Background: Few studies have evaluated the association between pre-existing vitamin D deficiency (VDD) and incident TB. We assessed the impact of baseline vitamin D on TB risk.
Methods:We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6751 household contacts of TB patients in Peru. We also conducted a one-stage individual participant data meta-analysis searching PubMed and Embase for studies of vitamin D and TB until December 31, 2017. We included studies that assessed vitamin D before TB diagnosis. We defined VDD as 25-(OH)D <50 nmol/L, insufficiency as 50-75 nmol/L and sufficiency as >75nmol/L. We estimated the association between vitamin D and incident TB using conditional logistic regression in the Peru cohort and generalized linear mixed models in the meta-analysis.
Findings:In Peru, baseline VDD was associated with a statistically insignificant increase in incident TB (aOR 1·70, 95% CI 0·84-3·46; p=0·14). We identified seven studies for the meta-analysis and analyzed 3544 participants. Individuals with VDD and very low vitamin D (<25nmol/L) had increased TB risk (aOR 1·48, 95% CI 1·04-2·10; p=0·03 and aOR 2·08, 95% CI 0·88-4·92; p trend=0·02 respectively). Among HIV-positive patients, VDD and very low vitamin D conferred a 2-fold (aOR 2.18, 95% CI 1·22-3·90; p=0·01) and 4-fold (aOR 4·28, 95% CI 0·85-21·44; p trend=0·01) increased risk of TB respectively.Interpretation: Our findings suggest vitamin D predicts TB risk in a dose-dependent manner and vitamin D supplementation may play a role in TB prevention.
Evidence before this studyNumerous studies have found lower serum vitamin D levels among patients with active TB disease compared to healthy controls. However, research has not clarified whether low vitamin D increases TB risk or whether TB disease leads to decreased vitamin D levels. We conducted PubMed and Medline searches for all studies available through December 31, 2017 on the association between vitamin D status and TB disease. We included the following keywords: "vitamin D," "vitamin D deficiency," "hypovitaminosis D," "25-hydroxyvitamin D," "1,25-dihydroxyvitamin D," "vitamin D2," "vitamin D3," "ergocalciferol," "cholecalciferol," and "tuberculosis." We found only seven studies had prospectively evaluated the impact of baseline vitamin D levels on risk of progression to TB disease.We report here the results of a case control study nested within a large prospective longitudinal cohort study of household contacts of TB cases and the results of an individual participant data (IPD) metaanalysis of available evidence on the association between vitamin D levels and incident TB disease.
Added value of this studyWe demonstrated that low vitamin D levels predicts risk of future progression to TB disease in a dosedependent manner.
Implications of all the available evidenceThese findings suggest the possibility that vitamin D supplementation among individuals at high risk for developing TB disease might play a role in TB prevention efforts.