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Control of the H5N1 influenza epidemic at the source Patrick Woo H5N1 influenza in human: A multi-organ infection with marked cytokine activation Alveolar exudation CD68+ macrophages TNF 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). Copyright Lancet 2005, Hong Kong Med J 2005 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 Historical timeline of influenza pandemic and recent avian influenza activity in human Excess death (US) 0.5M 0.07M 6/18 0.03M 0/2 H7N3 ? H2N? ? H3N? H3N8 H1N1 H2N2 H3N2 H1N1 H5N1 H9N2 H5N1 1889 1900 1918 1957 1968 1977 1997 1999 2003 H7N7 Human to human transmission Seroepidemiology ??? avian gene sequence H2, N2, PB1 genes from avian virus H3, PB1 genes from avian virus Poultry to human transmission H1N1 ? Leakage from Russian lab 0/2 1/89 124/218 2006 Nomenclature Types (NP) Subtypes of influenza A virus (HA, NA) 16 H, 9 N Genotypes of H5N1 A, B, C A, B, C, D, E, V, W, X0-3, Y, Z, Z+ Sublineages of Z Photo: courtesy of Dr W Lim, PHLC. Surveillance and molecular epidemiology study 2000-2004 Poultry markets Aquatic and terrestrial poultry Isolate H5N1 Sequence all 8 segments Assign genotypes Nature 2004 Nature 2004 Goose/Guangdong/1/96 (Gs/Gd) NS Ka/Ks >1 M Ka/Ks >1 Nature 2004 Yunnan Indonesia HA Thailand Vietnam M Nature 2004 Further surveillance and molecular epidemiology study 2004Systematic 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 90% of H5N1 isolates are from ducks and geese Migratory birds 45 H5N1 isolates (%) 40 n=13115 44 (0.34%) 35 30 Market poultry 25 n=51121 512 (1%) 20 15 10 5 0 Goose Duck chicken Minor poultry PNAS 2006 Guangdong Vietnam Hunan HA L. Qinghai L. Poyang Yunnan Indonesia NP To Europe, Africa,September Middle East HA sublineages 1. Guangdong, Hong Kong (GD) 2. Vietnam, Thailand, Malaysia (VTM) 3. Hunan, Yunnan, Indonesia (HN, YN, IDN) ? poultry trafficking ? migratory birds PNAS 2006 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 Environment: farms, homes, markets, transport, contaminated by virus Backyard farms or farms with poor biosecurity and erratic vaccination Migratory birds ? Local wild birds ? Proposed model for control of bird flu: Current situation Environment: farms, homes, markets, Moratorium at hottest transport, month for 2 weeks contaminated by virus Improvement of the biosecurity of industrial farms Migratory birds Segregation & Immunization of ducks & geese at industrial farms ? Human-bird segregation: central slaughtering, personal hygiene ? Proposed model for control of bird flu: Control of the H5N1 influenza epidemic at the source Local wild birds 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. 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