Thesis Reference - Archive ouverte UNIGE

Transcription

Thesis
Emergence de la maladie de Chagas en Suisse: contexte et défis de
santé publique
JACKSON, Yves-Laurent Julien
Abstract
La maladie de Chagas est l'une des maladies tropicales les plus négligées. Cette infection
parasitaire chronique, endémique en Amérique latine, affecte 8-10 millions de personnes. La
fin du XXème siècle a vu la migration de plus de 15 millions de personnes à risque vers
l'Europe, l'Amérique du Nord et l'Australie, transformant la maladie de Chagas en un
problème de santé global. La Suisse, et Genève en particulier, abrite une importante
communauté de migrants latinoaméricains. Cette thèse présente les investigations conduites
à Genève qui illustrent les dimensions épidémiologiques et sociales de cette émergence et
identifie le double fardeau de santé lié au phénomène de transition épidémiologique en cours
dans les pays d'origine. Les données locales sont discutées en regard du contexte européen
et illustrent les nouveaux défis de santé publique liés à l'hypermobilité des migrants.
Reference
JACKSON, Yves-Laurent Julien. Emergence de la maladie de Chagas en Suisse:
contexte et défis de santé publique. Thèse de privat-docent : Univ. Genève, 2014
Available at:
http://archive-ouverte.unige.ch/unige:41534
Disclaimer: layout of this document may differ from the published version.
[ Downloaded 20/11/2016 at 18:13:57 ]
Section de médecine clinique
Département de médecine
communautaire, de premier
recours et des urgences
Service de médecine de premier
recours
" Emergence de la maladie de Chagas en Suisse :
Contexte et défis de santé publique"
Thèse
présentée à la Faculté de Médecine
de l'Université de Genève
pour accéder à la fonction de privat-docent
par
______________________________________
Yves-Laurent JACKSON
Genève
2014
1
2
Résumé
La maladie de Chagas est l’une des maladies tropicales les plus négligées en raison de sa
distribution dans des populations vulnérables. Cette infection parasitaire chronique,
endémique en Amérique latine où elle est essentiellement transmise par voie vectorielle et
transplacentaire, affecte 8-10 millions de personnes. Son poids de santé publique est
important en raison des complications cardiaques tardives, sources de coûts de santé élevés.
La fin du XXème siècle a vu la migration de plus de 15 millions de personnes à risque vers
l’Europe, l’Amérique du Nord et l’Australie, transformant la maladie de Chagas en un
problème de santé global. Ceci rend nécessaire le développement de nouvelle connaissances
liées à ces changements épidémiologiques et à l’élaboration de mesures de santé publique
dans des contextes où la maladie est encore largement méconnue et insuffisamment
considérée. Outre permettre la provision de soins adaptés aux personnes infectées afin de
prévenir les conséquences tardives graves, il est impératif d’interrompre la chaîne de
transmission congénitale et par voie de transfusion et de transplantation de tissus infectés.
La Suisse, et Genève en particulier, abrite une importante communauté de migrants latinoaméricains à risque et des cas de complication sévère et de transmission ont été identifiés
dès le début des années 2000. Cette thèse présente les investigations conduites à Genève
qui illustrent les dimensions épidémiologiques et sociales de cette émergence. Elle souligne
en particulier la persistance des facteurs responsables de son statut de maladie négligée, à
savoir un fort lien avec la pauvreté et met en évidence l’apparition du concept de double
fardeau de santé (burden of disease) lié au phénomène de transition épidémiologique en
cours dans les pays d’origine. Les résultats genevois montrent l’ampleur de ce phénomène
encore largement sous-estimé et soulignent les besoins en termes d’intervention en santé
publique. Cette thèse met les données suisses en perspective avec celles de l’Europe et
discute certains nouveaux défis dans le contexte de la situation politique et économique
contemporaine.
3
Remerciements
L’exploration de l’émergence de la maladie de Chagas à Genève a été rendue possible par le
travail acharné de nombreux collaborateurs des HUG et d’institutions partenaires. Qu’ils
trouvent ici l’expression de ma sincère gratitude.
Je tiens à remercier tout particulièrement :
Le Prof. François Chappuis, mon mentor et proche ami, qui m’a ouvert à la recherche, guidé
tout au long de ces travaux, inspiré et aidé à donner le meilleur de moi-même, toujours avec
le sourire
Les Profs. Louis Loutan et Jean-Michel Gaspoz pour leur soutien et leur confiance
Les infirmières, réceptionnistes et médecins actuels et anciens de la CAMSCO (ex Umsco) qui
ont fortement contribué au succès des projets (en particulier Marylise Holst, Hans Wolff,
Tina Mazzocato, Martine Locatelli, Odile Colombel, Heidi Fowler, Gloria Griess, Elisabeth
Mouton, Graziella Singh, Claudia Estrada, Laurent Gétaz, Marius Besson, Monica Varcher,
Diana Urzola et bien d’autres)
Les membres du Groupe Chagas des HUG (Anne Mauris, Alessandro Diana, Begona Martinez
de Tejada, Claire-Anne Wyler, Cristina Reis, Klara Posfay-Barbe, Noémie Wagner)
Le Dr Pedro Albajar Vinas de l’OMS
Ainsi que toutes les organisations qui ont relayé l’information dans les communautés Latinos
à Genève
Cette thèse est dédiée à mes parents qui m’ont poussé à développer ma curiosité, à mes
amis et à Aless, Babur et Pema Lou pour la joie et la force qu’ils me donnent.
4
Table des matières
1. Introduction
1.1. Modes de transmission
p. 6
p. 7
1.2. Cours de l’infection, présentation clinique et diagnostic
p. 9
1.3. Traitement
p. 13
2. Epidémiologie et aspects de santé publique en Amérique Latine
2.1. Mouvements de population et changements épidémiologiques
p. 17
p. 18
3. Contexte suisse
3.1. Accès aux soins des migrants latino-américains
p. 19
p. 20
3.2. La maladie de Chagas en Suisse avant 2000
p. 21
3.3. Contexte des études
p. 21
4. Objectifs de la thèse
4.1 Organisation du manuscript
p. 22
p. 22
5. Prevalence, clinical staging and risk for blood-borne transmission of
Chagas disease among Latin American migrants in Geneva, Switzerland
p. 23
6. Congenital transmission of Chagas disease in Latin American immigrants
in Switzerland
p. 31
7. Paediatric Chagas disease in Europe: a series of 45 cases
from Spain and Switzerland
p. 35
8. Metabolic, mental health, behavioral and socioeconomic characteristics
in migrants with Chagas disease
p. 57
9. Chagas disease in Switzerland: history and challenges
p. 67
10. Chagas disease in European countries: the challenge of a surveillance system
p. 72
11. Need for comprehensive healthcare for T. cruzi infected immigrants in Europe
p. 83
12. Economic crisis and enhanced immigrants mobility: new challenges in the management
of Chagas disease in Europe
p.87
13. Discussion
13.1. Principaux résultats
13.2. Défis de santé publique à relever et futures orientations de recherche
p. 93
p. 93
p. 98
14. Conclusions
p.101
15. Références
p.102
5
1. Introduction
La maladie de Chagas, l’une des infections parasitaires majeures en Amérique du Nord,
Centrale et du Sud, affectes les humains depuis plusieurs millénaires. Des extraits d’ADN de
kinétoplaste de Trypanosoma cruzi identifiés dans des tissus biologiques extraits de momies
datant de plus de 7000 ans au Chili et au Pérou (Aufderheide et al., 2004). De nos jours,
cette maladie ancienne continue à peser d’un poids substantiel en termes de santé publique
et de coûts économiques dans les régions endémiques (WHO, 2010).
La première description de l’infection est l’œuvre de Carlos Chagas (1878-1934) en 1909, un
jeune médecin brésilien envoyé par l’Institut Oswaldo Cruz de Rio de Janeiro dans la
Province du Minais Gerais pour investiguer une épidémie de fièvre supposément d’origine
palustre (Chagas, 1909a, 1909b; Petraglia Kropf, 2011). Dr Chagas identifia alors non
seulement le parasite et son principal vecteur mais également le cycle parasitaire complet
ainsi que les principaux éléments cliniques de l’infection, ce qui lui valut d’être nommé deux
fois (1913 et 1921) pour recevoir le prix Nobel de médecine, sans succès.
L’Organisation Mondiale de la Santé (OMS) considère la maladie de Chagas comme l’une des
infections tropicales les plus négligées en raison de son association avec la pauvreté et du
fait qu’elle affecte essentiellement des populations vulnérables dénuées de poids politique
(WHO, 2010). Elle bénéfice de peu d’intérêt scientifique et ne fait pas l’objet
d’investissements en recherche et développement suffisants de la part de l’industrie
pharmaceutique en raison d’un potentiel commercial jugé trop faible (Chatelain & Loset,
2011; Trouiller et al., 2002). Ceci contribue à expliquer sa place marginale sur l’échiquier de
la santé globale.
Malgré plusieurs résolutions de l'Assemblée Mondiale de la Santé appelant à une attention
accrue aux conséquences de la maladie sur la santé humaine et à son poids socioéconomique, les efforts de santé publique et la recherche scientifique ont été limités par
l’écart important entre les besoins et les moyens à disposition (CHRD, 1990; Lancet, 2006).
Le fait que le dernier médicament mis sur le marché pour cette indication remonte à 1971
constitue un exemple de la négligence dans laquelle la maladie de Chagas se trouve
actuellement. Plusieurs initiatives transnationales centrées sur la lutte vectorielle en
Amérique Latine ont permis une réduction notable de la prévalence au cours de la seconde
moitié du XXème siècle (Schofield, Jannin, & Salvatella, 2006). Néanmoins, les résultats de
6
ces efforts ont été limités par les difficultés politiques, financières et administratives sur le
long terme et sur la persistance d’un important réservoir humain.
Certains indicateurs montrent néanmoins que cette situation évolue depuis quelques
années. Le nombre de publications scientifiques, tant cliniques que de santé publique ou de
recherche fondamentale, consacrés à la maladie de Chagas a substantiellement augmenté
depuis la fin du XXème siècle, attestant d’une attention accrue. De plus, l’émergence du
concept de Maladies Tropicales Négligées (NTD) sur la scène de la Santé Globale, attestée
par la création d’un Département de Contrôle des NTD au sein de l’OMS et d’initiatives
internationales d’envergure avec la mise à disposition de fonds importants telles que lors de
la Déclaration de Londres (The London Declaration on Neglected Tropical Diseases, 2012), a
permis aux efforts de lutte contre la maladie de Chagas de recevoir des ressources
jusqu’alors inégalées. Il est probable que l’arrivée d’un nombre croissant de personnes à
risques ou porteuse de la maladie dans les pays développés ait également facilité cette
évolution. Ainsi, c’est le processus d’internationalisation de la maladie qui pourrait s’avérer
être un facteur clé dans l’amélioration de sa prise en charge et la réduction de ses effets
délétères sur la santé humaine. La Suisse figure parmi les pays récemment touchés par cette
évolution, tant par le fait même de l’émergence locale de la maladie de Chagas que par le
développement de savoir qui y a eu lieu.
Cette thèse aborde donc ce phénomène d’émergence internationale avec un focus sur la
Suisse en mettant particulièrement l’accent sur les aspects de santé publique. Une thèse de
PhD auprès de l’Université d’Anvers (Belgique) rédigée en parallèle par l’auteur, se
concentre sur le développement du savoir en relation avec les aspects cliniques de la
maladie. Afin de faire le lien entre les deux travaux, le texte contient des encarts résumant
les principaux résultats présentés dans la thèse de PhD.
1.1. Modes de transmission
La maladie de Chagas est consécutive à l’infection par Trypanosoma cruzi, par un protozoaire
flagellé de la famille des kinétoplastes. C’est avant tout une zoonose qui affecte un grand
nombre d’espèces distinctes, dont des animaux péri-domestiques et domestiques, et
l’homme est considéré comme un hôte accidentel (WHO, 2002). Le mode de transmission
principal est vectoriel. Plusieurs vecteurs de la famille des triatominés, des insectes
7
hématophages, sont capables de transmettre le parasite, dont les principaux sont Triatoma
infestans, T.diminuta et Rhodnius prolixus dans un contexte domestique (image 1). Des
cycles vectoriels péri-domestiques ou sylvatiques sont impliqués dans un nombre moindre
d’infections humaines. La distribution géographique des vecteurs détermine les zones
d’endémicité en Amérique Latine.
Image 1 : Triatome vecteur de T. cruzi. (CDC, 2010).
Le cycle parasitaire entre le vecteur et l’hôte est relativement simple (figure 1). Après un
repas sanguin, le plus souvent nocturne, la reflexe gastro-colique du vecteur mène à
l’évacuation de fèces riches en parasites. Ceux-ci pénètrent alors l’organisme soit par le
point de ponction soit par voie trans-muqueuse telle qu’à travers les muqueuses digestives
ou conjonctivales. Le parasite se retrouve sous deux formes chez l’humain, à savoir une
forme trypomastigote flagellée motile dans le système vasculaire et une forme amastigote,
métaboliquement moins active, essentiellement présente dans les tissus musculaire et
nerveux.
Figure 1 : Cycle parasitaire de T.cruzi entre le vecteur et l’hôte humain. (CDC, 2010).
La transmission materno-fœtale représente le mode de transmission non-vectoriel principal.
Elle dépend de la parasitémie et de facteurs immunologiques complexes. Le risque s’élève à
1-10% (Howard, Xiong, Carlier, Sosa-Estani, & Buekens, 2013). La transfusion de produits
8
sanguin contaminés, surtout de concentrés plaquettaires, représente une autre voie de
transmission importante, surtout jusqu’à l’époque récente marquée par le manque de
dépistage systématique des donneurs à risque. On estime à 10-20% le risque de transmission
par cette voie (WHO, 2002). De façon similaire, la transmission par transplantation d’organes
ou de tissus infectés a pris de l’importance avec le développement de ces procédures en
zone endémiques au cours des dernières décennies (Altclas, Barcan, Nagel, Lattes, & Riarte,
2008). Bien que responsable d’un nombre d’infections limité, ce mode engendre des coûts
de santé très élevés. Récemment, la transmission par voie d’ingestion d’aliments et de
liquides contaminés a causé un nombre croissant de petites épidémies localisées lorsque des
vecteurs sylvatiques entrent en contact avec la chaine de production alimentaire tel que
dans l’industrie de la canne à sucre ou de l’huile de palme (Alarcon de Noya et al., 2010).
1.2. Cours de l’infection, diagnostic et présentation clinique
Le cours de l’infection par T.cruzi inclut plusieurs stades et se manifeste par une variété de
tableaux cliniques qui en fait une maladie souvent difficile à distinguer cliniquement (Figure
2). La pénétration du parasite dans l’organisme est le plus souvent silencieuse. Cette phase
aigüe, qui dure généralement deux à quatre semaines se caractérise par une importante
parasitémie. Elle se manifeste dans 10% des cas par un syndrome fébrile aspécifique parfois
associé à une polyadénopathie, une hépatosplénomégalie et plus exceptionnellement par
une myocardite ou une encéphalite potentiellement sévères. En cas de pénétration par voie
conjonctivale, une tuméfaction palpébrale et péri-oculaire localisée représente un signe
pathognomonique (signe de Romaña). Le diagnostic à ce stade repose sur des méthodes
parasitologiques telles que la recherche de trypomastigotes à l’examen sanguin
microscopique après concentration ou par l’identification d’ADN circulants par des tests de
dépistage d’acides nucléiques (PCR). La culture ou le xénodiagnostique (détection parasites
dans un vecteur après repas de sang d’un patient supposément infecté) ne se pratiquent
plus en raison de leur complexité et du délai pour obtenir des résultats.
9
Figure 2 : Evolution de l’infection par Trypanosoma cruzi chez l’homme (inspiré de Rassi et
al., 2010)
En l’absence de traitement antiparasitaire à ce stade, la parasitémie s’atténue alors que les
parasites se déposent dans les tissus sous forme d’amastigotes (image 2). L’infection devient
chronique. La phase indéterminée est caractérisée par une absence de symptômes et de
signes cliniques identifiables, un électrocardiogramme normal et une sérologie positive. La
vaste majorité des personnes infectées dans le monde présente cette forme clinique (Prata,
2001).
Image 2 : Formes amastigotes de T. cruzi regroupées en amas dans le stroma placentaire
A ce stade, le diagnostic repose sur des méthodes immunologiques indirectes en l’absence
de quantité suffisante de parasites dans la circulation sanguine pour être identifiés par les
méthodes décrites ci-dessus. La PCR à ce stade n’a au mieux qu’une sensibilité de 80%
(Schijman et al., 2011). Plusieurs techniques sérologiques (ELISA, immunofluorescence,
Western Blot, etc.) offrent une excellente spécificité diagnostique (Bern et al., 2007; Rassi,
10
Rassi, & Marin-Neto, 2010). La sensibilité imparfaite, bien que proche des 99% avec les tests
de nouvelle génération, la présence de résultats parfois discordants et le risque de réaction
croisée avec d’autres espèces de trypanosomes (T. rangeli notamment) ou de leishmanies
sous-tendent la recommandation d’utiliser deux tests sérologiques distincts avec différents
antigènes ou différentes techniques afin de diagnostiquer l’infection à ce stade (WHO,
2002).
Récemment, le développement de tests immunochromatographiques rapides a permis de
faciliter la démarche diagnostique en limitant le besoin de recourir à des méthodes de
laboratoires coûteuses et souvent peu faciles d’accès hors des centres médicaux principaux
en milieu urbain. Ceci a également un impact potentiel sur le dépistage de l’infection dans
des populations difficiles d’accès en milieu urbain en Europe (encart 1).
Encart 1 : Performance d’un test diagnostic rapide pour la détection de l’infection par
Trypanosoma cruzi dans une population migrante latino-américaine (Chappuis et al.,
2010)
Les résultats du test rapide immunochromatographique Chagas Stat-Pak® effectué sur le
sang complet et le sérum de 999 participants migrants latino-américains adultes vivant à
Genève ont été comparés aux résultats de deux tests ELISA (standard de référence).
Un total de 125 (12.5%) participants a présenté une infection. La sensibilité et la
spécificité du Chagas Stat-Pak® sur le sang complet étaient de 95.2% (95% intervalle de
confiance (95% IC) : 89.2% - 97.9%) et 99.9% (95% IC : 99.3% à 100%), respectivement.
Sur le sérum, elles étaient de 96% (95% IC : 91% à 98.3%) et de 99.8% (95% IC : 99.2% à
99.9%). La concordance des résultats entre sang complet et sérum était supérieure à
99.7% alors que les valeurs prédictives positives et négatives dans cette population
étaient supérieures à 98%.
Les performances de ce test permettent son utilisation parmi les adultes migrants à
risque en Europe. Le léger déficit de sensibilité doit être mis en balance avec la facilité
d’utilisation et sa capacité à produire un résultat immédiat qui facilitent l’accès au
diagnostic aux personnes à risque hors des centres de santé.
11
Cette infection silencieuse évolue dans 20-40% des cas vers une atteinte d’organe après
plusieurs décennies. Les mécanismes immunopathologique, encore mal compris,
impliquent probablement des processus auto-immuns s’ajoutant à une toxicité directe du
parasite (Lescure et al., 2010; Rassi et al., 2010).
L’atteinte cardiaque est la principale complication en termes de fréquence et de gravité.
Cette atteinte inflammatoire segmentaire chronique évolue vers une destruction du tissus
myocardique remplacé par de la fibrose, responsable d’une dilatation progressive (MarinNeto, Cunha-Neto, Maciel, & Simoes, 2007). La perte de fonction contractile et la
transformation morphologique mènent à une insuffisance cardiaque le plus souvent globale
(Blum, Zellweger, Burri, & Hatz, 2008). Une fois la cardiomyopathie dilatée établie, une
déformation sacculaire de l’apex du ventricule gauche fibrosé peut évoluer vers un
anévrisme associé à un fort risque d’une thrombose source d’embolies périphériques. De
plus, l’inflammation myocardique chronique engendre une hyperexcitabilité ventriculaire
source d’arythmies alors que le processus fibrosant peut porter atteinte à l’intégrité des
faisceaux de conduction (Rassi et al., 2010). Ainsi, la cardiomyopathie chagasique s’exprime
cliniquement par l’association de risque d’insuffisance cardiaque progressive bilatérale, de
troubles de la conduction intra-auriculaires, intra-ventriculaire ou atrio-ventriculaire,
d’arythmies ventriculaires et d’accidents vasculaires cérébraux (AVC) (Rassi et al., 2010). En
zone endémique, cette infection représente effectivement un facteur de risque majeur pour
les AVC (Carod-Artal & Gascon, 2010).
Le système digestif est le deuxième appareil le plus souvent atteint. L’infection chronique
mène à la destruction progressive des cellules nerveuses des plexus sous-muqueux (de
Oliveira, Troncon, Dantas, & Menghelli, 1998). Selon la localisation préférentielle de ce
processus, il s’ensuit une perte du tonus puis une dilatation soit de l’œsophage soit du colon
(de Rezende, Lauar, & de Oliveira, 1960). L’évolution et l’expression clinique ressemble à une
achalasie dans le cas d’atteinte oesophagienne ou de maladie de Hirschprung lorsque le
colon est atteint. Le stade final de ce processus est le syndrome des mégas organes en cas
de dilatation massive, souvent fatale.
12
1.3. Traitement et marqueurs de guérison
La prise en charge thérapeutique repose sur les traitements étiologiques (antiparasitaires)
ainsi que sur les traitements ciblant les organes secondairement endommagés. A l’heure
actuelle, seules deux molécules ont été enregistrées pour la maladie de Chagas. Le
benznidazole, un 2-nitroimmidazole, a été commercialisé par Roche en 1969 alors que le
nifurtimox, un 5-nitrofurans, l’a été par Bayer en 1971. Depuis lors, en l’absence de
conditions-cadres favorables à la recherche et d’un manque de potentiel économique pour
les fabricants, aucun autre médicament n’a été mis sur le marché malgré de récents efforts
de développements de nouveaux dérivés azolés (Chatelain & Loset, 2011; Ribeiro et al.,
2009). D’autres molécules telles que l’allopurinol ou d’anciens dérivés azolés ont montré une
efficacité partielle in vitro ou lorsqu’utilisées en combinaison mais n’ont pas fait l’objet d’une
reconnaissance et de recommandations d’utilisation (Apt, 2010; Apt et al., 2013; PerezMazliah et al., 2013).
Le cas du nifurtimox et le benznidazole reflète parfaitement la situation de négligence dans
laquelle se trouve la maladie de Chagas ainsi que d’autres infections tropicales dites
négligées. Ils partagent des caractéristiques communes telles qu’un relatif manque de
données d’efficacité et de sécurité dans les phases pré- et post-mise sur le marché, la
nécessité de longues durées de traitement (30 à 120 jours) et un profil de tolérance mal
connu, particulièrement chez l’adulte utilisant le nifurtimox (encart 2) (Le Loup, Pialoux, &
Lescure, 2011). Aucune étude comparative n’a permis de déterminer leur efficacité sur les
différentes souches de T. cruzi. Ceci explique la qualité relativement limitée des preuves
sous-tendant les recommandations thérapeutique et la place proéminente prise par les
recommandations basées sur des avis d’experts (Bern, 2011). De plus, leur production et
disponibilité a régulièrement fait l’objet d’incertitude, limitant leur utilisation à large échelle
(Ribeiro et al., 2009; Schofield et al., 2006).
Les objectifs et modalités du traitement antiparasitaire différent selon le stade de la
maladie. La guérison peut être obtenue dans environ 80-100% des cas lorsque le traitement
antiparasitaire est appliqué à la phase aigüe ou très précoce, essentiellement chez les
enfants de moins de deux ans (Bern, 2011; Lescure et al., 2010; Sosa-Estani & Segura, 2006).
L’efficacité réelle des traitements étiologiques dans les phases non-aigüe fait encore l’objet
de controverses mais il est communément admis qu’elle ne dépasse pas 30-50%, étant
13
inversement proportionnelle à la durée de l’infection (J. Coura & De Castro, 2002; Urbina,
2009). Chez l’adulte au stade chronique, l’objectif du traitement repose davantage sur la
prévention des complications que sur l’éradication de l’infection. Parmi les rares données
disponible figure une étude prospective non randomisée montrant une diminution
substantielle du risque d’évolution vers un changement de phase ou une aggravation des
dommages d’organe suite à la prise de benznidazole (Viotti et al., 2006). Cette étude est
quasiment la seule source des recommandations thérapeutiques récentes qui ont élargi
l’indication au traitement antiparasitaires aux adultes à la phase chronique de la maladie
(Bern et al., 2007). En effet, les pays endémiques ont traditionnellement restreint les
recommandations d’utilisation des antiparasitaires aux phases aigües ou très précoces
menant aux taux de guérison les plus importants (J. R. Coura, 2009). L’étude randomisée
contrôlée BENEFIT en cours, la plus large menée à ce jour, devrait permettre de récolter de
précieuses informations quant à l’efficacité et la sécurité du benznidazole chez l’adulte.
Encart 2 : Utilisation du nifurtimox chez l’adulte (Jackson, Alirol, et al., 2010)
Une étude observationnelle a évalué la tolérance et la sécurité du nifurtimox chez quatrevingt-un patients adultes à la phase chronique recevant 10mg/kg/j en 3 doses pendant 60
jours avec un suivi médical à J7, 21 et 60 et selon besoins. Les endpoints étaient
l’interruption de traitement et la survenue et le type des effets indésirables.
Huit patients ont été perdus de vue. Sur les 73 restants, 32 (43.8%) ont interrompu leur
traitement avant les 60 jours en raison d’effets indésirables (EI). 97.5% ont subis des EI, la
plupart de gravité légère ou moyenne et 7.4% ont présenté des EI sévères non attendus
(SUSARs). Les patients présentant 3ou plus EI avaient un risque augmenté d’interruption
définitive de traitement (hazard ratio : 8.42 ; 95% IC : 1.6-45.5).
Cette étude conclut que le nifurtimox est mal toléré chez les patients adultes en phase
chronique et mène à de fréquentes interruptions prématurées de traitement. De plus, la
survenue d’effets indésirables graves représente une limitation à la distribution de ce
traitement en situation ne permettant pas un suivi clinique rapproché.
Les traitements non-étiologiques servent à limiter les conséquences des atteintes d’organe.
Actuellement, il n’existe pas de traitement permettant de guérir ces dommages une fois
qu’ils sont présents (Le Loup et al., 2011; Rassi et al., 2010). IN cas d’atteinte cardiaque, des
14
médicaments anti-arythmiques et contre l’insuffisance cardiaques sont utilisés bien
qu’aucune données de qualité de permette de soutenir des recommandations (Bern, 2011;
Blum et al., 2008). En cas d’atteinte avancée, la pose d’un pacemaker, d’un défibrillateur
interne voir la transplantation cardiaque représentent les seules options thérapeutiques. A
ce titre, l’infection par T. cruzi représente une des étiologies principales à l’origine des
transplantations cardiaques en zone d’endémie, notamment en Argentine (Bestetti &
Theodoropoulos, 2009).
Concernant les atteintes du tractus digestif, encore moins de données permettent d’émettre
des recommandations solides (Pinazo, Canas, et al., 2010). Il est généralement admis qu’en
cas d’atteinte avancée avec troubles de la motilité marqués, voir en présence de dilatation,
le traitement chirurgical est le seul à permettre un contrôle des symptômes et à réduire les
risques de complication.
L’une des autres difficultés cliniques majeures actuelles réside dans l’absence de marqueur
de réponse au traitement chez l’adulte à la phase chronique. En effet, si lors de phase aigüe
ou précoce (<2 ans) on observe la disparition rapide de la parasitémie et la négativation de la
sérologie respectivement, la réponse humorale lors de la phase chronique persiste de
nombreuses années après l’administration du traitement et empêche de mesurer l’effet de
l’intervention (encart 3). De plus, cette absence de marqueur a un effet limitant sur la
capacité de tester de nouvelles substances antiparasitaires. Malgré cela, l’OMS recommande
l’utilisation de la sérologie comme marqueur de guérison chez l’adulte (WHO, 2002). Etant
donné la médiocre sensibilité de la PCR à la phase chronique, cette technique ne permet pas
non plus d’évaluer la réponse thérapeutique (Ramirez et al., 2009).
De nouveaux marqueurs de réponse au traitement et de nouvelles techniques d’analyse sont
actuellement en voie d’évaluation. Parmi ceux-ci figurent l’évaluation quantitative de la
réponse sérologique, de la réponse immune T-spécifique, le suivi de bio-marqueurs par
l’analyse protéomique et la cytométrie de flux (Fernandez-Villegas et al., 2011; Laucella et
al., 2009; Ndao et al., 2010; Vitelli-Avelar et al., 2007).
15
Encart 3 : Suivi sérologique et par PCR trois ans après traitement par nifurtimox
(Jackson et al., 2013)
Cette étude prospective a suivi 37 patients adultes à la phase chronique traités par
nifurtimox 3 ans auparavant. L’objective était d’observer la réponse thérapeutique en
comparant les résultats de deux tests sérologiques ELISA et d’un test diagnostique rapide
(Chagas Stat-Pak®) sur le sérum pré- et 3 ans post-traitement. De plus, une recherche de
parasite circulant à été effectuée par PCR sur le sérum post-traitement.
Aucun des tests sérologiques, ELISA ou rapides, effectués sur des sera post-traitement
n’était négatif mais 28 (75.3%) montraient des titres abaissés par rapport au niveau prétraitement. De plus, la PCR était positive dans un (2.7%) sérum.
Ces résultats démontrent le manque d’intérêt de la sérologie comme marqueur de
guérison chez des adultes au stade chronique traités par nifurtimox dans la pratique
clinique. Dans cette cohorte, 97.3% des participants avaient des résultats pouvant soit
indiquer un échec de traitement soit la persistance d’une réponse humorale malgré un
traitement efficace.
16
2. Epidémiologie et aspects de santé publique de la maladie de Chagas en
Amérique Latine.
La distribution géographique et populationnelle de la maladie de Chagas en Amérique latine
a subi d’importants changements au cours des dernières décennies. En effet, alors qu’elle se
rencontrait essentiellement dans les zone rurales des pays d’Amérique centrale et du Sud,
les efforts de lutte anti-vectorielle, les transformations écologiques consécutives au
développement de nouvelles pratiques d’agriculture industrielle associés aux mouvements
de population vers les zones urbaines ont profondément modifié son épidémiologie.
Traditionnellement, la zone d’endémie se définissait par la présence de vecteurs et couvrait
une vaste surface de 21 pays allant du sud des Etats-Unis jusqu’à l’Argentine (figure 3). Dans
les années 1980, environ 15-20 millions de personnes étaient infectées et 100 millions
étaient à risque d’infection (WHO, 2002). Des initiatives nationales et transnationales de
contrôle vectoriel ont permis une nette réduction du taux d’incidence (environ 40'000 par
an) et la prévalence s’est stabilisée autour de 10 millions de personnes en 2009 (PAHO,
2006; WHO, 2010). La transmission de T. cruzi par voie transfusionnelle a traditionnellement
joué un rôle important dans certains pays caractérisés par l’absence de régulation, la faible
capacité à les faire respecter et la popularité du don pour des motifs économiques (WHO,
2002). La progressive mise en place du screening universel des donneurs de sang contribué à
réduire le nombre de cas de transmission transfusionnelle, rendant cette route relativement
marginale (Schmunis, Rodriguez, Coenen, Bellorin, & Gianella, 2008). Il en va de même pour
la prévention secondaire de l’infection congénitale avec l’augmentation des programmes de
dépistages des femmes enceintes, le screening des nouveau-nés de mères infectées et
l’accès amélioré au traitement des femmes jeunes avant leur première grossesse.
De nos jours, la maladie est particulièrement prévalente en Bolivie (5-20% de la population
selon les provinces) et l’Argentine, le Mexique et le Brésil sont les pays avec le plus grand
nombre de personnes infectées.
La charge (burden of disease) sociale et économique de cette infection est substantielle en
Amérique Latine du fait de sa chronicité et de la potentielle sévérité des complications. Des
modèles montrent que dans cette région, l’infection est responsable de la perte annuelle de
0.51 DALY avec un coût de $ 474.- par personne au stade chronique et de 7 milliard
17
globalement, nettement plus que d‘autres infections parasitaires (malaria) ou virales (HIV)
(B. Lee, Bacon, Bottazzi, & Hotez, 2013).
Figure 3 : Distribution des cas de maladie de Chagas en Amérique Latine 2006-2009 (WHO,
2010)
Actuellement, aucun vaccin humain n’est disponible bien que plusieurs études sur des
animaux soient en cours avec des résultats prometteurs et que le potentiel économique d’un
tel vaccin ai été bien démontré (Gupta et al., 2013; B. Y. Lee, Bacon, Connor, Willig, & Bailey,
2010). Par ailleurs, certains auteurs ont argumenté que le succès des campagnes antivectorielle passées constituait un risque pour le contrôle de la maladie en raison de la baisse
de la vigilance et des investissements financiers et structurels dans les pays les plus à risque
(Jose Rodrigues Coura & Vinas, 2010; Schofield et al., 2006).
2.1. Mouvements de population et changements épidémiologiques
Depuis les années 80’, les transformations sociales, politiques et économiques des pays
endémiques ont générés des flux migratoires massifs des campagnes vers les zones urbaines
et entre pays voisins (Moscatelli et al., 2013). Ceci a eu pour conséquence une progressive
urbanisation de la maladie avec un nombre croissants de personnes infectées vivant en zone
(péri) urbaine et une adaptation de certains vecteurs à cet environnement les rendant
18
capable de transmettre T. cruzi associé à une augmentation de la proportion de la voie
congénitale parmi les nouveaux cas (Medrano-Mercado et al., 2008; Moscatelli et al., 2013).
Si cette évolution peut théoriquement être source de facilitation dans l’accès au dépistage et
aux soins des populations à risque, tel qu’attesté par l’augmentation du nombre de cas
congénitaux détectés, il semble qu’en fait ce soient les populations vulnérables,
généralement à plus faible potentiel d’accès aux services médicaux et de santé publique, qui
soient majoritairement affectées. A Buenos Aires par exemple, seules 16% des femmes
enceintes infectées étaient originaires de la ville, le reste étant des migrants des Provinces
endémiques argentines ou des pays voisins (Moscatelli et al., 2013). A Arequipa au Pérou et
à Cuernavaca au Mexique, la densité d’infestation de triatomes vecteurs augmente avec le
degré de pauvreté des quartiers examinés (Delgado et al., 2013; Ramsey et al., 2005). A cela
s’ajoutent les nouveaux risques liés à la transmission par voie alimentaire à grande échelle
comme lorsque plus de 1000 personne furent exposées à du jus de goyave infecté à Caracas
(Venezuela), résultant en plus de 100 infections (Alarcon de Noya et al., 2010).
3. Contexte suisse
La Suisse a une riche histoire de relations diplomatiques et commerciales et d’échange de
populations avec l’Amérique Latine. Au XIXème siècle, des suisses, paysans appauvris,
travailleurs qualifiés ou personnes tombées à l’aide sociale dont l’Etat fédéral cherchait à se
débarrasser, émigrent en grand nombre d’abord au Brésil puis dans les pays du cône sud
(Argentine, Chili, Uruguay) (Veyrassat, 2007). Des colonies suisses voient le jour (Nova
Friburgo près de Rio de Janeiro) et les échanges commerciaux s’intensifient. Au tournant du
XXème siècle, 15% des émigrants suisses vivent en Amérique Latine.
Les flux migratoires se renversent dans la seconde moitié du XXème siècle et s’accélèrent dans
les années 70’ et 80’ à la faveur des troubles politiques au Chili et en Argentine. La Suisse
accueille alors de nombreux réfugiés latino-américains et des travailleurs qualifiés
(Portmann-Tinguely & von Cranach, 2013). Les bouleversements politiques internationaux et
l’essor des échanges mondialisés des années 90’ favorisent l’arrivée d’une nouvelle – et
importante – population migrante à la recherche d’opportunités économiques. En 2004,
l’Offices migration publie un rapport dans lequel on estime que sur les 50'000 à 300'000
19
migrants sans permis de séjours (sans-papiers) résidants en Suisse, une proportion
importante est d’origine latino-américaine (Office des migrations, 2004). Quant à Genève,
elle abrite l’une des communautés latino-américaines principales du pays, estimées à
environ 10'000 personnes, incluant des migrants surtout femmes d’origine colombiennes,
équatoriennes, boliviennes et péruviennes (Fluckiger & Pasche, 2005).
Il faut également souligner que le développement du tourisme vers les zones d’endémies
avec la baisse des prix du transport aérien de masse dès la fin du XXème siècle amène un
nombre croissant de résidents suisses à s’exposer au risque d’infection par voie vectorielle.
De plus, les activités humanitaires du CICR et d’autres organisations internationales amènent
de nombreux expatriés à vivre en zone rurale endémique.
3.1. Accès aux soins des migrants latino-américains en Suisse
Si les migrants résidant ont l’obligation de contracter une assurance-maladie et accès aux
subsides cantonaux pour bénéficier des soins en Suisse en cas de difficultés financières, les
migrants sans-papiers sont dans un premier temps exclu de ce système mis en place lors de
la mise en application de la loi sur l’assurance-maladie (LAMal) en 1996. Cette exclusion est
ensuite levée mais la plupart des sans-papiers n’accèdent pas à l’assurance pour des motifs
économiques ou de méconnaissance du système (Wolff et al., 2005).
En 1997, le Conseil d’Etat genevois charge les HUG de mettre sur pieds une structure d’accès
aux soins pour les résidents les plus vulnérables socialement du canton. L’Unité Mobile de
Soins Communautaires (UMSCO) est alors rattachée au Département de Médecine
Communautaire et reçoit une clientèle latino-américaine rapidement croissante. Ces
patients peuvent alors bénéficier de soins de médecine générale et des spécialités,
permettant d’identifier un spectre de nouveaux problèmes de santé internationale. A
l’exception du canton de Vaud, aucune autre région ne se dote d’un tel système public
d’accès aux soins pour les sans-papiers.
20
3.2. La maladie de Chagas en Suisse avant 2000
Les premiers cas rapportés de maladie de Chagas en Suisse remontent aux années 80’
(Liechti, Baur, Gurtner, & Straub, 1990). Il s’agit alors de cas sporadiques, fortement
symptomatiques, identifiés chez des migrants latino-américains tardivement dans le cours
de la maladie. En 1996, Sztajzel rapporte le premier cas vu à Genève (Sztajzel et al., 1996). Il
s’agit d’une patiente bolivienne de 56 ans consultant au Département de Médecine
Communautaire pour une constipation sévère. Elle présente une cardiomyopathie avancée
associée à des troubles du rythme et de la conduction. Les auteurs concluent qu’il est
indispensable que les médecins de premier recours et spécialistes en Europe soient
conscients de l’émergence de cette maladie méconnue. En effet, outre la place très
modeste accordée à l’enseignement des maladies tropicales durant les études de médecine
en Suisse, aucune réglementation de santé ne dirige les cliniciens vers une meilleure
conscience du problème. A l’exception du paludisme, ces maladies ne sont généralement
pas à déclaration obligatoire. La seule mesure à visée préventive existante consiste en une
série de questions pré-donation permettant d’exclure des potentiels donneurs de sang à
risque. Le donneurs répondant positivement à l’une ou plusieurs des questions de
dépistages sont alors exclues sans que leur soit proposé un dépistage.
3.3 Contexte des études
Les études qui constituent le corps de cette thèse ont été menées dans le cadre des activités
du Département de Médecine Communautaire, de Premier recours et des Urgences des
Hôpitaux Universitaires de Genève (HUG) entre 2006 et 2011. Ces projets successifs ont fait
suite au nombre croissant de cas cliniques rencontrés aux HUG depuis le début des années
2000 et à la réalisation par les auteurs du manque de connaissance clinique et
épidémiologique en relation avec l’émergence de cette infection. Ces études ont été
rendues possible par la collaboration entre divers départements des HUG ainsi que grâce aux
collaborations et au soutien de l’OMS et de multiples organisations actives auprès des
communautés latino-américaines dans le Canton de Genève.
21
4. Objectifs de la thèse
Cette thèse a pour objectif principal de décrire l’émergence de la maladie de Chagas en
Suisse avec un focus sur Genève. Alors que les aspects cliniques de ce phénomènes sont
traités dans ma thèse de PhD (Jackson, 2014, in press), ce travail se concentre sur les aspects
de santé publique. Plus précisément, il aborde les aspects épidémiologiques, explore le
contexte de cette émergence par l’identification des caractéristiques socio-économiques des
personnes infectées et discute les défis de la prise en charge au niveau populationnel en
Europe en temps de crise économique et financière.
4.1. Organisation du manuscrit
Après avoir présenté des notions générales sur la maladie de Chagas et décrit le contexte
dans lequel les différentes études ont été menées à Genève, cette thèse inclut les
principales publications touchant aux aspects de santé publique et se conclut par une
discussion des résultats.
Le premier papier décrit une étude transversale menée auprès de communautés migrantes
latino-américaines à Genève visant à établir la prévalence de la maladie, sa description
clinique et le risque de transmission par voie de transfusion sanguine. Le second papier
décrit les premiers cas de transmission congénitale et évalue le risque chez les femmes
enceintes latino-américaines sans-papiers consultants aux HUG. Le papier suivant rapporte
la première série de cas pédiatriques en Europe. Le quatrième article explore la situation
socio-économique des personnes infectées à Genève dans une perspective de déterminants
sociaux de la santé.
Les papiers 5 et 6 rapportent des données au niveau suisse et européen afin de mettre la
situation genevoise en perspective, tandis que les deux derniers papiers ouvrent une
discussion sur les challenges et l’impact de la crise économique et financière sur le contrôle
de la maladie de Chagas en Europe.
22
5. Prevalence, clinical staging and risk for blood-borne transmission of Chagas
disease among Latin American migrants in Geneva, Switzerland
Cet article a été publié dans:
PLoS Negl Trop Dis 2010;4(2):e592 doi10.1371/journal.pntd.0000592
par:
Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin A, Sztajzel J, Besse V, Loutan L, Gaspoz
JM, Jannin J, Albajar-Vinas P, Luquetti A, Chappuis F.
23
Prevalence, Clinical Staging and Risk for Blood-Borne
Transmission of Chagas Disease among Latin American
Migrants in Geneva, Switzerland
Yves Jackson1*, Laurent Gétaz1, Hans Wolff1, Marylise Holst1, Anne Mauris2, Aglaé Tardin3, Juan
Sztajzel4, Valérie Besse5, Louis Loutan3, Jean-Michel Gaspoz1, Jean Jannin6, Pedro Albajar Vinas6,
Alejandro Luquetti7, François Chappuis3
1 Division of Primary Care Medicine, Department of Community Medicine And Primary Care, University Hospitals of Geneva and Faculty of Medicine, Geneva University,
Geneva, Switzerland, 2 Division of Humanitarian and International Medicine, Department of Community Medicine and Primary Care, University Hospitals of Geneva and
Faculty of Medicine, Geneva University, Geneva, Switzerland, 3 Department of Genetics and Laboratory, University Hospitals of Geneva and Faculty of Medicine, Geneva
University, Geneva, Switzerland, 4 Division of Cardiology, Department of General Internal Medicine, University Hospitals of Geneva and Faculty of Medicine, Geneva
University, Geneva, Switzerland, 5 Department of Radiology, University Hospitals of Geneva and Faculty of Medicine, Geneva University, Geneva, Switzerland, 6 Control of
Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland, 7 Laboratorio de Chagas, Hospital das Clinicas, Universidade Federal de Goiás, Goiania,
Brazil
Abstract
Background: Migration of Latin Americans to the USA, Canada and Europe has modified Chagas disease distribution, but
data on imported cases and on risks of local transmission remain scarce. We assessed the prevalence and risk factors for
Chagas disease, staged the disease and evaluated attitudes towards blood transfusion and organ transplant among Latin
American migrants in Geneva, Switzerland.
Methodology/Principal Findings: This cross-sectional study included all consecutive Latin American migrants seeking
medical care at a primary care facility or attending two Latino churches. After completing a questionnaire, they were
screened for Chagas disease with two serological tests (Biomérieux ELISA cruzi; Biokit Bioelisa Chagas). Infected subjects
underwent a complete medical work-up. Predictive factors for infection were assessed by univariate and multivariate
logistic regression analysis.1012 persons (females: 83%; mean age: 37.2 [SD 11.3] years, Bolivians: 48% [n = 485]) were
recruited. 96% had no residency permit. Chagas disease was diagnosed with two positive serological tests in 130 patients
(12.8%; 95%CI 10.8%–14.9%), including 127 Bolivians (26.2%; 95%CI 22.3%–30.1%). All patients were in the chronic phase,
including 11.3% with cardiac and 0.8% with digestive complications. Predictive factors for infection were Bolivian origin (OR
33.2; 95%CI 7.5–147.5), reported maternal infection with T. cruzi (OR 6.9; 95%CI 1.9–24.3), and age older than 35 years (OR
6.7; 95%CI 2.4–18.8). While 22 (16.9%) infected subjects had already donated blood, 24 (18.5%) and 34 (26.2%) considered
donating blood and organs outside Latin America, respectively.
Conclusions: Chagas disease is highly prevalent among Bolivian migrants in Switzerland. Chronic cardiac and digestive
complications were substantial. Screening of individuals at risk should be implemented in nonendemic countries and must
include undocumented migrants.
Citation: Jackson Y, Gétaz L, Wolff H, Holst M, Mauris A, et al. (2010) Prevalence, Clinical Staging and Risk for Blood-Borne Transmission of Chagas Disease among
Latin American Migrants in Geneva, Switzerland. PLoS Negl Trop Dis 4(2): e592. doi:10.1371/journal.pntd.0000592
Editor: Marleen Boelaert, Institute of Tropical Medicine, Belgium
Received September 24, 2009; Accepted December 9, 2009; Published February 2, 2010
Copyright: ß 2010 Jackson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The Foundation Simon I. Patino, Geneva, Switzerland, the WHO, the Geneva University Hospitals and the Department of Health and Community
medicine, Faculty of Medicine, University of Geneva sponsored this study. bioMérieux Switzerland and Ruwag Switzerland donated the serological tests. The
funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: yves.jackson@hcuge.ch
people worldwide and kills more than any other parasitic disease in
Latin America [2]. Until recently, its geographical distribution was
mostly determined by the area of endemicity of the infected
vectors. Successful vector control in endemic countries, urbanization, human migration and unpreparedness of newly affected areas
have contributed to modify the distribution of Chagas disease
[3,4]. Non-endemic countries (i.e. countries free of vectors) in
North America, Europe and Western Pacific Region have seen the
recent emergence of Chagas disease following the migration of
more than 15 million people from endemic areas [4]. Estimates of
Introduction
Chagas disease is a zoonosis caused by Trypanosoma cruzi (T.
cruzi), a flagellated protozoa transmitted to humans by the faeces of
blood-sucking triatomine bugs. The parasite can also be acquired
by blood transfusion, organ transplant, ingestion of food
contaminated with triatomines or their feces, or congenital
transmission [1]. In 2009, we celebrate the 100th anniversary of
the first complete description of the disease by Carlos Chagas, a
Brazilian physician. Chagas disease affects eight to ten million
www.plosntds.org
1
February 2010 | Volume 4 | Issue 2 | e592
Chagas Disease in Switzerland
donors at risk have yet to implement screening measures. The
attitude and practice of Latin American migrants towards blood
donation in non-endemic countries has yet to be investigated.
In 2008, Switzerland hosted 43’000 legal residents originating
from Central and South America [16]. This figure did not include
Swiss nationals from Latin American origin and the estimated 30–
50’000 undocumented Latin American migrants. Undocumented
migrants experience difficulties in accessing medical care in
Switzerland, as health insurance is mandatory and expensive
[17]. The first report of Chagas disease in Switzerland goes back to
1996. Since then, several imported and congenital cases have been
reported [18,19].
The objectives of this descriptive transversal study were to (1)
determine the prevalence of Chagas disease in a community of Latin
American adult migrants living in Geneva, (2) assess the risk factors
for T. cruzi infection, (3) clinically stage the disease, and (4) evaluate
the transfusional and transplantational risk to local recipients.
Author Summary
Chagas disease, a parasitic disease caused by Trypanosoma
cruzi, is a leading cause of cardiac and digestive tract
disorders in Mexico, Central and South America. An
increasing number of cases have recently been reported
in North America and Europe due to international human
migration, but data outside Latin America remains scarce.
This study showed that Chagas disease is an emerging
health problem in Switzerland, affecting a substantial
proportion of Latin American migrants (13%). Persons at
increased risk of infection were Bolivian, older than 35
years or had a mother infected with T. cruzi. Early signs of
cardiac or digestive tract disease were found in one out of
six infected patients. The risk of local transmission by
blood transfusion or organ transplant was illustrated by
the frequent willingness expressed by patients to donate
blood or organs in Switzerland. The authors recommend
the screening of persons at risk of infection and the
diffusion of appropriate information to the medical
community to increase awareness of this emerging health
problem. Considering that affected persons frequently lack
health insurance in Switzerland, a facilitated access to
medical care is an important step towards better
recognition and management of Chagas disease.
Methods
Setting
The study took place in a primary care centre (the Community
Care Mobile Unit) of the Geneva University Hospitals which
provides affordable care to more than 2000 Latin American
migrants yearly, the majority of them living in Geneva with
neither residency permit nor health insurance. Privacy is strictly
ensured for undocumented persons. This unit cooperates closely
with representatives of migrants communities. Information about
the study was widely diffused in cultural centres, churches and
migrant associations. In addition, two recruitment sessions took
place in churches attended by migrants.
the total number of T. cruzi infected people living in non-endemic
countries and reported cases are both on the rise, reaching an
estimated 25’000 to 40’000 in Western European countries in
2008. [4–11]. These estimates are usually based on the number of
registered Latin American migrants in the recipient country
multiplied by the mean prevalence of the disease among blood
donors in the home country. This mode of calculation has several
limitations, as it does not include migrants without legal
registration (undocumented), and does not take into account
regional variations of disease prevalence within endemic countries
[12].
Acute T. cruzi infection - frequently asymptomatic - is followed
by a long period of latency with few or no circulating parasites
(indeterminate form of the chronic phase) [1]. After decades, 20–
30% of infected persons develop chronic cardiac or digestive tract
complications. Chronic chagasic cardiopathy (CCC), which is
responsible for the high morbidity, mortality, and socio-economical impact of the disease in affected areas, is frequently
underdiagnosed, particularly in non-endemic countries [7]. ECG
is the recommended screening test for cardiac damage [13]. Up to
10% of T. cruzi infected persons may develop gastro-intestinal
motility disorder leading to progressive dilatation of the oesophagus (megaoesophagus) and/or the colon (megacolon). Suspected
digestive tract complications are investigated by barium studies.
Specific clinical features of Chagas disease in non-endemic
countries are not well characterized and may differ from those
found in Latin America for various reasons, including different
duration of exposure to infection. Until now, the few published
studies describing disease patterns in Europe were conducted in
specialized centres, and the findings may not be extrapolated to
the global Latin American migrant community [5,14].
Blood-borne transmission of T.cruzi has been reported in several
non-endemic countries [11,15]. Prevalence of infected blood
donations in Europe and North America varies widely, reaching
0.62% in at-risk donors in Spain [15]. Recently, USA, Spain and
France have implemented measures to reduce transfusional risk
through blood donors screening and deferral strategies [11].
However, most European countries that may harbour blood
www.plosntds.org
Participants and procedures
Between June and December 2008, all consecutive adult Latin
American migrants were invited to participate to the study. Other
inclusion criteria were age more than 16 years and signature of an
informed consent form. Pregnant women were excluded from the
study and were referred to the Maternity ward of the Geneva
University Hospitals where a specific program for Chagas
screening has been ongoing since January 2008 [9]. Written
informed consent was requested from participants. Participants
completed a questionnaire (available in Spanish, Portuguese and
French) that collected socio-demographic and medical data, and
assessed their prior and current attitudes towards blood donation
and organ transplant. A multilingual volunteer was available to
help onsite. Serological tests, clinical investigations and treatment
were free of charge. This study was approved by the ethics
committee of the Geneva University Hospitals in January 2008
(protocol 07-285).
Diagnosis of T. cruzi infection
Peripheral blood was drawn by a qualified nurse and serum was
kept refrigerated at 220uC. Two commercialized ELISA-based
serological tests (ELISA cruzi, Biomérieux, Brazil and Bioelisa
Chagas, Biokit, Spain), which detect antibodies against crude and
recombinant T. cruzi antigens respectively, were performed
according to manufacturers’ instructions with Dynatech-MRW
Microplate Washer. Chagas disease was diagnosed when both tests
were positive. The two tests were repeated in case of discrepant
results (e.g. positive-negative; doubtful-negative). External quality
control consisted of testing serum samples from all individuals with
positive or discordant ELISA tests and from 10% of individuals
with negative tests (Laboratory of Chagas disease, Goias
University, Brazil). A combination of four serological tests was
2
reference laboratory and proved to be negative. Socio-demographic
characteristics and clinical data of T. cruzi infected individuals
compared to non-infected ones and analysis of factors associated
with infection are shown in Tables 1 and 2, respectively.
Multivariate analysis showed that major predictive factors for T.
cruzi infection were Bolivian origin (adjusted odds ratio (OR 33.2;
95%CI 7.5–147.5), maternal infection with T. cruzi (OR 6.9; 95%CI
1.9–24.3), and age older than 35 years (OR 6.7; 95%CI 2.4–18.8).
performed (Chagatek ELISA, Biomérieux, Argentina; EIE Chagas
Bio-Manguinhos, Brasil; Chagatest HAI, Wiener, Argentina; inhouse immunofluorescent test using Biomerieux conjugate,
Biomérieux, Brazil). Results were sent back with an integrated
conclusion (positive, negative or non-conclusive).
Staging and management of the disease
All individuals with confirmed T. cruzi infection were contacted
by phone and underwent a clinical evaluation that included full
medical history, physical examination, and a 12-lead electrocardiogram (ECG) with a 30-second DII strip. In case of symptoms or
signs suggestive of cardiac failure, history of syncope, or ECG
changes consistent with CCC, an echocardiogram and a 24-hour
Holter recording were performed. Results of cardiac investigations
were independently reviewed by two cardiologists. The classification of CCC was based on the Brazilian Consensus [20]. Patients
with dysphagia to solid or liquid food and/or with severe
constipation (less than 2 stools per week and/or use of laxatives
more than 5 days per week for more than 6 months) underwent
gastro-intestinal tract barium examination. Oesophageal abnormalities were staged according to the classification of de Rezende
[21]. The colon was considered abnormal if its diameter exceeded
6cm. In the absence of abnormal findings by ECG, echocardiography, 24-hour Holter recording, and barium studies, Chagas
disease was classified in the indeterminate form of the chronic
phase. According to recent recommendations, all eligible cases
were treated with nifurtimox or benznidazole for 60 days [13].
Clinical description
Clinical evaluation was performed in 124 patients (95.4%),
whereas 6 patients were lost to follow-up due to unexpected
departure from Switzerland. Out of 14 patients (11.3%) with ECG
abnormalities consistent with CCC, 12 (9.7%) were classified as
grade A, one as grade B2 (0.8%) and one could not be fully
investigated (Table 3). Twelve (9.7%) other patients with normal
ECG had symptoms or signs consistent with heart disease. Seven of
them underwent further investigations. Four had echocardiographic
signs of low-grade diastolic dysfunction and one showed coronary
sinus dilatation. Two others presented rhythmic abnormalities on
Holter recording. In the absence of definite criteria defined by the
Brazilian consensus, we did not consider these seven patients as
cases of CCC. Twenty-one (16.9%) patients reported dysphagia
(n = 10) and/or severe constipation (n = 16). Barium studies were
performed in 16 patients. One patient (0.8%) had grade I
oesophageal involvement (Figure 1). 109 (87..9%) patients were
classified as chronic infection in the indeterminate form.
Statistical analysis
Blood and organ donation
In order to investigate the relationship between Chagas disease
and possible predictive factors, we used 262 tables and performed
Chi-square and Fisher’s exact tests for categorical variables and
unpaired Student’s t-tests for continuous variables. Univariate and
multivariate logistic regression analyses were used to assess factors
associated with Chagas disease. All analyses were performed using
SPSS for Windows (version 15.0).
Two-hundred forty seven participants (24.4%) and twenty-two
patients (16.9%) had already donated blood. Twenty-four (18.5%)
and 34 (26.2%) patients expressed willingness to donate blood and
organs outside Latin America, respectively (Table 4).
Discussion
We found a high (12.8%) prevalence of Chagas disease among
1012 Latin American migrants attending an urban primary care
centre and two Latino churches in Geneva, Switzerland. This
figure is much higher than previously reported in Canada (1%)
and Germany (2%), but lower than the very high (41%) prevalence
found at a referral centre in Spain [5,22,23]. Our finding is mostly
explained by the high proportion (48%) of Bolivian migrants in the
study cohort, of whom 26.2% were diagnosed with Chagas
disease. This figure is consistent with recent epidemiological
studies conducted in affected provinces of Bolivia (Santa Cruz,
Cochabamba), where most of the Bolivian migrants living in
Geneva originate from [24,25]. Bolivian participants were not
over-represented in our study as they constitute 42% of Latin
American migrants consulting in our primary care facility.
Bolivian origin was the main predictive factor for T. cruzi infection,
in concordance with other reports from non-endemic countries
[5,9]. Only three of the 130 patients originated from other
countries (Argentina and Brazil). This is unclear whether these
three patients were infected in their country of origin or in Bolivia,
where they lived for several years. The absence of cases diagnosed
in migrants from other endemic countries is likely to be explained
by the insufficient number of persons tested, the possible effect of
cluster sampling (as shown in Bolivians) and the lower average
national prevalence of T. cruzi infection in other Latin American
countries [4]. Nevertheless, cases originating from most Central
and South American countries have been reported in nonendemic countries [5,14]. Therefore, consideration for T. cruzi
infection should not be restricted to Bolivians.
Results
Thousand-and-twelve participants, with a mean age of 37.2
(standard deviation (SD) 11.3) years and a female predominance
(83%), were recruited in the study. Ninety-six percent of
participants were undocumented. Countries of origin were Bolivia
(n = 485; 48%), Brazil (n = 249; 25%), Colombia (n = 61; 6%),
Peru (n = 58; 6%), Ecuador (n = 47; 5%), Paraguay (n = 28; 3%),
Nicaragua (n = 24; 2%), Honduras (n = 24; 2%) and others (n = 36;
4%). The mean duration of stay outside Latin America was 4.9
(SD 4.0) years. Socio-demographic characteristics and medical
history data related to T. cruzi infection of the 1012 participants
are shown in Table 1. Previous bite by triatomine bugs were
reported by 11.2% of the participants, 12.7% had received blood
transfusion in Latin America and 7.7% were born from a T. cruzi
infected mother. Previous positive testing for Chagas disease was
reported by 2.6% of participants.
Prevalence of Chagas disease and predictive factors
On the basis of concordant positive serological tests, Trypanosoma
cruzi infection was diagnosed in 130 participants, resulting in an
overall prevalence of 12.8% (95% confidence interval (CI) 10.8–
14.9); prevalence among Bolivians was 26.2% (95%CI 22.3–30.1;
n = 127). External quality control confirmed all positive cases.
Three infected individuals originated from Argentina (n = 2) and
Brazil (n = 1); all had lived for several years in Bolivia. All (n = 12)
discordant serological results in Geneva were controlled at the
www.plosntds.org
3
Table 1. Description of Latin American migrants (n = 1012) with and without Chagas disease (CD) in Geneva, Switzerland.
Age (mean)
Total population N = 1012,
Mean (SD) or n (%)
Subjects with CD, N = 130, Mean
(SD) or n (% within CD)
Subjects without CD, N = 882,
Mean (SD) or n (% without CD)
37.4 (SD 11.3)
41.0 (SD 9.4)
36.9 (SD 11.5)
Age in 2 groups
p*
,0.0001
,0.0001
#35 years
494 (48.8%)
37 (28.5%)
.35 years
518 (51.2%)
93 (71.5%)
457 (51.8%)
425 (48.2%)
Sex (female)
835 (82.5%)
108 (83.1%)
727 (82.4%)
Bolivia
486 (47.5%)
127 (97.7%)
359 (40.7%)
other
528 (52.5%)
3 (2.3%)
523 (59.3%)
Years outside Latin America
4.9 (SD 4.0)
4.6 (SD 2.1)
4.9 (SD 4.2)
Yes
78 (7.7%)
26 (20.0%)
52 (5.9%)
No
604 (59.7%)
47 (36.2%)
557 (63.2%)
Don’t know
330 (32.6%)
57 (43.8%)
273 (31.0%)
Yes
80 (7.9%)
27 (20.7%)
53 (6.1%)
No
857 (84.7%)
95 (73.1%)
762 (86.4%)
Don’t know
75 (7.4%)
8 (6.2%)
67 (7.6%)
Yes
113 (11.2%)
35 (26.9%)
78 (8.8%)
Now
336 (33.2%)
20 (15.4%)
316 (35.8%)
Don’t know
563 (55.6%)
75 (57.7%)
488 (55.3%)
Yes
129 (12.7%)
30 (23.1%)
99 (11.2%)
No
879 (86.9%)
100 (76.9%)
779 (88.3%)
Don’t know
4 (0.4%)
0
4 (0.5%)
Yes
10 (1.0%)
5 (3.8%)
5 (0.6%)
No
1001 (98.9%)
125 (96.2%)
876 99.3%)
Don’t know
1 (0.1%)
0
1 (0.1%)
Origin
0.85
,0.0001
Mother with T. cruzi infection
0.41
,0.0001
Previous testing
,0.0001
Previous triatomine bite
,0.0001
Previous transfusion
0.001
Previous treatment
0.002
*p concerns difference between subjects with and without Chagas disease.
doi:10.1371/journal.pntd.0000592.t001
Older migrants were at increased risk for T. cruzi infection, most
likely due to a longer and more intense exposition to vectorial
transmission in their home country. Vector control campaigns
have resulted in a sharp reduction of transmission in endemic
countries during the last decades, therefore conferring relative
protection to younger generations [3]. History of maternal
infection (defined by positive serology in the home country) was
also a strong and independent predictive factor for infection. Being
borne from an infected mother cumulates the risk of vertical
transmission and shared exposure to vectorial transmission.
The risk of unrecognized vertical transmission in non-endemic
countries is increased by the low proportion of patients aware of being
infected, the lack of clinical signs in most infected newborns and the
absence of systematic prenatal screening program [1,9,10]. Screening
should be offered to women of childbearing age, pregnant women
and their offspring (in case of proven maternal infection) [9].
Only 4% of patients had valid residency permit and health
insurance. It is estimated that several millions of migrants at risk
for Chagas disease reside undocumented in Europe and in North
America [4,26]. In many countries, such as Switzerland,
undocumented migrants face difficulties to access preventive and
www.plosntds.org
curative care. This socio-economic dimension must be taken into
consideration by policy makers at the planning stage of screening
programs for Chagas disease in non-endemic countries.
ECG abnormalities consistent with CCC were found in 11.3%
of cases, a proportion comparable to previous reports [5,27]. Most
patients who could be classified were in grade A CCC according to
the Brazilian consensus classification. One patient presented with
advanced stage cardiopathy (grade B2) requiring specific therapy.
Interestingly, five symptomatic patients with normal ECG had
low-grade diastolic dysfunction or coronary sinus dilatation by
echocardiography and two others presented rhythmic abnormalities on Holter recording. In the absence of identified alternative
aetiology, the diagnosis of early stage CCC is possible. However,
the Brazilian criteria do not allow these patients to be classified as
such. More studies are needed to define the diagnostic and
prognostic value of echocardiography and Holter in symptomatic
cases with normal ECG. The low rate of advanced CCC in our
study can be explained by the overall young patients’ age and,
possibly, by the healthy migrant effect. The latter implies that
persons who initiate a long distance migration tend to be healthier
than persons who do not migrate [28]. Nevertheless, cases of
4
Table 2. Predictive factors, unadjusted and adjusted odds ratios (OR) for Chagas disease (CD) among T. cruzi infected Latin
American migrants in Geneva, Switzerland (n = 130).
Prevalence of CD,
n (%)
Unadjusted OR for CD
(95%CI)
Adjusted OR for CDu
(95%CI)
Adjusted OR for CD*
(95%CI)
Age (years)
#35
37/494 (7.5%)
.35
93/518 (18.0%)
2.7 (1.8;4.0)
3.6 (2.3;5.6)
6.1 (2.2;16.7)
Women
108/835 (12.9%)
1.04 (0.6;1.7)
0.85 (0.5;1.5)
1.04 (0.3;3.4)
Men
22/177 (12.4%)
61.7 (19.5;195.3)
71.2 (22.4;226.4)
31.7 (7.2;139.5)
Gender
Origin
Bolivia
127/486 (26.1%)
Other
3/528 (0.6%)
Mother with T. cruzi infection
26/78 (33.3%)
Mother without T. cruzi infection
47/604 (7.8%)
Previous triatomine bite
35/113 (31.0%)
No previous triatomine bite
20/336 (6.0%)
5.9 (3.4;10.3)
6.5 (1.9;22.8)
7.1 (3.9;12.0)
1.8 (0.7;4.6)
uAdjustment for age, sex and origin (patients included in this model: n = 1012).
*Adjustment for all variables in table 2 (patients included in this model: n = 378).
advanced CCC have also been diagnosed in Geneva outside the
study period [18,19]. The disease burden and treatment cost of
CCC is recognized as an emerging challenge in some nonendemic countries like the USA and Spain [8,14]. Only one
patient had radiological evidence of low-grade digestive tract
alteration consistent with Chagas disease. This low prevalence of
digestive tract complications is comparable to findings reported in
Spain [5]. As strict clinical criteria were used before undergoing
barium studies, we can not exclude to have missed one or more
paucisymptomatic case(s).
T. cruzi transmission by blood transfusion has been sporadically
reported in North America and in Europe [1,11,15]. Persistent
parasitemia in infected blood donors can lead to infected donations
over a long period of time [29]. In our cohort, 24.4% participants
and 16.9% of T. cruzi infected patients had a prior history of blood
donation. Despite a relatively short time (mean: 4.9 years) spent
outside Latin America, 6.9% of participants had already donated
blood in North America or in Europe. Moreover, a significant
proportion of participants and of T. cruzi infected patients expressed
the intention to donate blood outside Latin America in the future.
Table 3. Description and staging of patients with Chagas disease and ECG abnormalities in Geneva, Switzerland.
Patient (sex age)
Symptoms
Signs
ECG
Echocardiogram
Holter
Staging
F 28
chest pain
none
inversed T wave avF
normal
PVB (576/24h), bradycardia 459
A
F 35
-
none
partial RBBB
normal
normal
A
F 40
palpitation
none
inversed T wave v1-v3
normal
normal
A
F 43
-
none
AVB grade I
normal
sustained AT
A
F 45
-
none
RBBB
normal
PVB (480/24h), PSVB
A
F 45
dyspnea, syncope
none
RBBB
normal
PSVB, sustained AT
A
F 46
-
none
bradycardia
normal
PVB (264/24h), PSVB, bradycardia 399
A
F 46
-
none
PSVB, bigeminisme
-
-
unknown
F 50
dyspnea, chest pain,
palpitation
none
LBBB
LVEF 35%, global
hypokinesia
PVB (3960/24h), non-sustained VT
B2
F 51
syncope
none
RBBB, bradycardia
normal
bradycardia 349
A
F 54
chest pain, palpitation
none
PVB
diastolic dsyfunction
grade 2
PVB (9504/24h)
A
F 56
-
none
PVB, LAFB
normal
PVB (28464/24h), bi-trigeminisme
A
F 59
-
none
inversed T wave v2-v3, q wave
in D1, avL
diastolic dysfunction
grade 1, dilated LA
PVB (432/24h), PSVB, bradycardia 449
A
M 44
chest pain
none
LAFB, inversed T wave avF
normal
normal
A
RBBB, right bundle branch block; LBBB, left bundle branch block; LAFB, left anterior fascicular block; AVB, atrio-ventricular block; PSVB, premature supra-ventricular beat;
PVB, premature ventricular beat; LA, left atria; AT, atrial tachycardia; LVEF, left ventricular ejection fraction.
www.plosntds.org
5
This positive attitude towards blood donation and the large
proportion of patients unaware of being infected highlights the risk
of blood-borne transmission and support the implementation of
preventive measures in non-endemic countries.
Organ transplant is a rare mode of transmission that has been
reported both in endemic and non-endemic countries [30].
Chagas disease can present as a fulminant systemic disease in
immunosuppressed patients [1]. In our cohort, none of the
participants had donated organs and none of the T. cruzi infected
patients had a previous history of organ transplant. However, a
high proportion of participants and cases considered organ
donation while alive or after passing away. Health professionals
involved in organ transplantation should be informed or reminded
that organ donors or recipients at risk of being infected require
screening for Chagas disease.
The high proportions of migrants with no legal registration and
of Bolivian origin, as well as the recruitment limited to one city,
represent the main limitations of this study as they partially restrict
the extrapolation of our findings to other settings. We believe that
these limitations are counter-balanced by the large population
screened and by the choice of a primary care setting as a
recruitment site. Therefore, our study may offer a valuable insight
into the current trends of this emerging health problem in Europe.
According to our and others’ findings, we recommend screening
for Chagas disease in priority all Latin American persons at
increased chance of (1) infection (e.g. Bolivian origin, diagnosis of
Chagas disease in the mother or in other close family members,
prior history of blood transfusion in endemic countries, presence of
suggestive cardiac or digestive complaints), (2) severe illness (e.g.
immunosuppressed individuals), (3) transmitting T. cruzi to others
(e.g. pregnant women and women of child bearing age, blood or
organ donors), and (4) cure with existing treatments (newborns and
children). Cost-effectiveness studies may help to design more
rational recommendations. Considering the millions of persons at
risk who have recently migrated outside Latin America, medical
students and physicians in non-endemic countries must be made
aware of the emergence of this neglected tropical disease.
Supporting Information
Figure 1. Gastro-oesophageal barium examination in left
posterior oblique view in upright position in a T. cruzi infected
individual showing delayed bolus elimination without oesophageal dilatation (de Rezende stage I) one minute after
ingestion.
doi:10.1371/journal.pntd.0000592.g001
Alternative Language Abstract S1 Translation of the abstract
into French by YJ.
Found at: doi:10.1371/journal.pntd.0000592.s001 (0.02 MB
DOC)
Table 4. Frequency of history and intention of blood and organ donation in Latin American migrants living in Geneva,
Switzerland.
Latin American migrants
(n = 1012) N (%)
History of blood donation
Bolivian migrants
(n = 486) N (%)
Migrants with Chagas disease
(n = 130) N (%)
247* (24.4)
109 (22.4)
22 (16.9)
in Latin America
208 (84.2)
96 (88.1)
22 (100)
in Europe
17 (6.9)
1 (0.9)
0
not stated
27 (10.9)
13 (11.9)
0
Intention to give blood outside Latin America
206 (20.4)
70 (14.4)
24 (18.5)
History of organ donation
0
0
0
Intention to give organ
360 (35.6)
149 (30.7)
34 (26.2)
*Five individuals have donated blood in more than one geographical region.
www.plosntds.org
6
Checklist S1 STROBE checklist.
Found at: doi:10.1371/journal.pntd.0000592.s002 (0.09 MB
DOC)
Author Contributions
Conceived and designed the experiments: YJ HW LL JMG JJ PAV AL FC.
Performed the experiments: YJ LG MH AM AT JS VB AL FC. Analyzed
the data: YJ HW FC. Wrote the paper: YJ HW FC.
Acknowledgments
Authors wish to thank Odile Colombel, Tina Mazzocato, Martine
Locatelli, Heidi Fowler-Njie, Suelene Tavares and Tatiana Collipal for
their valuable help.
References
16. Swiss federal office for migration (2009) Number of permanent foreign resident
population by nationality; Available: http://www.bfm.admin.ch/etc/medialib/
data/migration/statistik/auslaenderstatistik/2008.Par.0047.File.tmp/
ts8_wohnbevoelkerung_staat_2008-12-e.pdf. Accessed 18 June 2009.
17. Berne GFS (2005) Sans-papiers en Suisse : c’est le marché de l’emploi qui est
déterminant, non pas la politique d’asile. Bern. Available: http://www.bfm.
admin.ch/etc/medialib/data/migration/illegale_migration/sans_papiers.Par.
0006.File.tmp/sans_papiers_studie.pdf. Accessed 18 June 2009.
18. Sztajzel J, Cox J, Pache JC, Badaoui E, Lerch R, et al. (1996) Chagas’ disease
may also be encountered in Europe. Eur Heart J 17: 1289.
19. Jackson Y, Chappuis F, Loutan L (2008) Chagas disease in Switzerland:
managing an emerging infection and interrupting its transmission. Rev Med
Suisse 4: 1212–4, 6–7.
20. Brazilian Ministerio do Salud (2005) Brazilian consensus on Chagas disease. Rev
Soc Bras Med Trop 38(suppl 3): 7–29.
21. de Rezende JLK, de Oliveira A (1960) Clinical and radiological aspects of
aperistalsis of the esophagus. Rev Bras Gastroenterol 12: 247–62.
22. Steele LS, MacPherson DW, Kim J, Keystone JS, Gushulak BD (2007) The
sero-prevalence of antibodies to trypanosoma cruzi in Latin American refugees
and immigrants to Canada. J Immigr Minor Health 9: 43–7.
23. Frank M, Hegenscheid B, Janitschke K, Weinke T (1997) Prevalence and
epidemiological significance of Trypanosoma cruzi infection among Latin
American immigrants in Berlin, Germany. Infection 25: 355–8.
24. Sosa-Estani S, Gamboa-Leon MR, Del Cid-Lemus J, Althabe F, Alger J, et al.
(2008) Use of a rapid test on umbilical cord blood to screen for Trypanosoma
cruzi infection in pregnant women in Argentina, Bolivia, Honduras, and
Mexico. Am J Trop Med Hyg 79: 755–9.
25. Breniere SF, Bosseno MF, Noireau F, Yacsik N, Liegeard P, et al. (2002)
Integrate study of a Bolivian population infected by Trypanosoma cruzi, the
agent of Chagas disease. Mem Inst Oswaldo Cruz 97: 289–95.
26. Senior K (2007) Chagas disease: moving towards global elimination. Lancet
Infect Dis 7: 572.
27. Blum JA, Zellweger MJ, Burri C, Hatz C (2008) Cardiac involvement in African
and American trypanosomiasis. Lancet Infect Dis 8: 631–41.
28. Kliewer E (1992) Epidemiology of diseases among migrants. Int Migr 30:
141–64.
29. Leiby DA, Herron RM, Jr., Garratty G, Herwaldt BL (2008) Trypanosoma
cruzi parasitemia in US blood donors with serologic evidence of infection.
J Infect Dis 198: 609–13.
30. Kun H, Moore A, Mascola L, Steurer F, Lawrence G, et al. (2009) Transmission
of Trypanosoma cruzi by heart transplantation. Clin Infect Dis 48: 1534–40.
1. Prata A (2001) Clinical and epidemiological aspects of Chagas disease. Lancet
Infect Dis 1: 92–100.
2. Hotez PJ, Bottazzi ME, Franco-Paredes C, Ault SK, Periago MR (2008) The
neglected tropical diseases of latin america and the Caribbean: a review of
disease burden and distribution and a roadmap for control and elimination.
PLoS Negl Trop Dis 2: e300.
3. Schofield CJ, Jannin J, Salvatella R (2006) The future of Chagas disease control.
Trends Parasitol 22: 583–8.
4. Schmunis GA (2007) Epidemiology of Chagas disease in non-endemic countries:
the role of international migration. Mem Inst Oswaldo Cruz 102 Suppl 1:
75–85.
5. Munoz J, Gomez i Prat J, Gallego M, Gimeno F, Trevino B, et al. (2009)
Clinical profile of Trypanosoma cruzi infection in a non-endemic setting:
immigration and Chagas disease in Barcelona (Spain). Acta Trop 111: 51–5.
6. Lescure FX, Canestri A, Melliez H, Jauréguiberry S, Develoux M, et al. (2008)
Chagas disease, France. Emerg Infect Dis 14: 644–6.
7. Guerri-Guttenberg RA, Grana DR, Ambrosio G, Milei J (2008) Chagas
cardiomyopathy: Europe is not spared! Eur Heart J 29: 2587–91.
8. Milei J, Guerri-Guttenberg RA, Grana DR, Storino R (2009) Prognostic impact
of Chagas disease in the United States. Am Heart J 157: 22–9.
9. Jackson Y, Myers C, Diana A, Marti HP, Wolff H, et al. (2009) Congenital
transmission of chagas disease in latin american immigrants in Switzerland.
Emerg Infect Dis 15: 601–3.
10. Munoz J, Coll O, Juncosa T, Verges M, del Pino M, et al. (2009) Prevalence and
vertical transmission of Trypanosoma cruzi infection among pregnant Latin
American women attending 2 maternity clinics in Barcelona, Spain. Clin Infect
Dis 48: 1736–40.
11. Castro E (2009) Chagas’ disease: lessons from routine donation testing. Transfus
Med 19: 16–23.
12. Schmunis GA, Rodriguez G, Coenen J, Bellorin EG, Gianella A (2008)
Prevention of blood-borne diseases in Bolivia, 1993–2002. Am J Trop Med Hyg
79: 803–8.
13. Bern C, Montgomery SP, Herwaldt BL, Rassi Jr A, Marin Nieto JA, et al. (2007)
Evaluation and treatment of chagas disease in the United States: a systematic
review. JAMA 298: 2171–81.
14. de Ayala AP, Perez-Molina JA, Norman F, Lopez-Velez R (2009) Chagasic
cardiomyopathy in immigrants from Latin America to Spain. Emerg Infect Dis
15: 607–8.
15. Piron M, Verges M, Munoz J, Casamitjana N, Sanz S, et al. (2008)
Seroprevalence of Trypanosoma cruzi infection in at-risk blood donors in
Catalonia (Spain). Transfusion 48: 1862–8.
www.plosntds.org
7
6. Congenital transmission of Chagas disease in Latin American immigrants in
Switzerland
Emerg Inf Dis 2009;15(4):601-3
Par:
Jackson Y, Myers C, Diana A, Marti HP, Wolff H, Chappuis F, Loutan L, Gervaix A.
31
Congenital
Transmission of
Chagas Disease in
Latin American
Immigrants in
Switzerland
Yves Jackson, Catherine Myers,
Alessandro Diana, Hans-Peter Marti, Hans Wolff,
François Chappuis, Louis Loutan,
and Alain Gervaix
International migration has changed the epidemiologic
patterns of Chagas disease. Recently, 2 cases of Chagas
disease transmitted from Latin American women to their
newborns were diagnosed in Geneva, Switzerland. A retrospective study to detect Chagas disease showed a prevalence of 9.7% among 72 Latin American women tested during pregnancy in Switzerland.
C
hagas disease, a zoonotic infection caused by Trypanosoma cruzi, is the most important endemic parasitic infection in Mexico and Central and South America
because of the number of persons who become ill or die
from this disease (1). An estimated 8–10 million persons
are infected, and ≈14,000 persons die each year from Chagas disease (1,2). Historically, transmission by triatomine
vectors has been the most common source of infection;
however, the populations affected, transmission routes,
and geographic distribution of Chagas disease cases have
been greatly modified by urbanization and international
migration. An estimated 14 million people from countries
in which Chagas disease is endemic have moved to North
America, Europe, Japan, and Australia. The number of persons currently infected by T. cruzi is probably >100,000 in
the United States and >6,000 in Spain (2).
In Europe, vertical, transfusional, and transplantational routes have accounted for all cases of transmission.
The risk for vertical transmission from an infected mother
to her newborn is ≈5% (3). Vertical transmission is likely
to go undetected in Europe because of lack of screening
programs for at-risk pregnant women, who are usually in
Author affiliations: Geneva University Hospitals and University of
Geneva, Geneva, Switzerland (Y. Jackson, C. Myers, A. Diana, H.
Wolff, F. Chappuis, L. Loutan, A. Gervaix); and Swiss Tropical Institute, Basel, Switzerland (H.-P. Marti)
DOI: 10.3201/eid1504.080438
the long-lasting, chronic, asymptomatic phase of the disease and are unaware of their infection. An estimated 2,000
babies may have been born with T. cruzi infection in North
America in recent years, and 2 cases of vertical transmission
were recently reported from Spain (4–6). We report 2 additional cases of congenital infection with T. cruzi, detected
in 2001 and 2006, at the Geneva University Hospitals in
Switzerland. Subsequently, we conducted a retrospective
serologic survey of pregnant Latin American immigrants
to assess the potential for vertical transmission of Chagas
disease in Switzerland.
The Cases
In 2001, a 31-year-old woman from Santa Cruz, Bolivia, delivered a 2,860-g, full-term, apparently healthy baby
at the Geneva University Hospitals after an uncomplicated
pregnancy. Like most undocumented immigrants recently
arrived in Switzerland, she had received no medical supervision during her pregnancy. She stated that a blood
test for T. cruzi, conducted in Bolivia, had been negative.
Macroscopic examination of the fetal side of the placenta
showed a 3.5-cm, subchorial, liquid-filled cyst (Figure 1).
Histopathologic examination showed disseminated chorioamnionitis and associated funiculitis with large numbers of
nonflagellated parasites. A recent infection with Toxoplasma gondii was ruled out by serologic testing. Congenital
T. cruzi infection was confirmed by a positive blood microscopic examination for the infant, a positive serologic
test result for the mother (immunofluorescence assay using
killed T. cruzi parasites, Swiss Tropical Institute, Basel,
Switzerland), and a positive blood PCR with TCZ1/TCZ2
primers for both the mother and the newborn. Electrocardiogram and echocardiogram of the newborn showed no abnormalities. The newborn received nifurtimox (10 mg/kg/d
for 60 days) without notable adverse effects. Parasitemia
became undetectable at the end of treatment, and serologic
test result at 1 year of age was negative. The mother refused
to be treated, claiming that she was feeling fine.
Figure 1. Fetal side of the placenta from Latin American pregnant
woman who delivered her baby at Geneva University Hospitals,
Geneva, Switzerland. A macroscopic subchorial liquid-filled cyst
can be seen near the umbilical cord insertion.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 15, No. 4, April 2009
601
DISPATCHES
In 2006, a 25-year-old woman arrived in Switzerland
from Santa Cruz, Bolivia, when she was 5 months pregnant. She delivered a 2,480-g, premature but healthy baby
at 34 weeks’ gestation at the Geneva University Hospitals.
After discharge, histopathologic examination of the placenta showed funiculitis and chorioamnionitis with clusters of
nonflagellated parasites. The mother had not been previously tested for T. cruzi but related that her father had died
of Chagas disease–related heart complications. T. cruzi serologic testing by immunofluorescence was positive for the
mother, and blood microscopic examination and PCR were
positive for the newborn, confirming vertical transmission.
Electrocardiogram and echocardiogram of the baby showed
no abnormalities. The newborn began a 60-day course of
nifurtimox (10 mg/kg/d) at 20 weeks of age and had no adverse effects. Blood PCR and serologic testing at 5 and 26
weeks after treatment was started, respectively, produced
negative results. The mother was treated with nifurtimox
after completion of breast-feeding and showed good tolerance to the drug.
The Study
In response to these 2 cases, in 2007, a retrospective
serologic survey for T. cruzi infection was performed on
stored serum samples from 72 undocumented pregnant
Latin American women who had received prenatal care at
the Geneva University Hospitals during the previous year.
Median age was 30 years (range 20–43), and countries of
origin were Bolivia (n = 30), Brazil (n = 22), Peru (n = 6),
Ecuador (n = 5), Colombia (n = 4), Chile (n = 2), Honduras
(n = 1), and unknown (n = 2). Serum samples were tested
by IFA using T. cruzi parasites from in vitro culture (Swiss
Tropical Institute). No confirmatory test was available. Of
the 72 samples, 7 (9.7%) were positive, most from Bolivian
women (n = 5). The seroprevalence among Bolivian women was 16.6% (5/30), consistent with prevalence found by
similar surveys conducted recently in Bolivian maternity
hospitals (7). Limitations of the study include the small
number of samples tested and lack of a confirmatory test as
recommended by the World Health Organization.
Conclusions
Only a small number of congenital cases of Chagas disease have been reported in countries in which this infection
is nonendemic. The absence of routine screening programs
for Chagas disease in pregnant women and newborns at
risk most likely explains this low number, but other factors
may be involved. Chagas disease affects immigrants, who
frequently lack legal status and therefore experience difficulties (e.g., fear of deportation and financial and administrative constraints) in accessing quality healthcare during pregnancy. In Switzerland, undocumented immigrant
women have poor access to medical supervision during
602
pregnancy, so most consult a physician late in pregnancy
or at time of delivery (8). Chagas disease is rare in Europe,
and healthcare workers may simply not search for it, resulting in missed opportunities to diagnose the disease. In
addition, up to two thirds of infected newborns are asymptomatic at birth, so congenital infection may go undetected
if not actively sought.
Systematic screening of pregnant women at risk is
likely to be beneficial in several ways. Treatment of infected mothers after completion of breast-feeding may reduce the risk for vertical transmission during subsequent
pregnancies. Treatment of young women at the chronic,
indeterminate stage of infection is likely to lower their risk
for developing cardiac complications (9). Early screening
and treatment of infected newborns are associated with
high cure rates (10). Older children of mothers with newly
diagnosed Chagas disease also benefit from screening and
treatment (11). In addition, because immigrants with inadequate access to healthcare are at risk for being lost to
follow-up after delivery, perinatal screening offers a good
opportunity to screen other family members and offer treatment as needed.
Because most pregnant women receive their diagnosis
during the chronic, asymptomatic stage of Chagas disease,
screening with 2 sequential serologic tests is the most efficient strategy for detection of infection (12). PCR and parasitologic tests are ineffective for detection because they
show lower sensitivity during this phase (13). In contrast,
infected newborns usually have high levels of parasitemia.
Therefore, microscopic techniques such as microhematocrit and concentration methods in umbilical cord blood
Pregnant women from Mexico and
Central and South America
Serology
–
+
Confirmation -with
second
serology
-
Stop investigations
+
+
Microscopic exam of
cord blood
Newborn of infected mother
+
–
PCR of cord or
peripheral blood
+
Clinical
assessment
and
treatment
–
Stop investigations
–
–
Serology at 9 months
of age
+
+
Serology with
confirmation
Older children from
infected pregnant women
Figure 2. Algorithm for screening, diagnosis, and treatment of
Trypanosoma cruzi congenital infection at Geneva University
Hospitals, Geneva, Switzerland.
Chagas Disease in Latin American Immigrants
have fairly high (>80%) sensitivity (14). PCR is more
sensitive for detecting Chagas infection in infants than in
adults; however, few laboratories perform T. cruzi PCR in
Europe.
Launched in January 2008, a program of systematic
Chagas disease screening of pregnant women at risk and
of newborns delivered by infected mothers is under way at
the Geneva University Hospitals (Figure 2). All pregnant
women from Mexico and Central and South America are
screened by serologic testing. Newborns of infected mothers are screened by microscopic examination of cord blood
after concentration (microhematocrit, Strout’s method)
and, if negative, by PCR. If PCR is negative, serologic testing is performed when the child is 9 months of age. Blood
cultures are not performed because of time needed to obtain
results. Examination of the placenta, which is an unreliable screening method, is also not conducted for diagnostic purposes (15). All infected mothers (after completion
of breast-feeding), newborns, and their siblings are offered
treatment for this potentially fatal disease. Prenatal and delivery care of Latin American immigrants is an opportunity to screen for Chagas disease and its potential vertical
transmission. This strategy will help address this emergent
health problem in Europe.
Acknowledgments
We thank E. Couvreur for diagnosing Chagas disease from
the placenta of the newborn described in the first case.
Dr Jackson is an internal medicine specialist who works at
the Geneva University Hospitals in travel medicine and migrant
health. His research focuses on Chagas disease in immigrants living in Switzerland.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
References
1.
2.
3.
Jannin J, Salvatella, R, editors. Quantitative estimates of Chagas
disease in the Americas. OPS/HDM/CD/425-06. Washington: Pan
American Health Organization; 2006.
Schmunis GA. Epidemiology of Chagas disease in non-endemic countries: the role of international migration. Mem Inst Oswaldo Cruz. 2007;102(Suppl 1):75–85. DOI: 10.1590/S007402762007005000093
Torrico F, Alonso-Vega C, Suarez E, Rodriguez P, Torrico MC, Dramaix M, et al. Maternal Trypanosoma cruzi infection, pregnancy
outcome, morbidity, and mortality of congenitally infected and noninfected newborns in Bolivia. Am J Trop Med Hyg. 2004;70:201–9.
15.
Riera C, Guarro A, El Kassab H, Jorba J, Castro M, Angrill R, et al.
Congenital transmission of Trypanosoma cruzi in Europe (Spain): a
case report. Am J Trop Med Hyg. 2006;75:1078–81.
Munoz J, Portus M, Corachan M, Fumado V, Gascon J. Congenital
Trypanosoma cruzi infection in a non-endemic area. Trans R Soc Trop
Med Hyg. 2007;101:1161–2. DOI: 10.1016/j.trstmh.2007.06.011
Buekens P, Almendares O, Carlier Y, Dumonteil E, Eberhard M,
Gamboa-Leon R, et al. Mother-to-child transmission of Chagas’ disease in North America: why don’t we do more? Matern Child Health
J. 2008;12:283–6. DOI: 10.1007/s10995-007-0246-8
Torrico F, Alonso-Vega C, Suarez E, Rodríguez P, Torrico M, Dramaix M, et al. Endemic level of congenital Trypanosoma cruzi
infection in the areas of maternal residence and the development
of congenital Chagas disease in Bolivia. Rev Soc Bras Med Trop.
2005;38(Suppl 2):17–20.
Wolff H, Epiney M, Lourenco AP, Costanza MC, DelieutrazMarchand J, Andreoli N, et al. Undocumented migrants lack access
to pregnancy care and prevention. BMC Public Health. 2008;8:93.
DOI: 10.1186/1471-2458-8-93
Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez
MG, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazol versus no treatment. Ann Intern Med.
2006;144:724–34.
Altcheh J, Biancardi M, Lapena A, Ballering G, Freilij H. Congenital Chagas disease: experience in the Hospital de Ninos, Ricardo Gutierrez, Bueno Aires, Argentina. Rev Soc Bras Med Trop.
2005;38(Suppl 2):41–5.
de Andrade AL, Zicker F, de Oliveira RM, Almeida e Silva S, Luquetti A, Travassos LR, et al. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet.
1996;348:1407–12. DOI: 10.1016/S0140-6736(96)04128-1
Bern C, Montgomery S, Herwaldt B, Rassi A Jr, Marin-Neto J, Dantas R, et al. Evaluation and treatment of Chagas disease in the United States: a systematic review. JAMA. 2007;298:2171–81. DOI:
10.1001/jama.298.18.2171
Solari A, Ortíz S, Soto A, Arancibia C, Campillay R, Contreras
M, et al. Treatment of Trypanosoma cruzi–infected children with
nifurtimox: a 3 year follow-up by PCR. J Antimicrob Chemother.
2001;48:515–9. DOI: 10.1093/jac/48.4.515
Mora MC, Sanchez Negrette O, Marco D, Barrio A, Ciaccio M,
Segura M, et al. Early diagnosis of congenital Trypanosoma cruzi
infection using PCR, hemoculture, and capillary concentration, as
compared with delayed serology. J Parasitol. 2005;91:1468–73.
DOI: 10.1645/GE-549R.1
Azogue E, La Fuente C, Darras C. Congenital Chagas disease in
Bolivia: epidemiological aspects and pathological findings. Trans
R Soc Trop Med Hyg. 1985;79:176–80. DOI: 10.1016/0035-9203
(85)90328-1
Address for correspondence: Yves Jackson, Department of Community
Medicine and Primary Care, Geneva University Hospitals, Rue Michelidu-Crest 24 1211, Geneva 14, Switzerland; email: yves.jackson@
hcuge.ch
603
7. Paediatric Chagas disease in Europe : a series of 45 cases from Spain and
Switzerland
Ped Inf Dis J. 2014. Epub ahead of print
Par:
Rodriguez L, Posfay-Barbe K, Monsonis Cabedo M, Juncosa Morros T, Diana A, Wyler C-A,
Martinez de Tejada B, Chappuis F, Fumadó Pérez V, Jackson Y.
35
The Pediatric Infectious Disease Journal Publish Ahead of Print
DOI: 10.1097/INF.0000000000000139
Pediatric Chagas Disease in Europe: 45 Cases from Spain and Switzerland
Luciana Rodriguez Guerineau1,2, MD, Klara M. Posfay-Barbe1, MD, MS, Manuel
Monsonis Cabedo3, Teresa Juncosa Morros3, PhD, Alessandro Diana1, MD, Claire-Anne
D
Wyler Lazarevic1, MD, Begoña Martinez de Tejada4, MD, PhD, François Chappuis5 ,
MD, PhD, Victoria Fumadó Pérez2, MD, PhD, and Yves Jackson6, MD
Department of Pediatrics, University Hospitals of Geneva and University of Geneva,
TE
1
Switzerland;
Department of Pediatrics, Sant Joan de Déu Hospital, University of Barcelona, Spain;
3
Laboratory of Microbiology, Sant Joan de Déu Hospital, University of Barcelona, Spain;
4
Department of Gynecology & Obstetrics, University Hospitals of Geneva and University of
EP
2
Geneva, Geneva, Switzerland;
Division of international and humanitarian medicine, Department of community medicine,
C
5
primary care and emergency medicine, University Hospitals of Geneva and University of
6
C
Geneva, Geneva, Switzerland;
Division of primary care, Department of community medicine, primary care and emergency
A
medicine, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland;
Address correspondence to: Luciana Rodriguez Guerineau, International Health Unit,
Department of Pediatrics, Sant Joan de Déu Hospital, Passeig Sant Joan de Déu 2, 08950
Esplugues de Llobregat, Barcelona, Spain. Phone: +34 93 253 21 00. Fax: +34 93 203 39 59. Email: lrodriguez@hsjdbcn.org
Abbreviated title: Pediatric Chagas Disease in Europe
1
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Running head: Pediatric Chagas Disease
Key words: Chagas disease, Trypanosoma cruzi, children, migration, Europe
Funding source: No external funding was received for this study.
Financial Disclosure: The authors have no financial relationships relevant to this article to
disclose.
D
Conflict of Interest: The authors have no conflicts of interest to disclose.
Acknowledgement
TE
C. Reis, M. Varcher and A. Mauris gave us permission to be mentioned in the acknowledgments
A
C
C
EP
section.
2
Abstract
Background
Chagas disease, a potentially fatal parasitic infection, is emerging in Europe in the context of
international migration but there is little public health attention and frequent lack of clinicians’
awareness. To date, there is no published information about clinical characteristics in chilren.
D
Methods
We reviewed the medical files of all children (<18 years) with Chagas disease managed in two
TE
hospitals in Barcelona, Spain and Geneva, Switzerland between January 2004 and July 2012.
Results
Forty-five cases were identified. Two children (4.4%) were diagnosed during the acute phase and
EP
the remaining 43 (95.6%) were in the chronic phase of the infection. All but one were
asymptomatic. Forty (97.6%) of the 41 treated children completed 60-days of treatment. Thirtyfive (85.4%) received benznidazole, five (12.2%) nifurtimox and one (2.4%) both drugs
C
consecutively. There were 2 (4.9%) treatment interruptions due to adverse events. The most
frequent adverse events were skin rash (24.4%), anorexia or insufficient weight gain (14.6%) and
C
anemia (2.4%). Twenty-nine (64.4%) children were followed-up by serology after 2 years. Five
(17.2%) were cured.
A
Conclusion
Pediatric Chagas disease is an emerging health issue in Europe that requires enhanced attention.
Greater emphasis should be put on screening pregnant women at risk and their newborns in case
of infection along with older children and relatives. Pediatricians have a central role to play in
providing families with information and offering testing in situations of risk.
3
Chagas disease, a parasitic zoonosis caused by Trypanosoma cruzi predominates in Latin
America. It puts 8 - 10 million infected persons at risk of potentially life-threatening
cardiomyopathy and disabling chronic digestive tract complications occurring decades after the
initial infection.1 Despite past successes of regional control initiatives, there is currently an
epidemiological shift entailing new challenges following enhanced local and transnational
D
population movements in Latin America and alongside the progressive urbanization of the
infection.2,3 As a result, vertical infection is becoming a prominent route of transmission.3,4
TE
Recently, a growing number of T. cruzi infections have been recorded outside Latin America,
after more than 18 million people at risk moved to non-endemic countries, mostly to North
America, Europe, and Australia.5 In 2009, more than 3.2 million immigrants from endemic
EP
regions lived in Europe, of whom around 1 million were without valid residence permits
(undocumented) thus facing difficulties in accessing to medical care.6 It is estimated that 60,000
to 120,000 infected persons currently live in Europe.6,7 Sixteen European countries have reported
cases, mostly in adult immigrants from Latin America, and T. cruzi transmission via blood
A large proportion of cases in Europe affect immigrants originating from Bolivia, where high
C
11
C
transfusion, organ transplant and from mother-to-child has been identified in several countries.8-
prevalence rate and operational difficulties represent consequent challenges in controlling
A
Chagas disease.2,3,12 While most endemic countries have put emphasis on detecting infection in
children because of more favorable treatment outcomes as compared to adults, non-endemic
countries have so far paid only very limited attention to Chagas disease in children.2,11 Yet, it has
been shown that screening for Chagas disease in pregnant women or newborns provide the
opportunity of detecting further cases among siblings and relatives as infections often occur in
clusters.13 Only few cities or regions in Western Europe have implemented screening programs
4
in mothers and newborns to detect congenital transmission. Detection in older children is even
less practiced as no recommendations on systematic or regular opportunistic screening exists in
this age group.11 Considering the frequent vulnerable socioeconomic conditions in which
affected immigrant family live and the long-lasting course of the infection, a holistic whole-offamily approach within a longitudinal perspective is required to effectively tackle this issue.
D
Several health institutions in Europe have initiated programs along this line in recent years. This
paper reports a series of cases of pediatric T. cruzi infections diagnosed and managed in two
TE
hospitals in Barcelona, Spain and Geneva, Switzerland. It discusses the clinical and
epidemiological significance of this emerging health issue and presents a set of recommendations
EP
regarding the management of pediatric Chagas disease in this region.
METHODS
Setting
C
Spain is the country with the largest number of Latin Americans in Europe. There were more
than 1,400,000 Latin American immigrants registered in Spain in 2012, not considering the
C
unknown number of non-registered persons.14 In Barcelona, the seroprevalence of T. cruzi
infection in pregnant Latin American women is 3.4%, and 7.3% of their newborns have been
A
shown as congenitally infected.15 The Sant Joan de Déu Hospital is one of the reference centers
for pediatric Chagas disease in the city. Geneva, Switzerland, hosts a community of Latin
American immigrants with high T. cruzi infection rate and congenital transmission has been
documented since 2001.9,16 The Geneva University Hospitals are the reference centers for
Chagas disease management and research in the country. Immigrants without the mandatory
5
health insurance can access to care through a special scheme, which has proven capital in the
identification of Chagas disease emergence in Switzerland.
Systematic management of pediatric Chagas disease started in 2004 in Barcelona and in 2007 in
Geneva. Both programs entail a multidisciplinary approach focusing on the whole family and are
based on clinical protocols published elsewhere.9,15 The diagnosis of Chagas disease in children
D
entails a complex multi-step process requiring strict adherence to published international
TE
recommendations to ensure optimal performance and comparability.
Case definition
We present here all children up to18 years with a diagnosis of T. cruzi infection identified in
Diagnostic procedures
EP
and/or managed by our two Hospitals between January 2004 and July 2012.
C
Previous papers thoroughly explained the diagnostic procedures used in both Hospitals.9,10 In
summary, when an acute infection, including congenital, was suspected, the diagnostic procedure
C
included a microscopic blood examination and an in-house real-time PCR if the blood
examination was negative. If both tests were negative, children underwent serological testing
A
nine months later. In Barcelona two enzyme-linked immunosorbent assays (ELISA) were used,
one with recombinant antigens (BioELISA Chagas; Biokit S.A.) and the other with crude antigen
from T. cruzi epimastigotes (in-house ELISA) in older infants. Positive results were confirmed
by a third test, the CHAGAS ELISA IgG+IgM (Vircell microbiologists). In Geneva, the
BioELISA Chagas test and an in house Immunofluorescence assay using killed T. cruzi parasites
(Swiss Tropical Institute, Basel) were performed for diagnosis. In children without clinical and
6
epidemiological argument for an acute infection, the diagnostic procedure included the same
serological tests with the optional use of PCR in Barcelona.
In case of proven infection, patients underwent full clinical assessment, including a 12-leads
ECG with a 30 seconds DII strip and an echocardiogram allowing for the staging of the disease.
D
The ECG was also performed annually during follow-up.
Staging
TE
We staged the infection according to the WHO guidelines.2 Newborns of T. cruzi seropositive
mothers or older children with epidemiological arguments in favor of a recent (<2 months)
exposure to T.cruzi and presenting with positive parasitological tests were considered having an
EP
acute infection. All others were considered being in the chronic phase of the infection. The
indeterminate form of the chronic phase was diagnosed in presence of positive serological tests,
normal ECG and echocardiogram and in absence of clinical signs or symptoms evocative of
C
organ complications. The diagnosis of chronic Chagas disease with cardiac or digestive
complication was made in presence of characteristic symptoms or clinical signs confirmed by
C
radiological exams and after thorough clinical investigations excluding alternative etiologies.
A
Treatment, follow-up and assessment of cure
Anti-parasitic therapy, either nifurtimox 10mg/kg/day or benznidazole using different protocols
(8-10 mg/kg/day in Barcelona; 10 mg/kg/day in children below 12 years and 5 mg/kg/day in
older children with a maximum dose of 300 mg/day in Geneva), was given under close
monitoring for 60 days. All efforts were put to provide an annual clinical and serological followup to assess the response to treatment as recommended.2 Healthcare workers made all due efforts
7
to contact families not presenting to their follow-up appointments. Cure was determined by two
negative serological tests after treatment.
Management of other family members
In presence of an index case (mother or infant), siblings and relatives were offered the
D
opportunity to undergo a screening test. Mothers and other infected family members were then
managed according to recommendations.2,17 This paper only presents and discusses results
TE
pertaining to the infected children.
Statistics
EP
We performed simple descriptive statistical analysis and compared groups using Student’s t or
Mann-Whitney U tests for continuous variables and Chi-square or Fisher's exact tests for
categorical variables, according to their distribution. P-values less than 0.05 were considered
C
RESULTS
C
significant. All analyses were performed using SPSS 19.0 (IBM Corp., Armonk, NY).
Demographic and clinical characteristics
A
Forty-five children, all from Latin American origin, 35 in Spain and 10 in Switzerland have been
diagnosed with T. cruzi infection in the two Hospitals (Table 1). Children were aged 1 month to
18 years at time of diagnosis. They originated from Bolivia (n=41), Argentina (n=3) and
Nicaragua (n=1). 18 (40%) were born in Europe and 27 (60%) in Latin America. Two children
(4.4%) were diagnosed during the acute phase and the remaining 43 (95.6%) were in the chronic
phase of the infection. One (2.2%) child, a 9-year-old girl from Bolivia, was suffering from the
8
digestive form of the chronic infection in presence of a megaesophagus confirmed by
characteristic imaging and endoscopic exams. All others were in the indeterminate form of the
chronic phase. No child presented or developed symptoms or ECG alteration suggestive of
cardiac complication during the follow-up period. Besides the two cases responding to the
criteria of an acute congenital infection, trans-placental transmission was the route of infection
D
for those children born in Europe who never travelled abroad. For those born in Latin America,
this was also the most likely route although vectorial transmission could not be formerly ruled
TE
out.
Treatment
EP
All children received anti-parasitic treatment, three of whom in their country of origin and one in
another hospital in Barcelona. Of the forty-one treated in our two Hospitals, thirty-five (85.4%)
received benznidazole, five (12.2%) nifurtimox, and one (2.4%) both drugs consecutively.
C
Thirteen (31.7%) presented one adverse event (AE), while two (4.9%) had two. The most
frequent AEs were skin rash (n=10, 24.4%), anorexia or insufficient weight gain (n=6, 14.6%),
C
and anemia (n=1, 2.4%). There were two (4.9%) treatment interruptions due to drug intolerance.
The first case followed a generalized rash appearing at day 13 after benznidazole initiation,
A
leading to definite treatment interruption. The second followed a nifurtimox-related generalized
rash appearing at day 8, leading to a switch to benznidazole without complication. In other
patients with rash, antihistaminic use and/or transient anti-parasitic treatment dose reduction
were effective in alleviating symptoms without the need for treatment interruption. The
occurrence of adverse events was neither associated with the type of drug (p=1) nor with age
(p=0.14).
9
Follow-up and assessment of cure
Serological follow up at 2 years was possible in 29 children (64.4%). In 8 cases, the follow-up
serology is not available yet and 8 children were lost to follow-up after treatment. At 2 years,
five patients (17.2%) presented negative serology indicating definitive cure and twenty-four
(82.8%) still presented positive results. Of those, 17 (58.6%) showed a serological titer reduction
D
less than 50% compared to pre-treatment levels and 7 (24.1%) had a >50% titer reduction. When
comparing cured with not cured children, there was no significant statistical difference in origin
TE
(Bolivia versus other South American countries, p=0.32), gender (p=0.34), type of drug received
(p=0.17), and PCR positivity at time of diagnosis (p=0.48). The only factor associated with cure
was the age at diagnosis and treatment (p=0.008). All infants (n=4) treated before one year of
age was cured.
C
DISCUSSION
EP
age were cured, whereas only 1 (4.2%) out of 24 children diagnosed and treated after one year of
We present the first series of cases of pediatric Chagas disease diagnosed and managed outside
C
Latin America, which attests that T. cruzi infection is an emergent health issue among children in
Europe. We found that most children tolerated treatment well but that the cure rate two years
A
after treatment was low. Moreover we experienced difficulties in adequately following-up this
immigrant and vulnerable population over years.
Our data add to previous studies illustrating the emergence of Chagas disease in adult immigrant
populations in Europe and about its vertical transmission outside Latin America.11 Currently,
there is no information about the number of children infected in Europe. Epidemiological models
10
showed that pediatric cases could include 20 to 184 congenitally infected newborns and 474 to
919 infected adoptees born in Latin America in 2009 but we don’t know how many older
children born in Latin America and infected with T. cruzi infection reside in European countries
following early age migration.6 Given the current migration dynamics and the indolent course of
the disease during the initial decades after infection, it can be presumed that a substantial number
D
of older children and teenagers living in Europe host undetected T.cruzi infection and present
risks of complication for the medium term. Epidemiological evaluation is further hampered by
TE
the unknown number of undocumented children at risk and by the fact that Latin American
adoptees are a poorly studied group. In Spain, between 1998 and 2009, 7359 adoptees originated
from countries at risk for Chagas disease, representing 17.2 % of all international adoptees.18 In
EP
Switzerland, between 1979 and 2008, 5043 children born in endemic countries were adopted,
accounting for 25.7% of all foreign-born adoptees.19 In absence of systematic screening, it is
likely that a number of adoptees are currently infected, which calls for enhanced attention for this
C
group.
Taking a life-long perspective, economic analysis showed that Chagas disease incurred high
C
costs to societies in endemic and non-endemic regions.20 On the other hand, pre-natal screening
in non-endemic countries, even in situation of low prevalence and low transmission rate, has
A
been shown to have a favorable cost-benefit ratio. 21 Therefore, there is an urgent need for
accrued public health and clinical attention to Chagas disease in children living in Europe and to
the development of appropriate interventions to tackle health and economic risks pertaining to
the long-term complications of the infection and to its unnoticed transmission.
11
All children at the acute and chronic phase were asymptomatic at time of diagnosis except one
child previously diagnosed in Bolivia who already had developed the digestive form of the
chronic phase. There is no similar data outside Latin America allowing for comparison. In Latin
America, it is estimated that less than 5% of congenitally infected infants develop Chagas
disease-related symptoms during the acute phase.2 Further longitudinal studies are required to
TE
infected children living outside area with risk of reinfection.
D
more precisely assess the development and the Chagas disease-related health outcomes of
All children but one could finish the 60-days treatment and they presented relatively low rates of
adverse events. This is in sharp contrast with the poor tolerance to benznidazole and nifurtimox
EP
found in adults, leading to frequent treatment interruptions.22,23 This represents a strong argument
in favor of deploying efforts to detect and treat cases as early as possible. Current therapeutic
recommendations state that treatment should be provided to all infected newborns, children and
adolescents less than 18 years of age, irrespective of the stage of the disease.2,17 Two drugs,
C
nifurtimox and benznidazole, are currently available and offer similar efficacy in children.24,25
C
Yet, the recently available benznidazole pediatric formulation will likely facilitate treatment of
A
young children, making of it the first-line option.
We found an overall strikingly low cure rate compared to data from Latin America.26,27 This may
be explained by the fact that most children with serological follow-up were probably already
infected for several years. Indeed, cure in children, as attested by conversion to negative
serological results after treatment, has been shown to be inversely proportional to the duration of
infection.24,28 A second explanation may pertain to the natural prolonged latency before return to
12
negative serology after treatment and therefore to the need for a prolonged serological follow-up,
as shown in adults treated decades after the initial infection and presenting long-lasting humoral
responses.29 This might be illustrated by the fact that children who still tested positive after 2
years of follow-up had lower serological titers as compared to pre-treatment values, suggesting a
possible favorable ongoing outcome as recently proposed by some authors.30 In absence of
D
consensus on that issue, there is a need for further research on the clinical meaning of decreasing
antibody titers after treatment in children living in non-endemic countries. More studies are also
TE
needed to better assess treatment efficacy in children in non-endemic countries and to understand
the factors associated with treatment failure.
EP
Following-up mobile and vulnerable immigrant families over years was a major challenge for
our two Hospitals. The consequent rate of loss to follow-up represents a limitation of our study.
In absence of specific investigation, we cannot provide precise explanations but mobility within
C
and between countries in Europe in search of better economic opportunities, the influence of the
global financial crisis on the job market, and difficulties to accessing to care due to
C
administrative reasons are likely factors that would deserve further investigation. A survey in
Geneva showed that most immigrants with Chagas disease lived in very disadvantaged
A
conditions and had to face multiple barriers to access appropriate care.31 This highlights the need
for considering the socioeconomic condition in which affected families live when organizing
care for Chagas disease patients. It also calls for strengthening coordination between health
institutions, as well as between family physician and specialized units, within and across
countries over time.
13
CONCLUSION
Considering the available epidemiological information about infection risks in children, the
dynamic of T. cruzi transmission in Europe and the experience gathered in our two Hospitals, we
suggest screening the following groups of children either systematically or at least in an
opportunistic way depending on the local context: a) children born from T. cruzi infected
D
mothers; b) children of families in which a first or second-degree relative has T. cruzi infection;
c) children born or having lived in an area where active vectorial transmission occurs; d) children
TE
who have received blood or tissue products in Latin America; and e) adoptees originating from
an endemic country. In addition, the finding of any pediatric case should entail thorough
investigation within the family, including the parents and the siblings. Serologically positive
EP
children should be informed about not donating blood or other tissues and female teenagers
should be informed of the theoretical persistent risk of transmission to their offspring.
C
Specific attention should be paid to children living in the most vulnerable groups of migrants,
such as immigrants without valid residency documents. Finally, the possibility of co-infection
C
with HIV in the mother and the child should be kept in mind and actively searched for in case of
risk factors given the aggravated clinical consequences in that context.32 We acknowledge the
A
central role of pediatricians in providing children at risk and their families with appropriate
information, counseling and testing, and call for more research at clinical and public health levels
on the challenges related to the emergence of Chagas disease in children in Europe. Like other
neglected diseases, Chagas disease illustrates the necessity to develop comprehensive,
collaborative and holistic approaches to provide the optimal health outcome to affected families.
This collaboration between two cities in different countries reflects this concern and should serve
14
as a starting point to further collaborations aiming at improving the management of pediatric
Chagas disease in Europe.
ACKNOWLEDGEMENT
The authors wish to acknowledge the contribution of C. Reis, Dr M. Varcher and A. Mauris in
A
C
C
EP
TE
D
identifying, diagnosing and managing the patients.
15
REFERENCES
1.
World Health Organization. Sustaining the drive to overcome the global impact of
neglected tropical diseases. Geneva: WHO, 2013.
2.
World Health Organization. Control of Chagas disease. Brasilia (Brazil): WHO, 2002
3.
Alonso-Vega C, Billot C, Torrico F. Achievements and challenges upon the
2009. PLoS Negl Trop Dis. 2013;7(7):e2304.
Moscatelli G, Garcia Bournissen F, Freilij H, Berenstein A, Tarlovsky A, Moroni S, et al.
TE
4.
D
implementation of a program for national control of congenital Chagas in Bolivia: results 2004-
Impact of migration on the occurrence of new cases of Chagas disease in Buenos Aires city,
Argentina. J Infect Dev Ctries. 2013;7(8):635-7.
Schmunis GA, Yadon ZE. Chagas disease: a Latin American health problem becoming a
EP
5.
world health problem. Acta Trop. 2009;115(1-2):14-21.
6.
Basile L, Jansa JM, Carlier Y, Salamanca DD, Angheben A, Bartoloni A, et al. Chagas
2011;16(37).
8.
World Health Organization. Chagas disease in Europe. Geneva: WHO, 2010.
C
7.
C
disease in European countries: the challenge of a surveillance system. Euro Surveill.
Castro E. Chagas' disease: lessons from routine donation testing. Transfus Med.
A
2009;19(1):16-23.
9.
Jackson Y, Myers C, Diana A, Marti HP, Wolff H, Chappuis F, et al. Congenital
transmission of Chagas disease in Latin American immigrants in Switzerland. Emerg Infect Dis.
2009;15(4):601-3.
10.
Munoz J, Portus M, Corachan M, Fumado V, Gascon J. Congenital Trypanosoma cruzi
infection in a non-endemic area. Trans R Soc Trop Med Hyg. 2007;101(11):1161-2.
16
11.
World Health Organization. Control and prevention of Chagas disease in Europe. Report
of a WHO Informal Consultation (jointly organized by WHO headquarters and the WHO
Regional Office for Europe) Geneva, Switzerland, 17–18 December 2009. Geneva: WHO, 2009.
12.
Organizacion Panamericana de la Salud. Estimacion cuantitativa de la enfermedad de
Chagas en las Americas. Montevideo, Uruguay: PAHO, 2006
Zulantay I, Apt W, Ramos D, Godoy L, Valencia C, Molina M, et al. The
D
13.
epidemiological relevance of family study in chagas disease. PLoS Negl Trop Dis.
14.
TE
2013;7(2):e1959.
Spanish National Institute of Statistics. Estadística de Migraciones. 2013; Available at:
http://www.ine.es. Accessed March 31 2013.
Munoz J, Coll O, Juncosa T, Verges M, del Pino M, Fumado V, et al. Prevalence and
EP
15.
vertical transmission of Trypanosoma cruzi infection among pregnant Latin American women
attending 2 maternity clinics in Barcelona, Spain. Clin Infect Dis. 2009;48(12):1736-40.
Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin A, et al. Prevalence, clinical
C
16.
staging and risk for blood-borne transmission of Chagas disease among Latin American migrants
17.
C
in Geneva, Switzerland. PLoS Negl Trop Dis. 2010;4(2):e592.
Bern C, Montgomery SP, Herwaldt BL, Rassi A, Jr., Marin-Neto JA, Dantas RO, et al.
A
Evaluation and treatment of chagas disease in the United States: a systematic review. JAMA.
2007;298(18):2171-81.
18.
Spanish National Institute of Statistics. Adopciones internacionales por países y periodo.
2012; Available at:
http://www.ine.es/jaxi/tabla.do?type=pcaxis&path=/t25/a072/a02/l0/&file=c70004.px. Accessed
November 11 2012.
17
19.
Swiss Federal Bureau of Statistics. 2010; Available at: http://www.pxweb.bfs.admin.ch/.
Accessed September 5 2012.
20.
Lee BY, Bacon KM, Bottazzi ME, Hotez PJ. Global economic burden of Chagas disease:
a computational simulation model. Lancet Infect Dis. 2013;13(4):342-8.
21.
Sicuri E, Munoz J, Pinazo MJ, Posada E, Sanchez J, Alonso PL, et al. Economic
in a non endemic area. Acta Trop. 2011;118(2):110-7.
Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis F. Tolerance and safety
TE
22.
D
evaluation of Chagas disease screening of pregnant Latin American women and of their infants
of nifurtimox in patients with chronic chagas disease. Clin Infect Dis. 2010;51(10):e69-75.
23.
Pinazo MJ, Guerrero L, Posada E, Rodriguez E, Soy D, Gascon J. Benznidazole-related
EP
adverse drug reactions and their relationship to serum drug concentrations in patients with
chronic chagas disease. Antimicrob Agents Chemother. 2013;57(1):390-5.
24.
Sosa-Estani S, Segura EL. Etiological treatment in patients infected by Trypanosoma
25.
C
cruzi: experiences in Argentina. Curr Opin Infect Dis. 2006;19(6):583-7.
Urbina JA. Specific chemotherapy of Chagas disease: Relevance, current limitations and
26.
C
new approaches. Acta Trop. 2009 ;115(1-2):55-68
Yun O, Lima MA, Ellman T, Chambi W, Castillo S, Flevaud L, et al. Feasibility, drug
A
safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras,
Guatemala, and Bolivia: 10-year experience of Medecins Sans Frontieres. PLoS Negl Trop Dis.
2009;3(7):e488.
27.
Escriba JM, Ponce E, Romero Ade D, Vinas PA, Marchiol A, Bassets G, et al. Treatment
and seroconversion in a cohort of children suffering from recent chronic Chagas infection in
Yoro, Honduras. Mem Inst Oswaldo Cruz. 2009;104(7):986-91.
18
28.
Rassi A, Jr., Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010;375(9723):1388-402.
29.
Jackson Y, Chatelain E, Mauris A, Holst M, Miao Q, Chappuis F, et al. Serological and
parasitological response in chronic Chagas patients 3 years after nifurtimox treatment. BMC
Infect Dis. 2013;13:85.
30.
Viotti R, Vigliano C, Alvarez MG, Lococo B, Petti M, Bertocchi G, et al. Impact of
Negl Trop Dis. 2011;5(9):e1314.
Jackson Y, Castillo S, Hammond P, Besson M, Brawand-Bron A, Urzola D, et al.
TE
31.
D
aetiological treatment on conventional and multiplex serology in chronic Chagas disease. PLoS
Metabolic, mental health, behavioural and socioeconomic characteristics of migrants with
Chagas disease in a non-endemic country. Trop Med Int Health. 2012. 17(5):595-603.
Almeida EA, Ramos Junior AN, Correia D, Shikanai-Yasuda MA. Co-infection
EP
32.
Trypanosoma cruzi/HIV: systematic review (1980-2010). Rev Soc Bras Med Trop.
A
C
C
2011;44(6):762-70.
19
Table 1: Demographic and clinical characteristics of 45 children with Chagas disease in
Barcelona, Spain and Geneva, Switzerland.
Characteristics
Switzerland (N=10)
Total (N=45)a
n
n
n (%)
4
1
4
1 month -18 years
1 month – 16 years
1 month – 18
Spain (N=35)
Age in years (median)
Range
17
Female
18
4
22 (48.9)
33
8
41 (91.1)
1
2
3 (6.7)
1
0
1 (2.2)
1
1
2 (4.4)
Chronic indeterminate
33
9
42 (93.3)
Chronic digestive
1
0
1 (2.2)
Benznidazole
31
4
35 (85.4)
Nifurtimox
0
5
5 (12.2)
Both
0
1
1 (2.4)
Presence of AE
11
4
15 (36.6)
Skin rash
6b
4
10b (24.4)
Origin
Bolivia
Argentina
Nicaragua
Stage of infection
C
C
Acute
6
23 (51.1)
TE
Male
EP
Gender
D
years
A
Treatment (n=41)
Tolerance (n=41)
20
Insufficient weight gain/
anorexia
6b
0
6b (14.6)
Anemia
1
0
1 (2.4)
Treatment interruptions
2
0
2 (4.9)
21
3
24 (82.8)
↓ <50%
16
1
17 (58.6)
↓ >50%
5
2
7 (24.1)
Negative
TE
Positive
D
Serology at 2 year follow-up (n=29)
3
2
5 (17.2)
AE: Adverse event. aUnless specified otherwise. bTwo children had skin rash and
A
C
C
EP
insufficient weight gain
21
8. Metabolic, mental health, behavioral and socioeconomic characteristics in
migrants with Chagas disease
Trop Med Int Health. 2012;17(5):595-603
Par:
Jackson Y, Castillo S, Hammond P, Besson M, Brawand-Bron A, Urzola D, Gaspoz J-M,
Chappuis F.
57
Tropical Medicine and International Health
doi:10.1111/j.1365-3156.2012.02965.x
volume 00 no 00
Metabolic, mental health, behavioural and socioeconomic
characteristics of migrants with Chagas disease in a
non-endemic country
Yves Jackson1, Sara Castillo2, Perle Hammond2, Marius Besson1, Anne Brawand-Bron1, Diana Urzola1,
Jean-Michel Gaspoz1 and François Chappuis3
1 Department of Community Medicine, Primary Care and Emergency Medicine, University Hospitals Geneva, Switzerland
2 Geneva Medical School (University), Geneva, Switzerland
3 Division of International and Humanitarian Medicine, University Hospitals Geneva, Switzerland
Abstract
objectives Chronic Chagas disease causes cardiopathy in 20–40% of the 8–10 million people
affected. The prevalence of atherogenic factors increases rapidly in Latin America. Somatic, mental,
behavioural and social characteristics of the 80 000 Latino migrants with Chagas disease in Europe are
not known. We postulate that they may accumulate these factors for poor health – notably
cardiovascular-outcomes.
methods This study took place at the Geneva University Hospitals in 2011. Latin American
migrants with Chagas disease diagnosed in Geneva since 2008 were contacted. Interviews and blood
tests assessed behavioural, socioeconomic, metabolic and cardiovascular factors.
results One hundred and thirty-seven patients (women: 84.7%; median age: 43 years) with chronic
Chagas disease were included in the study. The majority were Bolivians (94.2%), undocumented
(83.3%), uninsured (72.3%) and living below the Swiss poverty line (89.1%). Prevalence of obesity was
25.5%, of hypertension 17.5%, of hypercholesterolemia 16.1%, of impaired fasting glucose 23.4%,
of diabetes 2.9%, of metabolic syndrome 16.8%, of anxiety 58.4%, of depression 28.5%, of current
smoking 15.4% and of sedentary lifestyle 62.8%. High (>10%) 10-year cardiovascular risk affected
12.4%.
conclusions Latin American migrants with Chagas disease accumulate pathogenic chronic conditions
of infectious, non-transmissible, socioeconomic and behavioural origin, putting them at high risk of poor
health, notably cardiovascular, outcomes. This highlights the importance of screening for these factors
and providing interventions to tackle reversible disorders; facilitating access to care for this hard-toreach population to prevent delays in medical interventions and poorer health outcomes; and launching
prospective studies to evaluate the long-term impact of these combined factors on the natural course
of Chagas disease.
keywords Chagas disease, migrants, Europe, risk factors, prevention, cardiovascular disease
Introduction
Major social and demographic transformations are
occurring in Latin America: alongside with rapid
urbanization, life expectancy steadily rises and the main
burden on population health is shifting from infectious
diseases to chronic non-communicable disorders (Andrade
2009). The increase in overweight prevalence in Latin
America has been among the world’s fastest since 1980,
twice the rate observed in other parts of the world (Finucane
et al. 2011). Southern and tropical regions of Latin America
display among the world’s fastest increase in hypertension
ª 2012 Blackwell Publishing Ltd
prevalence in men (Danaei et al. 2011a). The same is true for
diabetes in both men and women (Danaei et al. 2011a,b).
The diabetes and obesity epidemic and the resulting cardiovascular diseases are expected to heavily impact on
population health and economics in this region.
Eight to ten million people are infected with
Trypanosoma cruzi, the causative agent of Chagas disease
(PAHO 2006). The majority lives in Central and South
(Latin) America, where the disease is present in 21
countries. After decades, chronic T. cruzi infection causes
cardiac damage in 20–40%, resulting in premature
mortality and in a serious public health burden, with an
1
volume 00 no 00
Y. Jackson et al. Health of migrants with Chagas disease in Europe
estimated 667 000 DALYs lost each year (PAHO 2006;
Rassi et al. 2010). Arrhythmia, heart failure and cardioembolic events account for premature morbidity and
mortality (Rassi et al. 2010). In recent years, the
distribution of the disease has evolved following the
adaptation of vectors to urban settings, ecological changes
and global migrations, causing new public health
challenges (Coura & Vinas 2010). Millions of people have
left endemic countries towards North America, Western
Pacific Region and Europe, which harbors 3 millions
migrants at risk of carrying Chagas disease (Gascon et al.
2009). Consequently, imported cases and transmission of
Chagas disease have been increasingly reported in
Western Europe where more than 80 000 Latin American
migrants are infected (Jackson et al. 2009a,b, 2010a,b;
WHO 2009). Migrants with Chagas disease in Europe are
predominantly women of child-bearing age, with 11.3–
22.5% already affected by T. cruzi cardiopathy (Munoz
et al. 2009; Jackson et al. 2009a,b, 2010a,b; Perez-Ayala
et al. 2011).
Non-medical factors such as poor living conditions and
socioeconomic inequalities are massive contributors to
global premature morbidity and mortality (Wilkinson &
Marmot 2003). Migrants are particularly exposed,
considering their social and mental health vulnerability,
and the risk of not accessing optimal medical care.
Therefore, Latin American migrants in Europe presenting
with the chronic form of Chagas disease may accumulate
chronic risks for cardiac disease and adverse health
outcomes from infectious, metabolic, psychological and
social origins. If so, this could impact the usual prognosis
of patients with chronic Chagas and thus require specific
management to prevent adverse outcomes. So far,
recommendations and experts opinions have favored a
disease-centered approach for the clinical management of
Chagas disease patients, focusing on the infectious
component and its complication and giving low
importance to associated multidimensional factors (WHO
2002; Rassi et al. 2010). We aimed to evaluate the presence
of cumulative metabolic, mental health, behavioural and
socioeconomic factors in a cohort of Latin American
migrants with Chagas disease in Geneva, Switzerland. As
hypothesized, we found high prevalence of chronic adverse
factors for global, notably cardiovascular, health in this
cohort of migrants with Chagas disease.
Methods
Ethical statement
This study was approved by the ethical board for medical
research of the Geneva University Hospitals. Written
informed consent was obtained from all participants.
2
Study design and setting
This cross-sectional study took place at the Geneva
University Hospitals, which are the reference centre for the
clinical management of Chagas disease in the Geneva state.
Migrants’ communities and support groups were informed
about the study.
Participants
Between January and June 2011, all adult patients with
Chagas disease diagnosed in Geneva since 2008 were
invited to participate. The diagnosis of Chagas disease was
based on two positive serological tests using different
methods, as recommended by WHO. Inclusion criteria
were age > 15 years and signature of the informed consent
form (with a parent signature for 16–18-year-old individuals). Patients were individually contacted by phone. In the
event of five unanswered phone calls, investigators sent an
invitation letter to the last recorded address. All study
documents were available in Spanish.
Data collection and definition
Demographic, behavioural and socio-economic variables
were collected by multilingual (French, Spanish) investigators in a one-to-one setting at the Geneva University
Hospitals. Three or five-item Likert scales were used to
collect some categorical data (e.g. job satisfaction,
behavioural modification). Investigators recorded information on economic items (e.g. income, remittance) based
on oral information without requesting documentary
evidence. Weight modification following migration was
assessed by comparing the weight measured during the
study consultation with the weight last measured before
the participant left his ⁄ her home country. To address a
possible memory bias, we used a proxy by comparing the
current self-assessed and measured weights in a subsample
of 38 consecutive participants. Results showed no significant differences (68.5 vs. 68.6 kg).
Screening for anxiety and depression was performed
using the Spanish version of Hospital Anxiety and
Depression Scale (HADS) (Quintana et al. 2003). This
questionnaire investigates both dimensions with seven
items each, with a maximal score of 28 points per
dimension. The threshold for a positive screening was
8 points in both dimensions (Hermann 1997). Investigators
were available for help if the subject faced difficulties in
reading or understanding questions.
Anthropomorphic measures were collected in participants wearing light clothes after removing shoes. Blood
pressure was measured three times consecutively on the left
volume 00 no 00
arm with a calibrated automated Omron M7 device while
the patient was sitting in a calm environment, at least 20
min after the beginning of the consultation. The median
systolic and diastolic values were used for the diagnosis of
hypertension. Staging of Chagas disease was assessed by
performing a 12-lead electrocardiogram (ECG) with a 30-s
DII strip unless a recent (< 12 months) similar ECG was
available in the patients’ medical file. Presence of Chagas
disease typical ECG abnormalities (right bundle-branch
block, atrio-ventricular blocks, left anterior fascicular
block, supraventricular or ventricular premature beats,
ST-T changes, abnormal Q wave and low QRS voltage) in
absence of other documented cause of cardiopathy was
considered diagnostic for T. cruzi cardiopathy. Digestive
involvement, which had been previously diagnosed in one
participant, was not actively searched for in this study.
Fasting serum glucose and cholesterol levels were measured
in early morning according to standard laboratory methods
in use at the Geneva University Hospitals.
Ten-year risk of cardiovascular disease was determined
using the male and female version of the Framingham
10-year risk calculator (D’Agostino et al. 2008). This
Table 1 Diagnostic criteria for metabolic,
behavioural, anthropomorphic and mental
health disorders in patients with Chagas
disease in Geneva, Switzerland
composite measure includes sex, age, systolic blood
pressure, total cholesterol, HDL cholesterol, current
anti-hypertensive therapy, cigarette smoking and diabetes.
The score being validated for individuals aged 30 onwards,
we plotted younger participants (n = 8, aged 25–29) as
being 30. Ten-year risk was graded as low if <5%,
intermediate if between ‡5% and <10%, and high if
‡10%.
Diagnostic criteria for metabolic, behavioural,
anthropomorphic and mental health items are summarized
in Table 1. To adapt to participants’ limited availability,
fasting blood tests were only done once. All results were
communicated to participants. In case of detection of new
health problem(s), participants were referred for clinical
management to the Division of Primary Care Medicine of
the Geneva University Hospitals, or to their general
practitioner.
Statistics
Results are presented as proportions with 95% confidence
intervals, and continuous data are presented as median and
Criteria for diagnosis
High blood pressure
Systolic pressure or
Diastolic pressure or
Anti-hypertensive treatment
Hypercholesterolemia Total fasting serum
cholesterol or
Hypolipemiant treatment
Impaired fasting
Fasting serum glucose
glucose
Diabetes
Fasting serum glucose or
Random serum glucose or
Antidiabetic treatment
Metabolic syndrome ‡3 of the following items:
Waist circumference
Serum triglyceride
Serum HDL-cholesterol
Blood pressure
Fasting serum glucose
Self-reported diabetes
Abdominal obesity
Waist circumference
Overweight
BMI
Obesity
BMI
Smoking
Physical activity
Anxiety
Depression
HADS anxiety subscale
HADS depression subscale
Values
>140 mmHg
>90 mmHg
>6.5 mmol ⁄ l
‡ 5.6 to <7 mmol ⁄ l
‡7 mmol ⁄ l
‡ 11.1 mmol ⁄ l
‡102 cm (m); ‡88 cm (f)
‡ 1.7 mmol ⁄ l
<1.03 mmol ⁄ l (m); <1.29 mmol ⁄ l (f)
‡130 ⁄ 85 mmHg
‡6.1 mmol ⁄ l
‡102 cm (m); ‡88 cm (f)
‡25 to <30
‡30
>1 cigarette in last 30 days
>1 weekly period of physical
activity inducing above
the average sweating
>8
>8
Abbreviations: BMI: body mass index (meter of body surface ⁄ kg2); HADS: Hospital
Anxiety and Depression Scale; m: male; f: female.
3
volume 00 no 00
range. Statistics were performed using Stata 11 Software
(StataCorp LP, College Station, TX 77845).
Results
Participants
Of 222 eligible patients with Chagas disease diagnosed
since 2008, 137 (61.7%) were included in the study; 67
(30.1%) did not answer to phone calls and to the invitation
letter, 9 (4.1%) refused to participate, and 9 (4.1%) were
in Latin America during the study period. Most participants were Bolivians women of child-bearing age who had
lived in Switzerland for 7 years (Table 2). Participants did
not differ in origin, age and sex from the 85 eligible
patients who were not included. All participants were in
the chronic stage of Chagas disease: 111 (81%) were in the
indeterminate phase, 25 (18.3%) had signs of T. cruzi
cardiopathy and 1 (0.7%) had digestive tract involvement.
Table 2 Demographic characteristics of 137 patients with Chagas
disease in Geneva, Switzerland
Subcategory
Gender
Origin
Age
Age groups
Years outside
Latin America
Civil status
Children
*Denominator n = 72.
Denominator n = 116.
4
Female
Male
Bolivia
Argentina
Brazil
16–30
31–40
41–50
51–60
60+
Married or
in couple
Live away
from partner*
Single
Widow
Divorced
0
1
2
3
4-7
Living away
from children*
n (%) or
median
(range)
116
21
129
4
4
43
9
43
54
28
3
7
(84.7)
(15.3)
(94.2)
(2.9)
(2.9)
(25–69)
(6.6)
(31.4)
(39.4)
(20.4)
(2.2)
(3–31)
72 (52.6)
24 (33.3)
28
9
28
21
14
32
38
32
49
(20.4)
(6.6)
(20.4)
(15.3)
(10.2)
(23.4)
(27.7)
(23.4)
(42.2)
Actual health self assessment
When asked about their current global health, 2 (1.5%)
participants rated it as very poor, 8 (5.8%) as poor,
78 (57%) as average, 43 (31.4%) as good and 6 (4.4%) as
very good. In comparison with pre-migration status,
34 (24.8%) rated their current global health as worse, 44
(32.1%) as similar and 59 (43.1%) as better.
Socioeconomic characteristics
A large majority of participants were living without
residency permit (83.3%) and health insurance (72.3%) in
Switzerland (Table 3). Whereas most participants were
employees or running a small business at home, 81.2%
worked as domestic employees in Geneva under unsatisfactory conditions. Only 10.9% were earning a monthly
income above the poverty threshold and 54% declared a
poorer social situation than in their home country. Participants declared frequent communication problems with
health professionals and 65.7% had to share a bedroom
with two or more persons.
Behavioural characteristics
Weight control was markedly disrupted with 59.1% and
40.1% having gained or lost a mean of 5 kg since
migration, respectively (Table 4). A large majority lacked
regular physical activity (62.8%), a situation identical to
(26.3%) or worse (41.6%) than that in Latin America.
Sleep quantity and quality had fallen after migration. Few
were current smokers (15.3%) and 47.4% declared an
increased daily fruit and vegetable intake.
Metabolic and mental health disorders
Overweight (74.5%), obesity (25.5%) and excessive waist
circumference (63.5%) were highly prevalent (Table 5).
High prevalence of chronic non-communicable disorders
such as hypertension (17.5%), high cholesterol (16.1%),
and impaired fasting glucose (23.4%) were associated with
a high rate of metabolic syndrome (16.8%), whereas
diabetes was present in 2.9%. We found high rate of
positive screening for depression (28.5%) and anxiety
(58.4%).
Cardiovascular risk
Among the 137 participants, median 10-year risk for
cardiovascular disease was 2.8% (range: 0.2–49.8). When
categorized according to severity, 96 (70.1%), 24 (17.5%)
and 17 (12.4%) participants were at low, intermediate and
volume 00 no 00
Table 3 Socio-economic characteristics of
the 137 patients with Chagas disease in
Geneva, Switzerland
Subcategory
Legal status in
Switzerland
Access to care in Switzerland
Ability to communicate in French*
Difficulty communicating
adequately with health
professionals in Switzerland
Number of persons
sharing the participants
bedroom
Occupation in Latin America
Occupation in Switzerland
Job satisfaction in Latin America*
Job satisfaction in Switzerland
Number of current employers
Income (past month) Income below poverty lineà
Remittance (past month) Number of beneficiary in home country
Social situation in Switzerland (global)
compared to pre-migration status*
n (%) or
median (range)
No residency permit
Legal resident
No health insurance
Have health insurance
Very poor
Poor
Average
Good
Very good
Yes
No
110
27
99
38
27
33
57
9
11
80
57
<2
2–3
>3
At home ⁄ unemployed
Student
Employee
Small business
High qualification job
At home ⁄ unemployed
Student
Employee
Domestic employee
Small business
High qualification job
Very poor
Poor
Average
High
Very high
Very poor
Poor
Average
High
Very high
0–1
2–3
>3
47
40
50
14
7
43
66
7
2
0
128
111
5
2
4
6
23
62
42
10
17
40
57
13
74
47
16
1784
122
412
3
63
30
44
Better
Equivalent
Worse
(83.3)
(16.7)
(72.3)
(27.7)
(19.7)
(24.1)
(41.6)
(6.6)
(8)
(58.4)
(41.6)
(34.3)
(29.2)
(36.5)
(10.2)
(5.1)
(31.4)
(48.2)
(5.1)
(1.4)
(0)
(93.4)
(81.2)
(3.6)
(1.4)
(2.8)
(4.4)
(16.8)
(45.3)
(30.7)
(7.3)
(12.4)
(29.2)
(41.6)
(9.5)
(54)
(34.3)
(11.7)
(0–7058)
(89.1)
(0–2352)
(0-10)
(46)
(19.1)
(34.9)
*Self-assessed on a 3- or 5-item Lickert scale.
US dollar. Exchange rate on September 29, 2011: 1 Swiss Franc = 0.85 US dollar.
àPoverty line defined as £60% of the median national income (2010: USD 3105).
high risk, respectively. In the low risk group, 15 (15.6%)
participants presented electrocardiographic signs of
T. cruzi cardiopathy, compared to 10 (24.4%) in the
intermediate and high risk groups.
Discussion
This study shows the coexistence of chronic metabolic,
mental health and behavioural disorders with very poor
5
volume 00 no 00
Table 4 Behavioural characteristics of the 137 patients with
Chagas disease in Geneva, Switzerland
Subcategory
n (%) or
median
(range)
Weight modification
following migration
Weight change
Weight change
136 (99.3)
No change
1 (0.7)
Weight gain
81 (59.9)
Number of
5.6 (0.4–33)
extra kg
Weight loss
55 (40.1)
Number of
5 (0.4–27)
lost kg
Physical activity in
Active
51 (37.2)
Switzerland*
Sedentary
86 (62.8)
Physical activity compared
Decrease
57 (41.6)
to Latin America
Equivalent
33 (24.1)
Increase
47 (34.3)
Consumption of fruit and
Decrease
36 (26.3)
vegetables compared to
Equivalent
36 (26.3)
Latin America
Increase
65 (47.4)
Tobacco smoking
In Switzerland
21 (15.3)
In Latin America 38 (27.7)
Sleep quality in Switzerland
Decrease
11 (8)
compared to Latin America
Equivalent
59 (43.1)
Increase
67 (48.9)
Weekly number of nights of less Decrease
20 (14.6)
than 7 hours compared to
Equivalent
35 (25.5)
Latin America
Increase
82 (59.9)
*Defined as any physical activity inducing increased body heat or
sweating at least once weekly.
socioeconomic conditions in a cohort of young-to-middle
aged Latin American migrants suffering the chronic form
of Chagas disease, and resulting in a substantial risk for
adverse health – notably cardiovascular – outcomes.
Excessive waist circumference
Overweight or obesity
Obesity
High blood pressure
High serum cholesterol
Impaired fasting glucose
Diabetes
Metabolic syndrome
Depression
Anxiety
The high prevalence of chronic non-communicable
disorders, such as excessive waist circumference, overweight and obesity among study participants is in accordance with the rapidly growing trends reported in Latin
America. The prevalence of obesity reached 23% in urban
dwellers in Latin America; in Bolivia, the country most
affected by Chagas disease, 10% of adult men and 27.1%
of women were obese in 2009 (Schargrodsky et al. 2008;
WHO 2011). Notably, 59.1% of participants in our study
had put on weight since migrating to Europe, with a
mean gain of 0.8 kg ⁄ year. Behavioural changes may
explain this finding, as 62.8% participants declared no
regular physical activity in Switzerland, with only one third
reporting increased energy expenditure after migrating,
which confirms findings in Bolivian migrants in Spain
(Posada et al. 2011). Posada et al. (2011) have shown that
diet modifications after migration in Bolivian migrants are
complex and frequently associated with changes in bowel
habits. These are intimately connected to sociocultural,
professional and economic factors. In contrast to migrants
in Spain, half of the participants (47.3%) in Geneva
reported increased daily fruit and vegetable intake as
compared to Latin America. Of note was the decreasing
proportion of smokers after migration. Overall, these
findings are of concern, as abdominal obesity is associated
with higher risk of cardiovascular, metabolic, osteoarticular, and cancer related morbidity and mortality (Finucane
et al. 2011). In contrast to high blood pressure, the
prevalence of hypercholesterolemia has been stable in Latin
America since 1980 (Danaei et al. 2011; Farzadfar et al.
2011). We found prevalences of 16.1% for hypercholesterolemia and of 17.5% for hypertension, comparable to
rates reported from urban areas of Latin America
(Schargrodsky et al. 2008). In Brazil, 20% and 57% of
n (%)
95% confidence
interval
Diagnosis in
Switzerland n (%)
87
102
35
24
22
32
4
23
39
80
55.3–71.7
67–81.8
18.2–32.9
11.1–24
9.8–22.3
16.2–30.5
0.6–5.8
10.5–23.1
20.8–36.1
50–66.8
*
19 ⁄ 102
3 ⁄ 35
21 ⁄ 24
20 ⁄ 22
31 ⁄ 32
4⁄4
23 ⁄ 23
35 ⁄ 39
73 ⁄ 80
(63.5)
(74.5)
(25.5)
(17.5)
(16.1)
(23.4)
(2.9)
(16.8)
(28.5)
(58.4)
Table 5 Prevalence of metabolic and
mental health disorders including the proportion of diagnosis made in Switzerland in
137 patients with Chagas disease
(18.6) (8.6) (87.5)à
(90.9)à
(96.9)à
(100)à
(100)à
(89.7)à
(91.3)à
*Data not available: waist circumference in home country not known.
BMI in Latin America calculated with reported last weight before leaving home country.
àPreviously not known by patient and diagnosed during the study or since arrival in
Switzerland.
6
volume 00 no 00
older Chagas disease patients were suffering dyslipidemia
and hypertension, respectively (De Angelis Alves et al.
2009). Whereas impaired fasting glucose was highly
prevalent in our cohort (23.4%), diabetes affected only a
small proportion of individuals (2.9%). This may be
explained by the overall young age of participants.
Nevertheless, the 16.8% prevalence of metabolic syndrome, which is associated with a 3.5–5.2-folds increase in
the risk of diabetes, highlights the need for behavioural and
medical intervention (Ford et al. 2008).
Chagas disease is a chronic infection resulting in a 20–
40% risk of cardiopathy over decades. Its pathogenesis
includes immunologically mediated tissue damages,
autonomic dysfunction and coronary microvascular
abnormalities (Rassi et al. 2010). Metabolic syndrome is
associated with a 65% and 27% increase in cardiovascular
risk and all cause mortality, respectively (Ford 2005). We
postulate that persistent exposure to atherogenic factors
secondary to chronic non-communicable diseases could
add to the T. cruzi chronic infection to produce myocardial
damage and increase risk for cardiovascular events on the
long term. At the time of the study, 18.3% participants
already suffered T. cruzi cardiac damages and most were at
low to intermediate risk for cardiovascular disease. This
can be explained by protective factors such as young age
and pre-menopausal status. Further studies are needed to
better evaluate the impact of the coexistence of these
factors on the pathogenesis, evolution and prognosis of
T. cruzi cardiopathy.
We found a consequent proportion of subjects with
positive screening for anxiety (58.4%), depression (28.5%)
and altered sleep duration (59.9%) and quality (48.9%).
As no physiopathology rational supports a relation
between Chagas disease and poor mental health, this
association is probably mediated by socioeconomic factors.
A study in Brazil found depressive symptoms in 40.9% of
110 patients with advanced Chagas disease and the
presence of chronic complication of the infection put
patients at higher risk (Ozaki et al. 2010). Poor mental
health, chronic stress and insufficient quantity and quality
of sleep negatively affect mental, metabolic and
cardio-vascular health, resulting in increased mortality (De
Hert et al. 2009; Marmot 2009; Cappuccio et al. 2010).
Concomitant emotional distress and sleep disturbance
might also alter patients’ ability to tolerate antiparasitic
treatment. Indeed, nifurtimox has significant
neuropsychiatric effects in adults resulting in a high
proportion of premature treatment interruption (Jackson
et al. 2010a,b). Therefore, poor mental health in chronic
Chagas disease patient may impact both on the global
health prognosis and on the ability to undergo antiparasitic
treatment.
This study shows that Chagas disease affects a vulnerable group of population in Europe. Most participants
were living below the national poverty line, lacked
residency permit and could not access to the national
health care system through the mandatory health insurance. These factors, associated with poor housing and
working conditions, low job satisfaction, social exclusion
and heavy economical burden, are known to combine
towards increased morbidity and mortality both at individual and at population levels (Ferrie et al. 2002;
Wilkinson & Marmot 2003). The Swiss poverty line is,
alongside with cost of living, higher than in most other
European countries. Therefore, migrants incomes need to
be evaluated both in terms of absolute and relative poverty.
Of note, most participants were women, a constant finding
in different studies done in Europe so far, that highlight
the need to tailor intervention strategies to this group
(Munoz et al. 2009; Jackson et al. 2010a,b). In Latin
America, the association of Chagas disease with poverty
and the impact of social determinants on adverse chronic
Chagas disease outcome have been thoroughly described
(Briceno-Leon & Mendez Galvan 2007; Viotti et al. 2009).
This is the first study identifying the socioeconomic
disadvantage of migrants with Chagas disease outside
Latin America. European countries have different policies
regarding migrants’ access to care and to residency permits.
Spain is more liberal than other Western European
countries, including Switzerland. Still, most vulnerable
migrants with Chagas disease experience difficulties and
barriers in accessing to optimal quality care and preventive
medicine in Western Europe (Jackson et al. 2009a,b). So
far, only 4000 of the 80 000 patients in Europe have been
properly diagnosed and treated (WHO 2009). In addition,
communication problems between patients and health
professionals, which are known to adversely affect quality
of care, were frequently identified in our cohort (The
Institute of Medicine 2002).
Our findings can be generalized to other recent Latin
American migrants in Europe who are not infected by
T. cruzi, as their demographic characteristics are similar to
those infected (Jackson et al. 2009a,b; Munoz et al.
2009; Perez-Ayala et al. 2011). These results stress the need
for a more comprehensive approach to Chagas disease
patients – and other Latin American migrants – than
previously proposed, both at clinical and at public health
levels (WHO 2009). Specifically, they highlight the need to
apprehend this infection, and possibly other parasitic
chronic infections such as strongyloidiasis, within the
framework of the globally increasing prevalence of
non-communicable diseases and of the factors of social,
cultural and economic vulnerability related to international
migration (Angheben et al. 2011).
7
volume 00 no 00
Our study is purely descriptive and does not aim at
identifying a causal relationship between these factors and
Chagas disease or the fact of being a Latin American
migrant. We acknowledge that these factors are not specific
to Latin American migrants with Chagas disease, but more
a reflection of the global health of a vulnerable group of
population. The relative homogeneity of the cohort constitutes a study limitation, but the characteristics of our
participants were comparable to cohorts in Spain and Italy,
the most affected countries in Europe (Jackson et al.
2009a,b; Munoz et al. 2009). Another limitation results
from the single fasting serum test used for diagnosing
glucose metabolism abnormality. As most participants
could not afford missing work to attend a second study
visit, we directly referred individuals with glucose abnormality to their general practitioner. This is a frequently
reported limitation in cross-sectional studies that may
contribute to over-estimation of the reported rate of
glucose intolerance or diabetes. We acknowledge that
migrants’ socioeconomic conditions vary between countries and therefore may influence their global health status.
Nevertheless, we believe that our results appropriately
reflect the condition of the majority of 80 000 Latin
American individuals infected with T. cruzi who recently
migrated to Europe.
In conclusion, migrants with Chagas disease in Switzerland suffer from pathogenic chronic conditions of infectious, non-communicable, socioeconomic and behavioural
origin putting them at high risk of poor health, notably
cardiovascular, outcomes and that should modify the
traditional disease-centered approach. These findings
highlight the importance of (i) screening for these associated factors and providing interventions to tackle reversible
disorders, (ii) facilitating access to care for this hard-toreach population to prevent delays in medical interventions
and poorer health outcomes and (iii) launching prospective
studies to evaluate the long-term impact of these combined
factors on the natural course of Chagas disease.
Acknowledgement
This study was supported by a grant from the Foundation
Simon I. Patiño in Geneva, Switzerland.
References
Andrade F (2009) Estimating diabetes and diabetes-free life
expectancy in Mexico and seven major cities in Latin America
and the Caribbean. Revista Panamericana de Salud Pública
26(1), 9–16.
Angheben A, Anselmi M, Andreoni F, et al. (2011)
Stronglyoidiasis and Chagas disease sero-prevalence in a
8
Bolivian community, Italy. Tropical Medicine & International
Health 16(S1), 94.
Briceno-Leon R & Mendez Galvan J (2007) The social determinants of Chagas disease and the transformations of Latin
America. Memórias do Instituto Oswaldo Cruz 102(Suppl 1),
109–112.
Cappuccio FP, D’Elia L, Strazzullo P & Miller MA (2010) Sleep
duration and all-cause mortality: a systematic review and
meta-analysis of prospective studies. Sleep 33(5), 585–592.
Coura JR & Vinas PA (2010) Chagas disease: a new worldwide
challenge. Nature 465(n7301_supp), S6–S7.
D’Agostino RB, Vasan RS, Pencina MJ, et al. (2008) General
cardiovascular risk profile for use in primary care: the
Framingham Heart Study. Circulation 117(6), 743–753.
Danaei G, Finucane MM, Lin JK, et al. (2011a) National, regional,
and global trends in systolic blood pressure since 1980:
systematic analysis of health examination surveys and
epidemiological studies with 786 country-years and 5.4 million
participants. Lancet 377(9765), 568–577.
Danaei G, Finucane MM, Lu Y, et al. (2011b) National, regional,
and global trends in fasting plasma glucose and diabetes
prevalence since 1980: systematic analysis of health examination
surveys and epidemiological studies with 370 country-years
and 2.7 million participants. Lancet 377(9765), 31–40.
De Angelis Alves R, De Almeida E, Da Silva Wanderley J &
Guariento M (2009) Chagas’ disease and ageing: the coexistence
of other chronic diseases with Chagas’ disease. The Revista da
Sociedade Brasileira de Medicina Tropica 42(6), 622–628.
De Hert M, Dekker JM, Wood D, Kahl KG, Holt RI & Moller HJ
(2009) Cardiovascular disease and diabetes in people with severe
mental illness position statement from the European Psychiatric
Association (EPA), supported by the European Association for
the Study of Diabetes (EASD) and the European Society of
Cardiology (ESC). European Psychiatry 24(6), 412–424.
Farzadfar F, Finucane MM, Danaei G, et al. (2011) National,
regional, and global trends in serum total cholesterol since 1980:
Ferrie JE, Shipley MJ, Stansfeld SA & Marmot MG (2002) Effects
of chronic job insecurity and change in job security on self
reported health, minor psychiatric morbidity, physiological
measures, and health related behaviours in British civil servants:
the Whitehall II study. Journal of Epidemiology & Community
Health 56(6), 450–454.
Finucane MM, Stevens GA, Cowan MJ, et al. (2011) National,
regional, and global trends in body-mass index since 1980:
Ford ES (2005) Risks for all-cause mortality, cardiovascular
disease, and diabetes associated with the metabolic syndrome: a
summary of the evidence. Diabetes Care 28(7), 1769–1778.
Ford ES, Li C & Sattar N (2008) Metabolic syndrome and incident
diabetes: current state of the evidence. Diabetes Care 31(9),
1898–1904.
volume 00 no 00
Gascon J, Bern C & Pinazo MJ (2009) Chagas disease in Spain, the
United States and other non-endemic countries. Acta Tropica
115(1–2), 22–27.
Hermann C (1997) International experiences with the Hospital
Anxiety and Depression Scale: a review of validation data and
clinical results. Journal of Psychosomatic Research 42(1), 17–41.
Jackson Y, Angheben A, Carrilero Fernandez B, et al. (2009a)
Management of Chagas disease in Europe. Experiences and
challenges in Spain, Switzerland and Italy. Bulletin de la Société
de Pathologie Exotique 102(5), 326–329.
Jackson Y, Myers C, Diana A, et al. (2009b) Congenital transmission of Chagas disease in Latin American immigrants in
Switzerland. Emerging Infectious Diseases 15(4), 601–603.
Jackson Y, Alirol E, Getaz L, et al. (2010a) Tolerance and safety of
nifurtimox in patients with chronic chagas disease. Clinical
Infectious Diseases 51(10), e69–e75. Available: http://cid.
oxfordjournals.org/content/51/10/e69.full.pdf+html. Accessed
2011 July 15
Jackson Y, Getaz L, Wolff H, et al. (2010b) Prevalence, clinical
staging and risk for blood-borne transmission of Chagas disease
among Latin American migrants in Geneva, Switzerland. PLoS
Neglected Tropical Diseases 4(2), e592. http://www.plosntds.
org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.
0000592. Accessed 14 ⁄ 7 ⁄ 2011.
Marmot M (2009) Closing the health gap in a generation: the work
of the Commission on Social Determinants of Health and its
recommendations. Global Health Promotion (Suppl 1, 23–27.
Munoz J, Gomez i Prat J, Gallego M, et al. (2009) Clinical profile
of Trypanosoma cruzi infection in a non-endemic setting:
immigration and Chagas disease in Barcelona (Spain). Acta
Tropica 111(1), 51–55.
PAHO (Organizacion Panamericana de la Salud) (2006). Estimacion cuantitativa de la enfermedad de Chagas en las Americas.
PAHO, Montevideo, Uruguay.
Posada E, Pell C, Angulo M, et al. (2011) Bolivian migrants with
Chagas disease in Barcelona, Spain: a qualitative study of dietary changes and digestive problems. International Health 3,
289–294.
Ozaki Y, Guariento ME & de Almeida EA (2010) Quality of life
and depressive symptoms in Chagas disease patients. Quality
of Life Research 20(1), 133–138.
Perez-Ayala A, Perez-Molina JA, Norman F, et al. (2011) Chagas
disease in Latin American migrants: a Spanish challenge.
Clinical Microbiology 17(7), 1108–1113.
Quintana JM, Padierna A, Esteban C, et al. (2003) Evaluation of
the psychometric characteristics of the Spanish version of the
Hospital Anxiety and Depression Scale. Acta Psychiatrica
Scandinavica 107(3), 216–221.
Rassi A Jr, Rassi A & Marin-Neto JA (2010) Chagas disease.
Lancet 375(9723), 1388–1402.
Schargrodsky H, Hernandez-Hernandez R, Champagne BM, et al.
(2008) CARMELA: assessment of cardiovascular risk in seven
Latin American cities. American Journal of Medicine 121(1),
58–65.
The Institute of Medicine (2002) Unequal Treatment: Confronting
Racial and Ethnic Disparities in Health Care: Institute of
Medicine. National Academy of Science, Washington DC,
764 pp.
Viotti R, Vigliano CA, Alvarez MG, et al. (2009) The impact of
socioeconomic conditions on chronic Chagas disease progression. Revista Española de Cardiologı́a 62(11), 1224–1232.
Wilkinson R & Marmot M (2003) Social Determinants of Health:
The Solid Facts. World Health Organization, Geneva.
World Health Organization (WHO) (2002) Control of Chagas
Disease. Second report of the WHO experts committee.
Technical report series no 995. World Health Organization,
Geneva.
World Health Organization (WHO) (2009) Control and Prevention of Chagas Disease in Europe. Report of a WHO informal
consultation (jointly organized by WHO headquarters and the
WHO regional office for Europe). World Health Organization,
Geneva. http://www.who.int/whosis/whostat/EN_WHS2011_
Full.pdf. Accessed 14 ⁄ 7 ⁄ 2011.
World Health Organization (WHO) (2011) World Health Statistics 2011. WHO, Geneva; http://www.who.int/whosis/whostat/
EN_WHS2011_Full.pdf. Accessed 15 ⁄ 7 ⁄ 2011.
Corresponding Author Yves Jackson, Division of Primary Care Medicine, Geneva University Hospitals, rue Gabrielle-Perret-Gentil 6
1211 Geneva 14, Switzerland. Email: yves.jackson@hcuge.ch
9
9. Chagas disease in Switzerland: history and challenges
Euro Surveill. 2011;16(37):pii=19968
Par:
Jackson Y, Chappuis F.
67
Surveillance and outbreak reports
Chagas disease in Switzerland: history and challenges
Y Jackson (yves.jackson@hcuge.ch)1, F Chappuis2
1. Division of primary care medicine, Department of community medicine, primary care and emergency medicine, Geneva
University Hospitals and University of Geneva, Switzerland
2. Division of humanitarian and international medicine, Department of community medicine, primary care and emergency
medicine, Geneva University Hospitals and University of Geneva, Switzerland
Citation style for this article:
Jackson Y, Chappuis F. Chagas disease in Switzerland: history and challenges.
Euro Surveill. 2011;16(37):pii=19963. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19963
Article published on 15 September 2011
Chagas disease, endemic in Latin America, is an
emerging health problem in Europe affecting an estimated 80,000 persons. Around 60,000 Latin American
migrants live in Switzerland, and cases of Chagas disease have been reported since 1979. As of June 2011,
258 cases have been diagnosed, mostly adults in the
indeterminate phase of the chronic stage of the disease. Vertical transmission has been identified and
there is a high potential for blood- and organ-borne
transmission in the absence of systematic screening.
Major challenges include (i) raising awareness among
migrants and healthcare professionals, (ii) developing national protocols for screening and treatment
targeting high-risk groups such as pregnant woman,
newborns, migrants from highly endemic areas (e.g.
Bolivia), and immunocompromised migrants, (iii)
preventing blood- and organ-borne transmission
by appropriate screening strategies, (iv) taking into
account the social vulnerability of individuals at risk
in the design and implementation of public health programmes, and (v) facilitating contacts with the communities at risk through outreach programmes, for
example in churches and cultural groups
Introduction
The parasite Trypanosoma cruzi, the causative agent
of Chagas disease, has been affecting humans for at
least 9,000 years, but Europe has experienced the
emergence of this disease as a significant health issue
only very recently [1,2]. In humans, T. cruzi is responsible for a chronic infection causing potentially lethal
cardiac damages in up to 30% of cases. It was traditionally confined to the Americas, resulting in a high
social and financial burden primarily in rural areas [3].
In the absence of T. cruzi vectorial transmission outside
Latin America, Chagas disease in non-endemic countries is predominantly an imported infection, affecting
migrants more than travellers [4]. Besides, transplacental and blood-borne transmissions have been reported
in Europe [5,6]. In 2010, the World Health Organization
(WHO) estimated that 80,000 persons could be infected
in Europe, making Chagas disease one of the predominant emerging parasitic infections in the continent [2].
www.eurosurveillance.org
In Switzerland, a small country of 7.8 million inhabitants, foreigners accounted for 22.4% of the total
population in 2010. Currently, 35,000 Latin American
migrants originating from the 21 countries endemic for
Chagas disease are legal residents in Switzerland. This
figure does not include adopted children or migrants
who have received the Swiss citizenship. Moreover,
since the 1990s, a large number of Latin American
migrants have been settling in Europe without residence permit and are not recorded in the official registries. For example, 1,229 residents of Bolivian origin
were officially registered in Switzerland in 2009, but
migrants associations estimate that around 9,000
Bolivians live in the canton of Geneva alone, most
of them undocumented (F. Anda, Association des
Boliviens de Genève, June 2010, personal communication). A large majority of recent Latin American
migrants are women employed in the domestic industry. Thus, it can be estimated that the real number of
Latin American migrants at risk of having Chagas disease currently living in Switzerland may be as high
as 60,000 to 90,000 [2]. Undocumented migrants are
legally entitled to access the Swiss healthcare system
by purchasing a health insurance. Yet, the expensive
premium (EUR 200–300 per month), lack of knowledge
of the system and administrative barriers prevent the
vast majority of them from contracting an insurance,
thus making access to care difficult, especially outside
the main urban areas, where communities and support
groups are less organised.
The first recorded case of Chagas disease in Switzerland
dates back to 1979 [7]. Since then, the number of cases
recorded has increased in parallel with the growth
of the population at risk, alongside higher awareness among health professionals and with improved
access to reliable diagnostic tools [8,9]. Several studies have documented the emergence and transmission
of Chagas disease in Latin American communities in
Switzerland [5,10,11]. Here, we review epidemiological,
clinical and social data on all cases of Chagas disease
diagnosed and recorded in Switzerland.
1
Methods
We used several sources of information to identify
cases and their characteristics before aggregation: (i)
the clinical databases of two studies done in Geneva
in 2008: a community-based cross-sectional study in
adult Latin American immigrants over the age of 16
years [10] and a prospective study in pregnant Latin
American women attended at the Geneva University
Hospitals [11], (ii) the database of all cases seen at
the Geneva University Hospitals and (iii) information
collected from the main laboratories performing diagnosis of T. cruzi infection, the major Swiss healthcare
institutions and experts active in international health
and infectious diseases in Switzerland. To optimise
data collection, an internet search for published cases
was conducted using two major electronic databases
(Pubmed and Embase). The keywords ‘Switzerland’,
‘Chagas disease’, and ‘Trypanosoma cruzi’ were used.
To avoid duplication of cases from different sources,
the date of birth, nationality, sex and place of diagnosis
and treatment were cross-checked. Cases were defined
as any individual in whom T. cruzi testing was positive,
either by serology (≥9 month after birth in newborns),
nucleic-acid assay or microscopy. Up to 2008, the Swiss
Tropical Institute in Basel was the only Swiss laboratory performing serology for T. cruzi infection (in-house
indirect immunofluorescent assay), haemoculture and
nucleid acid assay (in-house PCR). Since 2008, Geneva
University Hospitals have been using two different
serological tests (ELISA cruzi, Biomerieux, Brazil and
Chagas Stat-Pak, Chembio Diagnostic Systems, United
States). Moreover, several Swiss reference laboratories perform microscopical examination in blood and
tissues. Since 2008, screening programmes in Geneva
have focused on Latin American individuals who fulfil
one or more of the following criteria: Bolivian origin,
relative of a patient with Chagas disease, suggestive
symptoms, recipient of a blood transfusion in the home
country, or pregnancy.
Table 1
Socio-demographic characteristics of patients with Chagas
disease, Switzerland, January 1979–June 2011 (n=258)
Results
Number of cases and place of diagnosis
From 1979 to June 2011, a total of 258 persons have
been diagnosed with T. cruzi infection in Switzerland.
All but five patients were diagnosed in Geneva.
Time variation of frequency of
cases and clinical features
From 1979 to 2007, in the absence of screening programmes, 11 cases of T. cruzi infection had been identified including eight symptomatic cases: five with
cardiac, one with cardiac and digestive complications,
and two congenital infections with placental abnormalities [5,7-9]. After screening programmes were
initiated in Geneva, 247 cases were diagnosed from
January 2008 to June 2011, with a lower proportion of
symptomatic cases (53 of the 231 clinically evaluated
patients).
Socio-demographic characteristics
Table 1 shows the socio-demographic characteristics of the 258 patients. The median age was 41 years
and women were overrepresented with 83% of cases.
The vast majority of patients were Bolivians (n=241).
Information on whether they had a residence permit
was available for 176 patients. Most of those (n=171)
were living in Switzerland without a residence permit
and without health insurance.
Mode of transmission and clinical staging
Congenital transmission (acute phase) was diagnosed
in four newborns, all of them from Bolivian mothers.
In addition, five children between 1 and 11 years of age
were diagnosed at the early indeterminate phase of the
chronic stage. Table 2 shows the clinical staging of the
258 patients. One fatal case occurred following a fulminant T. cruzi infection reactivation in an immunosuppressed patient who had received a heart transplant
[10].
Diagnosis
All patients in the indeterminate phase of the chronic
stage and one newborn (aged nine months) were
N (%) or median (range)
Sex
Female
215 (83.3)
Male
43 (16.7)
Age
41 (0–77)
Children (<16 years)
9 (3.5)
Country of origin
Argentina
Bolivia
241 (93.4)
Brazil
8 (3.1)
Chile
2 (0.8)
Colombia
1 (0.4)
Lack of valid residency permit
(undocumented)a
a
6 (2.3)
Denominator=176.
2
171 (97.1)
Table 2
Clinical staging of patients with Chagas disease,
Switzerland, January 1979–June 2011 (n=258)
Stage
N (%)
Acute – congenital
4 (1.6)
Acute – reactivation
1 (0.4)
Chronic – early indeterminate
5 (2)
Chronic – indeterminate
178 (69)
Chronic with cardiac involvement
51 (19.8)
Chronic with digestive tract involvement
3 (1.2)
Chronic with cardiac and digestive tract involvement
1 (0.4)
Information not available
15 (5.6)
diagnosed by positive results in at least one, mostly
two, serological assays (immunofluorescence, ELISA or
immunochromatography) with the strategies or combinations varying depending on the diagnosing centre. One newborn was diagnosed by positive T. cruzi
nucleic acid test of umbilical cord blood. Two other
newborns were diagnosed by detection of amastigote
forms of T. cruzi in the placenta with confirmation by
positive serology and nucleic acid assay. The patient
with T. cruzi reactivation was diagnosed by identifying amastigote forms in the skin and in a bone marrow
biopsy, and by a positive peripheral blood buffy coat.
Treatment
Criteria for treatment initiation were based on recommendations from the World Health Organization and on
guidelines from the United States [11,12]. Until 2009,
nifurtimox was used for availability reasons. Since
then, benznidazole has been more easily available
and has become the first-line treatment. Anti-parasitic
treatment was initiated in 129 patients (50%). Ninetythree patients received nifurtimox (10 mg/kg/day) and
36 received benznidazole (5 mg/kg/day; max:300 mg/
day). Overall, adverse events caused premature treatment termination (less than 60 days) in 41 patients
(31.8%; nine with benznidazole and 32 with nifutimox).
A full description on tolerance of nifurtimox in patients
treated in Switzerland has been published [13].
Discussion
To our knowledge, 258 cases of Chagas disease were
diagnosed and recorded in Switzerland between 1979
and 2011. Considering the limited number of medical
centres and laboratories working on parasitic diseases
in Switzerland, this figure probably reflects the actual
situation correctly. Almost all cases were diagnosed in
Geneva, which has several reasons: (i) a large community of Bolivian migrants live in Geneva, (ii) local policies allow access to primary healthcare for uninsured
individuals, (iii) repeated epidemiological investigations on Chagas disease and information sessions with
the community have created confidence and reinforced
the cooperation between migrants and the Geneva
University Hospitals (HUG), (iv) screening programmes
have been implemented in the Canton of Geneva. Such
programmes have so far not been put in place in blood
banks, maternity wards and health institutions of other
Swiss cantons, with the exception of Lausanne in the
Canton of Vaud. The implementation of screening in
Geneva is the main explanation for the shift from a
low number of detected cases with a high proportion
of symptomatic individuals (until 2007) to a higher
number of cases with a high proportion of asymptomatic individuals (since 2008). Previous studies in
Geneva showed 25% prevalence within the Bolivian
community, mostly in women of child-bearing age
who had a positive attitude towards blood donation in
Geneva, which highlighted the risk of blood-borne and
congenital transmission [5,14].
Chagas disease represents an emerging and complex
health issue in Switzerland considering (i) the presence of a significant number of infected persons, (ii)
their social situation with poor access to healthcare
and very low socioeconomic status, (iii) the active
vertical transmission and the potential for transmission through blood and organ donations, and (iv) the
low awareness and consideration by public health
authorities and health professionals [15]. The situation of Chagas disease in Switzerland is emblematic
of the European context, as until now only Spain and
France have adopted public health policies to control
the spread of this emerging infection [16]. National recommendations or programmes of case detection and
management or prevention of local transmission do not
currently exist in Switzerland. Specific tests to diagnose chronic Chagas disease are available in a limited
number of laboratories. Neither of the two drugs active
against T. cruzi, benznidazole and nifurtimox, are registered by the Federal Pharmaceutical Office and thus
require specific agreement for each treatment, nor are
they easily available.
Since 2008, some progress has been made regarding
the management of Chagas disease in Switzerland.
Serologies are now available in two laboratories (HUG
and the Swiss Tropical and Public Health Institute in
Basel). A rapid diagnostic test has been validated and
is being used in HUG and the University Hospital of
Lausanne [17]. Systematic screening of Latin American
pregnant women was first implemented at HUG in
2008, followed in 2010 by a wider strategy of screening
all persons at risk, i.e. Latin American immigrants, persons who received blood transfusion in Latin America
or persons born to a Latin American mother. In 2011,
the University Hospital of Lausanne is expected to
adopt similar protocols. Systematic screening of blood
donors at risk is under discussion at local (Geneva,
Lausanne) and national levels. Ties with Latin American
communities have been strengthened through information exchange and awareness campaigns. Education
of medical students and health professionals through
clinical meetings, presentations in congresses and
publications in national medical journals has been
initiated.
Considering the number of Latin American immigrants
living in Switzerland and the proportion of T. cruzi
infections in this community, up to 3,000 cases could
be present in the country. The main challenges for the
control of this emerging health threat are: (i) raising
awareness both in communities at risk of infection and
in health professionals, e.g. primary care physicians,
gynaecologists/obstetricians, paediatricians, cardiologists, gastroenterologists, and radiologists, (ii) developing national protocols for screening and treatment,
targeting high-risk groups such as pregnant woman,
newborns, Bolivian citizens, immunosuppressed
migrants, (iii) preventing blood- and organ-borne transmission by appropriate screening strategies, (iv) taking
into account the social vulnerability of individuals at
3
risk in the design of programmes and their implementation, and (v) facilitating contacts with the communities at risk through outreach programmes, for example
in churches and cultural groups.
17. Chappuis F, Mauris A, Holst M, Albajar-Vinas P,
Jannin J, Luquetti AO, et al. Validation of a rapid
immunochromatographic assay for diagnosis of Trypanosoma
cruzi infection among Latin-American Migrants in Geneva,
Switzerland. J Clin Microbiol.;48(8):2948-52.
Acknowledgments
The authors wish to thank Hanspeter Marti (Swiss Tropical
and Public Health Institute, Basel, Begona Martinez de
Tejada, Cristina Reis, Alessandro Diana, Anne Mauris
and Claire-Anne Wyler (Geneva University Hospitals) and
Valérie D’Acremont (CHUV Lausanne) for helping gathering
information
References
1. Aufderheide AC, Salo W, Madden M, Streitz J, Buikstra J, Guhl
F, et al. A 9,000-year record of Chagas’ disease. Proc Natl Acad
Sci U S A. 2004;101(7):2034-9.
2. World Health Organisation (WHO). Statement – Chagas disease
in Europe. Geneva: WHO; 20 January 2010. Available from:
http://www.who.int/neglected_diseases/integrated_media_
chagas_statement/en/index.html
3. Hotez PJ, Bottazzi ME, Franco-Paredes C, Ault SK, Periago
MR. The neglected tropical diseases of latin america and the
Caribbean: a review of disease burden and distribution and
a roadmap for control and elimination. PLoS Negl Trop Dis.
2008;2(9):e300.
4. Lescure FX, Le Loup G, Freilij H, Develoux M, Paris L, Brutus L,
et al. Chagas disease: changes in knowledge and management.
Lancet Infect Dis. 2010;10(8):556-70.
5. Jackson Y, Myers C, Diana A, Marti HP, Wolff H, Chappuis F, et
al. Congenital transmission of chagas disease in latin american
immigrants in Switzerland. Emerg Infect Dis. 2009;15(4):601-3.
6. Flores-Chavez M, Fernandez B, Puente S, Torres P, Rodriguez
M, Monedero C, et al. Transfusional chagas disease:
parasitological and serological monitoring of an infected
recipient and blood donor. Clin Infect Dis. 2008;46(5):e44-7.
7. Liechti M, Baur HR, Gurtner HP, Straub PW. Cardiac
complications of American trypanosomiasis (Chagas disease).
Various case reports and general observations. Schweiz Med
Wochenschr. 1990;120(41):1493-6.
8. Jackson Y, Chappuis F, Loutan L. [Chagas disease in
Switzerland: managing an emerging infection and interrupting
its transmission]. Rev Med Suisse. 2008;4(157):1212-4, 6-7.
French.
9. Sztajzel J, Cox J, Pache JC, Badaoui E, Lerch R, Rutishauser W.
Chagas’ disease may also be encountered in Europe. Eur Heart
J. 1996;17(8):1289. Eur Heart J. 1996 Aug;17(8):1289.
10. Jackson Y, Dang T, Schnetzler B, Pascual M, Meylan P.
Trypanosoma cruzi fatal reactivation in a heart transplant
recipient in Switzerland. J Heart Lung Transplant.
2010;30(4):484-5.
11. Bern C, Montgomery SP, Herwaldt BL, Rassi A Jr., Marin-Neto
JA, Dantas RO, et al. Evaluation and treatment of chagas
disease in the United States: a systematic review. JAMA.
2007;298(18):2171-81.
12. World Health Organisation (WHO) Expert Committee on the
Control of Chagas disease (2000: Brasilia, Brazil). Control of
Chagas disease: second report of the WHO expert committee.
WHO technical report series; 905. Geneva: WHO; 2002.
Available from: http://whqlibdoc.who.int/trs/WHO_TRS_905.
pdf
13. Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis
F. Tolerance and safety of nifurtimox in patients with chronic
chagas disease. Clin Infect Dis.;51(10):e69-75.
14. Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin
A, et al. Prevalence, clinical staging and risk for bloodborne transmission of Chagas disease among Latin
American migrants in Geneva, Switzerland. PLoS Negl Trop
Dis.2010;4(2):e592.
15. Jackson Y, Angheben A, Carrilero Fernandez B, Jansa i Lopez
del Vallado JM, Jannin JG, Albajar-Vinas P. [Management
of Chagas disease in Europe. Experiences and challenges
in Spain, Switzerland and Italy]. Bull Soc Pathol Exot.
2009;102(5):326-9.
16. Castro E. Chagas’disease: lessons routine donation testing.
Transfus Med 2009;19(1):16-23.
4
10. Chagas disease in European countries: the challenge of a surveillance
system
Euro Surveill. 2011;16(37):pii=19968
Par:
Basile L, Jansà JM, Carlier Y, Salamanca DD, Angheben A, Bartoloni A, Seixas J, Van Gool T,
Cañavate C, Flores-Chávez M, Jackson Y, Chiodini PL, Albajar-Viñas P.
72
Surveillance and outbreak reports
Chagas disease in European countries: the challenge of a
surveillance system
L Basile1, J M Jansà2, Y Carlier 3, D D Salamanca4 , A Angheben5, A Bartoloni6, J Seixas7, T Van Gool8, C Cañavate9, M FloresChávez9, Y Jackson10, P L Chiodini11, P Albajar-Viñas (albajarvinasp@who.int)12, Working Group on Chagas Disease13
1. Department of Health, Generalitat of Catalonia, Barcelona, Spain
2. Directorate General of Public Health and Foreign Healthcare, Ministry of Health, Social Affairs and Equality, Madrid, Spain
3. Faculty of Medicine, Free University of Bruxelles, Brussels, Belgium
4. French Institute for Public Health Surveillance (Institut de Veille Sanitaire, InVS), Saint Maurice, France
5. Centre for Tropical Diseases, COHEMI network, Hospital S. Cuore, Don Calabria, Negrar, Verona, Italy
6. University Hospital Centre Careggi, COHEMI network, Firenze, Italy
7. Clinical unit of Tropical Diseases, Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisbon, Portugal
8. Department of Medical Microbiology, University of Amsterdam, Amsterdam, the Netherlands
9. National Centre of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
10.Division of primary care medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland
11. Hospital for Tropical Diseases, London, United Kingdom
12.World Health Organization (WHO) Programme on Control of Chagas disease, Department of Control of Neglected Tropical
Diseases, WHO, Geneva, Switzerland
13.The members of this group are listed at the end of the article
Citation style for this article:
Basile L, Jansà JM, Carlier Y, Salamanca DD, Angheben A, Bartoloni A, Seixas J, Van Gool T, Cañavate C, Flores-Chávez M, Jackson Y, Chiodini PL, Albajar-Viñas P,
Working Group on Chagas Disease. Chagas disease in European countries: the challenge of a surveillance system.
Euro Surveill. 2011;16(37):pii=19968. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19968
Article published on 15 September 2011
A study of aggregate data collected from the literature and official sources was undertaken to estimate
expected and observed prevalence of Trypanosoma
cruzi infection, annual incidence of congenital transmission and rate of underdiagnosis of Chagas disease
among Latin American migrants in the nine European
countries with the highest prevalence of Chagas disease. Formal and informal data sources were used to
estimate the population from endemic countries resident in Europe in 2009, diagnosed cases of Chagas
disease and births from mothers originating from
endemic countries. By 2009, 4,290 cases had been
diagnosed in Europe, compared with an estimated
68,000 to 122,000 expected cases. The expected
prevalence was very high in undocumented migrants
(on average 45% of total expected cases) while the
observed prevalence rate was 1.3 cases per 1,000 resident migrants from endemic countries. An estimated
20 to 183 babies with congenital Chagas disease
are born annually in the study countries. The annual
incidence rate of congenital transmission per 1,000
pregnancies in women from endemic countries was
between none and three cases. The index of underdiagnosis of T. cruzi infection was between 94% and
96%. Chagas disease is a public health challenge in
the studied European countries. Urgent measures
need to be taken to detect new cases of congenital
transmission and take care of the existing cases with a
focus on migrants without legal residency permit and
potential difficulty accessing care.
Introduction
Chagas disease is caused by the parasite Trypanosoma
cruzi and is considered endemic in 21 Latin American
countries. It currently affects around 10 million people
in Latin America, and 10 to 30 per cent of cases have
developed or will develop cardiac, digestive or nervous system disorders [1]. In the last two decades many
efforts have been made to reduce the incidence of
Chagas disease in endemic countries [2], but exchange
of population between Latin America and Europe, the
United States, Australia and Japan has resulted in
increased detection of T. cruzi in these countries [3].
In non-endemic regions, the parasite can be transmitted vertically (congenital transmission from mother to
fetus), and by infected blood and organ donors [4].
In 2008, more than 38 million migrants were living in
Europe, of whom 11% came from Latin America [5]. This
figure did not include migrants without valid residency
permit (irregular, undocumented migrants) [6], people
born outside Europe who have acquired citizenship
of a European country, or children from foreign countries adopted by European families. Official figures
thus clearly underestimate the number of migrants
from endemic areas, and therefore also the number of
T. cruzi-infected people.
Currently, only a small number of persons infected with
T. cruzi have been detected in Europe [4]. Several reasons account for this fact:
1
• Most European health professionals have little or no
experience with the detection and management of
Chagas disease [7].
• Access to screening programmes for the communities at risk is very limited as only a few institutions
offer screening, mostly in major urban areas.
• The diagnosis of the chronic phase is usually
delayed as most patients remain asymptomatic for
many years [8].
There is no common European legislation to prevent the
transmission of T. cruzi by blood donation, although in
Spain and France screening of Latin American donors
is mandatory, while in countries like Italy or the
United Kingdom (UK) blood donation by migrants from
endemic Latin American countries is prohibited and
their country of origin is recorded by questionnaire [4].
Only some autonomous communities of Spain, such
as Valencia [9] and Catalonia [10], have protocols for
screening of pregnant women from Latin America to
prevent congenital transmission. The rest of Spain and
other European countries, except for some focal institutional experiences [11], have not adopted any governmental preventive measures yet.
Very few studies have estimated the prevalence of
Chagas disease in European countries [12-15]. In Spain,
it was estimated that between 40,000 and 65,000
residents were infected with T. cruzi in 2009 [4], while
in other European countries the estimate range was
between 12,000 and 15,000 [16].
The lack of an information system to report Chagas
disease cases and transmission in all European countries makes it difficult to provide an overall figure of
all diagnosed cases in Europe so far, and therefore no
exact overview of the burden and public health impact
of Chagas disease in Europe can be made.
For this reason, the World Health Organization
(WHO) set up in 2009 a working group of experts on
Chagas disease from those European countries where
T. cruzi-positive cases had been detected (Austria,
Belgium, Croatia, Denmark, France, Germany, Italy,
the Netherlands, Portugal, Romania, Spain, Sweden,
Switzerland and United Kingdom). The aim was to
collect and asses the available information, create a
network of experts to exchange information and experience between countries and define a common strategy for the epidemiological surveillance of Chagas
disease [17].
This paper presents the efforts of this group of experts
to provide a preliminary view of the situation in Europe,
using a consensual, homogeneous methodology. The
objectives of this study were to estimate the expected
and observed prevalence of cases of T. cruzi-infected
people from endemic countries of origin, the annual
incidence of congenital transmission and the estimated
2
rate of underdiagnosis among cases of T. cruzi infection in 2009 in the participating countries.
Methods
Study design and population
An epidemiological study was designed to analyse
aggregate measures of the prevalence of T. cruzi infection and the incidence of congenital transmission of
Chagas disease in 2009. The units of observation were
the European countries that according to the WHO estimate, had more than 400 cases of Chagas disease [4],
i.e. Belgium, France, Germany, Italy, the Netherlands,
Portugal, Spain, Switzerland and the UK.
Case definition
For the purposes of this study, according to the WHO
case definition [18], a case of Chagas disease was considered as any individual who, as a result of a screening programme or of testing as a possible case, was
positive for antibodies against T. cruzi in two serological (ELISA) assays.
Inclusion and exclusion criteria
The target population included three categories:
• Subjects of any age born in countries endemic for
Chagas disease who were regular residents of the
above-mentioned European countries in the year
2009 or the latest year for which this information
was available.
• The undocumented migrants from disease endemic
countries resident in the above-mentioned
European countries.
• Children born in countries endemic for Chagas disease and adopted by families from the above-mentioned European countries.
Latin Americans not born in countries endemic for
Chagas disease (e.g. the Caribbean islands) were
excluded.
European travellers to endemic countries and cases of
Chagas disease diagnosed in European travellers presumably infected in endemic countries were excluded
due to the small expected number of cases and the difficulty in obtaining information about them.
Information sources
The study population was quantified using official published data obtained from national institutions in the
included European countries, Eurostat and data collected by the working group and collaborators of the
project. All these sources are listed in Table 1 and the
corresponding data are shown in Table 2.
The numbers of diagnosed cases of Chagas disease in
each European country was provided by members of
the national reference institutions and members of the
WHO working group.
The infection rates used to calculate the expected
prevalence rate among the estimated resident population of Latin Americans in European countries (Table
3) were those published by the WHO in 2006 [19]. The
rates for Bolivia were calculated according to available data on the Bolivian population living in Europe
[20,21]. The rates for French Guyana and Surinam
were provided respectively by the Institute of Health
Surveillance (Institut de Veille Sanitaire, France) and
by the Department of Medical Microbiology of the
University of Amsterdam (the Netherlands) and rely on
estimations on immigrants from these countries living
in Europe.
Table 1
Information sources for estimates of migrant residents (legal and undocumented), adoptions and annual births in nine
studied European countries
Country
Belgium France
Germany
Category
Institution and reference year
Legal immigration
National register, Directorate of Statistics and Economic Information (DGSIE),
2006
Estimated undocumented immigration
Faculty of Medicine, Free University of Bruxelles, Brussels, Belgium 2006
Adoptions
Adoption in French and Dutch-speaking Belgium, Belgian Directorate of
adoption, 2001–2009
Annual births
National register, Directorate of Statistics and Economic Information (DGSIE),
2006
Legal immigration
Institute of Health Surveillance (INVS), 2008
Adoptions
Institute of Health Surveillance (INVS), 1980–2007
Annual births
Legal immigration
Eurostat, 2008
Legal immigration
Italian National Institute of Statistics (ISTAT), 2009
Centre for Tropical Diseases, Hospital Ospedale Sacro Cuore Don Calabria,
Verona, Italy, 2009
Adoptions
Commission for international adoptions, Presidency of the Council of Ministers,
2000–2009
Annual births
ISTAT, 2008
Legal immigration
Statistics Netherlands, 2008
Central government (Rijksoverheid), 2005
Legal immigration
Statistics Portugal (INE), 2009
Institute of Hygiene and Tropical Medicine, New University of Lisbon, Lisbon,
Portugal
Annual births
INE Portugal, 2009
Legal immigration
Statistics Spain (INE), 2009
Adoptions
Statistics Spain (INE), 2000–2007
Annual births
Legal immigration
Federal departement of justice and police, 2009
Division of primary care medicine, Geneva University Hospitals and University
of Geneva, Geneva, Switzerland , 2009
Adoptions
Federal office of statistics, Section demography and migration, 1979–2008
Annual births
Demographic portrait of Switzerland, 2008
Legal immigration
Office for National Statistics, Social Surveys Dataservice, 2009
1.Sveinsson, Kjartan Páll. Bolivians In London - Challenges and Achievements
of a London Community, Runnymede Community Studies, Runnymede Trust.
2007
2.Buchuck S. Crossing borders: Latin American exiles in London. Untold
London, 2010
3.Bérubé M. Colombia: In the crossfire. Migration Information Source.
Migration Policy Institute. 2005
4.James M. Ecuadorian identity, community and multi-cultural integration.
Runnymede Trust. 2005
Annual births
Office for National Statistics, Vital Statistics Outputs Branch, 2009
Italy
the Netherlands
Portugal
Spain
Switzerland
United Kingdom
3
The applied rates of congenital transmission (1.4% and
7.3%) came from cohorts of migrant pregnant women
living in Europe [11,22].
Data collection and analysis
To estimate the expected prevalence of T. cruziinfected people in the studied countries, we first calculated the number of regular residents originating from
endemic countries, according to the data published by
the national statistical institutes in each country. When
there were no published data, these were obtained
from governmental sources or from members of the
working group (Table 1).
To calculate the undocumented migrant population, we
used estimates from governmental sources, national
referral centres and indexed and non-indexed publications (Table 1). In the case of Spain, the official number
of regular residents was subtracted from the number of
migrants included in the municipal census.
In the case of children born in endemic countries and
adopted by European families, we sought official data
sources on adoption by country of birth (Table 1). The
inclusion of this population in the study depended on
the availability of data on adoptions, and finally data
from five countries (Belgium, France, Italy, Spain, and
Switzerland) were included.
To obtain the expected absolute number of cases of
T. cruzi infection, the number of regular and undocumented migrants from Latin America and the number
of adopted children, stratified by country of origin, was
multiplied by the corresponding national infection rates
in the countries of origin. A two-sided confidence intervals method with continuity correction for the single
proportion [23] was applied to calculate the expected
number of cases in migrants for every endemic country
of origin. The expected number of cases obtained was
divided by the corresponding reference population to
obtain the expected prevalence rate (shown as percentage). In the case of minimum and maximum values
for reference population, an average value was applied
to calculate the expected prevalence.
To calculate the observed prevalence of T. cruzi-infected
people, the members of the working group were asked
to actively search for cases diagnosed in their country
up to the year 2009, dividing this amount by the total
reference population to obtain the observed prevalence rate, shown as percentage.
To estimate the expected annual incidence of congenital transmission, national data on annual births
of children of women from endemic areas stratified by
country of birth or nationality of the mother as registered in 2009 or the latest year available was collected
(Table 1). These figures were multiplied by the respective rates of infection in endemic countries, which
provided an estimate of the absolute number of mothers infected with T. cruzi who gave birth in one year.
Applying the range of congenital transmission rates
(1.4% to 7.3%) to this result gave an estimate of the
number of T. cruzi-infected children born in each participating European country. The annual incidence rate of
congenital transmission in the population at risk was
obtained by dividing the number of children infected in
one year by the number of pregnancies in that year.
To estimate the index of underdiagnosis we calculated
the rate ratio between the observed and expected prevalence rates. The result represents the proportion of
diagnosed cases divided by the total estimated cases.
The index is presented as a percentage obtained from
the following formula: 1-rate ratio.
Table 2
Estimates of migrants resident in nine studied European countries, legal and undocumented, originating from countries
endemic for Chagas disease, and births to mothers from endemic countries, 2009
Country
Estimated undocumented
(min–max)
Adoptions
Total (min–max)
Annual births
Nb
%
Nb
%a
Nb
%
Nb
%a
Nb
28,880
1
14,440
1
490
1
43,810
1
722
1
France
97,981
4
51,500
5
19,389
51
168,870
5
5,545
10
Germany
85,313
4
Not reported
- Not reported
-
85,313
3
Not reported
-
260,864
12
112,000–120,000
6,784
18
379,648–387,648
12
3,351
6
220,172
10
17,400
2 Not reported
-
237,572
7
Not reported
-
110,113
5
11,011
1 Not reported
-
121,124
4
3,950
7
1,263,342
56
484,509
1,754,205
53
35,525
67
Belgium
Italy
The Netherlands
Portugal
Spain
Switzerland
United Kingdom
Total
a
Resident immigrants
Regular
population
35,761
2
38,000–42,000
162,517
7
250,000–335,000
2,264,943
101b
978,860–1,075,860
11
%
47
6,354
17
4
4,994
13
78,755–82,755
2
375
1
28 Not reported
-
412,517–497,517
14
3,433
6
100 3.281,814–3,378,814
101b
52,901
98b
99b
38,011
In the case of minimum and maximum values, the percentage refers to the average value.
The deviation is due to rounding.
b
4
Results
More than three million migrants from endemic countries (MEC) were estimated to live in the nine European
countries included in the study, representing 1% of the
total population living in Europe. Due to immigration
from Brazil, Portugal was the country with the highest
percentage of migrants coming from endemic areas.
Among the countries where no Romance language is
spoken, the Netherlands had the highest percentage of
migrants coming from endemic countries, mainly from
Surinam (84% of MEC in the Netherlands), a former
Dutch colony and an endemic country for Chagas disease with a low infection rate.
Prevalence in migrants and adoptees
For details about MEC living in Europe, multiple sources
of information were used (Tables 1 and 2). However, it
was not possible to identify all people at risk due to
the lack of data stratified by endemic country. Between
40,227 and 62,724 people infected with T. cruzi resided
regularly in the included countries, accounting for
between 1.8% and 2.8% of all regular MEC (Table 4).
The highest prevalence estimation for regular MEC was
seen in Spain, where between 2.3% and 3.8% of them
were infected with T. cruzi.
The estimated numbers of undocumented MEC infected
by T. cruzi were very high: prevalence estimations were
substantially higher than for regular MEC, with the
Table 3
Distribution of the migrant population from countries endemic for Chagas disease resident in nine studied European
countries, and estimated number of people infected, 2009
Endemic country
Infection
rate
Nb %c
Nb 95% confidence interval
%c
Argentina
4.13
237,678
7.1
9,815
9,626–10,006
10.4
0.74
2,464
0.1
18
11–29
0
Brazil
Chile
Colombia
min
10
268,926
max
27.5
290,926
1.02
670,299
20.1
0.99
99,483
3.0
min
max
Costa Rica
Ecuador
Guatemala
Surinam
Uruguay
6,837
6,703–6,971
7.2
1.0
985
925–1,045
4,496
4,334–4,620
5,168
5,025–5,353
5.1
0.1
25
16–37
0
18.4
10,662
10,479–10,847
11.2
3.37
15,389
0.5
519
476–565
0.5
1.98
9,183
0.3
182
157–210
0.2
1.29
23,555
0.7
13
7–24
0
18,987
0.6
3.05
27,121
1.03
1.14
min
0.25
max
0.5
min
max
47
36–63
94
78–116
0.8
827
773–884
0.9
74,346
2.2
766
714–825
0.8
13,317
0.4
152
129–178
0.2
0.01
4,555
0.1
0
0–5
0
2.54
87,550
2.6
2,224
2,136–2,320
2.3
0.69
min
0.15
max
0.5
Venezuela
268,957
273,957
183,216
8.2
5.5
1,856
1,775–1,936
1,890
1,808–1,972
287
257–330
954
898–1,008
0.1
2.0
0.7
0.66
69,702
2.1
460
418–502
0.5
1,16
93,836
2.8
1,089
1,023–1,154
1.1
0.3
100
Undeterminedd
19,389
0.6
165
384
Total
3,281,814–3,378,814
100
68,318–123,078
c
d
56.4
4,808
Paraguay
Peru
79,539–80,470
612,809
Nicaragua
Panama
15.4
26,597–27,188
80,014
1.74
Honduras
Mexico
546,244
26,893
0.53
Guyana
French Guyana
0.96
476,244
8.4
El Salvador
b
%
Estimated number of infected peopleb
Belize
Bolivia
a
Total regular and undocumented
immigrant populationa
The total immigrant population from Bolivia, Colombia and Peru is a range of values due to estimations of undocumented population.
Estimates based on infection rate of the country of origin.
In the case of minimum and maximum values, the percentage refers to the average value.
This number refers to adoption in France, for which no data is available stratified by endemic country, and the estimate of people infected
was calculated by the Institut de Veille Sanitaire, France.
5
highest estimated prevalence in Spain (between 3.9%
and 7.8% of undocumented MEC), and Switzerland
(between 2.5% and 7.8% of undocumented MEC).
France had the highest number of positive cases
among children adopted from endemic countries,
although these were from countries with low infection rates. Cases represented between 0.8% and 2%
of French adoptions from endemic countries. The overall expected prevalence in the participating countries
ranged from 1.2% to 2.4% of total adoptions of children
from endemic settings.
Congenital transmission
In the studied countries almost 53,000 children were
born in 2009 from mothers originating from endemic
countries. Of these, between 1,347 and 2,521 were
born from mothers infected with T. cruzi, and there was
congenital transmission in between 20 and 184 cases.
This corresponds to between none and three infected
children per 1,000 births to mothers at risk (Table
5). With 67% of births from mothers originating from
endemic countries occurring in Spain, almost 90% all
of cases of congenital transmission occurred in that
country. In other countries, there were between none
and six cases of congenital transmission per year.
Underdiagnosis
By 2009, 4,290 cases of infection with T. cruzi were
diagnosed in the study countries (Table 6), and 89%
of all cases were detected in Spain. The total observed
prevalence rate was 0.13% of the total MEC. The lowest
observed rates occurred in Germany (0.002%) and the
Netherlands (0.003%) and the highest in Switzerland
(0.223%).
The index of underdiagnosis shows that, in general,
between 94% and 96% of expected cases were not
diagnosed (Table 6). The index of underdiagnosis was
lowest in Switzerland, where between 89% and 95% of
expected cases were not detected, while in Germany,
the Netherlands, Portugal and the UK, more than 99%
of expected cases in migrants were not diagnosed.
Overall, the Latin American nationalities with the greatest presence in Europe were Brazilans, Colombians and
Ecuadorians, although most expected cases of Chagas
were attributed to Bolivian migrants (Table 3).
Discussion
The Control of Chagas disease is a recent public health
challenge in many countries in Europe. The reason
is that it is an imported disease mainly affecting the
migrated poor population from different Latin American
countries who often have limited access to diagnosis
and treatment of this disease. This also makes it difficult to quantify the disease impact in terms of expected
cases. However, it is a challenge that requires urgent
action due to the risks involved in the context of blood,
organ and tissue donation, and the risk of congenital
transmission to infants of infected mothers. In addition, the presence of potentially infected population
groups who may present with heart, digestive tract and
general disorders in the medium and long term, needs
to be considered also with a view to the individual
patient and the impact on clinical costs.
To quantify the European expected prevalence the
authors decided to use initially the WHO official infection rates for every disease endemic country [18]. On
the other hand, it was observed that all prevalence
studies on Latin American immigrants living in Europe
showed rates in the Bolivian community higher than
the 6,75% WHO official estimated rate [20,21,24,25].
For this reason we preferred to use a more realistic
range for Bolivian migrants (minimum 10.0%, maximum
27.5%) that was based on the known epidemiological
situation in Europe. This choice could have introduced
some bias at the methodological level by elevating the results in only one community. Nevertheless,
the authors believe that this decision was necessary
because the final results were closer to the reality that
Table 4
Estimated numbers of migrants from Chagas disease-endemic countries infected with Trypanosoma cruzi and expected
prevalence in the nine studied European countries in 2009
Country
Estimated undocumented
(min-max)
Legal (min-max)
Prevalence
Belgium
Adoptions (min-max)
Prevalence
Total (min-max)
Prevalence
Prevalence
451-601
1.6-2.1
226-301
1.6-2.1
6-19
1.2-3.9
683-921
1,6-2.1
France
1,253-1,542
1.3-1.6
730-897
1.4-1.7
165-384
0.8-2
2,148-2,823
1.3-1.7
Germany
1,123-1,481
1.3-1.7
Not reported
-
Not reported
-
1,123-1,481
1.3-1.7
Italy
4,133-5,322
1.6-2
2,220-6,520
1.9-5.6
111-194
1.6-2.9
6,464-12,036
1.7-3.1
776-1,528
0.3-0.7
191-245
1.1-1.4
Not reported
-
967-1773
0.4-0.7
Netherlands
Portugal
Spain
Switzerland
United Kingdom
Total
6
1,141
1
114
1
Not reported
-
1,255
1
28,974-48,510
2.3-3.8
18,884-37,874
3.9-7.8
126-234
2-3.7
47,984-86,618
2.7-4.9
535-750
1.5-2.1
982-3,132
2.5-7.8
66-88
1.3-1.8
1,584-3971
2-4.8
1,841-1,849
1.1
4,270-10,352
1.5-3.5
-
-
6,111-12,201
1.3-2.4
40,227-62,724
1.8-2.8 27,617-59,435
2.7-5.8 474-919
1.2-2.4 68,318-123,078
2-3.6 www.eurosurveillance.org
professionals involved in the detection of cases see
every day in health systems.
Another relevant point is that other applied national
infection rates, based on the population in diseaseendemic countries, do not take into account the effects
of heterogeneity of the immigrant population living in
Europe (i.e. age groups, socio-economic differences,
rural-urban origin, etc.) and these differences are not
reflected in the results.
The results of this study highlight the difficulty in
obtaining accurate data on the population at risk and
specific information on diagnosed cases, the lack of
official national data, the underestimation of migrants
in the official figures, and the lack of a system for
reporting detected cases in non-endemic countries.
According to the estimations of expected cases in the
different non-endemic countries, and to offer a better
view of the situation, we classified the countries in
three groups. The first category includes only Spain,
which accounts for almost 75% of expected cases.
The second group is represented by France, Italy and
the UK, while the third group is represented by the
other non-endemic countries (Belgium, Germany, the
Netherlands, Portugal and Switzerland). The key role
played by Spain in the prevention and control of Chagas
disease in Europe is not only due to the high expected
prevalence of T. cruzi infection, but also relates to its
pivotal position in the migrant flow to Europe and the
cultural and linguistic proximity to Latin American
countries. France has played a key role in the development of recent studies and specific interventions and
regulations for Chagas disease [26], although the country had a low expected number of cases. This and the
existence of French national territory in the endemic
region of Latin America (French Guyana) places France
in a distinctive position in the prevention and control
plans for Chagas disease in non-endemic European
countries.
Table 5
Estimated congenital transmission and prevalence rate per 1,000 pregnancies in women from Chagas disease-endemic areas,
residing in nine studied European countries, 2009
Infected pregnant women (min–max)
Country
Belgium
France
Germany
Italy
The Netherlands
Annual births
Infected infants (min–max)
Number
of cases
Cases per 1,000
pregnancies
Number
of cases
Cases per 1,000
pregnancies
722
10–13
14–18
0–1
<1
5,545
53–74
10–13
1–5
<1
Not reported
Not applicable
-
Not applicable
-
3,351
55–76
16–23
1–6
1
Not reported
Not applicable
-
Not applicable
-
Portugal
3,950
40
10
1–3
<1
Spain
35,525
1,125–2,226
32–63
16–162
0-5
375
6–8
16–21
0–1
1
United Kingdom
3,433
58–84
17–24
1–6
1
Total
52,901
1,347–2,521
25–48
20–184
0–3
Switzerland
Table 6
Diagnosed cases, observed and expected prevalence rates and percentage of underdiagnosis of Chagas disease in migrants
from endemic areas residing in nine studied European countries, up to 2009
Country
Cases diagnosed
Observed prevalence rate
(%)
Expected prevalence rate
(min–max, %)
Index of underdiagnosis
(min–max, %)
Belgium
19
0.043
1,6-2.1
97.2–97.9
France
111
0.066
1.3-1.7
94.8–96.1
Germany
Italy
The Netherlands
Portugal
Spain
2
0.002
1.3-1.7
99.8–99.9
114
0.03
1.7-3.1
98.3–99.0
7
0.003
0.4-0.7
99.3–99.6
8
0.007
1
99.4
3,821
0.218
2.7-4.9
92.0–95.6
89.2–95.2
Switzerland
180
0.223
2-4.8
United Kingdom
28
0.006
1.3-2.4
99.6–99.7
4,290
0.13
2-3.6 93.9–96.4
Total
7
The observed prevalence was extremely low, compared
with the expected rates, in Belgium, the Netherlands,
Portugal and the UK, suggesting a lack of awareness
and interventions (protocols, studies, etc) against
Chagas disease in those countries. The UK, especially
London where most Latin American immigrants to the
UK reside [27], ranks second in Europe in terms of residents estimated to be infected with T. cruzi and cases
of congenital transmission, with numbers nearly identical to those of Italy. These results are entirely novel
and in contrast to UK estimates published in previous
studies [16]. This discrepancy could be due to potential underestimation in official statistics of the Latin
American population actually resident in the UK.
The study highlights the presence of positive cases in
undocumented migrants, especially in Spain, Italy and
Switzerland. These countries have large Bolivian communities not represented in official statistics [24,28]
that makes it even harder for the national authorities to
identify the population at risk. On the other hand these
results can offer only an incomplete picture of the reality due to the limitations of estimating the reference
population. Nevertheless the present study offers new
information not included in previous studies that only
included documented migrants [3,15]. The fact that
being an undocumented migrant could be associated
with originating from poor endemic areas with higher
prevalence rates highlights the value of developing
demographic studies that can contribute to providing
more reliable estimates of this population.
The estimated results on underdiagnosis are a good
indicator of the limited epidemiological impact of
Chagas disease in the context of European health and
surveillance systems. Epidemiological silence, understood as the lack of detected cases, which is common
in some European countries, shows the need for greater
involvement of European health authorities in controlling neglected tropical diseases, among others Chagas
disease. The priority could be the implementation of
screening programmes of target populations and the
training of professionals in the detection of possible cases. The legislation or protocols already implemented in countries such as Spain or France would be
very useful to reduce the differences in preparedness
and available programmes between European countries. Such collaboration would be of help in developing a European surveillance system, which is essential
for further progress in controlling Chagas disease.
The control of congenital transmission is undoubtedly one of the most important measures for the prevention and control of Chagas disease that should be
addressed by surveillance systems because of the
effectiveness of treatment in infants. Likewise, the
establishment of regulations for blood and organ donation is essential to limit the impact of Chagas disease
in countries where there is no vector transmission.
Systematic screening of the risk population, at present
only carried out in some regions of France, Spain and
8
Switzerland, should also be introduced after carrying
out cost-effectiveness analyses to decide which measures could be most appropriate.
In terms of public health, the authors believe that the
main proposals and challenges for European countries
where cases have already been identified or that have
residents from endemic areas are:
• To create an international information and surveillance system for the reporting of cases, control of
transmission, exchange of information between
European countries, and training of primary healthcare workers.
• To carry out studies to define the risk of congenital transmission in pregnant women from Latin
America and to evaluate the impact of potential
screening protocols for the control of congenital
transmission according to the results obtained.
• To carry out epidemiological studies allowing for
reliable estimation of true prevalence rates among
immigrants resident in Europe.
• To consider systematic screening (by questionnaire or serological tests) blood, organ and tissue
donors from endemic Latin American regions.
• To publish official statistics of migrants from
Chagas-endemic countries in each European country containing data by regular and irregular status
according to their country of origin.
• To facilitate access to diagnosis and treatment to
groups of migrants at risk of being excluded from
the national health systems such as undocumented
immigrants.
• To reinforce the teaching on international health and
tropical diseases in the curricula of health sciences
in European Universities.
Acknowledgments
In addition to the members of the working group on Chagas
disease in Europe, we would like to thank the collaboration of: Dr. Zeno Bisoffi (Centro per le Malattie Tropicali,
Ospedale S. Cuore, Don Calabria, Negrar, Verona. COHEMI
network), Dr. Manuel Segovia (Hospital Universitario Virgen
de la Arrixaca, Murcia, Spain), Dr. Pere Godoy (Departament
de Salut, Generalitat de Catalunya, Barcelona, Spain), Ms.
Beatriz Camps Carmona (WHO Programme on Control of
Chagas disease, Department of Control of Neglected Tropical
Diseases, WHO, Geneva, Switzerland), Ms. Mar Velarde
(WHO Programme on Control of Chagas disease, Department
of Control of Neglected Tropical Diseases, WHO, Geneva,
Switzerland)
The study presented in this article is part of a European
project called “Development of a system of epidemiological
surveillance for Chagas disease in Europe” financed by the
WHO Programme on Control of Chagas disease, Innovative &
Intensified Disease Management, Department of Control of
Neglected Tropical Diseases)
Members of the Working Group on Chagas Disease in Europe:
Apart from the authors of this article, the present working
group is composed of:
Dr. Mariella Anselmi (Centro per le Malattie Tropicali,
Ospedale S. Cuore, Don Calabria, Negrar, Verona, Italy.
COHEMI network), Dr. Luigi Gradoni (Dipartimento di Malattie
Infettive, Parassitarie e Immunomediate, Istituto Superiore
di Sanità, Roma, Italy), Dr. José Antonio Pérez Molina
(Hospital Ramon y Cajal, Madrid, Spain), Dr. Joaquim Gascón
(Hospital Clínic, Barcelona, Spain. COHEMI network), Dr.
Jordi Gomez i Prat (Centre de Salut Internacional i Medicina
Tropical Drassanes, Barcelona, Spain), Dr. Luisa Sánchez
Serrano (Instituto de Salud Carlos III, Madrid, Spain), Dr.
Magdalena García (Consorcio Hospital General Universitario
de Valencia, Valencia, Spain), Dr. Bartolomé Carrilero
Fernández (Hospital Universitario Virgen de la Arrixaca,
Murcia, Spain), Dr. Jane Jones (Health Protection Agency,
London, UK), Dr. Emmanuel Bottieau (Institute of Tropical
Medicine, Antwerp, Belgium), Dr. Xavier Lescure (Hôpital
Tenon, Paris, France), Dr. Pierre Ambroise-Thomas (Académie
nationale de Médecine, Meylan, France), Dr. Jean Delmont
(Centre de formation et recherche en médecine et sante
tropicales, Marseille, France), Dr. Guillaume Le Loup (Service
de Maladies infectieuses tropicales, Hôpital Tenon, Paris,
France), Dr. Luc Paris (Service de Parasitologie-Mycologie,
Groupe Hospitalier Pitié-Salpêtrière, Paris, France), Dr.
Françoise Gay-Andrieu (Laboratoire de ParasitologieMycologie, Institut de Biologie - Hôtel Dieu, Nantes, France),
Dr. Aldert Bart (Parasitology Section, Dept Med Microbiol,
Academic Medical Center, Amsterdam, the Netherlands),
Dr. August Stich (Tropenmedizin Missionsärztliche Klinik,
Würzburg, Germany), Dr. Israel Molina (Hospital Vall
d’Hebron, Barcelona, Spain), Dr. Carmen Muñoz (Hospital
Sant Pau, Barcelona, Spain), Dr. Carmen Cabellos (Hospital
de Bellvitge, Barcelona, Spain), Dr. Lluis Valerio (Unitat
de Salut International Metropolitana Nord, Barcelona,
Spain), Dr. Angel Lluis Ballesteros (Hospital de Badalona,
Barcelona, Spain), Dr. Cristina Soler (Hospital de Santa
Caterina, Girona, Spain), Dr. Toni Soriano (Hospital Joan
XXIII, Tarragona, Spain) and Dr. Jean Jannin (Innovative and
Intensified Disease Management Unit, Department of Control
of Neglected Tropical Diseases, WHO, Geneva, Switzerland)
References
1. World Health Organization (WHO). Working to overcome the
global impact of neglected tropical diseases: first WHO report
on neglected tropical diseases. Geneva: WHO; 2010. Report
No.: WHO/HTM/NTD/2010.1. Available from: http://whqlibdoc.
who.int/publications/2010/9789241564090_eng.pdf
2. Dias JC, Silveira AC, Schofield CJ. The impact of Chagas
disease control in Latin America: a review. Mem Inst Oswaldo
Cruz. 2002;97(5): 603-12.
3. Schmunis GA, Yadon ZE. Chagas disease: A Latin American
health problem becoming a world health problem. Acta Trop.
2010;115(1-2):14-21.
4. World Health Organization (WHO). Control and prevention
of Chagas disease in Europe. Report of a WHO Informal
Consultation (jointly organized by WHO headquarters and the
WHO Regional Office for Europe) Geneva, Switzerland, 17-18
December 2009. Final report. Geneva: WHO; 2010. Report
No.: WHO/HTM/NTD/IDM/2010.1. Available from: http://www.
fac.org.ar/1/comites/chagas/Chagas_WHO_Technical%20
Report_16_06_10.pdf
5. Vasileva K. Statistics in focus. Citizens of European countries
account for the majority of the foreign population in EU-27
in 2008. Luxembourg: Eurostat; 2009. Report No.: 94/2009.
Available from: http://epp.eurostat.ec.europa.eu/cache/ITY_
OFFPUB/KS-SF-09-094/EN/KS-SF-09-094-EN.PDF
6. European Commission (EC). Size and development of irregular
migration to the EU, Clandestino Research Project, Counting
the Uncountable: Data and Trends across Europe. Bruxelles:
EC; 2009 [Accessed: 27 Feb 2011]. Available from: http://
clandestino.eliamep.gr/wp-content/uploads/2009/12/
clandestino_policy_brief_comparative_size-of-irregularmigration.pdf
7. Jackson J, Angheben A, Carrilero Fernández B, Jansa i Lopez
del Vallado JM, Jannin JG, Albajar-Viñas P. Prise en charge
de la maladie de Chagas en Europe. Expériences et défis en
Espagne, Suisse et Italie. [Management of Chagas disease in
Europe. Experiences and challenges in Spain, Switzerland and
Italy]. Bull Soc Pathol Exot. 2009;102(5):326-9. French.
8. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet.
2010;375(9723):1388-402.
9. Autonomous Government of Valencian Community. Enfermedad
de Chagas importada. Protocolo de actuación en la Comunitat
Valenciana. [Imported Chagas Disease. Protocol of actions in
the Valencian Community]. Valencia: Conselleria de Sanitat,
Generalitat Valenciana; 2009 [Accessed: 14 Jun 2010]. Spanish.
Available from: http://biblioteca.sp.san.gva.es/biblioteca/
publicaciones/MATERIAL/PUBLICACIONES/INFAN_MUJER/
PERINATAL/MAMUAL_ENF_CHAGAS.PDF
10. Autonomous Government of Catalonia. Protocol for screening
and diagnosing Chagas disease in pregnant Latin American
women and their newborns. Barcelona: Departament de
Salut, Genaralitat de Catalunya; 2010 [Accessed: 14 Jun 2010].
Available from: http://www.gencat.cat/salut/depsalut/html/
en/dir3559/chagasprot_eng.pdf
11. Gonzalez-Granado L, Rojo P, Gonzalez-Tomé M, Camaño I,
Salto E, Flores M. Cribado sistemático de la enfermedad de
Chagas en embarazadas bolivianas y seguimiento de los
recién nacidos. Experiencia de un año. [Systematic screening
of Chagas Disease in Bolivian pregnant women and newborn
follow-up. One-year experience]. Enf. Emerg. 2009;11 Supl1:1819. Spanish.
12. Salamanca DD, La Ruche G, Tarantola A, Degail MA, Jeannel
D, Gastellu-Etchegorry M. Maladie de Chagas en France:
estimation du nombre de personnes infectées et d’atteintes
cardiaques en 2009, selon les groups à risqué [Chagas disease
in France: estimated number of infected persons and cardiac
diseases in 2009, by risk groups].. Bull Soc Pathol Exot.
2009;102(5):285-90. French
13. Jackson Y, Gétaz L, Wolff H, Holst M, Mauris A, Tardin A, et
al. Prevalence, Clinical Staging and Risk for Blood-Borne
Transmission of Chagas Disease among Latin American
Migrants in Geneva, Switzerland. PLoS Negl Trop Dis.
2010;4(2):e592.
14. Guerri-Guttenberg RA, Ciannameo A, Di Girolamo C, Milei
JJ.Mal di Chagas : Un problema emergente di salute pubblica in
Italia ? [Chagas disease: an emerging public health problem in
Italy?]. Infez Med. 2009;17(1):5-13. Italian.
15. Pérez de Ayala A, Pérez-Molina JA, Norman F, López-Vélez R..
Chagasic cardiomyopathy in Immigrants from Latin America to
Spain. Emerg Infect Dis. 2009;15(4):607-8.
16. Guerri-Guttenberg RA, Grana DR, Ambrosio G, Milei J.
Chagas cardiomyopathy: Europe is not spared!. Eur Heart J.
2008;29(21):2587–91.
17. World Health Organization (WHO). New global effort to
eliminate Chagas disease. Partners set out strategy against
the ‘kissing bug’ disease. Geneva: WHO; 3 Jul 2007. Available
from: http://www.who.int/mediacentre/news/releases/2007/
pr36/en/
18. World Health Organization (WHO). Control of Chagas disease.
Technical report. Geneva: WHO; 2002. Available from: http://
whqlibdoc.who.int/trs/WHO_TRS_905.pdf
19. Pan American Health Organization (PAHO). Estimación
cuantitativa de la enfermedad de Chagas en las Américas.
[Quantitative estimation of Chagas Disease in the Americas].
Montevideo: PAHO; 2006. Report No.: OPS/HDM/CD/425-06.
Spanish.
20. Piron M, Vergés M, Muñoz J, Casamitjana N, Sanz S, Maymó
RM, et al, Seroprevalence of Trypanosoma cruzi infection
in at-risk blood donors in Catalonia (Spain). Transfusion.
2008;48(9):1862-8.
21. Muñoz J, Coll O, Juncosa T, Vergés M, del Pino M, Fumado V, et
al. Prevalence and vertical transmission of Trypanosoma cruzi
infection among pregnant Latin American women attending
2 maternity clinics in Barcelona, Spain. Clin Infect Dis.
2009;48(12):1736-40.
22. Yadon ZE, Schmunis GA. Congenital Chagas disease:
Estimating the potential risk in the United States. Am.J.Trop.
Med.Hyg. 2009;81(6):927–33.
23. Newcombe RG. Two-sided confidence intervals for the
single proportion: comparison of seven methods. Stat Med.
1998;17(8):857-72.
24.Jackson Y, Myers C, Diana A, Marti HP, Wolff H, Chappuis F,
et al. Congenital Transmission of Chagas Disease in Latin
American Immigrants in Switzerland. Emerg Infect Dis. 2009;
15(4): 601-3.
25. Patricio-Talayero JM,,Benlloch-Muncharaz MJ, Collar-delCastillo JI, Rubio-Soriano A, Serrat-Pérez C, Magraner-Egea J,
et al. Vigilancia epidemiológica de la transmisión vertical de la
enfermedad de Chagas en tres maternidades de la Comunidad
Valenciana. [Epidemiological surveillance of verticallytransmitted Chagas disease at three maternity hospitals
9
in the Valencian Community]. Enferm Infecc Microbiol Clin.
2008;26(10):609-13. Spanish.
26. Société de pathologie exotique. Atelier de consensus sur la
Maladie de Chagas en zone non endémique (Paris – 26 Juin
2009). [Consensus workshop about the Chagas disease in
non-endemic areas (26 June 2009, Paris, France)]. Bull Soc
Pathol Exot. 2009;102(5):273-352. French.
27. BBC News. Born abroad, an immigration map of Britain, South
America special report. London: BBC MMXII; 2010. [Accessed:
18 Jan 2011]. Available from: http://news.bbc.co.uk/2/shared/
spl/hi/uk/05/born_abroad/countries/html/south_america.stm
28.Orihuela M. Boliviani in Italia. [Bolivians in Italy].
Latinoamericando s.r.l., il portale del mondo latino. [
Latinoamericando Ltd., the portal of the Latin world.] 28 Jul
2009. Italian. Available from: http://www.latinoamericando.
it/cms/index.php?option=com_flexicontent&view=ite
ms&cid=51:focus-immigrazione&id=3827:boliviani-initalia&Itemid=33&lang=es
10
11. Need for comprehensive healthcare for T. cruzi infected immigrants in
Europe
Rev Soc Bras Med Trop. 2009; 42 (suppl 2): 92-95
Par:
Velarde-Rodríguez M, Avaria-Saavedra A, Gómez-i-Prat J, Jackson Y, Alves de Oliveira W,
Camps-Carmona B, Albajar-Viñas P.
83
Rev Soc Bras Med Trop - Vol: 42: Suplemento II, 2009
25a Reunião Annual de Pesquisa Aplicada em Doença de Chagas
13a Reunião Annual de Pesquisa Aplicada em Leishmanioses
Need of comprehensive health care for T. cruzi infected
immigrants in Europe
Mar Velarde-Rodríguez1, Andrea Avaria-Saavedra2, Jordi Gómez-i-Prat3, Yves Jackson4,
Wilson Alves de Oliveira Junior5, Beatriz Camps-Carmona1 and Pedro Albajar-Viñas1
Abstract
Paleoparasitology studies have evidenced that Chagas disease is almost as
old as man's presence in the Americas. At the beginning of the twentieth
century the disease was mostly confined to the rural areas of South America,
Central America and Mexico. Later, the increase of population mobility,
facilitated by the new different means of transport, greatly contributed to
spread the disease and even the vector first across Latin America, secondly
to the urban and peri-urban environment, and finally to the so-called disease
non-endemic countries. Consequently, new areas harbouring people with
T. cruzi infection have faced the risk of autochthonous transmission. Since
the last decade of the twentieth century, Chagas disease has become an
emerging public health challenge in Europe. This challenge stems from
the considerable diversity observed among Latin American immigrants:
a variety of origins and social groups; a heterogeneous geographical
distribution in the continent; a wide range in their prevalence rates of T.
cruzi infection; and different predominance of clinical forms of the chronic
phase and different severity of morbidity. The identification of the main
health determinants of the Latin American immigrant communities in a
specific area (including their diversity and barriers such as their immigrant
condition and their socio-cultural-economic characteristics) is crucial to
design and implement comprehensive health-care strategies for the care
of people with Chagas disease in Europe. Specific innovative approaches
are needed to make possible the meeting between the health system and
the T. cruzi infected patients, such as: the multidisciplinary approach; the
community approach; and the Expert Patient Programme. The associations
of Chagas disease patients have also been proven to be very helpful as voice
of these usually neglected patients.
Key-words: Comprehensive health care. Immigrants. Europe. Disease nonendemic. T. cruzi infection. Chagas disease.
Human mobility and Chagas disease
distribution in the world
According to one of the most accepted hypothesis, America was
first settled by people from Asia who migrated across the Bering Strait
around 20.000-25.000 years ago1. It is believed that groups of this
early population migrated from North America to South America,
on foot or using primitive boats along the coastline approximately
12.000-15.000 years ago2.
Paleoparasitology studies have evidenced that Chagas disease is
almost as old as man's presence in the Americas. At present, the most
ancient human infection by Trypanosoma cruzi (flagellate protozoa
of the kinetoplastida order and trypanosomatidae family), is known
from mummies dated as 9.000 years old and found in the coastal and
low valley sites in northern and southern Chile3.
1. Chagas disease programme. Department of Control of Neglected Tropical Diseases.
World Health Organization, Geneva. 2. Universidad Santo Tomás, Santiago de Chile.
3. Unitat de Medicina Tropical i Salut Internacional Drassanes. Catalan Institute
of Health, Barcelona. 4. Department of community medicine and primary care,
Geneva University Hospitals and University of Geneva. 5. Ambulatório de Doença
de Chagas e Insuficiência Cardíaca, Oswaldo Cruz University Hospital, University
of Pernambuco.
Address to: Dr. Pedro Albajar Vinas. WHO/HTM/NTD/IDM/Chagas disease. Av.
Appia 20, 1211 - Geneva 27, Switzerland.
92
Carlos Ribeiro Justiniano Chagas discovered the disease in 1909
in Brazil. At the beginning of the twentieth century the disease
was mostly confined to the rural areas of South America, Central
America and Mexico. Later, the population mobility through new
transportation routes, especially railroads and roadways, greatly
contributed to disseminate the disease across 21 Latin American
countries (Argentina, Belize, Bolivia, Brazil, Chile, Colombia,
Ecuador, French Guiana, Guyana, Paraguay, Peru, Uruguay,
Suriname and Venezuela, in South America; Costa Rica, El Salvador,
Guatemala, Honduras, Nicaragua, Panama, in Central America; and
Mexico, in North America). Afterwards, in the second half of the
twentieth century, driven by population's flows from the countryside
to the cities and also, in some cases, with the adaptation of some
vectors to the urban and peri-urban environment, Chagas disease
became an urban phenomenon4,5.
At present, Chagas disease can also be found in the so called
disease non-endemic countries as a result of the population mobility,
mainly migrations occurred in the last decades from Latin American
countries where Chagas disease is endemic to the USA, Canada,
many European countries (especially Belgium, France, Italy, Spain,
Switzerland and the United Kingdom, but also Austria, Croatia,
Denmark, Germany, Luxembourg, the Netherlands, Norway,
Portugal, Romania and Sweden) and some Western Pacific countries
(mainly Australia and Japan). Additionally, the disease expansion
outside Latin America has also been associated to foreigners
visiting disease-endemic areas, for work or tourism reasons, and
returning to their home countries infected by T. cruzi. Consequently,
countries harbouring people with T. cruzi infection face the
risk of autochthonous transmission through blood transfusion,
transmission from mother to son infection (vertical) and through
organ transplantation6,7.
Initial spread of Chagas disease vectors
linked to the population movements
The vectors of Chagas disease are blood-sucking Hemiptera of
the Triatomine subfamily (family Reduviidae). There are more than
140 species of insect vectors of Chagas disease, mainly of American
origin. Triatomine bug species with the capacity to transmit T. cruzi
have also been identified outside America in parts of Africa, Middle
East, Southeast Asia and the Western Pacific. Current theories
indicate that those species in Southeast Asia have probably derived
from American species transported to seaports by sailing ships since
the sixteenth century.
The construction of railways and roadways have also played
a significant role as means of dispersal for these vectors. There is
evidence of the spread of the main intradomiciliary vector species,
the Triatoma infestans, from its origin in the Bolivian Andean valleys
to the rest of South America. This spread has mainly occurred over
the last 150 years and it has been associated to human migrations.
For example, T. infestans has been reported in chairs and passengers’
commodities on long-distance trains in Chile during the 1960s, buses
in Bolivia during the 1980s, and suitcases of passengers travelling
from Bolivia to Argentina in the 1990s8 .
In addition to maritime and overland routes, at present time, the
risk of spreading the Triatomine vector by air transportation routes
has also been demonstrated.
Current diversity of the Latin American
population in Europe at risk of being
infected by T. cruzi
According to the International Organization for Migration
(IOM), Latin American immigrants living in Europe at present are
mainly young, at reproductive age and with a high proportion of
women9. Nevertheless, a considerable diversity has been observed
among those Latin American immigrants in Europe at risk of being
infected by T. cruzi.
The geographical distribution of the Latin American population
living in Europe is not homogeneous. For example, according to official
sources, Brazilians constitute the largest group of Latin American
immigrants in France; Peruvians and Ecuadorians have the highest
number of residents in Italy; and Argentineans, Bolivians, Colombians
and Ecuadorians have the most significant presence in Spain7.
A diversity of social groups has been identified within the
Latin American population at risk of being infected in Europe. At
country level, one of the most common ways of classifying the
immigrant population is according to their legal (documented)
or illegal (undocumented) status. For certain European countries,
such as France, the groups of adopted children from Latin American
countries and children born in France from Latin American
mothers, have also been found to be significant in number7. Despite
the difficulty of the task, it is important to try to obtain accurate
estimations of authorized and unauthorized immigrants by country,
due to the high estimated proportion of immigrants at risk of having
T. cruzi infection in Europe.
Prevalence rates for T. cruzi infection are also heterogeneous
among the Latin American population living in Europe, which
reflects geographical variations in the distribution of the infection in
their countries of origin. In different studies carried out in European
countries, a higher prevalence has been found in the population
coming from Latin American regions of high endemicity10,11,12,13,
for instance, in the case of Bolivian immigrants who come from
Chuquisaca, Cochabamba, Santa Cruz and Tarija Departments.
Moreover, since the 1970s, progressive implementation of various
national control programmes in Chagas disease endemic countries,
principally focused on eliminating the domestic vectors and establishing
blood donation screening for T.cruzi, have resulted in a significant
reduction of transmission13. Therefore, in their countries of origin, older
Latin American immigrant generations now living in Europe were often
exposed to a higher risk of infection than younger ones. For most of these
adult immigrants, their infection occurred decades ago and they are now
presumably in the late chronic phase of the disease14.
Geographical variations in Latin American countries also show
different predominance of clinical forms of the chronic phase and
different severity of morbidity. Therefore, in the coming years infected
individuals in Europe coming from countries such as Argentina,
Bolivia and Brazil may develop myocardiopathy and/or digestive
abnormalities, whereas infected people coming from Central
American countries may show chronic Chagas cardiopathy without
evident digestive abnormalities15.
European health services and the necessity
of meeting health-care needs of Latin
American immigrants with T. cruzi infection
Until the last decade of the twentieth century, Chagas disease
was almost unknown in Europe. At the beginning of the twenty-first
century, as an emerging disease, it has represented a big challenge
to the health system and society itself. After the first approaches
implemented and experiences acquired, a range of challenges
involving the care of people with Chagas disease were identified16:
 Detection
of an infection mostly without evident clinical
manifestations (asymptomatic);
 Availability of appropriate serological tests for screening
and diagnosis purposes and the need of trained health-care
professionals able to perform accurate clinical diagnosis;
 Awareness among health and public health professionals about
this emerging disease;
 Access to parasitological and non-parasitological treatment;
treatment compliance; patient tolerability; patient follow-up;
and assessment of therapeutic response;
 Primary prevention of transmission by blood transfusion, cell,
tissue or organ transplantation;
 Early diagnosis and treatment (secondary prevention) of
congenital transmitted cases;
 Collection and analysis of epidemiological data (baseline) and
establishment of an information and surveillance system;
 Understanding and consideration of the complex psycho-social,
socio-labour-economic and cultural-linguistic conditions of the
Latin American immigrant population in Europe;
 Overcoming the frequently encountered assumption in
immigrants from disease endemic countries that adults infected
with T. cruzi cannot be treated;
 Bridging the gap and creating trust between the health system
and communities of documented and especially undocumented
immigrants, in order to increase acceptation and adaptation of
public health programmes;
 Implementation of public health strategies for the care of people
with Chagas disease.
The identification of the main health determinants of the Latin
American immigrant communities in a specific area is crucial to
design and implement public health strategies for the care of people
with Chagas disease in Europe. Among others, some of these health
determinants could be their legal and insurance status, cultural
and linguistic barriers, their labour conditions and their socialeconomical situation.
Typically, immigrants in an unauthorized condition have a more
limited access to health care. In Switzerland, for example, immigrants
93
frequently face difficulties in accessing health care because health
insurance is expensive. A study conducted in Geneva among 1,012
Latin American immigrants showed that only 4% of the participants
had a valid residence permit and health insurance11. Programmes
and strategies ensuring that immigrants without documents have
access to health care in European countries could improve the health
condition of this population17.
Within the range of challenges regarding access to health care,
the utilization of health services by foreign-born communities can
be conditioned or influenced by linguistic, cultural or social barriers
between these communities and the health-care systems in their host
country. It has also been shown that these barriers can be associated
with negative health outcomes17. Consequently, health education
and disease prevention activities that are linguistically and culturally
tailored for Latin American communities in Europe are needed to
ensure the effectiveness of health-care programmes and, ideally, a
better use of health services.
Even when immigrants have access to health care and use
medical services, the continuity of care can be hampered by the
precarious working conditions of immigrants, their frequent
geographical mobility and their complex social situations. In a study
conducted in Spain between 2004 and 2007, 43/483 (8%) of Latin
American adults who attended specialized centres for infectious
diseases withdrew from medical care after serological tests had
been performed but before specific medical examinations had been
conducted10. The reasons for withdrawal included: conflicting work
schedules and health service opening hours; complicated referral
arrangements between primary health-care services and medical
specialists; and lack of information and sensitization of pregnant
Latin American women and their families about the need of diagnosis
and treatment8,19,20.
Three innovative methodological approaches have been proposed
in order to offer comprehensive health care with a major focus on
people in the chronic phase of Chagas disease.
Multidisciplinary approach
A proven successful approach for the care of people with
Chagas disease has been the creation of expert teams composed by
different professionals, where each member has a distinct role and
all members interact with each other in an interdisciplinary process.
This professional team will work with close collaboration with the
patient and the family (the so-called therapeutic triangle) in order
to provide the best health care. It has been shown that the support of
the family has a remarkable influence on the adherence to treatment
by the patient.
For instance, this professional team can be composed by a
diversity of health professionals such as: a cardiologist, who evaluates
the patient and advises on the cardiac follow-up and treatment; a
nurse, who has frequent contact with the patient and educates him
and his family about the disease; a social worker, whose work mainly
focuses on minimizing the impact of socio-economic factors on the
patient follow-up and his disease; a psychologist, who assesses and
counsels on the psycho-emotional factors that are impairing the
patient’s quality of life; a nutritionist, who, taking into consideration
the socio-economic, cultural and environmental background of
the patient, designs a feasible diet, thereby facilitating the patient’s
adherence to the dietary regimen21. Primary health-care physicians,
94
paediatricians, obstetricians, radiologists and gastroenterologists
are also key actors to compose the team in order to increase the
opportunities to screen and care for infected individuals.
Community approach
In the context of immigration, the meeting between the patient
and the health system is only promoted when the condition of the
human being and his close family and community links are taken
into account (including the immigrant, social, work, language and
cultural barriers faced). This meeting between the patient and the
health system requires a highly skilled and committed team of health
personnel: culturally and professionally diverse and able to work in
an interdisciplinary way, as in the above-mentioned approach. The
main characteristic of this second approach is the presence of the
community health agent as a key member of this team, who is the
link between the patient and his family and community, and is a social
and political actor with a high capacity of working within the health
system and the community.
In the community approach, to better understand the social and
cultural diversity of the immigrant population (country of origin, age,
gender and others), including their external interactions, it is essential
to carry out quantitative and qualitative research that will facilitate
the approximation to the reality with its full complexity. The ultimate
objective is to create unique strategies to adapt the health system to
the needs of the immigrant communities (developing health-care
protocols and educational material, among others) and to lower
its threshold regarding accessibility (with minimal administrative
requests, economically affordable, culture and migrant-friendly and
delocalized from main health centres). This will definitely facilitate
the implementation of community and family work strategies, with
a cross-cultural approach, key to the prevention, diagnosis, treatment
and follow-up of infected and ill people18,19,20.
Expert Patient Programme
The recent application of the Expert Patient Programme to
Chagas disease is a pioneer methodology because it involves Chagas
disease chronically-infected people as active actors in the health-care
process. Additionally to medical care, the unique characteristic of this
programme is the organization of complementary sessions facilitated
by a patient who has first-hand experience in the disease, the "expert
patient”, who counsels others suffering from similar symptoms and
problems. In this approach, the health-care professional attending
these sessions has an observer role and can intervene in the session
only if requested by the "expert patient"22.
In countries like the United Kingdom this programme has already
shown positive effects on the health of people with chronic diseases
such as diabetes. At present, a pilot project applying this methodology
to Chagas disease patients is being implemented by the Institut Català
de la Salut in Barcelona, Catalonia, Spain, in collaboration with the
World Health Organization.
The objectives of the Expert Patient Programme for Chagas
disease include increasing the knowledge of people with Chagas
disease about their condition, improving their degree of self-care,
ensuring therapeutic compliance, and improving the quality of their
lives and that of their families.
Finally, the authors would like to highlight the current existence
of associations of Chagas disease patients in the regions of the
Americas, Europe and the Western Pacific. They have had a key
role as voice of the frequently neglected disease carriers. The first
assembly of a new International Federation of world associations
is being organized in the city of Recife, Pernambuco, Brazil, in the
second semester of 2010.
Conclusions
The comprehensive health care of Chagas disease patients in
Europe requires taking into account their significant determinants of
health, including their diversity and barriers such as their immigrant
condition and their socio-cultural-economic characteristics.
Specific innovative approaches are needed to make possible the
meeting between the health system and the T. cruzi infected patients,
such as: the multidisciplinary approach, with the interaction of
several health professionals from different disciplines; the community
approach, with the community health agent as a key actor; and the
Expert Patient Programme, with the involvement of the patient in
his own care. The associations of Chagas disease patients have also
been proven to be very helpful as voice of these usually neglected
patients.
8. Schofield CJ, Grijalva M. J, Diotaiuti L. Distribución de los vectores de la
Enfermedad de Chagas en países “no endémicos”: la posibilidad de transmisión
vectorial fuera de América Latina. Enf Emerg 2009; 11 (suppl 1): 20-27.
9. Pellegrino A. Migration from Latin America to Europe: Trends and Policy.
International Organization for Migration 2004.
10. Muñoz J, Gómez i Prat J, Gállego M, Gimeno F, Treviño B, López-Chejade P
et al. Clinical profile of Trypanosoma cruzi infection in a non-endemic setting:
immigration and Chagas disease in Barcelona (Spain). Acta Trop 2009; 111
(suppl 1): 51-55.
11. Jackson Y, Gétaz L, Wolff H, Holst M, Mauris A, Tardin A et al. Prevalence, Clinical
Staging and Risk for Blood-Borne Transmission of Chagas Disease among Latin
American Migrants in Geneva, Switzerland. PLoS Negl Trop Dis 2010; 4 (issue
2): e592.
12. Lescure FX, Canestri A, Melliez H, Jauréguiberry S, Develoux M, Dorent R et
al.Chagas Disease, France. Emerg Infect Dis 2008; 14(4): 644-646.
13. Anselmi M, Angheben A, Degani M, Tais S, Spreafico I, Bonifacio E et al. Imported
Chagas disease in Italy: Preliminary screening results of selected immigrant
populations. Trop Med Int Health 2009; 14(suppl .2): 74-75.
14. Dias JCP. Elimination of Chagas disease transmission: perspectives. Mem Inst
Oswaldo Cruz 2009; 104(suppl. 1): 41-45.
15. Pérez de Ayala A, Pérez-Molina JA, Norman F, López-Vélez R. Chagasic
cardiomyopathy in immigrants from Latin America to Spain. Emerg Infect Dis
2009; 15(suppl 4): 607-608.
16. Coura JR, Albajar-Vinas P. Chagas disease: a new worldwide Challenge. Nature
2010; 465 (n7301_supp): S6-S7.
References
17. Jackson Y, Angheben A, Carrilero Fernández B, Jansà i López del Vallado JM,
Jannin JG, Albajar-Viñas P. Chagas disease in Europe. Experiences and challenges
in Spain, Switzerland and Italy. Bull Soc Pathol Exot 2009; 102(5): 326-329.
1. Guhl F, Jaramillo C, Vallejo GA, Cárdenas A, Arroyo F, Aufderheide A. Chagas
disease and human migration. Mem Inst Oswaldo Cruz 2000; 95(4): 553-555.
18. Gushulak B, Weekers J, MacPherson DW. Migrants in a globalized world — health
threats, risks and challenges: an evidence-based framework. Emerg Health Threats
J 2009; 2: e10.
2. Araújo A, Jansen AM, Reinhard K, Ferreira LF. Paleoparasitology of Chagas
disease - A review. Mem Inst Oswaldo Cruz 2009; 104 (suppl 1): 9-16.
3. Aufderheide AC, Salo W, Madden M, Streitz J, Buikstra J, Guhl F et al. A 9,000-year
record of Chagas' disease. Proc Natl Acad Sci USA 2004; 101(7): 2034-2039.
4. Briceño-León R, Méndez Galván J. The social determinants of Chagas disease
and the transformations of Latin America. Mem Inst Oswaldo Cruz 2007; 102
(suppl 1):109-112.
5. Levy MZ, Bowman NM, Kawai V, Waller LA, Cornejo del Carpio JG, Cordova
Benzaquen E et al. Periurban Trypanosoma cruzi–infected Triatoma infestans,
Arequipa, Peru. Emerg Infect Dis 2006; 12: 1345-1352.
6. Schmunis GA, Yadon ZE. Chagas disease: A Latin American health problem
becoming a world health problem. Acta Trop 2010; 115: 14-21.
7. WHO 2010. Control and prevention of Chagas disease in Europe. Report of a
WHO Informal Consultation (jointly organized by WHO headquarters and the
WHO Regional Office for Europe). Geneva, Switzerland, 17-18 December 2009.
WHO/HTM/NTD/IDM/2010.1.
19. Avaria A, Gómez i Prat J. "Si tengo Chagas es mejor que me muera" El desafío de
incorporar una aproximación socio-cultural a la atención de personas afectadas
por la enfermedad de Chagas. Enf Emerg 2008; 10 (Suppl 1): 40-45.
20. Avaria A, Gómez i Prat J. Mujer derivada por médicos de familia para descartar
enfermedad de Chagas. Capitulo 4: Atención Comunitaria a la población
inmigrante. In: UMTSID editor. 50 Casos clínicos de salud internacional. 25 años
de trabajo de la Unidad de Medicina Tropical y Salud Internacional. Gràfiques
Montseny; 2008. p. 229-236.
21. Avaria A. Migrar, enfermar-sanar lejos de casa. Bolivianos en Barcelona experiencia
hecha carne. In: Agar L, editor. Migraciones, salud y globalización, entrelazando
miradas. Santiago de Chile: OIM, OPS, MINSAL; 2010. p. 199-213.
22. Oliveira Jr W. All-around care for patients with Chagas disease: a challenge for
the XXI century. Mem Inst Oswaldo Cruz 2009; 104 (suppl 1): 181-186.
23. González Mestre A, Fabrellas Padrés N, Agramunt Perelló M, Rodríguez Pérez E,
Grifell Martín E. Expert patient program Institut Català de la Salut: From passive
to active patient. RISAI 2008; 1(1): 1-3.
95
12. Economic crisis and enhanced immigrants mobility: new challenges in the
management of Chagas disease in Europe
Cet article a été accepté pour publication dans:
Bull World Health Organ. 2014
Par:
Jackson Y, Varcher Herrera M, Gascon J.
87
Economic crisis and enhanced immigrants mobility: new challenges in the management of
Chagas disease in Europe
Yves Jackson1, Monica Varcher Herrera1, Joaquim Gascon2
1
Department of community medicine, primary care and emergency medicine, Geneva
University Hospitals and University of Geneva, Switzerland
2
Barcelona Centre for International Health Research (CRESIB), ISGLOBAL, Barcelona, Spain
Corresponding author
Yves Jackson
Department of community medicine, primary care and emergency medicine, Geneva
University Hospitals and University of Geneva
Rue Gabrielle-Perret-Gentil 6
1211 Geneva 4, Switzerland
yves.jackson@hcuge.ch
Ph. +61 (0)452 543 600
Key words
Public health policy, infection control, Chagas disease
Abstract
The financial and economic crisis affecting Europe since 2008 and the ensuing austerity
measures have caused adverse health impact on some populations, most notably on
vulnerable groups. Recession-led fiscal measures have often resulted in reduced public
health and clinical services to vulnerable immigrants as illustrated by the recent change of
national policy in Spain severely restricting undocumented immigrants’ access to care. At the
same time, Europe sees the emergence of new communicable health threats, some of them
in relation with new patterns of immigration. This article discusses new challenges pertaining
to Chagas disease management in the context of the current crisis. This emerging disease
affects 80’000 to 120’000 people in Europe with ongoing local transmission and is
particularly at risk of being exacerbated by the crisis given its complex clinical and social
characteristics. We present a set of suggestions to adapt and enhance the current responses
to Chagas disease in Europe in light of the ongoing crisis context.
Manuscript
Mounting evidences illustrate the health impact of the global financial crisis in Europe. Those
include increasing risk behaviours and poorer mental, maternal and child health among the
most vulnerable groups of population (1). Limited data are available about the relationship
between communicable diseases-related health outcomes and economic downfall in
developed countries. A meta-analysis suggested worsened health outcomes affecting the
whole population, while vulnerable and hard-to-reach groups such as infants, elderly, poor,
homeless, prisoners and immigrants carried the main burden (2).
Europe harbours a substantial burden of infectious diseases linked to social and economic
disadvantage borne by such vulnerable groups. The last two decades saw the arrival of more
than 3.5 millions Latin American immigrants in Europe, with a predominance of young-tomiddle age women and a proportion living in irregular situation (3). Chagas disease, a
parasitic infection endemic in Latin America, has recently emerged in Europe, affecting an
estimated 80’000 to 120’000 Latin American immigrants and entails annual costs of up to $
16 and 137 million due to healthcare costs and lost productivity, respectively (4).
Transmission through congenital and unscreened blood and organ donations has been
identified in several countries. Spain and Italy, two countries severely hit by the crisis, host
the largest Latino communities at risk and the highest number of cases (5). Undetected and
untreated, 20-40% of infected people will develop potentially severe cardiac, digestive or
neurologic complications requiring complex, costly and long-lasting medical attention.
Despite evidences showing the economic and health benefits of implementing targeted
screening and treatment strategies among at at-risk groups, Chagas disease-related health
needs remain largely unmet in Europe as attested by the limited number of cases identified
in regards to the estimated burden and to the dearth of health policies regarding its control
and management. The long clinically-silent phase, the poor specificity and high diversity of
symptoms when there are, the need for specific diagnostic procedures and the lack of
awareness among health professionals contribute to limit opportunities for identifying
infected individuals. Moreover, infected Latino immigrants in Europe often face
administrative and economic barriers hindering access to care. Recommended transmission
control strategies include screening pregnant women, their newborns and other family
members and testing blood and organ donors at risk.
The current crisis in Europe and the subsequent austerity measures impact on the
management of Chagas disease. Several European countries have cut health and social
services targeting vulnerable immigrants since 2008. In Spain for example, a Royal Decreelaw (2012) severely restricted access to preventive and primary healthcare for
undocumented immigrants. The decreasing economic opportunities in countries most
affected, such as Spain, Portugal and Italy, has led to enhanced immigrants mobility within
Europe and towards their home countries (3). Immigrant families have often been forced to
split with male and female members targeting gender-specific job opportunities in different
places.
This enhanced mobility jeopardizes continuity of care and challenges the implementation of
the recommended whole-of-family screening after a case of infection has been identified.
While most infected immigrants initially lived in Spain, a country that has developed
effective responses against Chagas disease over the last decade, a consequent number has
recently moved to less economically affected countries with fewer or no Chagas disease
programs, raising the challenge of further enhancing transmission.
In order to respond to these challenges entailed by the consequences of the current period
of economic hardship, the austerity measures and the enhanced mobility of immigrants at
risk of Chagas disease, there is a need for enhanced and coordinated multi-pronged,
sustained public health and clinical interventions grounded in evidences. Therefore, we
propose a set of recommendations to optimize Chagas disease management and control in
Europe in the current context of economic crisis:
i) Developing Chagas disease-related programs in countries/regions hosting communities at
high risk. The community at highest risk in Europe are Bolivians (5). Although difficult to
precisely quantify, it is estimated that around 300’000 live in Europe, frequently clustered in
closely-knit communities (3). In regions/countries where large-scale programs targeting all
Latin-American immigrants are not feasible, efforts should primarily focus on the Bolivian
community. While this may pose the risk of missing some cases from other communities, it
would provide acceptable effectiveness as Bolivians account for more than 90% of cases
identified so far in Europe. Therefore, all efforts should be made to identify new areas where
Bolivian immigrants settle and to develop preventive and curative Chagas disease programs
targeting them.
ii) Optimizing Chagas disease interventions effectiveness by grounding them into primary
health care systems. While developing de novo specialized Chagas disease programs might
entail too many financial and organisational constraints, grounding them into existing
primary health care programs targeting immigrants, where most people at risk are being
attended, is likely to be the most effective strategy. Indeed, improving awareness, ensuring
diagnostic facilities are available and developing capacities to correctly orientate patients
among the various therapeutical options within such settings (including paediatric and
gynaecology and obstetrics facilities) in regions hosting communities at-risk would allow for
multiplying the opportunities to identify cases and for providing a whole-of family approach
shown to be effective. Yet, close collaboration between primary and specialized care
services have proven very beneficial, especially in the management of treatment. Moreover,
the fact that Chagas disease patients frequently present concomitant non-communicable
diseases (NCD) requiring recurrent contacts with healthcare services also calls for merging
Chagas and NCD management strategies. Strong coordination and effective communication
between health institutions providing health services for immigrants across Europe would
allow for optimizing continuity of care in the context of immigrants enhanced mobility.
Among other benefits, this could reduce the consequent loss of follow-up in children
recently born from infected mothers during the multi-stage diagnostic procedure in the first
year of life and improve the clinical follow-up of adults after treatment.
iii) Fostering support from the communities. Chagas disease is deeply embedded in social,
economic and cultural factors and affected immigrants communities maintain patterns.
Immigrants may not engage with programs for different reasons including unawareness, fear
of stigma or negative representation about the disease. In recent years, Chagas disease
patients’ organizations have developed both in Latin and North America and in Europe
(http://www.findechagas.com). They have shown to be effective partners in raising
awareness, spreading information and facilitating contacts between communities and health
systems in cities with consequent Chagas disease burden. Strengthening community-based
interventions with the support of immigrants’ organizations may therefore harness great
benefits in terms of effectiveness of screening and transmission control programs in the
often hard-to-reach communities.
iv) Reinforcing measures to control vertical and blood-borne transmission. Except for a few
European countries, there is a dearth of public health policies regarding Chagas disease
control, which results in its persisting transmission. Considering that congenital infection is
the main route of transmission outside endemic areas, the high proportion of female Latin
American immigrants of child-bearing age and the proven favourable cost-effect ratio of
screening (6), priority attention should be paid to identify infected pregnant women in areas
hosting communities at risk. Adding Chagas disease serology to other pre-natal blood tests in
well defined populations would not incur important extra costs, while harnessing important
public health and individual benefits. Moreover, blood-transfusion transmission control,
would it be by pre-donation questionnaire and donors exclusion or by blood testing in
donors at risk, should be implemented in countries hosting populations at risk. By carefully
selecting the criteria for screening (for instance Bolivian origin or long-term residency in
rural area of endemic countries, history of unscreened blood transfusion in Latin America or
Chagas disease in the mother) a single or a limited number of reference centres would be
sufficient to process all samples with limited extra costs.
In conclusion, the current economic crisis entails risks and opportunities regarding the
control and management of Chagas disease in Europe and the containment of high
economic costs. Whereas crisis-related factors may lessen the public health and clinical
capacities to address this issue and increase immigrants’ vulnerability, the experience gained
in Europe about Chagas disease management during the last decade may hold great promise
in facilitating the decision-making about optimal control strategies in newly affected
countries. The current context also provides an excellent opportunity to reflect upon and
adapt those strategies and forces to rethink some long-established paradigms.
References
1.
Karanikolos M, Mladovsky P, Cylus J, Thomson S, Basu S, Stuckler D, et al. Financial crisis,
austerity, and health in Europe. Lancet. 2013;381(9874):1323-31.
2.
Suhrcke M, Stuckler D, Suk JE, Desai M, Senek M, McKee M, et al. The impact of economic
crises on communicable disease transmission and control: a systematic review of the evidence. PloS
one. 2011;6(6):10.
3.
IOM. Rutas y dinámicas migratorias entre los países de América Latina y el Caribe (ALC), y
entre ALC y la Unión Europea. Bruxelles: IOM, 2012.
4.
Lee B, Bacon K, Bottazzi M, Hotez P. Global economic burden of Chagas disease: a
computational simulation model. Lancet Infect Dis. 2013;13(4):342-8.
5.
Basile L, Jansa JM, Carlier Y, Salamanca DD, Angheben A, Bartoloni A, et al. Chagas disease in
European countries: the challenge of a surveillance system. Euro surveillance : bulletin europeen sur
les maladies transmissibles = European communicable disease bulletin. 2011;16(37).
6.
Sicuri E, Munoz J, Pinazo MJ, Posada E, Sanchez J, Alonso PL, et al. Economic evaluation of
Chagas disease screening of pregnant Latin American women and of their infants in a non endemic
area. Acta Trop. 2011;118(2):110-7.
13. Discussion
13.1 Principaux résultats
Les études épidémiologiques conduites à Genève, bien que basées sur un recrutement non
aléatoire (non-random sampling), illustrent l’émergence de la maladie de Chagas en Suisse
et son importance en termes de santé publique. Des données similaires récoltées en
Espagne, Italie et en France indiquent que ce phénomène touche simultanément plusieurs
pays d’Europe occidentale abritant des communautés de migrants Latino-Américains
(Angheben A, 2011; Lescure et al., 2008; Munoz, Gomez i Prat, et al., 2009). Ceci reflète la
nature chronique de cette infection le plus souvent acquise durant l’enfance en zone
endémique puis portée de manière chronique tout au long de l’existence. Ainsi, les taux de
prévalence au sein des diverses communautés migrantes reflètent les taux trouvés parmi les
populations adultes de ces pays endémiques respectifs (PAHO, 2006). A ce titre, tant à
Genève que dans les pays Européens de l’Ouest, les migrants d’origine bolivienne
constituent la population la plus affectée en termes de prévalence, élément concordant avec
le fait que la Bolivie présente les taux de prévalence nationaux et régionaux les plus élevés.
Autrement dit, les taux de prevalence d’infection parmi les communautés migrantes Latino
en Europe sont proportionnels à la proportion de Boliviens. En Suisse, Genève abrite la
communauté bolivienne la plus importante, ce qui contribue à expliquer la position
proéminente du canton dans le nombre de cas recensés à ce jours au niveau national
(Jackson & Chappuis, 2011).
Alors que plus de 40’000 personnes originaires de pays endémiques vivent en Suisse, le
nombre réel de personnes à risque reste mal connu en raison de la présence simultanée
d’une population migrante sans permis de séjour (sans-papiers) dont la taille est
probablement au moins équivalente (GFS.Berne, 2005; Swiss Federal Bureau of Statistics,
2010). En 2010, les pays de l’Union Européenne abritaient environ 4.5 millions de résidents
d’origine Latino-Américaine dans le contexte de flux migratoires s’étant fortement accélérés
au cours des années 2000’(IOM, 2012). En effet, le nombre annuel de migrants Latinos
entrant dans l’Espace Européen entre 2000 et 2006 a doublé pour atteindre 400’000
personnes. A noter également que ces flux transcontinentaux se superposent à des flux
massifs intra-nationaux et inter-régionaux en Amérique Latine où plus de 17 millions de
93
personnes à risque ont migré au cours des deux dernières décennies. Les données
démographiques récentes montrent que cette dynamique migratoire ne se tarit pas avec la
crise économique et financière que connait l’Europe depuis 2007 (IOM, 2012). L’une des
conséquences de la crise consiste en l’augmentation de la mobilité des migrants Latino entre
pays Européens, quittant les régions les plus affectées telles que l’Espagne et le Portugal
pour se diriger vers des régions plus prospères telles que la Suisse. Il est donc probable que
le nombre de personnes à risque de maladie de Chagas présentes en Suisse continue à
augmenter.
En 2009, il a été estimé que 80-120’000 personnes adultes d’origine Latino-Américaine
étaient porteuses de la maladie de Chagas en Europe, ce qui fait de cette infection la
maladie parasitaire émergente principale du continent (Hotez & Gurwith, 2011; WHO, 2009).
A l’heure actuelle, seules quelques milliers de cas ont été diagnostiqués (WHO, 2009). Les
modèles épidémiologiques estiment que plus de 90% des cas d’infection en Europe restent
actuellement non détectés (Basile et al., 2011). Ceci appelle donc à des efforts importants
des politique de santé publique afin de combler ce fossé avec la mise en place
d’interventions à divers niveaux et dans divers secteurs afin d’améliorer le taux de dépistage
des personnes infectées. En premier lieu, il convient d’adresser le problème du manqué
d’attention qui caractérise cette maladie au niveau des systèmes de santé et du manque de
connaissance des professionnels de santé (Jackson et al., 2009; Velarde-Rodríguez et al.,
2009).
Les données suisses et européennes montrent une très large prédominance de femmes
parmi les personnes infectées. Ceci peut s’expliquer par une plus grande demande soins de
la part des femmes mais surtout par des facteurs sociaux, économiques et conjoncturels
dans les pays d’origine et receveurs ayant favorisé une migration majoritairement féminine
en Europe (Benach, Muntaner, Delclos, Menendez, & Ronquillo, 2011; IOM, 2012). La
féminisation de la maladie de Chagas en Europe a pour conséquence de favoriser le risque
de transmission congénital de T. cruzi et souligne l’importance d’une approche familial plus
qu’individuelle de la gestion du risqué et du management de la maladie.
Nos résultats confirment la transmission verticale de l’infection en Suisse dans un contexte
initial d’absence de mesure de prévention et d’identification du risque. Ces résultats ont
94
sous-tendus la mise en place d’un programmes de screening prénatal chez les femmes
enceintes à risque à Genève qui a permis l’identification d’un nombre important de cas
(Martinez de Tejada, Jackson, Paccolat, & Irion, 2009). Des données similaires ont été
publiées dans les pays voisins avec initialement l’identification de cas de transmission puis
plus récemment la mise en évidence d’un large pool de femmes enceintes infectées et
dépistées pendant la grossesse supportant la mise en place de screening (Angheben A, 2011;
Flores-Chavez et al., 2011; Munoz, Coll, et al., 2009; Munoz, Portus, Corachan, Fumado, &
Gascon, 2007; Riera et al., 2006). Ces résultats montrent que la voie transplacentaire est la
route de transmission prédominante en Europe. Des modèles épidémiologiques estiment
que plusieurs centaines d’enfants naissent infectés chaque année en Europe (Basile et al.,
2011). A l’heure actuelle, il n’existe pas de données de qualité suffisante pour évaluer l’effet
de prévention primaire sur la transmission du traitement des jeunes femmes en âge de
procréer avant la grossesse. Néanmoins, certaines données récentes évoquent une possible
diminution du risque après traitement (Murcia et al., 2013). Les traitements antiparasitaires
disponibles ne sont pas applicables pendant la grossesse, il n’existe donc pas de moyens de
prévention secondaire de l’infection. Il en découle une nécessité de développer des
algorithmes de suivi séquentiels pour le dépistage et le traitement de la mère et de l’enfant
sur le moyen terme après la naissance. La description des 45 cas pédiatriques de Genève et
Barcelone illustre la difficulté d’assurer un tel suivi parmi cette population hautement
mobile et souvent précaire, ce qui débouche sur une perte conséquente de cas en cours de
route (Guerineau et al., 2013). La mitigation des conséquences de la transmission
congénitale en Europe passé par la mise en place systématique de programmes de dépistage
des femmes enceintes à risque. Dans les régions qui les appliquent, de tels programmes ont
montré un rapport coût-bénéfice très favorable (Sicuri et al., 2011). Il est également
impératif de développer de nouveaux outils diagnostiques permettant d’identifier l’infection
du nouveau-né dans la phase immédiate post-natale ainsi que des traitements utilisables
durant la grossesse.
Nos données supportent l’idée d’une approche familiale et communautaire du dépistage de
la maladie de Chagas en raison de la fréquente existence de facteurs de risques partagés
entre membres de la même famille/communauté. Une récente publication a démontré
l’impact positif d’un dépistage élargi autour d’un cas index permettant d’identifier des
95
clusters de cas (Zulantay et al., 2013). Plus globalement, l’approche communautaire permet
également de travailler sur les barrières d’accès aux soins et les représentations parfois
négatives de la maladie (Magnani, Oliveira, & Gontijo, 2007; Minneman et al., 2012). Un
programme d’éducation à la santé maternelle culturellement adapté à la clientèle latinoaméricaine à Madrid a permis d’augmenter le taux d’acceptation du screening de l’infection
chez les femmes enceintes (Navarro et al., 2011). Cet ancrage culturel et communautaire de
l’intervention préventive fait d’autant plus sens au vu du profil socioéconomique des
migrants à risque. En effet, à Genève et en Suisse, la très large majorité des cas sont
identifiés chez des personnes sans permis de séjour valables (sans-papiers) et sans
assurance-maladie (Demaurex et al., 2013; Jackson et al., 2012; Jackson, Getaz, et al., 2010).
Ainsi, en l’absence d’ancrage de ces programmes dans la communauté, souvent hors des
institutions de santé, il est probable que leur rendement soit très faible et ne permettent
d’identifier que les cas avancés d’infection se présentant avec des complications d’organes
comme ce fut le cas jusqu’au milieu des années 2000 en Suisse, en Espagne et en Italie
(Jackson et al., 2009; Jackson & Chappuis, 2011). En outre, l’une des garanties du succès des
programmes de dépistage et de prise en charge de la maladie de Chagas
Nos résultats identifient un risque conséquent de transmission par voie de transfusion ou de
transplantation. En effet, une proportion importante de personnes infectées se déclare
désireuses de donner leur sang ou leurs organes en Suisse. De plus l’absence fréquente de
procédure de dépistage efficaces dans les centres de transfusion sanguine et de
transplantation ont facilité cette transmission sanguine ou tissulaires ainsi que des cas de
réactivation chez des patients greffés immunosupprimés en Europe et aux Etats-Unis (Bern,
Kjos, Yabsley, & Montgomery, 2011; Flores-Chavez et al., 2008; Jackson, Dang, Schnetzler,
Pascual, & Meylan, 2011). Il convient de noter que dans notre cohorte, plus de 95% des
personnes ignoraient leur infection au moment du diagnostic, ce qui illustre les limites d’un
screening base sur un questionnaire quant à la présence de l’infection tel que pratiqué en
Suisse jusqu’en 2013. Heureusement, l’identification de donneurs infectés et nos données
ont permis de modifier les procédures avec l’instauration de tests sanguins chez les
personnes à risque depuis 2013 sur le modèle de ce qui se pratique en Espagne (Pizzi
Bosman & Rosochova, 2011). De plus, la récente publication de recommandations
américaines et européennes sur l’identification et le management de donneurs d’organes
96
infectés devrait également permettre de mieux prendre en charge le risque liés à ce mode
de transmission (Chin-Hong et al., 2011; Pinazo et al., 2011).
L’évaluation de l’état de santé physique, mentale et social des personnes avec maladie de
Chagas à Genève montre la présence de facteurs de risque cumulatifs de plusieurs ordres.
Sur le plan somatique, la présence de troubles métaboliques tels que l’hypertension,
l’hypercholestérolémie, le diabète et la surcharge pondérale étayent la transition de santé
qui a actuellement lieu dans les pays endémiques, à savoir la présence de maladies
infectieuses associée à l’émergence rapide des maladies non transmissibles. Ceci force à
redéfinir la façon d’appréhender la maladie de Chagas pour laquelle on peut faire
l’hypothèse que le pronostic pourrait être ultimement s’aggraver en présence de
comorbidités athérogènes. Ceci renforce le besoin d’interventions de santé préventive
précoces parmi la population à risque, tant pour identifier l’infection que pour agir sur les
comorbidités. Par ailleurs, la présence fréquente de troubles de la santé mentale est un
facteur d’importance dans la prise en charge des personnes infectées. En effet, le dépistage
de trouble psychique est important au vu du risque de troubles psychiques induits par les
médicaments antiparasitaires (Jackson, Alirol, et al., 2010; Perez-Molina et al., 2009; Pinazo,
Munoz, et al., 2010). De plus, cette souffrance psychique peut contribuer à fragiliser la
situation socioéconomique de migrants atteints, vivant déjà, pour la plupart, en situation de
précarité. En effet, notre étude montre une association étroite entre infection à T. cruzi et
précarité socioéconomique. Ce lien, bien décrit en région endémique, complexifie la prise en
charge des populations à risque en Europe de par la fréquente difficulté d’accès aux soins,
notamment préventives, des personnes infectées, la fréquente position des communauté
migrantes en marge de la société et de l’agenda politique et de par l’impact négatif sur la
santé de déterminants sociaux défavorables (Benach et al., 2011; Cuadra, 2012; Wolff et al.,
2005).
Le contexte actuel de crise économique et financière ayant forcé plusieurs pays abritant des
communautés à risque à adopter des mesures d’austérité fait poser une menace bien réelle
sur le contrôle de la maladie de Chagas en Europe. En effet, outre l’abandon de programmes
de santé préventive et de premier recours destinés aux populations migrantes et
défavorisées, on assiste également à la montée de la xénophobie et de l’intolérance face aux
résidents étrangers qui peuvent avoir des conséquences néfastes sur la santé migrants à
97
risque (MdM, 2013; Rechel, Mladovsky, Ingleby, Mackenbach, & McKee, 2013). Comme
indiqué plus haut, la crise s’accompagne d’une mobilité accrue des migrants précaires entre
régions et pays d’Europe, ce qui pose de nouveaux défis dans l’organisation des soins pour
cette infection chronique. L’expérience de terrain de la Consultation Ambulatoire Mobile de
Soins Communautaires à Genève reflète ce nouveau fait avec l’arrivée d’une forte
population de migrants Latino-américains ayant résidé en Espagne au cours de la dernière
décennie et venant chercher en Suisse de meilleures opportunités. Nombre de cas de
maladie de Chagas actuellement dépistés aux HUG arrivent d’Espagne où un diagnostic, voir
tout ou partie de la phase d’évaluation/traitement ont été pratiqués. La plupart de ces
nouveaux cas vivent en situation de grande précarité et d’incertitude quant à leur avenir
proche, les empêchant souvent de se projeter dans l’avenir et d’accepter un traitement et
un suivi sur plusieurs mois. Ceci rend nécessaire de renforcer la collaboration avec des
centres de santé recevant des patients migrants latino-américains dans les pays voisins et
dans les pays d’origine afin de garantir la continuité des soins. Par ailleurs, ce nouveau
contexte souligne l’importance de l’implémentation des programmes ciblant la maladie de
Chagas dans les services de médecine de premier recours (primary care). Ceci permet
d’optimaliser les chances de contact avec la population cible et donc d’améliorer l’efficacité
des programmes, de fournir une intervention centrée sur la famille, mais également afin de
fournir des soins pluridisciplinaires globaux au vu de la coexistence de maladies chroniques
non-transmissibles. Finalement, favoriser l’implication des communautés fait sens dans
étant donnés les facteurs sociaux et culturels dans lequel émerge la maladie de Chagas en
Europe (Ventura-Garcia et al., 2013).
13.2. Défis à relever et futures orientations de recherche
Au vu de l’intérêt scientifique limité qu’a suscité la maladie de Chagas jusqu’à présent, de
nombreuses questions fondamentales restent à élucider. Sur le plan de la recherche,
plusieurs priorités se dégagent.
La première concerne l’identification de traitements plus efficaces, mieux tolérés et de
moins longue durée permettant de prévenir la survenue de complications potentiellement
fatales à différents âges de la vie. Plusieurs molécules (dérivés azolés) sont en cours
98
d’évaluation mais à ce jour, aucune n’a montré de bénéfice substantiel. Etant donnés les très
longs délais de développement d’un médicament avant sa mise sur le marché, il conviendrait
d’investiguer de nouvelles stratégies avec les traitements existants. Un traitement
combinant les deux médicaments ou associant le benznidazole à un dérivés azolé devrait
être testé contre la monothérapie actuelle avec comme outcome primaire la tolérance et
l’efficacité. De plus, différents régimes de doses et de durées devraient être testés au vu de
l’aspect peu pratique et du besoin de ressources important des schémas actuels.
La seconde priorité concerne l’identification de marqueurs de guérison après traitement. En
effet, le suivi sérologique est le seul outil disponible actuellement mais il n’est d’aucune
utilité clinique chez les personnes au stade chronique étant donné la latence de plusieurs
années, voir décennies, avant un retour à la négativité. Notre groupe a initié une
collaboration avec la Fondation Drugs for Neglected Diseases Initiative (DNDi) et l’Université
de Mc Gill (Montréal) afin d’identifier des marqueurs sanguins de diagnostic et de guérison
utilisant des techniques d’analyse protéomique. Une première phase d’étude s’est déroulée
sur des patients adultes traités par nifurtimox compares à des contrôles et une seconde
phase devrait en explorer les performances chez des enfants.
Le troisième point concerne l’exploration du contexte dans lequel émerge la maladie de
Chagas en Suisse et en Europe. A ce jour, aucune étude n’a exploré plus avant nos trouvailles
publiées en 2012 concernant les facteurs socioéconomiques des patients. Outre une
meilleure compréhension de la dimension socioculturelle de la maladie au niveau de
l’individu, permettant également de donner une voix aux malades par le biais d’approches
qualitatives, une analyse approfondie des déterminants globaux, liés à la question
migratoire, du genre, de l’acculturation et à l’impact à la crise économique actuelle,
contribuerait à faciliter la sortie de l’ombre de cette maladie négligée, à sa meilleure prise en
considération par les milieux sanitaires et au développement de programmes de dépistage
et de prise en charge plus performants. Ultimement, le défi consistant à combler le fossé
entre la présence d’une importante population à risque et le faible nombre de cas dépistés
et à contrôler de manière plus efficace la transmission de T. cruzi hors d’Amérique latine. Sur
le plan pratique, la mobilité des personnes à risque appelle au développement de réseaux
d’institutions permettant de favoriser le dépistage des personnes à risque et le suivi des cas
à travers le temps et les zones géographiques.
99
La quatrième priorité tient à une meilleure compréhension des relations causales et des
conséquences de la coexistence de l’infection chronique à T. cruzi et de maladies non
transmissibles chroniques telles que les maladies métaboliques. En effet, il est probable que
ce cumul de charges de maladie (burden of disease) modifie profondément la présentation,
le développement et le pronostic de la maladie de Chagas. Cet état de fait requiert une
approche non plus isolée de l’infection mais bien plus globale tant sur le plan clinique que de
la santé publique
Finalement, cette émergence questionne la façon dont le savoir sur cette maladie évolue
depuis sa “sortie” d’Amérique latine. En effet, on assiste à une rapide augmentation des
publications et des connaissances issues des régions non-endémiques depuis la fin du
Millénaire. Ceci a mené à plusieurs changements de paradigmes bien ancrés dans une vision
latino-américaine de la maladie tels que la priorité mise sur la lutte anti-vectorielle, le peu
d’intérêt porté aux patients adultes et l’approche essentiellement biomédicale de l’infection.
Une investigation épistémologique permettrait ainsi de mieux comprendre ces changements
et leurs impacts sur la façon de penser la maladie au travers des continents et du temps.
100
14. Conclusions
L’émergence de la maladie de Chagas en Suisse et en Europe s’inscrit dans de le contexte de
processus globaux et mondialisés tels que l’augmentation des flux migratoires
transcontinentaux, leur féminisation et le développement d’une frange de population
migrante extrêmement précarisée. Par ailleurs, la population cible est porteuse d’une
double charge de maladie, combinant maladies infectieuses et maladies non-transmissibles
ce qui va certainement contribuer à redéfinir l’évolution du pronostic de santé des sujets
atteints.
Dans le contexte actuel, ceci engendre de nombreux défis cliniques et de santé publique au
vu du déficit de connaissance et de directives (policies) locales et nationales à propos de la
gestion de l’émergence de maladie de Chagas. Il persiste donc un risque sanitaire, social et
économique pour la population migrante latino et la population résidente auquel il s’agit de
faire face. Genève et la Suisse font partie des précurseurs et des rares régions européennes
ayant réagi à cette émergence tant par la mise en place de programmes destinés à identifier
les personnes infectées et à limiter l’impact de la transmission que par le développement de
projets de recherche permettant de mieux cerner ce phénomène. Une approche scientifique
pluridisciplinaire combinant des méthodes de recherche quantitatives et qualitatives
associée à la participation active des communautés à risque représente la voie à approfondir
en vue d’appréhender au mieux ce phénomène d’émergence et d’y répondre de manière la
plus complète possible.
101
15. Références
Alarcon de Noya, B., Diaz-Bello, Z., Colmenares, C., Ruiz-Guevara, R., Mauriello, L., ZavalaJaspe, R., . . . Noya, O. (2010). Large urban outbreak of orally acquired acute Chagas
disease at a school in Caracas, Venezuela. J Infect Dis, 201(9), 1308-1315.
Altclas, J. D., Barcan, L., Nagel, C., Lattes, R., & Riarte, A. (2008). Organ transplantation and
Chagas disease. JAMA, 299(10), 1134; author reply 1134-1135.
Angheben A, A. M., Gobbi F, Marocco S, Monteiro G, Buonfrate D, Tais S, Talamo M, Zavarise
G, Strohmeyer M, Bartalesi F, Mantella A, Di Tommaso M, Aiello KH, Veneruso G,
Graziani G, Ferrari MM, Spreafico I, Bonifacio E, Gaiera G, Lanzafame M, Mascarello
M, Cancrini G, Albajar-Viñas P, Bisoffi Z, Bartoloni A. . (2011). Chagas disease in Italy:
breaking an epidemiological silence. Euro Surveill, 16(37). doi:
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19969
Apt, W. (2010). Current and developing therapeutic agents in the treatment of Chagas
disease. Drug Res Devel Ther, 4, 243-253.
Apt, W., Arribada, A., Zulantay, I., Rodriguez, J., Saavedra, M., & Munoz, A. (2013).
Treatment of Chagas' disease with itraconazole: electrocardiographic and
parasitological conditions after 20 years of follow-up. J Antimicrob Chemother, 68(9),
2164-2169.
Aufderheide, A. C., Salo, W., Madden, M., Streitz, J., Buikstra, J., Guhl, F., . . . Allison, M.
(2004). A 9,000-year record of Chagas' disease. Proc Natl Acad Sci U S A, 101(7),
2034-2039.
Basile, L., Jansa, J. M., Carlier, Y., Salamanca, D. D., Angheben, A., Bartoloni, A., . . . AlbajarVinas, P. (2011). Chagas disease in European countries: the challenge of a
surveillance system. Euro Surveill, 16(37). doi: pii: 19968
Benach, J., Muntaner, C., Delclos, C., Menendez, M., & Ronquillo, C. (2011). Migration and
"low-skilled" workers in destination countries. PLoS Med, 8(6), e1001043.
Bern, C. (2011). Antitrypanosomal therapy for chronic Chagas' disease. N Engl J Med,
364(26), 2527-2534.
Bern, C., Kjos, S., Yabsley, M. J., & Montgomery, S. P. (2011). Trypanosoma cruzi and Chagas'
Disease in the United States. Clin Microbiol Rev, 24(4), 655-681.
Bern, C., Montgomery, S. P., Herwaldt, B. L., Rassi, A., Jr., Marin-Neto, J. A., Dantas, R. O., . . .
Moore, A. C. (2007). Evaluation and treatment of chagas disease in the United States:
a systematic review. JAMA, 298(18), 2171-2181.
102
Bestetti, R. B., & Theodoropoulos, T. A. (2009). A systematic review of studies on heart
transplantation for patients with end-stage Chagas' heart disease. J Card Fail, 15(3),
249-255.
Blum, J. A., Zellweger, M. J., Burri, C., & Hatz, C. (2008). Cardiac involvement in African and
American trypanosomiasis. Lancet Infect Dis, 8(10), 631-641.
Carod-Artal, F. J., & Gascon, J. (2010). Chagas disease and stroke. Lancet Neurol, 9(5), 533542.
CDC. (2010). American Trypanosomiasis. Retrieved 06.08.2013, from
http://www.cdc.gov/parasites/chagas/biology.html
Chagas, C. (1909a). Nova espécie morbida do homem, produzida por um Trypanosoma
(Trypanosoma cruzi). Brasil Médico, 23(161).
Chagas, C. (1909b). Nova tripanozomiase humana. Estudos sobre a morfolojia e o ciclo
evolutivo do Schizotrypanum cruzi n.g., n.s.p., ajente etiolójico de nova entidade
mórbida no homem. Mem. Inst. Oswaldo Cruz, 1(159-218).
Chappuis, F., Mauris, A., Holst, M., Albajar-Vinas, P., Jannin, J., Luquetti, A. O., & Jackson, Y.
(2010). Validation of a rapid immunochromatographic assay for diagnosis of
Trypanosoma cruzi infection among Latin-American Migrants in Geneva, Switzerland.
J Clin Microbiol, 48(8), 2948-2952.
Chatelain, E., & Loset, J. R. (2011). Drug discovery and development for neglected diseases:
the DNDi model. Drug Des Devel Ther, 5, 175-181.
Chin-Hong, P. V., Schwartz, B. S., Bern, C., Montgomery, S. P., Kontak, S., Kubak, B., . . . Ison,
M. G. (2011). Screening and treatment of chagas disease in organ transplant
recipients in the United States: recommendations from the chagas in transplant
working group. Am J Transplant, 11(4), 672-680.
CHRD. (1990). Health Research: Essential Link to Equity in Development. In Oxford University
Press (Ed.). New York: Commission on Health Research for Development.
Coura, J., & De Castro, S. (2002). A Critical Review on Chagas Disease Chemotherapy. Mem
Inst Oswaldo Cruz, 97(1), 3-24.
Coura, J. R. (2009). Present situation and new strategies for Chagas disease chemotherapy: a
proposal. Mem Inst Oswaldo Cruz, 104(4), 549-554.
Coura, J. R., & Vinas, P. A. (2010). Chagas disease: a new worldwide challenge. Nature,
465(n7301_supp), S6-S7.
Cuadra, C. B. (2012). Right of access to health care for undocumented migrants in EU: a
comparative study of national policies. Eur J Public Health, 22(2), 267-271.
103
de Oliveira, R. B., Troncon, L. E., Dantas, R. O., & Menghelli, U. G. (1998). Gastrointestinal
manifestations of Chagas' disease. Am J Gastroenterol, 93(6), 884-889.
de Rezende, J., Lauar, K. M., & de Oliveira, A. (1960). [Clinical and radiological aspects of
aperistalsis of the esophagus.]. Rev Bras Gastroenterol, 12, 247-262.
Delgado, S., Ernst, K. C., Pumahuanca, M. L., Yool, S. R., Comrie, A. C., Sterling, C. R., . . . Levy,
M. Z. (2013). A country bug in the city: urban infestation by the Chagas disease vector
Triatoma infestans in Arequipa, Peru. Int J Health Geogr, 12(1), 48
Demaurex, C., Cárdenas Núñez, M., Aparicio, H., Bodenmann, P., Genton, B., & D’Acremont,
V. (2013). Screening for Chagas Disease in Switzerland: “One Size Fits All”? Paper
presented at the 13th Congress of the International Society of Travel Medicine,
Maastricht.
Fernandez-Villegas, A., Pinazo, M. J., Maranon, C., Thomas, M. C., Posada, E., Carrilero, B., . .
. Lopez, M. C. (2011). Short-term follow-up of chagasic patients after benznidazole
treatment using multiple serological markers. BMC Infect Dis, 11, 206. doi:
10.1186/1471-2334-11-206
Flores-Chavez, M., Fernandez, B., Puente, S., Torres, P., Rodriguez, M., Monedero, C., . . .
Canavate, C. (2008). Transfusional chagas disease: parasitological and serological
monitoring of an infected recipient and blood donor. Clin Infect Dis, 46(5), e44-47.
doi: 10.1086/527448
Flores-Chavez, M., Merino, F., Garcia-Bujalance, S., Martin-Rabadan, P., Merino, P., GarciaBermejo, I., . . . Cuadros, J. (2011). Surveillance of Chagas disease in pregnant women
in Madrid, Spain, from 2008 to 2010. Euro Surveill, 16(38).
Fluckiger, Y., & Pasche, C. (2005). Analyse du secteur clandestin de l'industrie domestique à
Genève. Geneva: University of Geneva.
GFS.Berne. (2005). Sans-papiers en Suisse : c’est le marché de l’emploi qui est déterminant,
non pas la politique d’asile (pp. 37-38). Bern.
Guerineau, L. R., Posfay-Barbe, K. M., Cabedo, M. M., Morros, T. J., Diana, A., Lazarevic, C. A.,
. . . Jackson, Y. (2013). Pediatric Chagas Disease in Europe: 45 Cases from Spain and
Switzerland. Pediatr Infect Dis J. doi: 10.1097/INF.0000000000000139
Gupta, S., Wan, X., Zago, M. P., Sellers, V. C., Silva, T. S., Assiah, D., . . . Garg, N. J. (2013).
Antigenicity and diagnostic potential of vaccine candidates in human Chagas disease.
PLoS Negl Trop Dis, 7(1), e2018. doi: 10.1371/journal.pntd.0002018
Hotez, P. J., & Gurwith, M. (2011). Europe's neglected infections of poverty. Int J Infect Dis,
15(9), e611-619. doi: 10.1016/j.ijid.2011.05.006
Howard, E., Xiong, X., Carlier, Y., Sosa-Estani, S., & Buekens, P. (2013). Frequency of the
congenital transmission of Trypanosoma cruzi: a systematic review and metaanalysis. BJOG. doi: 10.1111/1471-0528.12396
104
IOM. (2012). Rutas y dinámicas migratorias entre los países de América Latina y el Caribe
(ALC), y entre ALC y la Unión Europea. Bruxelles: IOM.
Jackson, Y. (2014, in press). Chagas disease in non-endemic countries: Experience from
Geneva, Switzerland. (PhD thesis), University of Antwerp, Antwerp.
Jackson, Y., Alirol, E., Getaz, L., Wolff, H., Combescure, C., & Chappuis, F. (2010). Tolerance
and safety of nifurtimox in patients with chronic chagas disease. Clin Infect Dis,
51(10), e69-75. doi: 10.1086/656917
Jackson, Y., Angheben, A., Carrilero Fernandez, B., Jansa i Lopez del Vallado, J. M., Jannin, J.
G., & Albajar-Vinas, P. (2009). [Management of Chagas disease in Europe.
Experiences and challenges in Spain, Switzerland and Italy]. Bull Soc Pathol Exot,
102(5), 326-329.
Jackson, Y., Castillo, S., Hammond, P., Besson, M., Brawand-Bron, A., Urzola, D., . . .
Chappuis, F. (2012). Metabolic, mental health, behavioural and socioeconomic
characteristics of migrants with Chagas disease in a non-endemic country. Trop Med
Int Health, 17(5), 595-603.
Jackson, Y., & Chappuis, F. (2011). Chagas disease in Switzerland: history and challenges.
Euro Surveill, 16(37), pii: 19963.
Jackson, Y., Chatelain, E., Mauris, A., Holst, M., Miao, Q., Chappuis, F., & Ndao, M. (2013).
Serological and parasitological response in chronic Chagas patients 3 years after
nifurtimox treatment. BMC Infect Dis, 13, 85. doi: 10.1186/1471-2334-13-85
Jackson, Y., Dang, T., Schnetzler, B., Pascual, M., & Meylan, P. (2011). Trypanosoma cruzi
fatal reactivation in a heart transplant recipient in Switzerland. J Heart Lung
Transplant, 30(4), 484-485.
Jackson, Y., Getaz, L., Wolff, H., Holst, M., Mauris, A., Tardin, A., . . . Chappuis, F. (2010).
Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease
among Latin American migrants in Geneva, Switzerland. PLoS Negl Trop Dis, 4(2),
e592. doi: 10.1371/journal.pntd.0000592
Lancet. (2006). Chagas' disease--an epidemic that can no longer be ignored. Lancet,
368(9536), 619.
Laucella, S. A., Mazliah, D. P., Bertocchi, G., Alvarez, M. G., Cooley, G., Viotti, R., . . . Tarleton,
R. L. (2009). Changes in Trypanosoma cruzi-specific immune responses after
treatment: surrogate markers of treatment efficacy. Clin Infect Dis, 49(11), 16751684.
Le Loup, G., Pialoux, G., & Lescure, F. X. (2011). Update in treatment of Chagas disease. Curr
Opin Infect Dis, 24(5), 428-434.
105
Lee, B., Bacon, K., Bottazzi, M., & Hotez, P. (2013). Global economic burden of Chagas
disease: a computational simulation model. Lancet Infect Dis, 13(4), 342-348.
Lee, B., Bacon, K. M., Connor, D. L., Willig, A. M., & Bailey, R. R. (2010). The potential
economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America.
PLoS Negl Trop Dis, 4(12), e916. doi: 10.1371/journal.pntd.0000916
Lescure, F. X., Canestri, A., Melliez, H., Jaureguiberry, S., Develoux, M., Dorent, R., . . .
Pialoux, G. (2008). Chagas disease, France. Emerg Infect Dis, 14(4), 644-646.
Lescure, F. X., Le Loup, G., Freilij, H., Develoux, M., Paris, L., Brutus, L., & Pialoux, G. (2010).
Chagas disease: changes in knowledge and management. Lancet Infect Dis, 10(8),
556-570.
Liechti, M., Baur, H. R., Gurtner, H. P., & Straub, P. W. (1990). [Cardiac complications of
American trypanosomiasis (Chagas disease). Various case reports and general
observations]. Schweiz Med Wochenschr, 120(41), 1493-1496.
Magnani, C., Oliveira, B. G., & Gontijo, E. D. (2007). [Representations, myths, and behaviors
among Chagas disease patients with pacemakers]. Cad Saude Publica, 23(7), 16241632.
Marin-Neto, J. A., Cunha-Neto, E., Maciel, B. C., & Simoes, M. V. (2007). Pathogenesis of
chronic Chagas heart disease. Circulation, 115(9), 1109-1123.
Martinez de Tejada, B., Jackson, Y., Paccolat, C., & Irion, O. (2009). [Congenital Chagas
disease in Geneva: diagnostic and clinical aspects]. Rev Med Suisse, 5(222), 20912092, 2094-2096.
MdM. (2013). Accès aux soins en Europe en temps de crise et de montée de la xénophobie.
Paris: Médecins du Monde.
Medrano-Mercado, N., Ugarte-Fernandez, R., Butron, V., Uber-Busek, S., Guerra, H. L.,
Araujo-Jorge, T. C., & Correa-Oliveira, R. (2008). Urban transmission of Chagas
disease in Cochabamba, Bolivia. Mem Inst Oswaldo Cruz, 103(5), 423-430.
Minneman, R. M., Hennink, M. M., Nicholls, A., Salek, S. S., Palomeque, F. S., Khawja, A., . . .
Leon, J. S. (2012). Barriers to Testing and Treatment for Chagas Disease among Latino
Immigrants in Georgia. J Parasitol Res, 2012, 295034. doi: 10.1155/2012/295034
Moscatelli, G., Garcia Bournissen, F., Freilij, H., Berenstein, A., Tarlovsky, A., Moroni, S., . . .
Altcheh, J. (2013). Impact of migration on the occurrence of new cases of Chagas
disease in Buenos Aires city, Argentina. J Infect Dev Ctries, 7(8), 635-637. doi:
10.3855/jidc.2930
Munoz, J., Coll, O., Juncosa, T., Verges, M., del Pino, M., Fumado, V., . . . Gascon, J. (2009).
Prevalence and vertical transmission of Trypanosoma cruzi infection among pregnant
106
Latin American women attending 2 maternity clinics in Barcelona, Spain. Clin Infect
Dis, 48(12), 1736-1740.
Munoz, J., Gomez i Prat, J., Gallego, M., Gimeno, F., Trevino, B., Lopez-Chejade, P., . . .
Gascon, J. (2009). Clinical profile of Trypanosoma cruzi infection in a non-endemic
setting: immigration and Chagas disease in Barcelona (Spain). Acta Trop, 111(1), 5155.
Munoz, J., Portus, M., Corachan, M., Fumado, V., & Gascon, J. (2007). Congenital
Trypanosoma cruzi infection in a non-endemic area. Trans R Soc Trop Med Hyg,
101(11), 1161-1162.
Murcia, L., Carrilero, B., Munoz-Davila, M. J., Thomas, M. C., Lopez, M. C., & Segovia, M.
(2013). Risk factors and primary prevention of congenital Chagas disease in a
nonendemic country. Clin Infect Dis, 56(4), 496-502.
Navarro, M., Perez-Ayala, A., Guionnet, A., Perez-Molina, J. A., Navaza, B., Estevez, L., . . .
Lopez-Velez, R. (2011). Targeted screening and health education for Chagas disease
tailored to at-risk migrants in Spain, 2007 to 2010. Euro Surveill, 16(38).
Ndao, M., Spithill, T. W., Caffrey, R., Li, H., Podust, V. N., Perichon, R., . . . Ward, B. J. (2010).
Identification of novel diagnostic serum biomarkers for Chagas' disease in
asymptomatic subjects by mass spectrometric profiling. J Clin Microbiol, 48(4), 11391149.
Office des migrations. (2004). Rapport sur la migration illégale. Berne: ODM.
PAHO. (2006). Estimacion cuantitativa de la enfermedad de Chagas en las Americas.
Montevideo, Uruguay: PAHO.
Perez-Mazliah, D. E., Alvarez, M. G., Cooley, G., Lococo, B. E., Bertocchi, G., Petti, M., . . .
Viotti, R. (2013). Sequential combined treatment with allopurinol and benznidazole in
the chronic phase of Trypanosoma cruzi infection: a pilot study. J Antimicrob
Chemother, 68(2), 424-437.
Perez-Molina, J. A., Perez-Ayala, A., Moreno, S., Fernandez-Gonzalez, M. C., Zamora, J., &
Lopez-Velez, R. (2009). Use of benznidazole to treat chronic Chagas' disease: a
systematic review with a meta-analysis. J Antimicrob Chemother, 64(6), 1139-1147.
Petraglia Kropf, S. (2011). The art of medicine, Carlos Chagas: science, health, and national
debate in Brazil. Lancet, 377, 1741-1742.
Pinazo, M. J., Canas, E., Elizalde, J. I., Garcia, M., Gascon, J., Gimeno, F., . . . Trevino, B.
(2010). Diagnosis, management and treatment of chronic Chagas' gastrointestinal
disease in areas where Trypanosoma cruzi infection is not endemic. Gastroenterol
Hepatol, 33(3), 191-200.
107
Pinazo, M. J., Miranda, B., Rodriguez-Villar, C., Altclas, J., Brunet Serra, M., Garcia-Otero, E.
C., . . . Shikanai-Yasuda, M. A. (2011). Recommendations for management of Chagas
disease in organ and hematopoietic tissue transplantation programs in nonendemic
areas. Transplant Rev (Orlando), 25(3), 91-101.
Pinazo, M. J., Munoz, J., Posada, E., Lopez-Chejade, P., Gallego, M., Ayala, E., . . . Gascon, J.
(2010). Tolerance of benznidazole in treatment of Chagas' disease in adults.
Antimicrob Agents Chemother, 54(11), 4896-4899.
Pizzi Bosman, L., & Rosochova, J. (2011). First Swiss case of Chagas positive blood donor
detected by the transfusion center of Geneva. Blood Transfus, 9(Suppl 1), 41.
Portmann-Tinguely, A., & von Cranach, P. (2013). Réfugiés. Dictionnaire historique de la
Suisse. Retrieved 10.02.2014, from http://www.hls-dhs-dss.ch/textes/f/F16388.php
Prata, A. (2001). Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis,
1(2), 92-100.
Ramirez, J. D., Guhl, F., Umezawa, E. S., Morillo, C. A., Rosas, F., Marin-Neto, J. A., &
Restrepo, S. (2009). Evaluation of adult chronic Chagas' heart disease diagnosis by
molecular and serological methods. J Clin Microbiol, 47(12), 3945-3951.
Ramsey, J. M., Alvear, A. L., Ordonez, R., Munoz, G., Garcia, A., Lopez, R., & Leyva, R. (2005).
Risk factors associated with house infestation by the Chagas disease vector Triatoma
pallidipennis in Cuernavaca metropolitan area, Mexico. Med Vet Entomol, 19(2), 219228.
Rassi, A. J., Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. Lancet, 375(9723), 13881402.
Rechel, B., Mladovsky, P., Ingleby, D., Mackenbach, J. P., & McKee, M. (2013). Migration and
health in an increasingly diverse Europe. Lancet, 381(9873), 1235-1245.
Ribeiro, I., Sevcsik, A. M., Alves, F., Diap, G., Don, R., Harhay, M. O., . . . Pecoul, B. (2009).
New, improved treatments for Chagas disease: from the R&D pipeline to the
patients. PLoS Negl Trop Dis, 3(7), e484. doi: 10.1371/journal.pntd.0000484
Riera, C., Guarro, A., Kassab, H. E., Jorba, J. M., Castro, M., Angrill, R., . . . Portus, M. (2006).
Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report. Am J
Trop Med Hyg, 75(6), 1078-1081.
Schijman, A. G., Bisio, M., Orellana, L., Sued, M., Duffy, T., Mejia Jaramillo, A. M., . . . Ladzins,
J. (2011). International study to evaluate PCR methods for detection of Trypanosoma
cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis, 5(1),
e931. doi: 10.1371/journal.pntd.0000931
108
Schmunis, G. A., Rodriguez, G., Coenen, J., Bellorin, E. G., & Gianella, A. (2008). Prevention of
blood-borne diseases in Bolivia, 1993-2002. Am J Trop Med Hyg, 79(5), 803-808.
Schofield, C. J., Jannin, J., & Salvatella, R. (2006). The future of Chagas disease control. Trends
Parasitol, 22(12), 583-588.
Sicuri, E., Munoz, J., Pinazo, M. J., Posada, E., Sanchez, J., Alonso, P. L., & Gascon, J. (2011).
Economic evaluation of Chagas disease screening of pregnant Latin American women
and of their infants in a non endemic area. Acta Trop, 118(2), 110-117.
Sosa-Estani, S., & Segura, E. L. (2006). Etiological treatment in patients infected by
Trypanosoma cruzi: experiences in Argentina. Curr Opin Infect Dis, 19(6), 583-587.
Swiss Federal Bureau of Statistics. (2010). migration. Retrieved 05.09.2012, from
http://www.pxweb.bfs.admin.ch/
Sztajzel, J., Cox, J., Pache, J. C., Badaoui, E., Lerch, R., & Rutishauser, W. (1996). Chagas'
disease may also be encountered in Europe. Eur Heart J, 17(8), 1289.
The London Declaration on Neglected Tropical Diseases. (2012). Retrieved 09.05.2013, from
http://www.unitingtocombatntds.org/downloads/press/london_declaration_on_ntd
s.pdf
Trouiller, P., Olliaro, P., Torreele, E., Orbinski, J., Laing, R., & Ford, N. (2002). Drug
development for neglected diseases: a deficient market and a public-health policy
failure. Lancet, 359(9324), 2188-2194.
Urbina, J. A. (2009). Specific chemotherapy of Chagas disease: Relevance, current limitations
and new approaches. Acta Trop, 115(1-2), 55-68.
Velarde-Rodríguez, m., Avaria-Saavedra, A., Gómez-i-Prat, J., Jackson, J., Alves de Oliveira
Junior, W., Camps-Carmona, B., & Albajar-Viñas, P. (2009). Need of comprehensive
health care for T. cruzi infected immigrants in Europe. Rev Soc Bras Med Trop,
42(Suppl II), 92-95.
Ventura-Garcia, L., Roura, M., Pell, C., Posada, E., Gascon, J., Aldasoro, E., . . . Pool, R. (2013). Sociocultural aspects of chagas disease: a systematic review of qualitative research. PLoS Negl
Trop Dis, 7(9), e2410. doi: 10.1371/journal.pntd.0002410
Veyrassat, B. (2007). Amérique Latine. Dictionnaire historique de la Suisse. Retrieved
07.02.2014, from http://www.hls-dhs-dss.ch/textes/f/F28923.php
Viotti, R., Vigliano, C., Lococo, B., Bertocchi, G., Petti, M., Alvarez, M. G., . . . Armenti, A.
(2006). Long-term cardiac outcomes of treating chronic Chagas disease with
benznidazole versus no treatment: a nonrandomized trial. Ann Intern Med, 144(10),
724-734.
109
Vitelli-Avelar, D. M., Sathler-Avelar, R., Wendling, A. P., Rocha, R. D., Teixeira-Carvalho, A.,
Martins, N. E., . . . Martins-Filho, O. A. (2007). Non-conventional flow cytometry
approaches to detect anti-Trypanosoma cruzi immunoglobulin G in the clinical
laboratory. J Immunol Methods, 318(1-2), 102-112.
WHO. (2002). Control of Chagas disease World Health Organ Tech Rep Ser, (2002/07/03 ed.,
Vol. 905, pp. i-vi, 1-109, back cover). Brasilia (Brazil): WHO.
WHO. (2009). Control and prevention of Chagas disease in Europe. Report of a WHO
Informal Consultation (jointly organized by WHO headquarters and the WHO
Regional Office for Europe) Geneva, Switzerland, 17–18 December 2009. Geneva:
WHO.
WHO. (2010). Working to overcome the global impact of neglected tropical diseases: first
WHO report on neglected tropical diseases. Geneva: WHO.
Wolff, H., Stalder, H., Epiney, M., Walder, A., Irion, O., & Morabia, A. (2005). Health care and
illegality: a survey of undocumented pregnant immigrants in Geneva. Soc Sci Med,
60(9), 2149-2154.
Zulantay, I., Apt, W., Ramos, D., Godoy, L., Valencia, C., Molina, M., . . . Corral, G. (2013). The
epidemiological relevance of family study in chagas disease. PLoS Negl Trop Dis, 7(2),
e1959.
110

Thesis Reference - Archive ouverte UNIGE

Transcription

Similar documents

MALADIE D`ERDHEIM-CHESTER ASPECT DES ATTEINTES

Reversibiliteit van cirrose

Présentation Fonds d`investissement

Please view attachment

GENERAL AGREEMENT ON TARIFFS AND TRADE

Switzerland - Host State

in Danger? - Youth.gc.ca

Apport de l `entero-colo irm dAns le suivi de lA