I proposed the hypothesis that vitamin A amplifies not only the specific vaccine effects, as we saw for measles vaccine, but also the non-specific effects of vaccines on mortality from other infectious diseases. According to my hypothesis, vitamin A would enhance the non-specific beneficial effects on mortality of BCG and measles vaccine, but also the negative effects of DTP vaccine.
Hence, the hypothesis offered an explanation for the mortality-age pattern after vitamin A supplementation. Since it was formulated, I have aimed to test this hypothesis. Since it is associated with ethical problems to randomise children above 6 months of age to vitamin A supplementation, and to randomise children in general to recommended vaccines, we have had to be pragmatic when designing the trials.
Hence, our studies have taken many different forms. We conducted an observational study during a vitamin A campaign in which missing vaccines were also provided, and a randomised trial testing the effect of two different doses of vitamin A during another campaign; we tested the effect of providing vitamin A with BCG at birth in two randomised trials, and we reanalysed data from one of the original randomised trials of vitamin A supplementation from the perspective of vaccination status.
In all studies the main outcome was mortality. The results document that vitamin A supplements do more than protect against vitamin A deficiency.
They support the hypothesis that vitamin A supplements interact with vaccines with important consequences for mortality. The estimated mortality rate for measles there is closer to 15 per 1, cases, compared to 1 per 1, in industrialized nations. Certainly, malnutrition, lack of access to care and lack of a vaccine have all come together to hurt and kill many children in Madagascar.
There is no end in sight to the epidemic there since measles is endemic, meaning that it is constantly occurring with new generations of susceptible children being born each year.
Unlike Madagascar, the epidemic in Europe and the ones we have seen here in the United States is driven by misinformation and fear of the measles vaccine. Parents are refusing to immunize their children in the developed nations. In the developing countries, like Madagascar, parents are begging for the vaccine to save the lives of their children. Quite a contrast. Among the misinformation circulating in anti-vaccine circles in the United States is the falsehood that vitamin A somehow protects against measles, or that children who are getting measles in the United States are simply vitamin A deficient.
Needless to say, there is no scientific evidence that vitamin A supplementation prevents measles infection. However, vitamin A supplementation as an additional treatment of cases of measles in order to prevent death i s recommended by some researchers , particularly in places where malnutrition is known to be a problem. The best prevention of measles continues to be the measles vaccine. All scientific discoveries come with some level of apprehension, especially if the results are found to be revolutionary, like Dr.
This is why the scientific method has been developed and refined, helping us confirm these observations and expand on them.
Sommer and his colleagues found, vitamin A prevents deaths from measles and other infectious diseases, but it does not prevent the infections themselves. For that, we have a vaccine with an excellent track record of safety. Unfortunately, some parents are forgoing all vaccines for their children based on unfounded and non-scientific claims.
Other parents in developing nations simply lack the resources and access to the vaccine. Administration of vitamin A with tetanus toxoid in young children in Bangladesh did not result in an increased antibody response to the vaccine Brown et al.
Another study in Indonesian children reported an improved antibody response in the vitamin A-treated children compared to those given a placebo, when Diphtheria-Pertussis-Tetanus DPT vaccine was given 2 wk after supplementation Semba et al.
Animal studies have clearly demonstrated that vitamin A repletion of depleted animals causes significantly improved antibody response to protein T cell-dependent and polysaccharide T cell-independent type 2 antigens Ross In the multiple linear regression analysis restricted to malnourished infants, the factors associated with a higher post-immunization antibody titer were vitamin A administration, being not previously immunized with DPT or Oral Polio vaccines, and the presence of baseline measles antibody.
There is a plausible explanation for the paradoxical finding of higher antibody titer at the end of the study in those who had baseline antibody. As expected, both seroconversion rate Therefore, we attribute the higher post-immunization antibody titer in these infants to the remaining baseline antibody after decay in 12 wk, despite a poorer response to the measles vaccine. The observed improvement in vaccine immunogenicity in malnourished infants that were administered vitamin A in this study should be interpreted with caution; this finding is based on a subgroup analysis.
Because randomization was not performed at the subgroup level, baseline characteristics of the two intervention groups may have differed.
This seems unlikely in the present situation because, in a multiple linear regression model restricted to malnourished infants, the impact of vitamin A on post-immunization antibody titer remained significant even after the adjustment for potentially confounding factors. The most meaningful test for the serologic evaluation of immunity status to viral infections including measles is the neutralization test.
Also, the present study was designed to compare the antibody response between the two intervention groups and not for evaluating the absolute protection against measles. The major implication of these findings is that they set to rest the controversy about the current recommendation of combining vitamin A supplementation with measles immunization of infants at 9 mo of age in public health programs.
We thank Kiran Bhatia for help in the statistical analysis. Beaton , G. Google Scholar. Google Preview. Benn , C. Lancet : — Bhandari , N. Brown , K. Cantorna , M.
Cremer , N. De Souza , V. A comparison with haemagglutination inhibition, immunofluorescence and plaque neutralization tests. Fawzi , W. JAMA : — Friedman , A. Glasziou , P. Markowitz , L. Neumann , P. Pocock , S. Ross , A. Background document, October. Ross , D. Semba , R. Lancet : 5 — 8. Smith , P. Tokuyama , Y. Cell Immunol : — Voller , A. Infants were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization.
Antibodies to measles were measured by ELISA in serum samples obtained at before baseline and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A
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