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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.

Published on Sep 11, 2019in PLOS Medicine11.048
· DOI :10.1371/journal.pmed.1002907
Omowunmi Aibana4
Estimated H-index: 4
(University of Texas Health Science Center at Houston),
Chuan-Chin Huang4
Estimated H-index: 4
(Harvard University)
+ 37 AuthorsMegan Murray57
Estimated H-index: 57
(Harvard University)
Sources
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 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.
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References67
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#2Iris Mair (Edin.: University of Edinburgh)H-Index: 4
Last. Richard J. Mellanby (Edin.: University of Edinburgh)H-Index: 25
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Dendritic cells (DC) are specialized sentinel cells that bridge the innate and adaptive immune response and play a crucial role in shaping the adaptive immune response. Vitamin D, a known epidemiological risk factor for the development of several autoimmune diseases, influences the development of dendritic cells. Consequently, vitamin D metabolites are frequently used in protocols to develop therapeutic dendritic cell therapies for autoimmune diseases. However, the mechanisms by which vitamin D ...
4 CitationsSource
#1David A. Jolliffe (QMUL: Queen Mary University of London)H-Index: 13
#2Davaasambuu Ganmaa (Harvard University)H-Index: 10
Last. Adrian R. Martineau (QMUL: Queen Mary University of London)H-Index: 33
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Background Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. Methods We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear convers...
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#1Hong-xia Wu (Sichuan University)H-Index: 3
#2Xiao-feng Xiong (Sichuan University)H-Index: 3
Last. De-yun Cheng (Sichuan University)H-Index: 3
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Vitamin D is involved in the host immune response toward Mycobacterium tuberculosis. However, the efficacy of vitamin D supplementation on sputum conversion, clinical response to treatment, adverse events, and mortality in patients with pulmonary tuberculosis (PTB) remains controversial. We aimed to clarify the efficacy and safety of vitamin D supplementation in PTB treatment. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science for double-blind, randomized...
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#1Maria Angeles Jimenez-Sousa (ISCIII: Carlos III Health Institute)H-Index: 10
#2Isidoro Martínez (ISCIII: Carlos III Health Institute)H-Index: 14
Last. Salvador Resino (ISCIII: Carlos III Health Institute)H-Index: 27
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People living with human immunodeficiency virus (HIV) infection typically have hypovitaminosis D, which is linked to a large number of pathologies, including immune disorders and infectious diseases. Vitamin D is a key regulator of host defense against infections by activating genes and pathways that enhance innate and adaptive immunity. Vitamin D mediates its biological effects by binding to the vitamin D receptor (VDR), and activating and regulating multiple cellular pathways. Single nucleotid...
14 CitationsSource
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Last. Julio Croda (FIOCRUZ: Oswaldo Cruz Foundation)H-Index: 16
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Poor vitamin D status has been associated with tuberculosis (TB); whether poor status is cause or consequence of disease is uncertain. We conducted a case-control study and two nested case-control studies to determine whether vitamin D levels were associated with active TB, tuberculin skin test (TST) conversion, and risk of progression to the active TB in prisoners in Brazil. In multivariable conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI, 1.04–13.64) were more lik...
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#1Omowunmi Aibana (Brown University)H-Index: 4
#2Molly F. Franke (Brigham and Women's Hospital)H-Index: 20
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#1Bo Chen (McGill University)H-Index: 1
#2Andrea Benedetti (McGill University)H-Index: 33
In meta-analyses (MA), effect estimates that are pooled together will often be heterogeneous. Determining how substantial heterogeneity is is an important aspect of MA. We consider how best to quantify heterogeneity in the context of individual participant data meta-analysis (IPD-MA) of binary data. Both two- and one-stage approaches are evaluated via simulation study. We consider conventional I 2 and R 2 statistics estimated via a two-stage approach and R 2 estimated via a one-stage approach. W...
8 CitationsSource
#1Omowunmi Aibana (Brown University)H-Index: 4
#2Molly F. Franke (Harvard University)H-Index: 20
Last. Megan Murray (Harvard University)H-Index: 57
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Mark W. Tenforde, MD, MPH,* Ashish Yadav, MBBS, MD, MPH,† David W. Dowdy, MD, PhD, Nikhil Gupte, PhD,§ Rupak Shivakoti, PhD, MSPH,§ Wei-Teng Yang, MD, MPH,k Noluthando Mwelase, MBChB, Cecilia Kanyama, MD,# Sandy Pillay, MBChB,** Wadzanai Samaneka, MBChB, MSc,†† Breno Santos, MD,‡‡ Selvamuthu Poongulali, MBBS,§§ Srikanth Tripathy, MBBS,kk Cynthia Riviere, MD, Sima Berendes, MD, MPH,##*** Javier R. Lama, MD, MPH,††† Sandra W. Cardoso, MD,‡‡‡ Patcharaphan Sugandhavesa, MD,§§§ Rarul Christian, DrPH,...
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Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D3; 1,25-(OH)2D3) has been ever expanding. In this review, the attention is shifted towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system. The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system. In vitro...
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#2Claudia SalaH-Index: 5
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#1Hardy Kornfeld (UMMS: University of Massachusetts Medical School)H-Index: 47
Last. Vijay ViswanathanH-Index: 8
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BACKGROUND: Diabetes was identified as a tuberculosis (TB) risk factor mostly in retrospective studies with limited assessment of metabolic variables. The prospective Effects of Diabetes on Tuberculosis Severity study compared adults with pulmonary TB in Chennai, India, who were classified as having diabetes or normal glucose tolerance at enrollment. METHODS: Baseline TB severity, sputum conversion, and treatment outcomes (cure, failure, death, or lost) were compared between groups with respect ...
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