TY - JOUR
T1 - Vitamin D status and risk of incident tuberculosis disease
T2 - A nested case-control study, systematic review, and individualparticipant 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.
N1 - Publisher Copyright:
Copyright © 2019 Aibana et al.
PY - 2019
Y1 - 2019
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 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.
AB - 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.
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U2 - 10.1371/journal.pmed.1002907
DO - 10.1371/journal.pmed.1002907
M3 - Review article
C2 - 31509529
AN - SCOPUS:85072143222
SN - 1549-1277
VL - 16
JO - PLoS medicine
JF - PLoS medicine
IS - 9
M1 - e1002907
ER -