Dr Sunil BahlWHO

20 March 2014

Withdrawal of OPV type 2 in India

Implementing the Polio Endgame Strategy

Meeting of India Expert Advisory Group for Polio Eradication

2013 2014 2015 2016 2017 2018

Virus detection & interruption

Target last wild polio case

Certification

RI strengthening & OPV withdrawal

Containment & certification

Introduce IPV; withdraw OPV2

Wild virus interruption

Outbreak response (esp. cVDPVs)

RI strengthening & OPV2 withdrawal

preparations

OPV 1 & 3withdrawal

preparations

Legacy Planning

Finalize long-term containment plans

Complete containment & certification globally

Consultation & strategic plan

Initiate implementation of legacy plan

Last OPV2 use

1Objective

2

3

4

Major Objectives of Polio Eradication & Endgame Strategic Plan 2013-2018

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

1. Inactivated Polio Vaccine (IPV) introduction in RI

2. Bivalent OPV (bOPV) licensure & availability for use in RI

3. Surveillance & mOPV2 Stockpile

4. Containment of type 2 polioviruses

5. Verification of elimination of wild poliovirus type 2 (WPV2)

5 Preparedness Criteria for OPV2 withdrawal

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

14

27

5

81

100

67

0

10

20

30

40

50

60

70

80

90

100

Type 1 Type 2 Type 3

OPV Booster IPV Booster

Perc

ent s

erop

ositi

veSingle IPV dose closes humoral immunity gaps in

OPV-vaccinated infants(Côte d'Ivoire, 1990-91)

Impact of IPV vs. OPV booster in OPV vaccinated sero-negative children 9 months of age

N=346

0

10

20

30

40

50

60

70

80

90

100

Type 1 Type 2 Type 3

Baseline Day 28

• Age: 6-9 months • OPV primed children • Single dose of IPV given

at day 0 of study• Blood collected at

baseline & 28 days

Study in India confirms a single IPV dose closes humoral immunity gap in OPV primed children (Moradabad, 2009)

Perc

ent s

erop

ositi

ve

N= 862

Single IPV boosts mucosal immunity in children with multiple OPV doses (Moradabad, 2011)

010

2030

40

Day 31 Day 35 Day 42No Vaccin

ebOPV IPV

No Vaccin

ebOPV IPV

No Vaccin

ebOPV IPVP1

exc

retio

n aft

er d

ay 2

8 ch

alle

nge

(%)

6-11 months 5-6 yrs 10-11 yrs

N=990

50%

75%

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

*Hamid Jafari et al. Efficacy of inactivated poliovirus vaccine in India. Science 345, 922 (2014);

STUDYFINDINGS

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

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

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.

Single IPV provides high immunity base (seroconversion + priming) in OPV naïve children (Cuba, 2010)

N= 310

VAPP

num

ber

Year

In 1992, single-dose IPV at 3 months

In 2006, IPV-only schedule

Single dose IPV introduction in routine schedule eliminated VAPP in Hungary (Data:1961-2011)

Early versus later IPV administration

12

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)

• NTAGI recommendations (June 2014)o Introduction of IPV under routine

immunization in 2015

o Single, full dose of IPV at DPT3/OPV3 contact (14 weeks of age or later)

o IPV dose in addition to OPV

o Decision consistent with SAGE recommendations for IPV use

• Nationwide introduction of single dose of IPV in RI in October 2015

Introduction of IPV – Policy decision

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 : Oversight & Coordination Mechanism

• 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 requirement

• 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: Vaccine formulations/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 o 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: Cold chain availability

• Training modules under development

• One day operational/communication training for ANMs/ASHAs

• Independent monitoring of quality and completeness of trainings

National

• National orientation for state master trainers• May 2015

State

• State orientation for all DIOs/partners• May 2015

Distric

t

• District orientation for all BMOs• June-July 2015

Block

• Block orientation for all MOs/ANMs/ASHAs• August-September 2015

Introduction of IPV: Capacity building of health staff

• 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: Advocacy, communication & mobilization

• 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: Injection safety and waste management

• 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: Strengthening AEFI surveillance

• 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: Monitoring & evaluation

• Recording & reporting tools being modifiedo Mother & Child Protection

card revised to include IPVo Reporting formats and Health

Management Information System (HMIS) being modified to capture data on IPV

Introduction of IPV: Recording & reporting

Introduction of IPV: Role of partner agencies

WHO

• Evidence for policy• Planning & Operational

support• Capacity building• Monitoring preparedness

& implementation

UNICEF & other SM Net Partners

• Communication strategy development

• Communication & media, social mobilization & capacity development

• Cold chain support• Monitoring

ROTARY

• Advocacy• IEC activities• Operational support

OTHERS

• Engaging state & local bodies for information dissemination & advocacy

• Engaging IMA/IAP particularly in private sector

Introduction of IPV - Addressing key 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 modulesTraining 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 strategyVaccine acceptance , concern on additional injection

Key challenges Plans to address challenges

NTAGI approval

Plan development

Advocacy/Communication

Preparedness assessment

National Orientation followed by cascade to

state/district/block training

IPV LAUNCH

2014 20150

100

J un J ul Aug Sep Oct Nov Dec J an Feb Mar Apr May J un J ul Aug Sep Oct Nov Dec

IPV introduction timeline, India

Oversight by VIWG/state & district task force

IPV supply

Monthly state & district task force meetings

IPV licensure & procurement

1. Inactivated Polio Vaccine (IPV) introduction in RI

2. Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI

3. Surveillance & Stockpile

4. Containment of type 2 polioviruses

5. Verification of elimination of wild poliovirus type 2 (WPV2)

5 Preparedness Criteria for OPV2 withdrawal

• 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

Criteria 2: bOPV licensure and availability for use in RI

ArmSample size: 180 subject in each arm

A B C D E

Poliovirus type tOPVtOPV

+IPV at 14 wk

bOPVbOPV

+ IPV at 14 wk

bOPV+

IPV at 14 & 18 wk

Type 1 % 99.4 99.4 98.8 99.4 99.4

Type 2 % 98.2 99.4 23.8 78 83

Type 3 % 91.6 99.4 98.8 99.4 98.8

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

India EPI polio vaccine trial:Seroprevalence after OPV doses given at birth and 6,10 & 14 wk

Study conducted in Pune, Hyderabad, Visakhapatnam, 2013-14

1. Inactivated Polio Vaccine (IPV) introduction in RI

2. Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI

3. Surveillance & mOPV2 Stockpile

4. Containment of type 2 polioviruses

5. Verification of elimination of wild poliovirus type 2 (WPV2)

5 Preparedness Criteria for OPV2 withdrawal

• 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

Criteria 3: Surveillance and Stockpile

Additional sites in Mumbai

Hyderabad

Existing environmental surveillance sites

Expansion plans in 2015

1. Inactivated Polio Vaccine (IPV) introduction in RI

2. Bivalent oral polio vaccine (bOPV) availability for use in RI

3. Surveillance & mOPV2 Stockpile

4. Containment of type 2 polioviruses

5. Verification of elimination of wild poliovirus type 2 (WPV2)

5 Preparedness Criteria for OPV2 withdrawal

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.

Criteria 4: Containment of type 2 poliovirusesNational Task Force for laboratory containment lead by ICMR

National Task Force to submit documentation to the National Certification Committee for Polio Eradication/ Regional Certification Commission for Polio Eradication

1. Inactivated Polio Vaccine (IPV) introduction in RI

2. Bivalent oral polio vaccine (bOPV) licensure & availability for use in RI

3. Surveillance & mOPV2 Stockpile

4. Containment of type 2 polioviruses

5. Verification of elimination of wild poliovirus type 2 (WPV2)

5 Preparedness Criteria for OPV2 withdrawal

Last wild poliovirus type 2 case, India

WPV2 24/10/1999Aligarh (UP)

Criteria 5: Verification of elimination of WPV2

National Certification Committee for Polio

eradication to document elimination of WPV2 and

report to Regional Certification Commission for

Polio Eradication

Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

PLANEstablish management structure,

National Switch Validation Committee (NSVC)

Develop National Switch Plan

PREPAREtOPV inventory, adjust delivery

Secure funding, monitoring plan

2015 2016

Key components of tOPV to bOPV switch plan

PREPAREAdjust tOPV orders

Order bOPV

PREPARELast tOPV deliveryLaunch

communication strategy

PREPARELast tOPV delivery to periphery

Switch monitors identified

IMPLEMENTTrain monitors

Train health staffDistribute bOPV

SWITCH PERIOD

VALIDATEtOPV disposalValidation by

switch monitorsReport to NSVC

Validation by NSVC

World Health Assembly

SAGEConfirmation of

switch dates

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

• 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)

Addressing challenges: Achieving high type 2 immunity prior to tOPV to bOPV switch

Moradabad UP

2007AFP cases UP

2008–09Moradabad

UP2009

UP & Bihar2010

UP & Bihar2011

UP &Bihar2012

Bihar, MP & Mumbai 2014

Age 6-7 mo 6-11 mo 6-7 mo 6-7 mo 6-7 mo 6-7 mo 6-7 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%

Seroprevalence for polio in India

1. Periodic Sero-surveys: To assess the seroprevalence to poliovirus serotypes

2. Mucosal immunity study: To assess level of mucosal immunity against all three poliovirus types in the adolescents and adult age groups

3. mOPV1/IPV EPI polio vaccine study: To assess immunogenicity and safety of mOPV1/IPV when given in EPI schedule

Proposed research studies

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