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A simplified, combined protocol treats children with moderate acute malnutrition (MAM), defined by mid‐upper arm circumference (MUAC) of < 125 and ≥ 115 mm and no oedema, with 1 daily sachet of ready‐to‐use therapeutic food (RUTF) and those with severe acute malnutrition (SAM), defined by MUAC < 115 mm and/or oedema, with two daily sachets of RUTF. This protocol was previously shown to result in non‐inferior recovery compared to standard treatment that used higher, weight‐based RUTF dosing among children with SAM and ready‐to‐use supplementary food (RUSF) for MAM in a cluster‐based randomised controlled trial in Kenya and South Sudan. We conducted a secondary analysis of this trial to compare linear growth among children admitted with MUAC < 115 mm. Linear and ponderal growth were calculated from admission to discharge and visualised using aggregate growth curves. HAZ change adjusted for admission characteristics was negative across the course of treatment but similar across arms [−0.21 ± 0.18 SE in the standard arm, −0.24 ± 0.18 SE in simplified; difference (95% confidence interval) 0.03 (−0.12, 0.18)]. The unadjusted mean ± SE linear growth velocity from admission to discharge was 1.8 ± 0.7 mm/week in the standard arm compared to 1.7 ± 0.7 mm/week in the simplified arm [difference = 0.09 (−0.36, 0.53)] and similar in adjusted analysis. MUAC and weight gain velocities were not significantly different by treatment arm. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment. Summary Linear growth during acute malnutrition treatment is an understudied outcome, despite evidence suggesting a bidirectional relationship between stunting and wasting. We performed secondary data analysis of a randomised controlled trial of a simplified, MUAC‐based dose for acute malnutrition among children 6–59 months in Kenya and South Sudan, investigating the effect of the intervention on linear growth during treatment. Linear growth observed in this sub‐population was not sufficient to prevent a similar loss in HAZ in both arms. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment. Overall, this study adds to a growing body of evidence that suggests SAM can be treated effectively and result in similar anthropometric growth when treated with a simplified, MUAC‐based dose of RUTF and a standard weight‐based dose of RUTF. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment with a MUAC‐based protocol or with a standard weight‐based protocol.

IntroductionCurrent formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota metabolism and mucosal barrier functions. Heat-stabilised rice bran contains essential nutrients, prebiotics, vitamins and unique phytochemicals that have demonstrated favourable bioactivity to modulate gut microbiota composition and mucosal immunity. This study seeks to examine the impact of RUTF with rice bran on the microbiota during SAM treatment, recovery and post-treatment growth outcomes in Jember, Indonesia. Findings are expected to provide insights into rice bran as a novel food ingredient to improve SAM treatment outcomes.Methods and analysisA total of 200 children aged 6–59 months with uncomplicated SAM (weight-for-height z-scores (WHZ) <−3, or mid-upper arm circumference (MUAC) <115 mm or having bilateral pitting oedema +/++) or approaching SAM (WHZ<−2.5) will be enrolled in a double-blinded, randomised controlled trial. Children in the active control arm will receive a locally produced RUTF; those in the intervention arm will receive the local RUTF with 5% rice bran. Children will receive daily RUTF treatment for 8 weeks and be monitored for 8 weeks of follow-up. Primary outcomes include the effectiveness of RUTF as measured by changes in weight, WHO growth z-scores, MUAC and morbidity. Secondary outcomes include modulation of the gut microbiome and dried blood spot metabolome, the percentage of children recovered at weeks 8 and 12, and malnutrition relapse at week 16. An intention-to-treat analysis will be conducted for each outcome.Ethics and disseminationThe findings of this trial will be submitted to peer-reviewed journals and will be presented at relevant conferences. Ethics approval obtained from the Medical and Health Research Ethical Committee at the Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Madain Yogyakarta Ref. No.: KE/FK/0546/EC/2022 and KE/FK/0703/EC/2023 and from Colorado State University IRB#1823, OHRP FWA00000647.Trial registration numberNCT05319717.

International recommendations advise against the use of intravenous rehydration therapy in children with severe acute malnutrition because of the concern about fluid overload, but evidence to support this concern is lacking. Given the high mortality associated with the current recommendations, the adoption of intravenous rehydration strategies might improve outcomes. We conducted a factorial, open-label superiority trial in four countries in Africa. Children 6 months to 12 years of age with severe acute malnutrition with gastroenteritis and dehydration underwent randomization in a 2:1:1 ratio to one of three rehydration strategies: oral rehydration, plus intravenous boluses for shock; a rapid intravenous strategy that consisted of lactated Ringer's solution (100 ml per kilogram of body weight) administered over a period of 3 to 6 hours, with boluses for shock; or a slow intravenous strategy that consisted of the same solution administered over a period of 8 hours, with no boluses. The primary end point was death at 96 hours. A total of 272 children underwent randomization; 138 were assigned to the oral strategy, 67 to the rapid intravenous strategy, and 67 to the slow intravenous strategy. Participants were followed for 28 days. A nasogastric tube was used for oral rehydration in 126 of 135 participants (93%) in the oral group and in 82 of 126 (65%) in the intravenous groups. Intravenous boluses were administered at admission in 12 participants (9%) in the oral group, 7 (10%) in the rapid intravenous group, and none in the slow intravenous group. At 96 hours, 11 participants (8%) in the oral group and 9 (7%) in the intravenous groups (5 in the rapid group and 4 in the slow group) had died (risk ratio, 1.02; 95% confidence interval [CI], 0.41 to 2.52; P = 0.69). At 28 days, 17 participants (12%) in the oral group and 14 (10%) in the intravenous groups had died (hazard ratio, 0.85; 95% CI, 0.41 to 1.78). Serious adverse events occurred in 32 participants (23%) in the oral group, 14 (21%) in the rapid intravenous group, and 10 (15%) in the slow intravenous group. No evidence of pulmonary edema, heart failure, or fluid overload was noted. Among children with severe acute malnutrition and gastroenteritis, no evidence of a difference in mortality at 96 hours was noted between oral and intravenous rehydration strategies. (Funded by the Joint Global Health Trials scheme and others; GASTROSAM Current Controlled Trials number, ISRCTN76149273.).

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. 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. 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. ISRCTN registry ISRCTN50039021.

Malnutrition underlies 3 million child deaths worldwide. Current treatments differentiate severe acute malnutrition (SAM) from moderate acute malnutrition (MAM) with different products and programs. This differentiation is complex and costly. The Combined Protocol for Acute Malnutrition Study (ComPAS) assessed the effectiveness of a simplified, unified SAM/MAM protocol for children aged 6-59 months. Eliminating the need for separate products and protocols could improve the impact of programs by treating children more easily and cost-effectively, reaching more children globally. A cluster-randomized non-inferiority trial compared a combined protocol against standard care in Kenya and South Sudan. Randomization was stratified by country. Combined protocol clinics treated children using 2 sachets of ready-to-use therapeutic food (RUTF) per day for those with mid-upper arm circumference (MUAC) < 11.5 cm and/or edema, and 1 sachet of RUTF per day for those with MUAC 11.5 to <12.5 cm. Standard care clinics treated SAM with weight-based RUTF rations, and MAM with ready-to-use supplementary food (RUSF). The primary outcome was nutritional recovery. Secondary outcomes included cost-effectiveness, coverage, defaulting, death, length of stay, and average daily weight and MUAC gains. Main analyses were per-protocol, with intention-to-treat analyses also conducted. The non-inferiority margin was 10%. From 8 May 2017 to 31 March 2018, 2,071 children were enrolled in 12 combined protocol clinics (mean age 17.4 months, 41% male), and 2,039 in 12 standard care clinics (mean age 16.7 months, 41% male). In total, 1,286 (62.1%) and 1,202 (59.0%), respectively, completed treatment; 981 (76.3%) on the combined protocol and 884 (73.5%) on the standard protocol recovered, yielding a risk difference of 0.03 (95% CI -0.05 to 0.10, p = 0.52; per-protocol analysis, adjusted for country, age, and sex). The amount of ready-to-use food (RUTF or RUSF) required for a child with SAM to reach full recovery was less in the combined protocol (122 versus 193 sachets), and the combined protocol cost US$123 less per child recovered (US$918 versus US$1,041). There were 23 (1.8%) deaths in the combined protocol arm and 21 (1.8%) deaths in the standard protocol arm (adjusted risk difference 95% CI -0.01 to 0.01, p = 0.87). There was no evidence of a difference between the protocols for any of the other secondary outcomes. Study limitations included contextual factors leading to defaulting, a combined multi-country power estimate, and operational constraints. Combined treatment for SAM and MAM is non-inferior to standard care. Further research should focus on operational implications, cost-effectiveness, and context (Asia versus Africa; emergency versus food-secure settings). This trial is complete and registered at ISRCTN (ISRCTN30393230). The trial is registered at ISRCTN, trial number ISRCTN30393230.

Background: the aim of this study is to evaluate the effectiveness and coverage of a simplified protocol that is implemented in health centers (HCs) and health posts (HPs) for children who are suffering from severe acute malnutrition (SAM) in the humanitarian context of Diffa. Methods: We conducted a non-randomized community-controlled trial. The control group received outpatient treatment for SAM, without medical complications, at HCs and HPs with the standard protocol of community management of acute malnutrition (CMAM). Meanwhile, with respect to the intervention group, the children with SAM received treatment at the HCs and HPs through a simplified protocol wherein the mid-upper arm circumference (MUAC) and the presence of edema were used as the admission criteria, and the children with SAM were administered doses of fixed ready-to-use therapeutic food (RUTF). Results: A total of 508 children, who were all under 5 years and had SAM, were admitted into the study. The cured proportion was 87.4% in the control group versus 96.6% in the intervention group (p value = 0.001). There was no difference between the groups in the length of stay, which was 35 days, but the intervention group used a lower quantity of RUTF—70 sachets versus 90 sachets, per child cured. Coverage increases were observed in both groups. Discussion: the simplified protocol used at the HCs and HPs did not result in worse recovery and resulted in fewer discharge errors compared to the standard protocol.

Recent data suggest that case fatality from severe acute malnutrition (SAM) in India may be lower than the 10%-20% estimated by the World Health Organization (WHO). A contemporary quantification of mortality and recovery from acute malnutrition in Indian community settings is essential to inform policy regarding the benefits of scaling up prevention and treatment programmes. We conducted a cohort study using data collected during a recently completed cluster-randomised controlled trial in 120 geographical clusters with a total population of 121,531 in rural Jharkhand and Odisha, eastern India. Children born between October 1, 2013, and February 10, 2015, and alive at 6 months of age were followed up at 9, 12, and 18 months. We measured the children's anthropometry and asked caregivers whether children had been referred to services for malnutrition in the past 3 months. We determined the incidence and prevalence of moderate acute malnutrition (MAM) and SAM, as well as mortality and recovery at each follow-up. We then used Cox-proportional models to estimate mortality hazard ratios (HRs) for MAM and SAM. In total, 2,869 children were eligible for follow-up at 6 months of age. We knew the vital status of 93% of children (2,669/2,869) at 18 months. There were 2,704 children-years of follow-up time. The incidence of MAM by weight-for-length z score (WLZ) and/or mid-upper arm circumference (MUAC) was 406 (1,098/2,704) per 1,000 children-years. The incidence of SAM by WLZ, MUAC, or oedema was 190 (513/2,704) per 1,000 children-years. There were 36 deaths: 12 among children with MAM and six among children with SAM. Case fatality rates were 1.1% (12/1,098) for MAM and 1.2% (6/513) for SAM. In total, 99% of all children with SAM at 6 months of age (227/230) were alive 3 months later, 40% (92/230) were still SAM, and 18% (41/230) had recovered (WLZ ≥ -2 standard deviation [SD]; MUAC ≥ 12.5; no oedema). The adjusted HRs using all anthropometric indicators were 1.43 (95% CI 0.53-3.87, p = 0.480) for MAM and 2.56 (95% CI 0.99-6.70, p = 0.052) for SAM. Both WLZ < -3 and MUAC ≥ 11.5 and < 12.5 were associated with increased mortality risk (HR: 3.33, 95% CI 1.23-8.99, p = 0.018 and HR: 3.87, 95% CI 1.63-9.18, p = 0.002, respectively). A key limitation of our analysis was missing WLZ or MUAC data at all time points for 2.5% of children, including for two of the 36 children who died. In rural eastern India, the incidence of acute malnutrition among children older than 6 months was high, but case fatality following SAM was 1.2%, much lower than the 10%-20% estimated by WHO. Case fatality rates below 6% have now been recorded in three other Indian studies. Community treatment using ready-to-use therapeutic food may not avert a substantial number of SAM-related deaths in children aged over 6 months, as mortality in this group is lower than expected. Our findings strengthen the case for prioritising prevention through known health, nutrition, and multisectoral interventions in the first 1,000 days of life, while ensuring access to treatment when prevention fails.

Background Acute malnutrition treatment coverage remains low worldwide, causing significant morbidity and mortality. Decentralisation of treatment to Community Health Worker (CHW) sites has shown to be an effective strategy to improve access and increase coverage, but evidence on the cost and cost-effectiveness of this approach as well the use of simplified treatment protocols in conflict settings is lacking. The objective of this study was to determine cost per child treated as well as the cost-effectiveness of the hybrid model of treatment delivery (where treatment is provided at both health facilities and CHW sites) using either a standard protocol (Intervention 1) or simplified protocol (Intervention 2) compared to standard treatment at health facilities only (Control) in the conflict affected region of Gao in Northern Mali. Methods This economic evaluation was part of a three-arm cluster randomized controlled trial which enrolled 2038 children with moderate and severe acute malnutrition. Outcomes assessed were cost per child treated as well as average and incremental cost-effectiveness ratios for cost per child cured and disability adjusted life year (DALY) averted. A within study trial horizon, from March 2020 to July 2021, was used. Cost data were collected from accountancy records and through key informant interviews using a societal perspective. Treatment admission and outcome data were obtained from the main trial. Results In the base case scenario the cost per child treated was 272 US$, 179 US$ and 210US$ in the Control, Intervention 1 and 2 groups, respectively. Cost per child cured was 356 US$ in the Control, 219 US$ in the Intervention 1 and 226 US$ Intervention 2 groups. Ready-to-use therapeutic foods (RUTF) costs among SAM children treated with a simplified protocol were 5.7 US$ less per child. The average cost per DALY averted was 173.1 US$ in the Control compared to 60.3 US$ in the Intervention 1 and 53 US$ in the Intervention 2. Conclusion This study shows that involving CHWs in acute malnutrition treatment reduces the cost per child treated and is a cost-effective strategy, due to lower treatment costs and greater coverage in the decentralised model. Switching to a simplified protocol in a conflict setting can lead to cost savings particularly in terms of RUTF, and should be considered where weight-based admission, monitoring or dosage is not possible or RUTF stocks are running low. Trial registration The study protocol was registered under reference ISRCTN-60,973,756 on the 15th of October 2020.

The role of routine antibiotic use in the treatment of severe acute malnutrition is unclear. In this randomized, placebo-controlled trial in Niger, amoxicillin did not significantly improve nutritional recovery in children with severe acute malnutrition. Severe acute malnutrition affects approximately 19 million children under 5 years of age worldwide and contributes substantially to mortality and the disease burden among children. 1 To reduce the risk of death from severe acute malnutrition, specialized nutritional and medical intervention is required. Bacterial infection can complicate advanced cases of severe acute malnutrition, 2 – 9 and the risk of nosocomial infection in inpatient settings can be high. Therefore, in 1999, when all children with severe acute malnutrition were treated as inpatients, the World Health Organization (WHO) recommended routine use of broad-spectrum antibiotics for the management of severe acute malnutrition, irrespective of clinical . . .

HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.