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INACTIVATED POLIO VACCINE AND GLOBAL POLIO ERADICATION

Monday, 12th of December 2011 Print

 ‘Estívariz and colleagues' findings show the potential for a single IPV dose to improve protection for infants who have received trivalent OPV, according to recommendations from WHO's expanded programme on immunisation.’

  • INACTIVATED POLIO VACCINE AND GLOBAL POLIO ERADICATION

 

This discussion, also at http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70312-7/fulltext references original research on OPV and IPV from Moradabad, India, accessible at http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70190-6/fulltext

 

Original Text

John F Modlin a

2012 will mark the 24th year of WHO's Global Poliomyelitis Eradication Initiative.1 Eradication has proven more difficult than originally envisioned because of geopolitical events, such as war, social disruption, and political indifference; social and cultural issues, such as distrust of poliovirus vaccines and vaccinators; and the unanticipated emergence of virulent vaccine-derived polioviruses in many locations. Few of these obstacles have bewildered the scientific community as much as the low efficacy of the major weapon in the arsenal, trivalent oral polio vaccine (OPV) in regions with dense populations, high birthrates, and poor sanitation resulting from diarrhoea due to enteric pathogens, particularly rotaviruses, and perhaps nutritional deficiencies and other factors.2, 3 This dilemma has been most frustrating in northern India where, in some crowded, resource-poor areas, the overall effectiveness of each trivalent OPV dose is estimated to be 10% and some children have developed paralytic polio after as many as ten doses.4

Monovalent type-1 and type-3 OPVs avert the issue of heterotypic interference from the robust type-2 virus and induce higher seroconversion rates and mean titres of poliovirus neutralising antibodies than does trivalent OPV. Deployment of monovalent vaccines in supplemental immunisation programmes has resulted in improved control of both wild-type and virulent vaccine-derived poliovirus.5—7 In The Lancet Infectious Diseases, Concepcion Estívariz and colleagues8 report 99% seroprevalence of type-1 antibody in infants aged 6—9 months, which confirms the effectiveness of type-1 monovalent OPV. The development and distribution of bivalent type-1 and type-3 OPV should enable increased control of disease in areas where wild viruses of both serotypes continue to circulate. Because wild type-2 poliovirus was eradicated more than a decade ago, a compelling argument can be made for a switch to bivalent vaccine for routine immunisation of infants, while reserving trivalent OPV for control of outbreaks of virulent vaccine-derived type-2 polioviruses.

Estívariz and colleagues' findings show the potential for a single IPV dose to improve protection for infants who have received trivalent OPV, according to recommendations from WHO's expanded programme on immunisation. The study site was in Uttar Pradesh, which is one of the last locations in India to support continuous transmission of wild-type polio in association with low effectiveness of trivalent OPV.4 All three formulations of inactivated poliovirus vaccine (IPV) tested were better than standard-potency and high-potency monovalent type-1 OPV live vaccines for boosting titres of neutralising antibody when given at 6—9 months of age. Furthermore, intramuscular standard dose IPV vaccines were clearly better than 20% IPV doses delivered intradermally with a jet injector. The three IPV vaccines each produced higher than expected seroconversion rates to polivirus types 2 and 3 after one dose. The investigators speculate that immune priming by trivalent OPV is the probable explanation for these results. This explanation is supported by the detection of seroconversion 7 days after IPV administration and by other findings that detection of neutralising antibody is an insensitive measure of past poliovirus immunisation.9

These findings leave little doubt that children in resource-poor settings will be protected against paralytic poliomyelitis with as few as two doses of IPV in primary vaccines, and perhaps just one dose for those primed with trivalent OPV. Before IPV alone can be relied on to sustain polio control, the crucial question is whether IPV will induce sufficient mucosal immunity to reduce person-to-person transmission of live poliovirus. OPV challenge studies have repeatedly shown that children vaccinated with IPV excrete higher titres of the challenge OPV virus for longer periods than do those vaccinated with OPV; however, children vaccinated with IPV excrete less virus in stools than do non-immune children and do not excrete virus from the oropharynx. The importance of these experimental observations might be dependent on the ecological setting. Findings from studies10 of recipients of Salk IPV suggest little protection from reinfection after exposure to circulating live polioviruses, but the role of reinfected IPVs in transmission of polioviruses to susceptible contacts was unclear. In 1978, an outbreak of type-1 poliomyelitis occurred in an unvaccinated religious sect in the Netherlands, a country that has continuously used only IPV in the general population. The outbreak virus did not spread to susceptible people in the general population, which suggests a contribution of IPV to herd immunity.11 Whether IPV can contribute to herd immunity in resource-poor environments is unknown. The final answer will be dependent on the proportion of susceptible children immunised with IPV and the extent of effective mucosal immunity induced by IPV.

After eradication, use of all live vaccines will cease to prevent otherwise inevitable outbreaks of virulent vaccine-derived polioviruses.12 Inactivated vaccine will be needed for continuing protection against re-emergence of polio from immunodeficient, long-term excretors, laboratory mishap, or purposeful reintroduction.13 Clinical trials14—17 in Guatemala, India, Kenya, Oman, and other developing countries have shown encouraging results when IPV is given as the primary series to infants younger than 6 months. Optimum immunogenicity results when the first dose is given at 8—10 weeks of age and doses are separated by 8 weeks, rather than 4 weeks. Although a three-dose primary series is generally needed to achieve 100% seroconversion, two doses induce seroconversion rates of 86—99%, albeit at the cost of lower geometric mean titres.14—16,18 A two-dose schedule could be acceptable in resource-poor countries where the cost of IPV exceeds that of all other routinely given vaccines. Other methods to spare antigen include use of new delivery devices, intradermal fractional doses, and adjuvants. Findings from the study by Mohammed and colleagues16 in Oman showed satisfactory seroconversion rates to a fifth the standard IPV dose given subcutaneously to infants at 2, 4, and 6 months of age. Other strategies, such as combination of IPV with diphtheria, tetanus, and pertusiss vaccines and production of vaccine in low-cost facilities that meet high regulatory standards, will make access to IPV affordable for all nations.

The study by Estívariz and colleagues is a small, but important contribution that advances the global poliomyelitis eradication effort by better defining the use of IPV in resource-poor settings.

I declare that I have no conflicts of interest

References

1 WHO. Global eradication of poliomyelitis by the year 2000. Week Epidemiol Rec 1988; 63: 161-162. PubMed

2 Patriarca PA, Wright PF, John TJ. Factors affecting the immunogenicity of oral poliovirus vaccine in developing countries. Rev Infect Dis 1991; 13: 926-939. PubMed

3 Myaux JA, Unicomb L, Besser RE, et al. Effect of diarrhea on the humoral response to oral polio vaccination. Pediatr Infect Dis J 1996; 15: 204-209. CrossRef | PubMed

4 Grassly NC, Fraser C, Wenger J, et al. New strategies for the elimination of polio from India. Science 2006; 314: 1150-1153. CrossRef | PubMed

5 Caceres VM, Sutter RW. Sabin monovalent oral polio vaccines: review of past experiences and their potential use after polio eradication. Clin Infect Dis 2001; 33: 531-541. CrossRef | PubMed

6 Grassly NC, Wenger J, Durrani S, et al. Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case-control study. Lancet 2007; 369: 1356-1362. Summary | Full Text | PDF(147KB) | CrossRef | PubMed

7 Wright PF, Modlin JF. The demise and rebirth of polio—a modern phoenix?. J Infect Dis 2008; 197: 335-336. CrossRef | PubMed

8 Estívariz CF, Jafari H, Sutter RW, et al. Immunogenicity of supplemental doses of poliovirus vaccine for children aged 6—9 months in Moradabad, India: a community-based, randomised controlled trial. Lancet Infect Dis 201110.1016/S1473-3099(11)70190-6. published online Nov 8. PubMed

9 Krugman RD, Hardy GE, Sellers C. Antibody persistence after primary immunization with trivalent oral poliovirus vaccine. Pediatrics 1977; 60: 80-82. PubMed

10 Gelfand HM, LeBlanc DR, Potash L, Fox JP. Studies on the development of natural immunity to poliomyelitis in Louisiana. IV. Natural infections with polioviruses following immunization with a formalin-inactivated vaccine. Am J Hyg 1959; 70: 312-327. PubMed

11 Bijkerk H. Poliomyeltis epidemic in the Netherlands. Dev Biol Stand 1979; 43: 195-206. PubMed

12 WHO. Global Eradication Initiative Strategic Plan, 2004—2008. http://www.polioeradication.org/content/publications/2004stratplan.pdf. (accessed Dec 31, 2004).

13 WHO. Introduction of inactivated poliovirus vaccine into oral poliovirus vaccine-using countries. Wkly Epidemiol Rec 2003; 78: 241-250. PubMed

14 Asturias EJ, Dueger EL, Omer SB, et al. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis 2007; 196: 692-698. CrossRef | PubMed

15 Kok PW, Leeuwenburg J, Tukei P, et al. Serological and virological assessment of oral and inactivated poliovirus vaccines in a rural population. Bull World Health Organ 1992; 70: 93-103. PubMed

16 Mohammed AJ, AlAwaidy S, Bawikar S, et al. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med 2008; 362: 2351-2359. CrossRef | PubMed

17 Simoes EA, John TJ. The antibody response of seronegative infants to inactivated poliovirus vaccine of enhanced potency. J Biol Stand 1986; 14: 127-131. CrossRef | PubMed

18 The Cuba IPV Study Collaborative Group. Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba. N Engl J Med 2007; 356: 1536-1544. CrossRef | PubMed

a Department of Pediatrics, Dartmouth Medical School, Lebanon, NH 03756, USA

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