Stopping Oral Polio Vaccine (OPV) after Defeating Poliomyelitis: A Pyrrhic Victory? Systematic Review of the Non-Specific Effects of OPV

Abstract

Background: Previous studies revealed that the two live vaccines, BCG and measles vaccine (MV), have beneficial non-specific effects (NSEs) reducing morbidity and mortality more than could be explained by prevention of tuberculosis and measles infection. Since live oral polio vaccine (OPV) is stopped and replaced with inactivated polio vaccine (IPV) in high-income countries and will be stopped globally after polio eradication, we undertook a review of potential NSEs of OPV on mortality. Methods: We searched PubMed for all studies of OPV and death/mortality. In low-income settings, OPV has been provided in three different settings: First, as co-administration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine in three doses from 6 weeks of age. Second, as an early dose at birth (OPV0), often administered together with BCG. Third, in OPV campaigns to eradicate polio infection. We calculated relative risk (RR) of mortality for different combinations of vaccinations and RR of the mortality rate before and after OPV campaigns. Results: The majority of studies was from Guinea-Bissau. First, in three natural experiments, where DTP was missing, OPV-only compared with DTP+OPV co-administered was associated with 3-fold lower mortality rate in two community studies (RR=0.33 (0.14-0.77)) and in a hospital case fatality study (RR=0.29 (0.11-0.77)). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than co-administration of DTP+OPV (RR=3.23 (1.27-8.21)). Second, in two randomised controlled trials (RCTs), OPV0 vs. no OPV0 was associated with 32% lower infant mortality. The beneficial effects of OPV0 were stronger the earlier the vaccine had been given. Third, in six population-based studies from urban and rural Guinea-Bissau, Burkina Faso and Bangladesh, the mortality rate was lower with a RR=0.75 (0.69-0.82) after OPV campaigns than before OPV campaigns. Furthermore, OPV campaigns changed the mortality effect of health interventions in nine RCTs. The intervention had the strongest beneficial effect before OPV campaigns in all RCTs; hence, OPV campaigns reduced the mortality rate and the difference between randomisation groups disappeared. Interpretation: There have been no polio cases in Guinea-Bissau in this century and no confounding factors or bias would be able to explain these patterns. The only interpretation consistent with all data is that OPV has beneficial NSEs, reducing child mortality. Child mortality may increase again once OPV is removed or replaced with IPV. If no counter-measures are taken, eradicating polio and stopping OPV may become a Pyrrhic victory. Funding: The work on non-specific effects of vaccines has been supported by the Danish Council for Development Research, Ministry of Foreign Affairs, Denmark [grant number 104.Dan.8.f.], Novo Nordisk Foundation and European Union FP7 support for OPTIMUNISE (grant: Health-F3- 2011-261375). CSB held a starting grant from the ERC (ERC-2009-StG-243149). CVIVA was supported by a grant from the Danish National Research Foundation (DNRF108). PA held a research professorship grant from the Novo Nordisk Foundation. Declaration of Interest: Nothing to declare.