Lessons for the past : Third World evidence and the reinterpretation of developed world mortality declines

Measles is the largest single killing infection of children in the world, and it is likely that its toll is heightened by the occurrence of a serious delayed effect of early infection. Variations in measles mortality, and in the seriousness of infection, have often been explained in terms of nutritional factors, but intercountry comparisons within the Third World fail to bear this out. In this paper an alternative interpretation is developed, based on the severity of the infective dose to which individuals are exposed. It is shown that this can account for a wide variety of observations which are inexplicable on the nutritional hypothesis, and can also explain the severity of virginsoil epidemics without reference to the effects of genetic selection. The exposure hypothesis predicts that measles vaccination should have a marked effect on childhood mortality as a whole, and this prediction is born out in practice. The success of this interpretation has important implications for our understanding of historical mortality declines in the developed countries, particularly the decline in smallpox mortality

Ascertainment of childhood vaccination histories in northern Malawi

OBJECTIVE: To assess factors related to recorded vaccine uptake, which may confound the evaluation of vaccine impact.METHODS: Analysis of documented vaccination histories of children under 5 years and demographic and socio-economic characteristics collected by a demographic surveillance system in Karonga District, Malawi. Associations between deviations from the standard vaccination schedule and characteristics that are likely to be associated with increased mortality were determined by multivariate logistic regression.RESULTS: Approximately 78% of children aged 6-23 months had a vaccination document, declining to <50% by 5 years of age. Living closer to an under-5 clinic, having a better educated father, and both parents being alive were associated with having a vaccination document. For a small percentage of children, vaccination records were incomplete and/or faulty. Vaccination uptake was high overall, but delayed among children living further from the nearest under-5 clinic or from poorer socio-economic backgrounds. Approximately 9% of children had received their last dose of DPT with or after measles vaccine. These children were from relatively less educated parents, and were more likely to have been born outside the health services.CONCLUSIONS: Though overall coverage in this community was high and variation in coverage according to child or parental characteristics small, there was strong evidence of more timely coverage among children from better socio-economic conditions and among those who lived closer to health facilities. These factors are likely to be strong confounders in the association of vaccinations with mortality, and may offer an alternative explanation for the non-specific mortality impact of vaccines described by other studies

A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions.

Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32-.86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of 0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558

Changing pattern of malaria in Bissau, Guinea Bissau.

OBJECTIVE: To describe the epidemiology of malaria in Guinea-Bissau, in view of the fact that more funds are available now for malaria control in the country. METHODS: From May 2003 to May 2004, surveillance for malaria was conducted among children less than 5 years of age at three health centres covering the study area of the Bandim Health Project (BHP) and at the outpatient clinic of the national hospital in Bissau. Cross-sectional surveys were conducted in the community in different malaria seasons. RESULTS: Malaria was overdiagnosed in both health centres and hospital. Sixty-four per cent of the children who presented at a health centre were clinically diagnosed with malaria, but only 13% of outpatient children who tested for malaria had malaria parasitaemia. Only 44% (963/2193) of children admitted to hospital with a diagnosis of malaria had parasitaemia. The proportion of positive cases increased with age. Among hospitalized children with malaria parasitaemia, those less than 2 years old were more likely to have moderate anaemia (RR = 1.27; 95% CI: 1.02-1.56) (P = 0.03) or severe anaemia (RR = 1.67; 95% CI: 1.25-2.24) (P = 0.0005) than older children. The prevalence of malaria parasitaemia in the community was low (3%, 53/1926). CONCLUSION: In Bissau, the prevalence of malaria parasitaemia in the community is now low and malaria is over-diagnosed in health facilities. Laboratory support will be essential to avoid unnecessary use of the artemisinin combination therapy which is now being introduced as first-line treatment in Bissau with support from the Global Fund

Estimates of measles case fatality ratios: a comprehensive review of community-based studies.

BACKGROUND: Global deaths from measles have decreased notably in past decades, due to both increases in immunization rates and decreases in measles case fatality ratios (CFRs). While some aspects of the reduction in measles mortality can be monitored through increases in immunization coverage, estimating the level of measles deaths (in absolute terms) is problematic, particularly since incidence-based methods of estimation rely on accurate measures of measles CFRs. These ratios vary widely by geographic and epidemiologic context and even within the same community from year-to-year. METHODS: To understand better the variations in CFRs, we reviewed community-based studies published between 1980 and 2008 reporting age-specific measles CFRs. RESULTS: The results of the search consistently document that measles CFRs are highest in unvaccinated children under age 5 years; in outbreaks; the lowest CFRs occur in vaccinated children regardless of setting. The broad range of case and death definitions, study populations and geography highlight the complexities in extrapolating results for global public health planning. CONCLUSIONS: Values for measles CFRs remain imprecise, resulting in continued uncertainty about the actual toll measles exacts

No long-term excess mortality after measles infection : a community study from Senegal

Because measles immunization has been found in all studies to reduce mortality with more than the share of deaths attributed to acute measles, the authors examined mortality after measles infection in a study in a rural area of Senegal that included 6924 unimmunized children, of whom 1118 developped measles. Age-adjusted post-measles mortality was similar to the mortality of unvaccinated, uninfected children (mortality ratio (MR) = 1.04, 95% confidence interval (CI) 0.80-1.35). When controlling for source of infection, mortality rate was significantly different for children who contracted measles from a person outside the home (index cases vs. unvaccinated, uninfected MR = 0.27 95% CI 0.009-0.85) and for children infected at home (secondary cases vs. unvaccinated, uninfected MR = 1.10 95% CI 0.80-1.51). Hence, secondary cases had markedly higher long-term mortality than did index cases (MR = 4.13 95% CI 1.26-13.58). These estimates were essentially unchanged when the effects of season, period, separation from mother, size of community, and size of compound were investigated using a multivariate Cox regression model. The authors conclude that measles infection was not associated with increased mortality after the acute phase of infection and that index cases had lower mortality than uninfected, unvaccinated children. The reduction in mortality after measles immunization can therefore not be explained by the prevention of post-measles mortality