National Immunization Campaigns with Oral Polio Vaccine Reduce All-Cause Mortality: A Natural Experiment within Seven Randomized Trials

Abstract

BackgroundA recent WHO review concluded that live BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs) reducing mortality from non-targeted diseases. NSEs of oral polio vaccine (OPV) were not examined. If OPV vaccination campaigns reduce the mortality rate, it would suggest beneficial NSEs.SettingBetween 2002 and 2014, Guinea-Bissau had 15 general OPV campaigns and other campaigns with OPV plus vitamin A supplementation (VAS), VAS-only, MV, and H1N1 vaccine. In this period, we conducted seven randomized controlled trials (RCTs) with mortality as main outcome.MethodsWithin these RCTs, we assessed whether the mortality rate was lower after-campaign than before-campaign. We used Cox models with age as underlying time and further adjusted for low birth-weight, season and time trend in mortality. We calculated the adjusted mortality rate ratio (MRR) for after-campaign vs before-campaign.ResultsThe mortality rate was lower after OPV-only campaigns than before, the MRR being 0.81 (95% CI = 0.68–0.95). With each additional dose of campaign-OPV the mortality rate declined further (MRR = 0.87 (95% CI: 0.79–0.96) per dose) (test for trend, p = 0.005). No other type of campaign had similar beneficial effects. Depending on initial age and with follow-up to 3 years of age, the number needed to treat with campaign-OPV-only to save one life was between 68 and 230 children.ConclusionBissau had no case of polio infection so the results suggest that campaign-OPV has beneficial NSEs. Discontinuation of OPV-campaigns in low-income countries may affect general child mortality levels negatively.

Defining trained immunity and its role in health and disease

“…An increasing body of evidence suggests that trained immunity plays a critical role in humans. First, an extensive collection of epidemiological data argues that live vaccines such as the BCG vaccine, measles vaccine, smallpox vaccine and oral polio vaccine have beneficial, non-specific protective effects against infections other than the target diseases [40][41][42][43][44][45][46][47] (for a review, see also ReF. 48 ).…”

How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation?

“…Fourth, boosting with a second dose or further doses of campaign-OPV reduced mortality substantially [33,46].…”

“…Second, several studies have shown OPV-campaigns to be associated with a marked decline in the general mortality rate [45][46][47]. Third, OPV campaigns have modified estimated mortality outcomes in studies of other vaccines [45,48].…”

Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

“…To date, epidemiological evidence supporting the role of live attenuated vaccines in T cell-mediated H.I. is associated with the measles (55-62), the vaccinia (63-66), and the oral polio vaccine (67)(68)(69). These vaccines reduced overall mortality and/or risk for asthma, malignancies, and unrelated infections.…”