Treatment outcomes and associated factors for hospitalization of children treated for acute malnutrition under the OptiMA simplified protocol: a prospective observational cohort in rural Niger.

Introduction: Globally, access to treatment for severe and moderate acute malnutrition is very low, in part because different protocols and products are used in separate programs. New approaches, defining acute malnutrition (AM) as mid-upper arm circumference (MUAC) < 125 mm or oedema, are being investigated to compare effectiveness to current programs. Optimizing Malnutrition treatment (OptiMA) is one such strategy that treats AM with one product - ready-to-use therapeutic food, or RUTF - at reduced dosage as the child improves. Methods: This study aimed to determine whether OptiMA achieved effectiveness benchmarks established in the Nigerien National Nutrition protocol. A prospective cohort study of children in the rural Mirriah district evaluated outcomes among children 6-59 months with uncomplicated AM treated under OptiMA. In a parallel, unconnected program in one of the two trial sites, all non-malnourished children 6-23 months of age were provided small quantity lipid-based nutritional supplements (SQ-LNS). A multivariate logistic regression identified factors associated with hospitalization. Results: From July-December 2019, 1,105 children were included for analysis. Prior to treatment, 39.3% of children received SQ-LNS. Recovery, non-response, and mortality rates were 82.3%, 12.6%, and 0.7%, respectively, and the hospitalization rate was 15.1%. Children who received SQ-LNS before an episode of AM were 43% less likely to be hospitalized (ORa=0.57; 0.39-0.85, p = 0.004). Discussion: OptiMA had acceptable recovery compared to the Nigerien reference but non-response was high. Children who received SQ-LNS before treatment under OptiMA were less likely to be hospitalized, showing potential health benefits of combining simplified treatment protocols with food-based prevention in an area with a high burden of malnutrition such as rural Niger.

Potential Impacts of Mass Nutritional Supplementation on Measles Dynamics: A Simulation Study.

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.

Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis.

One feature of high-fat diet-induced neurodegeneration in the hypothalamus is an increased level of palmitate, which is associated with endoplasmic reticulum (ER) stress, loss of CoxIV, mitochondrial fragmentation, and decreased abundance of MC4R. To determine whether antidiabetic drugs protect against ER and/or mitochondrial dysfunction by lipid stress, hypothalamic neurons derived from pre-adult mice and neuronal Neuro2A cells were exposed to elevated palmitate. In the hypothalamic neurons, palmitate exposure increased expression of ER resident proteins, including that of SERCA2, indicating ER stress. Liraglutide reverted such altered ER proteostasis, while metformin only normalized SERCA2 expression. In Neuro2A cells liraglutide, but not metformin, also blunted dilation of the ER induced by palmitate treatment, and enhanced abundance and expression of MC4R at the cell surface. Thus, liraglutide counteracts, more effectively than metformin, altered ER proteostasis, morphology, and folding capacity in neurons exposed to fat. In palmitate-treated hypothalamic neurons, mitochondrial fragmentation took place together with loss of CoxIV and decreased mitochondrial membrane potential (MMP). Metformin, but not liraglutide, reverted mitochondrial fragmentation, and both liraglutide and metformin did not protect against either loss of CoxIV abundance or MMP. Thus, ER recovery from lipid stress can take place in hypothalamic neurons in the absence of recovered mitochondrial homeostasis.

Costs of Implementing an Integrated Package of Maternal and Pediatric Interventions Including SQ-LNS in Rural Niger.

BACKGROUND: In January 2015, the Alliance for International Medical Action and Bien Être de la Femme et de l'Enfant au Niger launched the 1000 Days Program in Mirriah District, Niger, to provide an integrated package of maternal and pediatric preventive and curative interventions. A new component of the package was the provision of small-quantity lipid-based nutritional supplements (SQ-LNS) for children 6 to 23 months. OBJECTIVE: The objective of this study was to estimate the costs associated with providing the 1000 days package. METHODS: Activity-based costing was used to estimate the total costs of the 10 activities included in the 1000 days package and also the incremental costs of new interventions, those beyond the standard of care. RESULTS: The total cost of the 1000 Days Program was US$2.31 million for 9000 mother-child pairs. The average cost per pair was US$257 or US$103 per year. Incremental costs for new interventions accounted for 56% of program costs. Small-quantity lipid-based nutritional supplement represented 30% of incremental costs. A combination of efficiency measures could lower program costs by 15%. CONCLUSIONS: This study is the first to estimate the costs of an integrated, preventative-curative package of maternal-child health interventions with SQ-LNS. Implementing the 1000 days package across Niger will be challenging with only the country's domestic health resources. Efficiency measures and creative financing arrangements, including support from external partners, should be explored. The approach and results described can inform future resource mobilization, financing, and budgeting efforts to scale the 1000 days or similar programs.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

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.

Association between admission criteria and body composition among young children with moderate acute malnutrition, a cross-sectional study from Burkina Faso.

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.

New approach to simplifying and optimising acute malnutrition treatment in children aged 6-59 months: the OptiMA single-arm proof-of-concept trial in Burkina Faso.

The Optimising treatment for acute MAlnutrition (OptiMA) strategy trains mothers to use mid upper arm circumference (MUAC) bracelets for screening and targets treatment to children with MUAC < 125 mm or oedema with one therapeutic food at a gradually reduced dose. This study seeks to determine whether OptiMA conforms to SPHERE standards (recovery rate > 75 %). A single-arm proof-of-concept trial was conducted in 2017 in Yako district, Burkina Faso including children aged 6-59 months in outpatient health centres with MUAC < 125 mm or oedema. Outcomes were stratified by MUAC category at admission. Multivariate survival analysis was carried out to identify variables predictive of recovery. Among 4958 children included, 824 (16·6 %) were admitted with MUAC < 115 mm or oedema, 1070 (21·6 %) with MUAC 115-119 mm and 3064 (61·8 %) with MUAC 120-124 mm. The new dosage was correctly implemented at all visits for 75·9 % of children. Global recovery was 86·3 (95 % CI 85·4, 87·2) % and 70·5 (95 % CI 67·5, 73·5) % for children admitted with MUAC < 115 mm or oedema. Average therapeutic food consumption was 60·8 sachets per child treated. Recovery was positively associated with mothers trained to use MUAC prior to child's admission (adjusted hazard ratio 1·09; 95 % CI 1·01, 1·19). OptiMA was successfully implemented at the scale of an entire district under 'real-life' conditions. Programme outcomes exceeded SPHERE standards, but further study is needed to determine if increasing therapeutic food dosages for the most severely malnourished will improve recovery.

Short Malnourished Children and Fat Accumulation With Food Supplementation.

BACKGROUND: In moderate acute malnutrition programs, it is common practice to not measure mid-upper arm circumference (MUAC) of children whose length is <67 cm. This is based on expert opinion that supplementation of shorter children with low MUAC and weight-for-height z score ≥-2 may increase risk of excessive fat accumulation. Our aim was to assess if shorter children gain more fat than taller children when treated for moderate acute malnutrition diagnosed by low MUAC alone. 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 <67 cm and long if ≥67 cm. Linear mixed-effects models were used to assess body composition on the basis of deuterium dilution and skinfold thickness. 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.

Intra-household use and acceptability of Ready-to-Use-Supplementary-Foods distributed in Niger between July and December 2010.

Few studies have looked at consumption of Ready-to-Use-Supplementary-Foods (RUSFs) during a nutritional emergency. Here, we describe the use and acceptability of RUSF within households in four districts of the region of Maradi, Niger during large scale preventive distributions with RUSF in 2010 targeted at children 6-35months of age. Our study comprised both quantitative and qualitative components to collect detailed information and to allow in-depth interviews. We performed a cross-sectional survey in 16 villages between two monthly distributions of RUSF (October-November 2010). All households with at least one child who received RUSF were included and a total of 1842 caregivers were interviewed using a structured questionnaire. Focus groups and individual interviews of 128 caregivers were conducted in eight of the selected villages. On average, 24.7% of households reported any sharing of RUSF within the household. Sharing practices outside the household remained rare. Most of the sharing reported occurred among children under 5years of age living in the household. On average, 91% of caregivers in all districts rated the child's appreciation of the products as good or very good. Program planning may need to explicitly accounting for the sharing of products among children under 5 within household.