Sabri Bromage

High-Dose Vitamin D3 During Tuberculosis Treatment in Mongolia: A Randomised Controlled Trial

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 1&agr;‐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).

Seasonal Epidemiology of Serum 25-Hydroxyvitamin D Concentrations among Healthy Adults Living in Rural and Urban Areas in Mongolia

Many factors put Mongolians at risk of vitamin D deficiency. Despite low levels observed in Mongolian children and pregnant women, there are few data published on the vitamin D status of non-pregnant adults. Between summer 2011 and winter 2013, paired summer and winter blood samples were collected from 320 healthy men and women (20–58 years) living in eight Mongolian provinces. Mean serum 25(OH)D concentrations were 22.5 ng/mL (95% CI: 14.5, 32.5) in summer and 7.7 ng/mL (95% CI: 4.6, 10.8) in winter, with a distribution (<10/10–20/20–30/≥30 ng/mL) of 3.1%/39.3%/39.6%/17.9% in summer and 80.1%/19.5%/0.3%/0.0% in winter. Residents of the capital, Ulaanbaatar, had lower levels in both seasons than any other region, whereas residents of the Gobi desert had the highest. In summer, indoor workers had significantly lower levels than outdoor workers (−2.3 ng/mL; 95% CI: −4.1, −5.7) while levels in males exceeded those in females (4.0 ng/mL; 95% CI: 2.3, 5.7). Effects of region, occupation, and sex were also significant in multivariable regression. In conclusion, Mongolian adults had extremely low serum 25(OH)D, particularly in winter, when 80.1% had concentrations below 10 ng/mL. These results indicate a need for effective vitamin D interventions for the Mongolian adult population, particularly among women and residents of Ulaanbaatar.

Calcium Deficiency in Bangladesh: Burden and Proposed Solutions for the First 1000 Days.

Background: Bangladesh incurs among the highest prevalence of stunting and micronutrient deficiencies in the world, despite efforts against diarrheal disease, respiratory infections, and protein-energy malnutrition which have led to substantial and continuous reductions in child mortality over the past 35 years. Although programs have generally paid more attention to other micronutrients, the local importance of calcium to health has been less recognized. Objective: To synthesize available information on calcium deficiency in Bangladesh in order to inform the design of an effective national calcium program. Methods: We searched 3 online databases and a multitude of survey reports to conduct a narrative review of calcium epidemiology in Bangladesh, including population intake, determinants and consequences of deficiency, and tested interventions, with particular reference to young children and women of childbearing age. This was supplemented with secondary analysis of a national household survey in order to map the relative extent of calcium adequacy among different demographics. Results: Intake of calcium is low in the general population of Bangladesh, with potentially serious and persistent effects on public health. These effects are especially pertinent to young children and reproductive-age women, by virtue of increased physiologic needs, disproportionately poor access to dietary calcium sources, and a confluence of other local determinants of calcium status in these groups. Conclusion: A tablet supplementation program for pregnant women is an appealing approach for the reduction in preeclampsia and preterm birth. Further research is warranted to address the comparative benefit of different promising approaches in children for the prevention of rickets.

Validation of a Dish-Based Semiquantitative Food Questionnaire in Rural Bangladesh

A locally validated tool was needed to evaluate long-term dietary intake in rural Bangladesh. We assessed the validity of a 42-item dish-based semi-quantitative food frequency questionnaire (FFQ) using two 3-day food diaries (FDs). We selected a random subset of 47 families (190 participants) from a longitudinal arsenic biomonitoring study in Bangladesh to administer the FFQ. Two 3-day FDs were completed by the female head of the households and we used an adult male equivalent method to estimate the FD for the other participants. Food and nutrient intakes measured by FFQ and FD were compared using Pearson’s and Spearman’s correlation, paired t-test, percent difference, cross-classification, weighted Kappa, and Bland–Altman analysis. Results showed good validity for total energy intake (paired t-test, p < 0.05; percent difference <10%), with no presence of proportional bias (Bland–Altman correlation, p > 0.05). After energy-adjustment and de-attenuation for within-person variation, macronutrient intakes had excellent correlations ranging from 0.55 to 0.70. Validity for micronutrients was mixed. High intraclass correlation coefficients (ICCs) were found for most nutrients between the two seasons, except vitamin A. This dish-based FFQ provided adequate validity to assess and rank long-term dietary intake in rural Bangladesh for most food groups and nutrients, and should be useful for studying dietary-disease relationships.

Trained Cohorts of University Students are a Useful Resource for Conducting Dietary Surveys in Mongolia

Background: Population-based dietary assessment is important for informing national nutrition policy. The developing country setting presents challenges for robust implementation of dietary surveys, yet effective nutrition interventions are often urgently required. Objective: To develop and evaluate a low-cost approach to epidemiologic dietary assessment in Mongolia, involving the use of large cohorts of local public health and medical students as research assistants for collecting diet records. Methods: From 2011 to 2016, over 200 Mongolian medical and public health university students were trained to collect paired summer and winter 3-day weighed diet records from urban and rural study populations across the geographic expanse of Mongolia. Students were supervised during data collection, and their performance and experience during training and data collection were qualitatively evaluated from their own perspectives as well as those of the investigators. Results: Students collected detailed and thorough diet records and generally reported positive feedback regarding training and data collection. Frequent supervision of students during data collection proved to be extremely worthwhile. While rural participants were amenable to having students follow them, students faced several challenges in assessing the diets of urban participants. These challenges may best be addressed by separately training these participants beforehand. Conclusions: With adequate training and supervision, university students may be a useful and cost-effective resource for large-scale dietary surveys in regions where their use would be practical and culturally appropriate. Further research is warranted to study how well this approach may be adapted outside Mongolia and to other dietary assessment methods and technologies.

Intervention study shows suboptimal growth among children receiving a food supplement for five months in a slum in Bangladesh

This study assessed weight and height changes among underweight children who received a locally produced, cereal‐based, ready‐to‐use supplementary food.

S113 High-dose vitamin D3 during intensive phase treatment of pulmonary tuberculosis in mongolia: a double-blind randomised controlled trial

Introduction and objectives Existing trials of adjunctive vitamin D to enhance response to antimicrobial therapy for pulmonary tuberculosis are variously limited by relatively small sample sizes, inadequate dosing regimens and low baseline prevalence of vitamin D deficiency among participants. Our objective was to conduct a large randomised controlled trial of high-dose vitamin D in a setting where profound vitamin D deficiency was common in patients with pulmonary TB. Methods We conducted a double-blind randomised placebo-controlled trial of high-dose adjunctive vitamin D3 in adults with sputum smear-positive pulmonary tuberculosis in Ulaanbaatar, Mongolia. 390 participants were allocated to receive 3.5 mg vitamin D3 (n = 190) or placebo (n = 200) at baseline and at 2, 4 and 6 weeks after starting standard tuberculosis treatment. The primary endpoint of the trial was time from initiation of antimicrobial therapy to sputum culture conversion. Secondary endpoints were time to sputum smear conversion, resolution of infiltrates on chest radiograph and serum 25-hydroxyvitamin D (25[OH]D) concentrations. This trial was registered with ClinicalTrials.gov (NCT01657656). Results At baseline, 81% of participants had profound vitamin D deficiency (serum 25[OH]D <25 nmol/L). Vitamin D supplementation elevated 8-week serum 25(OH)D concentrations to high-physiological levels (154.5 in intervention arm vs. 15.2 nmol/L in placebo arm, 95% CI: for difference 125.9 to 154.7 nmol/L, P < 0.001), but did not influence time to sputum culture conversion (adjusted hazard ratio 1.11, 95% CI: 0.88 to 1.39, P = 0.39). Allocation to vitamin D was associated with accelerated sputum smear conversion (adjusted HR 1.47, 95% CI: 1.09 to 1.98, P = 0.01) and a small but statistically significant reduction in the mean number of zones affected on chest radiograph at 8 weeks (5.48 vs. 5.69, 95% CI: for difference 0.06 to 0.77 zones, p = 0.02). Conclusions This is the largest randomised controlled trial to investigate effects of adjunctive vitamin D on time to sputum culture conversion in pulmonary tuberculosis conducted to date. Adjunctive high-dose vitamin D was effective in elevating serum 25(OH)D concentrations to high-physiological levels, but did not influence time to sputum culture conversion.

Projected effectiveness of mandatory industrial fortification of wheat flour, milk, and edible oil with multiple micronutrients among Mongolian adults

Industrial fortification of wheat flour is a potentially effective strategy for addressing micronutrient deficiencies in Mongolia, given its ubiquitous consumption and centralized production. However, Mongolia has not mandated fortification of any foods except for salt with iodine. This study modeled the effectiveness and safety of mandatory industrial fortification of wheat flour alone and in combination with edible oil and milk in reducing the prevalence of multiple micronutrient intake deficiencies among healthy non-pregnant adults in Mongolia. Six days of diet records (3 summer, 3 winter) were collected from 320 urban and rural adults across the country and analyzed for food and nutrient consumption using a purpose-built food composition table, and the Intake Monitoring and Planning Program (IMAPP) was used to project the effects of fortification on summer and winter bioavailable micronutrient intake and intake deficiency under different fortification guidelines within population subgroups defined by urban or rural locality and sex. Projections showed that flour fortification would be effective in reducing intake deficiencies of thiamin and folate, while marginal benefits of fortification with iron and riboflavin would be smaller given these nutrients’ higher baseline consumption, and fortification with zinc, niacin, and vitamin B12 may be unnecessary. Fortification of flour, oil, and milk with vitamins A, D, and E at levels suggested by international guidelines would substantially reduce vitamin A intake deficiency and would increase vitamin D intake considerably, with the greatest benefits elicited by flour fortification and smaller benefits by additionally fortifying oil and milk. These results support mandatory industrial fortification of wheat flour, edible oil, and milk with iron, thiamin, riboflavin, folate, and vitamins A, D, and E in Mongolia. Considerations will be necessary to ensure the fortification of these nutrients is also effective for children, for whom the potential benefit of zinc, niacin, and vitamin B12 fortification should be assessed.

Comparison of Methods for Estimating Dietary Food and Nutrient Intakes and Intake Densities from Household Consumption and Expenditure Data in Mongolia

Household consumption and expenditure surveys are frequently conducted around the world and they usually include data on household food consumption, but their applicability to nutrition research is limited by their collection at the household level. Using data from Mongolia, this study evaluated four approaches for estimating diet from household surveys: direct inference from per-capita household consumption; disaggregation of household consumption using a statistical method and the “adult male equivalent” method, and direct prediction of dietary intake. Per-capita household consumption overestimated dietary energy in single- and multi-person households by factors of 2.63 and 1.89, respectively. Performance of disaggregation methods was variable across two household surveys analyzed, while the statistical method exhibited less bias in estimating intake densities (per 100 kcal) of most dietary components in both of the surveys. Increasingly complex prediction models explained 54% to 72% of in-sample variation in dietary energy, with consistent benefits incurred by inclusion of basic dietary measurements. In conclusion, in Mongolia and elsewhere, differences in how household and dietary measurements are recorded make their comparison challenging. Validity of disaggregation methods depends on household survey characteristics and the dietary components that are considered. Relatively precise prediction models of dietary intake can be achieved by integrating basic dietary assessment into household surveys.

Prospective cohort study of overweight and obesity among rural Indian adults: sociodemographic predictors of prevalence, incidence and remission

Objectives To assess sociodemographic predictors of prevalence, incidence and remission of overweight including obesity among adults (aged ≥18 years) in rural Eastern India. Design Prospective cohort study. Setting Birbhum Health and Demographic Surveillance System, West Bengal, India. Participants Self-weighted sample of 24 115 adults (men: 10915, women: 13200) enrolled in 2008 were followed up for body mass index (BMI) reassessment in 2017. Primary and secondary outcome measures Measured BMI was categorised as: underweight (<18.5 kg/m2), normal weight (18.5–22.9 kg/m2) and overweight including obesity (≥23 kg/m2; hereinafter overweight). Incident overweight was defined as transition from normal weight in 2008 to overweight in 2017, whereas if overweight individuals in 2008 measured normal BMI in 2017, it was classified as remission from overweight. Results In 2008, 10.1% of men and 14.6% of women were overweight, whereas 17.3% of men and 24.7% of women were overweight in 2017. At the same time, in 2017, 35.6% of men and 33.3% of women were underweight. Incident overweight was 19.0% among men and 27.2% among women, whereas remission among men was higher (15.4%) than women (11.5%). Women were more likely to be overweight in 2008 and to experience incident overweight than men. For men and women, education level and wealth were positively associated with prevalence and incidence of overweight. Remission from overweight was less likely in Sainthia, a business hub in the district, as compared with Mohammad Bazar, a more rural area. Conclusion A nutrition transition to higher risk of overweight is evident in this rural setting in India, especially among women and individuals with high socioeconomic status. At the same time, a high prevalence of underweight persists, resulting in a significant double burden. Culturally sensitive interventions that address both ends of the malnutrition spectrum should be prioritised.