A Special Presentation to Pediatric Association of Nigeria on 8th July 2013 at Lagos.

1. IPV – A NEW PERSPECTIVE IN
POLIO PREVENTION
A SPECIAL PRESENTATION TO PAN STAKE HOLDERS
BY
R.RAMKUMAR

2. 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

3. 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)

4. Adapted from 1, 11
Summary of Key Attributes of
OPV and IPV
Sutter et al. Vaccines, 2008
Plotkin & Vidor . Vaccines, 2008

5. 1988
350,000 cases
125 countries
Polio Eradication Initiative: Progress
1988-2012
2012
222 cases
5 countries

6. Wild Poliovirus 2012

8. Wild virus type 1
Wild virus type 3
Impact of OPV Suspension, Kano-Nigeria
Poliovirus 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
?

9. Spread of African Epidemic
Low Season Spread
Dec 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

10. September 5, 2013
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)

14. – Suboptimal OPV efficacy
– Inadequate Herd effect
– Vaccine Associated Paralytic
Poliomyelitis (VAPP)
– Vaccine Derived Polio Virus
(VDPV)
Issues Surrounding the Use of
OPV

15. 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

16. 3-Dose TOPV Immunogenicity
(median seroconversion of developing country studies)
95
65
72
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.

17. 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%

18. 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

19. VAPP- A US
EXPERIENCE

20. 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, aVDPV
WHO. WER, 2006

21. 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. 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

23. 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

24. Source : www.polioeradication.org
DOR / HAITI
2000-01
VDPV 1
21 cases
DOR / HAITI
2000-01
VDPV 1
21 cases
NIGER
2006
VDPV 2
2 cases
NIGER
2006
VDPV 2
2 cases
NIGERIA
2005-12
VDPV 2
385 cases
NIGERIA
2005-12
VDPV 2
385 cases
DR CONGO
2008
VDPV 2
11 cases
DR CONGO
2008
VDPV 2
11 cases
MADAGASCAR
VDPV 2
2001-02
5 cases
2005
3 cases
MADAGASCAR
VDPV 2
2001-02
5 cases
2005
3 cases
MYANMAR
2006-07
VDPV 1
5 cases
MYANMAR
2006-07
VDPV 1
5 cases
INDONESIA
2005
VDPV 1
46 cases
INDONESIA
2005
VDPV 1
46 cases
CHINA
2004
VDPV 1
2 cases
CHINA
2004
VDPV 1
2 cases
CAMBODIA
2005-06
VDPV 3
2 cases
CAMBODIA
2005-06
VDPV 3
2 cases
PHILIPPINES
2001
VDPV 1
3 cases
PHILIPPINES
2001
VDPV 1
3 cases
ETHIOPIA
2008-09
VDPV 2
4 cases
ETHIOPIA
2008-09
VDPV 2
4 cases
658 circulating Vaccine-derived Polioviruses, 2000-13*
21 countries, 24 outbreaks
INDIA
2009
VDPV 1, 2
2 & 18
cases
INDIA
2009
VDPV 1, 2
2 & 18
cases
PAKISTAN
2012
VDPV 2
16 cases
PAKISTAN
2012
VDPV 2
16 cases
6 outbreaks with cVDPV1
15 outbreaks with cVDPV2
3 outbreak with cVDPV3
cVDPV type 1 (79 cases)
cVDPV type 2 (557 cases)
cVDPV type 3 (11 cases)
*as of 11th
June’13

28. 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)
cVDPV 24 independent cVDPV
outbreaks in 21 countries
since 2000
iVDPV 33 cases since 1962

29. 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

37. IAP 2012
Immunization Schedule

38. 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.

39. 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

40. 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. 41
Vaccines for children with HIV infection
Vaccine 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

42. 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

43. 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

44. 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 limited
to vaccinees
Paralytic Poliomyelitis Cases Expected with or
without Vaccine use, 1951-1954

45. 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 !

47. THANK