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Title:   Author  item
                                            Stephensen, Charles
  Submitted to: International Journal of Epidemiology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/1/2003
                                    Publication  Date: 1/1/2003
                                    Citation: Stephensen, C.B. 2003. Commentary: a hypothesis concerning vitamin a supplementation, vaccines and childhood mortality. International Journal of Epidemiology. 32(5):828-829.Interpretive Summary: The article is a Commentary invited by the Editor of 
the International Journal of Epidemiology on an article to be published in the October issue:  Benn, C. S., Bale, C., Sommerfelt, H., Friis, H.,& Aaby, P. (2003) Hypothesis. Vitamin A supplementation and childhood mortality: Amplification of the non-specific effects of vaccines? International Journal of Epidemiology (in press). The Commentary discusses the authors hypothesis that the beneficial effects of vitamin A supplements on reducing childhood mortality are linked to the non-specific protective effect of BCG and measles vaccinations. The hypothesis explains some anomalies in the current view of vitamin A supplementation effects but requires further work to be convincing as no mechanistic explanation explaining how vitamin A would have an effect similar to vaccination is presented.
                                Technical Abstract: Vitamin A supplements in community intervention trials seem to provide maximum protection against death from infectious diseases when provided at birth or after six months of age (Humphrey and Rice 2000).  Why this is so is not clear and part of the reason may be a lack of data in young infants.  However, Benn and colleagues (Benn et al. 2003) have other ideas and have proposed a hypothesis to explain this inconsistency.  First, a little background information is in order.  
The goals of vitamin A supplementation programs in areas of the world where vitamin A deficiency is a public health problem are, of course, to treat and prevent vitamin A deficiency.  The principal adverse consequences of vitamin A deficiency are xerophthalmia and increased risk of death from infectious diseases.   Decreasing mortality risk has become the principal goal of vitamin A supplementation programs in the past decade.  Many large-scale community intervention trials have been conducted and a definitive conclusion is that vitamin A supplementation decreases mortality in infants and young children over six months of age.
Speculation on the reason for a lesser effect when supplements are given between birth and six months have focused on differences in environmental influences on this age group (e.g., the protection of breastfeeding against malnutrition and infection) or on differences among the populations studied (e.g., different prevalence rates of infectious diseases among study sites may affect underlying mortality rates) (Villamor and Fawzi 2000).
However, the question of which improvements (e.g., improved mucosal integrity, enhanced T-cell mediated immunity) are causing the decreased mortality has not been answered.  Some may argue that understanding how a thing happens is not important in a public health context as long as the desired result of decreased mortality is achieved.  However, it is now quite clear that vitamin A improves recovery from some infections (e.g., some diarrheal diseases and measles) but not others (e.g., non-measles pneumonia) (Villamor and Fawzi 2000).   Better understanding the mechanism of action of vitamin A on immune function would presumably explain these observations and better allow public health practitioners to target their interventions to maximize benefit and minimize risk.


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