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
“Seven people stood waiting for an elevator in a hotel lobby (HotelM). One of them coughed.
Together for a chance moment, the group quickly scattered tosightseeing buses, business lunches and airport terminals. Withinhours, some had flown half the world away. Within days, three ofthe seven were dead, including the man who coughed.
That, according to epidemiologists, is how severe acuterespiratory syndrome (SARS) spread from Hong Kong to the world(first to Vietnam, Singapore, Canada, Germany)”
The SARS outbreak
Emerging diseasesNipah
Severe acute respiratory syndrome (SARS)Influenza H5N1Influenza H1N1
Ebola Reston virus in pigsSevere fever with thrombocytopenia syndrome (SFTS)
Re-emerging diseasesChikungunya fever
Dengue feverEnteroviruses
RabiesJapanese encephalitis
HIV/AIDSStreptococcus suis
Leptospirosis
Drug-resistant diseasesMDR tuberculosisXDR tuberculosis
MRD P. falciparum malaria
Outline
• Review of drivers for emergence
• One Health approach to diseaseprevention and control
• Future challenges/opportunities
SARS virus (coronavirus)
Drivers for emergence:
• Economic growth
• Desire for game meat
• Live animal trading
Hendra virus (Paramyxovirus)
Drivers for emergence:
• Population growth/urbanization
• Climate change
CSIRO.CSIRO.
Range expansion of P. alecto 1920s
A.Breed
CSIRO.CSIRO.A.Breed
Range expansion of P. alecto 1960s
CSIRO.CSIRO.A.Breed
Range expansion of P. alecto 2007
Nipah virus (Bangladesh)
Drivers for emergence:
• Date palm juice
• Cultural tradition
Nipah virus (Malaysia)
Drivers for emergence:
• Unusual farming practice
• Forest fire
Melaka virus (Reovirus)
Drivers for emergence:
• 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 emergingzoonotic viruses
• Although they all use bats as reservoir, theyrepresent a diverse group of viruses
• Different drivers are involved for emergence(even closely related viruses)
• It’s impossible to have a one-for-all approachto combat EID pathogens
• This trend of emergence is unlikely to stop inthe 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
0.05
BtCoV Hipposideros/GhanaKwam/19/2008
BtCoV/A912/2005AFCD126/08/05 Mm
AFCD68/08/05 MmAFCD112/08/05 MmAFCD103/08/05 MmAFCD101/08/05 Mm
AFCD82/08/05 MmBtCoV/A911/2005 Miniopterus schreibersi
BtCoV/A905/2005BtCoV/A910/2005
BtCoV/A909/2005BtCoV/A754/2005
AFCD118/08/05 MmAFCD122/08/05 MmAFCD140/08/05 MmAFCD220/12/05 MmAFCD219/12/05 Mm
BtCoV/A1203/2005BtCoV/A1201/2005
BtCoV/A893/2005BtCoV/A894/2005BtCoV/A914/2005
BtCoV/A895/2005AFCD183/12/05 MmAFCD264/03/06 Mm
BtCoV/A629/2005WCF86/05/04 MsWCF96/05/04 Mm
AFCD224/12/05 MmAFCD27/06/05 Mm
AFCD62/08/05 MmAFCD61/08/05 Mm
AFCD20/06/05 MmAFCD26/06/05 Mm
AFCD100/08/05 MmWCF20/05/04 MpAFCD333/03/06 Mp
WCF10/05/04 MpWCF12/05/04 MpWCF6/05/04 MpAFCD337/03/06 Mp
AFCD307/03/06 MpWCF17/05/04 MpAFCD274/03/06 MpAFCD169/12/05 Mp
AFCD187/12/05 MpBat CoV 61 MpWCF8/05/04 Mp
GT190240 btCoV BR98-55/BGR/2008BtCoV/A1074/2005BtCoV/A773/2005 Miniopterus schreibersiBtCoV/A1116/2005WCF88/05/04 Mm
HKU7GT190244 btCoV BR98-31/BGR/2008GT190243 btCoV BR98-30/BGR/2008BtCoV R.meg/Australia/CoV100/2007
BtCoV M.aus/Australia/CoV132/2007BtCoV M.aus/Australia/CoV088/2007
BtCoV M.sch/Australia/CoV146/2007BtCoV M.aus/Australia/CoV180/1996AFCD323/03/06 MpAFCD325/03/06 MpAFCD309/03/06 MpWCF4/05/04 MpWCF14/05/04 Mp
AFCD77/08/05 MmHKU8
BtCoV/A1196/2005GT190247 btCoV BR98-52/BGR/2008GT190246 btCoV BR98-40/BGR/2008GT190242 btCoV BR98-18/BGR/2008GT190241 btCoV BR98-14/BGR/2008GT190248 btCoV BR98-53/BGR/2008GT190245 btCoV BR98-37/BGR/2008
229E (Human)
BtCoV Hipposideros/GhanaKwam/10/2008BtCoV Hipposideros/GhanaKwam/8/2008
BtCoV/A535/2005BtCoV/A504/2005BtCoV/A515/2005BtCoV/512/2005 Scotophilus kuhliiBtCoV/A527/2005
HKU6-1 Ricketts big-footed batBtCoV/A613/2005BtCoV/A619/2005BtCoV/A620/2005BtCoV/A900/2005BtCoV/A897/2005BtCoV/A898/2005BtCoV/A604/2005BtCoV/A701/2005 Myotis ricketti
BtCoV/A821/2005 Myotis rickettiBtCoV/A633/2005
BtCoV/A819/2005BtCoV/A632/2005BtCoV/A634/2005M.dau/Germany/D7.3/2007M.dau/Germany/D8.45/2007
GT190216 btCoV NM98-62/GER/2008M.dau/Germany/D8.46/2007M.dau/Germany/D8.38/2007M.dau/Germany/D8.32/2007M.dau/Germany/D8.42/2007
P.pyg/Germany/D5.71/2007P.pyg/Germany/D5.85/2007P.pyg/Germany/D5.70/2007
P.nat/Germany/D5.16/2007P.nat/Germany/D5.73/2007
M.das/Germany/D3.5/2007M.das/Germany/D2.2/2007M.das/Germany/D3.15/2007M.das/Germany/D3.3/2007M.bec/Germany/D6.6/2007
M.das/Germany/D3.10/2007M.das/Germany/D5.17/2007
M.das/Germany/D3.4/2007M.das/Germany/D3.28/2007M.das/Germany/D3.33/2007M.das/Germany/D3.6/2007M.das/Germany/D3.38/2007
GT190236 btCoV BR98-12/BGR/2008GT190232 btCoV BB98-15/BGR/2008GT190234 btCoV BM48-39/BGR/2008GT190235 btCoV BM98-05/BGR/2008
NL63 (Human)RockMountain3 occult myotis
BtCoV/A970/2005 Rhinolophus ferrumequinumBtCoV/A977/2005
BtCoV/860/2005RockMountain48 occult myotisRockMountain11 occult myotisRockMountain27 occult myotis
PEDV (Swine)BtCoV M.mac/Australia/CoV034/2008
GT190239 btCoV BNM98-30/BGR/2008HKU2-1 chinese horseshoe batHKU2-2 chinese horseshoe bat
GT190238 btCoV BB98-41/BGR/2008GT190237 btCoV 1B BR98-19/BGR/2008
BtCoV S.Amer Trinidad/1FY2BA/2007BtCoV S.Amer Trinidad/1CO7BA/2007
RockMountain65 big brown batFIPV ((Feline)
TGEV (Swine)
GT190233 btCoV BM48-28/BGR/2008
BtCoV_Hipposideros/GhanaBoo/344/2008
Betacoronaviruses
BtCoV/367A/2005BtCoV/908/2005BtCoV/A906/2005BtCoV/310A/2005BtCoV/355A/2005 Pipistrellus pipistrellusBtCoV/364A/2005BtCoV/309/2005BtCoV/363A/2005BtCoV/303/2005BtCoV/301/2005BtCoV/311A/2005BtCoV/A957/2005
BtCoV/A434/2005 Pipistrellus pipistrellusBtCoV/365A/2005
HKU5-1 Japanese pipistrelleBtCoV/A1206/2005HKU5-5 Japanese pipistrelleHKU5-2 Japanese pipistrelleHKU5-3 Japanese pipistrelle
BtCoV/A421/2005BtCoV/A437/2005BtCoV/A433/2005BtCoV/427/2005BtCoV/A429/2005
BtCoV/242/2005BtCoV/133/2005 Tylonycleris pachypus
HKU4-4 lesser bamboo batHKU4-1 lesser bamboo batHKU4-3 lesser bamboo bat
BCoV (Bovine)
OC43 (Human)MHV (Mouse)
HKU1 (Human)
BtCoV Hipposideros/GhanaBoo/348/2008BtCoV Hipposideros/GhanaKwam/20/2008BtCoV Hipposideros/GhanaKwam/22/2008
BtCoV R.aur/Australia/CoV000/2006BtCoV/A1018/2005 Rhiniolophus sinicus
HKU3BtCoV/273/2005 Rhinolophus ferrumequinum
BtCoV/279/2005 Rhinolophus macrotisSARS-CoV (Human)
GT190215 btCoV BM48-31/BGR/2008GT190228 btCoV BM48-32/BGR/2008GT190220 btCoV BM48-48/BGR/2008GT190219 btCoV BM98-65/BGR/2008GT190218 btCoV BB98-18/BGR/2008GT190217 btCoV BB98-16/BGR/2008
GT190231 btCoV BNM98-29/BGR/2008GT190226 btCoV BB98-43/BGR/2008GT190224 btCoV BM48-12/BGR/2008GT190230 btCoV BM48-35/BGR/2008
GT190221 btCoV 2B BR98-19/BGR/2008GT190222 btCoV BM98-01/BGR/2008GT190223 btCoV BM98-13/BGR/2008GT190227 btCoV BM98-07/BGR/2008GT190225 btCoV BM98-05/BGR/2008
0.05
GT190229_btCoV_BM48-34/BGR/2008
BtCoV_Hipposideros/GhanaKwam/24/2008BtCoV_Hipposideros/GhanaKwam/27/2008BtCoV_Hipposideros/GhanaKwam/31/2008
L. Poon, HKU
Nature 2013, 495: 176
Recombinant subunit vaccineagainst 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)?
Hendra/Australia
Nipah/Malaysia
Nipah/Bangladesh
X
• Vaccine for horses
• Post-exposure therapeutics for humans
• Rapid diagnosis (ideally point-of-caretest platform)
The HeV attachment protein (G)
– Main target forneutralising antibody
– Recombinant solubleG (sG) maintainsconformation andbiological 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)
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