Vitamin D deficiency and the risk of tuberculosis: a meta-analysis

Huang, Shaojun; Wang, Xianhua; Liu, Zhidong; Cao, Weipeng; Han, Yi; Ma, Aiguo; Xu, Shaofa

doi:10.2147/dddt.s79870

Cited by 128 publications

(106 citation statements)

References 43 publications

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“…122 VitD3 deficiency is a risk factor for development of TB disease, 123 although a randomised control trial failed to show a profound effect on TB treatment outcome. 124 Further trials are required to accurately define the value of vitD3 as TB HDT.…”

Section: Vitaminsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

285

248

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Vitaminsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

285

248

View full text Add to dashboard Cite

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“…Numerous observational studies have also documented lower serum vitamin D levels among TB patients compared to healthy controls, and prior meta-analyses investigating the association between vitamin D and TB have concluded that low vitamin D increases TB disease risk. [7][8][9][10] However, most studies were cross-sectional studies and assessed vitamin D status after the diagnosis of active TB disease, rather than the impact of pre-existing vitamin D levels on the risk of progression to TB disease. Given TB disease can induce profound metabolic abnormalities, it remains unclear whether vitamin D deficiency increases TB disease risk or whether TB disease leads to decreased serum vitamin D levels.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, prior studies evaluating the association between vitamin D and TB disease have used different cutoffs to categorize vitamin D levels or define vitamin D deficiency. [7][8][9][10] Hence, it is challenging to determine whether there is a vitamin D threshold below which individuals are at risk of TB disease.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D status and risk of incident tuberculosis disease: a systematic review and individual participant data meta-analysis

Aibana

Huang

Aboud

et al. 2018

Preprint

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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.

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“…5 A recent meta -analysis demonstrated that vitamin D levels are significantly lower in patients with tuberculosis (TB) compared with controls (apart from the African population). 18 About 70% to 90% of patients with TB have 25(OH)D levels below 20 ng/ml. 19,20 Janssens et al 6 demonstrated that patients with COPD had significantly lower 25(OH)D levels compared with healthy smokers and that vitamin D deficiency correlated with disease severity.…”

Section: Vitamin D Pathway Most Vitamin D Is Produced In the Skin By mentioning

confidence: 99%

Vitamin D supplementation in respiratory diseases - evidence from RCT

Mathyssen¹,

Gayan‐Ramirez²,

Bouillon³

et al. 2017

Polish Archives of Internal Medicine

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Pulmonary diseases are one of the most important causes of morbidity and mortality. Although vitamin D is best known for its role in calcium, phosphorus, and bone homeostasis, it has gained attention in the recent years because of a wide range of extraskeletal effects, including its immunomodulatory and antibacterial potential. Vitamin D deficiency is highly prevalent in chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, tuberculosis, and asthma, and several clinical studies have been conducted investigating the effect of vitamin D supplementation on disease outcomes. In this review, we searched for positive evidence on vitamin D supplementation from randomized controlled trials and elaborated on the optimal serum vitamin D levels and dosing regimens for an effective intervention. While vitamin D supplementation seems to be beneficial as an add -on treatment for adult patients with asthma and a potent intervention to reduce exacerbations in patients with COPD, there is little evidence for its therapeutic use in cystic fibrosis, pneumonia, and tuberculosis. the debate on the appropriate levels of 25(OH)D is still ongoing, most studies define the levels of less than 20 ng/ml (50 nmol/l) as deficient because they are associated with chronic diseases. 5 This is also the threshold used in most governmental guidelines for vitamin D. 16 The levels below 10 ng/ml (25 nmol/l) are considered as severe deficiency because they are associated with an increased risk of rickets or osteomalacia. It is also assumed that patients with these levels exhibit a true risk for infections and chronic diseases. 17 Other research groups reported that the serum 25(OH)D concentrations of 30 ng/ml (75 nmol/l) or even higher, as found in native populations living around the equator, are needed for optimal health. 5,10 Importance of vitamin D in pulmonary diseases Vitamin D deficiency is associated with multiple diseases such as cancer, hypertension, and autoimmune diseases, but also with several lung diseases. 5 A recent meta -analysis demonstrated that vitamin D levels are significantly lower in patients with tuberculosis (TB) compared with controls (apart from the African population). 18 About 70% to 90% of patients with TB have 25(OH)D levels below 20 ng/ml. 19,20 Janssens et al 6 demonstrated that patients with COPD had significantly lower 25(OH)D levels compared with healthy smokers and that vitamin D deficiency correlated with disease severity. While 31% of the healthy smokers were vitamin D deficient, this percentage increased gradually to 60% in stage 3 of COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) to even 77% in the most severe stage of the disease.Vitamin D deficiency is also highly prevalent in CF. Up to 75% of adults and 95% of pediatric patients with CF are vitamin D deficient, [21][22][23] despite routine oral supplementation. 24 In patients with CF, vitamin D deficiency seems to be associated with a decreased pulmonary function in adult...

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Vitamin D deficiency and the risk of tuberculosis: a meta-analysis

Cited by 128 publications

References 43 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Vitamin D status and risk of incident tuberculosis disease: a systematic review and individual participant data meta-analysis

Vitamin D supplementation in respiratory diseases - evidence from RCT

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