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Previous studies have suggested that the bacille Calmette–Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25–0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24–0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23–0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27–0.79) or 0.42 (0.21–0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria–tetanus–pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.

Several studies have suggested that routine childhood immunisations may have non-specific effects on mortality. To examine which disease categories might be affected, we investigated whether immunisation status had an impact on the case fatality for hospitalised children. Between 1990 and 1996, the Bandim Health Project maintained a register of all children from the study area hospitalised at the paediatric ward of the central hospital in Bissau, Guinea-Bissau. The study included 2079 hospitalised children aged 1.5–17 months coming from the Bandim study area. Among children whose vaccination card had been seen at admission, the case fatality ratio for measles-vaccinated children versus measles-unvaccinated children was 0.51 (0.27–0.98), the beneficial effect being significantly stronger for girls than for boys (test of interaction, p = 0.050). The protective effect of measles vaccine remained unchanged when hospitalised measles cases were excluded from the analysis (0.49 (0.26–0.94)). The effect of measles vaccine was strongest for children with pneumonia (MR = 0.28 (0.07–0.91)) and presumptive malaria (MR = 0.40 (0.13–1.18)). For measles-vaccinated children, the female to male case fatality ratio was 0.54 (0.28–0.97). Among children having received diphtheria–tetanus–pertussis (DTP) and oral polio (OPV) as the last vaccines, girls had higher case fatality than boys, the mortality ratio being 1.63 (1.03–2.59). The female to male ratios were significantly inversed for DTP and OPV versus measles vaccine (test of interaction, p = 0.003). These results remained unchanged if 1-month post-discharge deaths were included in the analysis, and in multivariate analyses controlling for determinants of mortality. In conclusion, measles vaccine was associated with reduced mortality from diseases other than measles, the beneficial effect being stronger for girls than for boys. On the other hand, DTP and OPV vaccine were associated with higher case fatality for girls than for boys. Understanding the divergent non-specific effects of common vaccines may contribute to better child survival in developing countries.

Though previous studies have suggested a non-specific beneficial effect of oral polio vaccine (OPV), there has been no evaluation of the mortality impact of national polio immunization days. On the other hand, studies examining the effect of OPV and diphtheria–tetanus–pertussis (DTP) vaccines, which are usually administered together in routine immunisation programmes in low-income countries, have found no beneficial or even a negative effect on infant survival. In 1998, we used the opportunity of two national immunisation days to examine the impact of OPV administered alone on survival for the 6103 children less than 5 years of age in the Bandim Health Project's study area in Guinea-Bissau. Survival was ascertained through regular surveillance from March 1998 until the beginning of the war on June 7, 1998, the end of 1998, or the end of 1999, respectively. The child register was linked with a register for the only paediatric ward in Bissau to determine the risk of hospitalisations. Among children under 5 years of age, 82% had received 1 or 2 doses of polio vaccines during the campaign. Though polio vaccination during the campaign was associated with slightly lower mortality, this difference was not significant for all children under 5 years of age (mortality ratio (MR) = 0.46 (0.18–1.15)). However, oral polio vaccination was associated with a beneficial effect for children under 6 months of age at the time of the campaign, the mortality ratio being 0.09 (95% CI 0.01–0.85) in the 3 months before the war controlling for significant background factors, including routine immunizations, antenatal consultations, and arm circumference. The polio-vaccinated children aged 0–5 months had fewer hospitalisations than children who had not been polio vaccinated (RR = 0.27 (0.10–0.76)). With longer follow-up to December 1998 or December 1999, the difference in mortality gradually disappeared, the MR for polio-vaccinated children being 0.61 (0.32–1.14) and 0.83 (0.51–1.34), respectively. Among children aged 6–59 months of age, measles vaccine was associated with a 56% reduction in mortality (MR = 0.44 (0.28–0.69)) and no effect of oral polio vaccine was measurable in this age group. The effect of polio vaccine among children less than 6 months of age could be due to selection bias but might also represent a non-specific beneficial immune stimulation and there is nothing to suggest that OPV might have a negative effect on infant survival. Studies of the possible non-specific effects of oral polio vaccine are warranted before OPV is withdrawn.