Global Epidemiology of H5N1 in Humans Tim Uyeki MD, MPH, MPP Influenza Division, National Center for Immunization and Respiratory Diseases Coordinating Center for Infectious Diseases, CDC August 9, 2006
Natural reservoir for new human influenza A Natural reservoir for new human influenza A virus subtypes: Wild waterfowl, aquatic ducks Wild waterfowl, aquatic ducks virus subtypes: Human Influenza A Viruses Avian Influenza A Viruses H1 - H3 H1 - H16 N1 - N2 N1 - N9
Antigenic “shift” Emergence of a new human influenza A virus subtype (new HA subtype) through: • Genetic reassortment (human and animal viruses) • Direct animal (poultry) to human transmission A pandemic can occur if: • A novel influenza A subtype virus infects people • The new influenza A subtype virus causes disease • Efficient and sustained virus transmission occurs among humans (sustained person-to-person spread)
Avian Influenza A Viruses Avian Influenza A Viruses • Infect respiratory and gastrointestinal tracts of birds • Infect respiratory and gastrointestinal tracts of birds • Natural reservoir is wild waterfowl Natural reservoir is wild waterfowl - - usually infections usually infections • do not cause disease (wild ducks and geese) do not cause disease (wild ducks and geese) • Genetic re Genetic re- -assortment occurs assortment occurs • • Viruses are present in respiratory secretions, excreted • Viruses are present in respiratory secretions, excreted in feces in feces • Can survive at low temperatures and low humidity for Can survive at low temperatures and low humidity for • days to weeks days to weeks • • Can survive in water Can survive in water • Disinfection of the environment is needed Disinfection of the environment is needed •
Classification of Avian Influenza A Viruses Classification of Avian Influenza A Viruses • Two classes • Two classes • Low Pathogenic Avian Influenza viruses (LPAI) Low Pathogenic Avian Influenza viruses (LPAI) • • Highly Pathogenic Avian Influenza viruses (HPAI) Highly Pathogenic Avian Influenza viruses (HPAI) • • Determined by molecular and • Determined by molecular and pathogenicity pathogenicity criteria criteria
Avian Influenza A Viruses Avian Influenza A Viruses Criteria for High Pathogenicity Criteria for High Pathogenicity Any one of the following: • Any avian influenza A virus that is lethal for four- week old chickens • 6, 7 or 8 of 8 four-week-old chickens within 10 days following IV inoculation with 0.2ml of 1:10 dilution of infectious allantoic fluid. • Any H5 or H7 virus that has a multi-basic amino acid sequence at the hemagglutinin cleavage site compatible with HPAI. • Any non H5 or H7 that kills 1-5 of 8 inoculated chickens and grows in cell culture without trypsin Fulfillment of one or more of criteria would categorize the virus as an HPAI virus. United States Animal Health Association, 1994.
Pathogenicity of AI in Poultry of AI in Poultry Pathogenicity • Low Pathogenic Avian Influenza viruses (LPAI) • Low Pathogenic Avian Influenza viruses (LPAI) • Usually do not cause illness in wild birds Usually do not cause illness in wild birds • • May cause mild illness in domestic poultry May cause mild illness in domestic poultry • • Cause poultry outbreaks worldwide Cause poultry outbreaks worldwide • • Can evolve into highly pathogenic viruses • Can evolve into highly pathogenic viruses • Highly Pathogenic Avian Influenza viruses (HPAI) • Highly Pathogenic Avian Influenza viruses (HPAI) • Usually do not cause illness in wild birds Usually do not cause illness in wild birds • • Usually cause high mortality in domestic poultry Usually cause high mortality in domestic poultry • • Subtypes: H5, H7 Subtypes: H5, H7 •
Phylogeny of H5N1 viruses from Asia VietnamHN3040805 DkVietnamNCVD0105 Clade 1 CkVietnamNCVD1005 Vietnam120304 VietnamJPHN3032105 1’ HA Hong Kong21303 CkIndonesia703 nucleotide CkIndonesia1103 CkYunnan49305 CkGuangxi1204 CkYamaguchi704 CkKoreaES03 CkShantou423103 Clade 2 BarhdGooseQinghai1205 DkFujian173405 CkGuangdong19104 DkHunan19105 DkChinaE319203 CkGuangdong17804 CkShantou81005 GsShantou162105 CkVietnamNcvd803 tealChina2978102 Hong Kong15697 GsGuangdong196 0.005
H5N1 Virus Binding • H5N1 viruses bind to cells in the lower respiratory tract: different than for human influenza A viruses • Human influenza A viruses bind to receptor cells with sialic acid linked to galactose by α -2,6 linkage • Upper respiratory tract (epithelial cells in paranasal sinuses, pharynx, trachea, bronchi) • H5N1 viruses bind to receptor cells with sialic acid linked to galactose by α -2,3 linkage • Lower respiratory tract (Type II pneumocytes, non ciliated epithelial cells in terminal and respiratory bronchioles, alveolar macrophages) Van Riel D et al. Science Express March 26,2006; Shinya K et al. Nature 2006;440:435-436.
1997: H5N1 Emerges in Hong Kong 18 confirmed cases, 6 deaths • Median age: 9.5 years (range 1-60 yrs.) • 1 had active chronic illness (SLE) • Admission findings: • High fever, cough, sore throat, rhinorrhea, vomiting, diarrhea • Clinical complications • Severe pulmonary disease • 11 (61%) pneumonia; 6/11 died; 3 had pleural effusions • 6 (33%) had ARDS (5 fatal) • Other complications: • 5 (28%) had multi-organ dysfunction (all fatal) • Reactive hemophagocytosis, renal failure, Reye syndrome • None had evidence of bacterial pneumonia Chan PKS. CID 2002;34(Suppl 2):S58-S64; Mounts A et al., JID 1999;180:505-508; Yuen KY et al. Lancet 1998;351:467-71.
H5N1 Re-emerges 2003 • Hong Kong, February 2003 • 2 confirmed cases (5-person family) • Visited Fujian Province, China (Jan., Feb. 2003) • 7-year old girl died of pneumonia in China (not tested) • 33-year old man hospitalized in Hong Kong, died • 9-year old boy hospitalized in Hong Kong, survived (H5N1 virus isolated from both) • Clinical findings: • Fever, malaise, sore throat, cough • Pneumonia (1 with respiratory failure) Peiris J, et al. Lancet 2004;363:617-619
H5N1 Re-emerges 2003 • Beijing, China, November 2003 • 1 confirmed case • 24-year old male (military) hospitalized for pneumonia, suspected to have SARS. • Died on December 3, 2003. • H5N1 virus isolated from patient, reported in 2006 • Confirmed by Chinese CDC Zhu QY et al., NEJM 2006;354:2731-2; WHO August 8, 2006
At least 52 countries with H5N1 in poultry (36) or wild birds (16)
Seasonality of H5N1 Among Domestic Poultry, China Li KS, et al. Nature 2004; 430:209-13
Hanoi, Vietnam 2002 T. Uyeki, CDC
Hanoi, Vietnam 2002 T. Uyeki, CDC
Dead Market Poultry, Nigeria, February 2006 D. Klaucke CDC
Recent H5N1 Issues in Animals � Role of migratory birds increasing? � Die offs of migratory birds in western China, Siberia, Mongolia, introduction into Europe � Ducks may be infected without illness � Pigs can be infected (China, Vietnam, Indonesia) � Other animals • Domestic cats; civet cats • Tigers, leopards (Thailand, China) • Tiger-to-tiger transmission (Thailand) Li HY et al. Chinese Journal of Preventive Veterinary Medicine 2004;26:1-6; Kuiken T et al. Science 2004;306:241; Keawcharoen J et al EID 2004;10:189-91; Thanawongnuwech R et al. EID 2005;11:699-701. Choi et al. Virology 2005;79:10821-5.
H5N1 in poultry or wild birds in 2006
Human H5N1 cases, Nov. 2003-06* • 235 confirmed H5N1 cases, 137 deaths • Vietnam: 93 cases (42 deaths) • Indonesia: 55 cases (43 deaths) • Thailand: 24 cases (16 deaths) • China: 20 cases (13 deaths) • Egypt: 14 cases (6 deaths) • Turkey: 12 cases (4 deaths) • Cambodia: 6 cases (6 deaths) • Iraq: 2 cases (2 deaths) • Azerbaijan: 8 cases (5 deaths) • Djibouti: 1 case (0 deaths) � Case fatality: 58.3% *As of August 8, 2006: H5N1 cases reported to WHO
Human H5N1 cases, 2006* • 90 confirmed H5N1 cases, 60 deaths • Vietnam: 0 cases (0 deaths) • Indonesia: 38 cases (32 deaths; 84%) • Thailand: 2 cases (2 deaths) • China: 11 cases (7 deaths) • Egypt: 14 cases (6 deaths) • Turkey: 12 cases (4 deaths) • Cambodia: 2 cases (2 deaths) • Iraq: 2 cases (2 deaths) • Azerbaijan: 8 cases (5 deaths) • Djibouti: 1 case (0 deaths) � Case fatality: 66.7% *As of August 8, 2006: H5N1 cases reported to WHO
H5N1 human cases since 2003
H5N1 human cases in 2006
Epidemiology of Human H5N1 cases 2003-06 � Infrequent, sporadic avian-to-human transmission • Previously healthy children, young adults • WHO review of 205 confirmed H5N1 cases: • Median age: 20 years (range: 6 months - 75 years) • 90% of cases <40 years old • Median duration from illness onset to hospitalization: 4 days • Mortality highest in cases aged 10-19 years (73%) • Mortality lowest in cases aged ≥ 50 years (18%) • Median duration from illness onset to death: 9 days (range 2-31 days) • Clustering of cases � No evidence of sustained person-to-person spread WHO. Weekly Epidemiological Record 2006;81:249-257.
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