Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease.

The New England journal of medicine

Jul 2020

DOI: 10.1056/nejmoa1915176

Citations:131

Influential Citations:5

Interventional (Human) Studies

Enhanced Details

Methods

Phase 3, double-blind, randomized, placebo-controlled trial conducted in 18 public schools in Ulaanbaatar, Mongolia. Participants were schoolchildren aged 6 to 13 years with negative QFT at screening and vitamin D deficiency at baseline (25[OH]D < 20 ng/mL). A total of 8,851 children were randomized (4,418 to vitamin D, 4,433 to placebo); mean age 9.4 years; ~49% female; high prevalence of Bacille Calmette-Guérin vaccination.

Intervention

Vitamin D: 14,000 IU weekly for 3 years, taken as one oral capsule.

Results

Vitamin D supplementation did not reduce the risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection versus placebo. Primary outcome (positive QFT at 3 years) occurred in 3.6% of the vitamin D group vs 3.3% of placebo (adjusted risk ratio 1.10; 95% CI 0.87–1.38; P = 0.42). End-trial mean 25(OH)D was 31.0 ng/mL in the vitamin D group vs 10.7 ng/mL in placebo. Tuberculosis disease occurred in 21 vs 25 participants (adjusted RR 0.87; 95% CI 0.49–1.55). Acute respiratory infection requiring hospitalization occurred in 29 vs 34 participants (adjusted RR 0.86; 95% CI 0.52–1.40). Adverse events were similar in both groups; no hypercalcemia or hypervitaminosis D. Conclusion: Elevating vitamin D status with weekly 14,000 IU supplementation for 3 years did not reduce TB infection, TB disease, or ARI in vitamin D–deficient Mongolian schoolchildren.

Limitations

Lower-than-expected rate of TB infection conversion (QFT positive at 3 years) reduced power to detect smaller effects; exploratory subgroup analyses were not adjusted for multiple comparisons; some end-of-trial QFT results were missing; results may not generalize beyond vitamin D–deficient schoolchildren in Mongolia.

Abstract

BACKGROUND Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking. METHODS We randomly assigned children who had negative results for M. tuberculosis infection according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D3 or placebo for 3 years. The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. Secondary outcomes included the serum 25-hydroxyvitamin D (25[OH]D) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events. RESULTS A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval [CI], 0.87 to 1.38; P = 0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55). A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D-deficient schoolchildren in Mongolia. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02276755.). show less