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

• Published in: International journal of infectious diseases Vol. 134; pp. 63 - 70
• Main Authors: Middelkoop, Keren, Stewart, Justine, Walker, Neil, Delport, Carmen, Jolliffe, David A., Coussens, Anna K., Nuttall, James, Tang, Jonathan C.Y., Fraser, William D., Griffiths, Christopher J., Kumar, Geeta Trilok, Filteau, Suzanne, Hooper, Richard L., Wilkinson, Robert J., Bekker, Linda-Gail, Martineau, Adrian R.
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01.09.2023; Elsevier
• Subjects: Child; Cholecalciferol - therapeutic use; Dietary Supplements; Double-Blind Method; Humans; Interferon-gamma release assay; Latent Tuberculosis - drug therapy; Mycobacterium tuberculosis; Randomized controlled trial; South Africa - epidemiology; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - drug therapy; Tuberculosis - prevention & control; Vitamin D; Vitamins - therapeutic use; South Africa; Tuberculosis; Interferon-gamma release assay; Vitamin D; Randomized controlled trial
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2023.05.010

•We did a phase 3 randomized placebo-controlled trial of vitamin D to prevent tuberculosis (TB) infection in 1682 QuantiFERON-TB Plus-negative children in Cape Town, South Africa.•In total, 63.2% of participants had serum 25-hydroxyvitamin D (25[OH]D) concentrations <75 nmol/l at baseline.•The intervention was weekly oral administration of 10,000 IU vitamin D3 for 3 years.•This was effective in elevating serum 25(OH)D concentrations in participants randomized to the intervention arm of the trial.•The intervention did not influence the risk of QuantiFERON-TB Plus conversion. To determine whether weekly oral supplementation with 10,000 IU vitamin D3 for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline. We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect. 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D3 vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 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% confidence interval 0.62-1.19, P = 0.35). Weekly oral supplementation with 10,000 IU vitamin D3 for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.