Background Live attenuated vaccines have been observed to have particularly beneficial effects for child survival when given in the presence of maternally transferred immunity (priming). We aimed to test this finding and furthermore explore the role of paternal priming. Methods In an exploratory, retrospective cohort study in 2017, parental Bacillus Calmette-Guérin (BCG) scars were assessed for infants from the Bandim Health Project (BHP) who had participated in a 2008–2013 trial of neonatal BCG vaccination. Parental scar effects on mortality were estimated from birth to 42 days, the age of the scheduled diphtheria-tetanus-pertussis (DTP) vaccination, in Cox proportional hazard models adjusted with Inverse Probability of Treatment Weighting. Findings For 66% (510/772) of main trial infants that were still registered in the BHP area, at least one parent was located. BCG scar prevalence was 77% (353/461) among mothers and 63% (137/219) among fathers. In the first six weeks of life, maternal scars were associated with a mortality reduction of 60% (95%CI, 4% to 83%) and paternal scars with 49% (-68% to 84%). The maternal scar association was most beneficial among infants that had received BCG vaccination at birth (73% (-1% to 93%)). Although priming was less evident for paternal scars, having two parents with scars reduced mortality by 89% (13% to 99%) compared with either one or none of the parents having a scar. Interpretation Parental BCG scars were associated with strongly increased early-life survival. These findings underline the importance of future studies into the subject of inherited non-specific immunity and parental priming. Funding Danish National Research Foundation; European Research Council; Novo Nordisk Foundation; University of Southern Denmark.

Background The world is set on the eradication of measles. Continuation of measles vaccine (MV) after eradication could still reduce morbidity, since MV has so-called beneficial non-specific effects (NSEs). We evaluated the effect of a ‘booster’ dose of MV on overall severe morbidity. Methods We conducted a randomized controlled trial among children aged 17.5-48 months in Guinea-Bissau, where MV is recommended only at 9 months of age. At the time of this interim analysis, 3,164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or no vaccine. Severe morbidity (a composite outcome of non-accidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. Results There were no measles cases during the trial period. There were 43 non-accidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR: 0.72 (95%CI, 0.38-1.38)). At 12 months of follow-up the number needed to treat (NNT) to prevent one severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR: 0.91 (0.46-1.81)). Conclusion MV2 may reduce non-measles severe morbidity by 28% (-38% to 62%), although this did not achieve statistical significance in this study. If significant in higher-powered studies, this has major implications for child health, even after measles eradication.

Background Maternal priming with Bacille Calmette-Guérin (BCG) has been associated with reduced offspring mortality. We investigated this association in a cohort of frail neonates. Methods: We performed an observational study within a randomized BCG trial conducted at the Neonatal Intensive Care Unit (NICU) in Guinea-Bissau from 2015-2017. At NICU admission and following informed consent, the maternal scar status was evaluated by visual inspection before neonates were randomized 1:1 to receive BCG + Oral Polio Vaccine (OPV) immediately versus BCG + OPV at hospital discharge. Stratified by maternal scar status, we assessed overall in-hospital and post-discharge mortality up to 42 days of age in Cox Proportional Hazards models providing adjusted Mortality Rate Ratios (aMRRs). Results: 62% (903/1451) of mothers had a BCG scar. During NICU admission, the mortality risk was 1.7% (15/903) for neonates born to mothers with a scar vs 3.3% (18/548) for those born to mothers with no scar, the maternal scar/no scar aMRR = 0.53 (0.26-1.05); the aMRR was 0.39 (0.13-1.05) for unvaccinated neonates and 0.70 (0.26-1.87) for vaccinated neonates. Conclusion: This small study indicates that maternal BCG might be associated with reduced all-cause NICU mortality. If confirmed elsewhere, this finding would have substantial ramifications for global health.

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