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

“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)