BackgroundWe examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s.MethodsThe child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV were offered from 3 months of age at these sessions. Due to the 3-monthly intervals between sessions, the children were allocated by birthday in a ‘natural experiment’ to receive vaccinations early or late between 3 and 5 months of age. We included children who were < 6 months of age when vaccinations started and children born until the end of December 1983. We compared mortality between 3 and 5 months of age of DTP-vaccinated and not-yet-DTP-vaccinated children in Cox proportional hazard models.ResultsAmong 3–5-month-old children, having received DTP (± OPV) was associated with a mortality hazard ratio (HR) of 5.00 (95% CI 1.53–16.3) compared with not-yet-DTP-vaccinated children. Differences in background factors did not explain the effect. The negative effect was particularly strong for children who had received DTP-only and no OPV (HR = 10.0 (2.61–38.6)). All-cause infant mortality after 3 months of age increased after the introduction of these vaccines (HR = 2.12 (1.07–4.19)).ConclusionDTP was associated with increased mortality; OPV may modify the effect of DTP.

BackgroundWhole-cell diphtheria–tetanus–pertussis (DTP) and oral polio vaccine (OPV) were introduced to children in Guinea-Bissau in 1981. We previously reported that DTP in the target age group from 3 to 5 months of age was associated with higher overall mortality. DTP and OPV were also given to older children and in this study we tested the effect on mortality in children aged 6–35 months.MethodsIn the 1980s, the suburb Bandim in the capital of Guinea-Bissau was followed with demographic surveillance and tri-monthly weighing sessions for children under 3 years of age. From June 1981, routine vaccinations were offered at the weighing sessions. We calculated mortality hazard ratio (HR) for DTP-vaccinated and DTP-unvaccinated children aged 6–35 months using Cox proportional hazard models. Including this study, the introduction of DTP vaccine and child mortality has been studied in three studies; we made a meta-estimate of these studies.ResultsAt the first weighing session after the introduction of vaccines, 6–35-month-old children who received DTP vaccination had better weight-for-age z-scores (WAZ) than children who did not receive DTP; one unit increase in WAZ was associated with an odds ratio of 1.32 (95% CI = 1.13–1.55) for receiving DTP vaccination. Though lower mortality compared with not being DTP-vaccinated was, therefore, expected, DTP vaccination was associated with a non-significant trend in the opposite direction, the HR being 2.22 (0.82–6.04) adjusted for WAZ. In a sensitivity analysis, including all children weighed at least once before the vaccination program started, DTP (±OPV) as the most recent vaccination compared with live vaccines or no vaccine was associated with a HR of 1.89 (1.00–3.55). In the three studies of the introduction of DTP in rural and urban Guinea-Bissau, DTP-vaccinated children had an HR of 2.14 (1.42–3.23) compared to DTP-unvaccinated children; this effect was separately significant for girls [HR = 2.60 (1.57–4.32)], but not for boys [HR = 1.71 (0.99–2.93)] (test for interaction p = 0.27).ConclusionAlthough having better nutritional status and being protected against three infections, 6–35 months old DTP-vaccinated children tended to have higher mortality than DTP-unvaccinated children. All studies of the introduction of DTP have found increased overall mortality.

Symmetric independence relations are often studied using graphical representations. Ancestral graphs or acyclic directed mixed graphs with m-separation provide classes of symmetric graphical independence models that are closed under marginalization. Asymmetric independence relations appear naturally for multivariate stochastic processes, for instance in terms of local independence. However, no class of graphs representing such asymmetric independence relations, which is also closed under marginalization, has been developed. We develop the theory of directed mixed graphs with µ-separation and show that this provides a graphical independence model class which is closed under marginalization and which generalizes previously considered graphical representations of local independence.Several graphs may encode the same set of independence relations and this means that in many cases only an equivalence class of graphs can be identified from observational data. For statistical applications, it is therefore pivotal to characterize graphs that induce the same independence relations. Our main result is that for directed mixed graphs with µ-separation each equivalence class contains a maximal element which can be constructed from the independence relations alone. Moreover, we introduce the directed mixed equivalence graph as the maximal graph with dashed and solid edges. This graph encodes all information about the edges that is identifiable from the independence relations, and furthermore it can be computed efficiently from the maximal graph.

Purpose: The diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) were introduced in children 3 of 5 months of age in 1981e1983 in Bandim, in the capital of Guinea-Bissau. Because DTP has been linked to deleterious nonspecific effects (NSEs) and OPV to beneficial NSEs, we followed up this cohort to 3 years of age and examined the effects of DTP with OPV on all-cause mortality and the interactions of DTP and OPV with the measles vaccine (MV). Methods: DTP and OPV were offered at 3 monthly community weighing sessions. Vaccination groups were defined by the last vaccine received. We compared overall mortality for different groups in Cox proportional hazards regression models, reporting hazards ratios (HRs) with 95% CIs. Findings: The study cohort included 1491 children born in Bandim from December 1980 to December 1983. From 3 to 35 months of age, with censoring for MV, children vaccinated with DTP and/or OPV had higher mortality than both unvaccinated children (HR ¼ l.66; 95% CI, 1.03e2.69) and OPV-only vaccinated children (HR ¼ 2.81; 95% CI, 1.02e7.69); DTP-only vaccinated children had higher mortality than OPV-only vaccinated children (HR ¼ 3.38; 95% CI, 1.15-e9.93). In the age group of 3e8 months, before MV is administered, DTPonly vaccination was associated with a higher mortality than DTP with OPV (HR ¼ 3.38; 95% CI, 1.59e7.20). Between 9 and 35 months of age, when MV is given, DTP-vaccinated and MV-unvaccinated children had higher mortality (HR ¼ 2.76; 95% CI, 1.36e5.59) than children who had received MV after DTP, and among children who received DTP with MV or after MV, DTP-only vaccination was associated with a higher mortality than DTP with OPV (HR ¼ 6.25; 95% CI, 2.55e15.37). Implications: Because the 2 vaccines had differential effects and the healthiest children were vaccinated first, selection biases are unlikely to explain the estimated impact on child survival. OPV had beneficial NSEs, and administration of OPV with DTP may have reduced the negative effects of DTP.