Control of the H5N1 influenza epidemic at the source

Patrick Woo

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

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

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

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.

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

Nature 2004

NS Ka/Ks >1

M Ka/Ks >1

Goose/Guangdong/1/96 (Gs/Gd)

Nature 2004

HA MVietnam

Thailand

Indonesia

Yunnan

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

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%)

PNAS 2006

L. Qinghai L. PoyangHA NP

Indonesia

Hunan

Yunnan

Vietnam

Guangdong

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

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

?

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

?

?

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

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