Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicentre phase 3 double-blind randomized placebo-controlled trial (ViDiKids).

BACKGROUND: Vitamin D metabolites induce innate antimycobacterial responses in vitro. Observational studies consistently report independent associations between vitamin D deficiency and increased susceptibility to Mycobacterium tuberculosis infection. METHODS: We conducted a randomised placebo-controlled trial to determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduced risk of sensitisation to M. tuberculosis in Cape Town schoolchildren aged 6-11 years with negative QuantiFERON-TB Gold Plus (QFT-Plus) assay results at baseline. The primary outcome was a positive end-trial QFT-Plus result, analysed using a mixed effects logistic regression model with school of attendance included as a random effect. RESULTS: 1682 children attending 23 schools were randomised (829 to vitamin D, 853 to placebo). Mean end-study 25(OH)D concentrations in participants randomised to vitamin D vs. placebo were 104.3 vs. 64.7 nmol/L, respectively (95% CI for difference, 37.6 to 41.9 nmol/L). 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% CI 0.62 to 1.19, P=0.35). CONCLUSIONS: Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.