Academic journal article Bulletin of the World Health Organization

Potential Interventions for the Prevention of Childhood Pneumonia in Developing Countries: A Meta-Analysis of Data from Field Trials to Assess the Impact of Vitamin A Supplementation on Pneumonia Morbidity and Mortality

Academic journal article Bulletin of the World Health Organization

Potential Interventions for the Prevention of Childhood Pneumonia in Developing Countries: A Meta-Analysis of Data from Field Trials to Assess the Impact of Vitamin A Supplementation on Pneumonia Morbidity and Mortality

Article excerpt

Background

Several histopathological changes to epithelial tissue following vitamin A depletion have been described which suggest that vitamin A deficiency (VAD) might predispose to respiratory infections. Widespread keratinization of the epithelium in the nose, sinuses, larynx, trachea and bronchi in rats[1], autopsy findings of keratinizing metaplasia of the respiratory tract in children[2], and electron microscopy studies showing early, rapid squamous metaplasia with loss of ciliary and goblet cells in rats[3] have all established that vitamin A is essential to the normal growth and differentiation of respiratory tract epithelium. Reduced lysozyme activity that responds to vitamin A therapy has also been observed in children[4]. These changes result in a reduction of the trapping and clearing of airborne pathogens and irritants, and an increase of bacterial binding to respiratory epithelial cells[5]. The physical and biological integrity of epithelial tissue, which is the first barrier to infection, is thus compromised in vitamin A deficiency and this would be expected to result in an increase in the incidence of respiratory infections.

Abnormalities in systemic immunity also occur. These include changes in the mass and maturation of lymphoid tissue, abnormal production of immune response regulators, reduced natural killer cell activity, and abnormal phagocyte and cytotoxic function and antibody production[6-9]. Although the changes are less clear and varied for the different components of the immune system, the net effect appears to be a depression of the specific response to infection once the epithelial barriers have been breached.

Consistent with these results are findings from longitudinal field observational studies that children with VAD have an increased risk of acute respiratory infections[10-12]. Clinical studies have also shown that the severity of illness and case fatality are reduced when vitamin A is administered to children with measles[13-16]. It has therefore been hypothesized that improving the vitamin A status of children who are vitamin A deficient should lead to a reduction in respiratory morbidity and mortality. If this proves to be the case. promoting vitamin A programmes would be a potential strategy for the control of childhood pneumonia, which alone accounted for nearly 3.6 million out of the 12 million childhood deaths that occurred in developing countries in 1990[17].

In an initial review in February 1992, we examined the relationship between VAD and childhood pneumonia and the impact of vitamin A supplementation on pneumonia. At that time there were few published studies on this topic. Those studies that had been carried out had primarily evaluated the impact of vitamin A on overall childhood mortality, and contained very little information on-pneumonia-specific morbidity and mortality. Data from six field trials in Indonesia, India, and Nepal were reviewed[18-23], which showed large reductions in overall childhood mortality following supplementation with vitamin A.

A large beneficial impact on all-cause mortality cannot be expected without an impact on the leading causes of childhood deaths, i.e., pneumonia and diarrhoea, which together account for more than 60% of all childhood deaths in developing countries. However, although deaths due to diarrhoea and measles were reduced in these studies, there was no impact on deaths due to pneumonia. The data from the studies were not disaggregated by age. and an impact on pneumonia could have been missed because infants were underrepresented. Nearly 75% of nonprimary measles and pertussis pneumonia deaths among preschool-age children occur in infants - up to 58% before 6 months of age. Except for the two studies in Nepal, all the others were of children above 6 months of age (6-72 months), and individual studies had covered insufficient numbers of children in the most vulnerable age group to detect an impact on pneumonia. …

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