Stopping Oral Polio Vaccine (OPV) After Defeating Poliomyelitis in Low- and Middle-Income Countries: Harmful Unintended Consequences? Review of the Nonspecific Effects of OPV

Abstract

Background The live vaccines bacille Calmette-Guérin (BCG) and measles vaccine have beneficial non-specific effects (NSEs) reducing mortality more than can be explained by prevention of tuberculosis or measles infection. Live oral polio vaccine (OPV) will be stopped after polio eradication, we therefore reviewed the potential NSEs of OPV. Methods OPV has been provided in three contexts. First, co-administration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine at 6, 10 and 14 weeks of age. Second, at birth (OPV0) with BCG. Third, in OPV campaigns (C-OPV) initiated to eradicate polio infection. We searched PubMed and EMBASE for studies of OPV with mortality as an outcome. We used meta-analysis to obtain combined relative risk (RR) of mortality associated with different uses of OPV. Results First, in natural experiments when DTP was missing, OPV-only compared with DTP + OPV was associated with 3-fold lower mortality in community studies (RR = 0.33 (0.14-0.75)) and a hospital study (RR = 0.29 (0.11-0.77)). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than DTP + OPV (RR = 3.23 (1.27-8.21)). Second, in a randomised controlled trial, BCG + OPV0 vs. BCG + noOPV0 was associated with 32% (0-55%) lower infant mortality. Beneficial NSEs were stronger with early use of OPV0. Third, in five population-based studies from Guinea-Bissau and Bangladesh, the mortality rate was 24% (17-31%) lower after C-OPVs than before C-OPVs. Interpretation There have been few clinical polio cases reported in this century and no confounding factors or bias would explain all these patterns. The only consistent interpretation is that OPV has beneficial NSEs, reducing non-polio child mortality.

Immuno-persistence of the different primary polio vaccine schedules and immunogenicity of the booster dose by sabin inactivated or bivalent oral poliovirus vaccine in children aged 4 years: an open-label, randomised, controlled phase 4 trial in China

“…In addition, we found that the booster dose of bOPV after 2sIPV-bOPV resulted in a 14.81% increase in seropositivity rates against poliovirus type 2. This result may indicate the possible cross-protection from bOPV, 17 which is consistent with research findings in Chilean infants. 18 But the heterotypic protection may not sufficiently raise immunity against poliovirus type 2 and has been observed to be short lasting.…”

Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau

“…10 As for the BCG vaccine, increasing evidence supports that OPV has beneficial non-specific effects. 11 A trial comparing BCG only versus BCG+OPV0 in neonates found that OPV0 reduced infant mortality by 32% (95% CI: 0% to 55%) before the next OPV campaign. 12 In the present trial, we aimed to test the impact of combining the WHO-recommended home visits with provision of the vaccines recommended at birth (BCG and OPV0).…”

“…OPV at birth (OPV0) is part of the strategy for eradicating polio 10. As for the BCG vaccine, increasing evidence supports that OPV has beneficial non-specific effects 11. A trial comparing BCG only versus BCG+OPV0 in neonates found that OPV0 reduced infant mortality by 32% (95% CI: 0% to 55%) before the next OPV campaign 12…”