Heather C. Stobaugh

Background: Moderate acute malnutrition (MAM), affecting over 30 million children globally, substantially increases the risk of morbidity and mortality. In 2023, the World Health Organization recommended lipid-based nutrient supplements (LNS) for children requiring supplementation for MAM, either ready-to-use supplementary food (RUSF) or ready-to-use therapeutic food (RUTF). However, evidence on the optimal product (RUTF or RUSF) and dosing strategy for children with MAM remains limited. The Modified Dosages for Acute Malnutrition MAM (MODAM-MAM) trial evaluated whether one- or two-sachet daily RUTF dosing were non-inferior to the de facto standard of one RUSF sachet daily for MAM supplementation. Methods and findings: We conducted a three-arm, parallel, individually randomized controlled trial in Ethiopia. Children aged 6–59 months with MAM (mid-upper arm circumference (MUAC) 11.5–12.4 cm or WHZ between –3 and –2, without edema) were randomized to: one 540-kcal sachet of RUSF/day (“1-RUSF”), one 500-kcal sachet of RUTF/day (“1-RUTF”), or two sachets of RUTF/day (“2-RUTF”). Both intervention arms (1-RUTF and 2-RUTF) were evaluated for non-inferiority to the standard (1-RUSF) using a prespecified 6-percentage-point margin. The primary outcome was anthropometric recovery, defined as both MUAC ≥ 12.5 cm and WHZ ≥ −2 for two consecutive visits within 16 weeks. In total, 2,414 children were analyzed in the intention-to-treat analysis. Recovery proportions were 84.8% (679/801) for 1-RUSF, 85.0% (674/793) for 1-RUTF, and 88.1% (721/818) for 2-RUTF. Risk differences for recovery relative to the standard of care (1-RUSF) were +0.2 percentage points (95% CI [–3.3, 3.7]; p = 0.944) for 1-RUTF and +3.4 percentage points (95% CI [0.0, 6.7]; p = 0.050) for 2-RUTF, with both intervention arms meeting the non-inferiority criteria. Anthropometric gains and median length of stay (56 days) were similar across arms. Ration use was comparable for 1-RUSF and 1-RUTF, while 2-RUTF required 1.6-fold more product. Study limitations include evaluation of a single RUSF formulation and earlier-than-typical case-finding due to intensive screening. Conclusions: Both experimental arms, one RUTF sachet daily and two RUTF sachets daily, are non-inferior to the standard dosing of one RUSF sachet daily for MAM supplementation. Although two sachets of RUTF daily yielded slightly higher recovery, the marginal benefits do not justify substantially greater resource demands. Because one RUTF and one RUSF sachet daily yielded similar treatment outcomes, either product can be considered an effective option for supplementation. Product choice may therefore be guided by supply, cost, and operational considerations. Trial registration: clinicaltrials.gov NCT06056089.

Children successfully treated through community‐based management of acute malnutrition (CMAM) frequently relapse to acute malnutrition (AM) following recovery and discharge. This prospective cohort study examined associations between relapse and household water, sanitation and hygiene (WASH) conditions, as well as animal ownership, in Mali, South Sudan and Somalia. Between April 2021 and June 2022, 1115 children were enrolled, with 964 children followed for 6 months, 242 in Mali, 488 in South Sudan and 234 in Somalia. Relapse to AM occurred in 32%, 63% and 21% of children in Mali, South Sudan and Somalia, respectively. In Mali, relapse risk was higher in households using multiple drinking water sources (aRR 1.71, 95% CI: 1.21–2.43, p = 0.003) or lacking soap (aRR 1.71, 95% CI: 1.03–2.82, p = 0.037). In South Sudan, inadequate drinking water sources, open defecation and the presence of animal faeces in the compound were associated with an increased risk of relapse (aRR 1.20, 95% CI: 1.04–1.38, p = 0.010; aRR 1.16, 95% CI: 1.03–1.30, p = 0.016; aRR 1.13, 95% CI: 1.02–1.26, p = 0.019, respectively). Sheep ownership in Mali (aRR 0.57, 95% CI: 0.40–0.81, p = 0.002) and cattle ownership in South Sudan (aRR 0.78, 95% CI: 0.71–0.85, p = < 0.001) were protective. No significant WASH or animal‐related factors were associated with relapse in Somalia. As nearly all household drinking water samples were contaminated across settings and time points, no association could be detected between measured water quality and relapse. While many WASH indicators were not associated with relapse, some inadequate WASH conditions were identified as risk factors for relapse, although heterogeneous across contexts. These findings may help to identify at‐risk children during treatment and inform strategies to reduce relapse post‐recovery.

Background: Only a small percentage of children with severe and moderate acute malnutrition receive treatment due to resource limitations, relatively complex treatment protocols, persistent supply chain challenges, and limited early identification among high-risk populations. Several innovations to the current model of care for uncomplicated acute malnutrition have been proposed, including modified doses of nutritional supplementation and family-led mid-upper-arm circumference (MUAC) and edema screening (“Family MUAC”) for early identification. The evidence base for these innovations remains limited. Methods: The Modified Dosages for Acute Malnutrition (MODAM) study includes three integrated individually randomized clinical trials testing innovations in the identification and treatment of acute malnutrition in Ethiopia. One trial will enroll 2400 children aged 6–59 months with severe acute malnutrition, testing standard weight-based dosing of ready-to-use therapeutic food (RUTF) against two experimental RUTF dosing regimens: either two sachets (1000 kcal) daily of RUTF until discharge, or two sachets until achieving anthropometric criteria for moderate acute malnutrition (MAM), at which time dosing will be decreased to one sachet (500 kcal) daily until discharge as fully recovered. A second trial will enroll 2400 children with MAM and test a standard dose of one daily sachet (540 kcal) of ready-to-use supplemental food against two experimental dosing regimes: one sachet (500 kcal) or two sachets (1000 kcal) of RUTF daily until discharge. Children who recover from these two trials will be randomized again into a third trial evaluating post-recovery protocols designed for the early identification of relapse: (1) the control arm involving one scheduled return visit at 24 weeks post-recovery; (2) the first intervention arm involving three scheduled return visits at 4, 12, and 24 weeks post-recovery; and (3) the second intervention arm which involves caregivers receiving Family MUAC training and one scheduled visit at 24 weeks post-recovery. Discussion: This study will provide data on the effectiveness of multiple innovations in the management of childhood acute malnutrition. Results will add to the evidence base on the effectiveness and cost-effectiveness of such modifications in the identification and management of acute malnutrition, ideally adding to the global database on this topic and directly contributing to future WHO guidelines. Trial registration: Trials were registered on clinicaltrials.gov as NCT06038071 (registered September 8, 2023), NCT06056089 (registered September 20, 2023), and NCT06061484 (registered September 24, 2023).

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.

A non-randomized prospective cohort study was conducted in 2022 to compare recovery rate and length of stay (LoS) for acutely malnourished children treated under South Sudan’s standard Community Management of Acute Malnutrition (CMAM) protocol and a COVID-modified protocol. Children aged 6–59 months received acute malnutrition (AM) treatment under the standard or modified protocol (mid-upper-arm circumference-only entry/exit criteria and simplified dosing). Primary (recovery rate and LoS) were compared for outpatient therapeutic (OTP) and therapeutic supplementary feeding programs (TSFP) using descriptive statistics and mixed-effects models. Children admitted to OTP under both protocols were similar in age and sex; children admitted to TSFP were significantly older under the modified protocol than the standard protocol. Shorter LoS and higher recovery rates were observed under the modified protocol for both OTP (recovery: 93.3% vs. 87.2%; LoS: 38.3 vs. 42.8 days) and TSFP (recovery: 79.8% vs. 72.7%; LoS: 54.0 vs. 61.9 days). After adjusting for site and child characteristics, neither differences in adjusted odds of recovery [OTP: 2.63; TSFP 1.80] nor LoS [OTP −10.0; TSFP −7.8] remained significant. Modified protocols for AM performed well. Adjusted models indicate similar treatment outcomes to the standard protocol. Adopting simplified protocols could be beneficial post-pandemic; however, recovery and relapse will need to be monitored.

The effective management of the 33 million children with moderate acute malnutrition (MAM) is key to reducing childhood morbidity and mortality. In this review, we aim to evaluate the effectiveness of specially formulated foods (SFFs) compared to non-food-based approaches to manage MAM in children >6 months old. We conducted a search on ten databases until 23 August 2021 and included five studies, covering 3387 participants. Meta-analysis of four studies comparing SFFs to counselling or standard of care showed that SFFs likely increase recovery rate, reduce non-response, and may improve weight-for-height z-score, weight-for-age z-score and time to recovery, but have little or no effect on MUAC gain. One study on a multicomponent intervention (SFFs, antibiotics and counselling provided to high-risk MAM) compared to counselling only was reported narratively. The intervention may increase weight gain after 24 weeks but may have little or no effect on weight gain after 12 weeks and on non-response and mortality after 12 and 24 weeks of enrollment. The effect of this intervention on recovery was uncertain. In conclusion, SFFs may be beneficial for children with moderate wasting in humanitarian contexts. Programmatic recommendations should consider context and cost-effectiveness.

Background: The Community-Based Management of Acute Malnutrition (CMAM) model transformed the treatment of severe acute malnutrition (SAM) by shifting treatment from inpatient facilities to the community. Evidence shows that while CMAM programs are effective in the initial recovery from SAM, recovery is not sustained for some children requiring them to receive treatment repeatedly. This indicates a potential gap in the model, yet little evidence is available on the incidence of relapse, the determinants of the phenomena, or its financial implications on program delivery.Methods: This study is a multi-country prospective cohort study following “post-SAM” children (defined as children following anthropometric recovery from SAM through treatment in CMAM) and matched community controls (defined as children not previously experiencing acute malnutrition (AM)) monthly for six months. The aim is to assess the burden and determinants of relapse to SAM. This study design enables the quantification of relapse among post-SAM children, but also to determine the relative risk for, and excess burden of, AM between post-SAM children and their matched community controls. Individual -, household-, and community-level information will be analyzed to identify potential risk-factors for relapse, with a focus on associations between water, sanitation, and hygiene (WASH) related exposures, and post-discharge outcomes. The study combines a microbiological assessment of post-SAM children’s drinking water, food, stool via rectal swabs, dried blood spots (DBS), and assess for indicators of enteric pathogens and immune function, to explore different exposures and potential associations with treatment and post-treatment outcomes.Discussion: This study is the first of its kind to systematically track children after recovery from SAM in CMAM programs using uniform methods across multiple countries. The design allows the use of results to: 1) facilitate understandings of the burden of relapse; 2) identify risk factors for relapse and 3) elucidate financial costs associated with relapse in CMAM programs. This protocol’s publication aims to support similar studies and evaluations of CMAM programs and provides opportunities for comparability of an evidence-based set of indicators for relapse to SAM.

Undernutrition is more prevalent among children living in unsanitary environments with inadequate water, sanitation and hygiene (WASH). Despite good evidence for the effect of WASH on multiple infectious diseases, evidence for the effect of WASH interventions on childhood undernutrition is less well established, particularly for acute malnutrition. To assess the effectiveness of WASH interventions in preventing and treating acute childhood malnutrition, we performed electronic searches to identify relevant studies published between 1 January 2000 and 13 May 2019. We included studies assessing the effect of WASH on prevention and treatment of acute malnutrition in children under 5 years of age. Data were extracted by two independent reviewers. We included 26 articles of 599 identified references with a total of 43,083 participants. Twenty‐five studies reported on the effect of WASH on prevention, and two studies reported its effect on treatment of acute malnutrition. Current evidence does not show consistent associations of WASH conditions and interventions with prevention of acute malnutrition or with the improvement of its treatment outcomes. Only two high‐quality randomized controlled trials (RCTs) demonstrated that improved water quality during severe acute malnutrition treatment improved recovery outcomes but did not prevent relapse. Many of the interventions consisted of a package of WASH services, making impossible to attribute the effect to one specific component. This highlights the need for high‐quality, rigorous intervention studies assessing the effects of WASH interventions specifically designed to prevent acute malnutrition or improve its treatment.

Weight-for-age z-score (WAZ) is not currently an admission criterion to therapeutic feeding programs, and children with low WAZ at high risk of mortality may not be admitted. We conducted a secondary analysis of RCT data to assess response to treatment according to WAZ and mid-upper arm circumference (MUAC) and type of feeding protocol given: a simplified, combined protocol for severe and moderate acute malnutrition (SAM and MAM) vs. standard care that treats SAM and MAM, separately. Children with a moderately low MUAC (11.5–12.5 cm) and a severely low WAZ (<−3) respond similarly to treatment in terms of both weight and MUAC gain on either 2092 kJ (500 kcal)/day of therapeutic or supplementary food. Children with a severely low MUAC (<11.5 cm), with/without a severely low WAZ (<−3), have similar recovery with the combined protocol or standard treatment, though WAZ gain may be slower in the combined protocol. A limitation is this analysis was not powered for these sub-groups specifically. Adding WAZ < −3 as an admission criterion for therapeutic feeding programs admitting children with MUAC and/or oedema may help programs target high-risk children who can benefit from treatment. Future work should evaluate the optimal treatment protocol for children with a MUAC < 11.5 and/or WAZ < −3.0.