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Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.
PLoS Med. 2019 09; 16(9):e1002907.PM

Abstract

BACKGROUND

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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Internal Medicine, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, United States of America.Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania.Epidemiology Division, Public Health Center, Castellon, Spain.Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.Epidemiology Division, Public Health Center, Castellon, Spain.Department of Obstetrics & Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India.Partners in Health-Socios En Salud Sucursal, Lima, Peru.Department of Pediatrics, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.Partners in Health-Socios En Salud Sucursal, Lima, Peru.Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.School of Social Work, University of South Florida, Tampa, Florida, United States of America.Biochemical Laboratory, Hospital General, Castellon, Spain.Microbiology Laboratory, Hospital General, Castellon, Spain.Microbiology Laboratory, Hospital General, Castellon, Spain.Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University CRS, Pune, India.Department of Pathology and Microbiology, Aga Khan University, Karachi, Pakistan.Biochemical Laboratory, Hospital General, Castellon, Spain.Department of Pediatrics and Child Health and Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.Biochemical Laboratory, Hospital General, Castellon, Spain.Department of Pediatrics, Byramjee Jeejeebhoy Government Medical College, Pune, India.Partners in Health-Socios En Salud Sucursal, Lima, Peru.Byramjee Jeejeebhoy Government Medical College-Johns Hopkins University CRS, Pune, India.Epidemiology Division, Public Health Center, Castellon, Spain.Center for Biostatistics in AIDS Research and Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Upanga West, Dar es Salaam, Tanzania.Medical Research Council Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.Departments of Medicine and of Health Research and Policy, Stanford University School of Medicine, Stanford, California, United States of America.Laboratory Hospital Regional Antofagasta, Antofagasta, Chile.Epidemiology Division, Public Health Center, Castellon, Spain.Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America.Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.Partners in Health-Socios En Salud Sucursal, Lima, Peru.Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

31509529

Citation

Aibana, Omowunmi, et al. "Vitamin D Status and Risk of Incident Tuberculosis Disease: a Nested Case-control Study, Systematic Review, and Individual-participant Data Meta-analysis." PLoS Medicine, vol. 16, no. 9, 2019, pp. e1002907.
Aibana O, Huang CC, Aboud S, et al. Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Med. 2019;16(9):e1002907.
Aibana, O., Huang, C. C., Aboud, S., Arnedo-Pena, A., Becerra, M. C., Bellido-Blasco, J. B., Bhosale, R., Calderon, R., Chiang, S., Contreras, C., Davaasambuu, G., Fawzi, W. W., Franke, M. F., Galea, J. T., Garcia-Ferrer, D., Gil-Fortuño, M., Gomila-Sard, B., Gupta, A., Gupte, N., ... Murray, M. B. (2019). Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. PLoS Medicine, 16(9), e1002907. https://doi.org/10.1371/journal.pmed.1002907
Aibana O, et al. Vitamin D Status and Risk of Incident Tuberculosis Disease: a Nested Case-control Study, Systematic Review, and Individual-participant Data Meta-analysis. PLoS Med. 2019;16(9):e1002907. PubMed PMID: 31509529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis. AU - Aibana,Omowunmi, AU - Huang,Chuan-Chin, AU - Aboud,Said, AU - Arnedo-Pena,Alberto, AU - Becerra,Mercedes C, AU - Bellido-Blasco,Juan Bautista, AU - Bhosale,Ramesh, AU - Calderon,Roger, AU - Chiang,Silvia, AU - Contreras,Carmen, AU - Davaasambuu,Ganmaa, AU - Fawzi,Wafaie W, AU - Franke,Molly F, AU - Galea,Jerome T, AU - Garcia-Ferrer,Daniel, AU - Gil-Fortuño,Maria, AU - Gomila-Sard,Barbará, AU - Gupta,Amita, AU - Gupte,Nikhil, AU - Hussain,Rabia, AU - Iborra-Millet,Jesus, AU - Iqbal,Najeeha T, AU - Juan-Cerdán,Jose Vicente, AU - Kinikar,Aarti, AU - Lecca,Leonid, AU - Mave,Vidya, AU - Meseguer-Ferrer,Noemi, AU - Montepiedra,Grace, AU - Mugusi,Ferdinand M, AU - Owolabi,Olumuyiwa A, AU - Parsonnet,Julie, AU - Roach-Poblete,Freddy, AU - Romeu-García,Maria Angeles, AU - Spector,Stephen A, AU - Sudfeld,Christopher R, AU - Tenforde,Mark W, AU - Togun,Toyin O, AU - Yataco,Rosa, AU - Zhang,Zibiao, AU - Murray,Megan B, Y1 - 2019/09/11/ PY - 2019/02/04/received PY - 2019/08/12/accepted PY - 2019/9/12/entrez PY - 2019/9/12/pubmed PY - 2020/2/25/medline SP - e1002907 EP - e1002907 JF - PLoS medicine JO - PLoS Med VL - 16 IS - 9 N2 - BACKGROUND: 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. CONCLUSION: 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. SN - 1549-1676 UR - https://www.unboundmedicine.com/medline/citation/31509529/Vitamin_D_status_and_risk_of_incident_tuberculosis_disease:_A_nested_case_control_study_systematic_review_and_individual_participant_data_meta_analysis_ L2 - https://dx.plos.org/10.1371/journal.pmed.1002907 DB - PRIME DP - Unbound Medicine ER -