1. Control of the H5N1 influenza epidemic at the source Patrick Woo

2. F/24 Day 11 Fever, pneumonia, diarrhoea, ±  WBC / LYM / PLT, deranged LFT / RFT,  PT/APTT (rarely encephalitis, rhabdomyolysis) H5N1 in blood, CSF, intestine, faeces, lung, spleen Mortality >50% for pneumonic H5N1 infection (1997, 2004–06). H5N1 influenza in human: A multi-organ infection with marked cytokine activation Copyright Lancet 2005, Hong Kong Med J 2005 CD68+ macrophages  TNF  Alveolar exudation

3. Farm chicken outbreak (Mar/Apr) Farm / market chicken outbreak (Oct/Nov) Culling (1.5 M) First documented case of human influenza and fatality attributable directly to avian influenza

4. 188919181957196819771997200319992006 0.5M0.07M0.03M 6/18 0/2 H7N30/2 H7N71/89 H5N1124/218 H1N1H2N2H3N2H1N1 H5N1 1900 H9N2 ? H3N8 ? H2N? H3N? Excess death (US) Historical timeline of influenza pandemic and recent avian influenza activity in human Seroepidemiology ??? avian gene sequence H2, N2, PB1 genes from avian virus H3, PB1 genes from avian virus H1N1 ? Leakage from Russian lab Poultry to human transmissionHuman to human transmission

6. Nomenclature Types (NP) A, B, C Subtypes of influenza A virus (HA, NA) 16 H, 9 N Genotypes of H5N1 A, B, C, D, E, V, W, X 0-3, Y, Z, Z + Sublineages of Z Photo: courtesy of Dr W Lim, PHLC.

7. Surveillance and molecular epidemiology study 2000-2004 Poultry markets Aquatic and terrestrial poultry Isolate H5N1 Sequence all 8 segments Assign genotypes Nature 2004

9. NS Ka/Ks >1 M Ka/Ks >1 Goose/Guangdong/1/96 (Gs/Gd)

10. Nature 2004 HAM Vietnam Thailand Indonesia Yunnan

11. Further surveillance and molecular epidemiology study 2004- Systematic surveillance Poultry markets More provinces Migratory birds Mai Po Marshes, Hong Kong Lake Poyang Lake Qinghai (protected nature reserve, no poultry farms in vicinity) PNAS 2006

12. 90% of H5N1 isolates are from ducks and geese 0 5 10 15 20 25 30 35 40 45 H5N1 isolates (%) GooseDuckchickenMinor poultry Migratory birds n=13115 44 (0.34%) Market poultry n=51121 512 (1%)

13. PNAS 2006 L. Qinghai L. Poyang HANP Indonesia Hunan Yunnan Vietnam Guangdong

14. PNAS 2006 HA sublineages 1. Guangdong, Hong Kong (GD) 2. Vietnam, Thailand, Malaysia (VTM) 3. Hunan, Yunnan, Indonesia (HN, YN, IDN) To Europe, Africa, Middle East ? migratory birds ? poultry trafficking September

16. Conclusions Reassortment (South China)  new genotypes Selective pressure  predominant genotype (Z) 90% H5N1 in ducks and geese (migratory and local, healthy and ill) Distinct regional virus sublineages Transmitted probably by migratory birds and poultry trafficking

17. ? Migratory birds Local wild birds Backyard farms or farms with poor biosecurity and erratic vaccination Environment: farms, homes, markets, transport, contaminated by virus Proposed model for control of bird flu: Current situation ?

18. ? Migratory birds Local wild birds Environment: farms, homes, markets, transport, contaminated by virus Proposed model for control of bird flu: Control of the H5N1 influenza epidemic at the source ? Improvement of the biosecurity of industrial farms Moratorium at hottest month for 2 weeks Segregation & Immunization of ducks & geese at industrial farms Human-bird segregation: central slaughtering, personal hygiene

19. Suspect Sumatra H5N1 Cluster Raises Pandemic Concerns This cluster has 8 family members who have died or are hospitalized with bird flu symptoms, signaling a more efficient transmission of H5N1.

20. Acknowledgement Department of Microbiology, HKU Department of Microbiology, QMH University Grant Council Centre for Health Protection, DH Research Fund for the Control of Infectious Diseases of the Health, Welfare and Food Bureau of the Hong Kong SAR Government University Development Fund Public Health Laboratory Centre Providence Foundation Limited in memory of the late Dr. Lui Hac Minh Shantou University Other HA hospitals