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Control of the H5N1 influenza epidemic at the source
Patrick Woo
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F/24 Day 11Fever, 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
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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
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1889 1918 1957 1968 1977 1997 20031999 2006
0.5M 0.07M 0.03M 6/18 0/2 H7N3 0/2
H7N7 1/89
H5N1 124/218H1N1 H2N2 H3N2 H1N1 H5N1
1900
H9N2?
H3N8
?H2N?H3N?
Excessdeath (US)
Historical timeline of influenza pandemic and recent avian influenza activity in human
Seroepidemiology ???aviangenesequence
H2, N2,PB1genes fromavian virus
H3, PB1genes fromavian virus
H1N1 ?LeakagefromRussianlab
Poultry to human transmissionHuman to human transmission
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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, X0-3,
Y, Z, Z+
Sublineages of Z
Photo: courtesy of Dr W Lim, PHLC.
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Surveillance and molecular epidemiology study
2000-2004 Poultry markets Aquatic and
terrestrial poultry Isolate H5N1 Sequence all 8
segments Assign genotypes
Nature 2004
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Nature 2004
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Nature 2004
NS Ka/Ks >1
M Ka/Ks >1
Goose/Guangdong/1/96 (Gs/Gd)
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Nature 2004
HA MVietnam
Thailand
Indonesia
Yunnan
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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
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90% of H5N1 isolates are from ducks and geese
0
5
10
15
20
25
30
35
40
45
H5N
1 is
ola
tes
(%)
Goose Duck chicken Minorpoultry
Migratory birds
n=13115 44 (0.34%)
Market poultry
n=51121 512 (1%)
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PNAS 2006
L. Qinghai L. PoyangHA NP
Indonesia
Hunan
Yunnan
Vietnam
Guangdong
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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
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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
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?
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
?
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?
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 & geeseat industrial farms
Human-bird segregation: central slaughtering, personal hygiene
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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.
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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