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Background There is controversy regarding the potential influence of vitamin D deficiency, exposure to environmental tobacco smoke, BCG vaccination, season, and body habitus on susceptibility to Mycobacterium tuberculosis (MTB) infection. Methods We conducted a cross-sectional analysis to identify determinants of a positive QuantiFERON-TB Gold (QFT) assay result in children aged 6–13 years attending 18 schools in Ulaanbaatar, Mongolia. Data relating to potential risk factors for MTB infection were collected by questionnaire, physical examination, and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios (RRs) were calculated with adjustment for potential confounders, and population attributable fractions (PAFs) were calculated for modifiable risk factors identified. Results Nine hundred forty-six of 9810 (9.6%) participants had a positive QFT result. QFT positivity was independently associated with household exposure to pulmonary tuberculosis (adjusted RR [aRR], 4.75 [95% confidence interval {CI}, 4.13–5.46, P <.001]; PAF, 13.1% [95% CI, 11.1%–15.0%]), vitamin D deficiency (aRR, 1.23 [95% CI, 1.08–1.40], P =.002; PAF, 5.7% [95% CI, 1.9%–9.3%]), exposure to environmental tobacco smoke (1 indoor smoker, aRR, 1.19 [95% CI, 1.04–1.35]; ≥2 indoor smokers, aRR, 1.30 [95% CI, 1.02–1.64]; P for trend =.006; PAF, 7.2% [95% CI, 2.2%–12.0%]), and increasing age (aRR per additional year, 1.14 [95% CI, 1.10–1.19], P <.001). No statistically significant independent association was seen for presence of a BCG scar, season of sampling, or body mass index. Conclusions Vitamin D deficiency and exposure to environmental tobacco smoke are potentially modifiable risk factors for MTB infection. [ABSTRACT FROM AUTHOR]

Rationale: Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking.Objectives: To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3.Methods: We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment.Measurements and Main Results: The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P < 0.001) but did not influence time to sputum culture conversion overall (adjusted hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02).Conclusions: Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656). [ABSTRACT FROM AUTHOR]

Background: There is controversy regarding the relative influence of 'exogenous' versus 'endogenous' factors on the risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease in children.Methods: We conducted a cross-sectional analysis to identify risk factors for active tuberculosis in QuantiFERON®-TB Gold (QFT-G)-positive children aged 6-13 years attending 18 schools in Ulaanbaatar, Mongolia. Children underwent clinical and radiological screening for active tuberculosis, and data relating to potential risk factors for disease progression were collected by questionnaire and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios were calculated using generalized estimating equations with adjustment for potential confounders.Results: 129/938 (13.8%) QFT-positive children were diagnosed with active tuberculosis. Risk of active tuberculosis was independently associated with household exposure to pulmonary TB (adjusted risk ratio [aRR] 2.40, 95% CI 1.74 to 3.30, P < 0.001), month of sampling (adjusted risk ratio [aRR] for March-May vs. June-November 3.31, 95% CI 1.63 to 6.74, P < 0.001; aRR for December-February vs. June-November 2.53, 95% CI 1.23 to 5.19, P = 0.01) and active smoking by the child (aRR 5.23, 95% CI 2.70 to 10.12, P < 0.001). No statistically significant independent association was seen for age, sex, socio-economic factors, presence of a Bacillus Calmette-Guérin (BCG) scar, tobacco exposure or vitamin D status.Conclusions: Household exposure to active TB, winter or spring season and active smoking were independently associated with risk of active tuberculosis in QFT-positive children. Our findings highlight the potentially high yield of screening child household contacts of infectious index cases for active tuberculosis in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: Vitamin D supplementation has been shown to increase total hip areal bone mineral density in healthy children and adolescents. We aimed to investigate whether supplementing schoolchildren living in Mongolia with weekly vitamin D 3 for 3 years affected fracture risk., Methods: We did a multicentre, double-blind, randomised, placebo-controlled trial across 18 public schools in Ulaanbaatar, Mongolia. Schoolchildren were eligible if they were aged 6-13 years at screening, had a negative QuantiFERON-TB Gold In-tube assay (QFT) result, were not hypersensitive to vitamin D or immunocompromised, did not use vitamin D supplements, did not have clinical signs of rickets, and had no intention of leaving Ulaanbaatar within 3 years. Participants were randomly assigned (1:1) to receive either vitamin D (oral dose of 14 000 international units [IU] vitamin D 3 , once per week) or placebo for 3 years using permuted block randomisation stratified by school of attendance. Participants, care providers, and all trial staff were masked to group assignment during the intervention. Prespecified secondary outcomes were incidence of fractures and adverse events, ascertained using questionnaires. The fracture and safety analyses included participants who completed at least one follow-up fracture questionnaire. We estimated adjusted risk ratios (RRs) and 95% CIs using generalised linear models with binomial distribution and a log link function with adjustment for school of attendance. The trial is registered with ClinicalTrials.gov, NCT02276755, and the intervention ended in May, 2019., Findings: Between Sept 2, 2015, and March 20, 2017, 11 475 children were invited to participate in the study and 8851 were recruited and randomly assigned to receive either vitamin D (n=4418) or placebo (n=4433). 8348 participants were included in the fracture and safety analyses (4176 [94·5%] in the vitamin D group and 4172 [94·1%] in the placebo group). Of these, 4125 (49·4%) were female, 4223 (50·6%) were male, and 7701 (92·2%) were of Khalkh ancestry. Median age was 9·2 years (IQR 8·0-10·7) and 7975 (95·5%) participants had baseline serum 25-hydroxyvitamin D concentrations less than 50 nmol/L. During a median follow-up of 3·0 years (IQR 2·9-3·1), 268 (6·4%) participants in the vitamin D group and 253 (6·1%) in the placebo group reported one or more fractures (adjusted RR 1·10, 95% CI 0·93-1·29; p=0·27). Incidence of adverse events did not differ between study groups., Interpretation: Oral vitamin D supplementation at a dose of 14 000 IU/week for 3 years was safe, but did not influence fracture risk in schoolchildren living in Mongolia who had a high baseline prevalence of vitamin D deficiency., Funding: US National Institutes of Health., Competing Interests: Declaration of interests ARM declares receipt of funding to support vitamin D research from Pharma Nord, DSM Nutritional Products, Thornton & Ross, and Hyphens Pharma. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord, Synergy Biologics, and Cytoplan; support for attending meetings from Pharma Nord and Abiogen Pharma; receipt of consultancy fees from DSM Nutritional Products and Qiagen; receipt of a speaker fee from the Linus Pauling Institute (Corvallis, OR, USA); participation on data and safety monitoring boards for the VITALITY trial (PACTR20200989766029) and the trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (NCT04641195); and unpaid work as a programme committee member for the Vitamin D Workshop. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Population-based data relating to vitamin D status of children in Northeast Asia are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 9595 schoolchildren aged 6-13 years in Ulaanbaatar (UB), the capital city of Mongolia. Risk factors for vitamin D deficiency were collected by questionnaire, and serum 25-hydroxyvitamin D (25[OH]D) concentrations were measured using an enzyme-linked fluorescent assay, standardized and categorized as deficient (25[OH]D <10 ng/mL) or not. Odds ratios for associations between independent variables and risk of vitamin D deficiency were calculated using multivariate analysis with adjustment for potential confounders. The prevalence of vitamins D deficiency was 40.6% (95% CI 39.7% to 41.6%). It was independently associated with female gender (adjusted odds ratio [aOR] for girls vs. boys 1.23, 95% CI 1.11-1.35), month of sampling (aORs for December-February vs. June-November 5.28 [4.53-6.15], March-May vs. June-November 14.85 [12.46-17.74]), lower levels of parental education (P for trend <0.001), lower frequency of egg consumption (P for trend <0.001), active tuberculosis (aOR 1.40 [1.03-1.94]), household smoking (aOR 1.13 [1.02 to1.25]), and shorter time outdoors (P for trend <0.001). We report a very high prevalence of vitamin D deficiency among Mongolian schoolchildren, which requires addressing as a public health priority.