NVAC Meeting February 9-10 2005

1. NVAC Meeting February 9-10 2005

2. Purpose For NVAC to: Be informed and aware of key decisions and progress toward polio eradication. Support US participation in the global stockpile and response and access to mOPV Support WHO's efforts to stop the proliferation of wild polioviruses for IPV production and program to assess safety and efficacy of Sabin-IPV Endorse plans for a NAS meeting on antiviral agents

3. Overview Status of global polio eradication Post-eradication era: policies, strategies, products

4. In 1988, the World Health Assembly passed a resolution to eradicate polio globally. At the time, over 350,000 children were paralysed by polio in more than 125 countries. Since then, the initiative has become the largest public health initiative in history, as 20 million volunteers have been involved in immunizing over 2 billion children across the world. Six countries in the world remain polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan and Egypt. However, 5 African countries re-established polio transmission due to an imported poliovirus.In 1988, the World Health Assembly passed a resolution to eradicate polio globally. At the time, over 350,000 children were paralysed by polio in more than 125 countries. Since then, the initiative has become the largest public health initiative in history, as 20 million volunteers have been involved in immunizing over 2 billion children across the world. Six countries in the world remain polio endemic: Nigeria, India, Pakistan, Niger, Afghanistan and Egypt. However, 5 African countries re-established polio transmission due to an imported poliovirus.

5. Reported Polio Cases'Comparison of 2002�2004* In the past year Asia and the Middle east nearly halved its numbers of polio cases from 330 in 2003 to 187 in 2004 (at 25 January 2005): (132 cases in India, 50 in Pakistan and 4 in Afghanistan, 1 importation saudi arabia). Polio transmission in Asia is now limited to just six of 51 major geographic areas (i.e. state, province or region). However, a large outbreak in Africa has created a major challengeIn the past year Asia and the Middle east nearly halved its numbers of polio cases from 330 in 2003 to 187 in 2004 (at 25 January 2005): (132 cases in India, 50 in Pakistan and 4 in Afghanistan, 1 importation saudi arabia). Polio transmission in Asia is now limited to just six of 51 major geographic areas (i.e. state, province or region). However, a large outbreak in Africa has created a major challenge

6. Impact of 'Intensification', AsiaFocal Transmission in 2004 Pakistan: 8 large-scale SIAs, including 7 NIDs reaching 33 million children each time and 1 SNID reaching 16 million children. Afghanistan: 8 large-scale SIAs, including 4 NIDs reaching 7 million children each time, 2 SNIDs reaching 5 million children each time, and 2 mop-ups. India: 8 large-scale Supplementary Immunization Activities (SIAs), including 5 National Immunization Days (NIDs) reaching 170 million children each time; 1 Subnational Immunization Day (SNID) reaching 130 million children; and 2 mop-up campaigns in the highest-risk areas reaching 84 million children each time. India in particular has made much progress toward polio eradication in 2004. fewest # of cases ever. In sum, Asia now has the best opportunity ever to interrupt transmission of wild poliovirus in 2005. The fullest commitment of political and health leaders at all levels is needed to reach every child during upcoming polio campaigns Pakistan: 8 large-scale SIAs, including 7 NIDs reaching 33 million children each time and 1 SNID reaching 16 million children. Afghanistan: 8 large-scale SIAs, including 4 NIDs reaching 7 million children each time, 2 SNIDs reaching 5 million children each time, and 2 mop-ups. India: 8 large-scale Supplementary Immunization Activities (SIAs), including 5 National Immunization Days (NIDs) reaching 170 million children each time; 1 Subnational Immunization Day (SNID) reaching 130 million children; and 2 mop-up campaigns in the highest-risk areas reaching 84 million children each time. India in particular has made much progress toward polio eradication in 2004. fewest # of cases ever. In sum, Asia now has the best opportunity ever to interrupt transmission of wild poliovirus in 2005. The fullest commitment of political and health leaders at all levels is needed to reach every child during upcoming polio campaigns

7. Challenge: tenacious viral transmission and �fatigue� (public and staff) Planned response: Use of type 1 monovalent OPV in Egypt and parts of India by May 2005 �Underserved� strategy Integration with other interventions Prospects � Asia & Egypt Polio partners and vaccine manufacturers started development of a monovalent oral polio vaccine (type-1), to accelerate the interruption of wild poliovirus transmission in Egypt and parts of India. Seroconverson rates after 1 dose of mOPV are approximately double that of trivalent OPV. Polio partners and vaccine manufacturers started development of a monovalent oral polio vaccine (type-1), to accelerate the interruption of wild poliovirus transmission in Egypt and parts of India. Seroconverson rates after 1 dose of mOPV are approximately double that of trivalent OPV.

8. Impact of OPV Suspension, NigeriaPoliovirus Spread, 2004 In Africa, a polio epidemic spread from northern Nigeria to a total of 13 previously polio-free countries in 2003-2004. In Burkina Faso, the Central African Republic, Chad, C�te d'Ivoire and the Sudan, poliovirus transmission was re-established (i.e. the imported poliovirus circulated for over six months following initial importations). The epidemic was caused by the suspension of immunization activities in northern Nigeria and exacerbated by low population immunity levels in neighbouring countries. Following the resumption of polio immunization activities on 31 July in Kano, Nigeria, large, synchronized campaigns were conducted across 23 countries in west and central Africa, reaching more than 80 million children each time. The major country risks include Nigeria and Niger (where polio transmission has never been stopped), the Sudan (where the late 2004 outbreak threatens the polio-free status of Ethiopia and the Democratic Republic of the Congo) and C�te d'Ivoire (where immunization activities have not resumed following civil unrest in November 2004). In Africa, a polio epidemic spread from northern Nigeria to a total of 13 previously polio-free countries in 2003-2004. In Burkina Faso, the Central African Republic, Chad, C�te d'Ivoire and the Sudan, poliovirus transmission was re-established (i.e. the imported poliovirus circulated for over six months following initial importations). The epidemic was caused by the suspension of immunization activities in northern Nigeria and exacerbated by low population immunity levels in neighbouring countries. Following the resumption of polio immunization activities on 31 July in Kano, Nigeria, large, synchronized campaigns were conducted across 23 countries in west and central Africa, reaching more than 80 million children each time. The major country risks include Nigeria and Niger (where polio transmission has never been stopped), the Sudan (where the late 2004 outbreak threatens the polio-free status of Ethiopia and the Democratic Republic of the Congo) and C�te d'Ivoire (where immunization activities have not resumed following civil unrest in November 2004).

9. Summary India & Egypt: will intensify activities & add mOPV1 to stop polio during the 2005 low season.

10. Post-OPV Cessation Policies/Products

11. Priority of Post-OPV Cessation Planning ".. to manage the risk of paralytic disease caused by any polioviruses among current and future generations of children."* [Elimination of risk not possible!] *WER 2004;39:349-355.

13. iVDPV & Long-Term Excretion: WHO Registry 24 iVDPVs, including 22 long term excretors 2 currently known to excrete 7 type 1, 16 type 2, 1 type 3 cases have been from: Europe (9), USA (7), Japan (1), Argentina (1), Kuwait (1), Taiwan (1), Iran (1), Ireland/Zimbabwe (1), Thailand (1)

14. Risks of Polio After 'Eradication'

15. Policy Decision Cessation of OPV for routine immunization Consensus of September 2003 (endorsed in September 2004) meeting Risks > benefits in absence of wild poliovirus Expectation of countries and stakeholders High opportunity & financial costs of continued OPV.

16. Prerequisites for OPV Cessation Appropriate containment of all polioviruses. Global surveillance & notification capacity. mOPV stockpile & response mechanism. Coordinated cessation of OPV. 'Post OPV' immunization policy in place.

17. Routine Immunization Policy Discontinue OPV (as recommended) Remaining options: Discontinue all polio vaccination Replace OPV with IPV (country, region or globally) Develop a new polio vaccine

18. Polio Vaccine Use Worldwide, 2004

19. Current WHO Statement on IPV

20. Products Pursued & Rationale I mOPV Finish eradication in most difficult areas (anticipate licensure in Spring 2005 for mOPV1) Serve as principle stockpile vaccine Antivirals Clear chronic excretion among long-term excretors Available for post-exposure prophylaxis Option for outbreak control (example: pandemic flu)

21. Sabin-IPV Facilitate containment Serve as "warm-base" for restart OPV production Minimize the proliferation of new wild poliovirus amplification sites Facilitate the replacement of all wild poliovirus in vaccine production (longterm objective) �The AACPE (AdHoc Advisory Committee on Polio Eradication) is encouraged by the prospect of a potentially effective IPV using Sabin poliovirus strains, and urges acceleration of studies to demonstrate safety and protective efficacy.�� (WER 2004, 79,401-8) Products Pursued & Rationale II

22. Timelines depend primarily on interruption of wild poliovirus. Policy directions will be reviewed as new data becomes available.

23. Schematic: Risks & Timelines Main Risk Years after last wpv Containment Vaccines Surveillance

24. Summary/Conclusions OPV cessation prerequisite for maintaining eradication, elements: Poliovirus detection & notification Stockpile & emergency response Long-term containment National immunization policy decisions Key is to manage the risks (no �risk free� option)

25. Purpose For NVAC to: Be informed and aware of key decisions and progress toward polio eradication. Support US participation in the global stockpile & response and access to mOPV Support WHO's efforts to stop the proliferation of wild polioviruses for IPV production and program to assess safety and efficacy of Sabin-IPV Endorse plans for a NAS meeting on antiviral agents

26. THANK YOU!

27. EXTRA Slides-Polio Eradication Status

28. Selected Key Milestones Short-term (24 months): License monovalent OPV & establish response mechanism. Limit sites of wild poliovirus amplification (incl. IPV sites). Consensus on long-term containment (GAP ed. III). Introduce 'National Guidelines for OPV Cessation'. Medium term (24-60 months): Align surveillance/diagnostics with that of dangerous pathogens. Long-term: Promote use of Sabin strains only for IPV manufacture.

29. Ongoing Work Risks measurement & management iVDPVs: prevalence, re-introduction risk, clearance strategies (IgG, antivirals) cVDPV: define highest risk areas & potential strategies (e.g. limited pulses, IPV) IPV sites: define biosecurity 'gains' with Sabin; for new producers Lab stocks: verify survey/inventory process; Stockpiles: size of mOPV stockpiles; role of IPV; restart capacity (5 year period) IPV introduction define country expectations re future polio immunization model impact (esp. in terms of cVDPV emergence) determine whether specific conditions warrant a WHO IPV recommendation protective efficacy of Sabin-IPV

30. Potential World Health Assembly Resolutions (May 2005) OPV Cessation: consensus on globally coordinated OPV cessation as key goal of the eradication initiative. Containment (future handling of polioviruses): consensus on need for safe storage at secure biosafety levels for Sabin, vaccine-derived & wild polioviruses after OPV cessation. Outbreak Response (reintroduction of polioviruses): consensus on the need for vaccine stockpile and international controls, & mechanism for responding to polio outbreak should one occur.

31. Framework for National Guidelines for OPV Cessation Rationale for OPV Cessation Containment activities for OPV Cessation Surveillance before, during & after OPV Cessation Stopping routine use of OPV Polio vaccine stockpiles & outbreak response Implications of IPV introduction

32. Summary/Conclusions II Prevention of wild poliovirus amplification sites of paramount importance Development of mOPV, antiviral agents, and Sabin-IPV is integral part of post-OPV cessation planning

33. Show me the money�.for 2005-2008 2005 Financial Resource Requirements: $ 615m Contributions (Received/Projected): $ 515m Funding Gap: $ 100m 2006-2008 Financial Resource Requirements: $ 805m Stockpile: $ 250m

34. Sudan as of 18 Jan 05

35. Challenge: largest outbreak in recent history. Suspension of activities in Cote d�Ivoire Low population immunity in affected areas Possible spread to Ethiopia, DRC and other parts of E. Africa Response: New WHO/UNICEF team in Nigeria Improved NID quality Improved AFP surveillance Involvement of religious and local leaders Prospects � Africa

36. Challenges Funding gap � G8 and new donors Gaps in quality � both SIAs and surveillance Security/conflicts � polio ceasefires Burnout � recognition, incentives, staff support Political commitment, particularly in India, Pakistan and Egypt

37. Conclusions and Recommendations of the Ad Hoc Advisory Committee on Poliomyelitis Eradication, 21-22 Sept, 2004 Interrupting WPV transmission Global program priorities Enhancing the impact of SIAs Measures to limit the international spread of wild poliovirus Plans for globally coordinated cessation of use of OPV

38. Overview Overriding priority Risks of poliovirus infection Policy decision Prerequisites Products pursued & rationale Summary & conclusions