%0 Journal Article
%T Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis
%A Aarti Kinikar
%A Alberto Arnedo-Pena
%A Amita Gupta
%A Barbar芍 Gomila-Sard
%A Carmen Contreras
%A Christopher R. Sudfeld
%A Chuan-Chin Huang
%A Daniel Garcia-Ferrer
%A Ferdinand M. Mugusi
%A Freddy Roach-Poblete
%A Ganmaa Davaasambuu
%A Grace Montepiedra
%A Jerome T. Galea
%A Jesus Iborra-Millet
%A Jose Vicente Juan-Cerd芍n
%A Juan Bautista Bellido-Blasco
%A Julie Parsonnet
%A Leonid Lecca
%A Maria Angeles Romeu-Garc赤a
%A Maria Gil-Fortuˋo
%A Mark W. Tenforde
%A Megan B. Murray
%A Mercedes C. Becerra
%A Molly F. Franke
%A Najeeha T. Iqbal
%A Nikhil Gupte
%A Noemi Meseguer-Ferrer
%A Olumuyiwa A. Owolabi
%A Omowunmi Aibana
%A Rabia Hussain
%A Ramesh Bhosale
%A Roger Calderon
%A Rosa Yataco
%A Said Aboud
%A Silvia Chiang
%A Stephen A. Spector
%A Toyin O. Togun
%A Vidya Mave
%A Wafaie W. Fawzi
%A Zibiao Zhang
%J -
%D 2019
%R 10.1371/journal.pmed.1002907
%X 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每(OH)D < 50 nmol/L, insufficiency as 50每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每(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每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每2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87每4.87; p trend for decreasing 25每(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每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每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
%K Tuberculosis
%K Vitamin D
%K Metaanalysis
%K Tuberculosis diagnosis and management
%K Vitamin D deficiency
%K HIV
%K Mycobacterium tuberculosis
%K Cohort studies
%U https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002907