1. Withdrawal of OPV type 2 in India
Implementing the Polio Endgame Strategy
Meeting of India Expert Advisory Group for Polio Eradication
Dr Sunil Bahl
WHO
20 March 2014

2. Polio Eradication & Endgame Strategic Plan 2013-2018
Major Objectives of
Polio Eradication & Endgame Strategic Plan
Target last wild
polio case
Certification
Last OPV2 use
Objective 1
Virus detection & interruption
Introduce IPV; withdraw OPV2
Wild virus
interruption
Outbreak response
(esp. cVDPVs)
RI strengthening & OPV2 withdrawal preparations
OPV 1 & 3
withdrawal preparations 2
RI strengthening & OPV withdrawal 3
Containment & certification
Finalize long-term containment plans
Complete containment
& certification globally
Consultation & strategic plan
Initiate implementation of legacy plan 4
Legacy Planning

3. Rationale for OPV type 2 withdrawal (switch from trivalent OPV to bivalent OPV)
Currently, the risks associated with the type 2 component of tOPV outweigh the benefits
Since 1999, type 2 wild poliovirus has not been detected
The type 2 component of tOPV:
Causes more than 90% of vaccine-derived polio viruses (VDPVs)
Causes approx. 40% of vaccine-associated paralytic polio (VAPP) cases
Interferes with the immune response to poliovirus types 1 and 3 in tOPV

4. 5 Preparedness Criteria for OPV2 withdrawal
Inactivated Polio Vaccine (IPV) introduction in RI
Bivalent OPV (bOPV) licensure & availability for use in RI
Surveillance & mOPV2 Stockpile
Containment of type 2 polioviruses
Verification of elimination of wild poliovirus type 2 (WPV2)

5. National IPV introduction plan (August 2014) – key elements
Policy decision
Oversight & Coordination mechanism
Vaccine requirement
Vaccine formulations/ availability
Cold chain
Capacity building
Advocacy, communication & social mobilization
Injection safety & waste management
AEFI surveillance
Monitoring & evaluation
Recording & reporting
Roles of stakeholders
Addressing challenges
Introduction timelines

6. Single IPV dose closes humoral immunity gaps in OPV-vaccinated infants
(Côte d'Ivoire, )
Percent seropositive
Impact of IPV vs. OPV booster in OPV vaccinated sero-negative children 9 months of age
N=346

7. Study in India confirms a single IPV dose closes humoral immunity gap in OPV primed children (Moradabad, 2009)
Percent seropositive
Age: 6-9 months
OPV primed children
Single dose of IPV given at day 0 of study
Blood collected at baseline & 28 days
N= 862

8. Single IPV boosts mucosal immunity in children with multiple OPV doses (Moradabad, 2011)10 20 30 40
Day 31
Day 35
Day 42
No Vaccine
bOPV
IPV
P1 excretion after day 28 challenge (%)
50%
IPV reduced fecal excretion for poliovirus types 1 and 3 between % and %, respectively, compared to control
After challenge with vaccine viruses, the reduction in fecal excretion was also greater in children who received an additional dose of IPV prior to challenge, than children who received an additional dose of bOPV
75%
6-11 months
5-6 yrs
10-11 yrs
N=990
*Hamid Jafari et al. Efficacy of inactivated poliovirus vaccine in India. Science 345, 922 (2014);

9. STUDY
FINDINGS
A dose of IPV given to children aged 1–4 years previously vaccinated with OPV substantially increased humoral and intestinal mucosal immunity to poliovirus
Serum neutralizing antibodies were substantially increased and these children were significantly less likely to shed poliovirus after challenge with bOPV
Add hyperlink to the back-up graphics on the back up *

10. Single IPV provides high immunity base (seroconversion + priming) in OPV naïve children (Cuba, 2010)
Study summary
Poliovirus type 2
1st dose seroconversion
63%
Priming
98%
1st dose seroconversion & priming
99%
Cumulative two-dose seroconversion
100%
Single full dose IPV in OPV naive 4-month old infants sero- converts 63% and primes 98% infants against type 2.
N= 310 10

11. Single dose IPV introduction in routine schedule eliminated VAPP in Hungary (Data:1961-2011)
IPV at 3 months
VAPP number
In 2006,
IPV-only
schedule
Year

12. Early versus later IPV administration
Baseline (4-month IPV dose):
63% seroconversion, 98% priming; 99% seroconversion & priming
Later administration (potential gains):
?seroconversion (>63%), ?priming (>98%)
Earlier administration (potential losses):
seroconversion decreased (32-39% vs 63%)
2-dose IPV studies suggest priming also lower by early IPV(<90% seroconversion)

13. Introduction of IPV – Policy decision
NTAGI recommendations (June 2014)
Introduction of IPV under routine immunization in 2015
Single, full dose of IPV at DPT3/OPV3 contact (14 weeks of age or later)
IPV dose in addition to OPV
Decision consistent with SAGE recommendations for IPV use
Nationwide introduction of single dose of IPV in RI in October 2015

14. Introduction of IPV : Oversight & Coordination Mechanism
National
State
District
Vaccine Introduction Working Group (VIWG)
ICMR, WHO, UNICEF, BMGF, UNDP & ITSU
State Task Force for Immunization
District Task Force for Immunization

15. Introduction of IPV - Vaccine requirement
Target population: 27 million (birth cohort)
Annual vaccine requirement for 1st year:
Birth cohort + wastage + buffer = ~40 million doses
Cost:
10 dose vial: 1 USD/dose
5 dose vial: 1.9 USD/dose
1st year requirement of IPV to be supported by GAVI Alliance

16. Introduction of IPV: Vaccine formulations/availability
Vaccine formulations: Single dose, 5 dose & 10 doses formulations
Formulations currently licensed in India: pre-filled single dose, single dose vials, 10 dose vials
5 dose vials under consideration for licensure
Open vial policy to be applicable
A mix of different formulations may have to be used during 1st year considering the large requirement and limited availability of different formulations

17. Introduction of IPV: Cold chain availability
National cold chain assessment carried out in
Additional cold chain space required to manage IPV at state, district and sub-district levels worked out
Cold chain capacity being increased at national/state/ district/ sub-district stores to meet the requirements
Bulk space of central and state stores being increased & procurement of deep freezers, ILRs, solar direct drives for district/sub-district vaccine storage points underway
National Cold chain and vaccine management plan developed and being implemented to improve vaccine management
Introduction and scale-up of pentavalent vaccine in states freeing up cold chain space

18. Introduction of IPV: Capacity building of health staff
National
National orientation for state master trainers
May 2015
State
State orientation for all DIOs/partners
District
District orientation for all BMOs
June-July 2015
Block
Block orientation for all MOs/ANMs/ASHAs
August-September 2015
Training modules under development
One day operational/communication training for ANMs/ASHAs
Independent monitoring of quality and completeness of trainings

19. Introduction of IPV: Advocacy, communication & mobilization
Communication strategy for IPV introduction developed
Advocacy efforts with various stakeholders an integral part of the strategy
Sensitization of medical professionals through Indian Medical Association & Indian Academy of Pediatrics has begun
Social Mobilization Network for polio to be engaged for mobilization of communities in UP, Bihar and West Bengal
Media sensitization plan being developed

20. Introduction of IPV: Injection safety and waste management
Injection safety protocols as per RI guidelines
Injection safety to be part of the training module being developed for health workers
Waste management as per “Biomedical waste management & handling rules”

21. Introduction of IPV: Strengthening AEFI surveillance
Revised national guidelines on AEFI surveillance & causality assessment finalized
Capacity building of national and state committees on causality assessments planned
District level trainings planned to ensure systematic reporting & investigation of all AEFI cases
Capacity building of state spokespersons to handle media queries an integral part of plan

22. Introduction of IPV: Monitoring & evaluation
Standardized checklists for new vaccine introduction to be used for assessment of preparedness in all districts/states
National and state observers/partners to be involved with monitoring progress of activities
State and District Task forces to ensure preparedness & implementation at state and district levels is per timelines and protocol
National level monitoring by Vaccine Introduction Working Group

23. Introduction of IPV: Recording & reporting
Recording & reporting tools being modified
Mother & Child Protection card revised to include IPV
Reporting formats and Health Management Information System (HMIS) being modified to capture data on IPV

24. Introduction of IPV: Role of partner agencies
WHO
UNICEF & other SM Net Partners
Evidence for policy
Planning & Operational support
Capacity building
Monitoring preparedness & implementation
Communication strategy development
Communication & media, social mobilization & capacity development
Cold chain support
Monitoring
ROTARY
OTHERS
Advocacy
IEC activities
Operational support
Engaging state & local bodies for information dissemination & advocacy
Engaging IMA/IAP particularly in private sector

25. Introduction of IPV - Addressing key challenges
Plans to address challenges
Accountability through task forces
Oversight by VIWG
Strong coordination between stakeholders
Simultaneous launch of a new vaccine in entire country
Well planned cascading trainings with quality control
Simple and effective training modules
Training the large workforce
Advance planning followed by monitoring
Balancing supply of 5 and 10 dose vials rationally
Trainings to be adjusted depending on formulation supplied
Timely, appropriate and adequate supply of vaccine and logistics
Strengthening reporting, investigations, causality assessments and communication related to AEFIs
Managing AEFIs post- introduction
Targeted communication strategy
Vaccine acceptance , concern on additional injection

26. IPV introduction timeline, India
Plan development
IPV licensure & procurement
Monthly state & district task force meetings
Preparedness assessment
Advocacy/Communication
National Orientation followed by cascade to state/district/block training
IPV supply
IPV LAUNCH
NTAGI approval
Oversight by VIWG/state & district task force
2014
2015

27. 5 Preparedness Criteria for OPV2 withdrawal
Inactivated Polio Vaccine (IPV) introduction in RI
Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI
Surveillance & Stockpile
Containment of type 2 polioviruses
Verification of elimination of wild poliovirus type 2 (WPV2)

28. Criteria 2: bOPV licensure and availability for use in RI
Licensure of bOPV for use in routine immunization under process
EPI vaccine trial conducted : 5 arm study to assess efficacy of bOPV vs tOPV (with or without IPV) when given in EPI schedule
Trial report submitted by manufacturer to DCGI
Timeline for procurement of bOPV being worked out considering procurement lead time
tOPV procurement and supply to be adjusted to ensure no stock-outs prior to switch from tOPV to bOPV & minimal surplus stocks post-switch

29. India EPI polio vaccine trial:
Seroprevalence after OPV doses given at birth and 6,10 & 14 wk
Arm
Sample size:
180 subject in each arm A B C D E
Poliovirus type
tOPV +
IPV at 14 wk
bOPV
IPV at 14 & 18 wk
Type 1 %
99.4
98.8
Type 2 %
98.2
23.8 78 83
Type 3 %
91.6
An additional dose of IPV in arm E at wk 18 significantly boosted the immunity against poliovirus type 2 (to 97% at wk 19), exhibiting the priming effect of the first IPV dose
Study conducted in Pune, Hyderabad, Visakhapatnam,

30. 5 Preparedness Criteria for OPV2 withdrawal
Inactivated Polio Vaccine (IPV) introduction in RI
Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI
Surveillance & mOPV2 Stockpile
Containment of type 2 polioviruses
Verification of elimination of wild poliovirus type 2 (WPV2)

31. Criteria 3: Surveillance and Stockpile
Additional sites
in Mumbai
Hyderabad
Essential to maintain sensitive AFP surveillance system to ensure timely detection of WPV, VDPV and sabin viruses
Targeted expansion of environmental surveillance to supplement AFP surveillance
Global mOPV2 stockpile
Maintain preparedness for type 2 outbreak
Immediate type 2 notification
Outbreak response as per global guidelines
Existing environmental
surveillance sites
Expansion plans in 2015

32. 5 Preparedness Criteria for OPV2 withdrawal
Inactivated Polio Vaccine (IPV) introduction in RI
Bivalent oral polio vaccine (bOPV) availability for use in RI
Surveillance & mOPV2 Stockpile
Containment of type 2 polioviruses
Verification of elimination of wild poliovirus type 2 (WPV2)

33. Criteria 4: Containment of type 2 polioviruses
National Task Force for laboratory containment lead by ICMR
Phase I: Preparation for containment of poliovirus type 2
National laboratory survey and poliovirus type 2 inventory;
Destruction of unneeded poliovirus type 2 materials in non-essential facilities;
Transfer of needed poliovirus type 2 materials to essential facilities;
Designated essential facilities obtain certification for containment
Phase IIa: Containment of wild poliovirus type 2 (WPV2)
All WPV2 are contained in essential facilities that have been certified in Phase I
Phase IIb: Containment of OPV/Sabin type 2 polioviruses
All OPV2/Sabin2 are contained in essential facilities that have been certified in Phase I.
National Task Force to submit documentation to the National Certification Committee for Polio Eradication/ Regional Certification Commission for Polio Eradication

34. 5 Preparedness Criteria for OPV2 withdrawal
Inactivated Polio Vaccine (IPV) introduction in RI
Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI
Surveillance & mOPV2 Stockpile
Containment of type 2 polioviruses
Verification of elimination of wild poliovirus type 2 (WPV2)

35. Last wild poliovirus type 2 case, India
Criteria 5: Verification of elimination of WPV2
Last wild poliovirus type 2 case, India
WPV2
24/10/1999
Aligarh (UP)
National Certification Committee for Polio eradication to document elimination of WPV2 and report to Regional Certification Commission for Polio Eradication

36. Key components of tOPV to bOPV switch plan
Establish management structure, National Switch Validation Committee (NSVC)
SWITCH PERIOD
Develop National Switch Plan
PREPARE
tOPV inventory, adjust delivery
Secure funding, monitoring plan
PREPARE
Adjust tOPV orders
Order bOPV
PREPARE
Last tOPV delivery
Launch communication strategy
PREPARE
Last tOPV delivery to periphery
Switch monitors identified
IMPLEMENT
Train monitors
Train health staff
Distribute bOPV
VALIDATE
tOPV disposal
Validation by switch monitors
Report to NSVC
Validation by NSVC
World Health Assembly
SAGE
Confirmation of switch dates
2015
2016

37. Addressing challenges
Strong accountability mechanism, oversight by VIWG and monitoring
Pan-India inventory/recall of tOPV and supply of bOPV
Well planned cascading trainings, using the opportunity of NID vaccinator’s training
Awareness amongst health workforce about tOPV withdrawal & switch
Build on recently concluded task of phase 1 containment
Containment of WPV2 and tOPV
Targeted communications engaging technical bodies like IAP and IMA
Large private sector using tOPV

38. Seroprevalence for polio in India
Addressing challenges: Achieving high type 2 immunity prior to tOPV to bOPV switch
Introducing IPV in RI 6 mths prior to switch
Conducting 2 NIDs with tOPV in qtr 1, 2016
Improving routine immunization coverage through system strengthening
Catch- up campaigns (Mission Indradhanush)
Seroprevalence for polio in India
Moradabad UP
2007
AFP cases UP
2008–09
2009
UP & Bihar
2010
2011
UP &Bihar
2012
Bihar, MP & Mumbai 2014
Age
6-7 mo
6-11 mo
Type 1
78%
96.5%
99%
98%
98.5%
95.2%
97.3%
Type 2
56%
33.7%
75%
65%
85%
88.3%
97.9%
Type 3
69%
42.6%
49%
77%
88.2%
81.8%
86.9%

39. Proposed research studies
Periodic Sero-surveys: To assess the seroprevalence to poliovirus serotypes
Mucosal immunity study: To assess level of mucosal immunity against all three poliovirus types in the adolescents and adult age groups
mOPV1/IPV EPI polio vaccine study: To assess immunogenicity and safety of mOPV1/IPV when given in EPI schedule

40. Questions to the IEAG
Is the national preparedness plan for IPV introduction appropriate and adequate?
Is preparedness for type 2 withdrawal on track in India?
Does the IEAG agree with the proposed research studies?

41. Thank you

42. Backup slides research

43. Findings of recent studies on IPV
One dose of IPV provides significantly high humoral immunity in OPV primed children, especially against type 2 (Côte d'Ivoire study and Moradabad IPV study, India, 2009)
Single dose of IPV given in OPV primed children boosts mucosal immunity in all age groups (Moradabad mucosal immunity study 2011)
One dose of IPV provides excellent immunity base (sero-conversion and priming) (Cuba study 2010)

44. IPV Study Moradabad (2009)
IPV (IM) GSK
IPV (IM) Panacea
Single dose of IPV given in OPV primed children, closes humoral immunity gap, especially for type 2

45. Mucosal immunity study Moradabad-2011
Proportion of subjects excreting P1 after bOPV challenge
Single dose of IPV given in OPV primed children, substantially boosts mucosal immunity in all age groups (6-11 months, 5 and 10 years) – effect larger than with a dose of bOPV
Day 3
Day 7
Day 14

46. Cuba study 2010
One dose of IPV provides excellent immunity base against all three serotypes (nearly 100% seroconversion or priming for all serotypes)

47. Summary of existing information on poliovirus immunity
3 to 4 tOPV doses (SIAs plus RI) provide high immunity against type 2
bOPV provides better protection for type 1 and type 3 than an equivalent number of tOPV doses
One dose of IPV provides effective boost to humoral and mucosal immunity to all 3 types in OPV immunized children
One dose of IPV provides immunologic priming in > 95% children against all 3 serotypes

48. Excretion of poliovirus at day 7 (week 19) after tOPV challenge at week 18 in arms A,B & D
7 days after challenge
28 days after challenge
Inference:
Good mucosal response for type 1 & type 3 across all three arms
Poor mucosal response against type 2 for children receiving bOPV

49. Single dose IPV introduction in routine schedule eliminated VAPP in Hungary (Data:1961-2011)
IPV at 3 months
VAPP number
In 2006,
IPV-only
schedule
Year