1. January 2005 Polio Eradication Initiative NVAC Meeting February 9-10 2005 Polio Eradication: Global Progress and Post-Eradication Strategies

2. Polio Eradication Initiative 2 February 2005Purpose 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. Polio Eradication Initiative 3 February 2005Overview  Status of global polio eradication  Post-eradication era: policies, strategies, products

4. Polio Eradication Initiative 4 February 2005 1988 350 000 cases 125 countries Progress by End 2004 2004 1227 cases (as of 02 Feb 05) 6 + 11 countries

5. Polio Eradication Initiative 5 February 2005 Reported Polio Cases' Comparison of 2002–2004* Reported Polio Cases *Data as of 01 Feb 2005

6. Polio Eradication Initiative 6 February 2005 Impact of 'Intensification', Asia Focal Transmission in 2004 Pakistan/Afghan India 6 NIDs + 8 rounds in high risk areas

7. Polio Eradication Initiative 7 February 2005 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 Protection after 1 dose of mOPV vs. tOPV (for type 1 polio)

8. Polio Eradication Initiative 8 February 2005 Impact of OPV Suspension, Nigeria Poliovirus Spread, 2004 Nigeria 781 cases Transmission re-established in 5 polio-free countries Wild virus type 1 Wild virus type 3 ?

9. Polio Eradication Initiative 9 February 2005 Summary India & Egypt: will intensify activities & add mOPV1 to stop polio during the 2005 low season. Africa: rapid progress possible, if NID quality improves & is sustained, large-scale, synchronized activities continue, surveillance gaps are addressed.

10. January 2005 Polio Eradication Initiative Post-OPV Cessation Policies/Products February 2005

11. Polio Eradication Initiative 11 February 2005 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. January 2005

12. January 2005 Polio Eradication Initiative Outbreaks of Circulating Vaccine- Derived Polioviruses (cVDPVs) Philippines2001 3 cases Hispaniola 2000 2000 22 cases Madagascar2002 4 cases China2004 2 cases Egypt* 1988-93 32 cases * Based on retrospective analysis of isolates. January 2005

13. Polio Eradication Initiative 13 February 2005 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) January 2005

14. Polio Eradication Initiative 14 February 2005 Risks of Polio After 'Eradication' VAPP 2-4/million birthcohort 250-500stable iVDPV24 identified <1 decreases (since 1963) cVDPV1* per year 10increases IPV sites1 accident (1990s) <1decreases Lab accident 1 investigation NKdecreases Deliberate0NKunknown FrequencyAnnualEvolution Risk to dateburden over time *based on current understanding After interruption of wild poliovirus, continued use of OPV will compromise the goal of a polio-free world. Expert Consultation on Vaccine-derived Polioviruses (VDPVs), Sept 2003, Geneva January 2005

15. Polio Eradication Initiative 15 February 2005 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. Timing : must occur while population immunity & surveillance sensitivity (for cVPDV emergence) are high. January 2005

16. Polio Eradication Initiative 16 February 2005 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. January 2005

17. Polio Eradication Initiative 17 February 2005 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 January 2005

18. Polio Eradication Initiative 18 February 2005 Polio Vaccine Use Worldwide, 2004 IPV only IPV/OPV OPV only The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO 2005. All rights reserved

19. Polio Eradication Initiative 19 February 2005 Current WHO Statement on IPV Most important considerations: Risk of importation / spread of wild PV Vaccination coverage (IPV mostly direct effects) January 2005

20. Polio Eradication Initiative 20 February 2005 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) January 2005

21. Polio Eradication Initiative 21 February 2005  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 January 2005

22. Polio Eradication Initiative 22 February 2005  Timelines depend primarily on interruption of wild poliovirus.  Policy directions will be reviewed as new data becomes available. OPV Cessation Strategy January 2005

23. Polio Eradication Initiative 23 February 2005 Use mOPV for 'outbreaks' Implement ' BSL3 / polio ' for Sabin Schematic: Risks & Timelines Main Risk Years after last wpv Containment Vaccines Surveillance 012453 cVDPV emergence Inadvertant wpv release Undetected wild polio iVDPV &/or IPV accident Implement ' BSL3 / polio' for WPVs 'Final' IPV Procure decisions stockpile Add 'suspect polio' to IHR Potential Target Date for OPV Cessation 'Dangerous pathogen' lab & surveillance practices

24. Polio Eradication Initiative 24 February 2005 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) January 2005

25. Polio Eradication Initiative 25 February 2005Purpose 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. Polio Eradication Initiative 26 February 2005 THANK YOU!

27. Polio Eradication Initiative 27 February 2005 EXTRA Slides- Polio Eradication Status

28. Polio Eradication Initiative 28 February 2005 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. October 2004 January 2005

29. Polio Eradication Initiative 29 February 2005 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 January 2005

30. Polio Eradication Initiative 30 February 2005 Potential World Health Assembly Resolutions (May 2005) 1. OPV Cessation: consensus on globally coordinated OPV cessation as key goal of the eradication initiative. 2. Containment (future handling of polioviruses): consensus on need for safe storage at secure biosafety levels for Sabin, vaccine-derived & wild polioviruses after OPV cessation. 3. 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. Polio Eradication Initiative 31 February 2005 Framework for National Guidelines for OPV Cessation 1.Rationale for OPV Cessation 2.Containment activities for OPV Cessation 3.Surveillance before, during & after OPV Cessation 4.Stopping routine use of OPV 5.Polio vaccine stockpiles & outbreak response 6.Implications of IPV introduction January 2005

32. Polio Eradication Initiative 32 February 2005 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 January 2005

33. Polio Eradication Initiative 33 February 2005 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. Polio Eradication Initiative 34 February 2005 Sudan as of 18 Jan 05  Sudan had 112 cases.  Undetected circulation for several years.  Four rounds of NIDs planned for the first half of 2005.  Recently negotiated days of tranquility so that all children could be reached.  Concern about spread to Ethiopia, Eritrea, Uganda, Kenya and other countries.

35. Polio Eradication Initiative 35 February 2005 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 Synchronized NIDs, 2004-5

36. Polio Eradication Initiative 36 February 2005 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. Polio Eradication Initiative 37 February 2005 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. Polio Eradication Initiative 38 February 2005Overview  Overriding priority  Risks of poliovirus infection  Policy decision  Prerequisites  Products pursued & rationale  Summary & conclusions January 2005