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Ipv a new perspective in polio prevention

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

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Ipv a new perspective in polio prevention

  1. 1. IPV – A NEW PERSPECTIVE IN POLIO PREVENTION A SPECIAL PRESENTATION TO PAN STAKE HOLDERS BY R.RAMKUMAR
  2. 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. 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. 4. Adapted from 1, 11 Summary of Key Attributes of OPV and IPV Sutter et al. Vaccines, 2008 Plotkin & Vidor . Vaccines, 2008
  5. 5. 1988 350,000 cases 125 countries Polio Eradication Initiative: Progress 1988-2012 2012 222 cases 5 countries
  6. 6. Wild Poliovirus 2012
  7. 7. 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 ?
  8. 8. 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
  9. 9. 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)
  10. 10. – Suboptimal OPV efficacy – Inadequate Herd effect – Vaccine Associated Paralytic Poliomyelitis (VAPP) – Vaccine Derived Polio Virus (VDPV) Issues Surrounding the Use of OPV
  11. 11. 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
  12. 12. 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.
  13. 13. 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%
  14. 14. 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
  15. 15. VAPP- A US EXPERIENCE
  16. 16. 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
  17. 17. 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
  18. 18. 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
  19. 19. 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
  20. 20. 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
  21. 21. 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
  22. 22. 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
  23. 23. IAP 2012 Immunization Schedule
  24. 24. 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.
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. 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
  30. 30. 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
  31. 31. 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 !
  32. 32. THANK

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