Transcript Avian influenza in human

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
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Types (NP)
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Subtypes of influenza A
virus (HA, NA)
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16 H, 9 N
Genotypes of H5N1
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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
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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
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2004Systematic surveillance
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Poultry markets
More provinces
Migratory birds
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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
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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
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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