1. The Evolving 'Polio Endgame' Strategy
Orientation for IEAG
15 March 2012

2. Background

3. Main risks if routine OPV is continued after wild poliovirus eradication
Cases of Vaccine-Associated Paralytic Poliomyelitis (VAPP): very rare severe adverse event, occurring in OPV recipients or a close contact.
Outbreaks of circulating vaccine-derived poliovirus (cVDPV): very rare event; > 1 paralytic polio case with isolation of related but non-identical VDPV viruses.

4. Other risk: long-term poliovirus excretors (iVDPVs: 1o immunodeficiency-associated VDPVs)
53 iVDPVs (> 6 months excretion)
8 known to excrete >5 years.
Type 2 (34) > Type 1 > Type 3
From:
Industrialized countries (22)
Middle income countries (31)
Low income countries

5. 'After interruption of wild
poliovirus, continued use of OPV would compromise the goal of a polio-free world.
Expert Consultation on Vaccine-derived
Polioviruses (VDPVs), Sept 2003, Geneva

6. Evolution of the 'Post-Eradication' Timeline
Last WPV case
OPV cessation
Years
Wild virus eradication
Global Cert Comm (1995)
Certification
The 'Polio Endgame' refers to management of the 'post-eradication' risks due to OPV.
Expert Advisory Meeting (1998)
Wild virus eradication
Certification & containment
ACPE (2004)
VDPV elimination?
Wild virus eradication
Certification & containment
VDPV elimination & validation
World Health Assembly (2008)
Post-OPV surveillance

7. Why is the world now rethinking the Polio Endgame?

8. Recent developments allow a major 'rethink' of the polio endgame
New diagnostics and experience currently suggest type 2 cVDPV is the main 'post-eradication' problem.
New bivalent vaccine (bOPV) is proven to outperform tOPV for types 1 & 3 and a viable option to replace tOPV.
New, very low cost 'IPV options' could allow all countries to continue type 2 immunization if they want/need to.

9. Current Understanding of cVDPVs (Global)
Circulating Vaccine-Derived Poliovirus Oubreaks (cVDPVs)
Type 1 (79 cases)
Type 2 (450 cases)
Type 3 (9 cases)
Since 2009, 97% of cVDPV cases are due to type 2
(& 40% of VAPP)

10. Current Understanding of cVDPVs (India)
Spot map of VDPVs
India: 90% of VDPVs are type 2 & 100% of cVDPVs are type 2
Year
Type 1
Type 2
Type 3
Total a i c
2009 1 4 15 21
2010 2 5
2011 7
2012  1 10 3 17 34
Data as on 7 March 2012 10

11. Trend in Type 2 Polio Protection (India)
Moradabad
Nov 2007
(N=121)
AFP cases UP
Nov 08 – mid 09 (N =169)
Moradabad May 2009
(N=534)
UP & Bihar
Aug 2010
(N=1280)
Aug 2011
(N=1246)
Age
6-7 mos
6-11 mos
Type 2
56%
33.7%
75%
65%
85%
Reduced emergence of type 2 cVDPVs is associated with improving type 2 immunity

12. Bivalent OPV Efficacy & Use
Seroconversion after 2 x bOPV
vs. tOPV, India,
bivalent OPV use
as of Sept 2011
Introduced
Dec 09-Aug 11
Planned by end-2011
Type 1
Type 3

13. Affordable IPV options in the short-term,
1/5th of 1 dose of IPV can induce a response in >90% of children
Response* after 1 dose
(%, intradermal IPV, Cuba)
* includes seroconversion & priming
Full-dose $3
$0.6
Current price
(low volume)
< $0.3
IPV price
($ per dose)
** assumes full dose price of < US$1.5/dose at high volume
1/5th of 1 dose of IPV could be very affordable (<$0.5/dose)
1/5th fractional dose
Expected price
(high volume**)

14. What are the major elements of the 'New Polio Endgame'?

15. New Polio Endgame: Guiding Principles
phased removal of Sabin viruses, beginning with highest-risk (type 2).
elimination of VDPV type 2 in parallel with eradication of last wild polioviruses by switching from tOPV to bOPV for routine EPI & campaigns.
early introduction of at least 1 dose of IPV to boost immunity prior to a tOPV-bOPV switch (& provide type 2 priming if further doses required).

16. A new 'Endgame' strategy: parallel instead of sequential risk management
Last wild polio case
trivalent OPV cessation
Years
Sequential risk management
Wild virus eradication
Certification & containment
VDPV elimination & validation
Post-OPV surveillance
Wild virus eradication
Parallel risk management
Certification & containment
VDPV2 elimination & validation
Post-OPV surveillance
OPV2 cessation
& IPV introduction
bivalent OPV 1&3 (bOPV) cessation

17. Potential Advantages of the New Approach
accelerate eradication of type 1 & 3 wild poliovirus by routine use of bOPV (and possibly IPV)
address >90% of the VDPV risk when global surveillance/response capacity is highest
substantially shorten the post-eradication phase (& reduce a major source of donor/partner anxiety)
possibly boost eradication effort with new energy & routine immunization coverage (i.e. if IPV dose at DPT3)

18. Potential Disadvantages of the New Approach
distraction to wild poliovirus eradication efforts (to stop ongoing cVDPV2s; to coordinate tOPV-bOPV switch).
complications of adding a new vaccine (IPV) (however, GPEI has introduced many new vaccines already).
sudden 'price shock' for donors as requires early presentation of longer-term financing requirements.
risk of failure to stop new cVDPV2s (but, with this approach could even 'restart' tOPV temporarily if needed).

19. Impact of the new Endgame Strategy on Major Cost Drivers for 2013-2018
'Core costs*' - stable
OPV campaign costs - decrease
IPV costs - additional
* staff & technical assistance, surveillance & lab, research, outbreak response, stockpiles.

20. Some Implications for IPV
IPV could be scaled up much earlier than anticipated (i.e. tOPV-bOPV switch could be prior to April 2014).
standalone IPV would be used for the 'tOPV-bOPV switch' with hexavalent having a 'post-OPV' role (e.g. from ).
a fractional (1/5th dose) intradermal IPV option may be essential for acceptability, cost, supply, manufacturer risk.
the probability of expanded, longterm IPV use would increase substantially.

21. Recent Developments & Next Steps

22. SAGE Nov 2011: recommended endgame strategy be based on phased, not simultaneous, Sabin strain removal.
WHO Executive Board Jan 2012: requested endgame strategy & timeline for phased Sabin strain removal.
SAGE Apr 2012: to discuss introduction of 1 dose of IPV at DTP3 contact in all OPV-using countries at least 6 months prior to a global tOPV-bOPV switch (as early as Apr 2014).
World Health Assembly, May 2012: to consider a resolution on the tOPV-bOPV switch.

23. Summary
a new definition of, and strategy for, the 'endgame' may accelerate eradication & reduce long-term risks.
depending on IPV price and strategy, the new endgame could be cost-neutral through certification.
by emphasizing the delivery of 1 IPV dose at the DPT3 contact, the new strategy should help to strengthen the focus & coverage of routine immunization.

24. Extra Slides

25. Major Issues (examples)
Work streams
Major Issues (examples)
Phased vs. simultaneous removal of Sabin viruses
Geographic extent and schedule for IPV use
Policy development
Global bOPV availability (i.e. national producers)
Feasibility of restarting tOPV production from bOPV
Regulatory issues, supply & price for largescale ID IPV use
Supply & Product Development
Nature of immune response & duration of priming after 1 IPV dose
Further characterization of VDPV risks
Research
Criteria to validate WPV type 2 elimination; cVDPV2 elimination
Containment requirements for type 2 after tOPV-bOPV switch
Supplementary surveillance (incl. environmental surveillance)
Surveillance & containment
Operations & logistics
Synchronization of tOPV-bOPV switch globally
Safe handling/destruction of residual stocks
Budget & financing
Budget implication of IPV introduction
Multi-year business & financing plan 25