Polio End-game: What are the implications on polio vaccination policy? Dr Raju Shah

2010 * * data as on 30 October 2010 Last detected case January 2011 What more for – a polio free India! No WPV from any source since January 2011 India is no longer an endemic country!

cVDPV cases, India cVDPV cases detected in % due to type 2 District Type Badaun300 Bulandshahar200 Ghaziabad010 Meerut200 Moradabad200 Pilibhit400 Shahjahanpur210 Total1520

iVDPV & aVDPV cases, India 2009 to 2012* *: data as on 10 March 2012 iVDPVaVDPV ambiguous VDPV (aVDPV): origin uncertain e.g. single isolate from single AFP case, non-immunodeficient person

5 What is the polio 'endgame'?

6 '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

7 The endgame: addressing risks due to the oral polio vaccine (OPV) after eradication Cases of Vaccine-Associated Paralytic Poliomyelitis (VAPP): very rare severe adverse event; occurs in OPV recipients or a close contact. Outbreaks of circulating vaccine-derived poliovirus (cVDPV): very rare event; occurs when vaccine virus regains ability to paralyze and circulate.

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

9 Why is the world now rethinking the Polio Endgame?

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

11 Risks of Polio After 'Eradication' with Continued OPV Use VAPP 2-4/m birth cohort stable iVDPV39 identified ~1 decreases (since 1962) cVDPV0-3* per year ~20 increases FrequencyAnnual Evolution Risk to dateburden over time *based on current understanding

12 Recent developments allow a major 'rethink' of the endgame New bivalent vaccine (bOPV) outperforms trivalent OPV. New diagnostics show type 2 OPV is the main problem. New, very low cost 'IPV options' can allow all countries to continue type 2 immunization if they want/need to.

Best Solution Switch to IPV from OPV Problem is COST!!! Any developing country can afford?

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 All rights reserved Standalone IPV IPV - hexa combo Data in WHO HQ as of Sep 2010 IPV - penta combo Unknown Not applicable Background: Countries with IPV Use

“IPV would serve as a kind of Insurance policy.” Roland Sutter WHO, Research and production coordinator GPE

How does universal or selective use of IPV helps? Humoral immunity: a number of trials have addressed this question One dose of IPV after multiple doses of OPV effectively closes the remaining immunity gaps (~90% of seronegative cases will seroconvert) In seropositive individuals, a dramatic boosting of antibody titers is seen (~70-90%) After boosting, the antibody persist and then decline to a new baseline that is higher that before the IPV booster dose

Thinking of Affordable IPV Strategy: Approaches: Enables IPV production in developing countries with less or non-infectious strain Use adjuvant to reduce antigen contents per dose Develop intradermal (ID) device or micro- needle patch to stretch doses Use fewer doses per schedule Reduce number of doses Reduce amount of dose Reduce antigen content Reduce production cost

18 Affordable IPV options in the short-term: 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 1/5 th of 1 dose of IPV could be very affordable (<$0.5/dose) 1/5 th fractional dose Expected price (high volume**) 1/5 th of 1 dose of IPV can induce a response in >90% of children Response* after 1 dose (%, intradermal IPV, Cuba) * includes seroconversion & priming

IPV introduction Benefit – impact on RI ? Timing/Age/Doses/Route – follow global SAGE recs or our own ? Frequency: 2 doses to all or in known cVDPV risk areas?

Schedule of IPV administration How to harvest optimal immunity gains of IPV : (seroconversion and antibody titers) IPV performance is negatively affected by levels of maternally-derived antibody So the timing of IPV administration should be delayed to minimize the interference effect The DTP3 visit (14 weeks in the EPI schedule) may offer the best compromise in terms of timing IPV should be introduced in routine programs at least 6 months before an anticipated switch from tOPV to bOPV

21 What are the major elements of the 'New Polio Endgame'?

22 New Polio Endgame: Guiding Principles Phased removal of Sabin/OPV viruses, beginning with highest-risk (type 2). Elimination of type 2 in parallel by switching from tOPV to bOPV for routine EPI & campaigns. Introduction of 1 IPV dose to boost immunity 6 months prior to a tOPV-bOPV switch & provide type 2 'priming'.

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

24 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 (1/5 th dose) intradermal IPV option may be essential for acceptability, cost, supply, manufacturer risk. the probability of expanded, longterm IPV use would increase substantially.

25 Advantages of the New Approach Accelerate type 1 & 3 eradication (with bOPV) Address >90% of VDPV risk while surveillance & response capacity is optimized Substantially shorten the post-eradication phase Boost routine immunization coverage (i.e. IPV at DPT3) and bridge immunity gaps

26 Potential Disadvantages of the New Approach Distraction to wild poliovirus eradication efforts in few countries. (to stop ongoing cVDPV2s; to coordinate tOPV-bOPV switch). Complications of adding a new vaccine (IPV) to shedule. (however, GPEI has introduced many new vaccines already). Risk of failure to stop new cVDPV2s as this is totally new stretegy. (but, with this approach could even 'restart' tOPV temporarily if needed). Risk of outbreaks of cVDPV 3 & 1. ( introduce IPV two doses)

Key target dates for a tOPV-bOPV switch timeline – SAGE Polio Working Group (March 26, 2012) By end-2012: cessation of the ongoing cVDPV2 in Nigeria By September 2013 (latest): introduction of one supplementary IPV dose at an immunization contact (at or above age 14 weeks) in all OPV-using countries By April 2014: replacement of tOPV with bOPV for routine & supplementary immunization globally (possibly linked to a Global Immunization Week) IPV in all OPV-using countries could begin latest by 7 September 2013, to enable a global tOPV-bOPV switch by April 2014, possibly linked to the 'global immunization week'.

Thanks