Title
Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individualparticipant data meta-analysis
Date Issued
01 January 2019
Access level
open access
Resource Type
review
Author(s)
Aibana O.
Huang C.C.
Aboud S.
Arnedo-Pena A.
Becerra M.C.
Bellido-Blasco J.B.
Bhosale 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.
Hussain R.
Iborra-Millet J.
Iqbal N.T.
Juan-Cerdán J.V.
Kinikar A.
Mave V.
Meseguer-Ferrer N.
Montepiedra G.
Mugusi F.M.
Owolabi O.A.
Parsonnet J.
Roach-Poblete F.
Romeu-García M.A.
Spector S.A.
Sudfeld C.R.
Tenforde M.W.
Togun T.O.
Zhang Z.
Murray M.B.
Publisher(s)
Public Library of Science
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 HIVpositive 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.
Volume
16
Issue
9
Language
English
OCDE Knowledge area
Otras ciencias médicas
Sistema respiratorio
Enfermedades infecciosas
Scopus EID
2-s2.0-85072143222
PubMed ID
Source
PLoS Medicine
ISSN of the container
15491277
Sponsor(s)
MBM acknowledges funding from the National Institute of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID) (U19AI076217, U01AI057786, TBRU U19AI111224; https://report.nih.gov/). OA acknowledges funding from the National Institute on Drug Abuse (NIDA) (T32DA013911); https:// www.drugabuse.gov/international/researchfunding- landing) and National Institute of Mental Health (NIMH) (R25MH083620; https://report.nih. gov/). AG, GM, and SAS acknowledge funding for the NWCS113 International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) study provided by National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under award numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). Support of the sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network (NICHD contract number N01-DK-9-001/HHSN267200800001C), NIAID (UM1AI069465 to AG), and NINDS (5R01NS077874 to SAS; https://report.nih.gov/). MWT and AG acknowledge the NWCS319 project was supported by Award Number U01AI068636 to the AIDS Clinical Trials Group from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health (NIMH) and National Institute of Dental and Craniofacial Research (NIDCR). The work was also supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (U01AI069497, R01AI080417, UM1AI069465 to AG). The parent trial A5175 was also supported in part by Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline. MWT also acknowledges funding from NIH (F32AI140511; https://report.nih.gov/). AG, VM, and NG acknowledge research reported in this publication was supported by Gilead Foundation (https://www.gilead.com/purpose/ giving/gilead-foundation), Ujala Foundation (Newtown Square, PA, USA), and Wyncote Foundation (Philadelphia, PA, USA; https://www. gilead.com/purpose/giving/gilead-foundation). VM, NG, RB, AK, and AG acknowledge funding for the SWEN trial was supported by the NIAID (R01 AI45462), the NIH - Fogarty International Center Program of International Training Grants in Epidemiology Related to AIDS (D43-TW0000), the NIAID Byramjee Jeejeebhoy Medical College HIV Clinical Trials Unit (U01 AI069497), and the NIAID's Baltimore-Washington-India Clinical Trials Unit (UM1 AI069465; https://report.nih.gov/). CRS acknowledges funding from the National Institute of Child Health and Human Development (R01 HD32257; https://report.nih.gov/). NTI acknowledges funding from the National Commission on Biotechnology (PCST/NCB-AC3/2003), the Higher Education Commission (HEC#20/796/ R&D/06; http://www.hec.gov.pk/ english/pages/home.aspx), the International Research Support Initiative Program of the Higher Education Commission Government of Pakistan (http://www.hec.gov.pk/english/ scholarshipsgrants/IRSIP/Pages/default.aspx), and the Bill and Melinda Gates Foundation (https:// www.gatesfoundation.org/). SC acknowledges funding from the NIH Fogarty International Center (K01TW010829; https://report.nih.gov/). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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