The Effect of Vitamin D Supplementation on the Incidence of Pneumonia in Children in Afghanistan: a Randomized Controlled Trial

Vitamin D, an essential micronutrient has a biological function in the formation and maintenance of strong bones. Vitamin D may help maintain a healthy immune system. In vitro studies have shown that 1,25-dihydroxyvitamine D3 (1,25(OH)2D3), the active metabolite of vitamin D is important for promoting and regulating immune responses. 1,25(OH)2D3 is an immune system modulator and induces expression of the TLR co-receptor CD145. 1,25(OH)2D3 directly induces antimicrobial gene expression an activity points to important therapeutic uses in treatment of opportunistic and some antibiotic resistant infections. Sub-clinical vitamin D deficiency has been associated with an increased risk of tuberculosis in adults through modification of polymorphisms in the vitamin D receptor. Vitamin is acquired primarily from sunlight; ultraviolet rays trigger synthesis in the skin, which is reduced in darker skins. The required UV light also reduces with distance from the equator to zero at latitudes above 500 in winter. Vitamin D deficiency can cause rickets, a common problem in many developing countries; prevalences of 5 to 45% in under-5 year old children have been found, even in places with abundant sunlight. Pneumonia is the leading cause of childhood mortality, accounting for 19% of the 10.6 million deaths that occur each year. Hospital-based case-control studies from Ethiopia and India suggest that vitamin D deficiency may substantially increase the risk of severe pneumonia in young children. High rates of vitamin D deficiency have also been found among children admitted to hospital for pneumonia, ranging from 43% in Tehran and Kuwait 27 to 50% in Yemen. Afghanistan has a very high under-5 and infant mortality (257 and 165 deaths/1000 live births respectively), and pneumonia is a leading cause of death in children. Women and young children have little exposure to sunlight, and thus are at risk of vitamin D deficiency. Women do not travel out of the home regularly; wear burkas or clothing that covers all but their hands and face. Swaddling of infants reduces exposure to sunlight, as does keeping young children in the mother's vicinity indoors. A survey during the winter of 2005 confirmed very high levels of vitamin D deficiency among young children in Kabul.

Controlling this deficiency has the potential to dramatically reduce the incidence of pneumonia and by so doing save lives. Three-monthly oral doses of 100,000iu of vitamin D have been proven to be safe and effective in alleviating vitamin D deficiency in high risk normal or rackettic children. Thus we propose to conduct a randomized controlled trial (RCT) in Afghanistan to test this.

Study area:

The trial will be carried out in District 1,2,3,7 and 8 of Kabul (latitude 34.280 N), where the vitamin D deficiency prevalence study was conducted in 2005. Most of these are old parts of Kabul with narrow, shaded lanes often with roofed tops between high walled mud houses; most houses have small courtyards with high walls so that for much of the day sunshine does not reach the courtyard. The population is socio-economically deprived with large families (5-10 children).

Recruitment: