A
project in Switzerland looks at the needs of a special group of
migrant women, those who have undergone genital mutilation,
and at how the Swiss health services can best care for them.
Questions about people’s perception of health and illness, and
the best way to provide services for physical and mental health,
are also a concern of cultural epidemiology (Section 8).
7C.1
Health services in Chad
Constraints on scaling up health related interventions
As part of a working group of the WHO Commission on Macroeconomics and Health, a country case study in Chad examined
the determinants and constraints on scaling up health-related
interventions. Constraints at community, health service delivery,
policy, multi-sectoral and government levels were examined.
The analyses showed that emphasis should be on systemic
approaches, on the removal of structural constraints, on the efficient and equitable production of health services, and on performance improvements. With regard to the production of services, the development of human resources must precede the
development of infrastructures. Investments in initial and continuous training and in management skills are crucially important.
Contracting work to the private sector may be an instrument for
the rationalisation and extension of services. In addition, the
study revealed the importance of promoting health services that
actively seek to fulfil community demands and emphasise disadvantaged groups.
Prevention of HIV/AIDS
Midwife examining a pregnant woman; Burkina Faso. (Source: N. Lorenz)
In Chad, as in most sub-Saharan African countries, HIV/AIDS is
a massive public health threat as well as an economic burden.
Average prevalence rates are estimated at around 9% of adults.
It is essential to have a well-functioning national programme for
AIDS control, with well thought-out priorities as well as action
plans. Since 1996, a programme funded by the World Bank,
Projet Population et Lutte Contre le SIDA (PPLS), has achieved
notable successes in Chad in the prevention of HIV/AIDS. In
2000, the SCIH was commissioned to conduct research into the
socio-economic impact of HIV/AIDS which would contribute to
the definition of national control strategies in the next phase of
PPLS (2001– 4).
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Research conducted as part of this study included costeffectiveness analysis to help to identify the most efficient and
lowest-cost options for controlling the epidemic, so that in the
new phase of PPLS the limited resources can be used to produce the biggest possible reduction in HIV incidence in different risk groups. At a level of expenditure of less than US$ 100
per infection prevented the most cost-effective options were
found to be peer group education for sex workers, and
blood donor screening. At the next level (US$ 100 to
US$ 1 000 per infection prevented) the best options were education and information through the mass media, social marketing of condoms, peer group education for high risk men, peer
group education among young people, targeted administration
of AZT to pregnant women, and voluntary counselling and testing.
Scientists:
G. Hutton, K. Wyss
Collaboration:
CSSI, N’Djaména, Chad (M. Daugla, N’D. Yémadji); Projet
Population et Lutte Contre le SIDA, Chad; Government of
Chad; LSHTM, UK (A. Mills, C Kurowski)
Funding:
World Bank, SDC, WHO/TDR
7C.2
Burkina Faso; strengthening maternity services
In a community-based trial in a rural district in the south-west of
Burkina Faso, strengthened maternity services in six “intervention” areas are being compared with the current services in six
“control” areas. The strengthening consists of a variety of measures: ensuring the availability of essential equipment and medicines in the health centres; establishing a schedule of interventions for women attending antenatal clinics; training traditional
birth attendants; improving access to transport for emergency
cases; increasing health service utilisation through information,
education and communication (using community “motivators”),
and making care more affordable.
The Swiss Centre for International Health (SCIH) of the STI is
responsible for the economic evaluation component of this trial,
including the measurement of costs to health services, communities and patients; evaluation and testing of alternative financing mechanisms, and an evaluation of the economic determinants of health service utilisation. An assessment is being made
of how far the findings can be generalised to the national level in
Burkina Faso, with a view to national up-scaling of the interventions. The trial will be completed in 2004.
Scientist:
G. Hutton
Collaboration:
Centre Muraz, Bobo-Dioulasso, Burkina Faso; Ministry of
Health, Ougadougou, Burkina Faso
Funding:
European Union
7C.3
Drug donations to Tanzania
Drug donations in humanitarian relief and development assistance vary significantly in their relevance and quality. Donated
drugs can be important contributions to public heath goals – or
they can be immense and unusable burdens for the recipients.
A research study is focussing on in-kind drug donations to Tanzania. As development aid from Switzerland to Tanzania has a
long tradition in both secular and mission sectors, the study
focuses on drug donations from Switzerland.
58
Both the public and the private non-profit sectors of health
care delivery in Tanzania are still confronted with the issue of
drug donations. Even if donation processes have been
improved over past years, recipients of donations nevertheless
seem to be burdened with many structural and process-flow
problems. The goal of the study is to assess problems in donation processes, to estimate the value of donations as part of the
drug supply system, and to get information on the views of
recipients and other stakeholders on drug donations. Knowledge of and implementation of the Interagency WHO Guidelines
for Drug Donations will be investigated. The first year of the
main study was dedicated to the development of instruments for
data collection, the second year to data analysis. The results of
the survey were presented for the first time in a workshop in Dar
es Salaam (October 2002) to which people actively concerned
with the drug donation process were invited, to discuss interventions for optimising drug donation processes in Tanzania,
based on the results of the study. A case study of a specific
drug donation will follow, to evaluate in-depth structures and
processes and their context. When completed, the study should
provide support for donors and recipients in planning and carrying out donation processes more appropriately.
Scientists:
M. Tanner, K. Wiedenmayer
PhD student:
G. Gehler
Collaboration:
City Medical Office of Health Dar es Salaam, Tanzania (D.
Mtasiwa); Institute of Clinical Pharmacy, University of Basel
(K. Hersberger, R. Bruppacher)
7C.4
Costs and benefits of water and sanitation
interventions
The aim of this study was to estimate the costs of a range of
interventions to improve water and sanitation (W & S) services
which are not funded by the health sector, and their benefits.
Results were presented for each of the 17 WHO sub-regions,
and the conclusions will feed into the World Health Report 2002.
Five interventions were evaluated, focussing on increasing
access to W & S services, including the improvements required
to meet millennium targets, and low technology water purification methods. Costs included the full investment and annual
running costs for each type of improvement. Benefits included
time savings associated with better access to W & S facilities,
the gain in productive time due to a reduction in illness and
avoided deaths, and health sector and patients’ costs saved as
a result of a reduced need for treatment of disease.
The results showed that all the water and sanitation improvements evaluated were cost-beneficial (i.e. benefits exceeded
costs), for all world regions. In developing regions, the return on
a US$ 1 investment was in the range US$ 1.70 to over US$ 10.
The main contributor to benefits was the time saving associated
with better access to water and sanitation services. The study
found that there are many determinants of the cost-benefit of
different W & S improvements. There is a significant amount of
uncertainty in the estimates due to lack of data on costs and
benefits in each WHO region.
Scientist:
G. Hutton
Student:
L. Haller (based at WHO)
Collaboration:
Global Programme on Evidence, WHO; Department for the
Protection of the Human Environment, WHO
Funding:
WHO
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7C.5
ECOZOO: A model to assess the economic
advantages of control of zoonotic disease
The control of zoonotic disease brings benefits not only in the
agricultural sector but also for human health, in terms of reduction of treatment costs and of time lost owing to illness. Therefore any cost-benefit calculation should take both sectors into
account. We have started to develop a model for assessing the
potential economic effects of projects for controlling zoonotic
disease (ECOZOO), which can support policy makers in making decisions about interventions.
The model was developed using data collected in Mongolia
during an investigation of the potential economic benefits of a
mass livestock vaccination campaign against brucellosis. We
had been asked to carry out the analysis on behalf of WHO.
Since the end of the socialist period, Mongolia has been faced
with a rapid increase in human brucellosis, and WHO experts
had suggested the mass vaccination of cattle, sheep and goats
as a control measure. Since both the agricultural sector and the
health sector can benefit from an intervention such as the control of brucellosis it is not appropriate to assign the whole cost to
either sector alone. Therefore costs and benefits were allocated
to each of the different parties affected by the disease, e.g. livestock owners, families affected by brucellosis, and the health
sector. Based on this allocation, the cost-effectiveness of the
intervention for human health and for livestock production could
be calculated, and the profitability estimated. A cost-sharing
scenario was then proposed which allows a more equitable ratio
for cost-effectiveness and profitability to be calculated.
On the basis of this proposal for cost and benefit allocation
for the brucellosis vaccination campaign in Mongolia, the intervention cost per DALY (Disability Adjusted Life Year) saved was
approximately US$ 34. The benefit-cost ratio for society as a
whole was 4.1, for the health sector 7.6, and for the agricultural
sector 3.7. Thus, the intervention was clearly profitable for the
health sector as well as for the agricultural sector. Further savings could be achieved if brucellosis mass vaccination were
linked to control of foot and mouth disease. This intervention
could form part of the relief programme for the Mongolian herdsmen and their families following two consecutive years with disastrously high winter snow levels.
At the conceptual and basic science level, the data from
infection, disease and transmission are used to develop
Bayesian animal-human transmission models for the control of
Preparing fermented mare’s milk in Mongolia. (Source: J. Zinsstag)
zoonotic diseases. These models can be extended to include
various economic aspects. They can also be used for the
assessment of new systems for health care provision to people
who depend on livestock for their livelihood.
Scientists:
G. Hutton, F. Roth, P. Vounatsou, J. Zinsstag
Collaboration:
Food and Agriculture Organisation of the United Nations (FAO),
Rome, Italy (J. Otte); Royal Veterinary College, London
(D. Pfeiffer); Ministry of Public Health, Ulaan Baatar, Mongolia
(D. Orkhon); Infectious Disease Research Institute (G. Chimed
Ochir); WHO, Geneva, Switzerland (O. Cosivi)
Funding:
WHO, FAO
7C.6
Resource allocation in the Swiss health care system
There is much discussion in Switzerland about the financing of
the health care system and the causes of the continual increase
in the cost of health care. The study described here had the following aims: i) to analyse how the resources for health care provision are allocated, and what are the most important determinants and consequences of this allocation; ii) to see whether
there is a need for action to make the system more equitable,
and if so, what action should be taken, and iii) to promote a
more comprehensive debate on a cantonal and national level
about different options for the allocation of resources for health
care.
The study was a collaboration between the Institute Dialog
Ethik (Interdisciplinary Institute for Ethics in Health Care Delivery) and the STI. Dialog Ethik developed the “Zürich Manifesto”
to plead for a fair allocation of services and resources in health
care. The STI complemented this Swiss experience with its
expertise from working on health planning in countries with
severe resources constraints. The collaboration therefore
enabled methodological and technical knowledge and experience to be combined against the background of an ethical
framework.
The Cantons of Zürich and Basel-Stadt served as examples.
A broad public and political discussion on resource allocation
and ethics in the health care delivery system had already taken
place there. The focus of this study was not to compare the two
Cantons but to analyse costs and expenditures and trends in
public perception of priorities, aiming to elucidate general principles that could be valid for the whole Swiss health sector.
The study had four components: i) analyses of trends of
expenditures and of the mechanisms of financing both outpatient and in-patient care during the last 10 years; ii) an opinion poll among health professionals about their perceptions of
the extent of oversupply of services, the rationalisation and/or
rationing of services, and their ideas on how to overcome the
problems; iii) a press review about resource constraints in the
Swiss health care system; and iv) a summary of experience of
decision-making processes in the health care systems of other
countries.
The most important findings were:
• There is already a rationing of health care provision in Switzerland today, though to a much lesser extent than in other industrialised countries.
• There is a hidden rationing, mainly in the in-patient sector,
which originates from selective pressure to economise. At the
same time there is an oversupply of medical technology.
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• The Cantonal Governments take decisions on the allocation of
public money. This leads to frustration among health professionals, who consider that “top-down” decisions are often
arbitrary and difficult to put into action in a responsible and
coherent way while working with the patients. The decisionmaking process itself is not transparent.
• The source of finance for health care provision is gradually
shifting from taxation to a per capita premium for health insurance. This indicates that the principle of equity on a societal
level – which was never very strong – is becoming weaker.
• In future, rising costs will increase the pressure for cutbacks in
the supply of health care. This will lead to more rationing in all
areas.
• It therefore seems to be essential to set priorities in the Swiss
health care system, in the sense of restrictions. Experience
from other countries shows that this needs a structured opinion-making process in which all parties can participate.
Scientists:
F. Roth, D. Schopper, M. Tanner, K. Wyss
Collaboration:
Dialog Ethik (R Baumann-Hölzle, K. Büchi, T. Weidmann); Universitätsspital Zürich, Switzerland (I. Beeler); Institut für Publizistikwissenschaft und Medienforschung der Universität
Zürich (B. Hänsli)
Funding:
Dialog Ethik
7C.7
Female Genital Mutilation in the context of migration:
care for migrant women in the Swiss health care
system
The World Health Organisation estimates that 130 million
women have undergone female genital mutilation (FGM), and
every year some 2 million more girls in 28 countries, mainly in
sub-Saharan Africa, are subjected to these practices, often at a
very young age. FGM involves the excision of healthy parts of
the female external genitalia. It is classified into 4 categories
according to the severity of the intervention. The most invasive
forms, practised mainly in the Horn of Africa, involve the cutting
of all the external genitalia and stitching or narrowing of the
vaginal opening (infibulation).
International migration has brought the issue of FGM to
industrialised countries, including Switzerland. Most recipient
countries are unfamiliar with this traditional practice and health
care professionals, legislators and social workers are facing
many questions when confronted with an affected woman or
girl. Switzerland is host to some 10 000 female migrants from
sub-Saharan African countries where FGM is practised. A calculation based on the estimated prevalence rates for these
countries published by WHO in 2001 indicates that 5000 – 6000
women who have undergone FGM could be living in Switzerland.
Swiss health care professionals are confronted with the specific problems and needs of these women particularly in connection with pregnancy and birth. Previous studies have tried to
quantify the problem, and assess which health professionals
most often encounter the women concerned. So far, there has
been little qualitative information about the experiences and
needs of health care professionals, and hardly any information
from the perspective of the migrant women themselves.
To inform health care providers and policy makers, a study
was launched in August 2001 in Switzerland. Its aims were: i) to
estimate the number of genitally mutilated girls and women in
60
Switzerland, and to examine their distribution by country of origin, place of residence, and age-group; ii) to assess the specific objective and subjective health care problems of African
immigrant women living in Switzerland who have undergone
FGM; iii) to analyse the information that Swiss health care
providers need to treat genitally mutilated women according to
the best possible standards; iv) to establish the needs of genitally mutilated women in Switzerland with regard to the Swiss
health care system, and v) to generate a set of recommendations for Swiss health care providers based on the findings.
Information was collected through in-depth telephone interviews with health professionals (gynaecologists and midwives)
and focus group discussions with different groups of affected
women, combined with key informant interviews and a review of
the literature. So far, 38 interviews have been conducted with
health care professionals, mainly in the cantons where most of
the women live (Geneva, Lausanne, Zürich and Bern). Motivating immigrant women from countries where FGM is practised to
take part in focus group discussions proved to be a challenging
problem. Data analysis is still ongoing. It is hoped that the findings will assist the Swiss professional association of gynaecologists and obstetricians in elaborating specific guidelines. In
addition, by presenting the experiences and views of the
women concerned, the study should contribute to establishing
an appropriate offer of health care that can meet their specific
needs.
Scientists:
C. Kessler Bodiang, N. Lorenz, M. Tanner
MD Student:
C. Thierfelder
Collaboration:
International Association for Maternal and Neonatal Health
(IAMANEH) Switzerland, Basel; Swiss Federal Statistical
Office, Neuchâtel; Swiss Federal Office for Refugees, Berne;
UNICEF; Swiss Society of Gynaecology and Obstetrics, Berne.
Funding:
IAMANEH
Publications:
Bolay JC & Cissé G (2001) Urban environmental management: New tools for
urban players. In KFPE, 2001:Enhancing research capacity in developing and
transition countries. Swiss Commission for Research Partnerships with Developing
countries (KFPE). Berne: Geographica Bernensia, 316 pp, 175 –182.
Boller C, Wyss K, Mtasiwa D & Tanner M. (in press) Quality of antenatal care: a
comparison of the role and performance of public and private providers in urban
Tanzania. Bull World Health Org.
Bonfoh B, Fane A, Plea A, Tounkara K, Simbe F, Alfarouk IO, Schalch L, Farah Z,
Nicolet J & Zinsstag J (2002) Use of an indirect enzyme immunoassay for detection of antibody to Brucella abortus in fermented cow milk. Milk Science International 57, 361– 420.
Bonfoh B, Dem S, Keita O, Delorenzi S, Traoré H, Simbe CF, Alfaroukh IO, Farah Z,
Nicolet J & Zinsstag J (in press) Assessment of antibiotics residues by microbial
inhibitor tests in cow’s fresh milk sold in Bamako, Mali. Food control.
Borghi J, Fox-Rushby J, Bergel E, Abalos E, Hutton G & Carroli G (2002) The costeffectiveness of routine versus restrictive episiotomy in Argentina. Am J Obstet
Gynecol 186 (2), 221– 8.
Bovet P, Ross AG, Gervasoni J-P, Mkamba M, Mtasiwa D, Lengeler C, Whiting D &
Paccaud F (2002). Distribution of blood pressure, body mass index and smoking
habits in the urban population of Dar es Salaam, Tanzania, and associations with
socio-economic status. Int. J. Epidem. 31, 240 – 247.
Cissé G, Kientga M, Ouédraogo B & Tanner M (2002) Développement du
maraîchage autour des eaux de barrage à Ouagadougou: quels sont les risques
sanitaires à prendre en compte? Cahiers Agricultures 11, 31– 38.
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Dongbao Y, Sarol J, Hutton G, Tan D & Tanner M (2002) Cost effectiveness analysis of the impacts on infection and morbidity attributable to three chemotherapy
schemes against Schistosoma japonicum in hyperendemic areas of the Dongting
Lake region, China. Southeast Asian J Trop Med Public Health 33 (3).
Felber G, Othingué N, Yémadji N & Wyss K (2001) Lessons from malaria control
activities in urban West Africa using a research – action – capacity approach. Participatory Learning and Action Notes 40, 18 – 21.
Flury M & Cissé G (2001) Participation in Local Resource and Conflict Management. A review of experiences in the North and in the South. In: Local Environmental Management in a North-South Perspective. Issues of Participation and Knowledge Management Eds. Manuel Flury & Urs Geiser “Themenheft” Swiss Priority
Programme Environment.
Gerstl S, Cissé G & Tanner M (2002) The economic impact of urban agriculture on
home gardeners’ households in Ouagadougou. UA-Magazine 7, 12 –15.
Hutton G (2000) Considerations in evaluating the cost-effectiveness of environmental health interventions. Sustainable development and healthy environments
cluster, World Health Organization. WHO/SDE/WSH/00.10.
Hutton G (2001) Economic evaluation and priority setting in water and sanitation
interventions. In: Water Quality: guidelines, standards and health: assessment of
risk and risk management for water-related infectious disease. Eds Fewtrell L, Bartram J. London: IWA (on behalf of WHO), chapter 16.
Hutton G (2002) Evaluation of the global non-health costs and benefits of water
and sanitation interventions. Undertaken for the Effectiveness, Quality and Costs
Unit, Global Programme on Evidence, in collaboration with the Water, Sanitation
and Health Unit, Department for the Protection of the Human Environment, WHO.
Hutton G, Wyss K & Yémadji N (in press) Prioritization of prevention activities to
combat the spread of HIV/AIDS in resource constrained settings: a cost-effectiveness analysis from Chad, Central Africa. Int J Health Plann Management
Kessler Bodiang C, Eppel G & Guèye AS (2000) L’excision dans la région de Kolda
au Sénégal: perceptions, attitudes et pratiques. GTZ. www.gtz.de/fgm/frenchpub/pub1.html
Kessler Bodiang C (2001) Addressing Female Genital Mutilation: Challenges and
Perspectives for Health Programmes. Part I: selected approaches. Eschborn,
GTZ. www.gtz.de
Knopf L, Komoin C, Betschart B, Gottstein B, Jongejan F & Zinsstag J (2002) Epidemiology and seasonality of ticks and aspects of tick-borne diseases in N’Dama
cattle in the Central Guinea Savannah of Côte d’Ivoire. Prev Vet Med 53, 21– 30.
Ouédraogo B, Cissé G & Tanner M (2001) De la recherche épidémiologique à l’intervention socio-économique pour les maraîchers de Ouagadougou. Sempervira
10, 23 – 30.
Schopper D, Baumann-Hölzle R, Lange F, Beeler I, Roth F & Tanner M (in press)
Mittelverteilung im schweizerischen Gesundheitswesen am Beispiel der Kantone
Zürich und Basel Stadt. Schweizerische Ärzteztg.
Schopper D, Baumann-Hölzle R & Tanner M (in press) Rationierung im Gesundheitswesen: Was könnte die Schwiez von andern Ländern lernen? Schweizerische
Ärzteztg.
Teuscher A, Wiedenmayer K, Lorenz N, Teuscher T (2002) Natural insulin is costeffective, Bulletin Medicus Mundi Switzerland 84, 29.
Villar J, Ba’aqeel H, Piaggio G, Lumbiganon P, Belizan J, Farnot U, Al-Mazrou Y,
Carrolli G, Pinol A, Langer A, Nigenda G, Mugford M, Fox-Rushby J, Hutton G,
Bergso P, Bakketeig L & Berendes H (2001) WHO antenatal care randomised controlled trial for the evaluation of a new model of routine antenatal care. Lancet 357,
1551–1564.
Villes en Sursis au Sahel: Expériences au Tchad et au Sénégal. Eds. Wyss K,
Ndiaye M, Yémadji N & Jacolin P. Paris, Harmattan (2000).
Wiedenmayer K & Mtasiwa D (2000) Transforming drug supply in Dar es Saalam.
Essential Drug Monitor. Geneva: WHO 28 & 29, 25 – 27
Wyss K, Doumagoum MD & Callewaert B (in press) Constraints to Scaling-up
health-related interventions: The case of Chad, Central Africa. J. Int. Development.
Wyss K, Kilima P & Lorenz N (2001) Costs of tuberculosis for households and
health care providers in Dar es Salaam, Tanzania. Trop Med Int Health 1, 60 – 68.
Wyss K & Touré L (2001) Le secteur de santé privé à Lomé, Togo dans un contexte
de crise économique Bulletin Medicus Mundi Schweiz 80, 6 – 8.
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SECTION 8
Cultural Epidemiology
Introduction
(e.g. suicide), cultural epidemiology provides an account of the
In the quest for relevant health policy and effective clinical pracdistribution of illness-related experience, meaning, and behavtice, developments in the field of cultural epidemiology are coniour with reference to the “insider, local” (emic) vantage point to
tinuing to innovate an integrated approach to interdisciplinary
complement that of the “outsider, professional” (etic).
sociocultural and epidemiological research. Activities over the
Ultimately, this is an interdisciplinary task. Ethnographic
past two years maintain an earlier focus on mental health in
study describes the contexts of health status and identifies
India through clinic-based and community field studies, and an
appropriate categories to specify patterns of distress (experiexpanded scope of research has also given more attention to
ence), perceived causes (meaning), and health seeking
problems of infectious diseases in South Asia, Africa and other
(behaviour). Epidemiological methods clarify the distribution
regions. Cross-cutting topics of gender and stigma have
of these categories in descriptive, comparative, and analytic
become a prominent feature of much of this work, and studies of
accounts. Careful attention to the narrative in qualitative cultural
the clinic and community contexts of tuberculosis and malaria
epidemiological data sets portrays the meaning of these cateintegrate research capacities of the group and long-standing
gories as they apply locally. Over the past two years, efforts
STI priorities. Publications, training, and participation in internahave continued to develop both
tional professional conferences
statistical methods and qualitaare explaining the framework
tive research techniques for
and methods of cultural epiworking with integrated qualitademiology and its contributive and quantitative cultural
tions, and these activities idenepidemiological data sets. The
tify areas of health research in
analysis of stigma has been
which further contributions are
a focus of these efforts. Softexpected, and indicate how to
ware that permits import from
proceed.
and export to quantitative data
The motivation for cultural
entry and analysis programs
epidemiology can be traced
enhances our capacity to ansback in the literature of public
wer more sophisticated interhealth over nearly half a cendisciplinary questions. These
tury. A seminal contribution
developments have contributed
published in 1955, Benjamin
substantially to the integration
Paul’s Health, Culture, and ComComplementary approaches to health research.
of qualitative and quantitative
munity, began with a reflection
methods.
on the celebrated malarioloResearch carried out by the group has continued to include a
gist, Samuel Taylor Darling, who worked on the Panama Canal
number of collaborative projects in India. Over the last two years
project, and “made a remark which lingers in the memory of his
these studies have maintained a focus on problems in clinical
public health disciples. ‘If you wish to control mosquitoes,’ he
psychiatry, but at the same time developed a greater emphasis
said, ‘you must learn to think like a mosquito’.” This remark, Paul
on community mental health. Clinic studies have expanded the
noted, “applies not only to mosquito populations one seeks to
focus from depression to other common mental disorders and
damage but also to human populations one hopes to benefit.”
schizophrenia. Suicide and non-fatal deliberate self-harm have
Since then, many health professionals have acknowledged the
also become priorities. Because these are regarded as mental
importance of understanding local settings and concepts of
health problems – but are properly designated as behaviours,
health and illness, but it has nevertheless proved difficult to
rather than as disorders – these topics highlight the importance
bring the powerful methods of epidemiology to the study of the
of attention to the sociocultural contexts and triggers of suicidal
distribution of such local concepts and their implications.
behaviour. This is not just a theoretical issue, but also an imporDevelopments in medical anthropology, willingness to rethink
tant practical matter for mental health policy and clinical pracmethods of epidemiology, and ready availability of computing
tice.
hardware and software to facilitate integration of quantitative
Community mental health research is based at two sites; one
and qualitative research methods, have all contributed to recent
is a group of communities in the rural Sundarban region of West
advances towards an effective interdisciplinary collaboration
Bengal, and the second an urban slum community of Mumbai.
between epidemiology and anthropology. The cultural epidemiEffective research to guide health programmes requires that
ology that has resulted is mindful of the distinctive tasks
classical psychiatric epidemiological study of disorders should
required for improving international health globally, nationally
be complemented by cultural epidemiological study of mental
and locally, and the need for responsiveness to both profeshealth problems in these communities. Such research proceeds
sional and local values.
with the study of community concepts of illness among persons
While ethnographic methods of anthropology are needed to
seeking help in local clinics, among the general population of
clarify the various local concepts and features of illness, epipeople without overt mental illness, and among special populademiological methods are required to specify their distribution
tions, especially health care providers of diverse types who
and additional practical implications. Unlike most research in
practise locally – often without credentials – and comprise the
basic epidemiology, which aims to account for the prevalence
health system of many under-served communities.
and incidence rates of diseases, disorders or related concerns
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Over the past two years, cultural epidemiological study of
infectious diseases has received greater emphasis. There are
continuing studies of tuberculosis in the Philippines (8.6) and in
Maharashtra, India. A new multicountry study of gender and
tuberculosis was motivated by the latter, and STI is supporting
efforts of WHO/TDR in rural Bangladesh, and at urban sites in
Chennai, India; Lilongwe, Malawi; and Cali, Colombia. (8.5)
Malaria has become a new focus of research, and cultural
epidemiological studies form a bridge to other malaria research
at the STI as well as extending the scope and impact of previous medical anthropological studies. Two WHO/TDR-supported
studies are just getting under way. One study is in Ghana, in
communities in two ecological zones – a savannah area in the
Keta district of the Volta region, and the forest zone. This collaboration with the Noguchi Memorial Institute of Medical Research
and the University of Ghana will begin with an ethnographic
study to identify the relevant contexts and categories of malariarelated illness. Based on the findings, locally relevant categories will be incorporated in locally adapted EMIC interviews to
determine the distribution of patterns of distress, perceived
causes, and both risk-related and help-seeking behaviours.
Community healers treating malaria will also be identified, to
examine the distribution of various approaches to assessment,
treatment, and referral. Other special populations in the two
communities selected for study include pregnant women and
mothers of children under 5 years of age.
Attention to the implications for malaria control of cultural
contexts that influence risk-related and help-seeking behaviour
motivates another study in Nigeria, where STI is assisting the
Federal University of Technology, Yola, to develop a sociocultural malaria study supported by a WHO/TDR seed grant. This
research is linked to STI interests in nomad health as well as in
malaria, since it will examine the social and political contexts of
malaria among the Bororo, a nomadic Fulani ethnic group in
north-eastern Nigeria. It will focus on the types of health care
and services available to them, and consider the practical implications of the experience and meaning of malaria-related illness
for malaria control.
Although research in cultural epidemiology has had a serious
interest in tropical infectious diseases from the outset, more
experience and more contributions to the underlying theory and
methodology have come from studies in mental health and cultural psychiatry. In the field of psychiatric epidemiology, major
concerns with questions of reliability in the assessment of mental disorders are now giving way to new questions of validity,
previously considered too difficult to deal with adequately. Psychiatric epidemiology has characterised the occurrence and
the magnitude of the burden of mental illness clearly enough to
attract attention in the broader field of international health, but
simply demonstrating the burden is no longer considered a sufficient objective. With the publication of WHO’s World Health
Report in 2001 on Mental Health: New Understanding, New
Hope, the agenda of the field has changed, from questions
about the extent of the burden to the challenge of what can be
done about it.
A lack of historical experience in the provision of mental
health for populations places efforts to improve community
mental health at a disadvantage. For infectious diseases, a set
of population-based priorities for illness prevention and health
promotion already exists. Indeed, the field of public health itself
sprang from the work of sanitary commissions and early con-
cerns about the spread of infectious diseases through populations. In the past, population-based priorities of mental health
policy were concerned with removing mentally disordered persons from the community, so they would not disturb the rest of
the population. Subsequently, priorities shifted towards clinical
psychiatry and the treatment of individuals with mental illness.
The clinical models of psychiatric treatment, however, provide
little of the expertise required for effective population-based policy. Although case identification and treatment remain relevant
as one component of public health policy, a truly public health
approach requires attention to illness prevention and health promotion, and this requires effective interactions between professionals and communities, and cultural epidemiological data that
can translate professional concepts of disease and disorder
into local concepts of illness, and vice versa.
Our field research attempts to address the need for conceptual innovation to counter the historical lack of population-based
considerations in mental health, as well as applying the experience to infectious diseases in addition to mental health. We are
also pursuing this agenda in other ways, by undertaking concept and policy reviews. These have included a survey for
WHO’s Department of Mental Health to identify areas of consensus and controversy concerning mental health policy in the
aftermath of disaster. A background paper for the Fogarty International Centre, Global Conference on Stigma, in September
2001, Stigma Interventions and Research for International
Health, critically reviewed the concept of stigma, developing a
rational basis for health research priorities for problem-specific
and culture-specific studies. Another review of stigma as it concerns research and policy for tropical infectious diseases is also
in preparation for WHO/TDR.
Questions about the social impact of stigma and its implications for health policy were already highlighted in the last STI
report. Current interests in the role of gender, another important
social issue pertinent to various aspects of health and illness,
are rooted in previous studies of onchocercal skin disease and
reflected in ongoing studies of gender and tuberculosis. It is
anticipated that these cross-cutting interests in study of stigma
and gender will remain a priority of the research group, both in
designated studies and as a component of other studies.
The cultural epidemiology group also supports other
research at STI, especially activities concerning the environment, society and health systems research (Section 7). There is
a continuing concern with urban health, including both research
activities and graduate teaching, and also links to the project on
the health of nomadic populations (7B.1). The group has also
provided support for a study of female genital mutilation among
African migrants to Switzerland (7C.7), and for students working
for the degree of Master of International Health (MIH). One of
the MIH projects is a study of the culture and health of the marginalised Indian hijra community in Pune.
External collaboration in Europe included technical assistance for developing clinical applications of the cultural formulation, working with Dr. S. Jadhav at University College London,
and for a cultural epidemiological study of somatoform disorders at the University of Heidelberg with Dr. P. Henningsen.
Studies outside Europe that are supported by consultations
include a study on Development of culturally appropriate tools
for the assessment of mental health problems in Australian
indigenous people (A. Janca, University of Western Australia),
and an NIH-supported study, Improving antidepressant adher-
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ence in older adults (J. Sirey, Cornell Intervention Research
Center, USA).
To communicate developments in cultural epidemiology to
colleagues with related interests, a special issue of the journal
Anthropology and Medicine was published in April 2001. The
six articles sampled recent mental health research in the field,
and an Introduction and Overview outlined principles and
research priorities for clinical and community-based cultural
epidemiological studies. As our research in the STI proceeds, a
comparable volume with an overview of the cultural epidemiology of infectious diseases would provide a useful complement.
To promote awareness of cultural epidemiology among other
investigators and strengthen research capacity in the field,
the STI collaborated with the WHO Special Programme for
Research and Training in Tropical Diseases (TDR) in a workshop
in Basel in July 2002 on the principles and methods of cultural
epidemiology, focussing on tropical disease research. Participants included 18 investigators from Africa, South Asia, and
South America. Examples and data sets from previous studies
were used to enable participants to acquire skills for ethnographic study and for developing, administering and analysing
locally adapted, semi-structured EMIC interviews. Teaching and
8.1
Cultural research for rural mental health in the
Sundarban region of West Bengal, India
Aims of this research included anthropological study of mental
health and illness in three village communities in each of two
development blocks of the Sundarban region – Gosaba and
Sagar Island. With the benefit of ethnographic data to clarify the
cultural context and to identify relevant categories of locally
specified patterns of distress, perceived causes, and help
seeking (which constitute representations of illness), EMIC interviews were constructed. They were used to study the distribution of these illness representations among patients seeking
help for mental health problems in clinics established to provide
mental health services for these communities. For interviewing
respondents who were not patients, and therefore had no presenting symptoms as a focus of inquiry, EMIC interviews were
constructed with reference to clinical vignettes depicting locally
relevant examples of priority mental health problems (e.g. psychosis, depression, possession, a local illness concept called
“hystria”, and so forth). These vignette-based EMIC interviews
were used to study a sample from the general population without overt mental illness, and for a study of health care providers
whom people on the island might consult for mental health problems.
The research team completed EMIC interviews with 240 clinic patients, 164 community residents without overt mental
illness, and 120 local health care providers in the Sagar Island
development block. The Rudranagar rural clinic sample on
Sagar Island included 40 patients each with schizophrenia,
major depression, and somatoform disorders who sought treatment at the specialty mental health clinic established by Dr.
Chowdhury over the course of the study. Patients admitted for
treatment after episodes of deliberate self-harm (DSH), usually
by ingesting pesticides, were also interviewed. An urban comparison group of clinic patients at the Institute of Psychiatry,
Calcutta, was also studied.
64
training materials were developed that will be made more widely
available through STI and TDR.
WHO/TDR-STI Cultural Epidemiology Workshop at STI, Basel, 22 – 26 July 2002.
Top row (l. To r.): C. Auer, C. Naumann, M.G. Weiss, M. Konate, S. Atre, P. Anafi,
O. Akogun; 3rd row: L. Gomez, S. Wayling, S. Jawahar, B. Obrist, C. Ahorlu; 2nd
row: P. Vounatsou, N.L. Arias, I. Makwiza, C. Mayombana, L. Sanudi, N. Ahmad;
bottom row: G.K. Anzadi, S. Banerjee, D. Deshmukh, F. Kareem. (Source: R. Dürr)
This research carefully integrated ethnography and cultural
epidemiology. The ethnographic findings highlighted the categories and contexts of common mental health problems, showing how social contexts, social change, and cultural concepts
shape community representations of mental illness. Local concepts emphasised magico-religious, social, economic, and
medical formulations of various mental health problems. Gender
roles and social disparities were found to play a significant role
in explaining them. Specific findings showed how substance
abuse by men (primarily of alcohol) affected families and
increased the vulnerability of women at risk for abuse and
domestic violence. These findings have been incorporated into
the content of community participatory interactions with local
leadership groups (panchayats and teachers), women’s
groups, and school children.
Stigma (characterised by social exclusion and discrimination
– both real and self-perceived) was a prominent feature of the
social and psychological impact of mental illness. Even when
services were available, stigma complicated both help-seeking
and the provision of clinical care by providers. To study stigma
we developed and locally validated a scale for assessing the
magnitude of stigma, and studied qualitative dimensions in
a cultural epidemiological account of stigma. Findings show
the concept is more complex than it seemed initially to health
Woman fishing in a rural hamlet of Namkhana, Sundarban. (Source: M.G. Weiss)
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researchers, but it is clearly important, and merits the increasing
attention it is receiving in health research.
Awareness and concern about deliberate self-harm (DSH)
and suicide, and the local priority given to them, were greater
than anticipated. Findings indicating the frequent use of pesticides for DSH highlighted needs for greater attention to pesticide policies and social stressors. Findings have also motivated
further research on pesticides and DSH, and a project now
under way is developing community participatory activities for
mental health promotion, prevention of DSH and suicide, and
improved recognition and referral of serious mental illness.
The existing local health system of homeopaths, faith healers, and practitioners with either dubious credentials or no credentials of any kind, who are commonly consulted for mental
health problems in the community, was found to be far more
extensive than anticipated. We were especially interested in
learning how these practitioners explained such problems, how
they treated them, and under what circumstances they referred
the patients. Inasmuch as the practitioners constitute a locally
valued resource in the poorly-served village communities, it is
important to recognise who the health care providers are and
what they do – and to consider whether or not these local practitioners have a role to play that should be considered in the
plans and activities of mental health policymakers.
Efforts to rationalise community and professional priorities
for locally implementing policy suggested the value of a fourpronged approach to community mental health: i) case identification and either treatment or referral of serious mental disorders; ii) reduction of suicidal behaviour through community
interactions, and treatment addressing the underlying problems
in follow-up after providing emergency medical care of patients
brought for treatment after an episode of DSH; iii) improved
recognition of common mental disorders and enhanced capacity to treat them in the primary health clinics, and iv) building
local partnerships to promote mental health and prevent mental
health problems in the community.
STI Scientists:
B. Obrist van Eeuwijk, P. Vounatsou, M.G. Weiss
Research assistants:
L. Gomez, H. Keval
Collaborating Scientists: A.N. Chowdhury, J. Ramakrishna, R. Raguram,
A.K. Chakraborty, D. Sanyal
Students:
S. Banerjee (PhD), R. Begrich (MA),
A. Bhattacharya (MD), R. De (PhD), S.K. Dutta (PhD)
Collaboration:
Institute of Psychiatry and Department of Psychiatry,
Post-Graduate Institute of Medical Education &
Research, Calcutta, India (A.N. Chowdhury)
Funding:
SNSF
8.2
Cultural research for urban mental health in Mumbai
Urban mental health research at KEM Hospital continues to pursue clinical studies of common mental disorders and deliberate
self-harm (DSH), and a community study in a disadvantaged
slum of Mumbai is advancing an agenda in under-served communities that provides an urban complement to research in rural
West Bengal. As in the Sundarban region, field studies in the
Malvani community are also supporting development of a mental health system encompassing participatory community action
and clinical services in a local primary health centre. The primary health centre (PHC) is supported by the KEM Hospital, an
Mothers and children of the Malvani community, Mumbai. (Source: M.G. Weiss)
academic research, teaching, and tertiary care referral centre of
high repute, run by the Greater Mumbai municipality and situated 35 km away from central Mumbai.
Malvani is a community with seriously limited resources
where poverty and migrant status disenfranchise many residents and contribute to their vulnerability. The impact of social
stressors, communal tensions, and cultural values that work to
the particular disadvantage of women creates an environment
that must be recognised as a key factor for consideration in formulating an agenda for community action and clinical services
to improve mental health. Although the KEM Hospital has supported medical clinics at the PHC for more than two decades,
the establishment of a mental health component of community
health is a recent development, closely linked with this
research.
A baseline community cultural epidemiology study was
undertaken to determine how professional priorities relate to
local concepts of mental health and illness, bridging the language and interests of professionals and the local population.
This research has also emphasised questions of gender and
women’s health. Studies include both clinic and field-based
components, employing ethnographic methods and cultural
epidemiological study with EMIC interviews. Ethnographic and
community participatory methods engage women’s groups and
the leadership of the community. Clinical research is studying
patients who screen positive for common mental health problems in the PHC.
At the Malvani field site, activities have involved a mix of
community action, mental health services, and research. A
study of completed suicides (identified by police records and
other means) is using EMIC interviews (focussing on both the
suicidal event and the underlying problems), which are administered to survivors representing different social interests (e.g.
in-laws vis-à-vis parents of young married women who die by
suicide). The research is identifying the common themes and
contexts of suicide in the community, and it answers questions
about how suicides are portrayed by different family interests,
considering their consistency and their discrepancy.
The research interest in DSH and suicide pursued in Malvani
also remains an important focus of research at KEM Hospital
itself, where these DSH studies were developed. Preliminary
findings from study of patients admitted for DSH to KEM indicate the limitations of diagnostic assessment to ascertain
required relevant information for managing problems leading to
DSH. These findings suggest that although diagnosis remains
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Psychiatric diagnosis of patients admitted after episode of Deliberate SelfHarm to KEM Hospital, Mumbai, India
STI Scientists:
Research assistants:
L. Gomez, H. Keval
Diagnosis
Students:
S.R. Parkar (PhD), B. Nagarsekar (MD)
Female
n = 93
Male
n =103
Total
n =196
Collaborating Scientists: P. Subramaniam, V. Dawani
Psychotic disorder
2.2
2.8
2.6
Unipolar major depression
48.4
38.7
43.9
Other depressive disorder
6.5
3.8
5.1
Somatoform pain disorder
1.1
0.0
0.5
Alcohol or Substance use
2.2
34.0
19.4
Panic Disorder
1.1
0.9
1.0
Pathological gambling
0.0
0.9
0.5
Adjustment disorder
22.6
22.6
23.0
V-Codes (relational/academic)
12.9
9.4
11.2
No Diagnosis
12.9
7.5
10.2
Note: Diagnosis is based on Structured Clinical Interview for DSM-IV (SCID-IV).
Data from S.R. Parkar, KEM Hospital, Mumbai.
an important indication of suicidal risk, it has serious limitations
for management of patients admitted for DSH, many of whom
do not meet criteria for disorders most closely associated with
high risk for suicidal behaviour. Nearly half the women, and
nearly 40% of the men in a sample of 196 adults admitted to the
hospital after surviving an episode of DSH did not fulfil criteria for
any Axis I psychiatric disorders apart from adjustment disorders
or V-codes, which specify stressful situations rather than disorders. Findings also indicate that despite the value of psychiatric
case-finding and the need to identify and treat any treatable psychiatric disorders, case-finding in the community may have serious limitations as an approach to reducing suicide. Further
cross-cultural study of this question, to guide policy, is planned.
Another research study in metropolitan Mumbai on vulnerability and community perceptions of suicide has engaged
school students in discussions of their experience with suicide
and DSH among relatives and other people they have known.
As in the rural West Bengal communities, urban students in
Mumbai responded productively to requests that they prepare
posters and formulate strategies to promote mental health and
to identify positive alternatives to suicidal thinking.
High school student’s suicide prevention poster. (Source: S.R. Parkar)
66
Collaboration:
KEM Hospital, Mumbai, India (S.R. Parkar)
Funding:
SNSF; local KEM Hospital funding
8.3
Cultural study of fatigue and weakness in Pune, India
This research was initially motivated by cross-cultural comparative questions about the distinctiveness and the cultural validity
of chronic fatigue syndrome (CFS) and neurasthenia (NT)
among East Asian patients in China and Taiwan, East Asian
immigrants to North America (Los Angeles and Toronto), and
American residents of European ancestry in Los Angeles. In
Pune, India, a study of patients seeking treatment for medically
unexplained symptoms of fatigue and weakness has been
investigating the cultural basis of a common clinical problem
that has been difficult for clinicians to treat. Patients with a common profile of symptoms were identified and interviewed in four
clinics of the Sassoon Hospital, Pune: the outpatient clinics
of psychiatry, medicine, Ayurveda, and dermatology. Each of
these clinics represents a distinctly different option for help
seeking. A locally adapted EMIC interview was used to examine
the health problems that motivated the patients’ medical help
seeking, comparing the cultural epidemiology of patients in the
various clinics. In addition to a descriptive emic account, an
intracultural comparative research question asked how different
illness-related experiences and meanings are related to the
choice of different help seeking options that brought patients to
each clinic.
Complementing the emic assessment, patients were also
evaluated with psychiatric diagnostic instruments and symptom
scales. These included the Structured Clinical Interview for
DSM-IV and supplementary modules prepared for the collaborative study based on criteria for CFS of the Centers for Disease
Control and Prevention, and criteria for NT of the Chinese Classification of Mental Disorders, 2nd edition. Other standard clinical scales were also administered to help clarify the clinical status of patients’ problems.
Although data collection has just recently been completed,
preliminary findings suggest high rates of psychiatric comorbidity for common mental disorders, indicating a lack of specificity
for depressive, anxiety, and somatoform diagnoses. These findings are consistent with our previous collaborative studies of
depression at NIMHANS in Bangalore with Prof. R. Raguram,
and a recent study of somatoform disorders at the University of
Heidelberg with Dr. P. Henningsen.
Some preliminary findings from the illness narratives elicited
in the EMIC interviews have also been notable. Concerns about
the culturally defined dhat syndrome were frequently mentioned
by men, as expected, but the advance of HIV/AIDS has brought
to the fore fears of this “new” disease as a common theme.
Among women, recurring reports of domestic violence, unsupportive husbands, and challenging social and environmental
conditions were common. They were, however, less frequently
associated with psychopathology than one might have expected from the high impact of such stressors. Many of these
women appear to have accepted such conditions as normal,
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and so long as they were able to work, they reported no emotional problems. Functional disability, rather than emotional
distress, was the measure by which they identified clinical
problems serious enough to motivate medical and related help
seeking.
In the clinical setting of these research interviews, patients’
accounts of experience, meaning, and behaviour associated
with disorders of fatigue and weakness provided an account of
the illness that was deeply embedded in the social and cultural
contexts of patients’ lives. It appears that consideration of and
attention to these contexts, rather than just assessment and
treatment of psychopathology, is especially important for disorders of fatigue and weakness. As we analyse data from this
study, we expect findings to further clarify the role of such social
and cultural themes and to indicate more specifically how they
relate to the clinical management of these disorders, and to
public health efforts to mitigate or prevent them.
Another community-based study was motivated by clinical
experience suggesting that many patients admitted with psychotic disorders had previously sought help from healing temples and various types of healers. Research at such a healing
temple in Tamil Nadu used EMIC interviews to study the illness
of people seeking help there, and a NIMHANS psychiatrist
residing at the temple over the course of the study assessed the
course of symptoms using professional scales (e.g. Brief Psychiatric Rating Scale) on the arrival and departure of persons
coming for help to the temple. Although there were no particular
healing ceremonies or treatments, the period of residence in
this non-threatening, supportive environment resulted in a level
of clinical improvement comparable to effective pharmacological treatment. The research provided an account of the experience, meaning, and behaviour associated with psychotic illness
in that region, and findings also indicated the positive impact of
a culturally valued refuge for people with severe mental illness.
STI Scientists:
STI Scientists:
Collaborating Scientists: M. Agashe, V. Paralikar, M. Oke
Research assistant:
L. Gomez
Collaboration:
Maharashtra Institute of Mental Health, India; Harvard
Medical School, USA (A. Kleinman); University of California at Los Angeles, USA (K.M. Lin); University of
Toronto, Canada (R. Lee)
MD students:
T.M. Raghu, A. Venkateswaran
Collaboration:
NIMHANS, Bangalore, India
Indo-U.S. Special Foreign Currency Research Fund
Funding:
SNSF; local NIMHANS funding
Funding:
B. Obrist van Van Eeuwijk, P. Vounatsou, M.G. Weiss
Collaborating Scientists: R. Raguram, J. Ramakrishna
8.4
Cultural study of schizophrenia and psychosis in
South India
8.5
Gender and tuberculosis
Since the early studies undertaken with the EMIC at the National
Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, this centre has been a key collaborator and contributor
in developing the concept and methods of cultural epidemiology. Two recent studies have been completed over the past two
years, one a clinical cultural epidemiological investigation in a
NIMHANS outpatient clinic, and the second a field study of
patients with major mental illness, mainly schizophrenia, seeking treatment at a temple in Tamil Nadu known for its benefit to
people with serious mental health problems.
The study of 60 patients with schizophrenia at NIMHANS
employed an appropriately adapted EMIC interview with a designated caretaker, usually a relative of the patient. The structure
of the interview, distinguishing spontaneously reported and
probed responses, indicated that some ideas about experience, meaning, and behaviour were more attractive topics to
speak about than others. For example, in discussing the meaning of the patient’s illness, the vast majority of respondents readily attributed the condition to emotional issues (88.3%), including worries (70.0%), personality (48.3%), or loneliness (25.0%).
Such issues appeared easy to discuss, and they were reported
spontaneously in response to open-ended questions about
cause. Other perceived causes, however, were difficult to discuss, and they were elicited only after inquiring directly about
them, such as alcohol (8.3% reported spontaneously, 60.0%
after probing) and victimisation, either sexually or physically, as
an adult or child (15.0% spontaneously, 65.0% after probing). A
multivariate analysis of determinants of stigma, with reference to
a scale validated in the study, identified cultural epidemiological
variables associated with stigma. Qualitative data clarified the
nature of identified relationships.
STI has been supporting several cultural studies of gender and
tuberculosis that focus on women’s health. They examine barriers to quality care for women in low to middle-income countries
and sex differences at various points in the course of TB control,
considering influences of social contexts and cultural values on
case finding, help seeking, diagnosis, and adherence to treatment in DOTS programmes (the widely-used strategy in which
the compliance of patients with treatment is directly observed).
TB rates are higher among men, but it is an important health
problem for women as well, with high mortality. Because TB
tends to affect younger women when they are economically and
reproductively most active, the impact on children and families
is a matter of particular concern.
The first of these STI collaborative studies of gender and TB
was undertaken by the Foundation for Research in Community
Health (FRCH) in rural Pune district, India. It included an ethnographic study and EMIC interviews with TB clinic patients, the
general population, and the health care providers whom
patients consult in the community apart from the governmentdesignated TB clinics under the Revised National Tuberculosis
Control Programme (RNTCP). Findings clarify some of the
gender-specific features of TB in the region, notably the limited
access of women to financial and family resources for appropriate health care and sustained treatment, and the adverse
impact on men of lost wages, jobs, and inability to meet commitments to support their families. This study has also provided
an opportunity to examine different features and effects of
stigma from the vantage points of patients, the general population, and providers in the community.
Experience from the research in Pune highlighted the needs
and the potential value of enhancing the sensitivity of TB control
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programmes to questions of gender. Recognising that the social
contexts of TB may differ substantially from rural to urban sites
and across cultures, WHO/TDR, with technical support from STI,
undertook a multicentre study of gender and tuberculosis in four
countries, namely, Bangladesh, Colombia, India, and Malawi.
This research set out to answer basic and cultural epidemiological research questions about the gender basis of sex differences in rates of TB, clinical assessment and management, and
TB-related experience, meaning, and behaviour. The research
was designed to answer questions applicable to the control programmes at each site and to facilitate cross-site comparisons.
Aims include identification of sex differences for key aspects of
TB control; sociocultural and operational gender-based barriers
to case identification, treatment, and cure; and distinguishing
culture-specific issues and cross-cutting considerations for
introducing a gender perspective in TB control.
Although concerns about the primary symptoms of TB are
reported by both sexes, women are more vulnerable as targets
of stigma to the adverse impact of disease on family life and
on their ability to marry or stay married. Even when men and
women report the same perceived causes of TB, such as infection and contagion, men tend to focus on exposure outside the
home in public places, and women more typically report exposure while caring for others with TB in the home. Support available to people disabled by their illness, particular manifestations of stigma, specific disruptions of family life, and other
effects of TB, are expected to have both similar and culturally
distinctive features across sites, which these studies will specify.
Even though each of the sites is working with control programmes that implement a DOTS strategy, the setting, structure,
and organisation of services vary among them. In Bangladesh
BRAC (Bangladesh Rural Advancement Committee) supports
comprehensive rural health services that include treatment of
TB. Illiterate women health workers play a key role in initiating
and observing treatment. The rural experience in the BRAC
study and in the earlier FRCH (Foundation for Research in Community Health) study in Maharashtra is complemented by
research in the urban programmes in Chennai, India, where the
TRC (Tuberculosis Research Centre) study is underway and the
DOTS programme is implemented in RNTCP health centres. In
Lilongwe, Malawi, the gender focus on TB complements other
studies of the Equi-TB Knowledge Programme, operating in a
setting with a formidable level of interaction of HIV/AIDS and TB.
In Cali, Colombia, TB control programmes studied by CIDEIM
(Centro Internacional de Investigacion y Entrenamiento Medico)
are affected by the serious
impact of sociopolitical upheaval, and concerns about
security are a high priority with
both cross-cutting and gender-specific effects on the
operations and effectiveness
of the programmes.
Each of the project sites is
currently completing field research and data collection,
and it is anticipated that findings will be reviewed together
Rural health worker explaining the use
with policy-makers concerned
of TB drugs in BRAC programme,
with gender-sensitive policy
Bangladesh. (Source: M.G. Weiss)
68
for TB control in early 2003 in a meeting at WHO headquarters
in Geneva.
STI Scientists:
Research assistant:
L. Gomez
Collaborating Scientists: S.N. Morankar, S. Rangan, M. Uplekar, S. Atre,
A. Kudale, D. Deshmukh (FRCH); M. Chowdhury,
F. Karim, A. Islam (BRAC); E. Jaramillo, N.L. Arias
(CIDEIM); S. Jawahar, S. Ganapathy, B. Thomas (TRC);
J. Kemp, L. Sanudi, I. Makwiza (Equi-TB)
Collaboration:
FRCH, Pune, India; TRC, Chennai, India; Equi-TB,
Malawi; BRAC, Bangladesh; CIDEIM, Colombia
Funding:
WHO/TDR, SDC
8.6
Tuberculosis treatment trial in Metro Manila,
Philippines
The DOTS strategy for TB-control has been implemented successfully in 150 countries, but approximately two-thirds of TB
patients are still not being treated in such a programme. It is
important to make DOTS not only more cost-effective but also
more attractive for the patients. One potentially more convenient
and appealing approach to treatment is that patients are treated
using a regimen that requires medicines to be administered only
three times a week, instead of every day.
To compare the acceptability and effectiveness of the daily
and thrice-weekly treatment schedules, a randomised controlled trial is being carried out in Taguig, a municipality with a
population of 530,000 in Metro Manila, Philippines. For the trial,
thrice-weekly therapy has been randomly assigned to 10 of the
20 Health Centres (HCs) of Taguig. Since November 2000, all
newly enrolled TB patients in the designated HCs have been
receiving thrice-weekly therapy (except that patients who have
previously failed in treatment receive the established daily therapy). All TB patients of the other 10 HCs continue to receive
daily therapy. All smear-positive and culture-positive patients
are interviewed to assess their views about response, side
effects, and convenience of the regimen. By September 2002,
728 patients (411 assigned to thrice-weekly therapy and
317 assigned to daily therapy) had been interviewed shortly
after they began treatment. The trial will continue to enrol
patients until the end of 2002. Preliminary results were presented at the 4th World TB Congress (Washington DC, June
2002) and the World Conference on Lung Health (Montreal, Oct.
2002).
Baseline data were similar in the two groups of patients,
except for body weight under 35 kg and strong sputum
microscopy positivity, which were both more common among
those receiving daily therapy. One in five of the patients had
received prior treatment for TB for at least one month.
It was found that when therapy was given thrice-weekly,
HC personnel actually observed drug-taking more frequently
(49% vs. 32%; p < 0.0001). Thrice-weekly therapy was more
popular among patients and health personnel than daily therapy, and resulted in savings of about 40% of the cost of drugs.
There were also some disadvantages of thrice-weekly therapy:
patients had to take more drugs at one sitting than with daily
therapy, and some reported difficulty swallowing the pills, and
nausea. The sputum conversion rate assessed after two or three
months of treatment was lower with thrice-weekly therapy than
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with daily therapy (79% vs. 89%; p = 0.001). However, overall
treatment outcome was essentially the same (Table 8.2).
Outcome of two treatment regimens for TB (n = 535)
Chowdhury AN, Sanyal D, Chakraborty AK, De R, Banerjee S & Weiss MG (in
press) Community psychiatry clinics at Sundarban: a rich clinical and cultural
experience. Ind J Pub Health.
Thrice-weekly
(n= 303)
Daily therapy
(n= 232)
P-value
Chowdhury AN, Sanyal D, Dutta SK, De R, Banerjee S, Bhattacharya K, Palit S,
Bhattacharya P, Mondal RK & Weiss MG (2001) Interrater reliability of the EMIC in
a pilot study in West Bengal. Int Med J (Japan) 8, 25 – 29.
Successful treatment*
69% (208/303)
73% (169/232)
p = 0.3
Chowdhury AN, Shashmal R, Dutta S & Weiss MG (in press) Ethnographic survey
of deliberate self-harm from the Sundarban Delta. Ind J Anthropol Soc.
Lost (mostly due to leaving
Taguig)/Transferred-out
20% (60/303)
18% (41/232)
p = 0.5
Cultural Psychiatry: Euro-International Perspectives (2001) Eds Yilmaz AT, Weiss
MG & Riecher-Rössler A. Basel: Karger
Failure/possible failure**
9% (28/303)
6% (14/232)
p = 0.2
Relapse
1% (3/303)
1% (2/232)
p > 0.5
Died
1% (4/303)
3% (6/232)
p = 0.3
* Approximately 90% of these patients were confirmed cured with final sputum
test. ** Scantly positive.
Resistance to anti-TB drugs is a serious problem. Sputum
samples obtained before initiating treatment were studied for
drug sensitivity, and results for 326 patients are already available. Among the sputum samples, 70% were sensitive to all
drugs. The rate of resistance to isoniazid (with or without resistance to other drugs) was 26%. It was less for the 230 new cases
(22%) and more for the 63 previously-treated cases (40%). For
streptomycin, 7% of new and 16% of previously treated cases
were resistant, and for ethambutol, 1% of new and 10% of previously treated cases showed resistance. Multidrug-resistant TB
(that is, resistant to at least isoniazid and rifampicin) was found
among 8% of the patients (3% for new and 27% for previously
treated cases).
STI Scientists:
G. Pluschke, M. Tanner, M.G. Weiss
PhD Student:
C. Auer
Collaboration:
Center for Infectious Diseases, Department of Health, Manila,
Philippines (J. Lagahid); College of Public Health, University of
the Philippines Manila, Manila, Philippines (L. Montejo); TB
Research Laboratory, Philippine General Hospital, University
of the Philippines Manila, Manila, Philippines (C. Ang and
C. Roa); Institute of Tropical Medicine, Mycobacteriology Unit,
Antwerpen, Belgium (A. Van Deun)
Funding:
RGS; Novartis Foundation for Sustainable Development, Basel;
Roche Research Foundation, Basel
Publications:
Akogun OB, Audu Z, Weiss MG, Adelakun AO, Akoh JI, Akogun MK, Remme H &
Kale OO (2001) Community-directed treatment of onchocerciasis with ivermectin
in Takum, Nigeria. Trop Med Int Health 6, 232 – 243.
Chowdhury AN, Sanyal D, Dutta SK, De R, Banerjee S, Bhattacharya K, Palit S,
Bhattacharya P, Mondal RK & Weiss MG (2001) Prominence of symptoms and
level of stigma among depressed patients in Calcutta. J Indian Med Assoc 99,
20 – 23.
Chowdhury AN, Shasmal RK, Chakraborty AK, Ramakrishna J & Weiss MG (2001)
Eco-stress of human-animal conflicts in the Sundarban Delta of West Bengal,
India. Eastern Anthropol 54, 35 – 45.
Chowdhury AN, Sanyal D, Dutta SK, Banerjee S, De R, Bhatacharya K, Palit S,
Bhattacharya P, Mondal RK & Weiss MG (2000) Stigma and mental illness: pilot
study of laypersons and health care providers with the EMIC in rural West Bengal,
India. Int J Med 7, 257– 260.
Gilgen D, Gross CS, Maeusezahl D, Frey C, Tanner M, Weiss MG & Hatz C (2002)
The impact of organized violence on illness experience of Turkish/Kurdish and
Bosnian migrant patients in primary care. J Travel Med. 9, 236 – 243
Jadhav S, Weiss MG & Littlewood R (2001) Cultural experience of depression
among white Britons in London. Anthropol Med 8, 47– 69.
Lee R, Rodin G, Devins G & Weiss MG (2001) Illness experience, meaning and
help seeking among Chinese immigrants in Canada with chronic fatigue and
weakness. Anthropol Med 8, 89 –107.
Morankar S & Deshmukh D (2001) Socio-cultural aspects of tuberculosis among
women: implications for delivery of services. Pune/Mumbai: Foundation for Research in Community Health.
Morankar S & Weiss MG (in press) Impact of gender on illness experience and
behaviour: Implications for tuberculosis control in rural Maharashtra. Health
Administrator.
Raguram R, Venkateswaran A, Ramakrishna J & Weiss MG (2002) Traditional
community resources for mental health: a report of temple healing from India.
BMJ 325, 38 – 40.
Raguram R, Weiss MG, Keval H & Channabasavanna SM (2001) Cultural dimensions of clinical depression in Bangalore, India. Anthropol Med 8, 31– 46.
Uplekar M, Rangan S, Weiss MG, Ogden J, Borgdorff MW & Hudelson P (2001)
Attention to gender research in tuberculosis control. Int J Tub Lung Dis 5,
220 – 224.
Weiss MG Ed. (2001) Cultural Epidemiology. Special Issue of Anthropol Med 8.
Weiss MG (2001) Psychiatric diagnosis and illness experience. In: Cultural Psychiatry: Euro-International Perspectives. Eds Yilmaz AT, Weiss MG, RiecherRössler A. Basel: Karger
Weiss MG (2001) Cultural epidemiology: an introduction and overview. Anthropol
Med 8(1), 5 – 29.
Weiss MG, Cohen A & Eisenberg L (2001) Chapter 7: Mental health. In: Merson M,
Black B, Mills A (Eds), Introduction to International Health. Gaithersberg, MD:
Aspen.
Weiss MG, Isaac M, Parkar SR, Chowdhury AN & Raguram R (2001) Global,
national, and local approaches to mental health: examples from India. Trop Med
Int Health 6(1), 4 – 23.
Weiss MG, Jadhav S, Raguram R, Vounatsou P & Littlewood R (2001) Psychiatric
stigma across cultures: local validation in Bangalore and London. Anthropol
Med 8(1), 71– 87.
Weiss MG & Ramakrishna J (in press) Stigma interventions and research for international health. Background conference paper for “Stigma and Global Health:
Developing a Research Agenda,” 5 –7 September, Fogarty International Centre,
Bethesda, MD. Proceedings, currently on Web site: http://www.stigmaconference.gov.
Weiss MG & Yilmaz AT (2001) Introduction: Euro-international perspectives. In:
Cultural Psychiatry: Euro-International Perspectives. Eds Yilmaz AT, Weiss MG,
Riecher-Rössler A. Basel: Karger
Chowdhury AN & Banerjee S (2001) Pesticides and suicide epidemic among
Indian farmers: a grave public health challenge. Indian J Soc Psychiatry 17,
62 – 69.
Yilmaz AT & Weiss MG (2001) Cultural formulation: depression and back pain in a
young male Turkish immigrant in Basel, Switzerland. In: Cultural Psychiatry: EuroInternational Perspectives. Eds Yilmaz AT, Weiss MG, Riecher-Rössler A. Basel:
Karger
Chowdhury AN, Chakraborty AK & Weiss MG (2001) Community mental health
and concepts of mental illnes in the Sundarban Delta. Anthropol Med 8, 109 –129.
Zinsstag J & Weiss MG (2002) Livestock diseases and human health (Editorial).
Science 294, 477.
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SECTION 9
9.1 Teaching at the University of Basel
The Swiss Tropical Institute is an Associated Institute of the University of Basel. All senior staff have teaching responsibilities in
the University, especially in the Faculty of Sciences, but also in
Medicine and Arts. Members of staff also teach in other universities. The STI is also responsible for the inter-faculty PhD programme in Epidemiology. The STI courses in the Faculty of Science include Parasitologie & Parasitismus and Protozoologie in
the second year. A focal point of the revised curriculum in biology in the third year is the block course Infektionsbiologie und
Epidemiologie which will be taught for the first time in Autumn
2002. To develop and support the “teaching for learning”
approach to be used in the block course, a second didactic
workshop was organised in 2002 with Dr. Carol Bowie from the
Griffith Institute for Higher Education in Brisbane, Australia. Participants prepared the problem-based learning units of the new
block course and discussed methods for student assessment
and better feedback.
The lists of graduate students in the STI registered for
degrees in the University of Basel give an overview of the wide
range of subjects covered in the STI’s teaching and research
(pages 72 – 73).
Members of STI staff holding teaching appointments in the University of Basel
Faculty of Science
N.A. Weiss
R. Brun
G. Pluschke
L. Jenni
Professors
Chairs of Epidemiology and Medical
Parasitology.
Dean, Faculty of Science (from 2002)
Parasitology; Biology of Infectious Disease
Parasitology and Protozoology
Immunology
MGU (Mensch, Gesellschaft, Umwelt)
H.-P. Beck
I. Felger
C. Lengeler
W. Rudin
T. Smith
A. Zumstein
C. Daubenberger
University lecturers
Molecular parasitology
Molecular parasitology
Epidemiology
Parasitology and Functional Morphology
Epidemiology, Biostatistics
Parasitology
Immunology (University of Hanover)
M. Tanner
Faculty of Medicine
A. Degrémont
M.G. Weiss
Professors
Tropical Medicine
Social and Preventive Medicine
C. Hatz
B. Genton
University lecturers
Tropical Medicine
Tropical Medicine (University of Lausanne)
Faculty of Humanities
B. Obrist-van
Eeuwijk
70
Medical Anthropology
The post-graduate programme, “Urban Health in Developing
Countries”
The collaboration between epidemiology and anthropology in
the field of urban health research has been further strengthened
in research and teaching, with the development of a three-year
PhD and post-doctoral programme in the University of Basel
entitled Urban Health in Developing Countries. This is a joint
programme of the Faculty of Humanities, the Institute of Ethnology (Medical Anthropology), and the Faculty of Science with the
STI (Epidemiology). The programme builds on existing relationships with research partners in African and Asian cities. Its main
objective is to provide training and support for junior
researchers in the disciplines of epidemiology and ethnology.
Teaching staff and researchers come from both North and
South. An innovation in the teaching of postgraduate students in
Basel has been the organising of annual workshops, where all
the students in the programme come together for specific training, for example in project-writing or methods of data analysis.
The research projects address a variety of issues in the field
of urban health, in Abidjan (Côte d‘Ivoire), Ouagadougou (Burkina Faso), Dar es Salaam (Tanzania), Mumbai (India), Calcutta
(India), Manila (Philippines) and Manado, Tahuna and Tomohon
(Indonesia). Projects that form part of the programme are
described in Sections 7 and 8.
Centre for African Studies, Basel
The increasing importance of African Studies in Basel has led to
the foundation of the interdisciplinary Centre for African Studies
Basel (CASB), of which the STI is a founding member. A new
inter-faculty Master’s degree in African studies has been established in the University of Basel. The aim is to give students a
detailed understanding of the historical and present-day situation in Africa.
Master in International Health – a joint European programme
Since December 2001, the postgraduate degree MIH (Master of
Advanced Studies in International Health) has been fully
accredited by the University of Basel. It is one of the first joint
Master‘s degree programmes in the field of Public Health to be
recognised by a number of universities in different countries
(7 at the time of writing).
The MIH degree was established by an association of
27 institutions in Europe – mostly Tropical Institutes, but also
Public Health Departments and institutions involved in development studies, which are members of the European Network for
Education in International Health (tropEd). STI is founding member of tropEd, and since 1995 has been one of the two co-ordinating centres of the network. Besides some funding through
the European Commission, the input of STI and the co-ordination of the network was substantially supported by the Swiss
Agency for Development and Co-operation (SDC) and the
Swiss Federal Office of Education and Science (BBW).
The aim of tropEd is to promote excellence in postgraduate
education and training in International Health. It aims to foster
mobility of students and teachers – indeed, it is a requirement of
the programme that students must take courses in different
countries. TropEd has been very successful in bringing together
institutions with very different experience and histories, working
in 11 countries with various patterns of postgraduate education,
to plan a common curriculum. This takes into account the
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change in emphasis in international health from a concentration
on tropical medicine to a focus on public health issues. The
approach to the course includes an understanding of development as an exchange of ideas and resources, rather than the
classical one-way transfer of knowledge, and the promotion
of collaboration and co-ordination among institutions within
Europe, and between the Northern and the Southern hemispheres.
The MIH programme is designed for people who can only
study part-time. The workload is equivalent to one year of fulltime study, but can be distributed over a period of five years.
Each student is registered in one of the participating universities, and has a “home” institute associated with that university. A
tutor in the “home” institute gives advice and support, and guarantees the quality of the course of study. This requires a large
investment of time, so the STI has limited the places for the MIH
programme. As a result, the selection of candidates is highly
competitive.
The structure of the MIH curriculum is the same in each member institution. The programme starts with a mandatory core
course of about 3 months. One of these is the STI course Health
Care and Management in Tropical Countries (9.2). The core
course is followed by a series of optional modules, equivalent to
about 14 weeks of full-time study. To enable students to broaden
their experience and to see different teaching and learning
approaches, most of the optional modules must be taken outside the home institution. The course is completed by a project
leading to a dissertation, taking 3 – 6 months. The projects are
often directly connected with the student’s professional work.
The transfer of credits for courses taken in different places is
regulated by the European Credit Transfer System (ECTS). At
present, 35 students are enrolled in the MIH programme in the
University of Basel, and three have already completed the
degree course.
Brief portraits of three of our MIH students
Chandon Chattopadhyay is a medical doctor from Basel,
Switzerland, with family roots also in India. He enrolled in the
MIH programme in 2000. He attended optional modules in
many tropEd partner institutions, as a preparation for a two
year stay in Calcutta/India immediately after completing the
course. He graduated in May 2002 with a dissertation on
training for people participating in voluntary organisations.
Besides working as a physician, he has been active for many
years in the Calcutta Project in Basel, a voluntary organisation of medical students and young
doctors whose aim is to improve Primary Health Care Services in Calcutta.
Sabine Kampmüller is an Austrian nurse who took the
HCMTC course at STI. Soon after she started the MIH course
she began work with Médecins sans Frontières (MSF) Spain,
as the nurse in charge of a PHC programme in the slums of
Nairobi, Kenya. Other missions followed, always interrupted
by optional modules for the MIH course. Sabine graduated in
2001 with a dissertation on the critical appraisal of the
impact of programmes on their beneficiaries and on those
implementing them. She is now working for MSF Austria in Vienna, responsible for Human Resource Management.
tropEd Partner Institutions
Full Members
Belgium
Denmark
France
Germany
Italy
Netherlands
Norway
Portugal
Spain
Sweden
Switzerland
UK
Prins Leopold Instituut voor Tropische Geneeskunde, Antwerpen
Dept. of International Health, University of Copenhagen
Centre de Formation et de Recherche en Médecine et Santé
Tropicales, Université d’Aix-Marseille II ; Institut de Médecine et
d’Epidémiologie Africaines, Université Paris VII ; Centre René
Labusquière, Université Victor Segalen Bordeaux II
Institut für Tropenmedizin, Humboldt Universität zu Berlin;
Abteilung für Tropenhygiene und öffentliches Gesundheitswesen, Ruprecht-Karls-Universität Heidelberg
Clinica di Malattie Infettive e Tropicali, Università degli Studi di
Brescia
Koninklijk Instituut voor de Tropen, Amsterdam
Centre for International Health, University of Bergen
Instituto de Higiene e Medicina Tropical, Universidade Nova de
Lisboa
Seccion de Medicina Tropical, Hospital Clinic, Universidad de
Barcelona; Escuela Nacional de Sanidad, Madrid; Departamento
de Parasitología, Universidad de Valencia
Dept. of Public Health Sciences, Karolinska Institutet, Stockholm
STI, Basel ; Institut de Médecine Sociale et Préventive, Université
de Genève ; Institut Universitaire de Médecine Sociale et Préventive, Lausanne
Centre for Intl. Health Studies, Queen Margaret College, Edinburgh; Liverpool School of Tropical Medicine; Institute of Child
Health, University College London; LSHTM, London
Isa Dhikusooka Musulo completed the HCMTC in 1998 and
enrolled in the MIH programme in the same year. He graduated as a medical doctor from the University of Makerere in
Kampala, Uganda. In 1994 he joined MSF Switzerland to
serve as a Medical Officer with the Sudanese Refugee
Health Programme in Northern Uganda. Later he became
the Relief Health Co-ordinator of several refugee programmes in Uganda. He expects to complete his MIH in
2002 with a dissertation on the knowledge, attitudes, beliefs and practices
of refugees concerning HIV/AIDS.
Collaborating Institutions in Germany, Hungary, Italy and Spain.
The Co-ordinating Centres are at present in Basel and Berlin.
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Students awarded degrees from September 2000 –August 2002
PhD degrees of the University of Basel
Salim Abdulla* (2000) The effect of treated bednets on anaemia and
malaria episodes in children under five in the Kilombero Valley, Tanzania.
Alexandre Bischoff* (2001) Quality of care for allophone migrants?
Assessing the patient-carer communication in an outpatient department in
Geneva.
Annette Prüss* (2001) Estimation of disease burden from environmental
risk factors – a methodology.
Martin Röösli* (2001) Spatial variability of air pollutants in the City of Basel
and associated health risks.
Catherine Rossett-Burkhalter (2001) Le pharmacien comme partenaire en
réseau de santé dans le traitement de l’asthme.
Sébastien Gagneux (2001) Molecular epidemiology of meningococcal
meningitis and acute respiratory tract infections in Northern Ghana.
Joanna Armstrong Schellenberg (2001) Socially marketed treated nets
and child survival in Southern Tanzania.
Sybille Gerstl (2001) The economic and health impact of wastewater use
in home gardens in Ouagadougou.
Esther Schelling DVM (2002) Human and animal health in nomadic
pastoralist communities of Chad: zoonoses, morbidity and health
services.
Abraham Hodgson MD* (2002) Meningococcal meningitis and acute
respiratory tract infections in the Kassena-Nankana district of Northern
Ghana.
Tobias Spielmann (2002) Identification of genes coding for stress-induced
proteins in P. falciparum.
Andrea Irion (2001) Diversity of MSP2 proteins and their immune
recognition.
Till Voss (2002) Molecular analysis of var-gene associated putative
promotor elements in P. falciparum.
Sonja Kahlmeier* (2001) Promotion of environmental health, exemplified
by a study of perceived housing quality and subjective well-being.
Catherine Wiesner* (2001) Arzneimittelsicherheit in der Perihospitalphase.
George Keto* (2001) Development of targeted DNA-vaccines against
P. falciparum.
Immo Kleinschmidt* (2001) Spatial statistical analysis, modelling and
mapping of malaria in Africa.
Frank Krönke (2001) Interactions between nomadic communities in the
Chari-Baguirmi region, Chad, and the health system: for example,
vaccination and nutrition services.
Tanya Marchant (2002) The health of pregnant women in rural Tanzania
with specific emphasis on anaemia and the impact of socially marketed
insecticide treated bednets.
Happiness Minja* (2001) Public attitudes to the use and marketing of
impregnated mosquito nets.
Rafael Moreno (2001) Functional role of antibodies against P. falciparum
antigens.
Victor Mwanakasale* (2001) Efficacy of praziquantel in the treatment and
control of S. haematobium cases coninfected with HIV in Zambia.
Beatrice Nickel (2001) Human T-cell response to Plasmodium falciparumderived epitopes.
Seth Owusu-Agyei* (2001) P. falciparum genotypes, incidence of infection
and morbidity, and management of malaria in a rural community in Ghana.
MD and DVM degrees
Pascale Fluri (MD 2001) Migrants and the Swiss health system: illness as
seen by the doctors and by Turkish and Bosnian migrants.
Caroline Wirz (MD 2001) Comparison of the approaches of Westerntrained doctors and traditional African herbalists to dyspeptic patients.
Students collaborating in STI projects who completed PhD degrees in
other Universities
Louise Achi (2002) Gastrointestinal parasites of livestock in Northern
Côte d’Ivoire (University of Toulouse, France).
Ursula Kayali (DVM 2002): Epidemiology of rabies in N’Djaména, Chad.
(University of Berne).
Nassor Kikumbih (2000) Economic analysis of efficiency, equity and
malaria control policy in rural communities of Tanzania (University of
London).
Rose Nathan (2001) Child fostering and orphanhood in the Kilombero
Valley, Tanzania: levels, patterns and welfare implications (University of
London, UK).
Amal Noureldeen (2001) Anti-malaria activity of Sudanese plants
(University of Khartoum, Sudan).
John Paget* (2002) The surveillance and epidemiology of sexually
transmitted infections in Switzerland.
Martin Wiese (2002) Geomedical aspects of nomadism; a comparative
study among nomadic communities in the Central Chad Basin (University
of Freiburg, Germany).
Students who completed the degree of MIH in the University of Basel
Students who completed an MSc or ATA degree
Chandon Chattopadhyay (2002) Development of a Curriculum for
participants of voluntary organisations: Analysis of demand for the
Calcutta Project Foundation, Basel.
Marc Annaheim, Eliane Arnold, Kathrin Bettge,
Corinne Bouquet, Yolanda Brauchli, Richard Burki,
Rosine Buxtorf, Marija Curicic, Yvonne Ellner (ATA),
Christian Flierl, Beatrice Glinz (ATA), Felix Heckendorn,
Beatrice Hübner (ATA), Erwin Kump, Irène Küpfer,
Alexandra Lüscher, Michael Oberle, Giovanna Raso,
Maxence Salomon (Geneva), Sibylle Sigrist, André Tiaden,
Denise Vogel (MSc), Denise Vogel (ATA).
Sabine Kampmüller (2001) Critical appraisal of the impact of a program
on a local society in chronic conflict. Listening to how beneficiaries and
program implementers view changes.
Brigitte Müller (2001) The influence of contextual factors and knowledge
about HIV/AIDS on sexual risk or preventive behaviour.
* Students based outside Basel
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Students currently working on research projects
PhD students
Collins Ahorlu: Cultural epidemiology of malaria in Ghana.
Christian Auer: Strategies for TB control in the Philippines: intemittent
therapy and public-private collaboration.
Sohini Banerjee*: Pesticide poisoning and deliberate self-harm in the
Sundarban Delta, India.
Max Bastian: Human cellular immune responses to malaria antigens.
Shubhangi Parkar MD*: Women’s mental health needs and services in an
urban slum community of Mumbai.
Joachim Pelikan: Development of learning software in the field of
“Biology of Infection”.
Giovanna Raso: Demographic, ecological, environmental and socioeconomic factors and their relationship with spatial distribution of human
parasitoses in the region of Man, Côte d’Ivoire.
Sonja Bernhard: Pharmacological studies of new diamidines.
Simona Rondini: Molecular immunology of Mycobacterium ulcerans
infection.
Rita Bossart: Social networks in Abidjan (Côte d’Ivoire). An analysis of
the importance of social relations in case of illness.
Wilson Sama: Statistical analysis of within-host dynamics of P. falciparum
infections.
Diana Diaz: Humoral immunity to infection.
Noam Shani: Molecular epidemiology of tuberculosis in Chad.
Colette Djaibe-Diguimbaye*: Characterisation of tuberculosis nad
antibiotic resistance in Chad.
Cecile Schmid: Investigations on the efficacy of short-course melarsoprol
treatment in Gambian trypanosomiasis.
Christian Flück: Functional role of the structural domains of the
P. falciparum MSP2 gene.
Okitsu Shinji: Immune protection against malaria.
Rainer Fretz: Fall-Kontroll Studie zur Übertragung der Norwalk-Like
viruses (NLV) in der Nordwestschweiz.
Gabriela Gehler Mariacher: Drug-donations: is the patient in focus?
Analysing the impact of drug donations for the treatment of trachoma in
Tanzania.
Armin Gemperli: Development of spatial statistical methods for point
referenced data in malaria epidemiology.
Stefanie Granado: Der Umgang mit Krankheit seitens der einheimischen
Bevölkerung im Bereich der Côte d’Ivoire aus ethnologischer Perspektive.
Mike Hobbins: Solar disinfection of water; the health impact in a rural
Bolivian community.
Nicole Kälin: Gesundheitskosten und Gesundheitshandeln im Alltag.
Welche Rolle spielt das Geschlecht?
Mirjam Kästli: Analysis of var-gene expression in naturally-occurring
P. falciparum infections.
Phung Lang*: Vaccination status of children in Switzerland.
Julia Leimkugel: Bacterial meningitis in Africa.
Alexander Luginbühl: Naturally occurring antibodies in rosetting of
P. falciparum-infected erythrocytes.
Naomi Maina: Melarsoprol resistance in T. gambiense from South Sudan.
Kefas Mugittu*: Drug resistance monitoring using microarray technology.
Igor Niederwieser: Early diagnostic test/vaccine for Leishmania infection.
Rita Njao*: The determinants of effective private-public alliances in Africa:
going to national scale with insecticide treated nets (ITNs) in Tanzania.
Jorge Seixas MD: Risk factors for reactive encephalopathies during
melarsoprol treatment of human African trypanosomiasis.
Innocent Semali MD*: “Policy maker” as a tool to understand the health
sector reform process and its influence on the integration of a former
vertical programme (EPI) in Tanzania.
Martin Senn: Phytochemical investigation of medicinal plants from
Tanzania.
Hilde Strahl: The Cultural Construction of BP (blood pressure) in the urban
context of Dar-es-Salaam, Tanzania.
Monika Wymann: Calf mortality in Côte d’Ivoire with reference to
tick-borne diseases.
MD and DVM students
Claudia Barriga: Übersichtsarbeit zweier schweizerischen medizinischen
Zeitschriften im Rahmen der Cochrane Collaboration.
Bernhard Beck: Immunological responses to hepatitis A and B vaccines.
Caroline Candolfi: Evolution of pathological lesions of the urogenital
system due to Schistosoma haematobium, assessed by ultrasound over
a period of three months after standard treatment with praziquantel.
Eva Brenken-Ryser: Ultrasound studies of S. mekongi-related morbidity
in NE Cambodia.
Susi Freiburghaus: Health care provision for migrants from the perspective of the nursing staff in the Cantonal Hospital, Liestal.
Monique Lehky Hagen: Problems of imported malaria in Switzerland.
Clara Thierfelder: Female genital mutilation and the Swiss health care
system.
Lucy Ochola*: Assessment of sequestered parasite load of P. falciparum.
Nadjitolnan Othingué: Epidemiological and spatial study of malaria in an
urban area: N’Djaména, Chad.
Moustapha Ould Taleb*: Perception of tuberculosis by nomadic camel
pastoralists in Mauritania and Chad.
MSc and ATA students
MIH students (with country of origin)
Selina Bopp, Andri Christen, Verena Christen, Mahamat Bechir, Miriam
Cohn, Tobias Erlanger, Philip Graf, Manuel Hetzel, Rolande Mindekem,
Richard Ngandolo, Nils Pfeiffer, Sebastian Rusch, Verena Schäfer,
Nina Schild, Cornelia Spycher, Peter Steinmann, Franziska Schwager
Samir Ayar (Iran); Philip Bassey (Nigeria); Achuyt Bhattarai (Nepal);
Ramona Brühlmann, Regula Frei (Switzerland); Jianing Gao (China);
Patrick Haenggi (Switzerland); Minaleshoa Hailu Abye (Ethiopia); Annette
Hartmann, Wolfgang Jessen (Germany); Charlotte Kristiansson (Sweden);
Sarah Kyobe (Uganda); Dafrossa Lyimo (Tanzania); Parag Mankeekar
(India); Edeltraut Meyer-Siegert (Germany); Isa Musulo (Uganda);
Hemalata Pisal (India); André Reiffer (Switzerland); Norbert Rehlis
(Poland); Nicole Schinzel, Marcel Stoeckle, Katharina Stricker (Switzerland); Peter Ternes, Olivia Veit (Germany); Thomas Walker (Switzerland).
* Students based outside Basel
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9.2 STI Diploma Courses
The STI offers a large range of courses for health professionals
who wish to prepare themselves for work in Public Health at the
national or international level. All the courses encourage a student-centred learning approach – which also means that the
learner is responsible for her or his own learning. The main task
of the teacher is to facilitate the individual learning processes by
giving guidance and providing materials and adequate learning
opportunities. Ex cathedra lectures have largely been replaced
by a broad spectrum of teaching methods: group work and presentations, field exercises, laboratory practicals, visits, round
table discussions, seminars, demonstrations and tutorials.
Facilitators come from within the STI, from other institutions of
higher education and from international organisations. Most of
them have had substantial working experience in countries
where resources are limited. The involvement of teachers from
the South is promoted, and former course participants have
been invited to participate in the teaching. The courses are
taught in English.
Staff members responsible for STI courses
A. Hoffmann
B. Peterhans
C. Hatz
A. Zumstein
Unit Coordinator;
Coordinator for advanced modules, MIH
Course Coordinator HCMTC
Advanced modules; curative
General Tropical Course
Courses in parasite diagnosis
Health Care and Management in Tropical Countries (HCMTC)
The focus of this annual 3-month course is Public Health, particularly from the perspective of work at the district level. The
course is designed for people who already have a first qualification in a health-related profession, and at least two years‘ experience. Scholarships offered to participants from countries with
resource constraints by SDC and the Canton of Basel-Stadt
makes it possible for more than half of the 30 participants to
come from countries in the South or in the former Soviet bloc.
Participants from Europe or the USA are usually either working
in countries with scarce resources, or have definite plans to do
so. With participants coming from so many backgrounds, the
course offers an exciting intercultural teaching and learning setting. Participants learn both from the teaching of a wide range of
experts, and also from each others’ experience. The course is
accredited by tropEd and the University of Basel as a core
course for the degree of Master of International Health.
Short courses
The STI offers several self-contained short courses. Most of
them are accredited by the University of Basel as postgraduate
certificate courses, and by tropEd as optional modules which
can be taken by MIH students to obtain credit points. The
courses are also open to other suitably-qualified candidates
who want to broaden their professional experience or refresh
their knowledge. Besides the courses listed below, some modules of the longer HCMTC course can be taken as independent
courses. Some of these are accredited as courses for the
74
degree of Master of Public Health (MPH) of the Swiss universities of Bern, Basel and Zürich.
Health District Management: Planning and Programme Design
This 3-week course provides basic information and practical
tools for planning district health services. It is based on exercises that simulate real problems in planning and management
as closely as possible. First, the students try to plan a rural
Health District with all its facilities and services. The dataset is
from a real place. Rapid feedback on the appropriateness of the
resource allocations made is given using a computer program,
the “Health Resource Allocation Model”, developed by the STI.
The second part of the module is a realistic simulation of a programme design process, using the logical framework approach
and other tools for strategic management. Students work as
teams, and each team has to write a full programme design
document, including a detailed budget and time frame, for a
5-year programme. For this very intensive course, each group of
5-6 students has a facilitator. For the last two years, we have
invited former participants from developing countries to act as
group facilitators in this course. This has been very successful.
Medical Practice with Limited Resources
Since 1997, the STI has conducted a course in clinical tropical
medicine for medical and paramedical personnel, based in
health facilities in a rural district in Africa. The 3-week course
takes place in the St. Francis Designated District Hospital in
Ifakara, Tanzania. It combines new teaching methods, recent scientific knowledge, and medical practice with limited resources
into a new form of education for medical professionals working at
district level in developing countries. The mixture of expatriate
and Tanzanian facilitators, a highly motivated hospital staff, and
participants from many countries, creates a challenging educational atmosphere. The interaction between academic staff and
practitioners from the North and from the South facilitates knowledge exchange among all the people involved, which benefits
not only the course participants but also the local hospital staff,
who are incorporated into the teaching process. The course is
unique in combining theoretical knowledge directly with the reality of a hospital in a country with severe resource constraints.
Travellers’ Health
This 1-week course provides up-to-date information on tropical
diseases and their medical treatment. It is mainly designed for
participants from industrialised countries, who need to provide
travellers with reliable information and advice, and to assess
travel-related problems that occur in patients who have returned
from tropical countries. The course is organised in collaboration
with other Swiss and German institutes, under the patronage of
the International Society of Travel Medicine, the WHO, and the
Swiss Society for Tropical Medicine.
Surveillance of Communicable Diseases
This two-week course is jointly organized by the Swiss Tropical
Institute and the WHO Immunology Research and Training Centre in Lausanne, and is held alternately in French in Lausanne
and in English in the STI. Besides faculty members of both institutes there are external facilitators from the WHO and other
organisations and scientific institutes. Information is provided
about the general principles of surveillance of transmissible diseases and about surveillance systems for specific diseases,
e.g. HIV/AIDS, TB, cholera, meningitis, and malaria.
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Students in the STI library. (Source: A. Hoffmann)
Scientific Writing for International Health
Courses in scientific writing aim to help scientists and health professionals to write lucid and convincing documents and reports,
and to offer support for writing projects, proposals or scientific
papers. Workshops were held in the Institute for Tropical Medicine in Khartoum and in the CSRS in Abidjan. A new distancelearning course started in 2002, as a module for the MIH.
The STI is also developing learning software for the courses
which are modules in the new Biology curriculum of the University of Basel. These learning tools are designed to complement
face-to-face teaching, and not for distance learning. A beta version of the learning programme Parasitologie und Parasitismus
was evaluated in 2001 and the version 1.0 was used in the summer semester 2002. Students who used the software gave a
positive feedback.
A complementary project, supported by the FAG (Freie
Akademische Gesellschaft, Basel) is to design software for students to support the new 8-week block course Infektionsbiologie und Epidemiologie. In this course the phenomenon of infection is the focus, and will be presented from biological and
epidemiological perspectives. The significance of infectious
diseases for the individual as well as for society will be stressed.
The learning software deals with the 7 “model parasites”, and
the general concepts (from molecular to population levels). It
relates various concepts using a problem-based approach with
various “learning paths”, which allow the learner to select an
individual approach. The learners will have many opportunities
to test their progress by answering quizzes.
The General Tropical Course
The 7-week Allgemeine Tropenkurs (General Tropical Course) is
open to anybody who is interested in life in tropical countries
and in the problems of development. It gives an overview of
global economic, ecological, cultural, geographical and social
relations and their influence on the lives of people in tropical
countries. The STI also contributes to a series of 1-day preparation courses run by the foundation cinfo for people going to
work in the tropics.
Health Systems Management
The Dar es Salaam Urban Health Project (DUHP), with the
support of the STI teaching unit, initiated courses in Tanzania on
Health Systems Management for people working in management at the district level. When the DUHP comes to an end the
courses will continue, with the support of the SDC.
9.3 E-Learning
Several new courses take advantage of the teaching and learning possibilities offered by modern electronic media. The STIdriven project TropEduWeb is a joint venture between the Universities of Basel, Lausanne and Zürich, and started in July
2001. It receives funding from the Swiss Virtual Campus. The
main aim is to develop a system of software-tools for the implementation of learning modules for international health issues,
particularly in the fields of Tropical Medicine, Diagnostics in Parasitology, and Epidemiology, as well as Public and International
Health. The first distance-learning modules should be available
at the end of 2003. The project co-ordinator, Prof. Hans-Peter
Rohr, is an emeritus professor of the Medical Faculty of the University of Basel and has – as a founder and president of the
NeoCortex Foundation – a long experience in multimedia projects and distance-learning.
The STI Computer Laboratory. This picture shows an international group of students attending the Cultural Epidemiology Workshop. (Source: M.G. Weiss)
9.4 Teaching in universities other than Basel
Members of the STI staff have teaching appointments in universities other than Basel (see list). STI staff also supervise students carrying out research projects for the joint degree of Master of Public Health (MPH) of the universities of Bern, Basel and
Zürich, and the STI is represented in the Board of Directors and
the Board of Lecturers of this programme.
Teaching assignments of STI staff members in universities other
than Basel
C. Hatz: Faculty of Medicine, University of Zürich, Switzerland; Swiss Federal Institute of Technology (ETH), Zürich; University of Freiburg, Germany.
N. Lorenz: New England Epidemiology Institute, Boston, USA; ETH, Zürich; University of Heidelberg, Germany; School of Public Health, University of Innsbruck,
Austria.
M. Tanner: LSHTM, London, UK; Chulalongkorn University, Bangkok, Thailand;
University of Heidelberg, Germany; University of Queensland, Brisbane, Australia;
WHO Immunology Research and Training Centre, University of Lausanne, Switzerland; Institut de la Francophonie pour la Médecine Tropicale (IFMT), Vientiane,
Laos.
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M. G. Weiss: University College, London, UK; ETH, Zürich; Dept. of Social Medicine, Harvard Medical School, Boston, USA.
N. A. Weiss: WHO Immunology Research and Training Centre, University of Lausanne, Switzerland.
K. Wiedenmayer: Faculty of Pharmacy, Muhimbili University College of Health
Sciences, Dar es Salaam, Tanzania.
A. Zumstein: University of Neuchâtel, Switzerland; Swiss College of Agriculture.
C. Lengeler: WHO courses on Immunology, University of Lausanne, Switzerland;
WHO course on Surveillance: malaria surveillance; University of Freiburg,
Germany; University of Geneva, Switzerland.
J. Zinsstag: Veterinary Faculties of the Universities of Zürich, Switzerland, and
Münich, Germany.
9.5 Other teaching and training activities
It would be difficult to provide a comprehensive list of all the formal and informal teaching and training activities in which STI
staff are involved, in Basel and elsewhere. Almost any project
involves elements of on-the-job-training. In a number of projects, collaborators from overseas have come to Switzerland to
learn specific techniques, ranging from training in computer
applications to the identification of bacteria. The STI also participates in the practical training of Graduate Research Assistants
(ATA) and Medical Laboratory Technicians, and offers courses
in Basel and elsewhere on the Diagnosis of Human Pathogenic
Parasites.
In 2001 the STI was host to the European Course in Tropical
Epidemiology, which is held in a different institute every year. In
2002, a Cultural Epidemiology Workshop was organised jointly
by the STI and the UNDP/World Bank/WHO Special Programme
for Research and Training in Tropical Diseases (TDR). About
twenty participants from 10 different countries spent an intensive week learning about the concept of cultural epidemiology
and its application, and learning about the planning and implementation of research projects and the analysis of quantitative
and qualitative data (see pp. 64, 75).
Continuing education in tropical and travel medicine for
Swiss medical doctors has been offered for many years. In
2002, the STI was also recognised by the Swiss association of
pharmacists (FPH) as an official provider of continuing educa-
76
tion. Several courses in the fields of pharmaceutical competence, management, epidemiology, health promotion, etc. are
offered on a regular basis.
Teaching and training activities are important in the framework of many of the projects managed by the Swiss Centre for
International Health (SCIH). As an essential element of projects
in countries of the former Soviet bloc which include the supplying of new equipment to health facilities, the SCIH has run training courses for health service staff on the use and maintenance
of the equipment. The SCIH also participates in teaching in the
World Bank “flagship” courses to support health sector reform
in francophone countries which are held in Dakar, Senegal.
Other teaching and training activities in different parts of the
world include the continuing partnership between the STI and
the Institut de la Francophonie pour la Médecine Tropicale in
Vientiane, Laos. In Eritrea, an STI staff member organised a
workshop on Participatory Rural Appraisal on behalf of the
Swiss Red Cross, and project planning workshops in community-based health care together with the Eritrean Ministry of
Health.
Practical activites in a workshop course in Eritrea on Participatory Rural Appraisal.
A group of participants and local villagers work together on making a map of the
village and its resources, using materials found on the spot. (Source: B. Peterhans)
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SECTION 10
Medical and diagnostic services (MEDDIA)
Introduction
The Swiss Tropical Institute is the only institution in Switzerland
providing services in the prevention, diagnosis and management of imported infectious diseases. Collaborative contacts
exist with Swiss specialists in tropical and travel medicine and
all major University Travel Clinics and hospital Infectiology
Departments in Basel, Berne, Zürich, Lausanne and Geneva.
Formal collaboration with University Medical Faculties was
established with Basel in 2000, with Berne in 2001 and with
Zürich in 2002. The Medical and Diagnostic Department is one
of the co-founders of an internet-based information source on
travel medicine recommendations for lay people (www.safetravel.ch). We have been present at the annual Basel Travel Fair
regularly since 1992, and in the EuroAirport Basel-MulhouseFreiburg since 1998.
Senior staff of the department have teaching activities
amounting to more than 200 contact hours yearly in some
130 tropical and travel medicine courses and seminars, both in
Switzerland and internationally. An annual 3-week course in
Clinical Tropical Medicine is taught in rural Tanzania (see also
Section 9). These teaching activities, and collaboration in scientific projects, offer excellent opportunities for continuing education of the staff, and enable them to keep their knowledge up-todate for performing travel medicine in developed countries, and
tropical medicine both in developing countries and in Europe.
The private practice activities of two specialists in general and
internal medicine guarantee integrated health care for patients
of the Medical Department in Basel.
Regular training courses and seminars for practitioners
throughout Switzerland which are conducted in collaboration
with the Swiss Society of Specialists in Tropical Medicine keep
the physicians of the STI in step with recent developments in
general and tropical/travel medicine, and maintain contacts with
other practitioners in Switzerland concerning the management
of imported tropical diseases, for which the STI acts as reference centre. Medical students are regularly trained in the
department, both in the travel clinic as part of their practical
experience at Medical School, and in research projects leading
to the MD degree of the University of Basel.
MEDICAL AND DIAGNOSTIC SERVICES
Mission statement
The Medical and Diagnostic Department aims to maintain
its role as a centre of excellence in travel and tropical medicine and in parasitological diagnostic services in Switzerland. It is committed to further develop its national role
through collaborative networking in order to provide its
expertise to the medical community and serve the beneficiaries of the Swiss health system.
Services offered to medical persons and to the public
• Provision of care for sick travellers returning from tropical
and sub-tropical countries, as out-patients or in hospitals.
• Advice for short- and long-term travellers on preventive
measures (general health advice on travel, vaccinations,
disease prevention).
• Advisory services for physicians on tropical and travelrelated health problems, including emerging diseases.
• Telephone advice (24-hour service) for physicians and
travellers.
• Reference centre for malaria diagnosis and management.
• Provision of general information through internet services.
• Medical advice on management of accidents with venomous and poisonous animals.
• Diagnosis of parasitic diseases with a wide range of tests.
• Quality control partnership for diagnosis of parasitic diseases.
• Mosquito repellent testing and advisory centre.
The academic team of the MEDDIA department.
10.1
Medical Services
Travel clinic
The travel clinic is the largest in north-eastern Switzerland, and
also serves the populations of neighbouring areas in southern
Germany and France. It is open on 5 days a week in the afternoons. Pre-travel advice was given to more than 11 000 clients
yearly in 2000 –2002. Information is continuously updated and
harmonised with that given by other leading travel clinics in
Switzerland, to keep the pre-travel advice services at the highest possible standard of quality. A telephone advice (payphone)
service to which centres in Berne and Zürich are connected
serves more than 32 000 callers from Switzerland and abroad
each year. Collaboration with travel health units in francophone
Swiss universities is assured by the fact that the head of the
Lausanne Travel Clinic, who is an expert in tropical and travel
medicine, also has a part-time appointment in the STI.
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SECTION 10 Medical and diagnostic services (MEDDIA)
An exchange of sera for testing in other reference laboratories in Switzerland and Europe is ongoing in order to assure the
quality control of our results. Furthermore, the laboratory provides the malaria slides used in the National Quality Control Programme for Parasitic Diseases. The certification of the laboratory services according to EU-standards is planned to be completed within the next year.
Molecular Diagnostics Unit
The Molecular Diagnostics research group was established in
the STI laboratories two years ago in order to carry out research
and development of new diagnostic methods, both to support
epidemiological research and to provide novel diagnostic
approaches for the individual patient. The work of the Unit is
described in detail in Section 2 of this report.
Institut Tropical Rhénan (ITR) in France
Nicolas d’Aujourd’hui
Communication Services
Outpatient department
Three experienced specialists in tropical and travel medicine
offer diagnosis and treatment services for travel-related diseases and check-up investigations for people coming from or
going to tropical countries. Consultant services are offered to
neighbouring hospitals in the region of Basel and to other Swiss
hospitals. A free 24-hour emergency service for advice and
treatment of tropical and emerging diseases is offered to the
general public and to patients from national and international
organisations, and to medical doctors in private practice and
hospitals. The department recorded more than 2 700 patient
contacts each year from 2000 –2002.
10.2
Diagnostic Services
Reference Centre for Tropical and Travel Medicine and
Parasitological Diagnosis
Every year, the reference laboratory carries out more than
21 000 serological, 9 000 haematological and 14 000 coprological examinations. Additionally, the emergency diagnostic service examines more than 300 blood films a year for malaria, outside regular working hours.
Our commitment to the best possible diagnosis of parasitic
infections again resulted in the development and introduction of
new tests into our routine procedures. Differential diagnosis of
old and new world species of Leishmania has been established
as a routine procedure. New serological tests (Anisakis,
Angiostrongylus, Gnathostoma) have been introduced to meet
the need to diagnose an increasing array of imported parasitic
diseases. The performance of new tests and the value of novel
investigational methodologies are continuously evaluated.
78
Started as a joint project between the STI and the diagnostic
laboratory Bollwerk in Mulhouse, the ITR answers questions
concerning native and exotic parasitic infections, organises
seminars on parasitic diseases for medical doctors, and publishes the journal INFO parasitaires. Together with the STI, the
ITR also trains French laboratory technicians in parasitological
diagnostics. Information campaigns through the ITR’s own webpage (www.LABB.fr), leaflets distributed in the waiting areas of
practitioners, and posters displayed at the EuroAirport BâleMulhouse-Freiburg should help to sensitise travellers and to
promote the services of the ITR.
10.3
Vector Control Centre
The mosquito colonies (Aedes spp. and Anopheles spp.) kept
in the STI for many decades have been used for roughly 500
individual tests of the efficacy of insect repellents during the last
two years. These tests included the regular checks carried out
on products which have been given the right to use the STI
quality label, and tests of products already on the market or
ready to be introduced in the market. The largest number of
tests, however, were to evaluate the efficacy of products under
development. The number of clients increased, which was
doubtless an effect of publicity resulting from regular reports in
the media in Switzerland and the neighbouring countries.
The STI insect-breeding facilities were also increasingly used
for the testing of insecticide-impregnated mosquito nets and
fabric. The production of mosquito eggs was continuously high.
Eggs are regularly sold to universities, research institutions and
the agrochemical divisions of pharmaceutical companies, for
use for various purposes such as the breeding of mosquitoes
for research or to produce larvae to use for toxicity screening of
pesticides.
The production of maggots of the greenbottle fly, Lucilia sericata, for the debridement therapy of human wounds, was continued. Despite some psychological opposition, on the part of
the patients and the nursing staff, to having maggots crawling in
a human wound, there was an increase in the number of hospitals and physicians using this successful method of “biosurgery”.
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SECTION 10 Medical and diagnostic services (MEDDIA)
10.4
Operational research on travel medicine
Fluri P (2001) Aus der Sicht der Mediziner – Migranten im Schweizer Gesundheitssystem. MD Thesis, University of Basel.
Imported malaria in travellers from Kenya
Freiburghaus S (2001) Gesundheitsprobleme und allgemeinmedizinische Versorgung von Asylsuchenden und Flüchtlingen in der Schweiz aus der Sicht des
Pflegepersonals. MD Thesis, University of Basel.
Kenya is one of the leading destinations for Swiss travellers.
Malaria prophylaxis is considered mandatory for trips to the
coastal tourist sites. A retrospective survey of different data
sources from 1988 to 1996 was carried out to obtain the closest
possible approximation to the true incidence rates among Swiss
travellers. Records of the World Tourist Organisation (WTO), the
Kenyan General Consulate and of The Federal Office of Public
Health (BAG) were analysed.
Yearly incidence rates of malaria due to P. falciparum in travellers from Switzerland ranged from 4 –11.6/10 000. The seasonal fluctuation showed highly variable incidences with values
up to 44.8/10 000. Our data suggest a bimodal fluctuation of the
incidence rates with maximal rates in the first and third quarters,
following the rainy seasons. WTO figures suggest that tourists
from different countries tended to travel to Kenya at different
times of year.
The following factors were found to influence the observed
pattern of imported malaria: African citizenship, species of Plasmodia, choice and regimen of chemoprophylactic drugs, local
malaria situation, and seasonal variation in the number of tourists.
Hepatitis A vaccination in travellers
The newly-developed vaccine Epaxal® was shown to be successful in boosting immunisation following primary vaccination
with an alum-adsorbed vaccine, and the new vaccine is well
tolerated. The immunogenicity of a booster dose of the aluminium-free, virosome (IRIV) formulated hepatitis A vaccine was
not influenced by the length of the time interval since priming
when this had occurred up to 4.7 years earlier.
Scientists:
Genton B (2001) Prévention et traitement de la malaria: l’ère post-méfloquine?
Swiss Medical Forum 13, 337– 344.
Genton B & D’Acremont V (2001) Clinical features of malaria in returning travelers
and migrants. In: Travelers’ Malaria. Eds. Schlagenhauf P, Hamilton, B.C: Decker,
371– 392.
Genton B, D’Acremont V & Gehri M (2001) L’enfant voyageur. Méd Hyg 59,
1186 –1191.
Genton B (2002) E-health ou la télémédecine au services des voyageurs. Méd
Hyg 60, 934– 939.
Hamel T, Blum J, Harder F & Kocher T (2002) Nonoperative treatment of splenic
rupture in malaria tropica: review of literature and case report. Acta Trop 82, 1– 5.
Hanck C & Hatz C (2000) Treatment of strongyloides infections (letter). Gastroenterol 119, 1805 –1806.
Hatz C (2000) Reisemedizinische Beratung und Impfungen. Schweiz Rundsch
Med Prax 89, 868 – 877.
Hatz C, Thisyakorn U, Thisyakorn C & Wilde H (2001) Other important viral infections. In Textbook of Travel Medicine and Health. Eds. DuPont HL & Steffen R,
Hamilton: B.C. Decker, 312 – 324.
Hatz C, Schlagenhauf P, Blum J, Funk M, Beck B, Furrer HJ, Genton B, Holzer B,
Loutan L, Markwalder K, Raeber PA, Siegl G, Steffen R, Stürchler D & Wyss R
(2001) Malariaprophylaxe für Kurzzeitaufenthalter. Bull Bundesamt für Gesundheit,
Supplementum 1.
Hatz C (2001) Clinical treatment of malaria in returned travelers. In: Travelers’
Malaria. Ed. Schlagenhauf P. Hamilton: B.C. Decker, 431– 445.
Hatz C (2001) Malaria-Chemoprophylaxe 2001. Ther Umsch 58, 347– 351.
Hatz C & Schlagenhauf P (2001) Strategische Überlegungen zum Stellenwert
einer Notfall-Selbsttherapie in der Malariaprophylaxe. Med Welt 52, 201– 204.
Hatz C & Tanner M (2002) Tropenmedizin 2001: Lichter am Malariahorizont.
Schweiz. med. Forum Forum 1, 27– 28.
B. Beck, B. Blum, G. Bordmann, C. Hatz, HP. Marti, P. Vounatsou
Hatz C & Loutan L (2002) La rage chez le voyageur: prévenir et traiter. Med Hyg
60, 959 – 961.
MD Students:
P. Fluri, M. Lehky Hagen
Collaboration:
University of Zürich, Switzerland; University of Geneva,
Switzerland; Swiss Federal Office of Public Health, Berne
Hatz C, Beck B, Blum J, Funk M, Furrer HJ, Genton B, Holzer B, Loutan L, Markwalder K, Raeber PA, Schlagenhauf P, Siegl G, Steffen R & Wyss R (2002) Neue
und praxisrelevante Empfehlungen zum Malariaschutz 2002. Bull. Bundesamt für
Gesundheit 23, 896– 401.
Publications on travel medicine:
Andresen B, Blum J, von Weymarn A, Bürge M, Steinbrich W & Duewell S (2000)
Hepatic fascioliasis: report of two cases. Eur Radiol 10, 1713 –15.
Blum J, Wiestner A, Fuhr P & Hatz C (2001) Encephalopathy following Loa loa
treatment with albendazole. Acta Trop 78, 63 – 65.
Jelinek T, Schulte C, Behrens R, Grobusch MP, Coulaud JP, Bisoffi Z, Matteelli A,
Clerinx J, Corachan M, Puente S, Gjorup I, Harms G, Kollaritsch H, Kotlowski A,
Björkmann A, Delmont JP, Knobloch J, Nielsen LN, Cuadros J, Hatz C, Beran J,
Schmid ML, Schulze M, Lopez-Velez R, Fleischer K, Kapaun A, McWhinney P,
Kern P, Atougia J, Fry G, da Cunha S & Boecken G (2002) Imported falciparum
malaria in Europe: Sentinel surveillance data from the European Network on surveillance of imported infectious diseases. CID 34, 572– 576.
Blum J, Beck B & Hatz C (2002) Artemether/Lumefantrin. Internist Prax 42,
661– 664.
Kessler D, Hatz C & Schär A (2001) L’automédication comme mobilisation des
ressources médicales et personnelles. Dans: L’automédication, pratique banale,
motifs complexes. Eds. Buclin T & Ammon C, Genève: Cahiers Médico-Sociaux,
247– 256.
Borruat FX, Nater B, Robyn L & Genton B (2001) Prolonged visual illusions due to
mefloquine : a case report. J Trav Med 8, 148 –149.
Kiefer G, Battegay M, Gyr N & Hatz C (2002) Mansonella perstans-filariose nach
Aufenthalt in Kamerun. Praxis 91, 61– 66.
D’Acremont V, Burnand B & Genton B (2002) Recommandations cliniques pour
l’évaluation de la fièvre chez les voyageurs ou migrants. Med Hyg 60, 21– 23.
Lehky Hagen M (2002) Problematik der importierten Malaria in der Schweiz. Eine
Analyse der gemeldeten Malariafälle aus Kenia von 1988 –1996. MD Thesis, University of Basel.
D’Acremont V, Landry P, Darioli R, Stuerchler D, Pécoud A & Genton B (2002)
Treatment of imported malaria in an ambulatory setting: prospective study. BMJ
324, 875 – 877.
D’Acremont V, Landry P, Müller I, Pécoud A & Genton B (2002) Clinical and laboratory predictors of imported malaria: an aid to the medical decision making for
returning travelers with fever. Am J Trop Med Hyg. 66, 481– 6
Estlinbaum T & Hatz C (2002) 50-jähriger Rückkehrer aus Hawaii mit veränderten
Stuhlgewohnheiten. Praxis 91, 936 – 938.
Loutan L, Genton B (2002) Globalisation de la mobilité des personnes et de l’information (Editorial) Méd Hyg 60, 931.
Nothdurft HD & Hatz C (2000) Reisemedizinische Beratung. Tropenmedizin. In:
Klinik und Praxis. Eds. Lang W & Löscher T, Stuttgart: Georg Thieme, 598 – 602.
Oehler T, Büchel B, Hatz C & Furrer HJ (2000) Beratung HIV-Infizierter vor Reisen
in tropische und subtropische Gebiete. Schweiz Med Wochenschr 130,
1041–1050.
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SECTION 11
The Swiss Centre for International Health (SCIH)
Introduction
The Swiss Centre for International Health (SCIH) has expanded
considerably in the 6 years since it was founded as a department within the STI, with the aim of making the considerable
expertise of the Institute’s staff in the field of international development co-operation in the health sector widely availabe in
Switzerland and globally. The Centre now has two main areas;
the Health Systems Support Unit (HSSU) and the Pharmaceutical Medicine Unit (PMU). Below, we present some of the highlights of recent work in the SCIH. A complete list of our projects
is given in Tables 1 and 2.
There are more than 30 staff members, whose expertise covers a very wide area: public health, epidemiology, pharmaceuticals and pharmacology, health economics, informatics, biomedical technology, sociology, social geography and public
administration and medical anthropology. New staff members
bring wide experience in a number of important fields: health
economics, reproductive health, and health technology management. Members of the supporting staff are familiar with international procurement procedures, management of short-term
staffing, and the organisation of training programmes. The SCIH
can also draw on the experience of other professionals in the
STI, thus promoting interdisciplinary collaboration. To fulfil specific needs, we also have a wide network of professional collaborators outside the Institute. Many of the scientists on the SCIH
staff are engaged in research projects. This aspect of our work
is described elsewhere in this Report, mainly in Sections 6
and 7.
The members of the SCIH staff travel frequently on assignments, and have first-hand experience of the countries with
which they work. Some staff members are based in other countries, including Cameroon, Rwanda and Côte d’Ivoire. In Chad,
four professional and numerous support staff are working
in our Centre de Support en Santé Internationale (CSSI/T) in
N’Djaména, which is a basis for research as well as a consulting
agency. Our continuing commitment to work in countries of the
one-time Soviet bloc is reflected in the fact that early in 2002 our
office in the capital of Ukraine, Kyiv, was re-opened with a local
programme coordinator for the Swiss-Ukrainian Perinatal Health
Programme.
As well as carrying out assignments ourselves, we have also
been passing on our experience and expertise in training
courses A direct offspring of the DUHP is the annual management course in Tanzania, organised together with other STI staff
members. In addition, many of our projects involving health
technology include the training of local staff, either in their own
countries or in Switzerland. In the context of health sector
reform, the SCIH has been asked for the third consecutive year
to contribute to the organisation of the francophone “flagship”
training programme in Health Sector Reform and Sustainable
Financing run by the World Bank Institute.
All senior staff are also involved in teaching and training in
the STI, in the University of Basel and at other Swiss, African
and European Universities (see also Section 9). Students of the
University of Basel (5 PhD students, one MD student, 3 MScstudents and one MPH-student), as well as students of other
universities, have successfully carried out research projects
with the support and supervision of the SCIH.
80
The Swiss Centre for
International Health (SCIH)
Mission Statement
The SCIH strives to maintain and expand its role as a centre
of excellence in providing services in the field of International Health Collaboration, including drug and vaccine
development. The SCIH is committed to promoting and to
contributing to a balanced and sustainable development of
health systems in Switzerland, the East and the South.
Principles
Relationships with partners and customers are governed
by collaboration, partnership and mutual respect, including
respect for the policies of the partners involved. This
implies that the implementation of projects must follow the
national guidelines and priorities of the partner countries.
Contributing to achieving equity of care is a basic premise
of our activities. Ensuring the sustainability of health care
delivery systems is also an important concern for us. As a
contribution to this, novel approaches in models for health
sector/service financing are developed and tested within
the possibilities of national policies and directives.
Sound financial and administrative management of projects
and programmes is a fundamental pillar of our work.
Services offered by the SCIH
• Implementation of large-scale development projects
• Advisory services for government agencies and NGOs in
all fields related to international health
• Feasibility studies and assistance in the project planning
process
• Project planning, monitoring and evaluation
• Expertise in health sector reform
• Procurement of biomedical equipment and drugs
• Biomedical technology assessment and health technology input
• Expertise in health economics: health care financing
mechanisms, economic analysis, cost-benefit- and costeffectiveness analysis
• Reproductive health
• Teaching and training
• Pharmaceutical medicine.
All major aspects of drug discovery and development
of medicines against tropical diseases, with a focus on
countries where the implementation of such activities
requires a specialised expertise. The services primarily
offered are the conduct of phase II & III clinical trials,
study management, protocol development, investigator
and site recruitment, and consultancies in all areas.
Pre-clinical services: in vitro screening and animal testing of parasiticidal compounds, executed by Parascreen,
the screening centre for antiparasitic drugs at the STI.
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SECTION 11 The Swiss Centre for International Health (SCIH)
11.1
Health Systems Support Unit
The HSSU offers services to governmental, non-governmental
and international organisations in the field of international
health.
As in the past, major assignments have been mandates for
the Social Development Division of the Swiss Agency for Development and Co-operation (SDC). The SCIH has continued to
provide a large range of advisory services, focussing on diseases of poverty, health systems management, and poverty
reduction and health. Key activities in the reporting period were
the preparation of a proposal on the SDC’s HIV-AIDS-policy, and
the revision of the general health policy of the SDC.
The SCIH has a separate mandate from the East and Southern African Division of SDC, to build a repository of information
and experience in relation to Sector Wide Approaches (SWAp).
A database has been established on the basis of a comprehensive literature review, including “grey literature”, and is being
continuously updated, and we are developing networks of individuals and institutions to share experience and knowledge.
The aim is to stimulate communication within SDC (between
SDC co-ordinating offices in different countries, and between
co-ordinating offices and the headquarters in Berne), and also
between SDC and other interested parties (other donors, ministries of health, research institutions, etc.). A website and a discussion forum have been established (http://www.sti.ch/scih/
swap.htm).
The Dar es Salaam Urban Health Project (DUHP) will come to
an end in 2002, after 12 years. Since the end of 2001 there have
been no SCIH staff members permanently stationed in Tanzania, but support through short-term assignments has continued,
mainly in the fields of administration, drug supply management,
and advice on the ongoing process of health sector reform
(Section 7A.4 and box, right). The SCIH now has a new mandate for the support of health sector reform in Africa, this time in
Rwanda. The programme, planned initially to run until 2004,
includes the introduction of innovative methods of budget support to enable district health authorities to address priority
health problems like malaria and HIV/AIDS. An SCIH expert is
already stationed in Rwanda.
Rwanda: discussion of Health Sector Reform “in the field”. On the right, N. Lorenz.
(Source: G.Hutton)
Tanzania: Needs assessment and policy for clinical training to improve clinical practice and quality of care in Dar
es Salaam
One of the objectives of the Dar es Salaam Urban Health Project (DUHP/DSMPHDS) was to improve the quality of health
care in the city at all levels. Quality of care can be judged
both from the perspective of the health care provider and
that of the patient. DUHP studies and an external evaluation
have shown significant improvement in structural quality.
However, technical quality of care and interpersonal skills
and empathy remain weak. In March 2001 a situation analysis was conducted to assess existing training and training
needs as perceived by providers and to recommend methods and tools for clinical training and continuing professional
development. The survey found that the training that was
being done suffered from poor planning, co-ordination,
methodology, coverage and evaluation. Supervision suffered
from insufficient capacity, poor methodology and lack of
tools and funding. A workshop was conducted to elaborate
an appropriate, feasible and relevant policy and tools for
clinical training within the DUHP, to include private providers
as well. Political will and personal commitment are needed
for the implementation of the new clinical training program.
The Tanzanian Health Sector Review 2002 recommends integration and policy guidelines for continuing education. The
endeavour by DUHP to develop a clinical training program is
thus a timely initiative and may serve as a model and complement the Ministry of Health proposal.
Scientist:
K. Wiedenmayer
Collaboration:
City Medical Office of Health (D. Mtasiwa) and Municipal
Medical Office of Health, Kinondoni (Z. Majapa), Dar es
Salaam, Tanzania
Funding:
SDC
In N’Djaména, Chad, the Centre de Support en Santé Internationale (CSSI/T), which was founded in 1996, has been very
successful in providing a functional and reliable research base
for the STI. Furthermore, the Centre has almost achieved financial independence, as it has been able to obtain numerous contracts in the context of World Bank loans and from bilateral
agencies. For example, the economic impact of the HIV/AIDS
epidemic on Chad was assessed for the national AIDS programme, and in a competitive tender a contract was won for
the implementation of a regional support programme, funded
through a World Bank loan.
The CSSI/T is also in charge of the Mada District support
project in North Cameroon, close to the Chadian border, which
is funded by the Fondation Hélvetique. Our involvement in
Cameroon has also received a fresh impetus with a backstopping mandate for the regional office of the Swiss organisation
Leprahilfe Emmaus. The main focus of the work is on leprosy,
but tuberculosis and the growing problem of Buruli ulcer, due to
Mycobacterium ulcerans (Section 3.5) are also receiving attention. The SCIH also carried out a series of short assignments in
Togo and Chad on behalf of GTZ, Germany. Also for GTZ, a key
issue paper was elaborated on “Addressing Female Genital
Mutilation – challenges and perspectives for Health Programmes”.
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Although the STI’s long-standing connection with Africa has led
to some concentration of our activities there, projects in other
continents are becoming more and more important. Our involvement in Central Asia, in particular Tajikistan, is gaining shape.
Short-term assignments have provided the foundation for a
planned SDC project for medium-term technical assistance to
support the health sector reform process in this country, which
is one of those hit worst by the transition process. The collaboration with the Ukraine, which started in 1996 with projects
funded by SECO (the Swiss State Secretariat for Economic
Affairs), has evolved into the Swiss-Ukrainian Perinatal Health
Programme, which SCIH implements on behalf of the SDC, in
collaboration with the Ukrainian Ministry of Health. The project
has its own office in Kyiv, and a Ukrainian professional is stationed there. The aim of the programme is to improve perinatal
health through a combination of technical assistance and
capacity building, and the provision of medical equipment. The
project area covers five oblasts (Kyiv, Rivno, Lutsk, Donetsk and
Ivano-Frankivsk), which already received support through the
former projects.
sector in Zürich and Basel and possible policy options (Section
7C.6). A second assignment was to develop a concept for the
new clinical services centre of a drug mailing company in
Switzerland. The substitution of generics for branded drugs
received particular attention (Box). Together with the Swiss Red
Cross, the SCIH won a major assignment in a tender which was
organised by the Swiss Federal Office for Health, for a project
to improve HIV-prevention among migrants from sub-Saharan
countries living in Switzerland.
Managed care pharmacy in Switzerland
In 1997 the first mail order pharmacy was established in
Switzerland, offering home delivery of drugs by mail. Today
about 30,000 people, mostly with chronic health problems,
take advantage of this innovative concept of health care
delivery. Managed care pharmacy aims at cost reduction,
optimisation of drug therapy, better clinical outcomes, professionally-defined improved quality of care, and patient satisfaction, as well as better use of resources. Besides its distributive activities, the company is interested in exploring
how to utilise the patient and prescription databases, and in
ways to improve pharmacotherapy, compliance and case
management.
Collaboration was established with the STI with the goal of
building up a new clinical services department. The STI provides scientific expertise and coordination and the company
staff are responsible for implementation. As a first approach,
the substitution of generic for branded products was
selected. This coincides with current efforts in the Swiss
health care system to reduce drug spending, and also represents both a medically sound and commercially interesting
concept. Generic substitution will be an important step
towards reducing drug costs while maintaining quality care.
Main components of the project were i) database transfer
and analysis (conducted by the STI biostatistics unit), ii)
developing a concept for generics substitution, and iii) planning of the pilot phase.
Scientists:
Countries in transition where the SCIH is now working include Tajikistan. (Source:
N. Lorenz)
Our activities in Western Europe and North America are also increasing. The SCIH was asked by the UK Department for International Development (DFID) to evaluate its Concordat with the
Medical Research Council. The work done by the SCIH was
highly appreciated by DFID, and will help to improve the performance of the Concordat, which funds a substantial part of
the research in the UK geared towards the needs of countries
with limited resources. The SCIH, together with Management
Sciences for Health (Boston, USA) was successful in winning
another evaluation contract, against strong international competition, to evaluate the HRP, the highly prestigious special programme of research, development and research training in
human reproduction of WHO/World Bank/UNFPA and UNDP.
The expertise of the SCIH is increasingly meeting a demand
in Switzerland itself. During the reporting period two major
assignments were finished, and a third one started. One was a
study to assess resource allocation mechanisms in the health
82
K. Wiedenmayer, P. Vounatsou
Research assistant: S. Gelfand
Collaboration:
F. Rampelberg, Archimed, Medical Communication AG,
Brittnau, Switzerland
Funding:
MediService AG, Zuchwil, Switzerland
Health Technology
In the field of health technology, our management expertise has
been further strengthened. The recognition of the SCIH as a
WHO-collaborating centre for resource management is pending. Major assignments in Egypt, Jordan and China have provided a basis for investing in additional staff. In Egypt, the SCIH
is providing technical assistance to SECO in a major mid-term
project that includes large-scale loan financing. The objective is
to rehabilitate and strengthen the entire radiology system in
Egypt. This includes the development of diagnostic guidelines,
training of radiologists and radiographers, supply of equipment
and support for the biomedical engineering departments. Several activities will specifically target the improvement of radiation safety.
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11.2
Pharmaceutical Medicine Unit (PMU)
The Pharmaceutical Medicine Unit (PMU) was founded in the
year 2000, in response to the increasingly complex requirements and regulations in the field of drug evaluation and registration, and the rising demand for clinical investigation of drugs
against tropical diseases. The unit offers selected services in
the design, organisation, conduct and monitoring of clinical trials according to international guidelines The field of specialisation is tropical medicine; the projects may be executed in countries in the Northern or the Southern hemisphere.
Development of drugs against tropical diseases, and especially the conducting of clinical trials in developing countries,
requires a specialised expertise beyond an in-depth knowledge
of the current regulations and guidelines. The sharply increasing number of regulations and the harmonisation of the international regulations on Good Clinical Practice, by the International
Conference for Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH), go
beyond the needs and possibilities of developing countries to
plan or oversee the implementation of trials themselves at this
point in time. Ways have to be sought in each individual project
to reconcile the requirements of the drug registration authorities
and the local laws and restrictions.
Particular issues concerning the ethics of the conduct of clinical trials in developing countries have to be addressed, and the
problems arising must be solved in line with both international
standards and the cultural background of the country and people concerned. In addition, since in countries with limited
resources the technical installations of health facilities and the
training level of the personnel often do not match the requirements for the conduct of clinical trials according to international
standards, such projects usually involve considerable logistic
and training efforts. Last but not least, the competent planning
and implementation of clinical trials addressing tropical diseases demands a profound medical and biological understanding of the illness and of the confounding factors involved.
The specialised team of the PMU is dedicated to assisting in
or carrying out the design, organisation, conducting and monitoring of clinical trials. The activities may either be performed
according to the standard operating procedures (SOPs) of the
PMU or those of the client. The unit can provide support in particular areas, like clinical trial design, development of protocols
and Case Report Forms, investigative site selection and management, monitoring of clinical trials, and biostatistical support.
Alternatively, the PMU can undertake the full management of
phase II and III studies in developing countries.
The PMU is embedded in the STI framework of expertise
and know-how and can also call on support from an international network of individuals, organisations and institutions.
Through our long-standing collaborations and contacts we
can offer rapid service in a large number of countries in Africa,
Eastern and Central Europe. We value inquiries from any
organisations and corporations working in countries and situations that require the skills we can provide.
Clinical Trial of a new trypanocidal agent (DB 289)
A Phase IIA (proof of concept) trial was planned, with the primary objective of assessing the short term efficacy and
safety of DB 289 in patients with first stage T. b. gambiense
sleeping sickness. The regimen consisted of 100 mg of orally
applied DB 289 twice daily for 5 days. The secondary objective was to determine the plasma levels of DB289 and its
active metabolite (DB75) in the patients, to correlate possible
differences in clinical efficacy and adverse affects with
plasma levels, and to specify the pharmacokinetic parameters of the drug. Patients with early stage T. b. gambiense
sleeping sickness, i.e. parasite positive in blood or lymph
and <
_ 5 WBC mm-3 detected in the CSF, more than 16 years
old and with a minimal weight of 45 kg, will be included.
Exclusion criteria comprised amongst others concomitant
ailments and previous treatment for sleeping sickness.
Based on the previous experience with clinical trials and
the existing infrastructure, the trypanosomiasis reference
and research center Viana (Luanda), Angola, was selected
as the study center. It was planned to enrol 30 patients within
a period of 3 months, recruited from the refugee population
arriving in Luanda and by active case search in the extended
city area. However, due to the increasingly difficult political
situation in Angola during 2001, the flux of patients into the
city was much reduced and the radius of action very limited.
The number of eligible patients stayed far below that
expected on the basis of previous years.
One of the collaborating centres for DB 289 Phase IIA clinical trials: Trypanosomiasis Reference and Research Center, Viana, Angola. (C. Burri)
It was therefore necessary to select a second treatment center and integrate it into the trial. At that point no other center
treating trypanosomiasis was adequately equipped to conduct a study of this type. The decision was made to improve
the CDTC Maluku, Democratic Republic of Congo, to the
necessary standards. Within a period of four months, part of
the center was rehabilitated, a new laboratory installed, and
the staff trained for the new tasks. Enrolment for the DB 289
Phase IIA trial started in April 2002, and by September the
planned number of patients could be enrolled.
Scientists:
Collaboration:
One area in which the STI and the SCIH have been building up
expertise for some years is that of human sleeping sickness
(trypanosomiasis). In the present reporting period the major
client of the PMU has been an international consortium funded
by the Bill & Melinda Gates Foundation to do research on di-
Funding:
C. Burri, G. Pohlig (PMU), J. Blum (Medical Department),
T. Smith, P. Vounatsou (Biostatistics Unit)
University of North Carolina, Chapel Hill, USA; Immtech International Inc, Vernon Hills, USA (Dr. P. Yeramian, Dr. J. Allan);
Instituto de Combate e de Controlo das Tripanossomíases,
Luanda, Angola (Dr. T. Josenando); Bureau Central de la
Trypanosomiase, Kinshasa, RD Congo (Dr. M.B. Miaka)
Bill & Melinda Gates Foundation
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cationic compounds active against trypanosomes and leishmania, with the aim of bringing selected compounds to registration. Only a very limited number of drugs is available for
treatment of sleeping sickness and none of them is applicable
by the oral route. Screening and associated drug development
activities (Section 4.1) identified a prodrug, DB 289, which has
considerable trypanocidal activity and a very low toxicity.
Once preclinical testing of DB289 had been successfully completed, the PMU was subcontracted to plan and conduct the
phase II & III clinical trials needed for registration (Box p. 83).
The PMU also provided the Product Research and Development (PRD) area of TDR with scientific support for Phase II
clinical trials, in Côte d’Ivoire and the Democratic Republic of
Congo, for development of the trypanocidal drug eflornithine
for oral use. A long-standing and very important client is the
Swiss Agency for Development and Cooperation (SDC), for
whom a large-scale multinational study on a new schedule for
treatment of late sleeping sickness with melarsoprol was conducted (IMPAMEL, Section 6.4).
In the field of antimalarial drugs, Novartis Pharma has given
the PMU a mandate to coordinate and monitor a multicentre
Phase IV safety trial for the malaria drug combination arthemeter and lumefantrin in Switzerland and Germany.
Outlook of the SCIH
The SCIH has consolidated its role as one of the leading advisory agencies in Switzerland in its field of expertise. The major
Swiss governmental agencies that are active in the field of
international health development, SDC and SECO, appreciate
the quality of the work the SCIH does for them. The SCIH will
strive to maintain this excellent reputation in Switzerland, and
expand it also to other governmental and non-governmental
agencies.
It is envisaged that in the future the core expertise of the
SCIH will be further strengthened in the following fields:
• Pharmaceutical medicine
• Health sector reform and the sector-wide approach and aidinstruments
• Reproductive Health/HIV and AIDS
• Health Technology Management
In all four areas, the SCIH will try to attract mandates and
assignments in order to deepen the experience already
gained. For the PMU, clinical trials of new anti-malarials are
around the corner and provide promising perspectives. Health
sector reform offers many opportunities. There is a widespread
acknowledgement of the necessity of reform, but the process
has only just started, and there is a huge unmet need for
assessment of the performance of new instruments such as
SWAp, and of programme-financing mechanisms. SCIH will
continue to have a comparative advantage in this field, as it is
one of the few institutions that strive to combine scientific
soundness with the professional standards of business
consultants. Furthermore, the SCIH is currently practically
involved in supporting health sector reform projects.
Finally, reproductive health, including the aspect of
HIV/AIDS, is widely acknowledged to be one of the most
important public health and social challenges of the years to
come, and with the recruitment of staff with wide experience in
this area, SCIH is now in a position to respond to it.
Health Technology has not been very “fashionable” in
recent years, but is today receiving increasing attention, particularly as policy-makers dealing with developing or transitional countries have started to realise that appropriate health
technology is an essential pillar of efforts to improve health status. In the Northern hemisphere, too, concern about the cost of
health services has made the use of appropriate technology
an increasingly important issue. This opens up possibilities of
further challenging assignments in the Swiss and European
contexts, thus capitalising on the rich experience of the SCIH
and the STI in countries with limited resources.
Work on HIV/AIDS prevention will become increasingly important in the future. Social marketing of
condoms beside a highway in Nepal. (Source: C. Kessler)
84
Propaganda for condoms in the Ukraine.
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Short-term assignments of the SCIH between 2000 and 2002
Country
Client
Belgium
European Union; 5th framework programme
Burkina Faso
European Commission
Cape Verde Islands German Technical Cooperation (GTZ)
Chad
GTZ
Chad
World Bank (WB)
Chad
Int. Dev. Assoc. (IDA)
Chad
World Health Organisation (WHO)
China
Department for International Development (UK)
Year
Description
2001
Evaluation of research proposals which have been submitted to the EU in the
context of the 5. Framework
2000 – 01
Support for implementing and evaluation affordable MCH services
(1 district)
2000 – 01
Situation analysis and project proposal to improve resources management in
health services on the island of Praia
2000
Evaluation of a reproductive health project
2001
Impact of HIV/AIDS in Chad: Assessment of social and economic impact of
the HIV/AIDS epidemic over the next 5 to 10 years including the prioritisation
of current and future intervention strategies
2001
Evaluation of the Health Project Maternité sans Risques
2001
Country case study regarding improving health outcomes of the poor. Study
of constraints to scaling up health intervention
2001– 02
Urban health and poverty project in China: Implementation of mechanisms
aimed at increasing poor people’s access to primary health care and
strengthening of social health insurance
2001– 02
Appraisal of a mixed credit project in Xinjiang Autonomous Region & for a
mixed credit project in Urumqi, Xinjiang Autonomous Region
China
Swiss State Secretariat for Economic Affairs (SECO)
Egypt
SECO
2001
Appraisal Mission; improvement of radiological diagnostic services in Egypt
Egypt
SECO
2002
Project Planning Mission to improve radiological diagnostic services in Egypt
Germany
GTZ
2001
Jordan
SECO
2001
Elaboration of the first part of a booklet on integrating the issue of Female
Genital Mutilation into Health Projects of GTZ
Desk study to evaluate a project involving the set-up of a Nuclear Magnetic
Resonance Spectrophotometer for a University Hospital
Jordan
SECO
2002
Health sector assessment and project identification mission
Kenya
SDC
2001
Resource person in SDC workshop for mainstreaming HIV into development
projects and HIV/AIDS workplace policies
Madagascar
SDC
2000
Integration of health into a rural development programme
Mongolia
WHO
2000 – 01
Nepal
SDC
2002
External evaluation HIV/AIDS prevention in SDC Nepal
Poland
Fundacja Zdrowie
2000
Training programme for Polish health professionals in the context of health
systems administration
Romania
GVG Cologne
2000
Preparation and organisation of a series of training modules on Technology
Management in Health Care. In the Frame of the EU PHARE project: Reform
of Health Sector Financing
2002
Drafting of a Health Strategy proposal for Kibuye Health Region (4 districts)
Rwanda
SDC
Switzerland
World Health Organisation, TDR
Switzerland
World Health Organisation, CDS
Switzerland
Mediservice
Switzerland
WHO, World Bank, UNFPA, UNDP
Tanzania
UK Dept. for International Development
Tanzania
SDC
Tajikistan
SDC
Tajikistan
Economic aspects of Brucellosis control; development of an economic model
1999 – ongoing Planning and monitoring of clinical trials for the development of oral
eflornithine against sleeping sickness
1999 – ongoing
2001 –
2002 – 03
2000
2001– 02
Coordination of HATSENTINEL (Sentinel surveillance system of the WHO
sleeping sickness drug resistance network)
Concept for a new clinical services centre of a drug mailing company in
Switzerland
Evaluation of the Human Reproductive Health Programme
Support for evaluating cost-effectiveness of adding health interventions to
district services (2 districts)
Needs assessment survey and elaboration of new policy for clinical training
and continuing education of health staff
2001
Appraisal mission to explore intervention and support possibilities for the
SDC in the Tajik health sector
SDC
2001
Evaluation of the SDC-supported health components of the Aga Khan
Development Network in Tajikistan
Tajikistan
SDC
2002
Participation in the mid-term review World Bank health project
Togo
GTZ
2000 – 01
Analysis of health service coverage with private and public services of
the city of Lomé. Conception and elaboration of a new coverage plan and
promotion of the contractual approach
Togo
GTZ
2001
Evaluation of the GTZ country health programme
Ukraine
SDC
2001
Project identification and finalisation, perinatal health in 5 Ukrainian regions
Ukraine
SDC
2001
Backstopping mission of the Crimea Integration and Development
programme (CIDP): Community-based preventive health care
United Kingdom
DFID
USA/Senegal
World Bank Institute
2001
2000 – 02
Mid-term Review of the DFID/Medical Research Council (MRC) Concordat,
External Evaluation
Health Sector Reform and Sustainable Financing Initiative:
Conception and elaboration of the content of the course, including case
studies, teaching, identification of regional resource persons
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Long-term projects of the SCIH 1996 – 2002
Project
Country
Funding Agency
Partner Institution or
Organisation
DB 289 Development of new drug
against 1st stage
sleeping sickness
Angola
Congo
DRC
Bill & Melinda Gates
Foundation
International Consortium
Ministries of Health
Angola & Congo DRC
Projet santé urbain,
Nylon
Cameroon
Swiss Agency for
Development and
Cooperation (SDC)
Ministry of Health
Mada District
Health Support
Cameroon
Fondation Helvetique
Hôpital Mada
Ministry of Health
Support of Leprosy
programme
Cameroon
Leprahilfe Emmaus
Schweiz
Management of
deprived urban
setting by its
inhabitants
Chad and
Burkina Faso
a. Swiss National Science
Foundation for scientific
aspects (Priority
Programme
Environment)
b. Tropical Disease
Research programme,
WHO, UNDP
c. Various foundations for
small scale
interventions
Nomads: Towards
the “one medicine”
concept
Rehabilitation of
radiology services
Chad
Egypt
a. STI - Jubiläumsstiftung
b. Lotteriefonds BaselLand
c. Entwicklungsfonds
Basel-Stadt
d. UNICEF
e. Optimus
Swiss State Secretariat for
Economic Affairs (SECO)
Swiss mixed credit
support to the
Hashemite
Kingdom of Jordan
Jordan
Health Projects in
Samara, Nizhni
Novgorod and
Perm
Russia
Kibuye Province
Public Health
Project
Rwanda
Switzerland’s
contribution in the
Health Care Sector
Switzerland
Managed Care in
Switzerland
Switzerland
EQUAM-foundation
IMPAMEL program
for the
improvement of
sleeping sickness
therapy
Switzerland
Angola
Diverse
Swiss Agency for
Development and
Cooperation (SDC)
86
a. Local associations and
NGOs
b. University of N’Djaména
c. City council of N’Djaména
and public structures
d. Enda-Graf Sahel in Dakar
e. University of Avignon
f. University of Strasbourg
g. Group “Urban
Environmental
Management” of the PPE
Swiss Agency for
Development and
Cooperation (SDC)
Period
• Planning and implementation of clinical trials
2001– 2005
1996 – 2000
• Project planning
• Project implementation
• Technical assistance
• Monitoring and follow-up
1997– 2003
• Assistance in project definition
• Recruitment of short and long term technical
assistance
• Technical assistance for medical training programs
and management
2001–
• Support and Backstopping of the Representative of
the LES
1996 – 2000
1997– 2005
OSEC (official trade
promotion organisation of
Switzerland)
• Implementation of improved health services delivery
in the nomadic setting
• Comprehensive research
• Creation of platforms for communication and
exchange
• PhD- and MSc(MA)- theses
2002 – 2005
1997– 2002
• Assistance with selection and procurement of
equipment
• Training of staff
• Follow-up and monitoring
1996 – 2000
• Feasibility study
• Tendering and preparation of contract for
procurement
2002 – 2004
• Research in malaria and health care financing
• Technical assistance to planning and implementation
of district and provincial health plans
• Monitoring, peace and conflict indication
Health Departments of
Samara, Perm and Nizhni
Novgorod
a. Ministry of Health
b. Kibuye Province Health
Office
• Scientifically accompanied interactions between
actions initiated by the population and institutional
actors (municipality, NGOs, etc.) in the field of:
– Management of water and solid waste
– Street children
– Promotion of impregnated bednets
• Follow-up of PhD and Diploma-students
• Reporting and publishing
• Programme design and strategic planning
• Set up and management of a support office in Cairo
• Technical assistance on procurement arrangements
• Recruitment of specialists
• Project steering, monitoring and evaluation
Ministry of Health
a. Royal Medical Services
b. University of Jordan
c. Ministry of Health
Services provided
1998 –1999
1999 –
a. World Health Organization
b. Ministries of Health
• Editing of an overview of the Swiss Health market,
which was published.
• Development of accreditation criteria
• Executing agency of the foundation
• Planning and conduct of large scale clinical trials
• Research programs
1996 – 2003
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Project
Advisory mandate
for the Swiss
government
Country
Switzerland
Advisory mandate
for the Swiss
government
Switzerland
Support to health
sector reform
Tajikistan
Dar es Salaam
Urban Health
Project
Tanzania
Swiss-Ukrainian
Child Health
Project
Ukraine
Ukrainian Swiss
Perinatal Health
Programme
Ukraine
Funding Agency
Partner Institution or
Organisation
Period
Swiss Agency for
Development and
Cooperation (SDC)
Swiss Agency for
Development and
Cooperation (SDC)
a. SDC co-ordination offices
b. Other donor organisations
Swiss Agency for
Development and
Cooperation (SDC)
Ministry of Health
Swiss Agency for
Development and
Cooperation (SDC)
a. Ministry of Health
b. Ministry of Local
Government
Ministry of Health
Swiss Agency for
Development and
Cooperation (SDC)
Services provided
1992 – 2004
• Representation at international committees and
conferences, networking
• Development of proposals for policy papers and
guidelines
• Compilation of information
• Capitalisation of experience
2001– 2004
• Compilation of information
• Provision of information on website
• Fact sheets, briefing papers
2002 – 2005
• Strengthening of human resources and institutions’
capacities in the area of the health sector reform and
PHC
• Improvements in skills for the management,
monitoring and evaluation of health systems and
service delivery
• Discussion and establishment of models for
community participation
• Design and implementation of tuberculosis and
HIV/AIDS prevention and care activities
1989 – 2001
• Feasibility study and project planning
• Recruitment of short- and long-term staff
• Financial management
• International procurement
• Follow-up
1998 – 2000
• Feasibility study and project planning
• Procurement of equipment
2002 – 2004
• Programme Management
• Capacity building
• Operational Research
Ministry of Health
Selected Publications of the Swiss Centre for International Health (SCIH)
Borghi J, Fox-Rushby J, Bergel E, Abalos E, Hutton G & Carroli G (2002) The CostEffectiveness of routine versus restrictive episiotomy in Argentina. Amer J Obstet
Gynecol 186, 221– 8.
Borghi J, Bastus S, Belizan M, Carroli G, Hutton G & Fox-Rushby J (2003) Costs
of publicly provided maternity services in Rosario, Argentina. Salud Publica de
Mexico 45.
Burri C (2001) Are there new approaches to roll back trypanosomiasis? (Editorial)
Cloutier L (2001) Social transition and health development in Dar es Salaam. In:
L’Afrique orientale. Ed. Maupeu H. Paris: L’Harmattan, 275 – 312.
Felber G, Othingué N, Yemadji N & Wyss K (2001) Lessons from malaria control
activities in urban West Africa using a research – action – capacity approach. PLA
Notes 40, 18 – 21.
Hutton G (2001) Economic evaluation and priority setting in water and sanitation
interventions. In: Water Quality: Guidelines, Standards and Health. Eds. Fewtrell L
and Bartram J, London: IWA Publishing, chapter 16.
Hutton G and Baltussen R (2002) Valuation of goods in cost-effectiveness analysis: notions of opportunity costs and transferability across time and countries.
Global Programme on Evidence Discussion Paper, WHO.
http://www3.who.int/whosis/cea/background_documents.
Kessler Bodiang C (2001) Addressing female genital mutilation: challenges and
perspectives for health programmes. Eschborn: GTZ, www.gtz.de
Kessler C (2002) HIV Prävention bei afrikanischen Migrantinnen und Migranten:
eine Herausforderung für die schweizerische Gesundheitspolitik. AIDS INFOTHEK, 3.
Legros D, Ollivier G, Gastellu-Etchegorry C, Paquet C, Burri C, Jannin J & Büscher
P (2002) Treatment of human African trypanosomiasis – present situation and
needs for research and development. Lancet Infec. Dis. 2, 437– 40
Pichette P & Mtasiwa D (2001) The tanzanian Health Sector Reform. In: L’Afrique
orientale. Ed. Maupeu H. Paris: L’Harmattan, 203 – 274.
Raab M, Kadyrof F (2000) Technology management in healthcare – challenges
and opportunities for countries in transition. Geneva: WHO series 9.
Raab M (2001) Technology assessment in healthcare. Bull Medicus Mundi
Schweiz 82.
Raab M (2001) Plädoyer für ein verbessertes Ressourcenmanagement, Bull
Medicus Mundi Schweiz 82.
Teuscher A, Wiedenmayer K, Lorenz N, Teuscher T (2002) Natural Insulin is costeffective. Bull Medicus Mundi Schweiz 84.
Villar J, Ba’aqeel H, Piaggio G, Lumbiganon P, Miguel Belizan J, Farnot U,
Al-Mazrou Y, Carroli G, Pinol A, Donner A, Langer A, Nigenda G, Mugford M, FoxRushby J, Hutton G, Bergsjo P, Bakketeig L, Berendes H, Garcia J (2002) WHO
antenatal care randomised trial for the evaluation of a new model of routine antenatal care. Lancet 357, 1551– 64.
Wiedenmayer K, Mtasiwa D (2000) Transforming drug supply in Dar es Salaam,
Essential Drug Monitor (WHO) 28 & 29, 25 – 27.
Wyss K, Lorenz N (2000) Decentralization and central and regional coordination
of health services: the case of Switzerland. Int J Health Plann Manage 15,
103 –114.
Wyss K, Mtasiwa D (2000) Available financial resources in the public health care
sector in Dar es Salaam. Bull Medicus Mundi Schweiz 79, 32 – 35.
Wyss K, Kilima P & Lorenz N (2001) Costs of tuberculosis for households
and health care providers in Dar es Salaam, Tanzania. Trop Med Int Health 1,
60 – 68.
Further research papers will be found in other sections, especially 4, 6 and 7
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SECTION 12
STI Services
DICEL (Documentation, Information, Communication
and E-Learning)
This new unit was created in 2001 to emphasise the importance
of information and knowledge management in the STI. It brings
together various activities associated with information and communication: well-established services like the STI Library and
Documentation Centre, and newer ones like the growing field of
“e-learning”.
The STI Library and Documentation Centre
The library and documentation centre is open to the public. It
contains about 120 journals, 5 000 monographs, publications
and reports, and also CD-ROM disks, slides and films. Although
electronic publications and virtual libraries are increasing more
and more, print media still play an important role, and the
collection of books and journals is regularly improved and
updated. The library services are becoming increasingly complex, with numerous online databases such as library catalogues, scientific databases and electronic journals. The STI
library is part of a Swiss library network, and the catalogue can
be consulted and books borrowed through the Internet. The
library in Basel provides professional training in information and
documentation, and continues to provide training and advice for
partner institutions in the South.
Information Technology and E-Learning
The unit maintains the STI network and provides computer support and training for the STI staff, STI students and students
attending special courses in the Institute (picture p. 75). A
trainee from the CSRS, Abidjan, spent some months working in
Basel. In the field of E-Learning, software is being developed to
support courses taught in the STI and the University (see also
Section 9). The security and performance of the STI network
were the subject of an external analysis in 2002.
Biostatistics Unit
The Biostatistics Unit conducts long-term collaborative research
projects together with biomedical scientists, as well as its own
methodological research (Section 5). The unit also offers consulting and data services for the University and the research
community, and provides training in statistics for MSc and PhD.
students of the Institute. Basic services include consultation on
the design of studies, experiments and surveys; power and
sample size calculations, and statistical analysis.
Central Laboratory
The laboratory supports teaching by supplying materials for
courses in diagnostics, medical parasitology and biology of
infection. It also maintains parasitic protozoa, ectoparasites and
complex life cycles of various helminth parasites. Parasite material is also provided for research and is the basis for the antigen
supply for serological diagnosis.
Life Sciences Training Facility
This new collaborative facility is based at the Biocentre, Basel.
In 2000 the STI became a founding member, and one of the first
users. The facility provides GeneChipTM facilities (Affimetrix)
and also has equipment available for low density micro arrays.
The Training Facility also offers support for micro-array analysis
and bioinformatics. In 2002, the low density micro array facilities
were moved to a newly established laboratory at the STI, where
they are currently being used for the development of an SNP
analysis system for genes associated with antimalarial drug
resistance (Section 1.6).
Technical Services
The technical service staff of the STI were involved not only in routine maintenance work but also contributed substantially to the renovation of the buildings and the changes needed to make the rooms more appropriate for today’s needs. The renovation of the secondoldest part of the building, the “Mittelbau” was completed in 2000, and in 2001, Lecture Room 2 was converted into a friendly and
flexible “learning space” suitable for different learning methods and new media.
Renovation of Lecture Room 2. Left, work in progress (Source: N.A. Weiss). Right, a class in the renovated room (Source: M.G. Weiss).
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The STI Foundations
The STI Jubilee Foundation
The Jubilee Foundation was established in 1993, to mark the 50th anniversary of the foundation of the Institute. It aim is to promote
innovative research in the STI in three main areas: life-threatening malaria; urbanisation and urban health, and health and the environment in the Sahelian zone. The STI Directorate will be happy to provide further information.
The R. Geigy Foundation (RGS)
During his lifetime, Professor Rudolf Geigy established several Foundations to support the Swiss Tropical Institute. These have now
been amalgamated into the R. Geigy Foundation (R. Geigy-Stiftung, RGS), whose aim of the Foundation is to support activities that cannot be financed from other sources. One of the primary aims of the original Foundation was to support young scientists doing field work
and to help scientists to publish their results, and the RGS continues to do this. Grants are also made for the acquisition of special
pieces of equipment and for expenses such as renovation of the buildings. Support from the RGS for research is mentioned under
“Funding” in the individual sections of the Report.
The R. Geigy Foundation has also created an award for excellence in research, to help and encourage younger scientists who will go
on to contribute to scientific progress in their chosen field. The first award was presented in April 2001 to Professor Fred Binka from
Ghana. The second award will be presented to Dr Lea Knopf from Switzerland in December 2002.
Presentation of the first R. Geigy Award to Professor Fred Binka, Ghana, April
2001. (Source: R. Dürr)
Laboratory work in Côte d’Ivoire. At the microscope is Dr. Lea Knopf.
(Source: O. Girardin)
In December 2002, the STI will celebrate the centenary of the birth of the Founder, Professor Rudolf Geigy, STI Director until 1973, with
a symposium entitled: From Explorations to Research Partnership. We mark the occasion here with a short history, illustrated with
pictures from the STI picture archive. More details can be found in the German brochure “Bwana Ngiri”: Hommage à Rudolf Geigy, by
Urs Weber, available from the STI Secretariat.
Rudolf Geigy was born in 1902 in Basel. His father was head of
the family firm, Geigy AG, the chemical and pharmaceutical
manufacturing company that later became part of Ciba-Geigy.
However, Rudolf Geigy did not want to
follow in his father’s footsteps. His main
interest was in living things, and he
chose to study zoology rather than chemistry. In later life, he often expressed his
gratitude to his family for allowing him to
follow his own path. He soon acquired a
considerable reputation as a developmental biologist, and in 1938 he became
a professor in the University of Basel.
The story of the Swiss Tropical Institute begins towards the
end of the Second World War, when there was a lot of concern in
Switzerland about what would happen when the war was over –
the Depression that had followed the 1914 –18 war was fresh in
many people’s memories. The Swiss Government encouraged
the founding of institutions that could help to open up new opportunities. One suggestion, from Prof. A. Gigon of the Medical Faculty in Basel, was the founding of a Tropical Institute. Because of
its many links with tropical countries, Basel was seen as a suitable location. The idea was well received, and both the Federal
Government and the Canton of Basel promised their support. A
Board of Governors was set up, and Rudolf Geigy was invited to
become the Director of the newly-founded Institute.
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The original aims of the Tropical Institute were fairly limited.
One was to offer training for Swiss citizens so that they could
take up work in tropical countries – in business enterprises and
in agriculture as well as in humanitarian work such as medical
missions. The second was to establish a clinic where Europeans
returning from the tropics could obtain specialised medical
care.
Under Rudolf Geigy’s leadership, these aims were fulfilled. A
“General Tropical Course” started immediately, with students
from a variety of professions. A specialised course in Tropical
Medicine was added a few years later. A “Tropical School”
offered professional training in tropical agriculture and other
skills needed by future managers of plantations, sugar factories
and the like – including the maintenance of motor vehicles.
Medical services were also established, and though there were
never many in-patients there was a steady stream of people
needing advice and vaccinations before travelling to the tropics, and coming for out-patient consultations and treatment on
their return.
However, the new Tropical Institute did not limit itself to these
activities. In his official report on the STI in its first years, Geigy
lists not only the expected teaching and clinical services, but
also a series of other activities: the founding of the scientific
journal Acta Tropica; the development of a collection of materials for teaching; advisory services, and research. For the latter,
the field proposed was very wide indeed. It included, “all those
areas of work that are associated with the fight against tropical
diseases of humans and domestic animals”. And the Swiss
Tropical Institute should also promote, “general investigation of
medical, scientific, ethnographic, linguistic and other aspects of
the tropics”.
This breadth of research is reflected in the contents of the
early numbers of Acta Tropica. Research in the Institue during
Rudolf Geigy’s years as Director covered a wide variety of disease-causing parasites and their hosts, and also termites, and
venomous and poisonous animals. Live specimens and breeding colonies of many parasites and their hosts were maintained
in the laboratories in Basel, but there was no question for Rudolf
Geigy that research on the tropics could be done entirely in
Europe. In his first report he emphasised the importance of
expeditions to tropical countries to do research in the field. The
first of these took place as soon as travelling became feasible
after the end of World War II. Geigy described it as “Prospection” – not for minerals, but for interesting organisms to add to
the store of research and teaching materials in Basel. A few
years later another expedition, this time to Tanganyika (now Tanzania), led to the foundation of the Swiss Tropical Institute Field
Laboratory, in Ifakara. In West Africa, the foundation of the
CSRS in Côte d’Ivoire, by the Swiss Academy of Sciences, also
owed a great deal to Rudolf Geigy’s interest and support.
Scientists are sometimes accused of having one-track
minds, and ignoring the world around them. This could not be
said of Rudolf Geigy. The large collection of pictures that he
took on his “Prospections” show his interest not only in zoological specimens but in the countries and their people. He encouraged the recording of local traditional ceremonies. However, he
was also aware that African societies were changing, and that
there were needs beyond basic research on tropical diseases.
In 1962, when he became Rector of the University of Basel, he
90
made a speech on “The leap into independence; problems of
development and society”.
Rudolf Geigy was a scientist, but he was also a member of
the family that owned one of Basel’s biggest pharmaceutical
companies, and he did not hesitate to use the resources and
influence that this put at his disposal – in ways that ranged from
chartering aeroplanes for expeditions, or persuading an airline
to carry a cage of tsetse flies or an aardvark, to establishing
foundations to support young scientists to do research, or
donating substantial sums of money to the Basel Zoo, of which
he was President of the Board of Directors for 30 years.
A most important initiative was the creation of the Basel
Foundation for Assistance to Developing Countries, which was
set up and financed by the pharmaceutical industry, at the time
when Tanzania was about to become independent. Characteristically, Geigy went straight to the person who was expected to
become the first President, Julius Nyerere, to ask how the Foundation and the STI could best support the new nation. The reply
was that one of the most pressing needs was for the training of
more personnel for health services and development work in
rural areas. The result was the founding in 1961 of a Rural Aid
Centre, in Ifakara, near the Field Laboratory, which later became
the Medical Assistants Training Centre (MATC). Staff of the STI
were responsible for the teaching.
It is now nearly 30 years since Rudolf Geigy retired from the
position of Director of the STI. The institutions that he was instrumental in founding are still flourishing. The Field Laboratory is
now the Ifakara Health Research and Development Centre, affiliated to the Tanzanian National Institute of Medial Research. The
MATC was handed over to the Tanzanian Government in 1978,
and is now a Clinical Officers Training Centre. In Côte d’Ivoire,
the CSRS celebrated its 50th Anniversary in 2001.
In the Institute in Basel, many of the activities of the early
days are still important. The medical and diagnostic out-patient
services and the Travel Clinic are thriving – though now advice
is more often given to tourists than to potential emigrants. The
General Tropical Course is still popular, and the training in tropical medicine continues – though it is now carried out in Africa.
The founder would certainly have welcomed the fact that many
of the students in the STI come from Africa and Asia, and that
the Institute is part of the TropEd network of Tropical Institutes all
over Europe.
The research that is being done in the STI today includes
sophisticated molecular biological techniques and computerbased statistical methodology, but much of it is still concerned
with the same complex host-parasite relationships. Rudolf
Geigy’s successors, Thierry Freyvogel, Antoine Degrémont and
Marcel Tanner, have widened the scope of the Institute’s
research, for example with fundamental studies of health systems which are linked with support for development.
“Research on all aspects of the Tropics” is now research in
partnership with people and institutions from independent countries. But the pursuit of scientific excellence, both in the laboratory and in the field, is still a characteristic of the Institute as it
was when it was founded, and the lines on which the STI has
developed, which have enabled a fairly small institution in a
small country to achieve international recognition, are very
largely the result of the enthusiasm and the breadth of vision of
its founder.
15.11.2002
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Seite 91
Prospection, 1945, “on the way to Thysville, Congo”
The materials for teaching and research collected on this expedition included
288 tsetse flies, destined to set up the first breeding colony in Europe. These survived the 3-day air journey to Paris, but by then they needed reviving with a blood
meal. This was provided in a bathroom of the Ritz Hotel, which the manager had
made sufficiently “tropical” by running all the hot taps.
Support for the Basel Zoo, 1949
Looking after an aardvark collected in Tanzania on its way to the Basel Zoo. Geigy
wrote that the airline concerned “was always very helpful”. In Nairobi, the transport
crate proved to be too big, but “without a moment’s hesitation the pilot gave permission to let the animal loose in the luggage compartment, where …. it curled up
in a ball at the back and happily survived the long journey.”
The first STI laboratory in Ifakara, 1949
Early field studies in Tanzania were based on a small laboratory in the buildings of
the Capuchin Mission in Ifakara. This was replaced by the STI Field Laboratory,
which is now the Ifakara Health Research and Development Centre. On the right,
Prof. Geigy organising the feeding of tsetse flies on rabbits. In the background,
two young Swiss scientists, E. Gander and M. Lüscher.
Teaching in Tanzania
As a teacher, Rudolf Geigy made sure that his students experienced animal life in
the field as well as in the lecture room. He took his Basel students to the Swiss
lakes to study aquatic animals, and in Ifakara he organised expeditions into the
bush. The picture shows him teaching students of the Rural Aid Centre about
tsetse fly control.
The Medical Assistants Training Centre (MATC) in Ifakara
The inauguration of the Medical Assistants Training Centre in Ifakara by President
Nyerere. The teaching staff were supplied by the STI. Professor Geigy took a
strong personal interest in the Centre. He selected the staff personally, and took
part in the teaching of many of the courses himself.
The University of Basel
A formal procession on the Dies Academicus of the University of Basel in 1962,
when Prof. Geigy was Pro-Rector. Those who remember him say that he was an
inspiring teacher, full of enthusiasm for his subject – but one who did not suffer
fools gladly. The STI is now an Associated Institute of the University.
91
92-93_Further Activities
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Seite 92
Positions held by STI staff in other institutions and organisations
Switzerland
WHO and TDR/WHO
Basler Stiftung für experimentelle Zoologie: Chairman, R. Brun
E. Guggenheim-Schnurr Stiftung, Basel: R.Brun, N.A. Weiss
FMH Tropical and Travel Medicine: Committee, J. Blum
Freie Akademische Stiftung, Basel: R. Brun
Medicus Mundi Switzerland: President, N. Lorenz
R. Geigy Stiftung, Basel: L. Jenni, M. Tanner, N.A. Weiss
SDC representative at partner meetings, Roll Back Malaria:
C.Lengeler
Skat Foundation, Switzerland: Board Member, N. Lorenz
Swiss Society of Tropical Medicine and Parasitology:
Vice-President, B. Beck; Committee, B. Genton
Universities of Basel, Berne, Zürich, Master of Public Health
(MPH) Programme, President of the Faculty, A. Hoffmann;
Board, M. Tanner (Basel)
TDR Scientific & Technical Advisory Committee (STAC):
M. Tanner (from 2000)
TDR/WHO scientific working group on African trypanosomiasis:
R. Brun, C. Burri
TDR/WHO: PDT oral eflornithine: C. Burri
WHO Expert Committee on Control of African trypanosomiasis:
Temporary Adviser, R. Brun
WHO Expert Committee on Ultrasound Diagnosis in Schistosomiasis: C. Hatz
WHO Sleeping sickness treatment and drug resistance
network: R. Brun (Chair); C. Burri
WHO steering committees for the development of the malaria
vaccine candidates AMA-1 and PfCS102: B. Genton
WHO/FAO/OAU/IAEA Programme against African trypanosomiasis: C. Burri
International
Conseil d’Administration Institut de la Francophonie pour la
Médecine Tropicale, Laos : M. Tanner
Chinese Ministry of Public Health, Joint Research Coordination
Committee WHO/TDR & People’s Republic of China:
Eastern Africa Network for Trypanosomiasis (EANETT): Board
of Management, R. Brun; Secretary, M. Kaiser
ICDDR – B (International Centre of Diarrhoeal Diseases
Research) Dhaka, Bangaldesh: Board of Governors,
IHRDC, Ifakara, Tanzania:
Board of Trustees, M. Tanner (from 1997)
Board of Governors, C. Hatz, M. Tanner (from 1997)
London School of Hygiene and Tropical Medicine (LSHTM),
Research Strategy Review Team: M. Tanner (from 2002)
Institut de Recherche pour le Développement, IRD (formerly
ORSTOM), Conseil d’Administration: M. Tanner (2000 – 2002)
International Center of Insect Physiology and Ecology (ICIPE)
Nairobi, Kenya: Vice-Chairman (2001– 2003) N.A. Weiss
International Clinical Epidemiological Network (INCLEN)
Board of Directors INCLEN Inc: M. Tanner (from 1998)
Board of Trustees INCLEN Trust: M. Tanner, Chair (fr. 2000)
International Society of Travel Medicine: Chair of Publications
Committee, C. Hatz
Network for Education in International Health tropEd:
President-Elect, A. Hoffmann
Swiss Academy of Sciences: Commission for the Centre Suisse
de Recherches Scientifiques Adiopodoumé en Côte d’Ivoire:
M. Tanner (from 1997; Chair from 1998)
TAGs for the Malaria Vaccine Initiative (MVI) at the Programme
for Appropriate Technology in Health (PATH) of the
Bill & Melinda Gates Foundation: B. Genton
Prizes and Awards
June 2002: The “Medicines for Malaria Venture” (MMV)
award for the most promising project of the year was presented to the team working on synthetic peroxides (OZ
compounds) as antimalarials (Section 4.2). In the photograph from left to right: J. Vennerstrom (University of
Nebraska), R. Brun (STI), W. Charman (Monash University, Melbourne), H. Matile (Hoffmann-La Roche, Basel)
Sept. 2000: Leverhulme Medal to Marcel Tanner
Dec. 2001: Basel Science Prize to Leo Jenni
Oct 2002:
Paul Harris Fellowship, Rotary International,
to Christian Lengeler
Institutional membership
Medicus Mundi Switzerland
Swiss Commission for Research Partnership
with Developing Countries, KFPE
TropMedEurop
TropEd: European Network for Education in International Health
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11:45 Uhr
Seite 93
Advisory Boards and Review Teams
British Medical Research Council Advisory Board: T. Smith
DFID/WHO Knowledge and Research (KaR) health technology
procedures guide programme: M. Raab
Epicentre, clinical trials on sleeping sickness combination
therapy: C. Burri
University of Heidelberg: Scientific Advisory Board Research
focus on Tropical Medicine, Special Programme on Tropical
Medicine: Chair, M. Tanner (from 1995)
INDEPTH Scientific Advisory Board: T. Smith
London School of Hygiene and Tropical Medicine (LSHTM),
Research Strategy Review Team: M. Tanner (from 2002)
Netmark Project, Technical Advisory Group (USAID):
C. Lengeler
Roll Back Malaria Technical Support Network on Insecticide
Treated Materials: C. Lengeler
Society for the Study of Psychiatry and Culture, Advisory
Board: M.G. Weiss
Swiss Working Group on Travel Medicine: Committee,
B. Genton, C. Hatz
Trial Monitoring Boards
Data and Safety Monitoring Board: Improvement of the treatment of human sleeping sickness using the trypanocidal
drug melarsoprol (IMPAMEL I & II): Chair, B. Genton
Independent Safety Monitoring Committees:
Phase I study of Apovia’s malaria vaccine: Chair, B. Genton
Phase I – II studies of FSP-I malaria vaccine: M. Tanner
Phase I – IIa studies of MVA-CSO and RTS, S/ASO2A malaria
vaccine in adults: B. Genton
Public Events
April 2001: African Malaria Day. To draw attention to the
problem of malaria, the STI erected the world’s largest
mosquito net on the Theatre Square in Basel – on a very
wet day (Source: G. Hutton)
April 2001: Swiss Week in Dar es Salaam
Sept. 2001: Africa Day in the STI (see p. 96)
Sept. 2001: AIDS day
Editorial Boards
Acta Tropica: C. Hatz
Anthropology and Medicine: M.G. Weiss
Bulletin of the World Health Organisation: M. Tanner
Culture, Medicine and Psychiatry: M.G. Weiss
Health Policy and Planning: M.G. Weiss
Parasitology International: M. Tanner
Parasitology Today: M. Tanner (1987– 2001)
Transcultural Psychiatry: M.G. Weiss
Trends in Parasitology: C. Burri
Tropical Medicine and International Health:
C. Hatz, M. Tanner, T. Smith, N.A. Weiss
Guest Scientists
Dr. Ernestine Mensah-Quainoo, Ghana
Prof. Shuhua Xiao, Centre for Communicable Disease Control
and Chinese Academy of Preventive Medicine, Shanghai,
PR China
Other visitors
March 2002: Visit of the Minister of Higher Education and
Research of Côte d’lvoire, Prof. Sery Bailly
The STI Support Group for projects overseas
The Support Group is a small organisation founded in
1989 by collaborators of the Institute who had seen that in
the countries where they worked there were many situations where a little financial input could be a big help for
local groups working on projects to improve the quality of
life in their communities. The Support Group’s aim is to
provide assistance to small projects or groups of people
who are personally known to STI collaborators, and where
there is someone on the spot who can act as a link and
report on progress.
The Support Group is a registered society. It is completely independent of the STI, although most of the
approximately 100 members and supporters are working
in the Institute. Annual income from subscriptions, donations and various fund-raising activities is about CHF
15,000. Since there are hardly any administrative costs,
most of this goes to support 4 – 6 projects per year. Projects at present include the purchase of a motor bicycle
for a re-afforestation project in Bénin; a loan to a garage in
Tanzania where apprentices are trained; a loom for a
weaving project in Sudan, and a project working with
abused girls in Cambodia. A bulletin, the Buschtrommel,
provides information about the group’s activities. (Contact: Reto Brun).
93
94-95_Staff of the STI
15.11.2002
11:45 Uhr
Staff and doctoral students
of the Swiss Tropical
Institute during the period
September 1st 2000 –
August 31st 2002
Units of the Directorate
Administration
Wasser Ulrich, MA, Head
Bolliger Isabelle, Personnel Manager
(from 01.12.01)
Bourgau Dominique, Accountant
(from 13.08.01)
Buholzer Madeleine, Receptionist
Doré Agnès, Accountant
Dürr Rolf, Technical Services
Haas Paul, Technical Services
Jenkins Jennifer, MSc, Scientific Editor
Jost-Gerber Martha, Receptionist (to 05.06.01)
Roth Felix, MA, Controlling (to 09.2001)
Schüpbach Salome, MSc, Secretarial Assistant
Sedlmeier Elisabeth, Personnel Manager
(to 30.11.01)
Tanner Sabine, Office Auxiliary (from 01.03.01)
Tschudi Eduard, Technical Services
Walliser Christine, Assistant to the Directorate
Hoffmann Axel, PhD, Course Coordinator
Meyer Caroline MSc, Administrative Assistant
Pelikan Joachim, PhD student (E-learning)
Peterhans Bernadette, MPH,
Course Coordinator
Schäfer Erna, Administrative Assistant
Zumstein Adrian, PhD, Lecturer
Library and documentation
Immler Heidi, Chief Librarian
Hug Nils, Trainee (to 31.08.01) and Assistant
Librarian (to 31.05.02)
Isler Annina, Trainee (from 01.08.02)
Minder Manuel, Trainee (from 01.07.02)
Tosun Mehtap, Trainee
Information Technology
Baumann Martin, Computer Specialist
(from 01.02.02)
Hodel Urs, PhD, Computer Specialist
Roelly Simon, Computer Specialist
Roger Kpon, Trainee (6 months, 2002)
External Collaboration
Degrémont Antoine, Prof., MD, DTMH, Public
Health Specialist (Vientiane, PDR Laos)
Jenni Leo, Prof., PhD, External Collaborator
MGU, Basel
Müller Franziska, Project Coordinator, Bénin
Rohr H-P, Prof., MD, Swiss Virtual Campus
(from 07.2001)
Footnote/key:
* Staff of overseas projects; students based
overseas
Professor, Senior Lecturer, Lecturer: Teaching
appointments in the University of Basel
ATA (akademisch-technische AssistentIn):
Graduate technologist
Underlined: Responsible project leader(s)
94
Seite 94
Director: Tanner Marcel, Prof., PhD, MPH
Board of Directors
Hatz Christoph, MD, DTMH: Head, Clinical and Diagnostic Services
Lorenz Nicolaus, MD, MPH: Head, Swiss Centre for International Health
Weiss Mitchell, Prof., MD, PhD: Head, Public Health and Epidemiology
Weiss, Niklaus, Prof., PhD: Head, Medical Parasitology and Biology of Infection
Deputy Director STI
Medical and Diagnostic Services
Head: Hatz Christoph, MD, DTMH,
Senior Lecturer
Clinical and scientific staff
Balmer Eva, MD (from 01.01.01 to 31.12.01)
Beck Bernhard MD, DTMH
Blum Johannes MD, DTMH
Bordmann Gérard, PhD
Kummli Bleicher Dorothée (from 19.11.01)
Marti Hanspeter, PhD
Mossdorf Erik, MD (from 01.01.02 to 30.06.02)
Rudin Werner, PhD, Senior Lecturer
Salis Gross Corina, PhD (from 01.01.01 to
31.03.01)
Schenker Tanja, MD (from 11.02.02 to
31.07.02)
Veit Olivia, MD (to 31.12.01)
Werlein Jutta, MD (from 01.07.02)
Technologists
Barry Angelika
Bregenzer Sybille
Cattelan Beatrice
Cuche Julien (from 01.02.01 to 31.07.02)
Dobler Michelle (to 30.11.01)
Escher Elisabeth
Gregor-Bernauer Heidi (to 31.07.02)
Grilli Isabelle (from 19.08.02)
Heller Irene
Kobialka Genowefa
Krebs-Hollinger Christina
Misteli Kurt (from 01.03.01)
Oettli Annelis
Schmid Marie-Claire (from 01.07.02)
Steinmitz Monika (to 31.05.02)
Struchen-Rosskopf Anita (to 31.12.00)
Administrative and secretarial staff
Breiter Monika (from 01.08.01 to 30.09.02)
Buholzer Madeleine
Dimas Anita (from 15.07.02)
Gaspare Ramon (from 01.07.01)
Gessler Heidi
Gruber Marhild
Haas Astrid
Janssen Jochen (from 01.02.01)
Jenny Sally (from 01.07.02)
Jenzer Dorothea (from 01.05.02)
Krebs Jrène
Krebs Nicole (to 31.05.01)
Meyer Caroline MSc
Rimelin Lucie
Rudolf Gulino Denise (to 31.01.01)
Scherrer Yvonne (to 31.05.01)
Wäckerlin Beatrice
Widmer-Walliser Hanna (to 30.06.02)
MD Students
Brenken-Ryser Eva
Candolfi Caroline
Lehky Hagen Monique
Freiburghaus Susi
Wirz Caroline (MD 2001)
Head: Lorenz Nicolaus, MD, MPH
Based in the STI, Basel
Burri Christian, PhD, Pharmacist
Hutton Guy, BA, MSc, Health Economist
(from 30.06.00)
Kessler Bodiang Claudia, MD, MPH,
Public Health Expert (from 15.11.00)
Magdalinski Doris, BA, Project Assistant
(from 01.01.01)
Mittelholzer Marie-Louise, Clinical Research
Scientist (from 01.03.02)
Petersik Eva, Project Assistant (to 31.01.01)
Pohlig Gabriele, PhD, Clinical Research
Scientist (from 15.11.01)
Raab Martin, MSc, Health Technology
Specialist
Roth Felix, MA, Economist, Managed Care
Expert (to 31.12.01)
Seixas Jorge, MD, MSc, Scientific Collaborator
Slaoui Margrith, Project Assistant
Thierfelder Clara, MD student
Wasser Cédric, Admin. & Data Management
Assistance
Werlein Reinhold, Health Technology Specialist
(from 01.07.02)
Wiedenmayer Karin, PhD, MSc, Clinical
Pharmacologist, Expert on Essential Drugs
Wyss Kaspar, PhD, MPH, Epidemiologist,
Public Health Specialist
Zahorka Manfred, MD, MPH, Public Health
Expert (from 15.08.02)
Based in N’Djaména, Chad
Daugla Doumagoum Moto, MD, MPH,
STI representative in Chad
Gueim Morgaye, MD, Physician
Kossi Ganda, Logistics
Lardjïm Albertine, Secretary
Naïbeï Nathan, Computer Specialist
Naïssengar Jean, Administrator
Naditolnan Othingué, Geographer
N’Diekhor Yémadji, PhD, Geographer and
Researcher
Toh Gou Charline, Secretary
6 supporting staff (guards, drivers)
Based in Douala and Mada, Cameroon
Bakerura M’Pozé Sinda, MD, Surgeon
Idriss Mohammed, Maintenance Engineer
N’Tchakouté Ka’am Charlotte, IEC-Specialist
Um Book Alphonse, MD (to 31.12.01)
STI representative in Cameroon
Based in Dar es Salaam, Tanzania
Coppens Anne, MA, Economist (to 31.12.01)
Masanja Fred, Administration Assistant
(to 30.06.01)
Pichette Pierre, MA, Political Scientist,
Project Manager
Vesso Isack, Accountant
Singh Helen, Secretary
6 supporting staff
Based in Kiev, Ukraine
Solodarenko Andrei, MD, Physician,
Representative of STI in Ukraine
(from 1.10.01)
94-95_Staff of the STI
20.11.2002
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Seite 95
Research Groups: Staff and doctoral students
(MSc, ATA and MIH students are listed on page 73)
DEPARTMENT OF MEDICAL PARASITOLOGY AND BIOLOGY OF INFECTIONS (MPI)
Head: Weiss, Niklaus, PhD, Professor,
Deputy Director STI
Technical staff
Buehler Daniel
Endriss Yvette
Gysin Karin
Scheidegger Georg, PhD (to 28.02.01)
Molecular Epidemiology and Parasitology
(Section 1)
Scientist
Beck Hans-Peter, PhD, Senior Lecturer
Crameri Andreas (from 07.02.02)
Genton Blaise, MD, PhD, DTMH
Technologist
Steiger Sylvia, ATA
PhD students
Flück Christian
Irion Andrea (PhD 2001)
Kästli Mirjam
Keto George (PhD 2001)
Kigbafori Silue (visiting student; Côte d’lvoire)
Luginbühl Alexander
Mugittu Kefas
Niederwieser Igor
Spielmann Tobias (PhD 2002)
Voss Till (PhD 2002)
Parasite Chemotherapy (Section 4)
Scientists
Brun Reto, PhD, Professor
Kaiser Marcel, MSc
Scorneaux Bernard, PhD (to 31.03.02)
Wittlin Sergio, PhD (from 24.06.02)
Technologists
Chollet Jacques
Easterbrook Judith, BSc (from 01.04.01)
Gillingwater Kirstin (exchange student, UK)
Gobright Elke
Honegger Katharina (from 01.03.01 to
31.12.01)
Kunz-Renggli Christina
Oberle Michael, MSc
Riccio Guy
Santo Tomas Josefina
Scheurer Christian
Vogel Marie-Lynn, BSc
PhD students
Bernhard Sonja
Maina Naomi
Senn Martin
Noureldeen Amal (PhD 2001, Khartoum)
DEPARTMENT OF PUBLIC HEALTH AND
EPIDEMIOLOGY (GWE)
Head: Weiss, Mitchell: MD, PhD, Professor
Administrative and secretarial staff
Naumann Cornelia (to 30.08.02)
IHRDC, Tanzania
Schneider Achim, PhD
Schneiter Sorin
Scheuber Thomas
Biostatistics and Basic Epidemiology
(Section 5)
Molecular Diagnostics (Section 2)
Scientists
Smith Thomas, PhD, Senior lecturer
Vounatsou Penelope, PhD
Scientists
Felger Ingrid PhD, Senior Lecturer
Burckhardt Jean PhD (from 01.05.01)
Technologists
Makia Ntoh Divine Oscar (from 01.10.01)
Marfurt Jutta ATA
Molecular Immunology (Section 3)
Scientists
Pluschke Gerd, PhD, Professor
Daubenberger Claudia, PhD Senior Lecturer
Müller Markus, PhD (from 01.02.01)
Technologists
Curcic Djuric Marija (from 01.01.01)
Dangy Jean-Pierre (from 01.09.01)
Naegeli Martin
Pöltl-Frank Friederike, ATA (to 31.03.01)
PhD students
Bastian, Max
Diaz, Diana
Gagneux Sebastien (PhD 2001)
Leimkugel, Julia
Moreno Rafael (PhD 2001)
Nickel Beatrice (PhD 2001)
Okitsu Shinji
Rondini Simona
Research Assistants
Anderegg Daniel, MSc (from 01.04.2002)
Matthys Barbara, MSc (from 01.04.2002)
PhD students
Gemperli Armin
Hodgson Abraham* (PhD 2002)
Kleinschmidt Immo* (PhD 2001)
Müller Ivo (PhD 2000)
Mwanakasale Victor* (PhD 2001)
Ochola Lucy*
Owusu-Agyei Seth* (PhD 2001)
Raso Giovanna
Sama Wilson
Clinical and Intervention Epidemiology
(Section 6)
Scientists
Lengeler Christian, PhD, Senior Lecturer
Burri Christian, PhD
Genton Blaise, MD, PhD, DTMH
Grundmann Hajo*, MD, PhD, DTMH
(from 16.08.01)
Tami Grundmann* Adriana, MD, PhD
(from 01.04.01)
Wang Shr-Jie, MSc (from 01.04.02)
PhD and MD students
Abdulla Salim* (PhD 2000)
Armstrong Schellenberg Joanna (PhD 2001)
Barriga Claudia
Kikumbih Nassor* (PhD 2002, London)
Nathan Rose* (PhD 2002, London)
Njao Rita*
Schmid Cécile
Seixas Jorge, MD
Marchant Tanya (PhD 2002)
Minja Happiness (PhD 2001)
Environment, Society and Health Systems
(Section 7)
Scientists
Tanner Marcel, PhD, MPH, Professor
Wyss Kaspar, PhD, MPH
Zinsstag Jakob, DVM, PhD
Angaya Maho*, DVM
Bonfoh Bassirou*, DVM
Cissé Guéladio*, PhD
Hatz Christoph, MD, DTMH
Hutton Guy, PhD
Indergand Stefan* (from 1.11.2001)
Kessler Bodiang Claudia, MD, MPH
Obrist van Eeuwijk Brigit, PhD, Senior lecturer
Roth Felix, MA
Schelling Esther, PhD
Schopper Doris, MD, PhD, DPH (to 07.2001)
Wiedenmayer Karin, PhD
PhD and DVM students
Achi Louise* (PhD 2002 Toulouse, France)
Bischoff Alexander (PhD 2001)
Bossart Rita
Djaibe-Diguimbaye Colette*
Fretz Rainer
Gehler Mariacher Gabriela
Gerstl Sibylle (PhD 2001)
Granado Stefanie
Hobbins Mike
Jiagang Guo*
Kälin Nicole
Kahlmeier Sonja (PhD 2001)
Kayali Ursula (DVM 2002, Berne, CH)
Krönke Frank (PhD 2001)
Othingué Nadjitolnan
Ould Taleb Moustapha*
Paget John* (PhD 2002)
Prüss Annette(PhD 2001)
Röösli Martin (PhD 2001)
Rossett-Burkhalter Catherine (PhD 2001)
Semali Innocent, MD*
Shani Noam
Strahl Hilde
Wiese Martin* (PhD 2002, Freiburg, Germany)
Wymann Monica
Cultural Epidemiology (Section 8)
Scientists
Mitchell Weiss MD, PhD, Professor
Obrist van Eeuwijk Brigit, PhD, Senior Lecturer
Gilgen Denise, PhD (to 30.06.01)
Güngör Kenan, MA (to 31.12.00)
Research Assistants
Begrich Roger, MA (01.02.01 to 31.07.01)
Gomez Lara Maria MA, (from 01.02.02)
Keval Harshad, MA (to 31.12.00)
PhD and MD students
Ahorlu Collins
Auer Christian
Banerjee Sohini*
Fluri Pascale (MD 2001)
Parkar Shubhangi, MD*
95
96_Africa Day in the STI
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Seite 96
Africa Day in the STI
An Open Day was organised in September 2001, in the framework of the city-wide project Africa in Basel – Basel in Africa, in which
many organisations in Basel took part. The STI showed its varied activities, emphasising projects in partnership with African countries.
(Photos: R. Dürr)
Advice and information
Live parasites and vectors
Live parasites and vectors
Explanations of molecular parasitology
Tea and information in a nomad tent
Refreshments
96
UG 2+3
15.11.2002
11:10 Uhr
Seite 2
Published by the Swiss Tropical Institute, Basel, Switzerland, December 2002
Compiled and edited by Jennifer Jenkins. Cover design by Ritz & Häfliger Visual Design, Basel
Printed by KreisDruck AG, Basel
Available on the World Wide Web at http://www.sti.ch
UG 1+4
15.11.2002
11:07 Uhr
Seite 1
Swiss Tropical Institute (STI)
Socinstrasse 57
P.O. Box
CH-4002 Basel
Switzerland
Phone:
Fax:
Telex:
Web Site:
+41 (0) 61 284 81 11
+41 (0) 61 271 86 54
962508
http://www.sti.unibas.ch
Phone:
Fax:
E-Mail:
+41 (0) 61 284 82 29
+41 (0) 61 271 86 54
scih-sti@unibas.ch
Medical & Diagnostic Services
Phone:
Phone:
Fax:
+41 (0) 61 284 82 55
+41 (0) 61 284 82 56
+41 (0) 61 271 86 54
Medical Parasitology & Biology
of Infection
Phone:
Fax:
+41 (0) 61 284 82 51
+41 (0) 61 271 86 54
Public Health & Epidemiology
Phone:
Fax:
E-Mail:
+41 (0) 61 284 82 84
+41 (0) 61 271 79 51
gwe-sti@unibas.ch
Phone:
Fax:
E-Mail:
+41 (0) 61 284 82 80
+41 (0) 61 284 81 06
courses-sti@unibas.ch
Library
Phone:
Fax:
E-Mail:
+41 (0) 61 284 82 22
+41 (0) 61 284 81 06
library-sti@unibas.ch

2001/2002 - Swiss TPH

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