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

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 2009-2011•cVDPV cases detected in 2009-10

•100% due to type 2

DistrictType 2

2009 2010 2011

Badaun 3 0 0

Bulandshahar 2 0 0

Ghaziabad 0 1 0

Meerut 2 0 0

Moradabad 2 0 0

Pilibhit 4 0 0

Shahjahanpur 2 1 0

Total 15 2 0

State Type 1 Type 2

Assam 1Bihar 3Karnataka 1Madhya Pradesh 1Rajasthan 1Uttar Pradesh 4West Bengal 1

Total 1 11

iVDPV & aVDPV cases, India 2009 to 2012*

*: data as on 10 March 2012

iVDPV aVDPV

State Type 1 Type 2 Type 3

Chhattisgarh 1Punjab 1Tamil Nadu 1Uttar Pradesh 1Odisha 1

Total 1 3 1

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-derivedPolioviruses (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

0 2 4 6 8 10 12

Years

Wild virus eradication

Global Cert Comm (1995) Certification

Expert Advisory Meeting (1998)

Certification & containment


Last WPV case OPV cessation

ACPE (2004)VDPV elimination?Wild virus

eradicationCertification & containment

VDPV elimination & validation


World Health Assembly (2008)

Post-OPV surveillance


The 'Polio Endgame' refers to management of the

'post-eradication' risks due to OPV.

9

Why is the world now rethinkingthe Polio Endgame?

10

cVDPVs (Global): Problem in Eradication

Circulating Vaccine-Derived Poliovirus Oubreaks (cVDPVs) 2000-2010

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 250-500 stable

iVDPV 39 identified ~1 decreases

(since 1962)

cVDPV 0-3* per year ~20 increases

Frequency Annual Evolution

Risk to date burden 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 2010. 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 coordinatorGPE

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

1/5th of 1 dose of IPV could be very affordable (<$0.5/dose)

1/5th fractional dose

Expected price(high volume**)

1/5th of 1 dose of IPV can induce a response in >90% of children

0

10

20

30

40

50

60

70

80

90

100

P1 P2 P3

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

0 2 4 6 8 10 12

Years

Last wild polio case trivalent OPV cessation

VDPV elimination & validation


Sequential risk management



VDPV2 elimination & validation



Parallel risk management


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 2017-18).

• 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.

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

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

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