Reducing infection severity Vitamin A deficiency impairs systemic immunity and increases the incidence and severity of infections during childhood, particularly measles and infectious diarrhoea. There is also evidence that infectious diseases, such as measles, will in turn depress serum retinol concentrations, by >30% according to one study (Enwonwu & Phillips 2004). This phenomenon does not just occur in undernourished populations. A study of well-nourished children in the USA with measles identified that 50% had concurrent vitamin A deficiency (Arrieta et al 1992).

It is suspected that infectious diseases influence retinol metabolism through mechanisms that are more complex than simple loss of retinol stores (Enwonwu & Phillips 2004). Impaired synthesis of retinol-binding protein and transthyretin and decreased expression of the receptors for retinoic acid could also be responsible. As such, the use of vitamin A in the treatment of infectious disease is not limited to developing countries, but may also have application in well-nourished populations.

In areas where vitamin A deficiency may be present, the World Health Organization recommends administration of an oral dose of 200 000 IU (or 100 000 IU in infants) of vitamin A per day for 2 days to children with measles (D'Souza & D'Souza 2002a,b). It has also been recommended that prophylactic vitamin A supplements be given to all infants and young children (0-59 months), pregnant women and postpartum women 6 weeks after delivery, in these same areas (Ross 2002).

According to a 2005 Cochrane review, the WHO recommendation of two large doses of vitamin A does successfully lower the risk of death from measles in hospitalised children under the age of 2 years, but not in all children with measles (Huiming et al 2005).

Reducing secondary infections associated with measles A meta-analysis of six clinical trials found a 47% reduction in the incidence of croup in children with measles who were treated with 200 000 IU of vitamin A on 2 consecutive days. One study in the analysis reported a 74% reduction in the incidence of otitis media, but this was not confirmed in others. A statistically significant decrease in the duration of

diarrhoea, pneumonia, hospital stay and fever was also observed (D'Souza & D'Souza 2002a).

Reducing childhood mortality It has been estimated that a 23% reduction in young child mortality is possible with improvements in vitamin A status. This is most marked for deaths due to acute gastroenteritis and measles, but not acute respiratory infections or malaria (Ramakrishnan & Martorell 1998) and is particularly the case for older preschool children, whereas the effect on infants is less clear. Very low birth weight infants Supplementing VLBW infants with intramuscularly administered vitamin A is associated with a reduction in death or oxygen requirement at 1 month of age (Darlow & Graham 2002).

Reducing the risk of HIV transmission from mother to infant The dominant mode of acquisition of HIV infection for children is mother-to-child transmission. Currently this results in more than 2000 new paediatric HIV infections each day worldwide. A 2005 Cochrane review analysed results from four trials, which enrolled 3,033 HIV-infected pregnant women, and found no evidence to support the use of vitamin A supplementation for this indication (Wiysonge et al 2005). One benefit that was identified forvitamin A supplementation was an improvement in infant birth weight.

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