Avian Influenza A(H5N1) and

Risks to Human Health

Technical Meeting on Highly Pathogenic Avian Influenza and Human H5N1 infection

Rome

27 - 29 June 2007

Keiji FukudaGlobal Influenza ProgrammeWorld Health Organization

Major Public Health Threatsof Influenza

Major Public Health Threatsof Influenza

Seasonal– Greatest health impact over time

Avian influenza H5N1 virus– Most often direct/indirect zoonotic infection from infected birds– Infrequently direct contact with an infected person– Other exposures not clearly established

Emergence of a human pandemic strain – H5N1 most concern due to spread & pathogenicity– Another novel subtype possible

Laboratory-confirmed human H5N1 cases, since 2003 Laboratory-confirmed human H5N1 cases, since 2003

312 cases190 deaths

Hong Kong/156/97

Vietnam/JP14/05 ck/Cambodia/013LC1b/05

Vietnam/1194/04 Vietnam/1203/04

Vietnam/HN30408/05 Thailand/16/04

Vietnam/JPHN30321/05

Clade 1

Hong Kong/213/03 Indonesia/CDC523/06

Indonesia/CDC699/06 Indonesia/CDC326/06

Indonesia/5/05 Indonesia/CDC184/05

Indonesia/7/05 dk/KulonProgoBBVET9/04

ck/Indonesia/CDC25/05 Indonesia/6/05

ck/Brebes/BBVET2/05

Indonesia/CDC594/06* ck/Dairi/BPPVI/05

Clade 2.1

ck/Yunnan/374/04 ck/Yunnan/115/04

ck/Yunnan/493/05 ck/Yunnan/447/05

dk/Guangxi/13/04 ck/Guangxi/12/04

whooping swan/Mongolia/244/05 bar headed gs/Qinghai/1A/05 *

Turkey/65596/06 Turkey/15/06 Iraq/207NAMRU3/06

ck/Nigeria/641/06 mld/Italy/332/06

turkey/Turkey/1/05 Egypt/2782NAMRU3/06 Djibouti/5691NAMRU3/06

ck/Nigeria42/06 migratory dk/Jiangxi/2136/05

gs/Kazakhstan/464/05 ck/Krasnodar/01/06

Azerbaijan/011162/06 swan/Iran/754/06

Clade 2.2

dk/Laos3295/06 Anhui/1/05

Anhui/2/05 Japanese white-eye/Hong Kong/1038/06 ck/Malaysia935/06

Vietnam/30850/05 Guangxi/1/05

dk/Hunan/15/04 qa/Guangxi/575/05

dk/Vietnam/Ncvdcdc95/05

Clade 2.3

migratory dk/Jiangxi/1653/05

gs/Guangdong/1/96

* Karo cluster Indonesia/CDC625/06*

Phylogenetic tree based on H5 HAStrains in yellow: vaccine strains

Vietnam

Thailand

Cambodia

Indonesia

Middle east

Europe

Africa

China

Laos

Characteristics of confirmed H5N1 human casesCharacteristics of confirmed H5N1 human cases

M:F = 0:9

All age groups affected– Higher incidence in age group < 40 years

Case fatality ~ 63%

Median duration of illness– Onset - hospitalization 4 days

– Onset - death 9 days

Clinical features – Severe cases feature pneumonia, ARDS

– Asymptomatic infection appears rare

Risk factors and exposuresH5N1 in humans

Risk factors and exposuresH5N1 in humans

Primary known exposures associated with infected birds– Unprotected handling– Sharing living areas

Route of virus entry into humans uncertain

Risk appears highest in countries with infected birds where– Human contact with poultry is frequent– Animal disease detection and/or control is a challenge

No identifiable exposures for some cases

Human-to-Human H5N1 TransmissionHuman-to-Human H5N1 Transmission

Epidemiological diagnosis of exclusion– Plausible epidemiological link – No other probable exposures– Viruses consistent– " Limited human-to-human transmission cannot be ruled

out"

Typically associated with very close prolonged contact between susceptible and severely ill person

No occurrence of human-to-human transmission capable of sustained community outbreaks

Prevention and treatment of human H5N1 infectionPrevention and treatment of human H5N1 infection

One H5N1 vaccine licensed but not yet field tested– Others applications in submission

Optimal antiviral treatment regimen is yet unknown– Early oseltamivir treatment might reduce H5N1-associated

mortality

Antiviral resistance requires monitoring

Limited evaluation of other therapies – E.g, immuno-modulators, convalescent sera

WHO Strategic Action Plan Pandemic Influenza

WHO Strategic Action Plan Pandemic Influenza

Strengthen Early Warning system

Reduce Human Exposure to H5N1 virus

Intensify Rapid Containment operations

Build Capacity to cope with pandemic

Coordinate Global Scientific Research and Vaccine Development5

4

3

2

1

WHO Global Influenza Surveillance NetworkWHO Global Influenza Surveillance Network

Important Current ActivitiesImportant Current ActivitiesImportant Current ActivitiesImportant Current Activities

Implementation of IHR

Continuing development of framework to facilitate sharing of influenza viruses and related benefits

Maintain rapid global threat assessment & response

Clearer operating terms & conditions

Greater access of developing countries to benefits

Short to long term solutions for improving pandemic & H5 vaccine situation

Stockpiles

Global Pandemic Influenza Vaccine Action Plan

H5N1 Cluster GraphH5N1 Cluster Graph

Cluster

– Two or more epidemiologically linked cases

– At least one has a lab-confirmed H5N1 infection

– Inclusion of fatal probable cases

Unexplained deaths linked epidemiologically to a confirmed case (probable case)

0

5

10

15

20

25

4 Q 1 Q 2 Q 3 Q 4 Q 1 Q 2 Q 3 Q 4 Q 1 Q 2 Q 3 Q

Number of cases in clusters

2003 2004 2005 2006

Cas

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