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.
ABSTRACT: 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.
Project description:Childhood malnutrition is a major public health concern, as it is associated with significant short- and long-term morbidity and mortality. The objective of this review was to comprehensively review the evidence for the management of severe acute malnutrition (SAM) and moderate acute malnutrition (MAM) according to the current World Health Organization (WHO) protocol using facility- and community-based approaches, as well as the effectiveness of ready-to-use therapeutic food (RUTF), ready-to-use supplementary food (RUSF), prophylactic antibiotic use, and vitamin A supplementation. We searched relevant electronic databases until 11 February 2019, and performed a meta-analysis. This review summarizes findings from a total of 42 studies (48 papers), including 35,017 children. Limited data show some benefit of integrated community-based screening, identification, and management of SAM and MAM on improving recovery rate. Facility-based screening and management of uncomplicated SAM has no effect on recovery and mortality, while the effect of therapeutic milk F100 for SAM is comparable to RUTF for weight gain and mortality. Local food and whey RUSF are comparable to standard RUSF for recovery rate and weight gain in MAM, while standard RUSF has additional benefits to CSB. Prophylactic antibiotic administration in uncomplicated SAM improves recovery rate and probably improves weight gain and reduces mortality. Limited data suggest that high-dose vitamin A supplementation is comparable with low-dose vitamin A supplementation for weight gain and mortality among children with SAM.
Project description:Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM.This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant.We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies.ISRCTN 30393230 , date: 16/03/2017.
Project description:<h4>Background</h4>Globally, moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) affect approximately 52 million children under five. This systematic review evaluates the effectiveness of interventions for SAM including the World Health Organization (WHO) protocol for inpatient management and community-based management with ready-to-use-therapeutic food (RUTF), as well as interventions for MAM in children under five years in low- and middle-income countries.<h4>Methods</h4>We systematically searched the literature and included 14 studies in the meta-analysis. Study quality was assessed using CHERG adaptation of GRADE criteria. A Delphi process was undertaken to complement the systematic review in estimating case fatality and recovery rates that were necessary for modelling in the Lives Saved Tool (LiST).<h4>Results</h4>Case fatality rates for inpatient treatment of SAM using the WHO protocol ranged from 3.4% to 35%. For community-based treatment of SAM, children given RUTF were 51% more likely to achieve nutritional recovery than the standard care group. For the treatment of MAM, children in the RUSF group were significantly more likely to recover and less likely to be non-responders than in the CSB group. In both meta-analyses, weight gain in the intervention group was higher, and although statistically significant, these differences were small. Overall limitations in our analysis include considerable heterogeneity in many outcomes and an inability to evaluate intervention effects separate from commodity effect. The Delphi process indicated that adherence to standardized protocols for the treatment of SAM and MAM should have a marked positive impact on mortality and recovery rates; yet, true consensus was not achieved.<h4>Conclusions</h4>Gaps in our ability to estimate effectiveness of overall treatment approaches for SAM and MAM persist. In addition to further impact studies conducted in a wider range of settings, more high quality program evaluations need to be conducted and the results disseminated.
Project description:BACKGROUND:Acute malnutrition is a continuum condition, but severe and moderate forms are treated separately, with different protocols and therapeutic products, managed by separate United Nations agencies. The Combined Protocol for Acute Malnutrition Study (ComPAS) aims to simplify and unify the treatment of uncomplicated severe and moderate acute malnutrition (SAM and MAM) for children 6-59 months into one protocol in order to improve the global coverage, quality, continuity of care and cost-effectiveness of acute malnutrition treatment in resource-constrained settings. METHODS/DESIGN:This study is a multi-site, cluster randomized non-inferiority trial with 12 clusters in Kenya and 12 clusters in South Sudan. Participants are 3600 children aged 6-59 months with uncomplicated acute malnutrition. This study will evaluate the impact of a simplified and combined protocol for the treatment of SAM and MAM compared to the standard protocol, which is the national treatment protocol in each country. We will assess recovery rate as a primary outcome and coverage, defaulting, death, length of stay, average weekly weight gain and average weekly mid-upper arm circumference (MUAC) gain as secondary outcomes. Recovery rate is defined across both treatment arms as MUAC ?125 mm and no oedema for two consecutive visits. Per-protocol and intention-to-treat analyses will be conducted. DISCUSSION:If the combined protocol is shown to be non-inferior to the standard protocol, updating guidelines to use the combined protocol would eliminate the need for separate products, resources and procedures for MAM treatment. This would likely be more cost-effective, increase availability of services, enable earlier case finding and treatment before deterioration of MAM into SAM, promote better continuity of care and improve community perceptions of the programme. TRIAL REGISTRATION:ISRCTN, ISRCTN30393230 . Registered on 16 March 2017.
Project description:<h4>Background</h4>Community health worker (CHW)-delivered acute malnutrition treatment programs have been tested previously, but not with low-literate/-numerate cadres who operate in areas with the highest malnutrition burden and under-five mortality rates. The International Rescue Committee developed low-literacy-adapted tools and treatment protocol to enable low-literate/-numerate community-based distributors (CBD, the CHW cadre in South Sudan) to treat children for severe acute malnutrition (SAM) in their communities.<h4>Methods</h4>We conducted a prospective cohort study in March-September 2017, with 44 CBDs enrolling a total of 308 SAM children into treatment in their communities. Child treatment outcomes and length of treatment were documented. Uncomplicated SAM cases, defined for our study as children with mid-upper arm circumference (MUAC) of 90 to <115 mm or bilateral pitting oedema, without any medical complications, were treated for up to 16 weeks, and were considered fully recovered when they reached MUAC?125 mm for two consecutive weeks.<h4>Results</h4>The recovery rate from the severe to the moderate acute malnutrition (MAM) cut-off of MUAC 115 mm was 91% (95% confidence interval (CI)?=?88%-95%). The median length of treatment was five weeks. The recovery rate of children from SAM to full recovery was 75% (95% CI?=?69%-81%). The median time to full recovery was eight weeks. The recovery rates reported here exclude children referred for care from the denominator, per standard reporting of acute malnutrition treatment recovery rates. When the data were compared against routine monitoring and evaluation data from nearby static clinics, children treated by CBDs appeared to have improved continuity of care and shorter time to recovery.<h4>Conclusions</h4>The recovery rate for SAM children enrolled in acute malnutrition treatment by low-literate CBDs shows promise that deploying CHWs to treat SAM in areas with high prevalence and low treatment access may lead to higher recovery, better continuity of care in the transition between SAM and MAM, and shorter treatment time. Proper adaptations of tools and protocols can empower CHW cadres with low literacy and numeracy to successfully complete treatment steps. Key questions of scalability and cost-effectiveness remain.
Project description:Objective:This cross-sectional study set in a single school on the outskirts of a large city aimed to document the extent of double burden of malnutrition (coexistence of overnutrition and undernutrition) among Indian schoolchildren from lower socioeconomic groups, and to determine if mid-upper arm circumference (MUAC) can be used as a proxy for body mass index (BMI). Subjects:The total number of participants was 1444, comprising 424 girls and 1020 boys belonging to playgroups and grades 1 to 7. Measurements:Anthropometric measurements, such as participants' MUAC, height and weight were measured using standard techniques. Descriptive statistics for BMI and MUAC were obtained based on gender; z-scores were computed using age-specific and sex-specific WHO reference data. The distribution of variables was calculated for three groups: girls, boys and all participants. Homogeneous subsets for BMI and MUAC were identified in the three groups. Age-wise comparisons of BMI and MUAC were conducted for each gender. Main outcome measures:(1) To know if MUAC and BMI are correlated among boys and girls. (2) To study BMI and MUAC z-score distribution among the participants. Results:MUAC was positively correlated with BMI in both boys and girls. The following BMI z-score distribution was observed: severe acute malnutrition (SAM), 5 (0.3%); moderate acute malnutrition (MAM), 146 (10.1%) and undernourished, at risk of MAM/SAM, 141 (9.8%); obese, 21 (1.5%); overweight, 36 (2.5%) and pre-obese, 136 (9.4%). The distribution of categories of children based on MUAC z-scores was: SAM, 7 (0.5%); MAM, 181 (12.5%) and undernourished, at risk of MAM/SAM, 181 (12.5%); obese, 19 (1.3%); overweight, 178 (12.3%) and pre-obese, 135 (9.3%). Conclusions:SAM/MAM/undernourished states and obesity/overweight/pre-obese states, indicating undernutrition more than overweight, coexist among Indian schoolchildren from lower middle/lower socioeconomic categories. BMI and MUAC were significantly correlated. MUAC identifies both undernutrition and overnutrition by early detection of aberrant growth.
Project description:BACKGROUND: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. METHODS AND FINDINGS: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. CONCLUSIONS: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.
Project description:BACKGROUND:Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between -?2 and?-?3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3?months. METHODS:Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1?month, at the end of intervention (3?months), 1?month after cessation of intervention, and every 6?months thereafter for 4?years. DISCUSSION:This study will determine whether daily, controlled administration of MDCF-2 for 3?months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices. TRIAL REGISTRATION:The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).
Project description:BACKGROUND:Children with moderate acute malnutrition (MAM) have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. In parts of Ethiopia not considered chronically food insecure there are no supplementary feeding programmes (SFPs) for treating MAM. The short-term outcomes of children who have MAM in such areas are not currently described, and there remains an urgent need for evidence-based policy recommendations. METHODS:We defined MAM as mid-upper arm circumference (MUAC) of ?11.0 cm and <12.5 cm with no bilateral pitting oedema to include Ethiopian government and World Health Organisation cut-offs. We prospectively surveyed 884 children aged 6-59 months living with MAM in a rural area of Ethiopia not eligible for a supplementary feeding programme. Weekly home visits were made for seven months (28 weeks), covering the end of peak malnutrition through to the post-harvest period (the most food secure window), collecting anthropometric, socio-demographic and food security data. RESULTS:By the end of the study follow up, 32.5% (287/884) remained with MAM, 9.3% (82/884) experienced at least one episode of SAM (MUAC <11 cm and/or bilateral pitting oedema), and 0.9% (8/884) died. Only 54.2% of the children recovered with no episode of SAM by the end of the study. Of those who developed SAM half still had MAM at the end of the follow up period. The median (interquartile range) time to recovery was 9 (4-15) weeks. Children with the lowest MUAC at enrolment had a significantly higher risk of remaining with MAM and a lower chance of recovering. CONCLUSIONS:Children with MAM during the post-harvest season in an area not eligible for SFP experience an extremely high incidence of SAM and a low recovery rate. Not having a targeted nutrition-specific intervention to address MAM in this context places children with MAM at excessive risk of adverse outcomes. Further preventive and curative approaches should urgently be considered.
Project description:Mid-upper arm circumference (MUAC) was recently endorsed and recommended for screening for acute malnutrition in the community. The objective of this study was to determine whether a colour-banded MUAC strap would allow minimally trained mothers to screen their own children for malnutrition, without locating the mid-point of the left upper arm by measurement, as currently recommended.A non-randomised non-blinded evaluation of mothers' performance when measuring MUAC after minimal training, compared with trained Community Health Workers (CHW) following current MUAC protocols. The study was conducted in 2 villages in Mirriah, Zinder region, Niger where mothers classified one of their children (n = 103) aged 6-59 months (the current age range for admission into community malnutrition programs) using the MUAC tape.Mothers' had a sensitivity and specificity for classification of their child's nutritional status of > 90% and > 80% respectively for global acute malnutrition (GAM, defined by a MUAC < 125 mm) and > 73% and > 98% for severe acute malnutrition (SAM, defined by a MUAC < 115 mm). The few children misclassified as not having SAM, were classified as having moderate acute malnutrition (MAM). The choice of arm did not influence the classification results; weighted Kappa of 0.88 for mothers and 0.91 for CHW represent almost perfect agreement. Errors occurred at the class boundaries and no gross errors were made.Advanced SAM is associated with severe complications, which often require hospital admission or cause death. Mothers (with MUAC tapes costing $0.06) can screen their children frequently allowing early diagnosis and treatment thereby becoming the focal point in scaling-up community management of acute malnutrition.The trial is registered with clinicaltrials.gov (Trial number NCT01790815).