The Threat of Emerging Infectious Diseases in Asia

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The Threat of Emerging Infectious Diseases in Asia
Linfa Wang/Professor and Director
EID Program, Duke-NUS Graduate Medical School, Singapore
CSIRO Australian Animal Health Laboratory, Geelong, Australia
Linfa.wang@duke-nus.edu.sg
The SARS outbreak
“Seven people stood waiting for an elevator in a hotel lobby (Hotel
M). One of them coughed.
Together for a chance moment, the group quickly scattered to
sightseeing buses, business lunches and airport terminals. Within
hours, some had flown half the world away. Within days, three of
the seven were dead, including the man who coughed.
That, according to epidemiologists, is how severe acute
respiratory syndrome (SARS) spread from Hong Kong to the world
(first to Vietnam, Singapore, Canada, Germany)”
Emerging diseases
Nipah
Severe acute respiratory syndrome (SARS)
Influenza H5N1
Influenza H1N1
Ebola Reston virus in pigs
Severe fever with thrombocytopenia syndrome (SFTS)
Re-emerging diseases
Chikungunya fever
Dengue fever
Enteroviruses
Rabies
Japanese encephalitis
HIV/AIDS
Streptococcus suis
Leptospirosis
Drug-resistant diseases
MDR tuberculosis
XDR tuberculosis
MRD P. falciparum malaria
Outline
• Review of drivers for emergence
• One Health approach to disease
prevention and control
• Future challenges/opportunities
SARS virus (coronavirus)
Drivers for emergence:
• Economic growth
• Desire for game meat
• Live animal trading
Hendra virus (Paramyxovirus)
• Population growth/urbanization
• Climate change
Range expansion of P. alecto 1920s
A.Breed CSIRO.
CSIRO.
Range expansion of P. alecto 1960s
A.Breed CSIRO.
CSIRO.
Range expansion of P. alecto 2007
A.Breed CSIRO.
CSIRO.
Nipah virus (Bangladesh)
• Date palm juice
• Cultural tradition
Nipah virus (Malaysia)
• Unusual farming practice
• Forest fire
Melaka virus (Reovirus)
• Urbanization
• Tourism
Ebola virus (Filovirus)
Driver for emergence:
• Bush meat trading
Ebola Reston virus (Filovirus)
Driver for emergence:
• Monkey farming
• Intensive pig farming(?)
Summary
• Bats are important source of emerging
zoonotic viruses
• Although they all use bats as reservoir, they
represent a diverse group of viruses
• Different drivers are involved for emergence
(even closely related viruses)
• It’s impossible to have a one-for-all approach
to combat EID pathogens
• This trend of emergence is unlikely to stop in
the foreseeable future
The new SARS-like (SARI) virus
•
•
•
•
17 confirmed human cases (11 fatal, 65%)
Confirmed human-to-human transmission
Likely to be of bat origin
Use a different cellular receptor from SARS-CoV
Alphacoronaviruses
BtCoV/A912/2005
AFCD126/08/05 Mm
AFCD68/08/05 Mm
AFCD112/08/05 Mm
AFCD103/08/05 Mm
AFCD101/08/05 Mm
AFCD82/08/05 Mm
BtCoV/A911/2005 Miniopterus schreibersi
BtCoV/A905/2005
BtCoV/A910/2005
BtCoV/A909/2005
BtCoV/A754/2005
AFCD118/08/05 Mm
AFCD122/08/05 Mm
AFCD140/08/05 Mm
AFCD220/12/05 Mm
AFCD219/12/05 Mm
BtCoV/A1203/2005
BtCoV/A1201/2005
BtCoV/A893/2005
BtCoV/A894/2005
BtCoV/A914/2005
BtCoV/A895/2005
AFCD183/12/05 Mm
AFCD264/03/06 Mm
BtCoV/A629/2005
WCF86/05/04 Ms
WCF96/05/04 Mm
AFCD224/12/05 Mm
AFCD27/06/05 Mm
AFCD62/08/05 Mm
AFCD61/08/05 Mm
AFCD20/06/05 Mm
AFCD26/06/05 Mm
AFCD100/08/05 Mm
WCF20/05/04 Mp
AFCD333/03/06 Mp
WCF10/05/04 Mp
WCF12/05/04 Mp
WCF6/05/04 Mp
AFCD337/03/06 Mp
AFCD307/03/06 Mp
WCF17/05/04 Mp
AFCD274/03/06 Mp
AFCD169/12/05 Mp
AFCD187/12/05 Mp
Bat CoV 61 Mp
WCF8/05/04 Mp
GT190240 btCoV BR98-55/BGR/2008
BtCoV/A1074/2005
BtCoV/A773/2005 Miniopterus schreibersi
BtCoV/A1116/2005
WCF88/05/04 Mm
HKU7
GT190244 btCoV BR98-31/BGR/2008
GT190243 btCoV BR98-30/BGR/2008
BtCoV R.meg/Australia/CoV100/2007
BtCoV M.aus/Australia/CoV132/2007
BtCoV M.sch/Australia/CoV146/2007
AFCD323/03/06 Mp
AFCD325/03/06 Mp
AFCD309/03/06 Mp
WCF4/05/04 Mp
WCF14/05/04 Mp
AFCD77/08/05 Mm
HKU8
BtCoV/A1196/2005
GT190247 btCoV BR98-52/BGR/2008
GT190246 btCoV BR98-40/BGR/2008
GT190242 btCoV BR98-18/BGR/2008
GT190241 btCoV BR98-14/BGR/2008
GT190248 btCoV BR98-53/BGR/2008
GT190245 btCoV BR98-37/BGR/2008
BtCoV
229E Hipposideros/GhanaKwam/19/2008
(Human)
BtCoV_Hipposideros/GhanaBoo/344/2008
BtCoV Hipposideros/GhanaKwam/10/2008
BtCoV/A535/2005
BtCoV/A504/2005
BtCoV/A515/2005
BtCoV/512/2005 Scotophilus kuhlii
BtCoV/A527/2005
HKU6-1 Ricketts big-footed bat
BtCoV/A613/2005
BtCoV/A619/2005
BtCoV/A620/2005
BtCoV/A900/2005
BtCoV/A897/2005
BtCoV/A898/2005
BtCoV/A604/2005
BtCoV/A701/2005 Myotis ricketti
BtCoV/A821/2005 Myotis ricketti
BtCoV/A633/2005
BtCoV/A819/2005
BtCoV/A632/2005
BtCoV/A634/2005
M.dau/Germany/D7.3/2007
GT190216 btCoV NM98-62/GER/2008
P.pyg/Germany/D5.71/2007
P.nat/Germany/D5.16/2007
P.nat/Germany/D5.73/2007
M.das/Germany/D3.5/2007
M.bec/Germany/D6.6/2007
GT190236 btCoV BR98-12/BGR/2008
GT190232 btCoV BB98-15/BGR/2008
GT190234 btCoV BM48-39/BGR/2008
GT190235 btCoV BM98-05/BGR/2008
GT190233 btCoV BM48-28/BGR/2008
NL63 (Human)
RockMountain3 occult myotis
BtCoV/A970/2005 Rhinolophus ferrumequinum
BtCoV/A977/2005
BtCoV/860/2005
PEDV (Swine)
BtCoV M.mac/Australia/CoV034/2008
GT190239 btCoV BNM98-30/BGR/2008
HKU2-1 chinese horseshoe bat
HKU2-2 chinese horseshoe bat
GT190238 btCoV BB98-41/BGR/2008
GT190237 btCoV 1B BR98-19/BGR/2008
BtCoV S.Amer Trinidad/1FY2BA/2007
BtCoV S.Amer Trinidad/1CO7BA/2007
RockMountain65 big brown bat
FIPV ((Feline)
TGEV (Swine)
0.05
Betacoronaviruses
BtCoV/367A/2005
BtCoV/908/2005
BtCoV/A906/2005
BtCoV/310A/2005
BtCoV/355A/2005 Pipistrellus pipistrellus
BtCoV/364A/2005
BtCoV/309/2005
BtCoV/363A/2005
BtCoV/303/2005
BtCoV/301/2005
BtCoV/311A/2005
BtCoV/A957/2005
BtCoV/A434/2005 Pipistrellus pipistrellus
BtCoV/365A/2005
HKU5-1 Japanese pipistrelle
BtCoV/A1206/2005
BtCoV/A421/2005
BtCoV/A437/2005
BtCoV/A433/2005
BtCoV/427/2005
BtCoV/A429/2005
BtCoV/242/2005
BtCoV/133/2005 Tylonycleris pachypus
HKU4-4 lesser bamboo bat
BCoV (Bovine)
OC43 (Human)
MHV (Mouse)
HKU1 (Human)
BtCoV_Hipposideros/GhanaKwam/24/2008
BtCoV Hipposideros/GhanaBoo/348/2008
BtCoV R.aur/Australia/CoV000/2006
BtCoV/A1018/2005 Rhiniolophus sinicus
HKU3
BtCoV/273/2005 Rhinolophus ferrumequinum
BtCoV/279/2005 Rhinolophus macrotis
SARS-CoV (Human)
GT190229_btCoV_BM48-34/BGR/2008
GT190215 btCoV BM48-31/BGR/2008
GT190228 btCoV BM48-32/BGR/2008
GT190220 btCoV BM48-48/BGR/2008
GT190219 btCoV BM98-65/BGR/2008
GT190218 btCoV BB98-18/BGR/2008
GT190217 btCoV BB98-16/BGR/2008
GT190231 btCoV BNM98-29/BGR/2008
GT190226 btCoV BB98-43/BGR/2008
GT190224 btCoV BM48-12/BGR/2008
GT190230 btCoV BM48-35/BGR/2008
GT190221 btCoV 2B BR98-19/BGR/2008
GT190222 btCoV BM98-01/BGR/2008
GT190223 btCoV BM98-13/BGR/2008
GT190227 btCoV BM98-07/BGR/2008
GT190225 btCoV BM98-05/BGR/2008
0.05
L. Poon, HKU
Nature 2013, 495: 176
Recombinant subunit vaccine
against Hendra virus
- an One Health approach
Transmission
Risk factors:
Housed outside
Paddock with fruit trees
During flying fox birthing season
Hendra virus transmission between species
What is the best (realistic) countermeasure strategy (ies)?
X
Hendra/Australia
• Vaccine for horses
Nipah/Malaysia
• Post-exposure therapeutics for humans
• Rapid diagnosis (ideally point-of-care
test platform)
Nipah/Bangladesh
The HeV attachment protein (G)
– Main target for
neutralising antibody
– Recombinant soluble
G (sG) maintains
conformation and
biological function
Establishing the horse infection model: Redlands 2008
Post mortem in a BSL4 lab!
HeV vaccine studies in horses - summary
• Immunised horses exposed to an otherwise lethal dose of HeV
– Remained clinically healthy
– Did not develop histological lesions in target tissues
• No virus re-isolated
• No viral genome detected
– No virus re-isolated from clinical samples
• Genome recovered from nasal swab of one animal
– Self-limiting local infection
– Did not show a boost in antibody titre after virus exposure
Formal release: Nov 1, 2012
Equivac® HeV
Major features
• Effective against both Hendra and Nipah
• A truly One Health vaccine
• Compatible with different adjuvant formulations
• First licenced vaccine against any BSL4 agent
Challenges/Opportunities
• Active surveillance
• Targeting the “known unknowns” first
• Capacity building during “peace time’
(get ready for the “unknown unknowns”
• Multi-disciplinary approach (One Health)
• Stronger regional collaboration
Asian Communicable Disease Centre
(ACDC)

The Threat of Emerging Infectious Diseases in Asia

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