Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity

Abstract

The authors assessed the efficacy of the World Health Organization (WHO) recommendation of 200,000 IU of vitamin A in oil to treat acute non-xerophthalmic measles patients. Acute measles patients who did not require hospitalization were enrolled in a randomized, double-masked, clinical trial of vitamin A (n=90) versus placebo (n=110) carried out in Ndola, Zambia, in 1991. Measles-associated morbidity was defined by the presence of signs and symptoms of acute respiratory infection. Daily evaluations for the first 3 days were followed by weekly visits for a month at urban health centers. Baseline demographic, clinical, and biochemical characteristics were similar in both groups. Cross-sectional analysis of morbidity status, by group, at each weekly evaluation showed no significant differences until week 4, when more placebo-treated patients had cough or pneumonia (p=0.005). However, longitudinal analysis, which looked at changes among individuals and controlled for initial health status, showed more equivocal results. The odds ratio for the development of pneumonia in patients with measles cough in vitamin A-treated subjects was 0.73 (95% confidence interval (Cl) 0.30-1.80). The odds ratio for the development of measles-associated cough or pneumonia in asymptomatic measles patients was 0.52 (95% Cl 0.24-1.13), in favor of vitamin A, but the odds ratio for failing to improve from pneumonia in vitamin A-treated subjects was 1.23 (95% Cl 0.68-2.3), a result in favor of placebo. These results suggest that the evidence for the efficacy of one dose of vitamin A in oil to prevent measles complications is not as strong as that previously shown for two 200,000 IU doses of water-miscible vitamin A, and that the WHO recommendation may need to be reexamined.

PIP: In 1991, in Ndola, Zambia, staff at urban health centers randomly allocated children with acute measles who did not require hospitalization to receive either a single oral dose of 200,000 IU of oil-soluble vitamin A (90 children) or a placebo (110 children). (A single oral administration of vitamin A at this dose is recommended by the World Health Organization [WHO]). This double-blind placebo-controlled clinical study aimed to determine whether or not a single oral dose of vitamin A would minimize measles-associated morbidity in children who do not require hospitalization. The cross-sectional analysis revealed that at week 4 the vitamin A group was more likely than the placebo group to have no symptoms of acute respiratory infection (ARI) (93% vs. 78%) and less likely to have pneumonia (0 vs. 12%) (p = 0.005). It did not find any significant association prior to week 4, however. None of the three longitudinal analyses found vitamin A to have a significant benefit on morbidity. These analyses considered the effect of treatment on the movement of individual patients between ARI health states. The odds ratio for pneumonia in children with measles-associated cough and for measles-associated cough or pneumonia in asymptomatic measles patients suggested that vitamin A minimized morbidity (0.73 and 0.52, respectively). Yet vitamin A failed to improve pneumonia (odds ratio = 1.23, in favor of placebo). These findings suggest that a single oral dose of 200,000 IU of oil-soluble vitamin A is not as effective at preventing measles complications as that indicated earlier for two 200,000 IU doses of water-miscible vitamin A. Thus, the WHO recommendations need to be reconsidered.