Urine Se concentration poorly predicts plasma Se concentration at sub-district scales in Zimbabwe, limiting its value as a biomarker of population Se status.

Introduction: The current study investigated the value of urine selenium (Se) concentration as a biomarker of population Se status in rural sub-Saharan Africa. Method: Urine and plasma Se concentrations were measured among children aged 6-59 months (n = 608) and women of reproductive age (WRA, n = 781) living in rural Zimbabwe (Murehwa, Shamva, and Mutasa districts) and participating in a pilot national micronutrient survey. Selenium concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS), and urine concentrations were corrected for hydration status. Results: The median (Q1, Q3) urine Se concentrations were 8.4 µg/L (5.3, 13.5) and 10.5 µg/L (6.5, 15.2) in children and WRA, respectively. There was moderate evidence for a relationship between urine Se concentration and plasma Se concentration in children (p = 0.0236) and WRA (p = < 0.0001), but the relationship had poor predictive value. Using previously defined thresholds for optimal activity of iodothyronine deiodinase (IDI), there was an association between deficiency when indicated by plasma Se concentrations and urine Se concentrations among WRA, but not among children. Discussion: Urine Se concentration poorly predicted plasma Se concentration at sub-district scales in Zimbabwe, limiting its value as a biomarker of population Se status in this context. Further research is warranted at wider spatial scales to determine the value of urine Se as a biomarker when there is greater heterogeneity in Se exposure.

A pilot survey of selenium status and its geospatial variation among children and women in three rural districts of Zimbabwe.

Introduction: Selenium (Se) deficiency is increasingly recognized as a public health problem in sub-Saharan Africa. Methods: The current cross-sectional study assessed the prevalence and geospatial patterns of Se deficiency among children aged 6-59 months (n = 741) and women of 15-49 years old (n = 831) selected by simple random sampling in rural Zimbabwe (Murewa, Shamva, and Mutasa districts). Venous blood samples were collected and stored according to World Health Organization guidelines. Plasma Se concentration was determined by inductively coupled plasma-mass spectrometry. Results: Median, Q1, and Q3 plasma Se concentrations were 61.2, 48.7, and 73.3 µg/L for women and 40.5, 31.3, and 49.5 µg/L for children, respectively. Low plasma Se concentrations (9.41 µg/L in children and 10.20 µg/L in women) indicative of severe Se deficiency risk was observed. Overall, 94.6% of children and 69.8% of women had sub-optimal Se status defined by plasma Se concentrations of <64.8 µg/L and <70 µg/L, respectively. Discussion: High and widespread Se deficiency among women and children in the three districts is of public health concern and might be prevalent in other rural districts in Zimbabwe. Geostatistical analysis by conditional kriging showed a high risk of Se deficiency and that the Se status in women and children in Murewa, Shamva, and Mutasa districts was driven by short-range variations of up to ⁓12 km. Selenium status was homogenous within each district. However, there was substantial inter-district variation, indicative of marked spatial patterns if the sampling area is scaled up. A nationwide survey that explores the extent and spatial distribution of Se deficiency is warranted.

Anemia in children aged 6-59 months was significantly associated with maternal anemia status in rural Zimbabwe.

Globally, anemia is a public health problem affecting mostly women of reproductive age (WRA, n = 452) and children aged 6-59 months (n = 452) from low- and lower-middle-income countries. This cross-sectional study assessed the prevalence and determinants of anemia in WRA and children aged 6-59 months in rural Zimbabwe. The venous blood sample was measured for hemoglobin utilizing a HemoCue machine. Anthropometric indices were assessed and classified based on World Health Organization standards. Socioeconomic characteristics were assessed. The median (±inter quartile range (IQR)) age of WRA was 29 ± 12 years and that for children was 29 ± 14 months. The prevalence of anemia was 29.6% and 17.9% in children and WRA, respectively, while the median (±IQR) hemoglobin levels were 13.4 ± 1.8 and 11.7 ± 1.5 g/dl among women and children, respectively. Multiple logistic regression analysis was used to assess determinants of anemia. Anemia in children was significantly associated with maternal anemia (odds ratio (OR) = 2.02; 95% CI 1.21-3.37; p = .007) and being a boy (OR = 0.63; 95% CI 0.41-0.95; p = .029), while anemia in WRA was significantly associated with the use of unimproved dug wells as a source of drinking water (OR = 0.36; 95% CI 0.20-0.66; p = .001) and lack of agricultural land ownership (OR = 0.51; 95% CI 0.31-0.85; p = .009). Anemia is a public health problem in the study setting. The positive association between maternal and child anemia reflects the possibility of cross-generational anemia. Therefore, interventions that focus on improving preconceptual and maternal nutritional status may help to reduce anemia in low-income settings.

Modeling food fortification contributions to micronutrient requirements in Malawi using Household Consumption and Expenditure Surveys.

Large-scale food fortification may be a cost-effective intervention to increase micronutrient supplies in the food system when implemented under appropriate conditions, yet it is unclear if current strategies can equitably benefit populations with the greatest micronutrient needs. This study developed a mathematical modeling framework for comparing fortification scenarios across different contexts. It was applied to model the potential contributions of three fortification vehicles (oil, sugar, and wheat flour) toward meeting dietary micronutrient requirements in Malawi through secondary data analyses of a Household Consumption and Expenditure Survey. We estimated fortification vehicle coverage, micronutrient density of the diet, and apparent intake of nonpregnant, nonlactating women for nine different micronutrients, under three food fortification scenarios and stratified by subpopulations across seasons. Oil and sugar had high coverage and apparent consumption that, when combined, were predicted to improve the vitamin A adequacy of the diet. Wheat flour contributed little to estimated dietary micronutrient supplies due to low apparent consumption. Potential contributions of all fortification vehicles were low in rural populations of the lowest socioeconomic position. While the model predicted large-scale food fortification would contribute to reducing vitamin A inadequacies, other interventions are necessary to meet other micronutrient requirements, especially for the rural poor.

Preparing for a community-based agriculture-to-nutrition trial in rural Malawi: formative research to assess feasibility and inform design and implementation decisions.

BACKGROUND: This study reports findings from formative research conducted to assess the feasibility and inform the design and implementation of the Addressing Hidden Hunger with Agronomy (AHHA) trial. The AHHA trial was a randomised, controlled trial conducted in rural Malawi, in which participants were given maize flour biofortified with selenium or control flour not biofortified with selenium for a period of 10 weeks, after which blood samples were taken to measure selenium status. METHODS: Formative research was conducted in villages near to the AHHA trial study site 1 year before the planned intervention. A short questionnaire with adult women (n = 50), focus group discussions with male (n groups = 3) and female (n groups = 3) community members, and in-depth key informant interviews (n = 7) were conducted to understand community practices and perceptions. FINDINGS: Meals were typically cooked and eaten at home in this community, while participants reported that maize flour would be less readily sold than maize grain - important considerations for the design of the trial. Regarding intervention delivery, we identified potential concerns around effects on fertility, links between blood sampling and witchcraft, and the potential for social stigma if community members considered participants lazy for receiving free flour. Participants reported that involvement of the Malawi government partners including health extension workers would increase trust. INTERPRETATION: Following the formative research, the AHHA trial appeared feasible. However, community sensitisation would be essential to address potential fears and concerns; effective sensitisation would support recruitment and treatment adherence, and would protect the safety and wellbeing of participants and researchers. People in positions of authority and trust including village headmen, religious leaders, health and agriculture extension workers, and community care groups should be involved in community sensitisation.

Spatial analysis of urine zinc (Zn) concentration for women of reproductive age and school age children in Malawi.

Zinc (Zn) is an essential micronutrient, and Zn deficiency remains a major global public health challenge. Recognised biomarkers of population Zn status include blood plasma or serum Zn concentration and proxy data such as dietary Zn intake and prevalence of stunting. Urine Zn concentration is rarely used to assess population Zn status. This study assessed the value of urine Zn concentration as a biomarker of population Zn status using a nationally representative sample of non-pregnant women of reproductive age (WRA) and school-aged children (SAC) in Malawi. Spot (casual) urine samples were collected from 741 WRA and 665 SAC. Urine Zn concentration was measured by inductively coupled plasma mass spectrometry with specific gravity adjustment for hydration status. Data were analysed using a linear mixed model with a spatially correlated random effect for between-cluster variation. The effect of time of sample collection (morning or afternoon), and gender (for SAC), on urine Zn concentration were examined. There was spatial dependence in urine Zn concentration between clusters among SAC but not WRA, which indicates that food system or environmental factors can influence urine Zn concentration. Mapping urine Zn concentration could potentially identify areas where the prevalence of Zn deficiency is greater and thus where further sampling or interventions might be targeted. There was no evidence for differences in urine Zn concentration between gender (P = 0.69) or time of sample collection (P = 0.85) in SAC. Urine Zn concentration was greater in afternoon samples for WRA (P = 0.003). Relationships between urine Zn concentration, serum Zn concentration, dietary Zn intake, and potential food systems covariates warrant further study.

Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial.

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency. Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting. Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita -1 day-1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS). Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) µg L-1 (n = 88) to 107.9 (16.4) µg L-1 (n = 88) among WRA and from 46.4 (14.8) µg L-1 (n = 86) to 97.1 (16.0) µg L-1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups. Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings. Clinical Trial Registration: http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451.

Urine selenium concentration is a useful biomarker for assessing population level selenium status.

Plasma selenium (Se) concentration is an established population level biomarker of Se status, especially in Se-deficient populations. Previously observed correlations between dietary Se intake and urinary Se excretion suggest that urine Se concentration is also a potentially viable biomarker of Se status. However, there are only limited data on urine Se concentration among Se-deficient populations. Here, we test if urine is a viable biomarker for assessing Se status among a large sample of women and children in Malawi, most of whom are likely to be Se-deficient based on plasma Se status. Casual (spot) urine samples (n = 1406) were collected from a nationally representative sample of women of reproductive age (WRA, n =741) and school aged children (SAC, n=665) across Malawi as part of the 2015/16 Demographic and Health Survey. Selenium concentration in urine was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary dilution corrections for specific gravity, osmolality, and creatinine were applied to adjust for hydration status. Plasma Se status had been measured for the same survey participants. There was between-cluster variation in urine Se concentration that corresponded with variation in plasma Se concentration, but not between households within a cluster, or between individuals within a household. Corrected urine Se concentrations explained more of the between-cluster variation in plasma Se concentration than uncorrected data. These results provide new evidence that urine may be used in the surveillance of Se status at the population level in some groups. This could be a cost-effective option if urine samples are already being collected for other assessments, such as for iodine status analysis as in the Malawi and other national Demographic and Health Surveys.

The risk of selenium deficiency in Malawi is large and varies over multiple spatial scales.

Selenium (Se) is an essential human micronutrient. Deficiency of Se decreases the activity of selenoproteins and can compromise immune and thyroid function and cognitive development, and increase risks from non-communicable diseases. The prevalence of Se deficiency is unknown in many countries, especially in sub-Saharan Africa (SSA). Here we report that the risk of Se deficiency in Malawi is large among a nationally representative population of 2,761 people. For example, 62.5% and 29.6% of women of reproductive age (WRA, n = 802) had plasma Se concentrations below the thresholds for the optimal activity of the selenoproteins glutathione peroxidase 3 (GPx3; <86.9 ng mL-1) and iodothyronine deiodinase (IDI; <64.8 ng mL-1), respectively. This is the first nationally representative evidence of widespread Se deficiency in SSA. Geostatistical modelling shows that Se deficiency risks are influenced by soil type, and also by proximity to Lake Malawi where more fish is likely to be consumed. Selenium deficiency should be quantified more widely in existing national micronutrient surveillance programmes in SSA given the marginal additional cost this would incur.

Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial.

BACKGROUND: Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers - a process known as agronomic biofortification (agro-biofortification) - and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi. METHODS: A double-blind, randomised, controlled trial will be conducted in a rural community in Kasungu District, Central Region, Malawi. The hypothesis is that consumption of maize flour agro-biofortified with Se will increase serum Se concentration. We will recruit 180 women of reproductive age (WRA) (20-45 years) and 180 school-age children (SAC) (5-10 years) randomly assigned in a 1:1 ratio to receive either maize flour enriched through agro-biofortification with Se or a control flour not enriched with Se. Households will receive flour (330 g per capita per day) for 12 weeks. The primary outcome is Se concentration in serum (µg/L). Serum will be extracted from venous blood samples drawn at baseline (prior to flour distribution) and end-line. Selenium concentration will be measured by using inductively coupled plasma mass spectrometry. DISCUSSION: Findings will be communicated to policy stakeholders and participating communities and reported in peer-reviewed journals. TRIAL REGISTRATION: The Addressing Hidden Hunger with Agronomy (Malawi) trial is registered (5th March 2019; ISCRTN85899451).

Reduced Morbidity Motivated Adoption of Infant and Young Child Feeding Practices after Nutrition Education Intervention in Rural Malawi.

This study assessed caregivers' knowledge and practices and factors that influence the adoption of improved infant and young child feeding (IYCF) practices after nutrition education in Kasungu and Mzimba districts among 198 caregivers. Mixed-methods convergent-parallel design, including knowledge tests, focus group discussions, and in-depth interviews in the intervention areas, was used to collect quantitative and qualitative data. Data were analyzed using count regression and content analysis, which showed that knowledge increased among caregivers after nutrition education. The knowledge about diet diversification for young children as well as about hygienic practices when preparing food and during feeding improved in addition. Enhanced health among children motivated caregivers to apply improved IYCF practices. The study was based on the caregivers' reports. Long-term effects of exposure to nutrition education are unknown. However, the nutrition education that focused on the child's health benefits motivated mothers to adopt improved IYCF practices.

Dietary mineral supplies in Africa.

Dietary micronutrient deficiencies (MNDs) are widespread, yet their prevalence can be difficult to assess. Here, we estimate MND risks due to inadequate intakes for seven minerals in Africa using food supply and composition data, and consider the potential of food-based and agricultural interventions. Food Balance Sheets (FBSs) for 46 countries were integrated with food composition data to estimate per capita supply of calcium (Ca), copper (Cu), iron (Fe), iodine (I), magnesium (Mg), selenium (Se) and zinc (Zn), and also phytate. Deficiency risks were quantified using an estimated average requirement (EAR) 'cut-point' approach. Deficiency risks are highest for Ca (54% of the population), followed by Zn (40%), Se (28%) and I (19%, after accounting for iodized salt consumption). The risk of Cu (1%) and Mg (<1%) deficiency are low. Deficiency risks are generally lower in the north and west of Africa. Multiple MND risks are high in many countries. The population-weighted mean phytate supply is 2770 mg capita(-1) day(-1). Deficiency risks for Fe are lower than expected (5%). However, 'cut-point' approaches for Fe are sensitive to assumptions regarding requirements; e.g. estimates of Fe deficiency risks are 43% under very low bioavailability scenarios consistent with high-phytate, low-animal protein diets. Fertilization and breeding strategies could greatly reduce certain MNDs. For example, meeting HarvestPlus breeding targets for Zn would reduce dietary Zn deficiency risk by 90% based on supply data. Dietary diversification or direct fortification is likely to be needed to address Ca deficiency risks.

Soil-type influences human selenium status and underlies widespread selenium deficiency risks in Malawi.

Selenium (Se) is an essential human micronutrient with critical roles in immune functioning and antioxidant defence. Estimates of dietary Se intakes and status are scarce for Africa although crop surveys indicate deficiency is probably widespread in Malawi. Here we show that Se deficiency is likely endemic in Malawi based on the Se status of adults consuming food from contrasting soil types. These data are consistent with food balance sheets and composition tables revealing that >80% of the Malawi population is at risk of dietary Se inadequacy. Risk of dietary Se inadequacy is >60% in seven other countries in Southern Africa, and 22% across Africa as a whole. Given that most Malawi soils cannot supply sufficient Se to crops for adequate human nutrition, the cost and benefits of interventions to alleviate Se deficiency should be determined; for example, Se-enriched nitrogen fertilisers could be adopted as in Finland.

The impact of an integrated community-based micronutrient and health programme on stunting in Malawian preschool children.

OBJECTIVE: To assess the impact of the 1996-2005 integrated community-based micronutrient and health (MICAH) programme on linear growth retardation (stunting) in Malawian preschool children living in rural areas. DESIGN: Prospective study of three large-scale cross-sectional surveys conducted in 1996, 2000 and 2004 in MICAH and Comparison populations. SETTING: Rural areas in Malawi. SUBJECTS: Preschool children (6.0-59.9 months) from randomly selected households (474 from the 1996 baseline survey; 1264 from 2000 MICAH areas; 1500 from 2000 Comparison areas; 1959 from 2004 MICAH areas; and 1008 from 2004 Comparison areas), who responded to a household questionnaire, were weighed and measured using standard protocols. RESULTS: At the baseline in 1996, the prevalence of stunting (60.2 %) was very high. By 2000, the prevalence of stunting had declined to 50.6 % and 56.0 % (chi2 = 7.8, P = 0.005) in MICAH and Comparison areas, respectively. In 2004, the prevalence of stunting did not differ significantly between MICAH and Comparison areas (43.0 % v. 45.1 %; chi2 = 1.11, P = 0.3). Severe stunting affected 34.7 % of children at baseline, which declined to 15.8 % and 17.1 % (chi2 = 0.86, P = 0.4) in MICAH and Comparison areas, respectively, by 2004. Regional variations existed, with proportionately fewer children from the Northern region being stunted compared to their Central and Southern region counterparts. CONCLUSION: Given the length of implementation, wide-scale coverage and positive impact on child growth in Phase I (1996-2000), the MICAH programme is a potential model for combating linear growth retardation in rural areas in Malawi, although the catch-up improvement in Comparison areas during Phase II (2000-2004) cannot be adequately explained.

The impact of an integrated community-based micronutrient and health programme on anaemia in non-pregnant Malawian women.

OBJECTIVE: To assess the impact of an integrated community-based micronutrient and health (MICAH) programme on anaemia (Hb < 120 g/l) among non-pregnant rural Malawian women aged 15-49 years from communities that participated in the 1996-2005 MICAH programme. DESIGN: Prospective study of two large-scale cross-sectional surveys conducted in 2000 and 2004 as part of programme evaluation in MICAH and Comparison areas. SETTING: Rural areas across Malawi. The MICAH programme implemented a comprehensive package of interventions to reduce anaemia, based on a broad range on direct and indirect causes in Malawi. The project approaches included: Fe supplementation; dietary diversification and modification; food fortification; and strengthening primary health care. PARTICIPANTS: Non-pregnant women of childbearing age (15-49 years old, n 5422), from randomly selected households that responded to a household questionnaire, had their Hb measured from finger-prick blood samples using the HemoCue. RESULTS: In 2000, there was no significant difference in Hb concentration between MICAH and Comparison areas (mean (SE): 117.4 (0.4) v. 116.8 (0.5) g/l, P > 0.05) and the corresponding prevalence of anaemia (53.5 % v. 52.9 %, P > 0.05). By 2004, Hb concentration had increased significantly in MICAH but not in Comparison areas (mean (SE): 121.0 (0.4) v. 115.7 (0.6) g/l, P < 0.001), and the prevalence of anaemia had declined significantly in MICAH areas (53.5 % to 44.1 %, chi2 = 28.2, P < 0.0001) but not in Comparison areas (52.8 % to 54.0 %, chi2 = 0.3, P = 0.6). CONCLUSIONS: The MICAH programme was an effective public health nutrition programme that was associated with significant reductions in the prevalence of anaemia among non-pregnant rural Malawian women.