Facilitators and barriers to implementing complex community-based interventions for addressing acute malnutrition in low- and lower-middle income countries: A scoping review.

Background: Community-based nutrition interventions have been established as the standard of care for identifying and treating acute malnutrition among children 6-59 months in low- and lower-middle-income countries. However, limited research has examined the factors that influence the implementation of the community-based component of interventions that address severe acute malnutrition and moderate acute malnutrition among children. Aim: The objective of this review was to identify and describe the facilitators and barriers in implementing complex community-based nutrition interventions to address acute malnutrition among children in low- and lower-middle-income countries. Methods: This review used a systematic search strategy to identify existing peer-reviewed literature from three databases on complex community-based interventions (defined as including active surveillance, treatment, and education in community settings) to address severe acute malnutrition and moderate acute malnutrition in children. Results: In total, 1771 sources were retrieved from peer-reviewed databases, with 38 sources included in the review, covering 26 different interventions. Through an iterative deductive and inductive analysis approach, three main domains (household and interpersonal, sociocultural and geographical; operational and administrative) and eight mechanisms were classified, which were central to the successful implementation of complex community-based interventions to address acute child malnutrition. Conclusion: Overall, this review highlights the importance of addressing contextual and geographical challenges to support participant access and program operations. There is a need to critically examine program design and structure to promote intervention adherence and effectiveness. In addition, there is an opportunity to direct resources towards community health workers to facilitate long-term community trust and engagement.

Effectiveness of a nonweight-based daily dosage of ready-to-use therapeutic food in children suffering from uncomplicated severe acute malnutrition: A nonrandomized, noninferiority analysis of programme data in Afghanistan.

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready-to-use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight-for-height z-score ≥ -3 or mid-upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight-based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per-protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (-0.9; 7.2) %] and length-of-stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of -10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = -1.5 (-1.8, -1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight-based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource-constrained contexts.

Micronutrient supplementation practices in relation to the World Health Organisation 2013 guidelines on management of severe acute malnutrition.

In 2013, the World Health Organisation (WHO) updated the recommendations for micronutrient deficiency correction in hospitalised under-5 children with complicated severe acute malnutrition (SAM). This study aimed to describe the micronutrient deficiency correction practices in relation to WHO 2013 recommendations. Data from medical records of under-5 children admitted for SAM management at two hospitals in South Africa and three tertiary hospitals in Ghana were extracted. Micronutrient correction practices were compared to the WHO 2013 recommendations by considering the dosage, timing of micronutrient supplementation (vitamin A, iron and folic acid) and therapeutic feeds administered. In total, 723 medical records were included. Nearly half (48.3%) of the children received at least one of the studied micronutrients as a supplement. Vitamin A was supplemented in 27.4% of the children, while iron and folic acid were supplemented in 9.5% and 34.9%, respectively. Among the children who received vitamin A, 60.1% received the first dose on Day 1 of admission. Also, 46.4% of the iron-supplemented children received iron within the first week of admission. Vitamin A, iron and folic acid were administered within the dose range of 100,000-180,000 IU, 3.1-7.7 mg per kg per day, and 3-5 mg per day, respectively. Additionally, 71.7% of the children reportedly received therapeutic feeds that met WHO recommendations. The micronutrient deficiency correction practices regarding dose and timing differed from the 2013 WHO guidelines. Qualitative studies investigating the reasons for the disparities are recommended.

Adequacy of Nutrient Intakes of Severely and Acutely Malnourished Children Treated with Different Doses of Ready-To-Use Therapeutic Food in Burkina Faso.

BACKGROUND: Ready-to-use therapeutic foods (RUTF) are designed to cover the daily nutrient requirements of children with severe acute malnutrition (SAM). However, with the transfer of uncomplicated SAM care from the hospital environment to the community level, children will be able to consume complementary and family foods (CFF) in addition to RUTF, and this might decrease the quantity of RUTF needed for recovery. OBJECTIVES: Using an individually randomized clinical trial, we investigated the effects of a reduced RUTF dose on the daily energy and macronutrient intakes, the proportion of energy coming from CFF, and the mean probability of adequacy (MPA) of intake in 11 micronutrients of 516 children aged 6-59 mo who were treated for SAM in Burkina Faso. METHODS: The data were collected using a single 24-h multipass dietary recall, 1 mo after starting treatment, from December 2016 to August 2018, repeated on a subsample of 66 children. Differences between children receiving the reduced RUTF (intervention arm) and those receiving standard RUTF (control arm) were assessed by linear mixed models. RESULTS: Daily energy intake was lower (P < 0.01) in the intervention arm (mean ± SD 1321 ± 339 kcal) than in the control arm (1467 ± 319 kcal). CFF contributed to 40% of the daily energy intake in the intervention and 35% in the control arm. The MPA for 11 micronutrients was 0.89 ± 0.1 in the intervention arm and 0.95 ± 0.07 in the control arm (P = 0.06). CONCLUSIONS: Reducing the dose of RUTF during SAM treatment had a negative impact on daily energy intake of the children. Despite this, children covered their recommended energy intake. The energy intake coming from CFF was similar between arms, suggesting that children's feeding practices did not change due to the reduction in RUTF in this context. This trial was registered at the IRSCTN registry as ISRCTN50039021.

Treatment of severe acute malnutrition with oat or standard ready-to-use therapeutic food: a triple-blind, randomised controlled clinical trial.

OBJECTIVE: We hypothesised that an alternative RUTF (ready-to-use therapeutic food) made with oats (oat-RUTF) would be non-inferior to standard RUTF (s-RUTF). DESIGN: This was a randomised, triple-blind, controlled, clinical non-inferiority trial comparing oat-RUTF to s-RUTF in rural Sierra Leone. Children aged 6-59 months with severe acute malnutrition (SAM) were randomised to oat-RUTF or s-RUTF. s-RUTF was composed of milk powder, sugar, peanut paste and vegetable oil, with a hydrogenated vegetable oil additive. Oat-RUTF contained oats and no hydrogenated vegetable oil additives. The primary outcome was graduation, an increase in anthropometric measurements such that the child was not acutely malnourished. Secondary outcomes were rates of growth, time to graduation and presence of adverse events. Intention to treat analyses was used. RESULTS: Of the 1406 children were enrolled, graduation was attained in 404/721 (56%) children receiving oat-RUTF and 311/685 (45%) receiving s-RUTF (difference 10.6%, 95% CI 5.4% to 15.8%). Death, hospitalisation or remaining with SAM was seen in 87/721 (12%) receiving oat-RUTF and in 125/685 (18%) receiving s-RUTF (difference 6.2%, 95% CI 2.3 to 10.0, p=0.001). Time to graduation was less for children receiving oat RUTF; 3.9±1.8 versus 4.5±1.8 visits, respectively (p<0.001). Rates of weight in the oat-RUTF group were greater than in the s-RUTF group; 3.4±2.7 versus 2.5±2.3 g/kg/d, p<0.001. CONCLUSION: Oat-RUTF is superior to s-RUTF in the treatment of SAM in Sierra Leone. We speculate that might be because of beneficial bioactive components or the absence of hydrogenated vegetable oil in oat-RUTF. TRIAL REGISTRATION NUMBER: NCT03407326.

A simplified, combined protocol versus standard treatment for acute malnutrition in children 6-59 months (ComPAS trial): A cluster-randomized controlled non-inferiority trial in Kenya and South Sudan.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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). TRIAL REGISTRATION: The trial is registered at ISRCTN, trial number ISRCTN30393230.

Acceptability and efficacy of ready-to-use therapeutic food using soy protein isolate in under-5 children suffering from severe acute malnutrition in Bangladesh: a double-blind randomized non-inferiority trial.

BACKGROUND AND OBJECTIVE: Globally, around 20 million children suffer from severe acute malnutrition (SAM). Identifying a more economical treatment for those affected has the potential to make treatment more available and improve prognosis for recovery and future health. DESIGN/METHODS: The double-blind randomized study compared taste acceptability (measured by the eagerness to eat) and efficacy of soy-based RUTF (S-RUTF) with milk-based RUTF (M-RUTF) in 6- to 59-month-old children suffering from SAM (WHZ < -3) at icddr,b, in Bangladesh. These SAM children were enrolled in the study after completion of their stabilization phase of treatment. Tolerance of test-RUTF was also tested during the efficacy trial. RESULTS: The cross-over taste acceptability study, conducted in 36 children, revealed similar results between products and an absence of side effects. The efficacy trial enrolled 260 children (130, each group) with similar baseline characteristics, including mean ± SD age 15.0 ± 8.0 months, WHZ - 3.41 ± 0.40 and mid-upper arm circumference (MUAC) 11.1 ± 0.7 cm. The features at the end of study by RUTF group were (in S-RUTF vs. M-RUTF, respectively): total days from enrollment: 44 ± 34 versus 39 ± 30; weight gain (kg): 0.698 ± 0.438 versus 0.741 ± 0.381 and rate of weight gain (g/kg/d): 3.9 ± 3.2 versus 5.2 ± 4.6; MUAC gain (cm): 0.9 ± 0.7 versus 0.9 ± 0.6; and improvement of WHZ: 1.12 ± 0.82 versus 1.22 ± 0.68 (all data were man ± SD and none were significantly different between the groups). At enrollment and the end of intervention, the body composition [total body water (TBW): 70.3 ± 3.2 vs. 69.9 ± 3.5%, and fat: 11.0 ± 4.0 vs.11.5 ± 4.3% at baseline; and TBW: 65.5 ± 4.1 vs. 65.9 ± 4.6%; and fat: 16.8 ± 5.2 vs. 16.2 ± 5.8% in S-RUTF and M-RUTF group, respectively] was found similar. Moreover, the increment of total TBW, FM, and FFM was also observed similar between the groups. CONCLUSIONS: This is the first randomized trial comparing S-RUTF using soy protein isolate with milk-based RUTF including comparison of body composition. S-RUTF was found equally acceptable as of milk-based RUTF without any adverse event. Children receiving S-RUTF showed similar pattern of changes in anthropometric indices, and body composition as of milk-based RUTF. Greater number of SAM children can be managed in the community with comparatively low-cost soy-based RUTF. TRIAL REGISTRATION: NCT01634009.

Combined protocol for severe and moderate acute malnutrition in emergencies: Stakeholders perspectives in four countries.

Each year, acute malnutrition affects an estimated 52 million children under 5 years of age. Current global treatment protocols divide treatment of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) despite malnutrition being a spectrum disease. A proposed Combined Protocol provides for (a) treatment of MAM and SAM at the same location; (b) diagnosis using middle-upper-arm circumference (MUAC) and oedema only; (c) treatment using a single product, ready-to-use-therapeutic food (RUTF), and (d) a simplified dosage schedule for RUTF. This study examines stakeholders' knowledge of and opinions on the Combined Protocol in Niger, Nigeria, Somalia, and South Sudan. Data collection included a document review followed by in-depth interviews with 50 respondents from government, implementing partners, and multilateral agencies, plus 11 global and regional stakeholders. Data were analysed iteratively using thematic content analysis. We find that acute malnutrition protocols in these countries have not been substantially modified to include components of the Combined Protocol, although aspects were accepted for use in emergencies. Respondents generally agreed that MAM and SAM treatment should be provided in the same location, however they said MUAC and oedema-only diagnosis, although more field-ready than other diagnostic measures, did not necessarily catch all malnourished children and may not be appropriate for "tall and slim" morphologies. Similarly, using only RUTF presented inherent logistical advantages, but respondents worried about pipeline issues. Respondents did not express strong opinions about simplified dosage schedules. Stakeholders interviewed indicated more evidence is needed on the operational implications and effectiveness of the Combined Protocol in different contexts.

A reduced-carbohydrate and lactose-free formulation for stabilization among hospitalized children with severe acute malnutrition: A double-blind, randomized controlled trial.

BACKGROUND: Children with medically complicated severe acute malnutrition (SAM) have high risk of inpatient mortality. Diarrhea, carbohydrate malabsorption, and refeeding syndrome may contribute to early mortality and delayed recovery. We tested the hypothesis that a lactose-free, low-carbohydrate F75 milk would serve to limit these risks, thereby reducing the number of days in the stabilization phase. METHODS AND FINDINGS: In a multicenter double-blind trial, hospitalized severely malnourished children were randomized to receive standard formula (F75) or isocaloric modified F75 (mF75) without lactose and with reduced carbohydrate. The primary endpoint was time to stabilization, as defined by the World Health Organization (WHO), with intention-to-treat analysis. Secondary outcomes included in-hospital mortality, diarrhea, and biochemical features of malabsorption and refeeding syndrome. The trial was registered at clinicaltrials.gov (NCT02246296). Four hundred eighteen and 425 severely malnourished children were randomized to F75 and mF75, respectively, with 516 (61%) enrolled in Kenya and 327 (39%) in Malawi. Children with a median age of 16 months were enrolled between 4 December 2014 and 24 December 2015. One hundred ninety-four (46%) children assigned to F75 and 188 (44%) to mF75 had diarrhea at admission. Median time to stabilization was 3 days (IQR 2-5 days), which was similar between randomized groups (0.23 [95% CI -0.13 to 0.60], P = 0.59). There was no evidence of effect modification by diarrhea at admission, age, edema, or HIV status. Thirty-six and 39 children died before stabilization in the F75 and in mF75 arm, respectively (P = 0.84). Cumulative days with diarrhea (P = 0.27), enteral (P = 0.42) or intravenous fluids (P = 0.19), other serious adverse events before stabilization, and serum and stool biochemistry at day 3 did not differ between groups. The main limitation was that the primary outcome of clinical stabilization was based on WHO guidelines, comprising clinical evidence of recovery from acute illness as well as metabolic stabilization evidenced by recovery of appetite. CONCLUSIONS: Empirically treating hospitalized severely malnourished children during the stabilization phase with lactose-free, reduced-carbohydrate milk formula did not improve clinical outcomes. The biochemical analyses suggest that the lactose-free formulae may still exceed a carbohydrate load threshold for intestinal absorption, which may limit their usefulness in the context of complicated SAM. TRIAL REGISTRATION: ClinicalTrials.gov NCT02246296.

Ready-to-use therapeutic food (RUTF) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Management of severe acute malnutrition (SAM) in children comprises two potential phases: stabilisation and rehabilitation. During the initial stabilisation phase, children receive treatment for dehydration, electrolyte imbalances, intercurrent infections and other complications. In the rehabilitation phase (applicable to children presenting with uncomplicated SAM or those with complicated SAM after complications have been resolved), catch-up growth is the main focus and the recommended energy and protein requirements are much higher. In-hospital rehabilitation of children with SAM is not always desirable or practical - especially in rural settings - and home-based care can offer a better solution. Ready-to-use therapeutic food (RUTF) is a widely used option for home-based rehabilitation, but the findings of our previous review were inconclusive. OBJECTIVES: To assess the effects of home-based RUTF used during the rehabilitation phase of SAM in children aged between six months and five years on recovery, relapse, mortality and rate of weight gain. SEARCH METHODS: We searched the following databases in October 2018: CENTRAL, MEDLINE, Embase, six other databases and three trials registers. We ran separate searches for cost-effectiveness studies, contacted researchers and healthcare professionals in the field, and checked bibliographies of included studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, where children aged between six months and five years with SAM were, during the rehabilitation phase, treated at home with RUTF compared to an alternative dietary approach, or with different regimens and formulations of RUTF compared to each other. We assessed recovery, deterioration or relapse and mortality as primary outcomes; and rate of weight gain, time to recovery, anthropometrical changes, cognitive development and function, adverse outcomes and acceptability as secondary outcomes. DATA COLLECTION AND ANALYSIS: We screened for eligible studies, extracted data and assessed risk of bias of those included, independently and in duplicate. Where data allowed, we performed a random-effects meta-analysis using Review Manager 5, and investigated substantial heterogeneity through subgroup and sensitivity analyses. For the main outcomes, we evaluated the quality of the evidence using GRADE, and presented results in a 'Summary of findings' table per comparison. MAIN RESULTS: We included 15 eligible studies (n = 7976; effective sample size = 6630), four of which were cluster trials. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. Six studies received funding or donations from industry whereas eight did not, and one study did not report the funding source.The overall risk of bias was high for six studies, unclear for three studies, and low for six studies. Among the 14 studies that contributed to meta-analyses, none (n = 5), some (n = 5) or all (n = 4) children were stabilised in hospital prior to commencement of the study. One small study included only children known to be HIV-infected, another study stratified the analysis for 'recovery' according to HIV status, while the remaining studies included HIV-uninfected or untested children. Across all studies, the intervention lasted between 8 and 16 weeks. Only five studies followed up children postintervention (maximum of six months), and generally reported on a limited number of outcomes.We found seven studies with 2261 children comparing home-based RUTF meeting the World Health Organization (WHO) recommendations for nutritional composition (referred to in this review as standard RUTF) with an alternative dietary approach (effective sample size = 1964). RUTF probably improves recovery (risk ratio (RR) 1.33; 95% confidence interval (CI) 1.16 to 1.54; 6 studies, 1852 children; moderate-quality evidence), and may increase the rate of weight gain slightly (mean difference (MD) 1.12 g/kg/day, 95% CI 0.27 to 1.96; 4 studies, 1450 children; low-quality evidence), but we do not know the effects on relapse (RR 0.55, 95% CI 0.30 to 1.01; 4 studies, 1505 children; very low-quality evidence) and mortality (RR 1.05, 95% CI 0.51 to 2.16; 4 studies, 1505 children; very low-quality evidence).Two quasi-randomised cluster trials compared standard, home-based RUTF meeting total daily nutritional requirements with a similar RUTF but given as a supplement to the usual diet (213 children; effective sample size = 210). Meta-analysis showed that standard RUTF meeting total daily nutritional requirements may improve recovery (RR 1.41, 95% CI 1.19 to 1.68; low-quality evidence) and reduce relapse (RR 0.11, 95% CI 0.01 to 0.85; low-quality evidence), but the effects are unknown for mortality (RR 1.36, 95% CI 0.46 to 4.04; very low-quality evidence) and rate of weight gain (MD 1.21 g/kg/day, 95% CI - 0.74 to 3.16; very low-quality evidence).Eight studies randomised 5502 children (effective sample size = 4456) and compared standard home-based RUTF with RUTFs of alternative formulations (e.g. using locally available ingredients, containing less or no milk powder, containing specific fatty acids, or with added pre- and probiotics). For recovery, it made little or no difference whether standard or alternative formulation RUTF was used (RR 1.03, 95% CI 0.99 to 1.08; 6 studies, 4188 children; high-quality evidence). Standard RUTF decreases relapse (RR 0.84, 95% CI 0.72 to 0.98; 6 studies, 4188 children; high-quality evidence). However, it probably makes little or no difference to mortality (RR 1.00, 95% CI 0.80 to 1.24; 7 studies, 4309 children; moderate-quality evidence) and may make little or no difference to the rate of weight gain (MD 0.11 g/kg/day, 95% CI -0.32 to 0.54; 6 studies, 3807 children; low-quality evidence) whether standard or alternative formulation RUTF is used. AUTHORS' CONCLUSIONS: Compared to alternative dietary approaches, standard RUTF probably improves recovery and may increase rate of weight gain slightly, but the effects on relapse and mortality are unknown. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given as a supplement to the usual diet, but the effects on mortality and rate of weight gain are not clear. When comparing RUTFs with different formulations, the current evidence does not favour a particular formulation, except for relapse, which is reduced with standard RUTF. Well-designed, adequately powered, pragmatic RCTs with standardised outcome measures, stratified by HIV status, and that include diarrhoea as an outcome, are needed.

Soya, maize and sorghum ready-to-use therapeutic foods are more effective in correcting anaemia and iron deficiency than the standard ready-to-use therapeutic food: randomized controlled trial.

BACKGROUND: The prevalence of anaemia and iron deficiency (ID) among children with severe acute malnutrition (SAM) and their correction during nutritional rehabilitation are not well documented. This study assessed anaemia and ID prevalence and their predictors at start of SAM treatment, and the efficacy of their treatment and effect on gut health of two novel Ready-To-Use Therapeutic foods (RUTF) prepared from soybean, maize and sorghum (SMS) with (MSMS-RUTF) or without added milk (FSMS-RUTF) compared to those of the standard formulation prepared from peanut and milk (PM-RUTF). METHODS: This was a 3-arms parallel groups, simple randomised, controlled non-inferiority trial in 6-59 months old Central Malawian children with SAM. Anaemia was defined using altitude- and ethnicity-adjusted haemoglobin. Iron status was defined using soluble transferrin receptor (sTfR) and body iron stores (BIS). We used Pearson's chi-square test, t-test for paired or unpaired data, Kruskal-Wallis test for between-arm differences as appropriate and logistic regression to identify independent predictors of anaemia or iron deficiency anaemia (IDA). RESULTS: The sample size was 389. At admission, the prevalence [%(95%CI)] of anaemia was 48.9(41.4-56.5)% while that of ID and IDA were 55.7(48.6-62.5)% and 34.3(28.2-41.0)% when using sTfR criterion and 29.1(24.4-34.4)% and 28.9(23.7-34.9)% when using BIS criterion, respectively. At discharge, nutrition rehabilitation with SMS-RUTF was associated with the lowest prevalence of anaemia [12.0(6.9-20.3)% for FSMS-RUTF, 18.2(11.9-26.8)% for MSMS-RUTF and 24.5(15.8-35.9)% for PM-RUTF; p = 0.023] and IDA [7.9(3.4-17.3)% for FSMS-RUTF, 10.9(4.8-22.6)% for MSMS-RUTF and 20.5(10.7-35.5)% for PM-RUTF; p = 0.028]. SMS-RUTF was also associated with the highest increase in BIS [Change in BIS (95%CI)] among the iron deplete at admission [6.2 (3.7; 8.6), 3.2 (0.8; 5.6), 2.2 (0.2; 4.3) for the same study arms; Anova p = 0.045]. Compared to P-RUTF, FSMS-RUTF had the highest adjusted recovery rate [OR (95%CI = 0.3 (0.2-0.5) with p < 0.001 for FSMS-RUTF and 0.6 (0.3-1.0) with p = 0.068 for MSMS-RUTF]. No effect of iron content on risk of iron overload or gut inflammation was observed. CONCLUSIONS: Anaemia and ID are common among children with SAM. FSMS-RUTF is more efficacious in treating anaemia and correcting BIS among this group than PM-RUTF. TRIAL REGISTRATION: This study was registered on 15 April 2015 ( PACTR201505001101224 ).

MUAC as the sole discharge criterion from community-based management of severe acute malnutrition in Burkina Faso.

The use of mid upper arm circumference (MUAC) measurement to screen and determine eligibility for admission to therapeutic feeding programs has been established, but evidence and programmatic experience to inform guidance on the use of MUAC as a discharge criterion is limited. We present results from a large-scale nutritional program using MUAC for admission and discharge and compare program outcomes and response to treatment when determining eligibility for discharge by proportional weight gain versus discharge by MUAC. The study population included all children admitted to the Ministry of Health therapeutic feeding program supported by Médecins Sans Frontières in northern Burkina Faso from September 2007 to December 2011 (n = 50,841). Recovery was high overall using both discharge criteria, with low risks of death, nonresponse, and transfer to inpatient care and high daily gains in weight, MUAC, weight-for-height Z score, and height. When discharge was made by MUAC only, recovery increased, while all adverse program outcomes and length of stay decreased, with increasing MUAC on admission. MUAC-based programming, where MUAC is integrated into program screening, admission, and discharge, is one of several new approaches that can be used to target resources to the most at-risk malnourished children and improve program efficiency and coherency. This analysis provides additional programmatic experience on the use of MUAC-based discharge criterion, but more work may be needed to inform optimal discharge thresholds across settings.

Severe acute malnutrition.

PURPOSE OF REVIEW: Advances in our understanding of the treatment of severe acute malnutrition (SAM) in a resource-limited environment are needed to improve outcome. RECENT FINDINGS: Ready-to-use therapeutic foods (RUTFs) made from local products and with reduced milk content lower costs and may be effective in older children. None of the therapeutic foods used to treat severely malnourished children correct long chain polyunsaturated fatty acid deficiencies.Routine short-term antibiotic (amoxicillin) treatment, in the context of adequate healthcare supervision, does not improve the recovery rate. Long-term antibiotic (cotrimoxazole) treatment also does not provide significant benefit to non-HIV-infected children.Increased pathogenic bacteria have been found in the intestinal microbiome of malnourished children and candidate organisms for use as probiotics have been identified. There is, however, no evidence to support the routine use of probiotics in these children. Although exocrine pancreatic function is reduced in malnourished children, routine pancreatic enzyme supplementation does not lead to accelerated recovery. SUMMARY: Alternative RUTF may provide a cheaper and more acceptable alternative to standard RUTF in the near future. Further research is needed to understand the implications of fatty acid deficiencies and dysbiosis that occur in malnourished children. Routine antibiotic administration in the appropriate setting is unnecessary.

Estimating program coverage in the treatment of severe acute malnutrition: a comparative analysis of the validity and operational feasibility of two methods.

BACKGROUND: Many health programs can assess coverage using standardized cluster survey methods, but estimating the coverage of nutrition programs presents a special challenge due to low disease prevalence. Used since 2012, the Semi-Quantitative Evaluation of Access and Coverage (SQUEAC) employs both qualitative and quantitative methods to identify key barriers to access and estimate coverage of therapeutic feeding programs. While the tool has been increasingly used in programs, the validity of certain methodological elements has been the subject of debate. METHODS: We conducted a study comparing a SQUEAC conjugate Bayesian analysis to a two-stage cluster survey estimating the coverage of a therapeutic feeding program in Niger in 2016. RESULTS: We found that the coverage estimate from the conjugate Bayesian analysis was sensitive to the prior estimation. With the exception of prior estimates produced by an external support team, all prior estimates resulted in a conflict with the likelihood result, excluding interpretation of the final coverage estimate. Allowing for increased uncertainty around the prior estimate did not materially affect conclusions. CONCLUSION: SQUEAC is a demanding analytical method requiring both qualitative and quantitative data collection and synthesis to identify program barriers and estimate coverage. If the necessary technical capacity is not available to objectively specify an accurate prior for a conjugate Bayesian analysis, alternatives, such as a two-stage cluster survey or a larger likelihood survey, may be considered to ensure valid coverage estimation. TRIAL REGISTRATION: NCT03280082 . Retrospectively registered on September 12, 2017.

Management of severe acute malnutrition by cow milk in resource constraints settings: experience of the Nutritional Centre of the University Clinics of Graben.

BACKGROUND: Severe acute malnutrition is defined as a weight for height z-score < - 3 standard deviation. Since 2000, joint efforts of the World Health Organization and United Nations Children's Fund allowed to standardize the management of acute malnutrition by improving outcome and preventing complications with the introduction of therapeutic milk and ready-to-use therapeutic foods. However, in the Democratic Republic of Congo, many health facilities face therapeutic milk shortage while managing severe acute malnutrition. At the University Clinics of Graben, cow milk with porridge made of maize, soybean, vegetal oil and sugar is used during stockouts periods. This study was carried out to analyse the efficiency and safety of this treatment compared to the conventional one in SAM patients. METHODS: This study is based on the experience of the University Clinics of Graben in eastern Democratic Republic of Congo whose nutritional centre is often confronted with stockouts in nutritional supplements. During a three months shortage in 2015, patients received cow milk alternating with preparations made from sugar-maize-soybean- vegetal oil. The study compared the evolution of these children with those who had previously been treated with the WHO conventional preparations by analysing weight changes, oedema resolution, gastrointestinal tolerability and clinical outcome over 21 days. Data were analysed with SPSS 20. We used the ANOVA, Chi-square test, odd ratio and p-value to compare the differences. RESULTS: Seventy-nine patients had received cow milk while fifty-seven were submitted to classical therapeutic milk. There was no significant difference between the two groups regardless the type of malnutrition in terms of weight changes, oedema resolution, gastrointestinal tolerability and clinical outcome over 21 days. CONCLUSION: Cow milk alternately with sugar-maize-soybean- vegetal oil preparations is an acceptable alternative in case of stockouts in conventional therapeutic milk in these settings.

An integrated community-based outpatient therapeutic feeding programme for severe acute malnutrition in rural Southern Ethiopia: Recovery, fatality, and nutritional status after discharge.

A scaled up and integrated outpatient therapeutic feeding programme (OTP) brings the treatment of severely malnourished children closer to the community. This study assessed recovery from severe acute malnutrition (SAM), fatality, and acute malnutrition up to 14 weeks after admission to a programme integrated in the primary health care system. In this cohort study, 1,048 children admitted to 94 OTPs in Southern Ethiopia were followed for 14 weeks. Independent anthropometric measurements and information on treatment outcome were collected at four home visits. Only 32.7% (248/759) of children with SAM on admission fulfilled the programme recovery criteria at the time of discharge (i.e., gained 15% in weight, or oedema, if present at admission, was resolved at discharge). Of all children admitted to the programme for whom nutritional assessment was done 14 weeks later, 34.6% (321/928) were severely malnourished, and 37.5% (348/928) were moderately malnourished; thus, 72.1% were acutely malnourished. Of the children, 27/982 (2.7%) had died by 14 weeks, of whom all but one had SAM on admission. Children with severe oedema on admission had the highest fatality rate (12.0%, 9/75). The median length of admission to the programme was 6.6 weeks (interquartile range: 5.3, 8.4 weeks). Despite children participating for the recommended duration of the programme, many children with SAM were discharged still acutely malnourished and without reaching programme criteria for recovery. For better outcome of OTP, constraints in service provision by the health system as well as challenges of service utilization by the beneficiaries should be identified and addressed.

Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi.

BACKGROUND: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6-60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ≤ 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. RESULTS: The proportion of children with acidic stool (pH ≤5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p < 0.05). There was no significant difference in mortality (n = 6) between diets during the transition phase nor were there any differences in other secondary outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular transition phase diet is significantly better or worse since biochemical and clinical outcomes in children with SAM did not differ. However, larger and more tightly controlled efficacy studies are needed to confirm these findings. TRIAL REGISTRATION: ISRCTN13916953 Registered: 14 January 2013.

Changes in whole-blood PUFA and their predictors during recovery from severe acute malnutrition.

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-blood n-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, particularly n-3 LCPUFA, in children with SAM. Increased attention is needed to the contents of n-3 LCPUFA in therapeutic feeds.

Serum phosphate and magnesium in children recovering from severe acute undernutrition in Ethiopia: an observational study.

BACKGROUND: Children with severe acute malnutrition (SAM) have increased requirements for phosphorus and magnesium during recovery. If requirements are not met, the children may develop refeeding hypophosphatemia and hypomagnesemia. However, little is known about the effect of current therapeutic diets (F-75 and F-100) on serum phosphate (S-phosphate) and magnesium (S-magnesium) in children with SAM. METHODS: Prospective observational study, with measurements of S-phosphate and S-magnesium at admission, prior to rehabilitation phase and at discharge in children aged 6-59 months admitted with SAM to Jimma Hospital, Ethiopia. Due to shortage of F-75, 25 (35 %) children were stabilized with diluted F-100 (75 kcal/100 ml). RESULTS: Of 72 children enrolled, the mean age was 32 ± 14 months, and edema was present in 50 (69 %). At admission, mean S-phosphate was 0.92 ± 0.34 mmol/L, which was low compared to normal values, but increased to 1.38 ± 0.28 mmol/L at discharge, after on average 16 days. Mean S-magnesium, at admission, was 0.95 ± 0.23 mmol/L, and increased to 1.13 ± 0.17 mmol/L at discharge. At discharge, 18 (51 %) children had S-phosphate below the normal range, and 3 (9 %) had S-phosphate above. Most children (83 %) had S-magnesium above normal range for children. Both S-phosphate and S-magnesium at admission were positively associated with serum albumin (S-albumin), but not with anthropometric characteristics or co-diagnoses. Using diluted F-100 for stabilization was not associated with lower S-phosphate or S-magnesium. CONCLUSION: Hypophosphatemia was common among children with SAM at admission, and still subnormal in about half of the children at discharge. This could be problematic for further recovery as phosphorus is needed for catch-up growth and local diets are likely to be low in bioavailable phosphorus. The high S-magnesium levels at discharge does not support that magnesium should be a limiting nutrient for growth in the F-100 diet. Although diluted F-100 (75 kcal/100 mL) is not designed for stabilizing children with SAM, it did not seem to cause lower S-phosphate than in children fed F-75.

Evaluation of the acceptability of improved supplementary foods for the treatment of moderate acute malnutrition in Burkina Faso using a mixed method approach.

The objective of this study was to evaluate, within the context of a randomized controlled trial of product effectiveness, the acceptability of new formulations of six corn-soy blended flours (CSB) and six lipid-based nutrient supplements (LNS) with different quantities of milk and qualities of soy for the treatment of children with moderate acute malnutrition (MAM). Our study included 1546 children aged 6-23 months and involved questionnaires after one month of supplementation home visits and interviews with a sub-sample of 20 trial participants and their caretakers, and nine focus group discussion. All 12 products were well accepted in terms of organoleptic qualities and received good ratings. However, LNS were more appreciated by caretakers and children. Additionally, an effect of soy isolate was detected on child appreciation where products with high milk content also received better ratings. CSB were not consumed as readily; 33.9% (n = 257) of children receiving CSB were reported to have leftovers compared to 17.3% (n = 134) of children receiving LNS (p=<0.001). Both CSB and LNS were referred to as foods with medicinal properties and perceived as beneficial to child health. They were both reported to have high priority in the daily feeding of the child. In conclusion, there were minimal differences in acceptability of the various CSB and LNS formulations, although CSB were less readily consumed and required smaller meal volumes. Since all products were well-accepted, decisions regarding whether the more expensive products should be used for the treatment of MAM will need to be based on their effect on child nutrition, growth and health. Future supplementary feeding programs in similar contexts could furthermore consider introducing supplementary foods as a medical treatment, as this may increase adherence and decrease sharing.