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Background Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. Methods We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. Results BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114–118) whereas SBP decreased (125–123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3–4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6–1.1) increase in SBP. Conclusions Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

OBJECTIVE Better understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow-up for diabetes risk and other non-communicable diseases in resource-limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months. METHODS One-year follow-up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30-minute (30mPG) and 2-hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p-insulin), homeostatic model assessment index for insulin resistance (HOMA-IR) and blood pressure. RESULTS: The mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p-insulin (10B 3.1; 95% CI2.4, 4.0), HOMA-IR (10B 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat-free mass at baseline predicted higher increments in p-insulin, HOMA-IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c. CONCLUSIONS Among Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12-month of ART. Only longer-term follow-up will tell us whether insulin increase is due to insulin resistance or from recovering β-cells.

Background Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM. Methods This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM. Results Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm2, p 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01). Conclusion The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Background & Aims: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery.Methods: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted.Results: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Δ0.2 kg/m2; 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m2 higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Δ0.22 cm; p = 0.25) and higher FFM (Δ0.11 kg; p = 0.078) in the reduced dose group.Conclusions: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

The global prevalence of metabolic syndrome (MS) is increasing due to lifestyle changes. Studies have found that MS is associated with human immunodeficiency virus (HIV) and antiretroviral treatment (ART), but controversies still exist on associations between HIV and MS.To assess associations between HIV and MS among ART-naïve HIV positive individuals compared to HIV negative individuals.A cross-sectional study among ART-naïve HIV positive and HIV negative individuals recruited from HIV treatment and testing facilities in Ethiopia. Information was collected on components of MS: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure and fasting plasma glucose (FPG). Data were analysed using logistic and linear regression stratified by sex and adjusted for age, wealth and education.Data from 329 HIV positive and 100 HIV negative individuals were included. HIV positive status was associated with higher odds of MS in women (OR: 3.56, 95%CI: 1.25; 10.15) (HIV was associated with MS among ART-naïve women, suggesting that MS should be evaluated before initiating ART and monitored during treatment to identify those at risk of developing diabetes and cardiovascular disease (CVD).

Introduction In the HIV-infected individuals, physical activity improves physical strength, quality of life and reduces the risk of developing non-communicable diseases. In Sub-Saharan Africa, HIV-infected patients report being less active compared to HIV-uninfected individuals. We assessed the levels and correlates of objectively measured physical activity and capacity among HIV-infected antiretroviral therapy (ART)-naive individuals compared to HIV-uninfected individuals in Mwanza, Tanzania. Method We conducted a cross-sectional study among newly diagnosed HIV-infected ART-naive individuals and HIV-uninfected individuals frequency-matched for age and sex. Socio-demographic data, anthropometrics, CD4 counts, haemoglobin level, and C-reactive protein (CRP) were collected. Physical activity energy expenditure (PAEE) was assessed as measure of physical activity whereas sleeping heart rate (SHR) and grip strength were assessed as measures of physical capacity. Multivariable linear regression was used to assess the correlates associated with physical activity and capacity. Results A total of 272 HIV-infected and 119 HIV-uninfected individuals, mean age 39 years and 60% women participated in the study. Compared to HIV-uninfected individuals, HIV-infected had poorer physical activity and capacity: lower PAEE (-7.3 kj/kg/day, 95% CI: -11.2, -3.3), elevated SHR (7.7 beats/min, 95%CI: 10.1, 5.3) and reduced grip strength (-4.7 kg, 95%CI: -6.8, -2.8). In HIV-infected individuals, low body mass index, moderate-severe anaemia, low CD4 counts and high CRP were associated with lower physical activity and capacity. In HIV-uninfected individuals, abdominal obesity and moderate anaemia were associated with lower physical activity and capacity. Conclusion HIV-infected participants had lower levels of physical activity and capacity than HIV-uninfected participants. Correlates of physical activity and capacity differed by HIV status. Management of HIV and related conditions needs to be provided effectively in health care facilities. Interventions promoting physical activity in these populations will be of importance to improve their health and reduce the risk of non-communicable diseases.

Background Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. Methods We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR2) were determined using linear regression and logistic regression, respectively. Results 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). Conclusion Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

Objective: We aimed to determine the associations of non-alcoholic fatty liver disease (NAFLD) with cardio-metabolic risk factors for diabetes in adult Kenyans.Methods: A cross-sectional study was undertaken among rural and urban Kenyans of different ethnic origin. Ultrasonography scanning (USS) methods were used for the assessment of hepatic fat accumulation for NAFLD assessment and abdominal fat distribution, and simple anthropometry measurements were performed. All participants underwent a 2-h oral glucose tolerance test, and biochemical, haemodynamic and lifestyle data were obtained. Multivariate logistic regression analyses were used to assess sex, age, residency and ethnic differences in the association between NAFLD and various metabolic parameters.Results: In total, 743 individuals (59.1% women) with a mean age of 38.0 (range 18-68) years participated in the study. Overall, 118 individuals (15.9%) had NAFLD, of whom 94.1% had mild steatosis. Age >40 years was significantly associated with having NAFLD compared to p < 0.045 for OR).Conclusion: Finding lower odds for NAFLD in men was unexpected, as was the lack of differences in NAFLD among the ethnic groups, while higher odds for NAFLD with increasing age and in urban vs. rural populations was expected. Especially the sex-specific results warrant further studies in black African populations on biology of body composition for having NAFLD, and whether this translates into insulin resistance and higher risk of diabetes and consequently cardiovascular disease in black African women.

Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates.A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood.Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 μmol/L, P 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/μl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP)10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis.Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.

Background: Children with severe acute malnutrition (SAM) are prone to infections due to immune dysfunction including severe thymus atrophy which recovers during nutritional rehabilitation. Aim: To investigate predictors of thymus size recovery, including probiotics during nutritional rehabilitation of children admitted with complicated SAM. Methods: In this prospective study nested in a randomized controlled trial, children 6-59 months admitted with SAM received standard care and either probiotics or placebo during hospitalization until 8 weeks post-discharge. Thymus size was measured using ultrasound at admission, discharge, 8 weeks post-discharge and among 27 community controls. Predictors of thymus size recovery were assessed using linear regression. Results: Among 388 children with SAM, mean (SD) thymus size was 1.06 cm2 (0.41), 1.24 cm2 (0.48), 2.85 cm2 (1.07) and 4.2 cm2 (0.93) at admission, discharge, follow-up and in the healthy controls respectively (p 15mg/L (β -0.13, 95%CI -0.25; -0.02) and neutrophils (β -0.01, 95%CI -0.02; -0.002). During OTC, HIV negatively predicted thymus recovery. Conclusion: Children with SAM failed to regain thymus size at 8 weeks post-discharge. Probiotics did not predict thymus recovery during nutritional rehabilitation. More research is needed to find interventions which can accelerate immune recovery. Abbreviations: ART, Antiretroviral therapy; BB-12, Bifidobacterium animalis subsp. Lactis; CRP, C-reactive protein; ITC, inpatient therapeutic care; LGG, Lactobacillus rhamnosus; MNU, Mwanamugimu Nutrition Unit; MUAC, mid-upper arm circumference; OTC, outpatient therapeutic care; PCR, Polymerised chain reaction; RUTF, ready-to-use therapeutic food; SAM, severe acute malnutrition; VAS, visual analogue score; WHO, World Health Organization; WHZ, weight-for-height score.

Changes in body composition and muscle strength are common among individuals with HIV. We investigated the associations of inflammation with body composition and grip strength in adults with and without HIV.Cross-sectional study among Ethiopian treatment-naïve individuals with and without HIV. Fat mass and fat-free mass adjusted for height (kg/m288/100 individuals with/without HIV were included between July 2010 and August 2012. Females with HIV had lower fat mass index (FMI) and fat-free mass index (FFMI) than females without HIV, whereas no difference was seen between males with and without HIV. Males and females with HIV had lower grip strength than their counterparts without HIV. Serum alpha-1-acid glycoprotein (s-AGP) was negatively correlated with FMI (-0.71 kg/mInflammation was positively associated with FMI in individuals without HIV while it was negatively associated with FMI in those with HIV, indicating that inflammation may be one of the drivers of depleting energy reserves among treatment-naïve individuals with HIV. Inflammation was associated with decreased muscle quantity and functional capacity among individuals with HIV, but not in those without HIV.

Objective: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of β-cell dysfunction and insulin resistance on pre-diabetes and diabetes.Methods: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition, and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of β-cell dysfunction and insulin resistance and categorized as: normal β-cell function and insulin sensitivity, isolated β-cell dysfunction, isolated insulin resistance, and combined β-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.1 and ≥11.1 mmol/L, respectively. Multinomial regression assessed the association of β-cell dysfunction and insulin resistance with outcome measures.Results: β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated β-cell dysfunction (adjusted Relative Risk Ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined β-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to β-cell dysfunction, insulin resistance and combined β-cell dysfunction and insulin resistance, respectively.Conclusions: β-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Background Abdominal obesity predict metabolic syndrome parameters at low levels of waist circumference (WC) in Africans. At the same time, the African lipid profile phenotype of low high-density lipoprotein (HDL) cholesterol without concomitant elevated triglyceride levels renders high triglyceride levels detrimental to cardiometabolic health unsuitable for identifying cardiometabolic risk in black African populations. Objectives We aimed to identify simple clinical measures for cardiometabolic risk based on WC and HDL in an adult Kenyan population in order to determine which of the two predictors had the strongest impact. Methods We used linear regression analyses to assess the association between the two exposure variables WC and HDL with cardiometabolic risk factors including ultrasound-derived visceral (VAT) and subcutaneous adipose tissue (SAT) accumulation, fasting and 2-h venous glucose, fasting insulin, fasting lipid profile, and blood pressure in adult Kenyans (n = 1 370), and a sub-population with hyperglycaemia (diabetes and pre-diabetes) (n = 196). The same analyses were performed with an interaction between WC and HDL to address potential effect modification. Ultrasound-based, semi-quantitative hepatic steatosis assessment was used as a high-risk measure of cardiometabolic disease. Results Mean age was 38.2 (SD 10.7) (range 17–68) years, mean body mass index was 22.3 (SD 4.5) (range 13.0–44.8) kg/m2, and 57.8% were women. Cardiometabolic risk was found in the association between both WC and HDL and all outcome variables (p Conclusion In adult Kenyans, increasing WC identified more cardiometabolic risk factors compared to HDL.

Background Lipid-based nutrient supplements (LNS) and corn–soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. Methods and findings We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks’ supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6–23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2–16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [−0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (−0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. Conclusions In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. Trial registration ISRCTN42569496, In this analysis of secondary trial outcomes, Mette F. Olsen and colleagues show the effects of different supplements on child language and motor skill development., Author summary Why was this study done? Moderate acute malnutrition (MAM) affects more than 33 million children globally with long-term consequences for their development. There has been a call for research on the effects of MAM treatment on functional outcomes, but previous trials have not assessed effects of the treatments on child development. What did the researchers do and find? We conducted a randomised trial of 1,609 children with MAM in Burkina Faso to investigate the effectiveness of supplemental foods, including a comparison of matrix (lipid-based nutrient supplements [LNS] or corn–soy blend [CSB]), soy quality (soy isolate or dehulled soy), and content of milk protein (0%, 20%, or 50% of protein). We assessed child development as gross motor, fine motor, language, and cognitive skills using the Malawi Development Assessment Tool (MDAT). We found that child development improved across intervention groups during the supplementation and continued to improve after the supplementation had ended. Supplements containing milk protein were beneficial for fine motor and language development. Our findings also indicated a benefit of soy isolate over dehulled soy and a benefit of LNS over CSB among boys. What do these findings mean? Previously reported findings from this trial showed that children mainly put on fat-free mass during supplementation. With the data presented here, we show that motor, language, and cognitive development of children also improve during supplementation and that this improvement is sustained post-supplementation. Our results support the use of milk protein in food products, while suggested benefits of soy isolate and LNS merit further investigation. These findings contribute to the needed evidence of supplementation effects on functional outcomes, including child development, and allow better understanding of children’s ability to thrive following MAM treatment.

Background Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. Methods and findings A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn–soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Conclusions Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. Trial registration ISRCTN Registry ISRCTN42569496.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6–23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m2 (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m2 (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m2 lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI.Trial registration: ISRCTN42569496.

BackgroundLimited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF.MethodsHIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen.ResultOf 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (− 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2in eGFR at 12 month, respectively. However, none of the HIV patients declined to< 60 ml/min/1.73m2within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen.ConclusionRenal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health‐related correlates. This cross‐sectional study used baseline data from a nutritional trial in children with MAM aged 6–23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio‐economic status, anthropometry, body composition, whole‐blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z‐scores were −0.39 (−0.45, −0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and −0.91 (−0.96, −0.86) for language skills. Children with higher mid‐upper arm circumference, weight‐for‐height, height‐for‐age, fat‐free mass, n‐3 PUFAs, Hb, and iron status had better MDAT z‐scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z‐scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z‐scores. Associations between morbidity and z‐scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

Change in hydration is common in children with severe acute malnutrition (SAM) including during treatment, but is difficult to assess. We investigated the utility of bio-electrical impedance vector analysis (BIVA), a quick non-invasive method, for indexing hydration during treatment.We studied 350 children 0·5-14 years of age with SAM (mid-upper arm circumference11·0 cm or weight-for-height70% of median, and/or nutritional oedema) admitted to a hospital nutrition unit, but excluded medically unstable patients. Weight, height (H), resistance (R), reactance (Xc) and phase angle (PA) were measured and oedema assessed. Similar data were collected from 120 healthy infants and preschool/school children for comparison. Means of height-adjusted vectors (R/H, Xc/H) from SAM children were interpreted using tolerance and confidence ellipses of corresponding parameters from the healthy children.SAM children with oedema were less wasted than those without (p 0·001), but had BIVA parameters that differed more from those of healthy children (P 0·05) than those non-oedematous. Initially, both oedematous and non-oedematous SAM children had mean vectors outside the reference 95% tolerance ellipse. During treatment, mean vectors migrated differently in the two SAM groups, indicating fluid loss in oedematous patients, and tissue accretion in non-oedematous patients. At admission, R/H was lower (oedematous) or higher (non-oedematous) among children who died than those who exited the hospital alive.BIVA can be used in children with SAM to distinguish tissue-vs. hydration-related weight changes during treatment, and also identify children at high risk of death enabling early clinical interventions.

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania.Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes.Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT.Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.

The appetite test is used to risk stratify for children with severe acute malnutrition (SAM) in inpatient or outpatient care. The test is recommended in guidelines despite lack of evidence. We evaluated its ability to identify children at risk of a poor treatment outcome.We conducted an observational study of children diagnosed with SAM at three health facilities in Ethiopia. The appetite test was done independently, and the result did not affect decisions about hospitalisation and clinical care. Data were analysed using mixed linear and logistic regression models.Appetite was tested in 298 (89%) of 334 children enrolled; 56 (19%) passed. Children failing the appetite test had a 6.6% higher weight gain per day (95% CI: 2.6, 10.8) adjusted for type of treatment, oedema, duration of follow-up and age than children passing the test. We found medical complications in 179 (54%) children. Medical complications were associated with blood markers of metabolic disturbance. Children with medical complications tended to have lower weight gain than those without complications (3.5%, 95% CI: -0.25, 7.0). Neither the appetite test nor medical complications were correlated with bacteraemia or treatment failure.Our findings question the use of the appetite test to identify children who need inpatient care. An assessment of medical complications alone could be a useful risk indicator but needs to be evaluated in other settings.Le test de l'appétit est utilisé pour stratifier les risques chez les enfants souffrant de malnutrition aiguë sévère (MAS) en soins hospitaliers ou ambulatoires. Le test est recommandé dans les directives malgré le manque d’évidence. Nous avons évalué sa capacité à identifier les enfants à risque de mauvais résultats de traitement. MÉTHODES: Nous avons mené une étude observationnelle chez des enfants diagnostiqués avec une MAS dans trois établissements de santé en Ethiopie. Le test de l'appétit a été effectué indépendamment et le résultat n'a pas affecté les décisions d'hospitalisation et de soins cliniques. Les données ont été analysées à l'aide de modèles de régression linéaire et logistique mixtes. RÉSULTATS: : L'appétit a été testé chez 298 (89%) des 334 enfants inscrits; 56 (19%) ont réussi le test. Les enfants qui échouaient au test de l'appétit avaient un gain de poids de 6,6% plus élevé par jour (IC95%: 2,6 à 10,8) ajusté pour le type de traitement, l'œdème, la durée du suivi et l'âge que les enfants réussissant le test. Nous avons trouvé des complications médicales chez 179 (54%) enfants. Des complications médicales ont été associées à des marqueurs sanguins de troubles métaboliques. Les enfants souffrant de complications médicales avaient tendance à avoir un gain de poids plus faible que ceux sans complications (3,5% ; IC95%: -0,25 à 7,0). Ni le test de l'appétit ni les complications médicales ne corrélaient avec une bactériémie ou à un échec du traitement CONCLUSION: Nos résultats remettent en question l'utilisation du test de l'appétit pour identifier les enfants qui ont besoin de soins hospitaliers. Une évaluation des complications médicales à elle seule pourrait être un indicateur de risque utile, mais doit être évaluée dans d'autres contextes MOTS-CLÉS: malnutrition aiguë sévère, appétit, gestionnaire de communauté, évaluation des risques, aliments thérapeutiques.

Objectives Data on the role of helminths on diabetes in Africa are limited. We investigated whether Schistosoma and geohelminth infections are associated with β-cell function and insulin resistance among adults. Methods A cross-sectional study was conducted among adults during 2016–2017. Demography, Schistosoma and geohelminth infections, HIV and insulin data were collected. Insulin during an oral glucose tolerance test (fasting, 30, and 120-min), overall insulin secretion index, insulinogenic index, HOMA-β, and HOMA-IR were main outcome measures for β-cell function and insulin resistance, respectively. Generalized estimating equations and generalized linear models assessed the association of Schistosoma and geohelminth infections with outcome measures separately by HIV status. Outcomes were presented as marginal means with 95% CI. Results Data were obtained for 1718 participants. Schistosoma infection was associated with higher 30-min insulin (24.2 mU/L, 95% CI: 6.9, 41.6) and overall insulin secretion index (13.3 pmol/L/mmol/L; 3.7, 22.9) among HIV-uninfected participants but with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-12.0 mU/L; -18.9, -5.1), and HOMA-IR (-0.3 mmol/L; -0.6, -0.05) among HIV-infected participants not yet on antiretroviral therapy (ART). Among HIV-infected participants not on ART, geohelminth infection was associated with lower fasting insulin (-0.9 mU/L; -1.6, -0.2), 120-min insulin (-9.1 mU/L; -17.3, -1.0), HOMA-β (-8.9 mU/L)/(mmol/L; -15.3, -2.6) and overall insulin release index (-5.1 pmol/L/mmol/L; -10.3, 0.02), although this was marginally significant. There was no association among those on ART. Conclusions Schistosoma infection was associated with higher β-cell function among HIV-uninfected participants whereas Schistosoma and geohelminth infections were associated with reduced β-cell function among HIV-infected participants not on ART.

Early nutrition and growth have been found to be important early exposures for later development. Studies of crude growth in terms of weight and length/height, however, cannot elucidate how body composition (BC) might mediate associations between nutrition and later development. In this study, we aimed to examine the relation between fat mass (FM) or fat-free mass (FFM) tissues at birth and their accretion during early infancy, and later developmental progression. In a birth cohort from Ethiopia, 455 children who have BC measurement at birth and 416 who have standardised rate of BC growth during infancy were followed up for outcome variable, and were included in the statistical analysis. The study sample was restricted to mothers living in Jimma town who gave birth to a term baby with a birth weight ≥1500 g and no evident congenital anomalies. The relationship between the exposure and outcome variables was examined using linear-mixed regression model. The finding revealed that FFM at birth was positively associated with global developmental progression from 1 to 5 years (β=1·75; 95 % CI 0·11, 3·39) and from 4 to 5 years (β=1·34; 95 % CI 0·23, 2·44) in the adjusted model. Furthermore, the rate of postnatal FFM tissue accretion was positively associated with development at 1 year of age (β=0·50; 95 % CI 0·01, 0·99). Neither fetal nor postnatal FM showed a significant association. In conclusion, fetal, rather than postnatal, FFM tissue accretion was associated with developmental progression. Intervention studies are needed to assess whether nutrition interventions increasing FFM also increase cognitive development.

Background Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplements (LNSs) or corn-soy blends (CSBs) but little is known about the impact of these supplements on hemoglobin, iron status, and inflammation. Objective The objective of this study was to investigate the impact of supplementary foods for treatment of MAM on hemoglobin, iron status, inflammation, and malaria. Design A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6-23 mo with MAM received 500 kcal/d as LNS or CSB, containing either dehulled soy (DS) or soy isolate (SI) and different quantities of dry skimmed milk (0%, 20% or 50% of total protein) for 12 wk. The trial was double-blind with regard to quality of soy and quantity of milk, but not matrix (CSB compared to LNS). Hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), serum C-reactive protein (CRP), serum α1-acid glycoprotein (AGP), and malaria antigens were measured at inclusion and after supplementation. Results Between September 2013 and August 2014, 1609 children were enrolled. Among these, 61 (3.8%) were lost to follow-up. During the 12-wk supplementation period, prevalence of anemia, low SF adjusted for inflammation (SFAI), elevated sTfR, and iron-deficiency anemia decreased by 16.9, 8.7, 12.6 and 10.5 percentage points. Children who received LNS compared to CSB had higher hemoglobin (2 g/L; 95% CI: 1, 4 g/L), SFAI (4.2 µg/L; 95% CI: 2.9, 5.5 µg/L), and CRP (0.8 mg/L; 95% CI: 0.4, 1.2 mg/L) and lower sTfR (-0.9 mg/L, 95% CI: -1.3, -0.6 mg/L) after the intervention. Replacing DS with SI or increasing milk content did not affect hemoglobin, SFAI, sTfR, or CRP. Conclusion Supplementation with LNS compared to CSB led to better hemoglobin and iron status, but overall prevalence of anemia remained high. The higher concentrations of acute-phase proteins in children who received LNSs requires further investigation. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

Background Accelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years. Methods and findings Healthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0–3 and 3–6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0–3 and 3–6 months was associated with 339 g (95% CI: 243–435 g, p < 0.001) and 367 g (95% CI: 250–484 g, p < 0.001) greater FM at 5 years, respectively. Higher FM at birth and FM accretion from 0 to 3 months were associated with higher FFM and cholesterol concentrations at 5 years. Associations for cholesterol were strongest for low-density lipoprotein (LDL)–cholesterol, and remained significant after adjusting for current FM. A 100-g higher FM at birth and 100-g/month higher FM accretion from 0 to 3 months were associated with 0.16 mmol/l (95% CI: 0.05–0.26 mmol/l, p = 0.005) and 0.06 mmol/l (95% CI: 0.01–0.12 mmol/l, p = 0.016) higher LDL-cholesterol at 5 years, respectively. Higher FFM at birth and FFM accretion in infancy were associated with higher FM, FFM, waist circumference, and height at 5 years. For instance, 100-g/month higher FFM accretion in the periods 0–3 and 3–6 months was associated with 1,002 g (95% CI: 815–1,189 g, p < 0.001) and 624 g (95% CI: 419–829 g, p < 0.001) greater FFM at 5 years, respectively. We found no associations of FM and FFM growth with any of the other studied cardiometabolic markers including glucose, HbA1c, insulin, C-peptide, HOMA-IR, triglycerides, and blood pressure. Non-attendance at the 5-year follow-up visit was the main limitation of this study, which may have introduced selection bias and limited the power of the regression analyses. Conclusions FM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years., Rasmus Wibaek and colleagues reveal associations between fat mass and fat free mass in the first 6 months of life and cardiometabolic markers and growth later in childhood., Author summary Why was this study done? Suboptimal growth in fetal life and early childhood are important risk factors for later obesity, diabetes, and heart disease. Progression towards disease may start early in life, demonstrated by studies linking early growth with changes in fat mass, lean mass, and cardiometabolic risk markers in children as young as 4 years of age. In populations from low-income countries, currently experiencing a rapidly growing chronic disease burden, knowledge about these relationships is lacking. What did the researchers do and find? We followed a cohort of healthy preschool children from the city of Jimma, Ethiopia, for 5 years starting from birth. Using advanced statistical growth modelling and accurate assessment of body composition, we estimated individual fat and lean mass accretion in the periods 0–3 and 3–6 months of age in 507 children. We conducted regression analyses to test for associations of fat and lean mass growth in early infancy with body composition and cardiometabolic risk markers measured at 5 years of age. These analyses showed that children who gained more fat mass in early infancy had greater fat mass and waist circumference and higher concentrations of risk markers related to cholesterol metabolism at 5 years. Children who gained more lean mass in early infancy were taller and had more lean mass at 5 years. Fat and lean mass growth in early infancy were not associated with blood pressure and cardiometabolic markers related to glucose homeostasis at 5 years. What do these findings mean? This study showed that early infancy is an important developmental window for a child’s later body composition. This contemporary cohort of preschool children from a sub-Saharan African urban setting had markedly higher fat mass than similar-aged children from the UK and India, which may be a result of excess fat mass accretion during the first 6 months of life. Variable patterns of fat and lean mass growth did not appear to be consistently associated with markers of cardiometabolic risk, other than markers of cholesterol metabolism at 5 years.

Background Children with uncomplicated severe acute malnutrition (SAM) are treated at home with ready-to-use therapeutic foods (RUTFs). The current RUTF dose is prescribed according to the weight of the child to fulfil 100% of their nutritional needs until discharge. However, there is doubt concerning the dose, as it seems to be shared, resulting in suboptimal cost-efficiency of SAM treatment. We investigated the efficacy of a reduced RUTF dose in community-based treatment of uncomplicated SAM. Methods and findings We undertook a randomised trial testing the non-inferiority of weight gain velocity of children with SAM receiving (a) a standard RUTF dose for two weeks, followed by a reduced dose thereafter (reduced), compared with (b) a standard RUTF dose throughout the treatment (standard). A mean difference of 0.0 g/kg/day was expected, with a non-inferiority margin fixed at −0.5 g/kg/day. Linear and logistic mixed regression analyses were performed, with study site and team as random effects. Between October 2016 and July 2018, 801 children with uncomplicated SAM aged 6–59 months were enrolled from 10 community health centres in Burkina Faso. At admission, the mean age (± standard deviation [SD]) was 13.4 months (±8.7), 49% were male, and the mean weight was 6.2 kg (±1.3). The mean weight gain velocity from admission to discharge was 3.4 g/kg/day and did not differ between study arms (Δ 0.0 g/kg/day; 95% CI −0.4 to 0.4; p = 0.92) confirming non-inferiority (p = 0.013). However, after two weeks, the weight gain velocity was significantly lower in the reduced dose with a mean of 2.3 g/kg/day compared with 2.7 g/kg/day in the standard dose (Δ −0.4 g/kg/day; 95% CI −0.8 to −0.02; p = 0.041). The length of stay (LoS) was not different (p = 0.73) between groups with a median of 56 days (interquartile range [IQR] 35–91) in both arms. No differences were found between reduced and standard arm in recovery (52.7% and 55.4%; p = 0.45), referral (19.2% and 20.1%; p = 0.80), defaulter (12.2% and 8.5%; p = 0.088), non-response (12.7% and 12.5%; p = 0.95), and relapse (2.4% and 1.8%; p = 0.69) rates, respectively. However, the reduced RUTF dose had a small 0.2 mm/week (95% CI 0.04 to 0.4; p = 0.015) negative effect on height gain velocity with a mean height gain of 2.6 mm/week with reduced and 2.8 mm/week with standard RUTF dose. The impact was more pronounced in children under 12 months of age (interaction, p = 0.019) who gained 2.8 mm/week with reduced and 3.1 mm/week with standard dose (Δ −0.4 mm/week; 95% CI −0.6 to −0.2; p < 0.001). Limitations include not blinding participants to the RUTF dose received and excluding all children with negative appetite test. The results are generalisable for relatively food secure contexts with a young SAM population. Conclusions Reducing the RUTF dose provided to children with SAM after two weeks of treatment did not reduce overall weight or mid-upper arm circumference (MUAC) gain velocity nor affect recovery or lengthen treatment time. However, it led to a small but significant negative effect on linear growth, especially among the youngest. The potential effect of reducing the RUTF dose in a routine program on treatment outcomes should be evaluated before scaling up. Trial registration ISRCTN registry ISRCTN50039021., Suvi Kangas and colleagues reveal a lowered dose of ready-to-use therapeutic food for malnourished children does not reduce weight gain, but can reduce linear growth., Author summary Why was this study done? Severe acute malnutrition (SAM) affects 19 million children worldwide and is treated with ready-to-use therapeutic foods (RUTFs). The current RUTF formulation and dosage are based on an inpatient treatment model and aim at achieving fast weight gain and recovery. However, when used in a home-based setting, the RUTF dose prescribed is often considered too large, resulting in sharing and a suboptimal cost-efficiency of SAM treatment. We sought to investigate the efficacy of reducing the RUTF dosage used in community-based treatment of uncomplicated SAM. What did the researchers do and find? We conducted a randomised controlled trial testing the non-inferiority of a reduced RUTF dose in the management of uncomplicated SAM compared with standard dose. This was called the MANGO trial. We enrolled 801 children 6–59 months of age and randomised them individually into receiving (1) a standard dose of RUTF throughout the treatment and (2) a standard dose during the first two weeks, followed by a reduced dose from third treatment week onwards. The trial showed non-inferior weight gain velocity from admission to discharge and similar recovery and length of stay in treatment. However, the reduced dose also resulted in a significantly slower height gain velocity compared with the standard dose. What do these findings mean? Our findings suggest that the reduction of the RUTF dose after the first two weeks results in similar weight gain velocity and recovery rates as with the standard dose given throughout SAM treatment. However, the reduced RUTF dose seems to slow down the height gain velocity of children and might thus not be fully optimal for children’s healthy growth. The reduced dose approach should be tested in a routine programmatic setting and in different food security contexts before scale-up.

Background Although diabetes is more common in HIV patients, the direct link between HIV and diabetes is unknown. Glucose abnormalities should be assessed among antiretroviral treatment (ART)-naive patients to reduce confounding by ART. We assessed diabetes status, insulin function and association with inflammation among Ethiopian ART-naive HIV patients. Methods Among HIV patients initiating ART, we used glycosylated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to define prediabetes and diabetes. Insulin during OGTT was determined to calculate insulin function, and C-reactive protein and α1-acid glycoprotein were used as same-day markers of inflammation. Results Among 332 HIV patients, mean (SD) age was 32.9 (8.8) years, and 222 (66.9%) were women. None had known diabetes, but we found diabetes prevalence using OGTT and HbA1c to be 7.6 and 8.5%, respectively. C-reactive protein and α1-acid glycoprotein were positively associated with hyperglycemia and insulin deficiency, but not insulin resistance. We found poor correlation between traditional risk factors (age and anthropometry) and diabetes, but participants generally had low BMI and waist circumference. Conclusion ART-naive Ethiopian HIV patients had a high prevalence of prediabetes and diabetes, with a poor agreement between HbA1c and OGTT. Diabetes was associated with inflammation, but not with adiposity and age. Diabetes was linked to insulin deficiency, rather than insulin resistance, which may represent a different entity than type 1 and 2 diabetes. This has implications for choice of drugs, when managing diabetes in African HIV patients.

Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI 2were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VMv.LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or D2O. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI −0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or D2O but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients.

Background: Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults.Methods: Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR- 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance.Results: A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (PConclusion: Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed.

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-agez≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-lengthz(WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were –0·99 (95 % CI –1·26, –0·72) kg at 6 months and –1·44 (95 % CI –1·69; –1·19) kg at 15 months (interaction,P2at 6 months and –1·32 (95 % CI –1·77, –0·87) kg/m2at 15 months (interaction,P

Objectives: Physical activity is beneficial for metabolic health but the extent to which this may differ by ethnicity is still unclear. Here, the objective was to characterize the association between physical activity energy expenditure (PAEE) and cardiometabolic risk among the Luo, Kamba, and Maasai ethnic groups of rural Kenya.Methods: In a cross-sectional study of 1084 rural Kenyans, free-living PAEE was objectively measured using individually-calibrated heart rate and movement sensing. A clustered metabolic syndrome risk score (zMS) was developed by averaging the sex-specific z-scores of five risk components measuring central adiposity, blood pressure, lipid levels, glucose tolerance, and insulin resistance.Results: zMS was 0.08 (-0.09; -0.06) SD lower for every 10 kJ/kg/day difference in PAEE after adjustment for age and sex; this association was modified by ethnicity (interaction with PAEE P Conclusion: Free-living PAEE is strongly inversely associated with cardiometabolic risk in rural Kenyans. Differences between ethnic groups in this association were observed but were explained by differences in central adiposity. Therefore, targeted interventions to increase PAEE are more likely to be effective in subgroups with high central adiposity, such as Maasai with low levels of PAEE.

To assess the prevalence of prolonged and persistent diarrhoea, to estimate their co-occurrence with acute malnutrition and association with demographic and clinical factors.Case-control study where cases were children under 5 years of age with diarrhoea and controls were children without diarrhoea, frequency-matched weekly by age and district of residency. Controls for cases 0-11 months were recruited from vaccination rooms, and controls for cases 12-59 months were recruited by house visits using random locations in the catchment area of the study sites. Data were analysed by mixed model logistic regression.We enrolled 1134 cases and 946 controls. Among the cases, 967 (85%) had acute diarrhoea (AD), 129 (11%) had ProD and 36 (3.2%) had PD. More cases had acute malnutrition at enrolment (17% vs. 4%, P 0.0001) and more were born prematurely (5.7% vs. 1.8%, P 0.0001) than controls. About 75% of ProPD cases did not have acute malnutrition. Cases with AD and ProPD had different symptomatology, even beyond illness duration.ProPD is common among children presenting with diarrhoea and is not confined to children with acute malnutrition. There is an urgent need for studies assessing causes of ProPD with and without acute malnutrition to develop treatment guidelines for these conditions.Evaluer la prévalence des diarrhées prolongées et persistantes, estimer leur co-occurrence avec la malnutrition aiguë et leur association avec des facteurs démographiques et cliniques. MÉTHODES: Etude cas-témoins portant sur des enfants de moins de 5 ans souffrant de diarrhée et sur des témoins, des enfants sans diarrhée, appariées toutes les semaines, en fonction de l’âge et du district de résidence. Les témoins pour les cas de 0 à 11 mois ont été recrutés dans les salles de vaccination et les témoins pour les cas de 12 à 59 mois ont été recrutés au cours de visites à domicile en utilisant des endroits aléatoires dans la zone de recrutement des sites d’étude. Les données ont été analysées par la régression logistique de modèle mixte. RÉSULTATS: Nous avons inscrit 1134 cas et 946 témoins. Parmi les cas, 967 (85%) avaient une diarrhée aiguë (DA), 129 (11%) étaient atteints de diarrhées prolongée (ProD) et 36 (3,2%) de diarrhées persistante (DP). La malnutrition aiguë au moment de l'inscription était plus fréquente (17% contre 4%, P0,0001) et davantage étaient nés prématurément (5,7% contre 1,8%, P0,0001) par rapport aux témoins. 75% des cas de ProPD ne souffraient pas de malnutrition aiguë. Les cas de DA et de ProPD avaient une symptomatologie différente, même au-delà de la durée de la maladie.La ProPD est fréquente chez les enfants présentant une diarrhée et ne se limitait pas aux enfants souffrant de malnutrition aiguë. Il est urgent que des études évaluant les causes de ProPD avec et sans malnutrition aiguë développent des recommandations de traitement pour ces affections.

IntroductionHemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders.MethodsBlood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT).ResultsThe mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26,P< 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM.ConclusionsHbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.

BACKGROUND & OBJECTIVES: Restoration of body composition indicates successful management of severe acute malnutrition (SAM). Bioimpedance (BI) index (height(2)/resistance) is used to predict total body water (TBW) but its performance in SAM, especially with oedema, requires further investigation.SUBJECTS/METHODS: Children with SAM (mid-arm circumference RESULTS: Thirty five children (16 non-oedematous and 19 oedematous) with median (interquartile range) age of 42 (26-54) months were studied. Height-for-age z-score (mean ± SD) was low in both non-oedematous (-3.9 ± 2.8) and oedematous (-3.6 ± 1.7) children. Oedematous children had lower BI parameters than non-oedematous (p < 0.001) and hence higher H(2)/Z for a given amount of TBW. At both 50 and 200 kHz, association between H(2)/Z and TBW was stronger in non-oedematous children than oedematous (60% higher coefficient of determination and 20% lower standard error of estimate). Intercepts and regression estimates at 50 and 200 kHz were similar, in both oedematous and non-oedematous children.CONCLUSIONS: In children with oedematous SAM, BI index was weak in predicting TBW. Moreover, predicted TBWs at 200 kHz and 50 kHz did not differ and hence BI measurement at 50 kHz is still practical for TBW estimation.

Children with severe acute malnutrition (SAM) with complications require in-patient management including therapeutic feeding. Little attention has been given to the effects of these feeds on the essential fatty acid status of children with SAM. The objective of this study was to describe changes in the PUFA composition in whole blood in children with SAM during treatment and to determine predictors of change. This prospective study took place in a paediatric nutrition rehabilitation unit in Kampala, Uganda, and assessed whole-blood fatty acid composition of children with SAM at admission, transition, discharge and follow-up (8 and 16 weeks). ANCOVA was used to identify predictors of change in whole-blood PUFA. The study included 120 children with SAM and twenty-nine healthy control children of similar age and sex. Among the SAM children, 38 % were female and 64 % had oedema. Whole-bloodn-6 PUFA proportions increased from admission to follow-up, except for arachidonic acid, which decreased by 0·79 (95 % CI 0·46, 1·12) fatty acid percentage (FA%) from admission to transition and 0·10 (95 % CI 0·23, 0·44) FA% at discharge.n-3 Long-chain (LC) PUFA decreased by 0·21 (95 % CI 0·03, 0·40) FA% at discharge and 0·22 (95 % CI 0·01, 0·42) FA% at 8 weeks of follow-up. This decrease was greater in children from families with recent fish intake and those with nasogastric tube feeding. Current therapeutic feeds do not correct whole-blood levels of LCPUFA, particularlyn-3 LCPUFA, in children with SAM. Increased attention is needed to the contents ofn-3 LCPUFA in therapeutic feeds.

BACKGROUND: Children treated for severe acute malnutrition (SAM) are at risk of refeeding hypophosphatemia. Therapeutic diets have only recently become fortified with phosphorus to meet United Nations (UN) specifications but to our knowledge no studies have investigated the effect. OBJECTIVE: The aim was to assess concentrations and correlates of plasma phosphate (P-phosphate) at admission and during treatment and to identify correlates of changes in P-phosphate. DESIGN: This was a prospective observational study in 6- to 59-mo-old children admitted for treatment of SAM to Mulago Hospital Uganda. P-phosphate was measured at admission on the second day of treatment with a therapeutic formula containing 75 kcal/100 mL and 560 mg phosphorus/L (F-75 Nutriset) at the start of the transition to a therapeutic formula containing 100 kcal/100 mL and 579 mg phosphorus/L (F-100; Nutriset) at day 2 of transition and at discharge. RESULTS: Among 120 children mean +/- SD P-phosphate at admission was 1.04 +/- 0.31 mmol/L and increased by 0.43 (95% CI: 0.35 0.52) mmol/L during the first 2 d and more slowly toward discharge. Most (79%) children experienced their lowest P-phosphate concentration at admission and none developed severe hypophosphatemia. P-phosphate was lowest in children with edema and with elevated C-reactive protein and a lower increase was seen with increasing caretaker-reported severity of illness. Partially or fully replacing F-75 with rice porridge (i.e. a local practice to reduce diarrhea) during the first 2 d of stabilization was associated with a 0.34-mmol/L (95% CI: 0.18 0.50 mmol/L) lower increase in P-phosphate during the same first 2 d. CONCLUSIONS: F-75 which complies with UN specifications and provides 73 mg phosphorus . kg(-1) . d(-1) (130 mL . kg(-1) . d(-1)) seems to prevent refeeding hypophosphatemia in children with SAM. Replacing this formula with rice porridge during the first days of treatment to manage diarrhea may have an adverse effect on P-phosphate concentrations. This study was registered at http://www.isrctn.com as ISRCTN55092738. (c) 2016 American Society for Nutrition.

Background/Objectives Low and high birth weight and rapid weight gain during infancy are associated with childhood obesity. Associations of birth and infancy body composition (BC) growth with childhood BC remain unknown in low-income countries. We aimed to investigate the associations of fat mass (FM) and fat-free mass (FFM) at birth and its accretion during early infancy with FM and FFM at the age of 4 years. Methods In the infant Anthropometry and Body Composition (iABC) cohort, BC was assessed at six consecutive time points from birth to 6 months and at 4 years of age by air displacement plethysmography. Multiple linear regression models were used to determine the association between FM and FFM at birth and their accretion rates during infancy and FM index (FMI) and FFM index (FFMI) at 4 years in 314 children. Results One kilogram higher FFM at birth was associated with a 1.07 kg/m2 higher FFMI (95% CI 0.60, 1.55) at 4 years while a one SD increment in FFM accretion rate from 0 to 6 months was associated with a 0.24 kg/m2 increment in FFMI (95% CI 0.11, 0.36) and with a 0.20 kg/m2 higher FMI at 4 years (β = 0.20; 95% CI 0.04, 0.37). FFM at birth did not predict FMI at 4 years. FM at birth was associated with 1.17 kg/m2 higher FMI at 4 years (95% CI 0.13, 2.22) whereas FM accretion from 0 to 4 months was associated with an increase in FMI of 0.30 kg/m2 (95% CI 0.12, 0.47). FM at birth did not predict FFMI at 4 years, and neither did FM accretion from 0 to 4 months. Conclusions A higher FFM in early infancy predicted higher FFMI at 4 years while a higher FM accretion during early infancy predicted higher FMI at 4 years. Follow-up studies are merited to explore associations of childhood BC with cardio-metabolic risk later in life.

BACKGROUND: In moderate acute malnutrition programs, it is common practice to not measure mid-upper arm circumference (MUAC) of children whose length is METHODS: In this observational study, we included children aged 6 to 23 months with a MUAC between 115 and 125 mm and a weight-for-height z score ≥−2. On the basis of length at admission, children were categorized as short if RESULTS: After 12 weeks of supplementation, there was no difference in change in fat mass index (−0.038 kg/m2, 95% confidence interval [CI]: −0.257 to 0.181, P = .74) or fat-free mass index (0.061 kg/m2, 95% CI: −0.150 to 0.271, P = .57) in short versus long. In absolute terms, the short children gained both less fat-free mass (−230 g, 95% CI: −355 to −106, P < .001) and fat mass (−97 g, 95% CI: −205 to 10, P = .076). There was no difference in changes in absolute subscapular and triceps skinfold thickness and z scores (P > .5). CONCLUSIONS: Short children with low MUAC do not gain excessive fat during supplementation. With these data, we support a recommendation for policy change to include all children ≥6 months with low MUAC in supplementary feeding programs, regardless of length. The use of length as a criterion for measuring MUAC to determine treatment eligibility should be discontinued in policy and practice.

BACKGROUND: There is little information about serum phosphate levels among patients with pulmonary tuberculosis (TB) and HIV infection.OBJECTIVE: We aimed to assess the role of TB, HIV, inflammation and other correlates on serum phosphate levels.METHODS: A cross-sectional study was conducted among TB patients and age- and sex-matched non-TB controls. Pulmonary TB patients were categorized as sputum -negative and -positive, based on culture. Age- and sex-matched non-TB controls were randomly selected among neighbours to sputum-positive TB patients. Data on age, sex, alcohol and smoking habits were obtained. HIV status, serum phosphate, and the acute phase reactants C-reactive protein (serum CRP) and α1-acid glycoprotein (serum AGP) were determined. Linear regression analysis was used to identify correlates of serum phosphate.RESULTS: Of 1605 participants, 355 (22.1%) were controls and 1250 (77.9%) TB patients, of which 9.9% and 50.4% were HIV-infected. Serum phosphate was determined before start of TB treatment in 44%, and 1-14 days after start of treatment in 56%. Serum phosphate was up to 0.10 mmol/L higher 1-3 days after start of TB treatment, and lowest 4 days after treatment, after which it increased. In multivariable analysis, TB patients had 0.09 (95% CI: 0.05; 0.13) mmol/L higher serum phosphate than controls, and those with HIV had 0.05 (95% CI: 0.01; 0.08) mmol/L higher levels than those without. Smoking was also a positive correlate of serum phosphate, whereas male sex and age were negative correlates.CONCLUSION: While HIV and TB are associated with higher serum phosphate, our data suggest that TB treatment is followed by transient reductions in serum phosphate, which may reflect hypophosphataemia in some patients.

The impact of freshwater fish consumption on the status of long-chain n-3 fatty acids (n-3 LCPUFA) in infants in landlocked, low-income populations is unknown. We used secondary data from a randomized, single-blinded, controlled trial to evaluate the impact of daily consumption of complementary food products with small amounts of freshwater fish on whole blood n-3 LCPUFA in Cambodian infants. Infants (n = 419), received daily, one of four food products for 9 months. Two products contained freshwater fish: WinFood (10% fish by dry weight) and WinFood-L (12% fish by dry weight), while two products were non-fish-based: corn-soy blends (CSB+ and CSB++). Whole blood fatty acids and breastfeeding status were assessed at baseline and endline of the intervention. The WinFood products contributed to an estimated maximum intake of 86.5 mg/day n-3 LCPUFA. There was no difference in whole blood n-3 LCPUFA among the four intervention groups or between the fish-based and the non-fish-based groups (p ≥ 0.142). At endline, 71% of the children were still breastfed. Interaction analyses indicated a lower ratio of n-6/n-3 PUFA in non-breastfed infants in the WinFood groups compared to the CSB groups (pinteraction= 0.026). Thus, a high intake of n-3 LCPUFA from breastmilk may have blurred a potential impact of small amounts of freshwater fish effect on n-3 LCPUFA status in Cambodian infants.

OBJECTIVE: To assess the level and predictors of physical activity at discharge among children recovering from severe acute malnutrition (SAM). METHODS: We conducted a prospective study among 69 children 6-59 months of age admitted with SAM for nutritional rehabilitation at Mulago National Referral Hospital, Uganda. Using hip-mounted triaxial accelerometers, we measured physical activity expressed as counts per minute (cpm) during the last three days of hospital treatment. As potential predictors, we assessed clinical and background characteristics, duration to transition phase and duration of hospitalisation, serum C-reactive protein and whole-blood docosahexaenoic acid (DHA). Multiple linear regression analyses were used to identify predictors of physical activity. RESULTS: The median (IQR) age was 15.5 (12.6; 20.5) months. At discharge, the mean (SD) movement was 285 (126) cpm. Physical activity was 43 (19; 67) cpm higher for each unit increase in weight-for-height z-score (WHZ) and 72 (36; 108) cpm higher for each centimetre increase in MUAC. Whole-blood DHA on admission was also a positive predictor of physical activity, whereas duration to transition phase and duration of hospitalisation were both negative predictors. CONCLUSION: The level of physical activity at discharge among children treated for SAM was low. WHZ, MUAC and DHA on admission were positive predictors of physical activity, whereas duration of stabilisation and hospitalisation was negative predictors of physical activity. These results suggest that assessment of physical activity may be used as a marker of recovery.

ObjectiveTo examine the relationship between body composition—specifically fat mass (FM) and fat-free mass (FFM)—in early infancy, and mental health outcomes in early childhood.Study designIn the Infant Anthropometry and Body Composition birth cohort study from Ethiopia, body composition was measured at birth and 1.5, 2.5, 3.5, 4.5, and 6 months of age. Mental health was assessed at 5 years of age using the approved Amharic version of the Strengths and Difficulties Questionnaire (SDQ), a parent report scale covering 4 different domains providing a total difficulties score. The associations of FM or FFM at birth as well as during early infancy, with SDQ score at 5 years of age were examined using multiple linear regression analyses.ResultsAt 5 years of age, the mean ± SD for SDQ score was 10.4 ± 5.8. FM at birth was positively and FFM negatively associated with SDQ score. For each kg increase in FM at birth, the SDQ score at 5 years was 5.7 points higher (β = 5.7; 95% CI, 1.4-10.0). In contrast, for each kilogram increase in FFM at birth, the SDQ score was 3.9 points lower (β = -3.9; 95% CI, -7.0 to -0.8). Neither FM nor FFM accretion rate during early infancy were associated with SDQ score at 5 years of age.ConclusionsFetal rather than infant body composition was associated with SDQ score at 5 years of age. Greater FFM accretion during fetal life may have contributed to more optimal neurobehavioral development during early life. However, the potential mechanisms underlying the observed associations need further investigation.

The objective of this study was to identify subgroups with distinct fat and fat-free growth patterns in the first 6 months of life and describe predictors of these different patterns.A total of 510 apparently healthy Ethiopian infants were followed from birth to 6 months of age. Each infant had at least three and up to six repeated measurements of fat and fat-free mass using air-displacement plethysmography. Latent class trajectory analyses were used to categorize infants in groups with distinct body composition patterns.Four distinct fat mass and two fat-free mass growth patterns were identified. Of the infants measured, 5% presented a delayed fat growth pattern and 3% presented a catch-up fat growth pattern involving low birth weight but a significant fat growth velocity from 2.5 to 6 months. A large class had a high fat level at birth and an accelerated fat growth pattern in early infancy. Fat-free growth was represented by two distinct classes with less variability. Catch-up growth was primarily seen in fat mass.We identified distinct patterns of delayed, catch-up, and accelerated fat growth in early infancy. This variability is not detected in regular anthropometric assessment and could be a mechanism linking early growth with later obesity and cardiometabolic risk.

Background: A midupper arm circumference (MUAC)

BACKGROUND/OBJECTIVES: Gains in fat mass and lean mass during tuberculosis (TB) treatment may determine functional recovery and survival; yet, data are scarce. We aimed to assess predictors of fat and fat-free mass during 2 months of intensive TB treatment in a cohort in Mwanza, Tanzania.SUBJECTS/METHODS: Fat and fat-free mass were determined at the start of TB treatment and repeated after 2 months using the deuterium dilution technique. Gains in fat and fat-free mass were determined and predictors assessed using regression analysis.RESULTS: Data for 116 patients were available at baseline and during follow-up. Of these, 38.8% were females, mean age was 37.3 (s.d. 13.5) years, 69% (81) had sputum-positive TB, 45.7% (53) were HIV infected and 25% (29) were current smokers. The mean weight gain was 3.3 kg (95% confidence interval: 2.7; 3.8), and it did not differ by sex. However, compared with females, males had 1.0 (0.4; 1.6) kg/m(2) lower fat mass but 0.7 (0.2; 1.3) kg/m(2) higher fat-free mass gain. Current smoking was associated with higher fat mass (0.7 kg/m(2), 0.04; 1.4) but lower fat-free mass (-0.5 kg/m(2), -1.2; 0.07) gain. Among HIV-infected patients, antiretroviral therapy (ART) led to a lower fat gain (-1.2 kg/m(2), -2.2; -0.2) but to a higher fat-free mass among sputum-negative (2.9 kg/m(2), 0.8; 5.1) but not sputum-positive patients.CONCLUSIONS: During intensive phase of TB treatment, sex, smoking and ART were predictors of body composition. Larger studies are needed to further understand predictors of body composition during recovery, to help design interventions to improve treatment outcomes.

Background: Micronutrients play an important role in immune function. To our knowledge, there have been no comprehensive studies on the role of micronutrient supplementation in children with tuberculosis. Objective: We assessed the effect of micronutrient supplementation in children treated with antituberculosis therapy (ATT). Design: A randomized, double-blind, placebo-controlled trial that used a 2 3 2 factorial design was undertaken at 2 teaching hospitals in Delhi. Children with newly diagnosed intrathoracic tuberculosis were enrolled, and they received ATT together with daily supplementation for 6 mo with either zinc alone, micronutrients without zinc, micronutrients in combination with zinc, or a placebo. Main outcomes were weight gain and an improvement in a chest X-ray (CXR) lesion assessed at 6 mo of treatment. Results: A total of 403 children were enrolled and randomly assigned. A microbiological diagnosis of tuberculosis was confirmed in 179 children (44.4%). The median (95% CI) increase in weight-for-age z score at 6 mo was not significantly different between subjects who received micronutrients [0.75 (0.66, 0.84)] and those who did not receive micronutrients [0.76 (0.67, 0.85)] and between subjects who received zinc [0.76 (0.68, 0.85)] and those who did not receive zinc [0.75 (0.66, 0.83)]. An improvement in CXR was observed in 285 children, but there was no difference between those receiving zinc and no zinc or between those receiving micronutrients and no micronutrients after 6 mo of ATT. However, children who received micronutrients had a faster gain in height over 6 mo than did those who did not receive micronutrients (height-for-age z score D = 0.08; P = 0.014). Conclusions: Micronutrient supplementation did not modify the weight gain or clearance of lesions on CXR in children with intrathoracic tuberculosis. However, micronutrient supplementation during treatment may improve height gain in children with intrathoracic tuberculosis. This trial was registered at clinicaltrials.gov as NCT00801606. Am J Clin Nutr 2014;100:1287‐97.

BACKGROUND/OBJECTIVES: Birth weight (BW), independent of socioeconomic status, has been identified as a predictor for childhood cognitive development. However, it is not known whether this relation is related to low BW per se or particularly related to a deficit in fat mass (FM) or fat-free mass (FFM) at birth. This study therefore aimed at investigating the relation between body composition at birth and child development at 2 years of age.SUBJECTS/METHODS: An Ethiopian birth cohort was followed up at 2 years. Body composition was measured within 48 h of birth using infant air-displacement plethysmography. Child development was assessed at 2 years of age using Denver developmental screening test. Associations between body composition at birth and development at 2 years of age were tested using linear regression analysis.RESULTS: FFM but not FM at birth was positively associated with higher global developmental score at 2 years of age (β=2.48, 95% confidence interval (CI) 0.17; 4.79) adjusted for neonatal, postnatal and parental characteristics. This association was attributable to the association with the language developmental domain (β=1.61, 95 CI 0.33; 2.90).CONCLUSIONS: Among Ethiopian children, FFM at birth but not FM predicted better global and language development at 2 years of age. Higher FFM at birth might have exerted a positive effect on the growth and differentiation of the brain and neuronal circuits for better development. This study therefore highlights the need to improve mother's nutritional status during pregnancy in ways that stimulate fetal FFM growth.European Journal of Clinical Nutrition advance online publication, 27 September 2017; doi:10.1038/ejcn.2017.129.

Background Children with moderate acute malnutrition (MAM) are treated with lipid-based nutrient supplement (LNS) or corn-soy blend (CSB). We assessed the effectiveness of (a) matrix, i.e., LNS or CSB, (b) soy quality, i.e., soy isolate (SI) or dehulled soy (DS), and (c) percentage of total protein from dry skimmed milk, i.e., 0%, 20%, or 50%, in increasing fat-free tissue accretion. Methods and findings Between September 9, 2013, and August 29, 2014, a randomised 2 × 2 × 3 factorial trial recruited 6- to 23-month-old children with MAM in Burkina Faso. The intervention comprised 12 weeks of food supplementation providing 500 kcal/day as LNS or CSB, each containing SI or DS, and 0%, 20%, or 50% of protein from milk. Fat-free mass (FFM) was assessed by deuterium dilution technique. By dividing FFM by length squared, the primary outcome was expressed independent of length as FFM index (FFMI) accretion over 12 weeks. Other outcomes comprised recovery rate and additional anthropometric measures. Of 1,609 children, 4 died, 61 were lost to follow-up, and 119 were transferred out due to supplementation being switched to non-experimental products. No children developed allergic reaction. At inclusion, 95% were breastfed, mean (SD) weight was 6.91 kg (0.93), with 83.5% (5.5) FFM. In the whole cohort, weight increased 0.90 kg (95% CI 0.88, 0.93; p < 0.01) comprising 93.5% (95% CI 89.5, 97.3) FFM. As compared to children who received CSB, FFMI accretion was increased by 0.083 kg/m2 (95% CI 0.003, 0.163; p = 0.042) in those who received LNS. In contrast, SI did not increase FFMI compared to DS (mean difference 0.038 kg/m2; 95% CI −0.041, 0.118; p = 0.35), irrespective of matrix. Having 20% milk protein was associated with 0.097 kg/m2 (95% CI −0.002, 0.196) greater FFMI accretion than having 0% milk protein, although this difference was not significant (p = 0.055), and there was no effect of 50% milk protein (0.049 kg/m2; 95% CI −0.047, 0.146; p = 0.32). There was no effect modification by season, admission criteria, or baseline FFMI, stunting, inflammation, or breastfeeding (p > 0.05). LNS compared to CSB resulted in 128 g (95% CI 67, 190; p < 0.01) greater weight gain if both contained SI, but there was no difference between LNS and CSB if both contained DS (mean difference 22 g; 95% CI −40, 84; p = 0.49) (interaction p = 0.017). Accordingly, SI compared to DS increased weight by 89 g (95% CI 27, 150; p = 0.005) when combined with LNS, but not when combined with CSB. A limitation of this and other food supplementation trials is that it is not possible to collect reliable data on individual adherence. Conclusions Based on this study, children with MAM mainly gain fat-free tissue when rehabilitated. Nevertheless, LNS yields more fat-free tissue and higher recovery rates than CSB. Moreover, current LNSs with DS may be improved by shifting to SI. The role of milk relative to soy merits further research. Trial registration ISRCTN registry ISRCTN42569496, Malnourished children accrue more fat free tissue with lipid-based food supplements compared to corn-soy blend ones, as revealed in a trial in Burkina Faso led by Christian Fabiansen, Author summary Why was this study done? Moderate acute malnutrition (MAM) is widespread among children in low-income countries and is a risk factor for morbidity, severe acute malnutrition, and death. WHO recommends more research on food supplements for children with MAM. Currently, there is no consensus on either the effectiveness of lipid-nutrient supplement (LNS) compared to corn-soy blend (CSB), or on the role of key factors like milk and soy. There is concern that children receiving LNS might accumulate too much fat tissue. What did the researchers do and find? In a large randomised trial of 1,609 children with MAM, conducted in a humanitarian setting in Burkina Faso, we investigated the effectiveness of key factors in supplemental foods, namely (a) the matrix (LNS versus CSB), (b) the soy quality (soy isolate versus dehulled soy), and (c) the level of dry skimmed milk. We evaluated body composition to assess the quality of weight gain, and used fat-free mass tissue accretion as our primary outcome. Fat-free tissue accretion as well as recovery from MAM were both higher when using LNS compared to CSB. Children given LNS did not put on excessive fat. What do these findings mean? Our findings support a wider use of LNS in the treatment of children with MAM. A switch to LNS would lead to greater gain of fat-free tissue and recovery, and would benefit millions of children.

Background We have previously shown that fat-free mass (FFM) at birth is associated with height at 2 y of age in Ethiopian children. However, to our knowledge, the relation between changes in body composition during early infancy and later linear growth has not been studied. Objective This study examined the associations of early infancy fat mass (FM) and FFM accretion with linear growth from 1 to 5 y of age in Ethiopian children. Methods In the infant Anthropometry and Body Composition (iABC) study, a prospective cohort study was carried out in children in Jimma, Ethiopia, followed from birth to 5 y of age. FM and FFM were measured ≤6 times from birth to 6 mo by using air-displacement plethysmography. Linear mixed-effects models were used to identify associations between standardized FM and FFM accretion rates during early infancy and linear growth from 1 to 5 y of age. Standardized accretion rates were obtained by dividing FM and FFM accretion by their respective SD. Results FFM accretion from 0 to 6 mo of age was positively associated with length at 1 y (β = 0.64; 95% CI: 0.19, 1.09; P = 0.005) and linear growth from 1 to 5 y (β = 0.63; 95% CI: 0.19, 1.07; P = 0.005). The strongest association with FFM accretion was observed at 1 y. The association with linear growth from 1 to 5 y was mainly engendered by the 1-y association. FM accretion from 0 to 4 mo was positively associated with linear growth from 1 to 5 y (β = 0.45; 95% CI: 0.02, 0.88; P = 0.038) in the fully adjusted model. Conclusions In Ethiopian children, FFM accretion was associated with linear growth at 1 y and no clear additional longitudinal effect from 1 to 5 y was observed. FM accretion showed a weak association from 1 to 5 y. This trial was registered at www.controlled-trials.com as ISRCTN46718296.

Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. : The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index : In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. : In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition. This article is protected by copyright. All rights reserved.