Dehydroepiandrosterone sulfate levels associated with decreased malaria parasite density and increased hemoglobin concentration in pubertal girls from western Kenya

In areas where Plasmodium falciparum malaria is endemic, parasite density, morbidity, and mortality decrease with increasing age, which supports the view that years of cumulative exposure are necessary for the expression of maximal protective immunity. Developmental changes in the host also have been implicated in the expression of maximal resistance. To further evaluate the contribution of host developmental factors in malaria resistance, we examined the relationship between P. falciparum parasitemia and pubertal development in a cross-sectional sample of 12 - 18-year-old schoolgirls from an area of intense transmission in western Kenya. Among pubertal girls, dehydroepiandrosterone sulfate (DHEAS) levels were significantly associated with decreased parasite density, even after adjustment for age. DHEAS levels also were related to increased hemoglobin levels, even after accounting for age and other determinants of hemoglobin level. These findings support the hypothesis that host pubertal development, independent of age and, by proxy, cumulative exposure, is necessary for maximal expression of resistance to malarial infection and morbidity, as assessed by hemoglobin leve

Estimating regional centile curves from mixed data sources and countries.

Regional or national growth distributions can provide vital information on the health status of populations. In most resource poor countries, however, the required anthropometric data from purpose-designed growth surveys are not readily available. We propose a practical method for estimating regional (multi-country) age-conditional weight distributions based on existing survey data from different countries. We developed a two-step method by which one is able to model data with widely different age ranges and sample sizes. The method produces references both at the country level and at the regional (multi-country) level. The first step models country-specific centile curves by Box-Cox t and Box-Cox power exponential distributions implemented in generalized additive model for location, scale and shape through a common model. Individual countries may vary in location and spread. The second step defines the regional reference from a finite mixture of the country distributions, weighted by population size. To demonstrate the method we fitted the weight-for-age distribution of 12 countries in South East Asia and the Western Pacific, based on 273 270 observations. We modeled both the raw body weight and the corresponding Z score, and obtained a good fit between the final models and the original data for both solutions. We briefly discuss an application of the generated regional references to obtain appropriate, region specific, age-based dosing regimens of drugs used in the tropics. The method is an affordable and efficient strategy to estimate regional growth distributions where the standard costly alternatives are not an option. Copyright © 2009 John Wiley & Sons, Ltd

Developing regional weight-for-age growth references for malaria-endemic countries to optimize age-based dosing of antimalarials = Développer des références régionales de croissance pour le rapport poids/âge dans les pays où le paludisme est endémique, afin d’optimiser la posologie des médicaments antipaludiques en fonction de l’âge = Elaboración de referencias regionales sobre el crecimiento ponderal correspondiente a cada edad para los países donde la malaria es endémica a fin de optimizar la dosificación basada en la edad de los medicamentos contra la malaria

Methods: A weight-for-age database was constructed from pre-existing population-based anthropometric data obtained from household surveys and research groups. It contained data collected between 1995 and 2012 on 1 263 119 individuals (909 368 female, 353 751 male) older than 14 days and younger than 50 years in 64 malaria-endemic countries. Regional growth references were generated using a generalized additive model for location, scale and shape by combining data with varying distributions from a range of sources. Countries were weighted by their population at risk of malaria to enable references to be used in optimizing the dosing of antimalarials. Findings: Large differences in weight-for-age distributions existed between the regions and between the regions and global growth standards. For example, the average adult male from the Americas weighed 68.1 kg – 6.0 kg more than males in South-East Asia and the Western Pacific (average: 62.1 kg). For adult women, the difference was over 10.4 kg: the average was 60.4 kg in the Americas and 50.0 kg in South-East Asia and the Western Pacific. Conclusion: There were substantial variations in weight-for-age growth curves between malaria-endemic areas. The growth reference charts derived here can be used to guide the evidence-based optimization of aged-based dosing regimens for antimalarials and other drugs often prescribed by age. Objective: To derive regional weight-for-age growth references to help optimize age-based dosing of antimalarials in Africa, the Americas, South-East Asia and the Western Pacific