1. H5N1 Avian Influenza History and Current Status Elizabeth A. Krushinskie, DVM, PhD U.S. Agency for International Development Washington, DC

2. History of HPAI H5N1 ► The threat of an influenza pandemic has gripped the world for nearly 3 years with the unexpected and rapid spread of HPAI H5N1  Was confined to SE and East Asia, but has now spread westward thru Central Asia, Eastern Europe, Western Europe, Middle East, and Africa  Has infected 256 people in 10 countries and resulted in the death of 151 of them (Oct 2006)

3. Pre-History ► 1996 – 1997  HPAI H5N1 isolated from China and Hong Kong ► Thought to have been eradicated ► Total of 18 humans cases (6 fatal) ► Feb 2003  Two cases of H5N1 confirmed in Hong Kong family with travel history to China

4. WHO H5N1 Avian Influenza Timeline May 8, 2006 ► Appears to have spread in three separate waves  Wave I – mid-2003 to mid-March 2004  Wave II – June to November 2004  Wave III – December 2004 to May 2006 ► Is a 4 th wave likely to start?

5. History Wave I (mid-2003 to March 2004) ► H5N1 virus causes numerous outbreaks in poultry and people in SE Asia (7 new countries affected) ► Thailand- Cambodia ► Korea- Lao PDR ► Viet Nam- China ► Japan- Indonesia ► Kills tigers and leopards in zoo in Thailand  First report in big cats ► Human cases clustered in Thailand and Viet Nam  12 human cases (8 fatal) in Thailand; 23 cases (16 fatal) in Viet Nam

6. History Wave II (June to November 2004) ► Continues to spread in SE Asia  Z-genotype identified in poultry  Research shows that pigs, cats, and wild waterfowl can be infected  Research also showed that domestic ducks can be silent reservoir of the disease ► 5 human cases (4 fatal) in Thailand; 4 cases (4 fatal) in Viet Nam

7. History Wave III Dec 2004 - Jan 2005 ► Undetected poultry and human cases ongoing in SE Asia  Viet Nam is epicenter of new outbreaks  First report of probable secondary transmission (human-to-human) in Thailand ► Family clusters ► NO evidence of sustained transmission

8. History Wave III Feb – Mar 2005 ► Cambodia reports 3 fatal human cases

9. History Wave III April 2005 ► Wild birds die at Qinghai Lake in central China  First report of HPAI in wild waterfowl reservoir ever  Total 6,345 birds of different species affected  Caused by a new H5N1 variant that may be more lethal to wild birds and experimentally infected mice

10. History Wave III May 2005 ► China reports poultry outbreaks in Xinjiang region

11. History Wave III July 2005 ► Indonesia reports first human case ► Russia reports first outbreak in poultry in 6 regions of western Siberia  Associated with dead migratory birds ► Kazakhstan reports first outbreak in poultry  Associated with dead migratory birds ► Endangered Owston’s palm civets affected in Viet Nam

12. History Wave III August 2005 ► Viet Nam now has 64 confirmed cases in third wave (21 fatal) ► China reports outbreak in Tibet ► Mongolia reports death of 89 migratory birds at two lakes

13. History Wave III September 2005 ► Indonesia continues to report human cases ► Disease started moving out of Asia westward thru Central Asia, Eastern Europe, and Europe to Africa via wild birds (dead birds predominantly mute swans)

14. History Wave III October 2005 ► Research shows that lethal 1918 pandemic virus was entirely avian in origin with some similarities to current H5N1 ► Turkey, Romania, Croatia report H5N1 in wild birds and/or poultry ► Thailand reports first new case since October 2004

15. History Wave III October 2005 ► Research shows that HA amino acid sequence is changing  May affect antigenicity or transmissibility  Human isolate HA started to differentiate into at least two sublineages (clades) that are genetically and antigenically distinct ► Clade 1: HK, Thailand, VN, Cambodia, Malaysia ► Clade 2: Indonesia, Korea, Turkey, Iraq, Azerbeijan, swans

16. History Wave III November 2005 ► Viet Nam reports first new case since July 2005 ► China reports first human cases  25 poultry outbreaks in 9 provinces  Culled 20 million birds by end of November

17. History Wave III December 2005 ► Ukraine reports H5N1 in poultry ► Kuwait reports case in flamingo ► Turkey reports new cluster of poultry cases in eastern province of Igdir

18. History Wave III January 2006 ► Turkey reports first human cases  Poultry outbreaks reported in 11/81 provinces ► Iraq reports first human case

19. History Wave III February 2006 ► Human cases reported in China, Indonesia, Iraq  China reports its 12 th case and 8 th fatality ► Many of these cases occurred in areas with no reported poultry outbreaks  Indonesia reports its 25 th case and 18 th fatality

20. History Wave III February 2006 ► 13 countries report H5N1 in wild birds  Mostly swans, but also ducks, herons, and storks  Austria, Azerbeijan, Bosnia-Herzegovina, Bulgaria, France, Georgia, Germany, Greece, Hungary, Iran, Italy, Slovakia, and Slovenia ► Germany reports case in dead domestic cat

21. History Wave III February 2006 ► First detection in AFRICA  Nigeria reports first poultry cases ► 7 additional countries report poultry cases  Egypt, France, India, Iraq, Niger, and Malaysia

22. History Wave III February 2006 ► Research shows that multiple genetically and antigenically distinct sublineages established in poultry in Asia ► H5N1 isolated from clinically healthy wild migratory birds in China

23. History Wave III March 2006 ► Azerbeijan and Egypt have first human cases ► Cambodia has first case since April 2005 ► Research shows that preferred binding site for H5N1 in humans is on receptors deep in lung tissue rather than on cells lining nose and throat  Most patients present with infection in lower respiratory tract with rapid progression to pneumonia

24. History Wave III March 2006 ► 6 countries report H5N1 in wild birds (mostly swans)  Czech Republic, Denmark, Poland, Serbia-Montenegro, Sweden and Switzerland ► Austria and Germany report H5N1 in domestic cats ► Germany reports case in stone martin ► Sweden reports H5N1 from mink

25. History Wave III March 2006 ► 7 countries report cases in domestic poultry  Afghanistan, Albania, Cameroon, Israel, Jordan, Myanmar, and Pakistan

26. History Wave III April – May 2006 ► UK confirms case in one wild bird (swan) ► Wild bird case reporting stops abruptly worldwide ► Burkina Faso, Sudan, and Cote d’Ivoire report H5N1 in poultry

27. History Wave III April – May 2006 ► Djibouti reports first human case; Egypt has 14 cases (6 fatal)  Africa becomes epicenter of new poultry cases  WHO concerned about exposure to humans with concurrent immunosuppressive infections (HIV) plus other disease (malaria, polio, TB, etc)

28. History Wave IV? June 2006 - Present ► Recent human cases  China  Egypt  Indonesia  Thailand

29. PRESENT Wave IV? June 2006 – Present ► Poultry outbreaks  Reported in 15 countries since June  Essentially endemic in: ► Africa ► Egypt ► SE Asia

30. History Wave IV? June 2006 to Present ► Wild bird outbreaks (only) June – October  Mongolia (July – gull, swan, goose)  Russia (August – wild birds)  Spain (August – Great Crested Grebe) ► Waiting for fall migration to begin  Eastern Europe (circum-Black Sea region)  Caucuses (Azerbaijan, Armenia, Georgia)

31. History Wave IV? June 2006 to Present ► Are wild waterfowl still infected?  Recent FAO paper (EMPRES WATCH October 2006) suggests wetland region of south central Russia likely reservoir ► Disease has persisted for two years in 3 administrative regions ► Omskaya, Novosibirskaya, and Altayskiy Oblasts

32. History Wave IV? June 2006 to Present ► Are wild waterfowl still infected?  No HPAI H5N1 birds positive in USA surveillance to date  No HPAI H5N1 birds positive in European surveillance to date  Few HPAI H5N1 birds positive in Asian surveillance to date

34. Pandemic Risk? ► Worldwide strategy is to eradicate HPAI at its poultry source ► Several countries especially problematic  Indonesia ► Responsible for 28% of cases and 36% of deaths to date ► 30/33 provinces have poultry cases  Nigeria  Sudan

35. Persistence of HPAI Asia/Africa ► Most Asian/African countries are impoverished  Lack basic human health and animal health infrastructure  Lack resources, trained personnel, equipment  Poor transportation systems (road and air)  Poor communication systems (radio, TV)

36. Persistence of HPAI Asia/Africa ► Most of poultry production is in backyard flocks (70+ %)  A poultry H5N1 epizootic would be disastrous for the livelihoods and food security of millions of people  Spread is primarily thru movement of live birds to poultry markets within and between countries

37. Risk Factors Human Infection ► Human infections are most likely related to three key factors:  Preparing sick or dead poultry for consumption <7 days before illness onset  Having sick or dead poultry in the household <7 days before illness onset  Lack of an indoor water source (CDC, EID, Vol 12, No 12, 2006)

38. HPAI Control Efforts ► Primarily coordinated thru UN organizations  FAO is lead agency for avian influenza  WHO is lead agency for pandemic influenza  OIE’s role is still unclear ► Supported by a large variety of “donor” organizations  World Bank (WB)  UN Agencies (including UNICEF)  European Union (EU)  US Agency for International Development (USAID)

39. HPAI Control Efforts ► Key components:  Planning and preparedness efforts  Surveillance and diagnostic capacity improvement  Behavior change communication strategies  Emergency response capacity enhancement

40. HPAI Control Efforts EXPENSIVE! ► U.S. government committed $325 million to international HPAI control efforts in 2006  $55 million in commodity stockpile  $20 million directly to FAO  Remainder dispersed thru USAID, USDA, DOD, etc ► Funding for 2007???  Infrastructure improvement and behavior change still desperately needed worldwide

41. Summary ► HPAI is probably going to be with us for quite a while (years?)  Currently endemic in Africa, China and Indonesia  Possibly endemic in wild waterfowl ► Is causing significant damage to animal agriculture and food security worldwide  Poultry industries everywhere are economically affected  Rural poor significantly impacted

42. Summary ► The virus is mutating as it continues to spread  Definitely differentiating into multiple sub- lineages with different characteristics ► Human pandemic AI virus has NOT occurred yet ► Continued improvement in HPAI detection and eradication in poultry is still critical worldwide

43. CONTACT INFORMATION: Elizabeth Krushinskie, DVM, PhD Senior Technical Advisor Avian and Pandemic Influenza Preparedness and Response Unit U.S. Agency for International Development Washington, D.C. 301-793-9662 office bkrushinskie@gmail.com