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Background: Stunting affects ~25% of children <5 y of age and is associated with impaired cognitive and motor development and increased morbidity and mortality. The pathogenesis of stunting is poorly understood. Objective: The purpose of this study was to identify altered metabolic pathways associated with child stunting. Design: We measured 677 serum metabolites using liquid chromatography-tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged 12-59 mo, of whom 62% were stunted. Results: A low height-for-age z score (HAZ) was associated with lower serum concentrations of 1) ω-3 (n-3) and ω-6 (n-6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a role in brain development, 3) carnitine, a conditionally essential nutrient with an important role in the carnitine shuttle for the metabolism of fatty acids and energy production, and 4) g-glutamyl amino acids, which represent an altered γ-glutamyl cycle of glutathione metabolism. A low HAZ was associated with significantly higher serum concentrations of 5 biomarkers related to cigarette smoke exposure. Conclusions: This metabolomics study shows a cross-sectional association between stunting and low serum ω-3 and ω-6 long-chain PUFAs, which are essential for growth and development; low sulfated neurosteroids, which play a role in brain development; low carnitine, which is essential for β-oxidation of fatty acids; alterations in glutathione metabolism; and increased serum metabolites that are associated with secondhand tobacco smoke exposure. [ABSTRACT FROM AUTHOR]

Background: Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown. Objective: The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children. Design: We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross-sectional study in 325 Malawian children, aged 12-59 mo, of whom 62% were stunted. Results: Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) µmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were 20.57 (P, 0.0001), 20.26 (P < 0.0001), and 20.10 (P = 0.07), respectively. Correlation coefficients of height-for-age z score with serum choline, betaine-to-choline ratio, and TMAO-to-choline ratio were 0.31 (P < 0.0001), 20.24 (P < 0.0001), and 20.29 (P < 0.0001), respectively. Serum choline concentrations were strongly and significantly associated with stunting. Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) mmol/L (P < 0.0001). Conclusions: Linear growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012. [ABSTRACT FROM AUTHOR]

Background: Retention in antiretroviral therapy (ART) programmes remains a challenge in many settings including Malawi, in part due to high numbers of losses to follow-up. Concept Mapping (CM), a mix-method participatory approach, was used to explore why patients on ART are lost to follow-up (LTFU) by identifying: 1) factors that influence patient losses to follow-up and 2) barriers to effective and efficient tracing in Zomba, Malawi. Methods: CM sessions (brainstorming, sorting and rating, interpretation) were conducted in urban and rural settings in Zomba, Malawi. Participants included ART patients, ART providers, Health Surveillance Assistants, and health managers from the Zomba District Health Office. In brainstorming, participants generated statements in response to "A specific reason why an individual on ART becomes lost to follow-up is…" Participants then sorted and rated the consolidated list of brainstormed items. Analysis included inductive qualitative methods for grouping of data and quantitative cluster identification to produce visual maps which were then interpreted by participants. Results: In total, 90 individuals brainstormed 371 statements, 64 consolidated statements were sorted (participant n = 46), and rated on importance and feasibility (participant n = 69). A nine-cluster concept map was generated and included both patient- and healthcare-related clusters such as: Stigma and Fears, Beliefs, Acceptance and Knowledge of ART, Access to ART, Poor Documentation, Social and Financial Support Issues, Health Worker Attitudes, Resources Needed for Effective Tracing, and Health Worker Issues Related to Tracing. Strategies to respond to the clusters were generated in Interpretation. Conclusions: Multiple patient- and healthcare focused factors influence why patients become LTFU. Findings have implications particularly for programs with limited resources struggling with the retention of ART patients. [ABSTRACT FROM AUTHOR]

Background: There are approximately 3 million people aged 50 and older in sub-Saharan Africa who are HIV-positive. Despite this, little is known about the characteristics of older adults who are on treatment and their treatment outcomes. Methods: A retrospective cohort analysis was performed using routinely collected data with Malawi Ministry of Health monitoring tools from facilities providing antiretroviral therapy services in Zomba district. Patients aged 25 years and older initiated on treatment from July 2005 to June 2010 were included. Differences in survival, by age group, were determined using Kaplan-Meier survival plots and Cox proportional hazards regression models. Results: There were 10,888 patients aged 25 and older. Patients aged 50 and older (N = 1419) were more likely to be male (P<0.0001) and located in rural areas (P = 0.003) than those aged 25-49. Crude survival estimates among those aged 50-59 were not statistically different from those aged 25-49 (P = 0.925). However, survival among those aged 60 and older (N = 345) was worse (P = 0.019) than among those 25-59. In the proportional hazards model, after controlling for sex and stage at initiation, survival in those aged 50-59 did not differ significantly from those aged 25-49 (hazard ratio 1.00 (95% CI: 0.79 to 1.27; P = 0.998) but the hazard ratio was 1.46 (95% CI: 1.03 to 2.06; P = 0.032) for those aged 60 and older compared to those aged 25-49. Conclusions: Treatment outcomes of those aged 50-59 are similar to those aged 25-49. A better understanding of how older adults present for and respond to treatment is critical to improving HIV services. [ABSTRACT FROM AUTHOR]

The acute phase response and inflammation are associated with lower plasma retinol concentrations, but their effect on breast milk retinol concentrations is unclear. We measured plasma retinol concentrations, acute phase proteins, and breast milk retinol concentrations in 237 breast-feeding women at 2 wk postpartum in Blantyre, Malawi; 16.5% of the women had plasma retinol < 0.70 micromol/L and 14.8% had breast milk retinol < 1.05 micromol/L. Among women with and without inflammation [alpha(1)-acid glycoprotein (AGP) > 1 g/L and/or C-reactive protein (CRP) > 5 mg/L], geometric mean (95% CI) plasma retinol was 0.89 (0.84, 0.94) and 1.05 (1.01, 1.17) mumol/L, respectively (P < 0.0001). Among women with and without inflammation, geometric mean (95% CI) breast milk retinol was 2.12 (1.89, 2.36) and 2.05 (1.75, 2.39) micromol/L, respectively (P = 0.74). In multiple linear regression models adjusting for age, parity, education, BMI, and days postpartum, plasma retinol concentrations were associated with plasma AGP and CRP concentrations (P < 0.0001 and P = 0.01, respectively), whereas breast milk retinol concentrations were unaffected by plasma AGP and CRP concentrations (P = 0.22 and P = 0.86, respectively). These findings suggest that breast milk retinol concentrations are not affected by systemic inflammation. [ABSTRACT FROM AUTHOR]

Background: Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. Methods: In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. Results: Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 µmol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids. Conclusions: These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models, it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans. Objective: To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia. Methods: A randomized, double-blind, controlled clinical trial was conducted to examine the effect of daily vitamin A (3000 µg retinol equivalent), iron (30 mg), and folate (400 µg) versus iron (30 mg) and folate (400 µg) (control) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi, Africa. Results: Mean gestational age at enrollment was 23 wk, at which time 50% of the women were anaemic (haemoglobin <110 g/L). Mean (±SEM) change in haemoglobin from enrollment to 38 wk was 4.7±1.6 g/L (p=0.003) and 7.3±2.3 g/L (p=0.003) in the vitamin A and control groups, respectively. Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39±5.00 (p=0.63) and -2.87±3.92 IU/L (p=0.46) in the vitamin A and controls groups, respectively. There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk, and between enrollment and follow-up within either group. Conclusions: Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi. [ABSTRACT FROM AUTHOR]

Presents a study which discussed the relationship between the indicators of HIV disease severity and iron status among pregnant women in Malawi, Africa. Subjects and methods used; Results; Prevalence of anemia during pregnancy in developing countries.

Presents information on a study which characterized plasma transferrin receptor, ferritin and hemoglobin concentrations in a group of pregnant women in Malawi. Prevalence of anemia among pregnant women; Methodology; Results and discussion.

Examines vitamin A status in pregnant women as a risk factor for mother-to-child transmission of HIV in Malawi. Patients and methods; Association between vitamin A deficiency and increased mother-to-child transmission of HIV; Modes of mother-to-child transmission of HIV; Nutritional abnormalities during HIV infection.

Serum amino acid (AA) concentrations are correlated with childhood stunting, but their relation to linear growth velocity has not been explored. This was a secondary analysis of a clinical trial where Malawian infants aged 6–12 mo were given a legume supplement providing 8.2 g/d of protein; anthropometry was conducted at multiple intervals, and fasted serum AA concentrations were measured at 12 mo of age. Lysine, proline, tryptophan, tyrosine, and valine concentrations were higher in infants with a linear growth velocity z -score >0 than those <0. Corrected Spearman correlation coefficients between individual AA concentrations and weight-for-height and length velocity from 6 to 12 mo of age were positively correlated for glycine, isoleucine, proline, serine, threonine, tyrosine, and valine. Additionally, weight-for-height was correlated with arginine, asparagine, glutamine, leucine, lysine, methionine, and phenylalanine. The observed associations suggest that testing the hypothesis that essential AA provision will reduce linear growth faltering is warranted. This trial was registered at clinicaltrials.gov as NCT02472262. [ABSTRACT FROM AUTHOR]