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Partial defects in interferon (IFN)-γ signaling lead to susceptibility to infections with nontuberculous mycobacteria. The receptors for IFN-α and IFN-γ activate components of the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway. Some defects in STAT1 mainly affect IFN-γ signaling, thus resulting in mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a severe disease but patients show a favorable response to anti-mycobacterial chemotherapy. Other defects in STAT1 affect both IFN-α and IFN-γ signaling resulting in mycobacterial and lethal viral disease. We report here a patient with two novel STAT1 alleles, which in combination results in a recessive trait with partial STAT1 deficiency and mycobacterial disease. Cells from the patient did respond to mycobacterial antigen, but both the expression of STAT1 and phosphorylation of STAT1 in response to IFN-γ treatment were reduced. This is the first report of a mutation in the N-terminal part of STAT1 involved in causing mycobacterial disease.

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.

Oral polio vaccine (OPV) and diphtheria–tetanus–pertussis (DTP) vaccines are given simultaneously in routine immunisation programmes in developing countries. It is therefore difficult to determine the separate effects of these vaccines on survival. We used the shortage of DTP vaccine in Bissau to examine the impact of OPV on the case fatality at the paediatric ward in Bissau. For 719 children less than 5 years of age whose vaccination card had been seen at admission and who had not yet received measles vaccine, having received OPV only was associated with a case fatality of 6% compared with 15% for children having received combined DTP and OPV vaccinations, the case fatality ratio (CFR) being 0.29 (95% confidence interval (CI) 0.11–0.77). Even if children fleeing the hospital were assumed to have died shortly after leaving the hospital, the case fatality would still be lower for children having received OPV only (CFR=0.41 (95% CI 0.20–0.81)). The tendency was similar for children hospitalised with pneumonia, diarrhoea, and presumptive malaria. Control for background factors had no impact on the estimate. In areas with high mortality, OPV administered alone may have non-specific beneficial effects or DTP may have a negative effect for children who had received both DTP and OPV.

The sequence of routine immunisations may be important for childhood mortality. Three doses of diphtheria–tetanus–pertussis vaccine (DTP) should be given at 6, 10, and 14 weeks and measles vaccine (MV) at 9 months of age. The sequence is not always respected. We examined in-hospital mortality of children having received DTP with or after measles vaccine. The only paediatric ward in Bissau, Guinea-Bissau. Children hospitalised during two periods in 1990–1996 and 2001–2002 who had received MV prior to hospitalisation. The all-cause case fatality at the hospital for children aged 6–17 months. The case fatality was increased for children who had received DTP with or after measles vaccine compared with children who had received measles vaccine as the most recent vaccine, the ratio being 2.53 (1.37–4.67) and 1.77 (0.92–3.41) in the two periods, respectively. The combined estimate was 2.10 (1.34–3.28). These results were not explained by differences in nutritional status, number of doses of DTP or discharge policy. Administration of DTP with, or after MV, may reduce the beneficial effect of MV.

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.

[...]with reference to the policy of vaccinating children at curative health centre visits in the Gambia 25 years ago, it is suggested that DTP vaccination during a shortage may simply be a marker for failing health. [...]Hull claims that pre-existing disease or underlying malnutrition and cause of death are potential confounders which should have been controlled in the analysis.