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

Keren Middelkoop, Justine Stewart, Neil Walker, Carmen Delport, David A Jolliffe, Anna K Coussens, James Nuttall, Jonathan C Y Tang, William D Fraser, Christopher J Griffiths, Geeta Trilok Kumar, Suzanne Filteau, Richard L Hooper, Robert J Wilkinson, Linda-Gail Bekker, Adrian R Martineau

Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2023;134():63-70

PMID: 37211272

Abstract

OBJECTIVES

To determine whether weekly oral supplementation with 10,000 IU vitamin D 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.

METHODS

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.

RESULTS

829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D 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).

CONCLUSION

Weekly oral supplementation with 10,000 IU vitamin D 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.

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Address: Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.; Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.; Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa.; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Infectious Diseases and Immune Defense Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK; Departments of Laboratory Medicine, Clinical Biochemistry, and Departments of Diabetes and Endocrinology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK.; Delhi School of Public Health, Institute of Eminence, University of Delhi, Delhi, India; Trivedi School of Biosciences, Ashoka University, Sonipat, India.; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK; Imperial College London, London, UK.; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: [email protected].

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