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Ready-to-use therapeutic food (RUTF) with adequate quality protein is used to treat children with oedematous and non-oedematous severe acute malnutrition (SAM). The plasma amino acid (AA) profile reflects the protein nutritional status; hence, its assessment during SAM treatment is useful in evaluating AA delivery from RUTFs. The objective was to evaluate the plasma AAs during the treatment of oedematous and non-oedematous SAM in community-based management of acute malnutrition (CMAM) using amino acid-enriched plant-based RUTFs with 10% milk (MSMS-RUTF) or without milk (FSMS-RUTF) compared to peanut milk RUTF (PM-RUTF). Plasma AA was measured in a non-blinded, 3-arm, parallel-group, simple randomized controlled trial conducted in Malawi. The RUTFs used for SAM were FSMS-RUTF, MSMS-RUTF or PM-RUTF. A non-inferiority hypothesis was tested to compare plasma AA levels from patients treated with FSMS-RUTF or MSMS-RUTF with those from patients treated with PM-RUTF at discharge. For both types of SAM, FSMS-RUTF and MSMS-RUTF treatments were non-inferior to the PM-RUTF treatment in restoration of the EAA and cystine except that for FSMS-RUTF, methionine and tryptophan partially satisfied the non-inferiority criteria in the oedematous group. Amino-acid-enriched milk-free plant-source-protein RUTF has the potential to restore all the EAA, but it is possible that enrichment with amino acids may require more methionine and tryptophan for oedematous children.

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.

BackgroundStunting is the most common manifestation of childhood undernutrition worldwide. Children presenting with severe acute malnutrition (SAM) are often also severely stunted. We evaluated linear growth and its determinants after medically complicated SAM.MethodsWe performed secondary analysis of clinical trial data (NCT00934492) from HIV-uninfected Kenyan children aged 2–59 months hospitalised with SAM. Outcome was change in height/length-for-age z-score (HAZ) between enrolment and 12 months later. Exposures were demographic, clinical, anthropometric characteristics and illness episodes during follow-up.ResultsAmong 1169 children with HAZ values at month 12 (66% of those in original trial), median (IQR) age 11 (7–17) months and mean (SD) HAZ −2.87 (1.6) at enrolment, there was no change in mean HAZ between enrolment and month 12: −0.006Z (95% CI −0.07 to 0.05Z). While 262 (23%) children experienced minimal HAZ change (within ±0.25 HAZ), 472 (40%) lost >0.25 and 435 (37%) gained >0.25 HAZ. After adjusting for regression to the mean, inpatient or outpatient episodes of diarrhoea and inpatient severe pneumonia during follow-up were associated with HAZ loss. Premature birth and not being cared by the biological parent were associated with HAZ gain. Increases in mid-upper arm circumference and weight-for-age were associated with HAZ gain and protected against HAZ loss. Increase in weight-for-height was not associated with HAZ gain but protected against HAZ loss. No threshold of weight gain preceding linear catch-up growth was observed.ConclusionsInterventions to improve dietary quality and prevent illness over a longer period may provide opportunities to improve linear growth.

Mid‐upper arm circumference (MUAC) < 11.5 cm and weight‐for‐height Z‐score (WHZ) < −3 are used for screening for severe acute malnutrition (SAM). Underweight and concurrent wasting and stunting may better target those at the highest risk of mortality. We compared anthropometric outcomes in children enrolled in a trial of antibiotics for SAM based on categories of baseline anthropometry, including indicators for programme admission (WHZ < −3, MUAC < 11.5) and alternative indicators (weight‐for‐age Z‐score [WAZ] < −3, concurrent wasting and stunting [WHZ < −3 and height‐for‐age Z‐score < −3]). Participants were followed weekly until nutritional recovery and at 8 weeks. We evaluated changes in weight gain (g/kg/day), MUAC, and WHZ in children admitted by admissions criteria (MUAC only, WHZ only, or MUAC and WHZ) and by underweight or concurrent wasting and stunting. Of 301 admitted children, 100 (33%) were admitted based on MUAC only, 41 (14%) WHZ only, and 160 (53%) both MUAC and WHZ, 210 (68%) were underweight and 67 (22%) were concurrently wasted/stunted. Low MUAC and low WHZ children had the lowest probability of nutritional recovery (17% vs. 50% for MUAC‐only and 34% for WHZ‐only). There was no difference in weight gain velocity or WHZ by admissions criteria (WHZ and/or MUAC). Underweight and concurrently wasted/stunted children had lower MUAC and WHZ at 8 weeks compared with those who were not underweight or concurrently wasted and stunted. Children with both low MUAC and low WHZ had the worst outcomes. Relying on MUAC alone may miss children who have poor outcomes. Other indicators, such as WAZ, may be useful for identifying vulnerable children. Weight‐for‐height Z‐score (WHZ) and mid‐upper arm circumference (MUAC) are used for screening for severe acute malnutrition, but alternative indicators such as weight‐for‐age Z‐score (WAZ) may identify children at high risk of mortality. We evaluated anthropometric outcomes in children with severe acute malnutrition by baseline anthropometric status. Children with both low WHZ and MUAC had the worst outcomes, and low WAZ additionally identified children with poor outcomes Key messages Mid‐upper arm circumference (MUAC) and weight‐for‐height Z‐score (WHZ) are currently used for severe acute malnutrition (SAM) screening, but alternative indicators such as weight‐for‐age Z‐score (WAZ) may be additional options. Children admitted to the nutritional program based on both low MUAC and low WHZ had the worst outcomes, including the lowest probability of nutritional recovery and the worst anthropometric outcomes. While MUAC identified most children with SAM, WHZ may provide additional information about poor outcomes beyond MUAC alone. WAZ may be a useful alternative indicator to identify children who would benefit from a therapeutic feeding program without requiring height measurement.

Children with severe acute malnutrition (SAM) remain vulnerable after treatment at nutritional rehabilitation units (NRUs). The objective was to assess the concurrent pathways in a hypothesized model between caregiver body mass index (BMI), the home environment, and child nutritional status, and development (gross motor, fine motor, language, and social domains) in children with SAM following discharge from inpatient treatment. Structural equation modelling (SEM) was performed with data from a cluster-randomized controlled trial at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. This approach was undertaken to explore simultaneous relationships between caregiver BMI, the home environment (Home Observation for Measurement of the Environment Inventory scores), child nutritional status (anthropometric indicators including weight-for-age z-scores [WAZ]), and child development (Malawi Developmental Assessment Tool (MDAT) z-scores as a latent variable) in children with SAM. These data were collected at participants’ homes six months after discharge from NRU treatment. This analysis included 85 children aged 6–59 months with SAM and their caregivers recruited to the trial at the NRU and followed up successfully six months after discharge. The model with WAZ as the nutritional indicator fit the data according to model fit indices (χ 2 = 28.92, p = 0.42). Caregiver BMI was predictive of better home environment scores (β = 0.23, p = 0.03) and child WAZ (β = 0.30, p = 0.005). The home environment scores were positively correlated with MDAT z-scores (β = 0.32, p = 0.001). Child nutritional status based on WAZ was also correlated with MDAT z-scores (β = 0.37, p<0.001). This study demonstrates that caregiver BMI could ultimately relate to child development in children with SAM, through its links to the home environment and child nutritional status.

Background Severe acute malnutrition is a major problem among developing countries and it is one of the major causes of mortality and morbidity in Ethiopia. The impact is more severe among children aged 6–23 months. Severely malnourished children are nine times more likely to die than healthy children. Identification of the determinants of severe acute malnutrition under the age of two years can significantly reduce the burden of child morbidity and mortality. Therefore, this study was aimed to assess determinants of severe acute malnutrition among children aged 6–23 months at Bahir Dar city public hospitals, Northwest Ethiopia, 2020. Methods Institutional-based unmatched case–control study was conducted among a total sample size of 201 children (67 cases and 134 controls) in Felege Hiwot Comprehensive Specialized Hospital and Tibebe Ghion Specialized teaching hospital, from February 2020–March 2020. Children diagnosed with severe acute malnutrition were considered as cases and children with other problems were control groups. The study participants were randomly selected from pediatrics units in the two specialized hospitals. Data were collected using a structured pretested questionnaire through interviews and anthropometric measurements. The data were entered into Epi data version 3.1 and exported to SPSS software version 23 for analysis. Variables with ( p  < 0.25) in the bivariable analysis were entered into multivariable logistic regression. For multivariable analysis, a backward method was selected with a 95% confidence interval. Statistical significance was declared at P  < 0.05. Results In this study , 67 cases and 134 controls of children with their mothers had participated with an overall response rate of 100%. Family size > 5 [(AOR = 3.89, 95% CI:(1.19, -12.70)], average perceived birth weight [(AOR = 0.048, 95% CI: 0.015, -0.148)] and large perceived birth weight [(AOR = 0.023, 95% CI:(0.002, -0.271)], introduction of complementary feeding before six months [(AOR = 6.21, 95% CI: (1.44, -26.76)] and dietary diversity score < 5 groups [(AOR = 9.20, 95% CI; 3.40, -19.83)were significant factors associated with severe acute malnutrition. Conclusion In this study, dietary diversity, family size, perceived birth weight, and initiation of complementary feeding were significantly associated with severe acute malnutrition. Therefore, emphasis should be given to improving infant and young child feeding practices, especially timely initiation of complementary feeding and dietary diversity.

Objectives5.0 million annual deaths in low-income and middle-income countries are due to poor quality of care (QOC). We evaluated the QOC provided to malnourished children in West Nile Region in Uganda.DesignCross-sectional study.SettingWest Nile Region, an area hosting over one million refugees.ParticipantsAmong 148 facilities providing nutritional services, 30 randomly selected facilities (20%) and the records of 1467 children with severe acute malnutrition (100% of those attending the 30 facilities during last year) were assessed.OutcomesThe national Nutrition Service Delivery Assessment (NSDA) tool was used to assess capacity areas related to QOC. Case management, data quality and health outcomes were assessed from official health records. Multivariate analysis was performed to explore factors significantly associated with better cure rates.ResultsOf 305 NSDA scores allocated to 30 participating centres, 201 (65.9%) were ‘good’ or ‘excellent’. However, 20 (66.7%) facilities had ‘poor’ ‘quality improvement mechanisms’ and 13 (43.3%) had ‘poor’ ‘human resources’. Overall data quality in official records was poor, while recorded quality of case management was overall fair. Average cure rate was significantly lower than international Sphere standards (50.4% vs 75% p<0.001) with a higher default rate (23.2% vs 15% p<0.001). Large heterogeneity among facilities was detected for all indicators. Refugee-hosting and non-refugee-hosting facilities had a similar cure rate (47.1% vs 52.1%) though transfer rates were higher for those hosting refugees (21.5% vs 1.9%, p<0.001) despite better ‘equipment and supplies’. ‘Good/excellent’ ‘equipment’ and ‘store management’ were significantly associated with better cure rates in outpatient therapeutic centres (+55.9, p<0.001; +65.4, p=0.041, respectively) in multivariate analysis.ConclusionsThough most NSDA capacity areas were rated good or excellent, health outcomes of malnourished children in West Nile Region, both in refugee-hosting and non-refugee-hosting facilities, are significantly below international standards. Effective and sustainable approaches to improve malnourished child health outcomes are needed.

Hospital readmission is common among children with complicated severe acute malnutrition (cSAM) but not well‐characterised. Two distinct cSAM phenotypes, marasmus and kwashiorkor, exist, but their pathophysiology and whether the same phenotype persists at relapse are unclear. We aimed to test the association between cSAM phenotype at index admission and readmission following recovery. We performed secondary data analysis from a multicentre randomised trial in Kenya with 1‐year active follow‐up. The main outcome was cSAM phenotype upon hospital readmission. Among 1,704 HIV‐negative children with cSAM discharged in the trial, 177 children contributed a total of 246 readmissions with cSAM. cSAM readmission was associated with age<12 months (p = .005), but not site, sex, season, nor cSAM phenotype. Of these, 42 children contributed 44 readmissions with cSAM that occurred after a monthly visit when SAM was confirmed absent (cSAM relapse). cSAM phenotype was sustained during cSAM relapse. The adjusted odds ratio for presenting with kwashiorkor during readmission after kwashiorkor at index admission was 39.3 [95% confidence interval (95% CI) [2.69, 1,326]; p = .01); and for presenting with marasmus during readmission after kwashiorkor at index admission was 0.02 (95% CI [0.001, 0.037]; p = .01). To validate this finding, we examined readmissions to Kilifi County Hospital, Kenya occurring at least 2 months after an admission with cSAM. Among 2,412 children with cSAM discharged alive, there were 206 readmissions with cSAM. Their phenotype at readmission was significantly influenced by their phenotype at index admission (p < .001). This is the first report describing the phenotype and rate of cSAM recurrence.

The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with current ready-to-use therapeutic food (RUTF) interventions, is causally related to disease pathogenesis. To further characterize gut microbial community development in healthy versus malnourished infants/children, we performed a time-series metagenomic study of DNA isolated from virus-like particles (VLPs) recovered from fecal samples collected during the first 30 mo of postnatal life from eight pairs of mono- and dizygotic Malawian twins concordant for healthy growth and 12 twin pairs discordant for SAM. Both members of discordant pairs were sampled just before, during, and after treatment with a peanut-based RUTF. Using Random Forests and a dataset of 17,676 viral contigs assembled from shotgun sequencing reads of VLP DNAs, we identified viruses that distinguish different stages in the assembly of the gut microbiota in the concordant healthy twin pairs. This developmental program is impaired in both members of SAM discordant pairs and not repaired with RUTF. Phage plus members of the Anelloviridae and Circoviridae families of eukaryotic viruses discriminate discordant from concordant healthy pairs. These results disclose that apparently healthy cotwins in discordant pairs have viromes associated with, although not necessarily mediators, of SAM; as such, they provide a human model for delineating normal versus perturbed postnatal acquisition and retention of the gut microbiota’s viral component in populations at risk for malnutrition.

Background and Aims: Malnutrition is associated with poor clinical outcomes. Whether there is a causal relationship or it merely mirrors a severe patient condition remains unclear. We examined the association of malnutrition with biomarkers characteristic of different pathophysiological states to better understand the underlying etiological mechanisms. Methods: We prospectively followed consecutive adult medical inpatients. Multivariable regression models were used to investigate the associations between malnutrition - as assessed using the Nutritional Risk Screening (NRS 2002) - and biomarkers linked to inflammation, stress, renal dysfunction, nutritional status and hematologic function. Results: A total of 529 patients were included. In a fully adjusted model, malnutrition was significantly associated with the inflammatory markers procalcitonin (0.20, 95% CI 0.03-0.37), proadrenomedullin (0.28, 95% CI 0.12-0.43) and albumin (-0.39, 95% CI -0.57 to -0.21), the stress marker copeptin (0.34, 95% CI 0.17-0.51), the renal function marker urea (0.23, 95% CI 0.07-0.38), the nutritional markers vitamin D25 (-0.22, 95% CI -0.41 to -0.02) and corrected calcium (0.29, 95% CI 0.10-0.49) and the hematological markers hemoglobin (-0.27, 95% CI -0.43 to -0.10) and red blood cell distribution width (0.26, 95% CI 0.07-0.44). Subgroup analysis suggested that acute malnutrition rather than chronic malnutrition was associated with elevated biomarker levels. Conclusion: Acute malnutrition was associated with a pronounced inflammatory response and an alteration in biomarkers associated with different pathophysiological states. Interventional trials are needed to prove causality.