IPV – A NEW PERSPECTIVE IN POLIO PREVENTION

A SPECIAL PRESENTATION TO PAN STAKE HOLDERSBY

R.RAMKUMAR

A brief history of Polio• First described by Michael Underwood in 1789• First outbreak described in U.S. in 1843• 21,000 paralytic cases reported in the U. S. in

1952• Global eradication in near future

A brief history of Polio Vaccine

• 1955 Inactivated vaccine

• 1961 Types 1 and 2 monovalent OPV

• 1962 Type 3 monovalent OPV

• 1963 Trivalent OPV

• 1987 Enhanced-potency IPV (eIPV)

Adapted from 1, 11

Summary of Key Attributes of OPV and IPV

Sutter et al. Vaccines, 2008

Plotkin & Vidor . Vaccines, 2008

1988

350,000 cases

125 countries

Polio Eradication Initiative: Progress 1988-2012

2012222 cases

5 countries

Wild Poliovirus 2012

Wild virus type 1

Wild virus type 3

Impact of OPV Suspension, Kano-NigeriaPoliovirus spread, 2004

Nigeria -782 cases.

Polio re-established in 6 polio-free countries.

14 countries reported imported cases from

Nigeria

Kano, Nigeria restarted OPV on 31 July 2004

?

Spread of African Epidemic

Low Season SpreadDec 2004-Mar 2005

• Saudi Arabia Dec 04• Guinea Dec 04• Ethiopia Jan 05• Cameroon Feb

05• Yemen Mar 05• Indonesia Mar

05

?

2004-5 low season cases due to imported viruses.

2005- Yemen 300, Nigeria 194, Indonesia 122, Sudan 25, Ethiopia-13

April 8, 2023

10

What exactly is polio eradication?

AFP due to

Non-polios

Infection:

OPV virus

Infection:

wild virus

Endemicity + + +

Eradication

Phase “w” + + 0

Eradication

Phase “v” + 0 0

(John TJ. Frontiers in Pediatrics 1996; NEJM 2000)(John TJ. Frontiers in Pediatrics 1996; NEJM 2000)

– Suboptimal OPV efficacy– Inadequate Herd effect– Vaccine Associated Paralytic

Poliomyelitis (VAPP)– Vaccine Derived Polio Virus

(VDPV)

Issues Surrounding the Use of OPV

Polio is Still Endemic in 3 Countries, Reflecting both “Failure to Vaccinate” and “Vaccine Failure”

WHO. Polio Case count. Available at: http://www.who.int/immunization_monitoring/en/diseases/poliomyelitis/case_count.cfm, 2009

Graphs from WHO. Polioeradication. Progress & Prospect. 2008

Roberts. Science, 2009

High risk Medium risk Rest of country

In Nigeria, high “failure to vaccinate”

In Nigeria, high “failure to vaccinate”

0 doses 1-3 doses 4-6 doses 7+ doses

OPV doses administrated per area in Nigeria 2003-2008

3-Dose TOPV Immunogenicity(median seroconversion of developing country studies)

95

6572

0

10

20

30

40

50

60

70

80

90

100

Poliovirus type 1 Poliovirus type 2 Poliovirus type 3

Patriarca PA et al. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries: A review: Rev Infect Dis 1991;13: 926-39.

Seroconversion after 3 doses of OPV

• Industrialized versus low-income countries– 95% Seroconversion in industrialized countries

• Seroconversion in low-income countries

Review of 32 studies. Patriarca, Wright & John. Rev Infect Dis 1991; 13:926-39

Type Weighted average seroconversion

1

2

3

73%

90%

70%

VAPP: A Rare But Serious and Inevitable Adverse Event

Associated with OPV

• Vaccine-Associated Paralytic Polio:– Definition: PP in vaccinee following OPV administration

– Cause: Mutation of vaccine virus during replication in the gut of vaccinee (reversion to neurovirulence)

– Form: VAPP undistinguishable from naturally occurring polio• Same incubation period, range of severity and Case Fatality Rate

– May affect both vaccinees & close contacts

Sutter et al. Vaccines, 2008

Paul. Vaccine, 2004

John. Bull of the WHO, 2004

VAPP- A US EXPERIENCE

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 guts • Recombination with other enteroviruses

– Potential to cause paralytic polio in humans and sustained circulation – Factor favoring emergence & spread are same as for wPV:

• Low OPV coverage• Poor sanitation• High population density• Tropical conditions

– 3 Types cVDPV, iVDPV, aVDPVWHO. WER, 2006

iVDPV & long-term excretion cases

• 24 iVDPVs with long term excretion (> 12 months)

• cases have been from: Europe (9), USA (7), Japan (1), Argentina (1), Kuwait (1), Taiwan (1), Iran (1), Ireland/Zimbabwe (1), Thailand (1)

• It is not clear if they have potential to reseed population after eradication

Kew OL et al. Annu Rev Microbiol 2005;59:587-635

22

iVDPV & Long-Term Excretion: WHO Registry

• 24 iVDPVs excretors• 8 Type 1 + 15 Type 2 + 1

Type 3 • 3 currently known to

excrete • Cases have been from:

– Europe (8)– USA (8)– Japan, Argentina, Kuwait,

Taiwan, Iran, Peru, Ireland/Zimbabwe and Thailand (1)

Immuno-deficiencies linked to persistent poliovirus infections

cvid

agamma

Ab deficient

scid

hypogamma

ICF

MHC-II def

XLA

unknown

Kew OL et al. Annu Rev Microbiol 2005;59:587-635

iVDPV & long-term excretion cases

• It is not known whether immune-deficient infants born in developing countries survive to pose a threat

• Studies shows that risk of chronic poliovirus excretion is low. 0.1-1.0% in immunodeficient patients

• Not a single HIV infected children in developing countries found with prolonged poliovirus excretion

• More studies in HIV infected adults needed

Kew OL et al. Annu Rev Microbiol 2005;59:587-635

Source : www.polioeradication.org

DOR / HAITI2000-01VDPV 121 cases

DOR / HAITI2000-01VDPV 121 cases

NIGER2006

VDPV 22 cases

NIGER2006

VDPV 22 cases

NIGERIA2005-12VDPV 2

385 cases

NIGERIA2005-12VDPV 2

385 cases

DR CONGO2008

VDPV 211 cases

DR CONGO2008

VDPV 211 cases

MADAGASCARVDPV 22001-025 cases

20053 cases

MADAGASCARVDPV 22001-025 cases

20053 cases

MYANMAR2006-07VDPV 15 cases

MYANMAR2006-07VDPV 15 cases

INDONESIA2005

VDPV 146 cases

INDONESIA2005

VDPV 146 cases

CHINA2004

VDPV 12 cases

CHINA2004

VDPV 12 cases

CAMBODIA2005-06VDPV 32 cases

CAMBODIA2005-06VDPV 32 cases

PHILIPPINES2001

VDPV 13 cases

PHILIPPINES2001

VDPV 13 cases

ETHIOPIA2008-09VDPV 24 cases

ETHIOPIA2008-09VDPV 24 cases

658 circulating Vaccine-derived Polioviruses, 2000-13*21 countries, 24 outbreaks

INDIA2009

VDPV 1, 2 2 & 18 cases

INDIA2009

VDPV 1, 2 2 & 18 cases

PAKISTAN2012

VDPV 216 cases

PAKISTAN2012

VDPV 216 cases

6 outbreaks with cVDPV115 outbreaks with cVDPV23 outbreak with cVDPV3

cVDPV type 1 (79 cases)

cVDPV type 2 (557 cases)

cVDPV type 3 (11 cases)

*as of 11th June’13

The OPV Paradox – how OPV Use May Compromise the Final Goal of

Eradication

– Given risk of VAPP and VDPV associated with OPV, continued use of OPV may end up causing more cases of polio than wild polio virus (OPV paradox)

WHO. cVDPV 2000-2008. Available at: http://www.polioeradication.org/content/general/cvdpv_count.pdf, 2009

GPEI. Strategic Plan 2009-2013. Available at:http://www.polioeradication.org/content/publications/PolioStrategicPlan09-13_Framework.pdf,2009

WHO. WER, 2004 Jacob. Bull of the WHO, 2002 Dowdle et al. Rev Med Virol, 2003 GPEI 2013

RISK FREQUENCY GLOBAL ESTIMATES

VAPP 2-4 per million birth cohort

250-500 cases/year (WHO)400-800 cases/year (other experts’ estimate)

cVDPV24 independent cVDPV outbreaks in 21 countries since 2000

iVDPV 33 cases since 1962

But why talk about IPV now?

“The primary challenge to Nigeria’s energetic and comprehensive polio eradication efforts

is the failure of the vaccine to optimally protect children in the remaining infected areas of

the country.”

WHO (GPEI. Annual Report 2008)

• Concerns about VAPP is being increasingly realized.

• Reemergence of type 2 poliovirus in the form of VDPV

• Reintroduction of wild PV circulation in previously polio-free countries through

importations

FMH has recognized the need for IPV in our country and granted license for use in

Nigeria (56 years after its development).

Role of IPV in ‘Polio End Game’ – WHO position

IAP 2012 Immunization Schedule

Reasons for OPV+IPV

Reasons for continuous use of OPV along with IPV:

1. In concordance with the government policy of using

OPV for Polio Eradication

2. Mucosal immunity is superior with OPV and IPV use.

3. Not giving OPV might create confusion in the minds of

parents.

4. The risk of VAPP with this combined OPV and IPV

schedules is extremely low.

“The combined OPV and IPV schedule strive to provide the

best of protection to an individual child while not

deviating from the national immunization policies.”

Ref: Consensus Recommendations on Immunization,2008. IAPCOI. INDIAN PEDIATRCS VOL 45–

MAY 17 ‘08. pg 643.

Recommendations

Oral Polio Vaccine should NOT be given to a child if they have any of

the following:

• weakened immune systems

• are taking long-term steroids

• has cancer

• has AIDS or HIV infection

• allergies to neomycin, streptomycin, or polymyxin B

IPV TO IMMUNOCOMPROMISED CHILDRENS

Vaccine recommendations for immunosuppressed children

Inactivated poliovirus vaccine (IPV) is the only polio vaccine

recommended for HIV-infected people and their household contacts

(Parents & other family members)) because it cannot replicate or

spread from person to person.

Oral poliovirus vaccine (OPV) should not be administered to HIV-

infected people or their household contacts because it is a live

vaccine and can replicate and spread from person to person.

Ref: AIDS Project Los Angeles (APLA)

Recommendations

41

Vaccines for children with HIV infectionVaccine Birth 1 mo 2 mo 4 mo 6 mo 12 mo 15 mo 18 mo 24 mo 4–6 y 11–12 y

Recommendations for these vaccines are the same as those for immunocompetent children

Hep. B virus Hep B1 Hep B2 Hep B3 Hep B

DTaP TDaP TDaP TDaP TDaP TDaP Tdap

Hib Hib Hib Hib Hib

IPV IPV IPV IPV IPV

Hepatitis A virus Hep A Hep A

Recommendations for these vaccines differ from those for immunocompetent children

Pneumocccus PCV PCV PCV PCV PPV23 PPV23 (5–7 y)

MMR Do not administer to severely immunocompromised children MMR MMR MMR

Varicella Var Var Var

Ref: Florida/Caribbean AIDS Education and Training Center

Recommendations

eIPV: The Vaccine of Choice for Today and the Future

–High Immunogenicity Even After 2 Doses–Long-term Persistence of Antibodies

–Good Efficacy / Effectiveness–Good Herd Immunity –Favorable Health Economics

eIPV: High Immunogenicity, Even After 2 Doses

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

– High immunogenicity after 2 doses (including 27 developing countries) : • 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

– Comparative study in India, 1990s 92% efficacy of IPV vs 66% for OPV(3 doses of respective vaccines)

Polio Eradication Committee et al. Indian Pediatr, 2008

Plotkin & Vidor. Vaccines, 2008

IPV Provides Good Herd Immunity

• Herd immunity: – Protection of the population to a greater extent than that expected by the actual

population vaccination coverage

• Excellent herd immunity reported wherever IPV used on large scale – e.g. : USA

John. Expert Rev Vaccines, 2009

Stickle. Am J Public Health, 1954

Observed

Expected in absence of vaccine use

Expected with vaccine effect limitedto vaccinees

Paralytic Poliomyelitis Cases Expected with orwithout Vaccine use, 1951-1954

Role of OPV + eIPV

• Better mucosal immunity of OPV + IPV• Very low risk of VAPP – early OPV protection against VAPP by

maternal antibodies. Subsequently protected by IPV. IPV alone may not be enough.

• Higher seropositivity of OPV + IPV in multiple trials in Gambia, Oman, Thailand, Israel & Pakistan.

• Benefit of continuing the government policy regarding OPV with highly predictable immunogenicity & efficacy of IPV.

OPV & IPV are not contradictory but complementary !

THANK YOU