Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, west Africa

Abstract

WHO has recommended vitamin A supplementation for children aged 6 months or older in developing countries at the same time as immunisation. One study has reported significantly lower seroconversion ratios among children who have received vitamin A supplements with measles vaccine at age 6 months. The aim of our study was to assess the effect of vitamin A supplementation on antibody response to measles vaccination at age 9 months, which is the more common age for immunisation in developing countries. In an urban community in Guinea-Bissau, we did a randomised, double-blind, placebo-controlled study of the effect of simultaneous vaccination and vitamin A supplementation in 462 children who received either a two-dose schedule of measles vaccine at the ages of 6 months and 9 months (150 infants) or one dose of measles vaccine at age 9 months (312 infants). Children were followed up to the age of 18 months and a blood sample was then collected to assess the antibody response. 397 (86%) of the children took part in the follow-up (52 [11%] had moved and 13 [3%] had died). Among children who received a two-dose vaccine schedule, seroconversion was 98%. There was no difference in seroconversion or geometric mean titre (GMT) for children receiving vitamin A compared with children receiving no supplement. Among children receiving only one dose of measles vaccine at age 9 months, seroconversion was 95%. The GMT was significantly higher in children receiving vitamin A than in those receiving no supplement (3704 vs 2439 mIU; GMT ratio 1.52 [1.22-1.88]). The effect on plasma antibody concentration in the blood was stronger for boys (3902 vs 1916 mIU; GMT ratio 2.04 [1.53-2.72]) than for girls (3502 vs 3017 mIU; GMT ratio 1.16 [0.85-1.58]) who had received vitamin A with measles vaccine. In a multivariate analysis of variance adjusted for sex, vitamin A supplementation was associated with higher antibody titres (p < 0.001). There was a significant interaction between vitamin A supplementation and sex (p = 0.02). There is no indication that simultaneous administration of measles vaccine and vitamin A supplements has a negative effect on measles immunity. Among the children who had received two doses of measles vaccine at the ages of 6 months and 9 months, supplements of vitamin A had no significant effect. Among children only receiving one dose of measles vaccine at age 9 months, 100,000 IU vitamin A increased antibody concentrations, especially for boys.