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Introduction: Evidence gaps limit management of small and/or nutritionally at-risk infants under 6 months and their mothers, who are at higher risk of death, illness, malnutrition and poor growth and development. These infants may be low birth weight, wasted, stunted and/or underweight. An integrated care model to guide their management (MAMI Care Pathway) is being tested in a randomised controlled trial in Ethiopia. Evaluating the extent to which an innovation is consistent with national policies and priorities will aid evidence uptake and plan for scale., Methods and Analysis: This review will evaluate the extent to which the MAMI Care Pathway is consistent with national policies that relate to the care of at-risk infants under 6 months and their mothers in Ethiopia. The objectives are to describe the range and characteristics, concepts, strategic interventions, coherence and alignment of existing policies and identify opportunities and gaps. It will be conducted in accordance with the JBI methodology for scoping reviews (PRISMA-ScR). Eligible documents include infant and maternal health, nutrition, child development, food and social welfare-related policies publicly available in English and Amharic. The protocol was registered on the Open Science Framework Registry on 20 June 2022 (https://osf.io/m4jt6).Grey literature will be identified through government and agency websites, national and subnational contacts and Google Scholar, and published policies through electronic database searches (MEDLINE, EMBASE and Global and Health Information). The searches will take place between October 2023 and March 2024. A standardised data extraction tool will be used. Descriptive analysis of data will be undertaken. Data will be mapped visually and tabulated. Results will be described in narrative form. National stakeholder discussions will inform conclusions and recommendations., Ethics and Dissemination: Ethical approval is not required as data consist solely of publicly available material. Findings will be used to evidence national and international policy and practice., (© World Health Organization 2023. Licensee BMJ.)

Background: Linear catch-up growth after treatment of severe acute malnutrition (SAM) is low, and little is known about the association between ponderal and subsequent linear growth., Objective: The study assessed the association of weight-for-height z -score (WHZ) gain with subsequent linear growth during SAM treatment and examined its modifiers., Methods: This was a prospective study, nested in a trial (ISRCTN16454889), among 6-59-mo-old children treated for SAM in Uganda. Weight, total length (TL), and knee-heel length (KHL) were measured at admission, weekly during inpatient therapeutic care (ITC), at discharge, and fortnightly during outpatient therapeutic care (OTC) for 8 wk. Linear regression was used to assess the association between WHZ gain during ITC and linear growth during OTC., Results: Of 400 children, 327 were discharged to OTC and 290 were followed up for 8 wk. Mean WHZ gains were 0.45 in ITC and 1.24 in OTC, whereas mean height-for-age z -score (HAZ) declined by 0.41 during ITC and increased by 0.14 during OTC. WHZ gain during ITC was positively associated with HAZ, TL, and KHL gains during OTC [regression coefficients (β) (95% CI): 0.12 (0.09, 0.15) z -score; 3.1 (2.4, 3.8) mm and 0.5 (0.1, 0.7) mm, respectively]. The regression coefficients were highest for the middle tertile of WHZ gain with respect to HAZ and TL. Admission diarrhea and low plasma citrulline reduced the association between WHZ gain during ITC and HAZ and TL gain during OTC ( P  < 0.001). In contrast, pneumonia ( P  = 0.051) and elevated plasma C-reactive protein ( P  < 0.001) increased the association with TL gain, but reduced the association with KHL gain ( P  < 0.001)., Conclusions: Among children admitted with SAM, considerable WHZ gain during ITC was followed by very modest linear catch-up growth during OTC, with no indication of a WHZ gain threshold, above which linear growth was higher. To optimize linear growth in these children, early treatment of infections and conditions affecting the gut may be necessary., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6-59 mo-old children with complicated SAM by treatment phase and edema status., Methods: This was a prospective study, nested in a randomized/probiotic trial ( ISRCTN16454889 ). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models., Results: Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were - 11.26 (95% CI: - 20.73; - 1.79) g/kg/d and - 13.09 (95% CI: - 23.15; - 3.02) g/kg/d, respectively]. This gradually changed into positive weight gain velocity in transition and eventually peaked at 12 g/kg/d early in the rehabilitation phase, with no difference by edema status (P > 0.9). During outpatient therapeutic care (OTC), overall, weight gain velocity showed a decreasing trend over time (from 5 to 2 g/kg/d), [difference between edema and non-edema groups at week 2 was 2.1 (95% CI: 1.0;3.2) g/kg/d]. MUAC gain velocity results mirrored those of weight gain velocity [differences were - 2.30 (95% CI: - 3.6; - 0.97) mm/week at week 1 in ITC and 0.65 (95% CI: - 0.07;1.37) mm/week at week 2 in OTC]., Conclusions: Weight and MUAC gain velocities among Ugandan children with complicated SAM showed an increasing trend during transition and early in the rehabilitation phase, and a decreasing trend thereafter, but, overall, catch-up growth was prolonged. Further research to establish specific cut-offs to assess weight and MUAC gain velocities during different periods of rehabilitation is needed.

Declaration of the novel coronavirus disease as a Public Health Emergency of International Concern necessitated countries to get ready to respond. Here, we describe key achievements, challenges and lessons learnt during the readiness and early response to COVID-19 in Ethiopia. Readiness activities commenced as early as January 2020 with the activation of a national Public Health Emergency Operations Centre and COVID-19 Incident Management System (IMS) by the Ethiopian Public Health Institute. The COVID-19 IMS conducted rapid risk assessments, developed scenario-based contingency plans, national COVID-19 guidelines and facilitated the enhancement of early warning and monitoring mechanisms. Early activation of a coordination mechanism and strengthening of detection and response capacities contributed to getting the country ready on time and mounting an effective early response. High-level political leadership and commitment led to focused efforts in coordination of response interventions. Health screening, mandatory 14-day quarantine and testing established for all international travellers arriving into the country slowed down the influx of travellers. The International Health Regulations (IHR) capacities in the country served as a good foundation for timely readiness and response. Leveraging on existing IHR capacities in the country built prior to COVID-19 helped slow down the importation and mitigated uncontrolled spread of the disease in the country. Challenges experienced included late operationalisation of a multisectoral coordination platform, shortage of personal protective equipment resulting from global disruption of importation and the huge influx of over 10 000 returnees from different COVID-19-affected countries over a short period of time with resultant constrain on response resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Efforts towards slowing down coronavirus (COVID-19) transmission and reducing mortality have focused on timely case detection, isolation and treatment. Availability of laboratory COVID-19 testing capacity using reverse-transcriptase polymerase chain reaction (RT-PCR) was essential for case detection. Hence, it was critical to establish and expand this capacity to test for COVID-19 in Ethiopia. To this end, using a three-phrased approach, potential public and private laboratories with RT-PCR technology were assessed, capacitated with trained human resource and equipped as required. These laboratories were verified to conduct COVID-19 testing with quality assurance checks regularly conducted. Within a 10-month period, COVID-19 testing laboratories increased from zero to 65 in all Regional States with the capacity to conduct 18,454 tests per day. The success of this rapid countrywide expansion of laboratory testing capacity for COVID-19 depended on some key operational implications: the strong laboratory coordination network within the country, the use of non-virologic laboratories, investment in capacity building, digitalization of the data for better information management and establishing quality assurance checks. A weak supply chain for laboratory reagents and consumables, differences in the brands of COVID-19 test kits, frequent breakdowns of the PCR machines and inadequate number of laboratory personnel following the adaption of a 24/7 work schedule were some of the challenges experienced during the process of laboratory expansion. Overall, we learn that multisectoral involvement of laboratories from non-health sectors, an effective supply chain system with an insight into the promotion of local production of laboratory supplies were critical during the laboratory expansion for COVID-19 testing. The consistent support from WHO and other implementing partners to Member States is needed in building the capacity of laboratories across different diagnostic capabilities in line with International Health Regulations. This will enable efficient adaptation to respond to future public health emergencies., Competing Interests: The authors declare no competing interests., (Copyright: Adisu Kebede et al.)

Background: Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM., Methods: This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM., Results: Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm 2 lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm 2 , p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01)., Conclusion: The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. Klebsiella spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., Veilonella dispar ) and follow-up (e.g. Lactobacillus ruminis, Blautia spp., Faecalibacterium prausnitzii ), reaching similar β- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence β-diversity upon discharge or follow-up, but it increased ( p < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence ( p < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.

Objective: Children with severe acute malnutrition (SAM) may have impaired intestinal function, which can result in malabsorption, diarrhoea, and poor growth. This study evaluated the gut function of children with SAM using fecal and blood biomarkers and assessed their correlates., Methods: A cross-sectional study, nested in a randomized trial (www.isrctn.com, ISRCTN 16454889), was conducted at Mulago hospital, Uganda among subgroups of 400 children with complicated SAM and 30 community controls. Gut function was evaluated by 5 biomarkers: plasma citrulline, fecal myeloperoxidase and fecal neopterin, bacterially derived 16S rRNA gene and internal transcribed Spacer region (ITS) specific for Candida spp. in blood., Results: Compared with controls, children with SAM had lower median plasma citrulline (5.14 vs 27.4 μmol/L, P < 0.001), higher median fecal myeloperoxidase (18083 vs 7482 ng/mL, P = 0.001), and fecal neopterin (541 vs 210 nmol/L, P < 0.001). A higher blood concentration of 16S rRNA gene copy numbers was observed among children with SAM (95 vs 28 copies/μl, P = 0.05), whereas there was no difference in the blood concentration of Candida-specific ITS fragment.Among those with SAM, plasma citrulline was lower in children with edema, diarrhoea, dermatosis, and plasma C-reactive protein (CRP) >10 mg/L. Fecal neopterin was positively correlated with symptoms of fever and cough whereas it was negatively correlated with mid-upper arm circumference (MUAC), weight-for-height z score (WHZ), edema, and dermatosis., Conclusions: Children with complicated SAM seem to have impaired gut function characterized by reduced enterocyte mass, intestinal inflammation, and increased bacterial translocation.

Objective: To assess predictors of diarrhea and dehydration and to investigate the role of diarrhea in mortality among children with complicated severe acute malnutrition., Study Design: A prospective cohort study, nested in a probiotic trial, was conducted in children with complicated severe acute malnutrition. Children were treated according to World Health Organization and national guidelines, and diarrhea and dehydration were assessed daily. Multiple linear and log-linear Poisson regression models were used to identify predictors of days with diarrhea and dehydration, respectively, and multiple logistic regression was used to assess their role in mortality., Results: Among 400 children enrolled, the median (IQR) age was 15.0 months (11.2-19.2 months), 58% were boys, and 61% had caregiver-reported diarrhea at admission. During hospitalization, the median (range) number of days with diarrhea was 5 (0-31), the median duration of hospitalization was 17 days (1-69 days), and 39 (10%) died. Of 592 diarrhea episodes monitored, 237 were admission episodes and 355 were hospital acquired. During hospitalization, young age was associated with days with diarrhea, and young age and HIV infection were associated with dehydration. Both days with diarrhea and dehydration predicted duration of hospitalization as well as mortality. The odds of mortality increased by a factor of 1.4 (95% CI, 1.2-1.6) per day of diarrhea and 3.5 (95% CI, 2.2-6.0) per unit increase in dehydration score., Conclusions: Diarrhea is a strong predictor of mortality among children with complicated severe acute malnutrition. Improved management of diarrhea and prevention of hospital-acquired diarrhea may be critical to decreasing mortality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background : Children with severe acute malnutrition (SAM) are prone to infections due to immune dysfunction including severe thymus atrophy which recovers during nutritional rehabilitation. Aim : To investigate predictors of thymus size recovery, including probiotics during nutritional rehabilitation of children admitted with complicated SAM. Methods : In this prospective study nested in a randomized controlled trial, children 6-59 months admitted with SAM received standard care and either probiotics or placebo during hospitalization until 8 weeks post-discharge. Thymus size was measured using ultrasound at admission, discharge, 8 weeks post-discharge and among 27 community controls. Predictors of thymus size recovery were assessed using linear regression. Results : Among 388 children with SAM, mean (SD) thymus size was 1.06 cm2 (0.41), 1.24 cm2 (0.48), 2.85 cm2 (1.07) and 4.2 cm2 (0.93) at admission, discharge, follow-up and in the healthy controls respectively (p < 0.05).Probiotics did not affect thymus recovery. During both inpatient therapeutic care (ITC) and outpatient therapeutic care (OTC), thymus recovery correlated positively with anthropometry but negatively with caregiver-perceived illness severity and Haemoglobin <8 g/dl. Negative predictors of thymus recovery during ITC included grade 3 oedema (β -0.13, 95%CI -0.25; -0.01), dermatosis (β -0.21, 95%CI -0.41; -0.01), C-reactive protein (CRP) >15mg/L (β -0.13, 95%CI -0.25; -0.02) and neutrophils (β -0.01, 95%CI -0.02; -0.002). During OTC, HIV negatively predicted thymus recovery. Conclusion : Children with SAM failed to regain thymus size at 8 weeks post-discharge. Probiotics did not predict thymus recovery during nutritional rehabilitation. More research is needed to find interventions which can accelerate immune recovery. Abbreviations : ART, Antiretroviral therapy; BB-12, Bifidobacterium animalis subsp. Lactis; CRP, C-reactive protein; ITC, inpatient therapeutic care; LGG, Lactobacillus rhamnosus ; MNU, Mwanamugimu Nutrition Unit; MUAC, mid-upper arm circumference; OTC, outpatient therapeutic care; PCR, Polymerised chain reaction; RUTF, ready-to-use therapeutic food; SAM, severe acute malnutrition; VAS, visual analogue score; WHO, World Health Organization; WHZ, weight-for-height score.

Background: We determined the predictors of mortality among children admitted with severe acute malnutrition (SAM)., Methods: This was a prospective study nested in a randomized trial among 6-59-month-old children admitted with SAM. Socio-demographic and medical history data were collected using questionnaires and clinical examination, anthropometry and laboratory tests were performed. They were monitored daily until discharge or death during hospitalization while receiving care according to national guidelines. Predictors of death were assessed using Cox regression., Results: Of 400 children, 9.8% (n = 39) died during hospitalization. Predictors of mortality included diarrhoea at admission [hazard ratio [HR] 2.19, 95% confidence interval (CI): 1.06; 4.51], lack of appetite [HR 4.50, 95% CI: 1.76; 11.50], suspected sepsis [HR 2.23, 95% CI: 1.18; 4.24] and skin ulcers [HR 4.23, 95% CI: 1.26; 4.17]. Chest indrawing [HR 5.0, 95% CI: 1.53; 16.3], oxygen saturation below 94% [HR 3.92, 95% CI: 1.42; 10.83] and confirmed HIV infection [HR 3.62, 95% CI: 1.69; 7.77] also predicted higher mortality., Conclusion: Infections were major contributors to mortality. This underscores the need for improved prevention and management of these infections among children with severe malnutrition.

Background: World Health Organization now recommends the transition from F-75 to ready-to-use therapeutic foods (RUTF) in the management of severe acute malnutrition (SAM). We described the transition from F-75 to RUTF and identified correlates of failed transition., Methods: We conducted an observational study among children aged 6-59 months treated for SAM at Mulago hospital, Kampala, Uganda. Therapeutic feeding during transition phase was provided by first offering half of the energy requirements from RUTF and the other half from F-75 and then increasing gradually to RUTF as only energy source. The child was considered to have successfully transitioned to RUTF if child was able to gradually consume up to 135 kcal/kg/day of RUTF in the transition phase on first attempt. Failed transition to RUTF included children who failed the acceptance test or those who had progressively reduced RUTF intake during the subsequent days. Failure also included those who developed profuse diarrhoea or vomiting when RUTF was ingested., Results: Among 341 of 400 children that reached the transition period, 65% successfully transitioned from F-75 to RUTF on first attempt while 35% failed. The median (IQR) duration of the transition period was 4 (3-8) days. The age of the child, mid-upper arm circumference, weight-for-height z-score and weight at transition negatively predicted failure. Each month increase in age reflected a 4% lower likelihood of failure (OR 0.96 (95% CI 0.93; 0.99). Children with HIV (OR 2.73, 95% CI 1.27; 5.85) and those rated as severely ill by caregiver (OR 1.16, 95% CI: 1.02; 1.32) were more likely to fail. At the beginning of the rehabilitation phase, the majority (95%) of the children eventually accepted RUTF while only 5% completed rehabilitation in hospital on F-100., Conclusion: Transition from F-75 to RUTF for hospitalized children with SAM by gradual increase of RUTF was possible on first attempt in 65% of cases. Younger children, severely wasted, HIV infected and those with severe illness as rated by the caregiver were more likely to fail to transit from F-75 to RUTF on first attempt.

Objectives: The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low-income country., Methods: Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial., Results: Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55-0.77) and 0.75 (0.66-0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ≤6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4-point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07-0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3-0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more "watery + abnormally loose + loose" stools per day)., Conclusions: The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.

Objectives: The aim of the study was to assess the effect of probiotics on diarrhea during in- and outpatient treatment of children with severe acute malnutrition (SAM)., Methods: A randomized, double-blind, placebo-controlled study was conducted involving 400 children admitted with SAM. Patients received 1 daily dose of a blend of Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus (10 billion colony-forming units, 50:50) or placebo during hospitalization followed by an 8- to 12-week outpatient treatment period, depending on patients' recovery rate. All outcomes were reported for in- and outpatient treatment separately. The primary outcome was number of days with diarrhea during hospitalization. Secondary outcomes included other diarrhea outcomes, pneumonia, weight gain, and recovery., Results: There was no difference in number of days with diarrhea between the probiotic (n = 200) and placebo (n = 200) groups during inpatient treatment (adjusted difference +0.2 days, 95% confidence interval -0.8 to 1.2, P = 0.69); however, during outpatient treatment, probiotics reduced days with diarrhea (adjusted difference -2.2 days 95% confidence interval -3.5 to -0.3, P = 0.025). There were no effects of probiotics on diarrhea incidence and severity or pneumonia, weight gain or recovery during in- or outpatient treatment. Twenty-six patients died in the probiotic versus 20 in the placebo group (P = 0.38)., Conclusions: Bifidobacterium animalis subsp lactis and Lactobacillus rhamnosus had no effect on diarrhea in children with SAM during hospitalization, but reduced the number of days with diarrhea in outpatient treatment by 26%. Probiotics may have a role in follow-up of hospitalized children with SAM or in community-based treatment of malnourished children, but further studies are needed to confirm this.