Dataset Information

Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial.

ABSTRACT:

Background

By modulating immune function, vitamin D might increase innate immunity and inhibit the growth of initial bacterial invasion and protect against tuberculosis infection.

Objective

We examined the effect of vitamin D supplementation on tuberculin skin test (TST) conversion.

Design

A double-blind, placebo-controlled study was conducted in 120 Mongol schoolchildren. We estimated the prevalence of latent tuberculosis infection at baseline and examined the effect of vitamin D (800 IU/d) on serum concentrations of 25-hydroxyvitamin D [25(OH)D] and TST conversion.

Results

At baseline, the mean (±SD) 25(OH)D concentration was 7 ± 4 ng/mL, and all concentrations were <20 ng/mL. Vitamin D supplementation increased serum 25(OH)D by a mean of 12.7 ng/mL compared with placebo (P < 0.0001). At baseline, 16 children in the vitamin D group and 18 in the placebo group were TST positive (P = 0.7). Over 6 mo, TSTs converted to positive in 5 (11%) children receiving vitamin D compared with 11 (27%) receiving placebo (RR: 0.41; 95% CI: 0.16, 1.09; P = 0.06). Only one TST conversion occurred among those whose serum 25(OH)D concentration increased to >20 ng/mL, whereas 8 TST conversions occurred in those whose final 25(OH)D concentration remained <10 ng/mL (P = 0.05). The mean increase in stature was 2.9 ± 1.6 cm in the vitamin D group and 2.0 ± 1.7 cm in the placebo group (95% CI: 2.16, 2.81; P < 0.003).

Conclusions

Vitamin D supplementation for 6 mo had significant favorable effects on serum 25(OH)D concentrations and on growth in stature. A trend was seen toward fewer TST conversions in the vitamin D group. This trial was registered at clinicaltrials.gov as NCT01244204.

SUBMITTER: Ganmaa D

PROVIDER: S-EPMC3396446 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial.

Ganmaa Davaasambuu D Giovannucci Edward E Bloom Barry R BR Fawzi Wafaie W Burr Winthrop W Batbaatar Dulguun D Sumberzul Nyamjav N Holick Michael F MF Willett Walter C WC

The American journal of clinical nutrition 20120703 2

<h4>Background</h4>By modulating immune function, vitamin D might increase innate immunity and inhibit the growth of initial bacterial invasion and protect against tuberculosis infection.<h4>Objective</h4>We examined the effect of vitamin D supplementation on tuberculin skin test (TST) conversion.<h4>Design</h4>A double-blind, placebo-controlled study was conducted in 120 Mongol schoolchildren. We estimated the prevalence of latent tuberculosis infection at baseline and examined the effect of vi ...[more]

PMID: 22760564

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Project description:BackgroundA mechanistic understanding of uncommon immune outcomes such as resistance to infection has led to the development of novel therapies. Using gene level analytic methods, we previously found distinct monocyte transcriptional responses associated with resistance to Mycobacterium tuberculosis (Mtb) infection defined as persistently negative tuberculin skin test (TST) and interferon gamma release assay (IGRA) reactivity among highly exposed contacts (RSTR phenotype).ObjectiveUsing transcript isoform analyses, we aimed to identify novel RSTR-associated genes hypothesizing that previous gene-level differential expression analysis obscures isoform-specific differences that contribute to phenotype.Materials and methodsMonocytes from 49 RSTR versus 52 subjects with latent Mtb infection (LTBI) were infected with M. tuberculosis (H37Rv) or left unstimulated (media) prior to RNA isolation and sequencing. RSTR-associated gene expression was then identified using differential transcript isoform analysis.ResultsWe identified 81 differentially expressed transcripts (DETs) in 70 genes (FDR <0.05) comparing RSTR and LTBI phenotypes with the majority (n = 79 DETs) identified under Mtb-stimulated conditions. Seventeen of these genes were previously identified with gene-level bulk RNAseq analyses including genes in the IFNγ response that had increased expression among LTBI subjects, findings consistent with a clinical phenotype based on IGRA reactivity. Among the subset of 23 genes with positive differential expression among Mtb-infected RSTR monocytes, 13 were not previously identified. These novel DET genes included PDE4A and ZEB2, which each had multiple DETs with higher expression among RSTR subjects, and ACSL4 and GAPDH that each had a single transcript isoform associated with RSTR.Conclusion and limitationsTranscript isoform-specific analyses identify transcriptional associations, such as those associated with resistance to TST/IGRA conversion, that are obscured when using gene-level approaches. These findings should be validated with additional RSTR cohorts and whether the newly identified candidate resistance genes directly influence the monocyte Mtb response requires functional study.

Project description:BackgroundTuberculosis (TB) is one of the most widespread infectious diseases worldwide, typically persisting in the body as a latent TB infection (LTBI). Patients with type 2 diabetes have an increased risk of LTBI progressing to active TB. Therefore, this study determined the prevalence and predictors of LTBI and assessed the agreement between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in diagnosing LTBI among type 2 diabetics in Sana'a city, Yemen.MethodsA cross-sectional study was conducted among 150 type 2 diabetics in private health facilities in Sana'a in 2023. Data about demographics, diabetes-related characteristics, and potential risk factors for LTBI were collected using a structured questionnaire. Patients were then screened for LTBI using TST and IGRA. Univariate analysis was used to identify LTBI-associated risk factors, and multivariable binary logistic regression was used to identify independent predictors of LTBI. The agreement between TST and IGRA for diagnosing LTBI was assessed using Cohen's kappa coefficient (κ).ResultsLTBI was prevalent among 29.3% of type 2 diabetics using both types of tests (25.3% with IGRA and 21.3% with TST). Male gender was an independent predictor of LTBI (AOR = 4.4, 95% confidence interval: 1.30-15.08; P = 0.018). However, being employed (AOR = 0.3, 95% CI: 0.09-0.75; P = 0.013) and longer duration since diabetes diagnosis (AOR = 0.3, 95% CI: 0.12-0.98; P = 0.046) were identified as predictors of lower LTBI risk. The agreement between TST and IGRA for the diagnosis of LTBI was 88%, with a good and statistically significant agreement between the two test types (κ = 0.670; P < 0.001).ConclusionsLTBI is common among type 2 diabetics seeking medical care in Sana'a city, with about one-third of them possibly being latently infected. A higher LTBI risk can be predicted among males, while a lower risk can be predicted among those employed or being diagnosed with diabetes for at least five years. The TST shows good agreement with IGRA in diagnosing LTBI among type 2 diabetics, supporting its continued use as a cost-effective and easily accessible test for diagnosing LTBI in the country.

Dataset Information

Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial.

Background

Objective

Design

Results

Conclusions

Publications

Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age children: a randomized, double-blind, placebo-controlled feasibility trial.

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