Contents

Current Status of Polio

Polio: Global Caseload

. 1.Poliomyelitis. Available at: http://www.who.int/mediacentre/factsheets/fs114/en/. Cited on May 7, 2013.

Decrease in polio cases by 99% since 1988 in more than 125 endemic countries1

WPV Cases in 2009-2010

WPV-Wild polio virus; cVDPV2-circulating vaccine derived paralytic viruses type 2

1. CDC assessment of risks to the global polio eradication initiative (GPEI) strategic plan 2010-2012. Available at:http://www.cdc.gov/vaccines/programs/global/downloads/gid-polio-risk-analysis-q2.pdf. Cited on May 5, 2013.

Geographic distribution of wild poliovirus (WPV) cases by serotype and of circulating vaccine-derived polioviruses (VDPV), onset during January–June 2010 .

A total of 452 WPV1 cases were reported in Tajikistan during January–June 2010.

In Afghanistan 11 WPV cases in 2009 and 10 WPV cases in 2010 were identified.

In India, 25 WPV cases (7 WPV1 and 18 WPV3) were identified during January–June 2010 as compared with 151 (28 WPV1, 122 WPV3, 1 mixed WPV1/WPV3) during January–June 2009.1

Polio in India

WHO-World Health Organization1..Polio Eradication. Available at http://www.unicef.org/india/health_3729.htm. Cited on May 7, 2013.

Not Really a Time to Celebrate

• To achieve WHO certification for Polio eradication:

– 0 WPV case reported for 3 consecutive years i.e from 13-01-11 to 12-01-14

• To achieve actual polio eradication:

– 0 Polio 0 WPV 0 VDPV 0 VAPP

VDPV: No Longer Just a Theoretical Concern

• Vaccine Derived Polio Virus or VDPVs:

– Definition: derivatives of Sabin OPV strains exhibiting 1–15% divergence in the sequence of viral protein vp1

– Origin: accumulation of mutations by

• Replication of the live vaccine strains within the vaccinee’s gut

• Recombination with other enteroviruses

– Potential to cause paralytic polio in humans and sustained circulation

WHO. WER, 2006.

VDPV can Cause Sustained Person-to-Person Spread and Reintroduction of Poliovirus

• VDPVs are classified into 3 categories:

– Circulating VDPVs (cVDPVs)

• Emerge in areas with inadequate OPV coverage

• May lead to sustained person-to-person spread

– Immunodeficient-associated VDPVs (iVDPVs)

• Isolated from persons with primary immunodeficiencies who exhibit prolonged VDPV infection after OPV exposure

• Potential source of PV reintroduction in the future; they may excrete virus for up to 20 years

– Ambiguous VDPVs (aVDPVs)

• Clinical isolates from persons with no known immunodeficiency or

• Environmental isolates with unidentified source

WHO. WER, 2006 . McLennan, et al. Lancet, 2000

Outbreaks of cVDPV

Known risk

Philippines 2001

3 cases

Hispaniola* 2000

22 cases

Madagascar2002

4 cases

China2004

2 cases

Egypt** 1988-9332 cases

*Haiti & Dominique Rep.**Based on retrospective analysis of isolates.

VAPP: Rare But Serious

• Vaccine-Associated Paralytic Polio:– Defined as those cases of AFP from whose stool samples,

vaccine-related poliovirus but no wild polio virus is isolated – Caused by mutation of vaccine virus during replication in

the gut of vaccinee (reversion to neurovirulence)

• VAPP is indistinguishable from naturally occurring polio• Same incubation period, range of severity and Case

Fatality Rate• May affect both vaccinees & close contacts.

1. Sutter et al. Vaccines. 2008.2. Paul. Vaccine, 2004 .3. John. Bull of the WHO, 2004.

Burden of VAPP

1.Introduction of inactivated poliovirus vaccine into oral poliovirus vaccine-using countries. Weekly epidemiological record.2003; 78:241–252.

2. Kohler et al. Bulletin of the World Health Organization. 2002; 80 (3):210-216.

Challenges in Eradication of Polio

Current status, threats with OPV

Oral Polio Vaccine: Associated Risks

• Oral poliovirus vaccine (OPV) is highly effective tool in polio eradication. 1

• It is associated with noticeable, rare cases of vaccine-associated paralytic polio (VAPP).2

• Even 15 doses of OPV cannot provide immunity

• With insufficient coverage, viruses from OPV can evolve to become circulating vaccine-derived poliovirus (cVDPV) that causes paralytic polio cases and outbreaks.1

1.Thompson KM, et al. Expert Rev Vaccines. 2012;11:449–459.

2.Grassly NC et al. Science. 2006;314:1150-1153.

How many movie halls are there in ELANTE MALL?

VDPV: The Risk Persists

VDPV: Vaccine-derived polioviruses; OPV:Oral polio vaccine

1.Verma R, et al. Hum Vacc Immunother. 2012;8:956–958.

As long as OPV is used, the risk of VDPV persists among the unprotected children.1

India: Risk of Importation of Poliovirus

• Despite being declared non-endemic, the risk of polio still persists in India.

• Being in the neighbourhood of two polio endemic countries, the risk of importation of polio cannot be ignored.

• Earlier, India has exported polio to other countries (Nepal, Tajikistan and Angola). There is a risk of import of poliovirus from the same routes.

• Since 2000, about 44 polio free countries have suffered from one or more importations of WPV.1

WPV:Wild polio virus1.Key Messages:Avaiable at:www.unicef.org/india/13_Jan_Breifing_note.doc . Cited on May 2, 2013.

India needs to maintain high population immunity, especially in the high-risk areas and among the most vulnerable population.1

GPEI: Polio Endgame Strategy

Polio Endgame

The ‘Polio Endgame’ refers to management of the ‘post-eradication’ risks due to OPV.1

OPV:Oral polio vaccine; VDPV:Vaccine-derived polioviruses; WPV:Wild polio virus; bOPV:bivalent oral polio vaccine:tOPV:trivalent polio vaccine .1.A New Strategy for the ‘Polio Endgame’? Orientation for the SAGE IPV Working Group. 2011.Available at

:http://www.who.int/immunization/sage/1_SAGE_IPV_WG_PolioEndgame_22Sept2011_nov11.pdf. Cited May 3, 2013.

Why consider polio endgame?

•Type 2 cVDPV is the main ‘post-eradicaton’ concern.

•New bOPV is better than tOPV (for WPV1 and WPV3) and a possible option to replace tOPV.

•Low cost IPV options may allow all countries to continue type 2 immunization, according to the need.1

Polio-free World: What It Means?

Transition from all OPV to sequential OPV-IPV and all IPV schedules has been implemented in several countries, in order to eliminate live poliovirus.1

OPV: Oral polio vaccine; IPV-Inactivated polio vaccine; VAPP: Vaccine-associated paralytic poliomyelitis ; VDPV::Vaccine-derived polioviruses 

1.Verma R, et al. Hum Vacc Immunother. 2012;8:956–958.

Polio free world Phasing out of OPV to

eliminate the risk of VAPP or VDPV infections.

Global Polio Eradication Initiative: What has been Achieved so far?

According to October 2012 data,

• Over 99% reduction in polio cases.1

• Only three countries are polio-endemic: Afghanistan, Nigeria and Pakistan.1

• There has been a substantial reduction in number of WPV cases in the last two years.1

1. Poliomyelitis. Fact sheet N°114. October 2012. Available at: http://www.who.int/mediacentre/factsheets/fs114/en/#. Cited May 3, 2013.2. Polio this week-As of 17 April 2013. Available at: http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx. Cited May 3, 2013.

WPV Cases2

Total cases Year-to-date 2013 Year-to-date 2012 Total in 2012

Globally 18 41 223• in endemic countries 18 38 217• in non-endemic countries 0 3 6

Introducing IPV

In the post-eradication era, where

•OPV has to be discontinued (to interrupt VAPP and VDPV•Vaccination against polio cannot be stopped,

IPV has an important role. 1

OPV: Oral polio vaccine; VAPP: Vaccine-associated paralytic poliomyelitis ; VDPV::Vaccine-derived polioviruses ; IPV:Inactivated polio vaccine.1. Verma R, et al. Hum Vacc Immunother. 2012;8:956–958.2. Thompson KM, et al. Expert Rev Vaccines. 2012;11:449–459.

Introducing IPV

Risk of VAPP increases by 2000-3200 fold in immuno-compromised subjects OPV contraindicated

In countries where only OPV is implemented, VAPP has become major source of disease, hence increasing its unacceptability.

This prompted many countries to switch to full IPV-schedule

Atkinson. Pink Book, 2008 . WHO. WER, 2004. Jonh. Bull of the WHO, 2002.

WHO. GPEI Strategic Plan 2004-2008. Available at: http://www.polioeradication.org/content/publications/2004stratplan.pdf, 2009.

IPV in India: Why and When?

OPV: Oral polio vaccine; IPV-Inactivated polio vaccine; VAPP: Vaccine-associated paralytic poliomyelitis ; VDPV::Vaccine-derived polioviruses.

1.Thompson KM, et al. Expert Rev Vaccines. 2012;11:449–459.

IPV: High Immunogenicity, Even After 2 Doses

• Extensive data on high immunogenicity of IPV with various schedules in countries throughout the world:

– High immunogenicity of IPV even in developing and tropical countries where OPV is suboptimal

• In 54 trials with IPV/IPV-containing vaccines in 24 tropical and 30 low-income countries since 1977

– High immunogenicity after 2 doses: • In 30 trials involving >4500 subjects, seroprotection against poliovirus:

– 89–100% against type 1– 92–100% against type 2– 70–100% against type 3

– Immunogenicity expectedly reinforced after 3rd dose*: • In 48 trials involving >6000 subjects

– 95–100% seroprotection rates against all 3 types

Polio Eradication Committee et al. Indian Pediatr. 2008

Plotkin & Vidor. Vaccines. 2008

IPV Provides Good Herd Effect

• Herd Effect:

– Protection of the population to a greater extent than that expected by the actual population vaccination coverage

• Excellent herd effect reported wherever IPV used on large scale

– e.g. : USA

John. Expert Rev Vaccines. 2009

Stickle. Am J Public Health. 1954

Herd Immunity Effect Induced by IPV in the USA, 1958 to 1961

Stickle G. Am J Public Health. 1964;54:1222–1229.

Expected with IPV effect limited to vaccinees only

Observed average cases in pre IPV era

Herd Immunity Effect Induced by IPV in the USA, 1958 to 1961

Stickle G. Am J Public Health. 1964;54:1222–1229.

Expected in absence of IPV

Expected with IPV effect limited to vaccinees only

Observed average cases in pre IPV era

Stickle G. Am J Public Health. 1964;54:1222–1229.

Herd Immunity Effect Induced by IPV in the USA, 1958 to 1961

Expected in absence of IPV

Expected with IPV effect limited to vaccinees only

Observed cases

Observed average cases in pre IPV era

Two people who scored centuries in the THIRD ASHES test?

Adapted from 1, 11

Summary of Key Attributes of OPV and IPV

OPV (Oral, live attenuated vaccine) IPV (Injectable, inactivated vaccine

Produced from Sabin (attenuated) strains Produced from wild poliovirus strainsHigh systemic immunity High systemic immunityHigh mucosal immunity Lower mucosal immunityHigh efficacy (but suboptimal efficacy in tropical countries) High efficacy

Contact immunity No contact immunityHerd immunity Herd immunityRisk of VAPP No risk of VAPPRisk of VDPVs No risk of VDPVsContraindicated in immunodeficient individuals

The only polio vaccine recommended for immunodeficient individuals

Ease of administration (oral drops) but thermosensitive requiring efficient cold chain Necessity of skilled personnel for injection

Stand alone vaccine only Available as stand alone and in combination vaccines

Sutter, et al. Vaccines. 2008. Plotkin & Vidor . Vaccines. 2008 .

Rationale for shifting to IPV

• “At present, it is becoming more and more apparent that long-term global eradication of poliovirus is impossible without IPV”

– Safest polio vaccine (no risk of VAPP/VDPVs)

– Only polio vaccine recommended to immunodeficient individuals

– High immunogenicity:

– Strong evidence of efficacy/effectiveness

– Well-documented herd effect

Dutta. Vaccine, 2008. WHO. WER, 2003. Plotkin & Vidor . Vaccines, 2008.

Shifting from OPV to IPV: Challenges Faced

• Higher cost may pose further problem if type2 VDPV emerges during or immediately after the switch. In such a case, children immune to WPV1 and WPV3 will not be immune due to unaffordability of IPV.1

IPV:Inactivated polio vaccine; VDPV:Vaccine-derived polioviruses; WPV:Wild polio virus.

1.Ending polio: one type at a time. Available at: http://www.who.int/bulletin/volumes/90/7/12-020712/en/ . Cited May 2, 2013.

Reducing cost of IPV1

•Reduce the number of doses, •Use a fractional (1/5th) dose, •Increase the interval between doses and •Produce the vaccine in resource-limited settings.

IAP Recommendations for IPV

Indian Academy of Pediatrics: Recommendations

Indian Association of Pediatrics (IAP) has taken the initiative towards the post-eradication preparation and adopted a sequential IPV-OPV schedule.1

OPV:Oral polio vaccine: bOPV:bivalent oral polio vaccine; IPV:Oral polio vaccine; VAPPV : Vaccine-associated paralytic poliomyelitis;VDPV:Vaccine-derived polioviruses1.Indian Academy of Pediatrics Committee on Immunization. Consensus recommendations on immunization and IAP immunization timetable 2012. Indian Pediatrics. 2012;49:549–564. .

IAP Recommendations: Primary Schedule

• Alternatively, three doses of IPV can be used in the primary schedule at 8 and 16 weeks.

1.Indian Academy of Pediatrics Committee on Immunization. Consensus recommendations on immunization and IAP immunization timetable 2012. Indian Pediatrics. 2012;49:549–564.

Primary Schedule Recommendations1

•Birth dose of OPV •Three primary doses of IPV at 6, 10 and 14 weeks •Two doses of OPV at 6 and 9 months •Booster dose of IPV at 15–18 months and OPV at 5 years

IAP Recommendations: Primary Schedule

Additional Instructions on the Primary OPV/IPV Schedule1

• IPV should be given intramuscularly (preferably) or subcutaneously.

• It may be offered as a component of combination vaccines.

• In case of unaffordability or unavailability of IPV, the primary immunization schedule must be completed with three doses of OPV given at 6, 10, and 14 weeks.

• No child should be left without adequate protection against WPV.

• Also, all OPV doses (mono-, bi- or trivalent) offered through supplemental immunization activities, should be provided.

OPV: Oral polio vaccine; IPV: Inactivated polio vaccine1.Indian Academy of Pediatrics Committee on Immunization. Consensus recommendations on immunization and IAP immunization

timetable 2012. Indian Pediatrics. 2012;49:549–564.

IAP Recommendations: Catch-up Schedule

• In children less than 5 years of age who have completed primary immunization with OPV, IPV may be offered as ‘catch up vaccination’.

• Schedule: two doses at two months interval followed by a third dose 6 months after 1st dose.

• Such a schedule ensures long lasting protection against poliovirus.1

1.Indian Academy of Pediatrics Committee on Immunization. Consensus recommendations on immunization and IAP immunization timetable 2012. Indian Pediatrics. 2012;49:549–564.

Role of Pediatricians: Polio-Eradication

Improving Immunization

• Improving the coverage of routine immunization is the best way to eradicate polio1

1.Choudhury P, et al. Vaccine. 2011;29:8317–8322.

Barriers to Polio Eradication in India

a. Parents’ lack of awareness of the importance of polio vaccination

b. Parents’ lack of confidence in polio vaccine

c. Fear of side effects

d. Lack of time or priority

e. Religious beliefs

f. Superstition

g. Cultural beliefs1

1.Choudhury P, et al. Vaccine. 2011;29:8317–8322.

Thank you