Correction: Effectiveness of a monthly schedule of follow-up for the treatment of uncomplicated severe acute malnutrition in Sokoto, Nigeria: A cluster randomized crossover trial.

[This corrects the article DOI: 10.1371/journal.pmed.1003923.].

Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial.

BACKGROUND: Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition. METHODS: We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls. FINDINGS: In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome. INTERPRETATION: Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment. FUNDING: Bill & Melinda Gates Foundation; Médecins sans Frontières Operational Center Paris; National Institute of Allergy and Infectious Diseases; National Institute of General Medical Sciences; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Edward Mallinckrodt Jr Foundation; Doris Duke Foundation.

Health care seeking behaviors of pregnant women in rural Amhara, Ethiopia: a qualitative study of perceptions of pregnant women, community members, and health care providers.

Introduction: in Ethiopia, increasing access to basic antenatal and neonatal health services may improve maternal and newborn survival. This study examined perceptions regarding antenatal health seeking behaviors from pregnant women, their families, community members, and health care providers in rural Amhara, Ethiopia. Methods: the study was conducted in four rural districts of the Amhara region of Ethiopia. A total of forty participants who were living and working within the catchment areas of the selected health centres were interviewed from October 3rd through October 14th, 2018. A phenomenological qualitative study design was used to understand participants' perceptions and experiences about pregnant women's health care seeking behaviors. Results: early disclosure of pregnancy status was not common in the study area. However, the data from the present study further provided new information, suggesting that some women did disclose their pregnancy status early but preferentially only to their partners and close relatives. Most women did not seek care unless sick or experienced new discomfort or pain. Some reasons for the low utilization of available antenatal services include long distance to health facilities, lack of transportation, difficult topography, and discomfort with male providers. Conclusion: despite the rapid expansion of health posts and deployment of health extension workers since 2003, there are still critical barriers to accessing facility-based care that limit women's health care seeking practices.

Dietary Iron Intake and HIV-Related Outcomes Among Adults Initiating Antiretroviral Therapy in Tanzania.

OBJECTIVE: Anemia is highly prevalent among people living with HIV (PLWHIV) and is often due to iron deficiency. This study evaluated the relationship of dietary iron intake levels and sources with mortality and clinical outcomes among adults initiating HAART. DESIGN: We conducted a secondary analysis of a multivitamin supplementation trial among 2293 PLWHIV initiating HAART in Dar es Salaam, Tanzania. METHODS: Dietary iron intake was assessed with a food frequency questionnaire at HAART initiation, and participants followed until death or censoring. Total, animal-, and plant-sourced iron were categorized into quartiles. Intake of food groups was categorized into 0-1, 2-3, and ≥4 servings/wk. Cox proportional hazards models estimated hazard ratios for mortality and incident clinical outcomes. RESULTS: There were 175 deaths (8%). Red meat intake was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.35 to 0.83), AIDS-related mortality (HR: 0.49; 95% CI: 0.28 to 0.85), and severe anemia (HR: 0.57; 95% CI: 0.35 to 0.91), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Legume intake was a lower risk of associated with all-cause mortality (HR: 0.49; 95% CI: 0.31 to 0.77) and AIDS-related mortality (HR: 0.37; 95% CI: 0.23 to 0.61), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Although total dietary iron and overall plant-sourced iron intake were not associated with the risk of mortality or HIV-related outcomes, the highest quartile of animal-sourced iron intake was associated with a lower risk of all-cause mortality (HR: 0.56; 95% CI: 0.35 to 0.90) and a lower risk of AIDS-related mortality (HR: 0.50; 95% CI: 0.30 to 0.90), compared with the lowest quartile. CONCLUSION: Intake of iron-rich food groups may be associated with a lower risk of mortality and critical HIV-related outcomes among adults initiating HAART. TRIAL REGISTRATION: The parent trial was registered at Clinicaltrials.gov . Identifier: NCT00383669.

Dietary Perspectives and Practices during Pregnancy in Rural Amhara Region of Ethiopia: An Exploratory Qualitative Study.

Background: Nutrition during pregnancy has lifelong impacts on the mother and fetus. In Ethiopia, nearly a third of pregnant women experience undernutrition. When designing nutrition interventions during pregnancy, it is important to understand existing dietary perspectives and practices in local communities. Objectives: To explore the processes that shape dietary perspectives and practices during pregnancy in rural West Gojjam and South Gondar Zones of the Amhara region in Ethiopia. Methods: From October to November 2018, we conducted 40 in-depth interviews with pregnant women (n = 16), family members (n = 12), and healthcare providers (n = 12) using a semistructured interview guide. Interviews were conducted in Amharic, transcribed in Amharic, and translated into English. We used a thematic analysis approach to organize data per the predefined topic areas and identify emerging themes, as well as barriers and enablers to healthy nutrition during pregnancy. Results: Pregnant women and their family members recognized the benefits of a diversified diet to promote the health of the mother and the fetus. However, participants reported low dietary diversity because of limited access to nutritious foods and particular perspectives on food restrictions during pregnancy. The common practice of religious fasting also limited pregnant women's dietary intake. Women reported restricting their food intake in later pregnancy because of loss of appetite, as well as concerns about having a large infant, which might complicate delivery. Intake of locally made alcoholic drinks (Tella) was reported among pregnant women because participants thought it had low levels of alcohol that would not harm the fetus. Conclusions: Although participants understood the importance of a healthy and diverse diet in pregnancy, we identified several barriers and perspectives regarding nutrition during pregnancy. Low income and lack of access to diverse foods, particularly in certain seasons, religious fasting, intentional food restrictions to limit the size of the infant, and alcohol use were commonly reported. Locally appropriate counseling and interventions should be developed, with an emphasis on increasing access to and consumption of diverse foods. Curr Dev Nutr 2023;x:xx.

Analysis of Postdischarge Interventions for Children Treated for Moderate or Severe Wasting, Growth Faltering or Failure, or Edema: A Systematic Review.

Importance: Children treated for acute malnutrition remain at increased risk of relapse, infection, and mortality after programmatic recovery. Global guidelines for the management of acute malnutrition currently provide no recommendations to sustain recovery following treatment discharge. Objective: To inform guideline development by evaluating the evidence on postdischarge interventions to improve outcomes within 6 months after discharge. Evidence Review: In this systematic review, 8 databases were searched from inception through December 2021 and included randomized and quasi-experimental studies investigating interventions delivered after discharge from nutritional treatment for children aged 0 to 59 months. Outcomes were relapse, deterioration to severe wasting, readmission, sustained recovery, anthropometry, all-cause mortality, and morbidity within 6 months after discharge. The risk of bias was assessed using Cochrane tools, and the certainty of the evidence was evaluated with the GRADE approach. Findings: Of 7124 records identified, 8 studies, conducted in 7 countries between 2003 and 2019 with 5965 participants, were included. The study interventions included antibiotic prophylaxis (n = 1), zinc supplementation (n = 1), food supplementation (n = 2), psychosocial stimulation (n = 3), unconditional cash transfers (n = 1), and an integrated biomedical, food supplementation, and malaria prevention package (n = 1). Risk of bias was moderate or high for half the studies. Only unconditional cash transfers were associated with reduced relapse, while the integrated package was associated with improved sustained recovery. Zinc supplementation, food supplementation, psychosocial stimulation, and unconditional cash transfers were associated with improvements in postdischarge anthropometry, while zinc supplementation was associated with reductions in multiple postdischarge morbidities. Conclusions and Relevance: In this systematic review of postdischarge interventions to reduce relapse and improve other postdischarge outcomes among children treated for acute malnutrition, evidence was limited. Biomedical, cash, and integrated interventions showed promise in improving certain postdischarge outcomes for children treated for moderate or severe acute malnutrition in single studies. Further evidence on the efficacy, effectiveness, and operational feasibility of postdischarge interventions in other contexts is needed to inform global guidance development.

Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

OBJECTIVE: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. DESIGN: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. SETTING: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. PARTICIPANTS: Children aged 6 to 59 months. RESULTS: Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. CONCLUSIONS: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Prognostic value of different anthropometric indices over different measurement intervals to predict mortality in 6-59-month-old children.

OBJECTIVE: To compare the prognostic value of mid-upper arm circumference (MUAC), weight-for-height Z-score (WHZ) and weight-for-age Z-score (WAZ) for predicting death over periods of 1, 3 and 6 months follow-up in children. DESIGN: Pooled analysis of twelve prospective studies examining survival after anthropometric assessment. Sensitivity and false-positive ratios to predict death within 1, 3 and 6 months were compared for three individual anthropometric indices and their combinations. SETTING: Community-based, prospective studies from twelve countries in Africa and Asia. PARTICIPANTS: Children aged 6-59 months living in the study areas. RESULTS: For all anthropometric indices, the receiver operating characteristic curves were higher for shorter than for longer durations of follow-up. Sensitivity was higher for death with 1-month follow-up compared with 6 months by 49 % (95 % CI (30, 69)) for MUAC < 115 mm (P < 0·001), 48 % (95 % CI (9·4, 87)) for WHZ < -3 (P < 0·01) and 28 % (95 % CI (7·6, 42)) for WAZ < -3 (P < 0·005). This was accompanied by an increase in false positives of only 3 % or less. For all durations of follow-up, WAZ < -3 identified more children who died and were not identified by WHZ < -3 or by MUAC < 115 mm, 120 mm or 125 mm, but the use of WAZ < -3 led to an increased false-positive ratio up to 16·4 % (95 % CI (12·0, 20·9)) compared with 3·5 % (95 % CI (0·4, 6·5)) for MUAC < 115 mm alone. CONCLUSIONS: Frequent anthropometric measurements significantly improve the identification of malnourished children with a high risk of death without markedly increasing false positives. Combining two indices increases sensitivity but also increases false positives among children meeting case definitions.

Conceptualising factors impacting nutrition services coverage of treatment for acute malnutrition in children: an application of the Three Delays Model in Niger.

OBJECTIVE: The Three Delays Model is a conceptual model traditionally used to understand contributing factors of maternal mortality. It posits that most barriers to health services utilisation occur in relation to one of three delays: (1) Delay 1: delayed decision to seek care; (2) Delay 2: delayed arrival at health facility and (3) Delay 3: delayed provision of adequate care. We applied this model to understand why a community-based management of acute malnutrition (CMAM) services may have low coverage. DESIGN: We conducted a Semi-Quantitative Evaluation of Access and Coverage (SQUEAC) over three phases using mixed methods to estimate programme coverage and barriers to care. In this manuscript, we present findings from fifty-one semi-structured interviews with caregivers and programme staff, as well as seventy-two structured interviews among caregivers only. Recurring themes were organised and interpreted using the Three Delays Model. SETTING: Madaoua, Niger. PARTICIPANTS: Totally, 123 caregivers and CMAM program staff. RESULTS: Overall, eleven barriers to CMAM services were identified in this setting. Five barriers contribute to Delay 1, including lack of knowledge around malnutrition and CMAM services, as well as limited family support, variable screening services and alternative treatment options. High travel costs, far distances, poor roads and competing demands were challenges associated with accessing care (Delay 2). Finally, upon arrival to health facilities, differential caregiver experiences around quality of care contributed to Delay 3. CONCLUSIONS: The Three Delays Model was a useful model to conceptualise the factors associated with CMAM uptake in this context, enabling implementing agencies to address specific barriers through targeted activities.

How Can Nutrition Research Better Reflect the Relationship Between Wasting and Stunting in Children? Learnings from the Wasting and Stunting Project.

Childhood wasting and stunting affect large numbers of children globally. Both are important risk factors for illness and death yet, despite the fact that these conditions can share common risk factors and are often seen in the same child, they are commonly portrayed as relatively distinct manifestations of undernutrition. In 2014, the Wasting and Stunting project was launched by the Emergency Nutrition Network. Its aim was to better understand the complex relationship and associations between wasting and stunting and examine whether current separations that were apparent in approaches to policy, financing, and programs were justified or useful. Based on the project's work, this article aims to bring a wasting and stunting lens to how research is designed and financed in order for the nutrition community to better understand, prevent, and treat child undernutrition. Discussion of lessons learnt focuses on the synergy and temporal relationships between children's weight loss and linear growth faltering, the proximal and distal factors that drive diverse forms of undernutrition, and identifying and targeting people most at risk. Supporting progress in all these areas requires research collaborations across interest groups that highlight the value of research that moves beyond a focus on single forms of undernutrition, and ensures that there is equal attention given to wasting as to other forms of malnutrition, wherever it is present.

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Impact and cost-effectiveness of rotavirus vaccination in Niger: a modelling study evaluating alternative rotavirus vaccines.

OBJECTIVES: To evaluate the cost-effectiveness of alternative rotavirus vaccines in Niger, using UNIVAC, a proportionate outcomes model. SETTING: The study leverages global, regional and local data to inform cost-effectiveness modelling. Local data were collected as part of a clinical trial taking place in the Madarounfa district, Maradi region, Niger. PARTICIPANTS: The study models impact of infants vaccination on rotavirus gastroenteritis in children under 5 years of age. INTERVENTIONS: We compared the use of ROTARIX (GlaxoSmithKline, Belgium), ROTAVAC (Bharat Biotech, India) and ROTASIIL (Serum Institute, India) to no vaccination and to each other over a 10-year period starting in 2021. RESULTS: We estimated that ROTARIX, ROTAVAC and ROTASIIL would each prevent 13 million cases and 20 000 deaths of children under 5 years over a 10-year period in Niger. Compared with no vaccination, the cost to avert a disability-adjusted life-year was US$146 with ROTARIX, US$107 with ROTASIIL and US$76 with ROTAVAC from the government perspective. ROTAVAC dominated ROTARIX and ROTASIIL (eg, provided similar or higher benefits at a lower cost) and had 90% chance to be cost-effective at a US$100 willingness-to-pay threshold. CONCLUSIONS: This study can inform decision-making around rotavirus vaccination policy in Niger, demonstrating that ROTAVAC is likely the most cost-effective option. Alternative products (ROTASIIL and ROTARIX) may also be considered by decision-makers if they are priced more competitively, or if their cold chain requirements could bring additional economic benefits.

Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study: protocol of a pragmatic clinical effectiveness study to improve birth outcomes in Ethiopia.

INTRODUCTION: The WHO Nutrition Target aims to reduce the global prevalence of low birth weight by 30% by the year 2025. The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study will test the impact of packages of pregnancy interventions to enhance maternal nutrition and infection management on birth outcomes in rural Ethiopia. METHODS AND ANALYSIS: ENAT is a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. Eligible pregnant women presenting at antenatal care (ANC) visits at <24 weeks gestation are enrolled (n=2400). ANC quality is strengthened across all centres. Health centres are randomised to receive an enhanced nutrition package (ENP) or standard nutrition care, and within each health centre, individual women are randomised to receive an enhanced infection management package (EIMP) or standard infection care. At ENP centres, women receive a regular supply of adequately iodised salt and iron-folate (IFA), enhanced nutrition counselling and those with mid-upper arm circumference of <23 cm receive a micronutrient fortified balanced energy protein supplement (corn soya blend) until delivery. In standard nutrition centres, women receive routine counselling and IFA. EIMP women have additional screening/treatment for urinary and sexual/reproductive tract infections and intensive deworming. Non-EIMP women are managed syndromically per Ministry of Health Guidelines. Participants are followed until 1-month post partum, and a subset until 6 months. The primary study outcomes are newborn weight and length measured at <72 hours of age. Secondary outcomes include preterm birth, low birth weight and stillbirth rates; newborn head circumference; infant weight and length for age z-scores at birth; maternal anaemia; and weight gain during pregnancy. ETHICS AND DISSEMINATION: ENAT is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (001-A1-2019) and Mass General Brigham (2018P002479). Results will be disseminated to local and international stakeholders. REGISTRATION NUMBER: ISRCTN15116516.

Cost-effectiveness of routine versus indicated antibiotic therapy in the management of severe wasting in children.

BACKGROUND: In the outpatient management of severe wasting, routine antibiotic therapy is recommended for all children upon admission regardless of whether clinical signs of infection are present. Indicated antibiotic therapy, where antibiotics are provided only upon presentation of clinical signs of infection, may be considered for its potential to allow for more prudent antibiotic use and greater program coverage, reducing the risk of antibiotic resistance as well as costs and logistical burdens associated with treatment. We therefore conducted a cost-effectiveness analysis to measure the effects of indicated antibiotic therapy compared to routine antibiotic therapy in terms of incremental cost-per-life-year saved in Niger. METHODS: We used a cohort model to conduct a cost-effectiveness analysis from a healthcare system perspective to project and weigh the lifetime discounted costs and effects of indicated antibiotic therapy compared to routine antibiotic therapy in the treatment of uncomplicated severe wasting in children in Niger. We calculated incremental cost-effectiveness ratios (ICERs) in terms of treatment-related healthcare costs per discounted life-years saved (LYS), and conducted program coverage scenario and sensitivity analyses to assess model uncertainty. RESULTS: The ICER for indicated antibiotic therapy compared to routine antibiotic therapy was $8.5/LYS, which is under the cost-effectiveness threshold for Niger. The probability of the indicated strategy being optimal was 76.1% when program coverage was equal to coverage associated with routine therapy but was 100% likely to be optimal in probabilistic sensitivity analysis scenarios where indicated program coverage improved 5 percentage points. CONCLUSIONS: Indicated antibiotic therapy likely represents a cost-effective strategy, particularly if indicated treatment can result in expanded coverage. With the risk of increasing antibiotic resistance worldwide, antibiotic stewardship and simplified treatment protocols for severe wasting using indicated antibiotic therapy may represent good value for money in some low risk populations.

Burden and risk factors for relapse following successful treatment of uncomplicated severe acute malnutrition in young children: Secondary analysis from a randomised trial in Niger.

This study aimed to quantify the burden of relapse following successful treatment for uncomplicated severe acute malnutrition (SAM) and to identify associated risk factors in rural Niger. We used data from 1490 children aged 6-59 months discharged as recovered from an outpatient nutritional programme for SAM and followed for up to 12 weeks after admission. Postdischarge SAM relapse was defined as weight-for-height Z-score <-3, mid-upper arm circumference (MUAC) <115 mm or bipedal oedema after having been discharged as recovered. Postdischarge hospitalisation was defined as admission to inpatient SAM treatment or hospitalisation for any cause after having been discharged as recovered. We used multivariate log-binomial models to identify independent risk factors. After programmatic discharge, 114 (8%) children relapsed to SAM and 89 (6%) were hospitalised. Factors associated with SAM relapse were discharge during the lean season (relative risk [RR] = 1.80 [95% confidence interval [CI] = 1.22-2.67]) and larger household size (RR = 1.56 [95% CI = 1.01-2.41]), whereas older child age (RR = 0.94 [95% CI = 0.88-1.00]), higher child MUAC at discharge (RR = 0.93 [95% CI = 0.87-1.00]) and maternal literacy (RR = 0.54 [95% CI = 0.29-0.98]) were protective factors. Discharge during the lean season (RR = 2.27 [95% CI = 1.46-3.51]) was independently associated with postdischarge hospitalisation. Future nutritional programmes in the context of Niger may consider modification of anthropometric discharge criteria or the provision of additional home support or follow-up during the lean season as potential interventions to prevent relapse. More research including postdischarge follow-up is needed to better understand the sustainability of treatment outcomes after discharge and the type of intervention that may best sustain recovery over time. Clinical Trial Registration: ClinicalTrials.gov number, NCT01613547.

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.

BACKGROUND: It is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials. METHODS AND FINDINGS: We conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: -0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: -0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: -0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: -0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: -0.22, 0.44; p = 0.53) or motor scores (SMD: -0.04; 95% CI: -0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages. CONCLUSIONS: There was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones. TRIAL REGISTRATION: ClinicalTrials.gov NCT02145000.

Risk of community- and hospital-acquired bacteremia and profile of antibiotic resistance in children hospitalized with severe acute malnutrition in Niger.

OBJECTIVE: To estimate the prevalence and antibiotic resistance profile of community- and hospital-acquired bacteremia among hospitalized children with severe acute malnutrition in Niger. METHODS: A descriptive, longitudinal study was conducted in an intensive nutritional rehabilitation center in Madarounfa, Niger. Children aged 6 to 59 months admitted for inpatient treatment of complicated severe acute malnutrition (n=2187) had blood specimens drawn at admission to assess prevalence of community-acquired bacteremia. Subsequent specimens were drawn per physician discretion to assess incidence of hospital-acquired bacteremia. Antibiotic susceptibility testing was performed on positive blood cultures. RESULTS: The prevalence of community-acquired bacteremia at admission was at least 9.1% (95% confidence interval [CI]: 8.1, 10.4%), with non-typhoid Salmonella identified in over half (57.8%) of cases. The cumulative incidence of hospital-acquired bacteremia was estimated at 1.2% (95% CI: 0.8, 1.7%), among which the most common organisms were Klebsiella pneumoniae (19.4%), Acinetobacter baumannii (16.1%), Enterococcus faecalis (12.9%), and Escherichia coli (12.9%). In community-acquired bacteremia, 58% cases were resistant to amoxicillin-clavulanate; 100% of hospital-acquired bacteremia cases were resistant to amoxicillin and amoxicillin-clavulanate. Mortality risk was elevated among children with hospital-acquired bacteremia (risk ratio [RR] = 9.32) and community-acquired bacteremia (RR = 2.67). CONCLUSION: Bacteremia was a significant contributor to mortality. Antibiotic resistance poses a challenge to effective clinical management of severe acute malnutrition.

Acceptability of 11 fortified balanced energy-protein supplements for pregnant women in Nepal.

Evidence suggests that multiple micronutrient and balanced energy protein (BEP) supplementation during pregnancy can decrease the risk of stillbirth and small-for-gestational-age births and increase birth weight. We conducted a mixed-methods formative research study to identify the most acceptable among a range of 11 candidates fortified BEP supplements for use in pregnancy and lactation in a rural district in Nepal. Forty pregnant women aged 15-40 years participated in a test meal tasting of 11 different sweet and savoury candidate BEP supplements. Each participant rated the products on organoleptic properties using a 7-point hedonic scale (1 = Dislike it very much to 7 = Like it very much), ranked her 'top 3' most liked supplements, and subsequently discussed each product with peers in focus group discussions (FGDs). Five supplements (sweet lipid-based nutrient supplement (LNS), savoury LNS, sweet vanilla biscuits, vanilla instant drinks and seasoned pillows) achieved the maximum overall median hedonic score of 7, with sweet LNS and seasoned pillows ranking as the top 2. This was consistent with the assessments in FGDs. Women in the FGDs expressed dislike of the smell and taste of the cocoa drink, savoury masala bar, sweet mango bar and savoury curry biscuit, which was consistent with the hedonic scale scores. This study provides valuable insights into our understanding of women's acceptance of different BEP supplements during pregnancy in rural Nepal and has helped identify the two most accepted BEP supplements to be used in a two-month home trial to assess utilisation and compliance in this setting.

Effectiveness of a monthly schedule of follow-up for the treatment of uncomplicated severe acute malnutrition in Sokoto, Nigeria: A cluster randomized crossover trial.

BACKGROUND: Community-based management of severe acute malnutrition (SAM) involves weekly or biweekly outpatient clinic visits for clinical surveillance and distribution of therapeutic foods. Distance to outpatient clinics and high opportunity costs for caregivers can represent major barriers to access. Reducing the frequency of outpatient visits while providing training to caregivers to recognize clinical danger signs at home between outpatient visits may increase acceptability, coverage, and public health impact of SAM treatment. We investigated the effectiveness of monthly clinic visits compared to the standard weekly follow-up in the outpatient treatment of uncomplicated SAM in northwestern Nigeria. METHODS AND FINDINGS: We conducted a cluster randomized crossover trial to test the noninferiority of nutritional recovery in children with uncomplicated SAM receiving monthly follow-up compared to the standard weekly schedule. From January 2018 to November 2019, 3,945 children aged 6 to 59 months were enrolled at 10 health centers (5 assigned to monthly follow-up and 5 assigned to weekly follow-up) in Sokoto, Nigeria. In total, 96% of children (n = 1,976 in the monthly follow-up group and 1,802 in the weekly follow-up group) were followed until program discharge, and 91% (n = 1,873 in the monthly follow-up group and 1,721 in the weekly follow-up group) were followed to 3 months postdischarge. The mean age at admission was 15.8 months (standard deviation [SD] 7.1), 2,097/3,945 (53.2%) were girls, and the mean midupper arm circumference (MUAC) at admission was 105.8 mm (SD 6.0). In a modified intention-to-treat analysis, the primary outcome of nutritional recovery, defined as having MUAC ≥125 mm on 2 consecutive visits, was analyzed using generalized linear models, with generalized estimating equations to account for clustering. Nutritional recovery was lower in the monthly follow-up group compared to the weekly group (1,036/1,976, 52.4% versus 1,059/1,802, 58.8%; risk difference: -6.8%), and noninferiority was not demonstrated (lower bound of the confidence interval [CI] was -11.5%, lower than the noninferiority margin of 10%). The proportion of children defaulting was lower in the monthly group than in the weekly group (109/1,976, 5.5% versus 151/1,802, 8.4%, p = 0.03). Three months postdischarge, children in the monthly group were less likely to relapse compared to those in the weekly group (58/976, 5.9% versus 78/1,005, 7.8%, p = 0.03), but cumulative mortality at 3 months postdischarge was higher in the monthly group (159/1,873, 8.5% versus 106/1,721, 6.2%, p < 0.001). Study results may depend on context-specific factors including baseline level of care and the clinical status of children presenting to health centers, and, thus, generalizability of these results may be limited. CONCLUSIONS: Where feasible, a weekly schedule of clinic visits should be preferred to maintain effectiveness of SAM treatment. Where geographic coverage of programs is low or frequent travel to outpatient clinics is difficult or impossible, a monthly schedule of visits may provide an alternative model to deliver treatment to those in need. Modifications to the outpatient follow-up schedule, for example, weekly clinic visits until initial weight gain has been achieved followed by monthly visits, could increase the effectiveness of the model and add flexibility for program delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03140904.

Cost-effectiveness of monthly follow-up for the treatment of uncomplicated severe acute malnutrition: An economic evaluation of a randomized controlled trial.

Severe acute malnutrition (SAM) is a major source of mortality for children in low resource settings. Alternative treatment models that improve acceptability and reduce caregiver burden are needed to improve treatment access. We assessed costs and cost-effectiveness of monthly vs. weekly follow-up (standard-of-care) for treating uncomplicated SAM in children 6-59 months of age. To do so, we conducted a cost-effectiveness analysis of a cluster-randomized trial of treatment for newly-diagnosed uncomplicated SAM in northwestern Nigeria (clinicaltrials.gov ID NCT03140904). We collected empirical costing data from enrollment up to 3 months post-discharge. We quantified health outcomes as the fraction of children recovered at discharge (primary cost-effectiveness outcome), the fraction recovered 3 months post-discharge, and total DALYs due to acute malnutrition. We estimated cost-effectiveness from both provider and societal perspectives. Costs are reported in 2019 US dollars. Provider costs per child were $67.07 (95% confidence interval: $64.79, $69.29) under standard-of-care, and $78.74 ($77.06, $80.66) under monthly follow-up. Patient costs per child were $21.04 ($18.18, $23.51) under standard-of-care, and $14.16 ($12.79, $15.25) under monthly follow-up. Monthly follow-up performed worse than standard-of-care for each health outcome assessed and was dominated (produced worse health outcomes at higher cost) by the standard-of-care in cost-effectiveness analyses. This result was robust to statistical uncertainty and to alternative costing assumptions. These findings provide evidence against monthly follow-up for treatment of uncomplicated SAM in situations where weekly follow-up of patients is feasible. While monthly follow-up may reduce burdens on caregivers and providers, other approaches are needed to do so while maintaining the effectiveness of care.