Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis

Autoři: Omowunmi Aibana aff001;  Chuan-Chin Huang aff002;  Said Aboud aff003;  Alberto Arnedo-Pena aff004;  Mercedes C. Becerra aff002;  Juan Bautista Bellido-Blasco aff004;  Ramesh Bhosale aff005;  Roger Calderon aff006;  Silvia Chiang aff007;  Carmen Contreras aff006;  Ganmaa Davaasambuu aff008;  Wafaie W. Fawzi aff009;  Molly F. Franke aff002;  Jerome T. Galea aff010;  Daniel Garcia-Ferrer aff011;  Maria Gil-Fortuño aff012;  Barbará Gomila-Sard aff012;  Amita Gupta aff013;  Nikhil Gupte aff014;  Rabia Hussain aff015;  Jesus Iborra-Millet aff011;  Najeeha T. Iqbal aff016;  Jose Vicente Juan-Cerdán aff011;  Aarti Kinikar aff017;  Leonid Lecca aff006;  Vidya Mave aff014;  Noemi Meseguer-Ferrer aff004;  Grace Montepiedra aff018;  Ferdinand M. Mugusi aff019;  Olumuyiwa A. Owolabi aff020;  Julie Parsonnet aff021;  Freddy Roach-Poblete aff022;  Maria Angeles Romeu-García aff004;  Stephen A. Spector aff023;  Christopher R. Sudfeld aff009;  Mark W. Tenforde aff024;  Toyin O. Togun aff025;  Rosa Yataco aff006;  Zibiao Zhang aff026;  Megan B. Murray aff002
Působiště autorů: Department of Internal Medicine, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, United States of America aff001;  Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America aff002;  Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania aff003;  Epidemiology Division, Public Health Center, Castellon, Spain aff004;  Department of Obstetrics & Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India aff005;  Partners in Health—Socios En Salud Sucursal, Lima, Peru aff006;  Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America aff007;  Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff008;  Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America aff009;  School of Social Work, University of South Florida, Tampa, Florida, United States of America aff010;  Biochemical Laboratory, Hospital General, Castellon, Spain aff011;  Microbiology Laboratory, Hospital General, Castellon, Spain aff012;  Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff013;  Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University CRS, Pune, India aff014;  Department of Pathology and Microbiology, Aga Khan University, Karachi, Pakistan aff015;  Department of Pediatrics and Child Health and Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan aff016;  Department of Pediatrics, Byramjee Jeejeebhoy Government Medical College, Pune, India aff017;  Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America aff018;  Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania aff019;  Medical Research Council Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia aff020;  Departments of Medicine and of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America aff021;  Laboratory Hospital Regional Antofagasta, Antofagasta, Chile aff022;  Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America aff023;  Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America aff024;  Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada aff025;  Division of Global Health Equity, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America aff026
Vyšlo v časopise: Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med 16(9): e32767. doi:10.1371/journal.pmed.1002907
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002907



Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.

Methods and findings

We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25–(OH)D < 50 nmol/L, insufficiency as 50–75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25–(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75–3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04–2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87–4.87; p trend for decreasing 25–(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22–3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85–21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.


Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Klíčová slova:

Medicine and health sciences – Infectious diseases – Bacterial diseases – Tuberculosis – Tropical diseases – Diagnostic medicine – Tuberculosis diagnosis and management – Pathology and laboratory medicine – Pathogens – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Vitamins – Organic chemistry – Mathematics – Statistics – Research and analysis methods – Mathematical and statistical techniques – Statistical methods – Metaanalysis – Research design – Cohort studies – Biology and life sciences – Nutrition – Nutritional deficiencies – Vitamin D deficiency – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Immunodeficiency viruses – HIV – Retroviruses – Lentivirus – Organisms – Viruses – RNA viruses – Bacteria – Actinobacteria – Mycobacterium tuberculosis


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