Acute lower respiratory infections

Acute lower respiratory infections (ALRI) are a major cause of death among children in developing countries, and major causes of ALRI include respiratory syncytial virus (RSV) infection, parainfluenza, Haemophilus influenzae, Streptococcus pneumoniae and Bordetella pertussis. Secondary bacterial infection with high case fatality may follow a primary viral infection in the lungs. Community-based trials failed to demonstrate any effect of vitamin A supplementation upon morbidity and mortality of ALRI (Vitamin A and Pneumonia Working Group, 1995). Hospital-based studies have also shown that high-dose vitamin A supplementation has no therapeutic effect upon the morbidity of ALRI in children (Kjolhede et al., 1995; Nacul et al., 1997; Fawzi et al., 1998). In Chile and the USA, hospital-based trials showed that vitamin A supplementation had little impact upon RSV infection among infants and young children (Bresee et al., 1996; Dowell et al., 1996; Quinlan and Hayani, 1996).

High-dose vitamin A supplementation may have adverse consequences for some children who are not malnourished (Sempertegui et al., 1999; Fawzi et al., 2000a). In a study conducted in Dar Es Salaam, Tanzania, children hospitalized with pneumonia received high-dose vitamin A supplementation and, after discharge, they were monitored for diarrhoeal and respiratory disease. Vitamin A supplementation was associated with a higher rate of diarrhoeal disease among children who were better nourished, whereas a reduction in diarrhoeal morbidity was noted among wasted children. This apparent bidirectional effect has been termed 'the vitamin A paradox' (Griffiths, 2000). A recent controlled clinical trial conducted in Quito, Ecuador, also suggested that weekly vitamin A supplementation to children, aged 6-36 months, significantly reduced the incidence of ALRI in underweight (weight-for-age Z score < —2) children, but significantly increased the incidence of ALRI in normal-weight children (weight-for-age Z score > —1), compared with placebo (Sempertegui et al., 1999).

Although vitamin A status has been shown to be related to the severity of acute respiratory infection in children (Dudley et al., 1997), it is unclear why vitamin A therapy has no apparent effect in some trials upon the morbidity of acute respiratory infections among preschool children. Young age might be one contributing factor to the lack of an effect, as large community-based studies suggest that vitamin A supplementation has little effect on morbidity and mortality of infants (West et al., 1995; WHO/CHD Immunisation-Linked Vitamin A Supplementation Study Group, 1998). Studies have also been conducted in populations where vitamin A deficiency is not considered a public-health problem. In the recent clinical trials involving RSV infection, the apparent lack of impact of vitamin A supplementation on RSV infection might be due to the young age of the subjects and the lack of vitamin A deficiency in the population. It would be erroneous to consider vitamin A as ineffective in increasing immunity to ALRI completely, as vitamin A supplementation has been shown to reduce the life-threatening complication of pneumonia after acute measles infection (Barclay et al., 1987; Hussey and Klein, 1990).

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