The Threat of Emerging Infectious Diseases in Asia
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1 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
2 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)
3 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
4 Outline Review of drivers for emergence One Health approach to disease prevention and control Future challenges/opportunities
5 SARS virus (coronavirus) Drivers for emergence: Economic growth Desire for game meat Live animal trading
6 Hendra virus (Paramyxovirus) Drivers for emergence: Population growth/urbanization Climate change
7 Range expansion of P. alecto 1920s A.Breed CSIRO.
8 Range expansion of P. alecto 1960s A.Breed CSIRO. CSIRO.
9 Range expansion of P. alecto 2007 A.Breed CSIRO. CSIRO.
10 Nipah virus (Bangladesh) Drivers for emergence: Date palm juice Cultural tradition
11 Nipah virus (Malaysia) Drivers for emergence: Unusual farming practice Forest fire
12 Melaka virus (Reovirus) Drivers for emergence: Urbanization Tourism
13 Ebola virus (Filovirus) Driver for emergence: Bush meat trading
14 Ebola Reston virus (Filovirus) Driver for emergence: Monkey farming Intensive pig farming(?)
15 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
16 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
17
18 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 GT btcov BR98-55/BGR/2008 BtCoV/A1074/2005 BtCoV/A773/2005 Miniopterus schreibersi BtCoV/A1116/2005 WCF88/05/04 Mm HKU7 GT btcov BR98-31/BGR/2008 GT btcov BR98-30/BGR/2008 BtCoV R.meg/Australia/CoV100/2007 BtCoV M.aus/Australia/CoV132/2007 BtCoV M.aus/Australia/CoV088/2007 BtCoV M.sch/Australia/CoV146/2007 BtCoV M.aus/Australia/CoV180/1996 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 GT btcov BR98-52/BGR/2008 GT btcov BR98-40/BGR/2008 GT btcov BR98-18/BGR/2008 GT btcov BR98-14/BGR/2008 GT btcov BR98-53/BGR/2008 GT btcov BR98-37/BGR/2008 BtCoV 229E Hipposideros/GhanaKwam/19/2008 (Human) BtCoV_Hipposideros/GhanaBoo/344/2008 BtCoV Hipposideros/GhanaKwam/10/2008 BtCoV Hipposideros/GhanaKwam/8/2008 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 M.dau/Germany/D8.45/2007 GT btcov NM98-62/GER/2008 M.dau/Germany/D8.46/2007 M.dau/Germany/D8.38/2007 M.dau/Germany/D8.32/2007 M.dau/Germany/D8.42/2007 P.pyg/Germany/D5.71/2007 P.pyg/Germany/D5.85/2007 P.pyg/Germany/D5.70/2007 P.nat/Germany/D5.16/2007 P.nat/Germany/D5.73/2007 M.das/Germany/D3.5/2007 M.das/Germany/D2.2/2007 M.das/Germany/D3.15/2007 M.das/Germany/D3.3/2007 M.bec/Germany/D6.6/2007 M.das/Germany/D3.10/2007 M.das/Germany/D5.17/2007 M.das/Germany/D3.4/2007 M.das/Germany/D3.28/2007 M.das/Germany/D3.33/2007 M.das/Germany/D3.6/2007 M.das/Germany/D3.38/2007 GT btcov BR98-12/BGR/2008 GT btcov BB98-15/BGR/2008 GT btcov BM48-39/BGR/2008 GT btcov BM98-05/BGR/2008 GT btcov BM48-28/BGR/2008 NL63 (Human) RockMountain3 occult myotis BtCoV/A970/2005 Rhinolophus ferrumequinum BtCoV/A977/2005 BtCoV/860/2005 RockMountain48 occult myotis RockMountain11 occult myotis RockMountain27 occult myotis PEDV (Swine) BtCoV M.mac/Australia/CoV034/2008 GT btcov BNM98-30/BGR/2008 HKU2-1 chinese horseshoe bat HKU2-2 chinese horseshoe bat GT btcov BB98-41/BGR/2008 GT 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 HKU5-5 Japanese pipistrelle HKU5-2 Japanese pipistrelle HKU5-3 Japanese pipistrelle 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 HKU4-1 lesser bamboo bat HKU4-3 lesser bamboo bat BCoV (Bovine) OC43 (Human) MHV (Mouse) HKU1 (Human) BtCoV_Hipposideros/GhanaKwam/24/2008 BtCoV_Hipposideros/GhanaKwam/27/2008 BtCoV_Hipposideros/GhanaKwam/31/2008 BtCoV Hipposideros/GhanaBoo/348/2008 BtCoV Hipposideros/GhanaKwam/20/2008 BtCoV Hipposideros/GhanaKwam/22/2008 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 GT btcov BM48-31/BGR/2008 GT btcov BM48-32/BGR/2008 GT btcov BM48-48/BGR/2008 GT btcov BM98-65/BGR/2008 GT btcov BB98-18/BGR/2008 GT btcov BB98-16/BGR/2008 GT btcov BNM98-29/BGR/2008 GT btcov BB98-43/BGR/2008 GT btcov BM48-12/BGR/2008 GT btcov BM48-35/BGR/2008 GT btcov 2B BR98-19/BGR/2008 GT btcov BM98-01/BGR/2008 GT btcov BM98-13/BGR/2008 GT btcov BM98-07/BGR/2008 GT btcov BM98-05/BGR/ L. Poon, HKU
19 Nature 2013, 495: 176
20 Recombinant subunit vaccine against Hendra virus - an One Health approach
21 Transmission Risk factors: Housed outside Paddock with fruit trees During flying fox birthing season
22 Hendra virus transmission between species
23 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
24 The HeV attachment protein (G) Main target for neutralising antibody Recombinant soluble G (sg) maintains conformation and biological function
25 Establishing the horse infection model: Redlands 2008
26 Post mortem in a BSL4 lab!
27 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
28 Formal release: Nov 1, 2012 Equivac HeV
29 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
30 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
31 Asian Communicable Disease Centre (ACDC)
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