Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis

被引：95

作者：

Aibana, Omowunmi ^{[1
]}

Huang, Chuan-Chin ^{[2
]}

Aboud, Said ^{[3
]}

Arnedo-Pena, Alberto ^{[4
]}

Becerra, Mercedes C. ^{[2
]}

Bautista Bellido-Blasco, Juan ^{[4
]}

Bhosale, Ramesh ^{[5
]}

Calderon, Roger ^{[6
]}

Chiang, Silvia ^{[7
]}

Contreras, Carmen ^{[6
]}

Davaasambuu, Ganmaa ^{[8
]}

Fawzi, Wafaie W. ^{[9
]}

Franke, Molly F. ^{[2
]}

Galea, Jerome T. ^{[10
]}

Garcia-Ferrer, Daniel ^{[11
]}

Gil-Fortuno, Maria ^{[12
]}

Gomila-Sard, Barbara ^{[12
]}

Gupta, Amita ^{[13
]}

Gupte, Nikhil ^{[14
]}

Hussain, Rabia ^{[15
]}

Iborra-Millet, Jesus ^{[11
]}

Iqbal, Najeeha T. ^{[16
]}

Vicente Juan-Cerdan, Jose ^{[11
]}

Kinikar, Aarti ^{[17
]}

Lecca, Leonid ^{[6
]}

Mave, Vidya ^{[14
]}

Meseguer-Ferrer, Noemi ^{[4
]}

Montepiedra, Grace ^{[18
,19
]}

Mugusi, Ferdinand M. ^{[20
]}

Owolabi, Olumuyiwa A. ^{[21
]}

Parsonnet, Julie ^{[22
,23
]}

Roach-Poblete, Freddy ^{[24
]}

Angeles Romeu-Garcia, Maria ^{[4
]}

Spector, Stephen A. ^{[25
]}

Sudfeld, Christopher R. ^{[9
]}

Tenforde, Mark W. ^{[26
]}

Togun, Toyin O. ^{[27
]}

Yataco, Rosa ^{[6
]}

Zhang, Zibiao ^{[28
]}

Murray, Megan B. ^{[2
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, McGovern Med Sch, Houston, TX 77030 USA

[2] Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA 02115 USA

[3] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania

[4] Publ Hlth Ctr, Epidemiol Div, Castellon de La Plana, Spain

[5] Byramjee Jeejeebhoy Govt Med Coll, Dept Obstet & Gynecol, Pune, Maharashtra, India

[6] Partners Hlth Socios Salud Sucursal, Lima, Peru

[7] Brown Univ, Alpert Med Sch, Dept Pediat, Providence, RI 02912 USA

[8] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[9] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA

[10] Univ S Florida, Sch Social Work, Tampa, FL USA

[11] Hosp Gen, Biochem Lab, Castellon de La Plana, Spain

[12] Hosp Gen, Microbiol Lab, Castellon de La Plana, Spain

[13] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA

[14] Johns Hopkins Univ CRS, Byramjee Jeejeebhoy Govt Med Coll, Pune, Maharashtra, India

[15] Aga Khan Univ, Dept Pathol & Microbiol, Karachi, Pakistan

[16] Aga Khan Univ, Dept Pediat & Child Hlth & Biol & Biomed Sci, Karachi, Pakistan

[17] Byramjee Jeejeebhoy Govt Med Coll, Dept Pediat, Pune, Maharashtra, India

[18] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA

[19] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA

[20] Muhimbili Univ Hlth & Allied Sci, Dept Internal Med, Dar Es Salaam, Tanzania

[21] London Sch Hyg & Trop Med, Med Res Council Gambia, Banjul, Gambia

[22] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[23] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA

[24] Lab Hosp Reg Antofagasta, Antofagasta, Chile

[25] Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA

[26] Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA

[27] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada

[28] Harvard Med Sch, Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA

来源：

PLOS MEDICINE | 2019年 / 16卷 / 09期

基金：

美国国家卫生研究院;

关键词：

INITIATING ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; D DEFICIENCY; ANTIMICROBIAL ACTIVITY; ACTIVE TUBERCULOSIS; DIABETES-MELLITUS; POLYMORPHISMS; SUPPLEMENTATION; SEASONALITY;

D O I：

10.1371/journal.pmed.1002907

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Author summaryWhy was this study done? Although multiple lines of evidence suggest that vitamin D may play a role in host susceptibility to tuberculosis (TB) disease, the impact of low vitamin D on the risk of developing TB disease has not yet been firmly established. What did the researchers do and find? We conducted a study in Lima, Peru, in which we measured serum 25-(OH)D levels in individuals at high risk for TB disease and followed them for development of TB over 1 year. We pooled individual-level data from seven previously published prospective studies conducted worldwide and from our Lima cohort. We found that individuals with low levels of vitamin D were at higher risk of future progression to TB disease. What do these findings mean? These findings suggest that vitamin D deficiency is a risk factor for developing TB disease. Randomized control trials are needed to determine whether vitamin D supplementation reduces risk of TB disease. 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.

引用

页数：26

共 72 条

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