Overview of human cases of AI H5N1 since 1997 Dr Sylvie Briand WHO Global Influenza Programme 7 October 2008 1 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Review of the current H5N1 situation 387 cases and 245 deaths recorded since February 2003 15 countries affected in 3 continents (Africa, Asia, Europe) Azerbaijan, Bangladesh, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Lao People's Democratic Republic, Myanmar, Nigeria, Pakistan, Thailand, Turkey, Viet Nam In 2008, 36 cases with 28 deaths reported in 5 countries. Most cases are in countries where the disease in animals is already considered entrenched. SARS outbreak: mid-march 2003-5 July 2003 8098 cases, 774 deaths 26 countries affected 2 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 1
H5N1 Human Infection 2008 387 laboratory confirmed cases Primarily transmission from infected birds (poultry) Sporadic cases and small family clusters No evidence of sustained human to human transmission Limited un-sustained human-to-human transmission Intimate prolonged contact at a critical stage of illness Probable in Thailand in 2004 - NEJM; 2005 Jan 27;352(4):333-40 Confirmed H2H, 3 generations, Pakistan, December 2007 - WER N 40, 3 October 2008 3 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Increased geographical spread First signal : May 1997. First human case with H5 N1 virus in Hong Kong. December 1997. Increase in the number of cases 18 cases / 6 deaths Strong control measures : culling of poultry, closure of markets, no importation of poultry form neighbouring countries. February 2003: H5N1 comes back Hong Kong - 3 cases/2 deaths reported in the same family coming from China. Occurrence of the SARS outbreak at the same period End 2003 - end 2005: human infections reported in a number of countries in Asia Extension of the affected area since the end of 2005 European countries affected (Turkey Dec 2005) Africa affected (Egypt March 2006) Pakistan, Myanmar and Bangladesh in 2007-08 4 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 2
5 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Distribution of A(H5N1) cases, deaths and CFR by country 6 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 3
Risk of pandemic? The risk of pandemic has not decrease although a decrease in the yearly number of human cases is observed But There are concerns about : -countries with densely populated areas and ongoing circulation of A (H5N1) in poultry - poor surveillance system 7 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Laboratory-confirmed human avian influenza infections since 1999 8 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 4
Epidemiological review Behavioural factors & interventions Climate, seasons There are differences between countries. A number of factors can explain the differences and it is difficult to disentangles them Gender Animal Virus clade Country Profile -Time -Risk groups -Mortality Age Care 9 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Relationship between poultry outbreaks and human infections Viral circulation in poultry and occurrence of human cases are linked. Enhanced surveillance and integrated analysis at the human animal interface is needed to better understand the dynamic of avian and human infection Country data (Egypt) Dynamic patterns of avian and human influenza in east and southeast Asia Andrew W Park, Kathryn Glass Lancet, vol 7, 2007 10 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 5
11 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Seasonality of A (H5N1) infection in human Figure 2. Laboratory confirmed human H5N1 cases by month of disease onset date, 2004-2007 The global epidemic curve for human cases of H5N1 suggests a "seasonal" pattern that peaks during the Northern Hemisphere winter and diminishes towards summer. Individual country data demonstrate this pattern most clearly in Egypt and Viet Nam. 12 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 6
Distribution of Human A(H5N1) cases over time Human cases occur throughout the year in Indonesia with a slight increase in January. The pattern of human cases of H5N1 is similar to that for seasonal influenza in Indonesia and Egypt. Factors involved in the increase of A(H5N1) infection in different period of the year : Role of climate? Co-infection with other influenza viruses? Link with poultry outbreaks? 13 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Mortality in A(H5N1) human cases Overall CFR : 63 % Range from 44% in Egypt and 81.8 % in Indonesia Time to presentation to health care facility is probably a important factor to explain higher mortality. However other factors cannot be discarded. Surveillance bias Virus virulence Clinical management Population characteristics 14 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 7
Mortality and health care Survival is closely linked to early hospitalization. Percentage of surviving cases 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 1 2 3 4 5 6 >6 Days to hospitalization Fatal cases Surviving cases However, a more systematic and consistent approach is needed when reporting information about hospitalization. A case patient often visited more than one hospital and it was sometimes unclear which hospital admission date was reported. In addition, data is not always available on treatment modalities. 15 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Virus characteristics and mortality Virus A(H5N1) has changed since 1997 and continues to evolve (drifts) A(H5N1) clades (10 clades some divided in sub-clades) Clade 1 Viet Nam, Thailand, Cambodia Clade 2 2.1 Indonesia 2.2 Middle east, Europe, Africa 2.3 Laos China Difference in virulence related to virus clade? 16 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 8
Phylogenetic tree based on H5 HA Strains in yellow: vaccine strains Vietnam/JP14/05 ck/cambodia/013lc1b/05 Vietnam/1194/04 Vietnam/1203/04 Clade 1 Vietnam/HN30408/05 Thailand/16/04 Vietnam/JPHN30321/05 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/CDC625/06* Indonesia/CDC594/06* ck/dairi/bppvi/05 ck/yunnan/374/04 ck/yunnan/115/04 dk/guangxi/13/04 ck/guangxi/12/04 ck/yunnan/493/05 ck/yunnan/447/05 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 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 migratory dk/jiangxi/1653/05 Hong Kong/156/97 gs/guangdong/1/96 Vietnam Thailand Cambodia Clade 2.1 Indonesia * Karo cluster Clade 2.2 Middle east Europe Africa Clade 2.3 China Laos Distribution by age The overall median ages of cases : 20.0 years (range 3 months- 81 years). The mean = 21.7 years All age groups affected Higher incidence in age group < 40 years Sept 2007- N= 328 18 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 9
Egypt 38 cases -15 deaths Indonesia: 106 cases - 85 deaths 19 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Morbidity by age group in the most affected countries Viet Nam :100 cases - 46 deaths Laboratory-Confirmed H5N1 Cases Age-Specific Incidence in Viet Nam (n=91) 25 Nov03 to 24 Nov06 20 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 10
Summary of distribution of A(H5N1) cases by gender WER N 6, 2007, 82 41-48 Sex ratio of male (n=157) to female (n=171) = 0.9 Differences among countries Egypt Sex ratio M/F=0.5 (12/26) Thailand Sex ratio M/F =1.8 (16/9) No statistical difference in gender distribution among age group In 2008, in Egypt, of the 50 laboratory confirmed cases in Egypt, 16 (32%) were male and 34 (68%) were female. Gender - Number and Ratio by Country M F Ratio M/F Azerbaijan 2 6 0.3 Cambodia 2 5 0.4 China 11 14 0.8 Djibouti 0 1 0.0 Egypt 12 26 0.5 Indonesia 54 52 1.0 Iraq 2 1 2.0 Laos 0 2 0.0 Nigeria 0 1 0.0 Thailand 16 9 1.8 Turkey 7 5 1.4 Viet Nam 51 49 1.0 All Countries 157 171 0.9 21 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface A(H5N1) Mortality and gender Viet Nam Dead Alive Male 21 30 Female 25 24 46 54 Egypt Dead Alive Male 1 11 Female 14 12 15 23 51 49 100 12 26 38 O R:0.67 O R:0.083 22 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 11
Groups at risk? Poultry workers: Despite potentially high exposure, PW have develop the disease only on rare occasion. Health care workers: Nosocomial transmission exists but is very low compared to seasonal influenza viruses Family clusters: Genetic susceptibility to H5N1 virus infection? Common behaviours? Same Environment? Pregnancy 6 cases in pregnant women 4 deaths, 2 abortions 23 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface Acknowledgment Dr Keiji Fukuda, Director GIP Dr Mary Chamberland, GIP Dr Julia Fitzner, GIP Dr Liz Mumford, GIP M. Tim Nguyen, GIP Dr Nikki Shindo, GIP Dr Kaat Vandemaele, GIP Dr Wenqing Zhang, GIP Dr Johannes Schnitzler, ARO 24 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 12
THANK YOU 25 FAO-OIE- WHO Joint Technical Consultation on AI at the Human-Animal Interface 13