Avian Influenza A(H5N1) andRisks to Human Health: 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 Fukuda Global Influenza Programme World Health Organization


Major Public Health Threatsof Influenza: Major Public Health Threats of 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 cases 190 deaths


Slide4: 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 HA Strains in yellow: vaccine strains Vietnam Thailand Cambodia Indonesia Middle east Europe Africa China Laos


Characteristics of confirmed H5N1 human cases: Characteristics 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 exposures H5N1 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 Transmission: Human-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 infection: Prevention 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


WHO Global Influenza Surveillance Network: WHO Global Influenza Surveillance Network


Important Current Activities: Important 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 Graph: H5N1 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) Cases in clusters