Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia. A randomized trial of vitamin A supplements in relation to mortality among human immunodeficiency virus-infected and uninfected children in Tanzania. Effect of vitamin A on diarrhoeal and respiratory complications of measles. Effects of moderate doses of vitamin A as an adjunct to the treatment of pneumonia in underweight and normal-weight children: a randomized, double-blind, placebo-controlled trial. Effect of vitamin A supplementation on childhood morbidity and mortality. Vitamin A supplementation reduces measles morbidity in young African children: a randomized, placebo-controlled, double-blind trial. Vitamin A supplementation and severity of pneumonia in children admitted to the hospital in Dar es Salaam, Tanzania. Efficacy of vitamin A in reducing preschool child mortality in Nepal. Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity.
To evaluate the impact on clinical recovery and severity of the addition of large doses of vitamin A to the standard treatment for childhood pneumonia.
                A randomised, double blind, placebo controlled trial.
                Study children were recruited at a public hospital in Recife, north east Brazil, an area of marginal vitamin A deficiency.
                472 children aged 6 to 59 months with clinical diagnosis of pneumonia.
                200,000 IU (infants) or 400,000 IU (1-4 year olds) of vitamin A in oil or similar capsules of placebo divided into two daily oral doses, in addition to the standard treatment.
                Duration of the episode and incidence of adverse outcomes.
                The groups were similar with respect to overall duration of pneumonia and incidence of adverse outcomes. Children who received vitamin A, however, were less likely to have fever by day 3 (P = 0.008) and were 29% less likely to fail to respond to the first line antibiotic (P = 0.054).
                There was little evidence for an effect of vitamin A treatment on the immediate outcome of the pneumonia episode. To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children.
                Randomized, double blind, placebo-controlled trial.
                Starting in April, 1993, we randomized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia. Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded. At baseline children received placebo or 400 000 IU (or half that for infants) of vitamin A, in addition to standard treatment for pneumonia. They received further doses of the same regimen 4 and 8 months after hospital discharge. Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests. For positive children <15 months of age, HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays. HIV status was ascertained for 648 of 687 enrolled children. The mean duration of follow-up was 24.4 months (SD = 12.1).
                Of 648 children 58 (9%) were HIV-infected. Compared with uninfected children, all-cause mortality was higher among HIV-infected children, as was mortality caused by pneumonia or diarrhea (P < 0.001 for each). Overall vitamin A supplements resulted in a 49% reduction in mortality [relative risk (RR), 0.51; 95% confidence interval (CI), 0.29 to 0.90, P = 0.02]. Vitamin A supplements reduced all-cause mortality by 63% among HIV-infected children (RR 0.37; CI 0.14 to 0.95, P = 0.04) and by 42% among uninfected children (RR 0.58, CI 0.28 to 1.19, P = 0.14). Vitamin A supplements were also associated with a 68% reduction in AIDS-related deaths (P = 0.05) and a 92% reduction in diarrhea-related deaths (P = 0.01).
                Vitamin A deficiency, which is common among children in many developing countries, is particularly severe among HIV-infected children. Our findings indicate that vitamin A supplements, a low cost intervention, reduce mortality of HIV-infected children. A randomized placebo-controlled trial of high dose vitamin A in acute measles was performed in Nairobi, Kenya to determine if it reduced the incidence or severity of diarrhoeal and respiratory complications. On enrollment laryngotracheobronchitis (LTB) pneumonia, diarrhoea and otitis media were each found in 45-80% of children in the treatment and placebo groups. While 4 of 119 cases of LTB in the placebo group progressed to grade III (loud stridor, markedly diminished air entry, chest indrawing, cyanosis), none of 116 in the vitamin A group did. Episodes of diarrhoea, but not pneumonia, resolved faster and were less severe in the vitamin A group. There were no differences in the incidences of pneumonia, LTB or diarrhoea during hospitalization, but children treated with vitamin A had a lower rate of developing otitis media. The overall case fatality rate was 2.7% and did not differ by group. These findings, along with those from three other trials in Africa, suggest that high dose vitamin A reduces the severity of complications during measles. Randomized controlled trials have shown inconsistent responses of childhood pneumonia to the use of vitamin A as an adjunct to the standard treatment of pneumonia.
                We evaluated the effect of a moderate dose of vitamin A as an adjunct to standard antimicrobial treatment on the duration of respiratory signs in children with pneumonia.
                Children, aged 2-59 mo, with pneumonia and weight-for-age <50th percentile who had been admitted to the Baca Ortíz Children's Hospital in Quito, Ecuador, were randomly assigned to receive 50,000 IU (aged 2-12 mo) or 100,000 IU (aged >12-59 mo) vitamin A or a placebo.
                Of the 287 children enrolled, 145 received vitamin A and 142 received placebo. No overall differences were observed between the 2 groups in the duration of signs of pneumonia. Multiple linear regression showed a significant interaction between basal serum retinol concentration and vitamin A group for the time (in h) to remission of respiratory signs (beta = -3.57, SE = 1.09, P = 0.001). Duration of clinical signs was less in children with basal serum retinol concentrations >200 microg/L who received vitamin A supplements than in children with similar concentrations who received placebo (69.9 +/- 49.9 h compared with 131.3 +/- 143.9 h; P = 0.049).
                Overall, we found no effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged <5 y. However, a beneficial effect was seen in children with high basal serum retinol concentrations. In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high. The effects of vitamin A supplementation on measles morbidity are unclear. Sixty hospitalized children aged 4-24 mo with complicated measles received a World Health Organization--(WHO) recommended dose of vitamin A or placebo. The two groups were comparable in known covariants of measles severity: weight-for-age percentiles, overcrowding, rash, total lymphocytes, and serum concentrations of zinc, albumin, prealbumin, retinol-binding protein, and vitamins A and E. Ninety percent of the patients had hyporetinemia. Integrated morbidity scores, determined by severity of condition (eg, diarrhoea, herpes, and respiratory-tract infection) were assigned on day 8 and 6 wk and 6 mo; these were reduced by 82%, 61%, and 85%, respectively, in the supplemented group, which was mainly due to reduced respiratory-tract infection. There was one death in the placebo group. At 6 wk weight gain was significant in the supplemented group. Despite the selected sample, attention to multiple covariates enhances the validity of the data obtained and supports the current WHO recommendations for vitamin A supplementation during measles. Vitamin A deficiency and acute lower respiratory tract infections coexist as important public health problems in many developing countries. We carried out a randomized, double-blind, placebo-controlled trial to examine whether large doses of vitamin A given to Tanzanian children who are admitted to the hospital with nonmeasles pneumonia would reduce the severity of respiratory disease. Six hundred eighty-seven children were randomly assigned to receive either placebo or vitamin A [200 000 IU (60 mg retinol equivalents) for children > 1 y of age and 100000 IU (30 mg retinol equivalents) for infants] on the day of admission and another dose on the following day. Of the 346 children in the vitamin A group, 13 died in the hospital, compared with 8 of 341 children in the placebo group; the relative mortality was 1.63 (95% CI: 0.67, 3.97; P = 0.28). The mean number of days of hospitalization was the same in both groups (4.2 d). There were no differences between the vitamin A and placebo groups in the duration of hospital stay when examined within categories of children stratified by age, sex, breast-feeding status, nutritional status at baseline, or quartile of dietary vitamin A intake in the 4 mo before admission to the hospital. There were also no differences in the mean number of days of fever, rapid respiratory rate, or hypoxia, whether these endpoints were examined in the total number of subjects or in a subset with more severe clinical conditions at baseline. Large doses of vitamin A had no protective effect on the course of pneumonia in hospitalized Tanzanian children. Community trials of the efficacy of vitamin A supplementation in reducing preschool childhood mortality have produced conflicting results. To resolve the question, a randomised, double-masked, placebo-controlled community trial of 28,630 children aged 6-72 months was carried out in rural Nepal, an area representative of the Gangetic flood plain of South Asia. Randomisation was carried out by administrative ward; the vitamin-A-supplemented children received 60,000 retinol equivalents every 4 months and placebo-treated children received identical capsules containing 300 retinol equivalents. After 12 months, the relative risk of death in the vitamin-A-supplemented compared with the control group was 0.70 (95% confidence interval 0.56-0.88), equivalent to a 30% reduction in mortality. The trial, which had been planned to last 2 years, was discontinued. The reduction in mortality was present in both sexes (relative risk for boys 0.77; for girls 0.65), at all ages (range of relative risks 0.83-0.50), and throughout the year (0.76-0.67). The reduction in mortality risk was not affected by acute nutritional status, as measured by arm circumference. Thus, periodic vitamin A delivery in the community can greatly reduce child mortality in developing countries. 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.
No overall significant reduction in mortality with vitamin A therapy for children with measles was found. However two doses reduced overall and pneumonia-specific mortality in children aged less than two years. No trials directly compared a single dose with two doses.