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

Polio Eradication & Endgame Strategic Plan 2013-2018 Major Objectives of Polio Eradication & Endgame Strategic Plan 2013-2018 Target last wild polio case Certification Last OPV2 use 2013 2014 2015 2016 2017 2018 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

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

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)

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

Single IPV dose closes humoral immunity gaps in OPV-vaccinated infants (Côte d'Ivoire, 1990-91) Percent seropositive Impact of IPV vs. OPV booster in OPV vaccinated sero-negative children 9 months of age N=346

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

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 38.9-74.2% and 52.8-75.7%, 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);

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 *http://dx.doi.org/10.1016/S0140-6736(14)60934-X

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

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

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)

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

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

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

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

Introduction of IPV: Cold chain availability National cold chain assessment carried out in 2014-15 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

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

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

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”

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

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

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

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

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

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

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)

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

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, 2013-14

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)

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

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)

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

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)

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

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

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

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%

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

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?

Thank you

Backup slides research

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)

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

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

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

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

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

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