Vitamin D metabolites support innate immune responses to
. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking.
We randomly ...assigned children who had negative results for
infection according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D
or placebo for 3 years. The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. Secondary outcomes included the serum 25-hydroxyvitamin D (25OHD) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events.
A total of 8851 children underwent randomization: 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval CI, 0.87 to 1.38; P = 0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55). A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups.
Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D-deficient schoolchildren in Mongolia. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02276755.).
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.
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 (25OHD) concentrations. Risk ratios were calculated using generalized estimating equations with adjustment for potential confounders.
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.
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.
ObjectivesTo evaluate the feasibility of the Zero TB Indicator Framework as a tool for assessing the quality of tuberculosis (TB) case-finding, treatment and prevention services in ...Mongolia.SettingPrimary health centres, TB dispensaries, and surrounding communities in four districts of Mongolia.DesignThree retrospective cross-sectional cohort studies, and two longitudinal studies each individually nested in one of the cohort studies.Participants15 947 community members from high TB-risk populations; 8518 patients screened for TB in primary health centres and referred to dispensaries; 857 patients with index TB and 2352 household contacts.Primary and secondary outcome measures14 indicators of the quality of TB care defined by the Zero TB Indicator Framework and organised into three care cascades, evaluating community-based active case-finding, passive case-finding in health facilities and TB screening and prevention among close contacts; individual and health-system predictors of these indicators.ResultsThe cumulative proportions of participants receiving guideline-adherent care varied widely, from 96% for community-based active case-finding, to 79% for TB preventive therapy among household contacts, to only 67% for passive case-finding in primary health centres and TB dispensaries (range: 29%–80% across districts). The odds of patients completing active TB treatment decreased substantially with increasing age (aOR: 0.76 per decade, 95% CI: 0.71 to 0.83, p<0.001) and among men (aOR: 0.56, 95% CI: 0.36 to 0.88, p=0.013). Contacts of older index patients also had lower odds of initiating and completing of TB preventive therapy (aOR: 0.60 per decade, 95% CI: 0.38 to 0.93, p=0.022).ConclusionsThe Zero TB Framework provided a feasible and adaptable approach for using routine surveillance data to evaluate the quality of TB care and identify associated individual and health system factors. Future research should evaluate strategies for collecting process indicators more efficiently; gather qualitative data on explanations for low-quality care; and deploy quality improvement interventions.
PDF
