1. text WHO Regional Office for Europe Long wait for vaccine Influenza epidemic, New York, 1947. Times photograph Influenza Pandemic Preparedness Porto, October 2005 Dr Bernardus Ganter, WHO/EURO

2. text WHO Regional Office for Europe n Geographic spread unprecedented (11 countries: China, Cambodia, Indonesia, Japan, Kazakhstan*, Republic of Korea, Laos, Malaysia, Mongolia*, Russian Federation*, Thailand, Viet Nam) *since 2005 n Highly Pathogenic Avian Influenza (HPAI), up to 100% fatality in chicken n Increased mammalian host range (felines) n Healthy domestic ducks excrete large amount of virus (respiratory, feces) Avian H5N1 in Asia, 2004-2005 Control measures by Ministries of Agriculture, with support from FAO and OIE.

3. text WHO Regional Office for Europe n H5N1 infection in human is unprecedented - Growing number of reported human H5N1 cases Since Dec 2003: 112 cases (57 fatal) in 5 countries But unknown how widespread infection has occurred (mild or asymptomatic infection?) - 75 – 90% fatality rate in children and young adults.. but actual denominator unknown - Resistance to M2 inhibitors (e.g. amantadine) but sensitive to neuraminidase inhibitors (e.g. oseltamivir) Human H5N1 in Asia, 2004-2005

4. text WHO Regional Office for Europe Influenza virus Three types nA, B, C Subtypes defined by different antigens nH (haemaglutinin) nN (neuraminidase) e.g. Subtypes of virus A: H3N2 (common human), H7N7 (avian 2003, The Netherlands) H5N2 (avian vaccine) H5N1 (current avian / human)

5. text WHO Regional Office for Europe Migratory water birds Domestic birds Hong Kong 1997, H5N1 HK, China 1999, H9N2 Netherlands 2003, H7N7 Hong Kong 2003, H5N1 Thailand, Viet Nam, Cambodia, Indonesia, 2004- 2005, H5N1 From birds to human

6. text WHO Regional Office for Europe Reassortment (in human) Avian virus + Human virus Migratory water birds Pandemic potential

7. text WHO Regional Office for Europe Events with pandemic potential since 1968 l 1976: H1N1 Swine influenza USA (1 death) l 1986: H1N1 Swine virus derived from avian source: one severe pneumonia l 1988: H1N1 Swine virus USA: pregnant woman died after contact to sick pigs l 1993: H3N2 Swine virus recombinant with avian H1N1 Netherlands: 2 children, mild disease l 1995: H7N7 duck virus UK: adult mild conjunctivitis l 1997: H5N1 avian influenza Hong Kong: 18 cases/6 deaths l 1999: H9N2 quail virus: 2 mild cases l 2003: H5N1 avian virus Hong Kong: 1 death; 1 disease +1 related death from pneumonia l 2003: H7N7 avian virus Netherlands: 1 death; >80 conjunctivitis; few respiratory symptoms l 2003: H5N1 avian virus Guangdong: 1 detah l 2003: H9N2 avian virus Hong Kong: 1 mild upper respiratory symptoms l 2003: H7N2 avian virus New York: 1 pneumonia (HIV-coinfection) l 2004 A: H5N1 disease and death in Vietnam and Thailand (35 cases/24 deaths) l 2004: H7N3 avian virus Canada: 2 cases (conjunctivitis) l 2004 B: H5N1 disease and death in Vietnam and Thailand (9 cases/8deaths) l 2005 C: H5N1 disease and death in Vietnam and Cambodia (64cases/22deaths)  Indonesia (1/1death)

8. text WHO Regional Office for Europe Location of H5N1 Avian Influenza in the Russian Federation and suspected areas (www.oie.int) Aprx. 90.000 birds destroyed Infections mainly seen in wild ducks and geese and widespread

9. text WHO Regional Office for Europe PAVLODAR, KARAGHANDY & ASTANA, N - KAZAKHSTAN Avian Influenza (H5N1) in Kazakhstan to 17 Aug 2005 CONFIRMED H5N1 Influenza A confirmed PAVLODAR ASTANA KARAGHANDY YESIL nApprox.13.000 animals destroyed nSevere disease in animals nExpecting to continue with migration of wild birds

10. text WHO Regional Office for Europe Confirmed Outbreak HP Avian Influenza H5N1 in Domestic Birds Turkey 13 October 2005 Data source: Institute of Public Health, Bucharest Map production: WHO EURO Communicable Diseases Surveillance and Response (CSR) © WHO 2005. All rights reserved. Affected area Reported outbreaks in domestic birds

11. text WHO Regional Office for Europe Reported Outbreaks of HP H5N1 Avian Influenza in Domestic Birds Romania 10 October 2005 Data source: Institute of Public Health, Bucharest Map production: WHO EURO Communicable Diseases Surveillance and Response (CSR) © WHO 2005. All rights reserved. Affected Area Reported outbreaks in domestic birds

12. text WHO Regional Office for Europe Thank You

13. text WHO Regional Office for Europe Public Health Measures for Avian Influenza to protect people at risk Improve reporting of sick and dead birds General information on risk of transmission Personal protection equipment for cullers Post-exposure prophylaxis with AV drugs were H5N1 has been identified Prophylaxis to farmers of farms were H5N1 has been identified No mask !!

14. text WHO Regional Office for Europe 1: epidemic, 2: probable pandemic, 3: pandemic Source: Potter, C.W: Textbook of Influenza by Nichols, Webster, Hay, Blackwell Science 1998 Recorded Influenza Pandemics 0 1 2 3 1883 * 1918-19 "Spanish Flu" 1957-58 "Asian Flu" 1968 "HK Flu"

15. text WHO Regional Office for Europe Influenza Pandemics 20 th Century A(H1N1)A(H2N2)A(H3N2) 1918: “Spanish Flu”1957: “Asian Flu”1968: “Hong Kong Flu” 20-40 million deaths1-4 million deaths Credit: US National Museum of Health and Medicine

16. text WHO Regional Office for Europe Next pandemic? n Another influenza pandemic will occur … - when? How severe? … we cannot tell. n Emergence - Modeling shows that early intervention is possible.. but untested. - Surveillance remains difficult.. detection of emergence may be late. n Global spread - can not be stopped - will take less than a year (3-6 month) - will affect 1/4 to 1/3 of human population

17. text WHO Regional Office for Europe Pandemic Preparedness

18. text WHO Regional Office for Europe WHO Global Surveillance of Human Influenza Participating networks and laboratories, 2004 1 laboratory  1 laboratory national network l 115 National Influenza Centres; 7 WHO Collaborating Centres and Reference Laboratories l Annual output: 175,000-220,000 samples; 15,000-40,000 isolates; 2000-10,000 viruses characterized NEW VACCINE COMPOSITION EVERY YEAR  NEW VACCINE COMPOSITION EVERY YEAR

19. text WHO Regional Office for Europe Definition of WHO Pandemic Phases Note: 2005 definitions simplify and replace 1999 definitions n Pre-Pandemic Period Phase 1 – no avian virus poses a significant risk to human Phase 2 – new avian virus poses a risk to human n Pandemic Alert Period Phase 3 – but no human-to-human transmission Phase 4 – limited human-to-human transmission Phase 5 – human-to-human spread, larger clusters, but still localized n Pandemic Period Phase 6 – Transmission sustained, global spread Today's phase  Human infection

20. text WHO Regional Office for Europe WHO Strategy Objectives according to the different periods n Pre-Pandemic Period 1 – Reduce opportunities for human infection 2 – Strengthen the early warning system n Pandemic Alert Period 3 – Contain or delay spread at the source n Pandemic Period 4 – Reduce morbidity, mortality, and social disruption 5 – Conduct research to guide response measures

21. text WHO Regional Office for Europe WHO Strategy Actions according to the different periods n Pre-Pandemic Period n Pandemic Alert Period n Pandemic Period PANDEMIC PREPAREDNESS COUNTRIES VACCINE DEVELOPMENT RESEARCH / INDUSTRY ANTIVIRAL GLOBAL STOCKPILE WHO AVIAN INFLUENZA CONTROL FAO/OIE SURVEILLANCE WHO

22. text WHO Regional Office for Europe n Global stockpile – to contain or delay spread at source Only one manufacturer and huge cost bust modelling shows that if use within days of pandemic emergence, combined with other measures (e.g. social distancing), it could forestall international spread (Ferguson et al., Nature, Aug 2005). Three million treatments (30 million capsules of Tamiflu) donation to WHO (Roche, August 2005). n Countries to consider stockpiling – for priority groups For targeted use if vaccine not yet available; can significantly reduce morbidity/mortality if used within 48h of disease onset; good stability (particularly in bulk); but remains highly expensive, out of reach for many countries. Stockpile size of 20-25% of population could reduce hospitalisation by 50-77% (Gani et al.,EID, Sep 2005) Part of national plan of most developed countries Antivirals (Oseltamivir)

23. text WHO Regional Office for Europe Pandemic Vaccine n Opportunity to have a pandemic vaccine Clinical trial ongoing (H5N1); registration with a "template" influenza subtype; IPR for reverse genetics addressed; GMO issue; coordination to reduce time for commercial production from 7-8 to 2-3 months. n Advance stockpile of pandemic vaccine (national, global) Could be available for targeted use; raw materials (bulk antigen) would allow rapid formulation of vaccine conferring some protection; but final vaccine content depend on actual pandemic strain. n Increased manufacturing capacity Could be achieved through increased vaccine use for seasonal influenza. Value of experienced gained with logistics. 80% of capacity is in Europe.

24. text WHO Regional Office for Europe Key WHO Documents www.who.int/influenza n Responding to the Avian Influenza Pandemic Threat Recommended strategic actions n WHO Global Influenza Preparedness Plan The role of WHO and recommendations for national measures before and during pandemics n WHO Checklist for Influenza Pandemic Preparedness Planning Tests the capacity of countries for influenza pandemic planning n WHO Guidelines on the Use of Vaccine and Antivirals during Influenza Pandemic Guidance to health-policy makers n Existing national preparedness plans Show practical measures taken / planned by other countries.