Search

Context: Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.Objective: To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.Design, Setting, and Participants: A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.Main Outcome Measure: The composite of HIV disease progression or death from any cause.Results: The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.Trial Registration: Clinicaltrials.gov Identifier: NCT00383669. [ABSTRACT FROM AUTHOR]

Context: Ready-to-use therapeutic foods (RUTFs) are an important component of effective outpatient treatment of severe wasting. However, their effectiveness in the population-based prevention of moderate and severe wasting has not been evaluated.Objective: To evaluate the effect of a 3-month distribution of RUTF on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger.Design, Setting, and Participants: A cluster randomized trial of 12 villages in Maradi, Niger. Six villages were randomized to intervention and 6 to no intervention. All children in the study villages aged 6 to 60 months were eligible for recruitment.Intervention: Children with weight-for-height 80% or more of the National Center for Health Statistics reference median in the 6 intervention villages received a monthly distribution of 1 packet per day of RUTF (92 g [500 kcal/d]) from August to October 2006. Children in the 6 nonintervention villages received no preventive supplementation. Active surveillance for conditions requiring medical or nutritional treatment was conducted monthly in all 12 study villages from August 2006 to March 2007.Main Outcome Measures: Changes in weight-for-height z score (WHZ) according to the World Health Organization Child Growth Standards and incidence of wasting (WHZ <-2) over 8 months of follow-up.Results: The number of children with height and weight measurements in August, October, December, and February was 3166, 3110, 2936, and 3026, respectively. The WHZ difference between the intervention and nonintervention groups was -0.10 z (95% confidence interval [CI], -0.23 to 0.03) at baseline and 0.12 z (95% CI, 0.02 to 0.21) after 8 months of follow-up. The adjusted effect of the intervention on WHZ from baseline to the end of follow-up was thus 0.22 z (95% CI, 0.13 to 0.30). The absolute rate of wasting and severe wasting, respectively, was 0.17 events per child-year (140 events/841 child-years) and 0.03 events per child-year (29 events/943 child-years) in the intervention villages, compared with 0.26 events per child-year (233 events/895 child-years) and 0.07 events per child-year (71 events/1029 child-years) in the nonintervention villages. The intervention thus resulted in a 36% (95% CI, 17% to 50%; P < .001) reduction in the incidence of wasting and a 58% (95% CI, 43% to 68%; P < .001) reduction in the incidence of severe wasting. There was no reduction in mortality, with a mortality rate of 0.007 deaths per child-year (7 deaths/986 child-years) in the intervention villages and 0.016 deaths per child-year (18 deaths/1099 child-years) in the nonintervention villages (adjusted hazard ratio, 0.51; 95% CI, 0.25 to 1.05).Conclusion: Short-term supplementation of nonmalnourished children with RUTF reduced the decline in WHZ and the incidence of wasting and severe wasting over 8 months.Trial Registration: clinicaltrials.gov Identifier: NCT00682708. [ABSTRACT FROM AUTHOR]

Background: Balanced energy protein (BEP) supplementation in pregnant women in low-and middle-income countries may reduce the risk of stillbirth and low birth weight., Objectives: The objective of this study was to assess the adherence to and acceptability of a corn-soy blend (CSB) BEP product among pregnant women in rural Ethiopia., Methods: This formative study was conducted from October to November 2018 among pregnant women in the rural Amhara region of Ethiopia prior to initiation of a clinical effectiveness study (ISRCTN: 15116516). We assessed adherence and acceptability of a micronutrient-fortified CSB BEP supplement among 40 pregnant women during a 4-wk utilization period. Acceptability was assessed using a 7-point Likert-style scale about the hedonic characteristics of the BEP product at 2 wk and 4 wk. Adherence was assessed by weekly monitoring and empty sachet counts for BEP consumption over 4 wk., Results: Adherence to the BEP was, on average, 89% over the month-long pilot. The BEP product was rated favorably (mean Likert score >6 of 7) for the following domains: color, taste, odor, and likeability at mid and endpoints. Women found the product convenient to eat [mean (standard deviation [SD] = 5.9 (1.0))] and filling (mean (SD) = 6.1 (1.5) out of 7). Scores on acceptability and perception of the product remained stable throughout the duration of use. A majority of women (63%) reported consuming the BEP as a snack to supplement meals and splitting the serving over 2 or more sessions (68%). A quarter of respondents reported sharing the supplement with family members., Conclusions: Adherence and acceptability of the CSB BEP product were high among this population in rural Amhara, Ethiopia. This formative data was important to select the final product and shape the counseling and delivery of BEP in the parent study., (© 2024 The Authors.)

Introduction: Current guidelines for the outpatient treatment of severe acute malnutrition (SAM) recommend the provision of routine medications to all children at admission and prescribed medications as clinically indicated thereafter. The objective of this study was to describe the amount and purpose of medications prescribed during outpatient SAM treatment and explore the effect of routine antibiotics at admission on subsequent medication prescription., Methods: Medications prescribed during outpatient treatment were described by medication category, time from admission, and diagnoses among children with SAM in a placebo-controlled, double-blind trial of 7-day amoxicillin use. Total medications were compared by parent trial intervention arm (amoxicillin vs placebo) and differences assessed using Χ 2 and two-sample t-tests., Results: Of the 2399 children enrolled, 74.6% of children received ≥1 prescribed medication during outpatient treatment. Antipyretics/analgesics (44.1% of children), antimalarials (56.6%) and antibiotics (30.0%) were prescribed most frequently. Children who received placebo in the parent trial received fewer total medications (mean difference: -0.80, 95% CI: -0.96 to -0.65) and oral antibiotics (mean difference: -0.96, 95% CI: -0.99 to -0.92) during treatment compared with children who received routine amoxicillin., Conclusions: We found high rates of medication prescription during outpatient treatment for SAM, but fewer total medications and oral antibiotics prescribed to children receiving placebo in the parent trial. Our findings underscore the role of outpatient treatment programmes as an important source of medicine prescription and suggest that provision of antibiotics on a clinically indicated basis for outpatient SAM cases may be a strategy to support prudent antibiotic use in certain settings., Trial Registration Number: ClinicalTrials.gov Registry (NCT01613547; https://clinicaltrials.gov/ct2/show/NCT01613547)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 3 rd through October 14 th , 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., Competing Interests: The authors declare no competing interests., (Copyright: Fisseha Shiferie et al.)

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.

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.

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.

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., (© 2023 The Authors.)

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.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Menzies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

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., (© 2022. The Author(s).)

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., (© 2022 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

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., (Copyright © 2022. Published by Elsevier Ltd.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RFG is an Academic Editor on PLOS Medicine’s editorial board.

Some evidence suggests that balanced energy protein (BEP) supplements taken during pregnancy and lactation can have positive effects on birth outcomes such as small-for-gestational age and birthweight, but more evidence is needed on the long-term use and acceptability of such supplements. We conducted a mixed-methods formative research study to assess and compare compliance with and acceptability of two BEP supplements, a lipid-based peanut paste and a biscuit, to identify BEP supplements for subsequent inclusion in an efficacy trial. We conducted an 8-week feeding trial of daily supplementation among two groups of 40 pregnant women each in rural Nepal. Compliance data were collected and supplements distributed at the weekly visits. Sensory properties of the supplements were assessed using a 7-point Likert scale. In addition, in-depth interviews with women (n = 16), family members (n = 6) and health workers (n = 6) and focus group discussions (FGDs) (n = 4) were conducted to explore themes related to general use and intention of future use of the supplement. Overall self-reported compliance was high: medians of 91.1% in the lipid-based peanut paste group and 96.4% in the biscuit group. Both supplements were rated highly on overall likability (median score 6/7) and sensory properties. Qualitative findings showed that sustained use of the supplements was attributed to expected health benefits, favourable sensory attributes, and family support. The FGDs suggested providing the option to choose between more than one type/flavour of supplements to improve compliance. Sharing was mostly evident in the first week with higher sharing reported in the biscuit group., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Prenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) can improve birth outcomes relative to iron-folic acid supplementation (IFA); however, effects on child postnatal growth remain unclear., Objectives: The aim was to compare the effect of prenatal MMS, medium-quantity LNS (MQ-LNS), and IFA on child growth up to 2 y of age., Methods: We conducted a cluster randomized controlled trial of prenatal nutritional supplementation in Madarounfa, Niger. Villages were randomly assigned for pregnant women to receive IFA (17 villages, 1105 women), MMS (18 villages, 1083 women) or MQ-LNS (18 villages, 1144 women). Pregnant women received nutritional supplements weekly until delivery, and children were followed up monthly from 6-8 wk to 24 mo of age. We assessed the effect of prenatal MMS and MQ-LNS compared with IFA and the effect of prenatal MMS compared with MQ-LNS on child length-for-age z scores (LAZ), weight-for-age z scores (WAZ), and weight-for-length z scores (WLZ) at 24 mo of age using generalized linear models. In secondary analyses, we used mixed-effects models to assess the trajectories of anthropometric z scores longitudinally from 6-8 wk to 24 mo., Results: Compared with IFA, MMS and MQ-LNS had no effect on child LAZ, WAZ, or WLZ at 24 mo of age (P > 0.05). Children in the MQ-LNS arm had significantly higher mid-upper arm circumference at 24 mo than children in the MMS arm: mean difference 0.50 cm (95% CI 0.10, 0.91 cm). WAZ and WLZ trajectories were more negative in the MQ-LNS arm compared with IFA and MMS, with lower z scores from 14 to 20 mo of age. However, WAZ and WLZ trajectories converged after 20 mo of age, and there were no differences by 24 mo of age., Conclusions: Prenatal MMS and MQ-LNS had limited effect on anthropometric measures of child growth up to 24 mo of age as compared with IFA in rural Niger., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RFG is an Academic Editor on PLOS Medicine’s editorial board.

In 2014, the Emergency Nutrition Network published a report on the relationship between wasting and stunting. We aim to review evidence generated since that review to better understand the implications for improving child nutrition, health and survival. We conducted a systematic review following PRISMA guidelines, registered with PROSPERO. We identified search terms that describe wasting and stunting and the relationship between the two. We included studies related to children under five from low- and middle-income countries that assessed both ponderal growth/wasting and linear growth/stunting and the association between the two. We included 45 studies. The review found the peak incidence of both wasting and stunting is between birth and 3 months. There is a strong association between the two conditions whereby episodes of wasting contribute to stunting and, to a lesser extent, stunting leads to wasting. Children with multiple anthropometric deficits, including concurrent stunting and wasting, have the highest risk of near-term mortality when compared with children with any one deficit alone. Furthermore, evidence suggests that the use of mid-upper-arm circumference combined with weight-for-age Z score might effectively identify children at most risk of near-term mortality. Wasting and stunting, driven by common factors, frequently occur in the same child, either simultaneously or at different moments through their life course. Evidence of a process of accumulation of nutritional deficits and increased risk of mortality over a child's life demonstrates the pressing need for integrated policy, financing and programmatic approaches to the prevention and treatment of child malnutrition., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

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., Competing Interests: Competing interests: ACCL reports funding from the Bill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development and the WHO. YB reports funding from FORMAS, USAID, National Institute of Environmental Health Sciences and from the Bill & Melinda Gates Foundation. BJW reports funding from National Institute of Environmental Health Sciences and from the Bill & Melinda Gates Foundation., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: High-resolution data on the etiology of childhood diarrhea in countries with the highest burden and mortality remain sparse and are needed to inform burden estimates and prioritize interventions., Methods: We tested stool specimens collected between October 2014 and December 2017 from children under 2 years of age from the per-protocol population of a placebo-controlled clinical trial of a bovine rotavirus pentavalent vaccine (Rotasiil) in Niger. We tested 1729 episodes of moderate-to-severe diarrhea (Vesikari score ≥ 7) using quantitative PCR and estimated pathogen-specific burdens by age, season, severity, and trial intervention arm., Results: The 4 pathogens with the highest attributable incidence of diarrhea were Shigella (7.2 attributable episodes per 100 child-years; 95% confidence interval: 5.2, 9.7), Cryptosporidium (6.5; 5.8, 7.2), rotavirus (6.4; 5.9, 6.7), and heat-stabile toxin-producing enterotoxigenic Escherichia coli (ST-ETEC) (6.2; 3.1, 7.7). Cryptosporidium was the leading etiology of severe diarrhea (Vesikari score ≥ 11) and diarrhea requiring hospitalization. Shigella was the leading etiology of diarrhea in children 12-23 months of age but also had a substantial burden in the first year of life, with 60.5% of episodes of severe shigellosis occurring in infants. Shigella, Cryptosporidium, and ST-ETEC incidence peaked during the warmer and wetter period and coincided with peak all-cause diarrhea incidence., Conclusions: In this high-burden setting, the leading diarrheal pathogens were Shigella, Cryptosporidium, rotavirus, and ST-ETEC, and each was disproportionately seen in infants. Vaccine development should target these pathogens, and the impact of vaccine schedule on diarrhea burden in the youngest children will need to be considered., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society.)

Background: Poor diet quality is a major driver of both classical malnutrition and noncommunicable disease (NCD) and was responsible for 22% of adult deaths in 2017. Most countries face dual burdens of undernutrition and NCDs, yet no simple global standard metric exists for monitoring diet quality in populations and population subgroups., Objectives: We aimed to develop an easy-to-use metric for nutrient adequacy and diet related NCD risk in diverse settings., Methods: Using cross-sectional and cohort data from nonpregnant, nonlactating women of reproductive age in 10 African countries as well as China, India, Mexico, and the United States, we undertook secondary analyses to develop novel metrics of diet quality and to evaluate associations between metrics and nutrient intakes and adequacy, anthropometry, biomarkers, type 2 diabetes, and iteratively modified metric design to improve performance and to compare novel metric performance to that of existing metrics., Results: We developed the Global Diet Quality Score (GDQS), a food-based metric incorporating a more comprehensive list of food groups than most existing diet metrics, and a simple means of scoring consumed amounts. In secondary analyses, the GDQS performed comparably with the Minimum Dietary Diversity - Women indicator in predicting an energy-adjusted aggregate measure of dietary protein, fiber, calcium, iron, zinc, vitamin A, folate, and vitamin B12 adequacy and with anthropometric and biochemical indicators of undernutrition (including underweight, anemia, and serum folate deficiency), and the GDQS also performed comparably or better than the Alternative Healthy Eating Index - 2010 in capturing NCD-related outcomes (including metabolic syndrome, change in weight and waist circumference, and incident type 2 diabetes)., Conclusions: The simplicity of the GDQS and its ability to capture both nutrient adequacy and diet-related NCD risk render it a promising candidate for global monitoring platforms. Research is warranted to validate methods to operationalize GDQS assessment in population surveys, including a novel application-based 24-h recall system developed as part of this project., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2021.)

Background: The global diet quality score (GDQS) is a simple, standardized metric appropriate for population-based measurement of diet quality globally., Objectives: We aimed to operationalize data collection by modifying the quantity of consumption cutoffs originally developed for the GDQS food groups and to statistically evaluate the performance of the operationalized GDQS relative to the original GDQS against nutrient adequacy and noncommunicable disease (NCD)-related outcomes., Methods: The GDQS application uses a 24-h open-recall to collect a full list of all foods consumed during the previous day or night, and automatically classifies them into corresponding GDQS food group. Respondents use a set of 10 cubes in a range of predetermined sizes to determine if the quantity consumed per GDQS food group was below, or equal to or above food group-specific cutoffs established in grams. Because there is only a total of 10 cubes but as many as 54 cutoffs for the GDQS food groups, the operationalized cutoffs differ slightly from the original GDQS cutoffs., Results: A secondary analysis using 5 cross-sectional datasets comparing the GDQS with the original and operationalized cutoffs showed that the operationalized GDQS remained strongly correlated with nutrient adequacy and was equally sensitive to anthropometric and other clinical measures of NCD risk. In a secondary analysis of a longitudinal cohort study of Mexican teachers, there were no differences between the 2 modalities with the beta coefficients per 1 SD change in the original and operationalized GDQS scores being nearly identical for weight gain (-0.37 and -0.36, respectively, P < 0.001 for linear trend for both models) and of the same clinical order of magnitude for waist circumference (-0.52 and -0.44, respectively, P < 0.001 for linear trend for both models)., Conclusion: The operationalized GDQS cutoffs did not change the performance of the GDQS and therefore are recommended for use to collect GDQS data in the future., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2021.)

Background: Low birthweight (LBW) (< 2500 g) is a significant determinant of infant morbidity and mortality worldwide. In low-income settings, the quality of birthweight data suffers from measurement and recording errors, inconsistent data reporting systems, and missing data from non-facility births. This paper describes birthweight data quality and the prevalence of LBW before and after implementation of a birthweight quality improvement (QI) initiative in Amhara region, Ethiopia., Methods: A comparative pre-post study was performed in selected rural health facilities located in West Gojjam and South Gondar zones. At baseline, a retrospective review of delivery records from February to May 2018 was performed in 14 health centers to collect birthweight data. A birthweight QI initiative was introduced in August 2019, which included provision of high-quality digital infant weight scales (precision 5 g), routine calibration, training in birth weighing and data recording, and routine field supervision. After the QI implementation, birthweight data were prospectively collected from late August to early September 2019, and December 2019 to June 2020. Data quality, as measured by heaping (weights at exact multiples of 500 g) and rounding to the nearest 100 g, and the prevalence of LBW were calculated before and after QI implementation., Results: We retrospectively reviewed 1383 delivery records before the QI implementation and prospectively measured 1371 newborn weights after QI implementation. Heaping was most frequently observed at 3000 g and declined from 26% pre-initiative to 6.7% post-initiative. Heaping at 2500 g decreased from 5.4% pre-QI to 2.2% post-QI. The percentage of rounding to the nearest 100 g was reduced from 100% pre-initiative to 36.5% post-initiative. Before the QI initiative, the prevalence of recognized LBW was 2.2% (95% confidence interval [CI]: 1.5-3.1) and after the QI initiative increased to 11.7% (95% CI: 10.1-13.5)., Conclusions: A QI intervention can improve the quality of birthweight measurements, and data measurement quality may substantially affect estimates of LBW prevalence., (© 2021. The Author(s).)

Background: Wasting and stunting, physical growth manifestations of child undernutrition, have historically been considered separately with distinct interventions at the program, policy, and financing levels despite similar risk factors, overlapping burdens and multiplicative risk of death when the conditions are concurrent. The aim of this study was to elucidate shared risk factors and the temporal relationship between wasting and stunting among children under 2 years of age in rural Niger., Methods: From August 2014 to December 2019, anthropometric data were collected every 4 weeks from 6 to 8 weeks to 24 months of age for 6567 children comprising 139,529 visits in Madarounfa, Niger. Children were defined as wasted if they had a weight-for-length Z-score < - 2 and stunted if they had a length-for-age Z-score < - 2 using the 2006 World Health Organization child growth standards. Parental, child, and socioeconomic risk factors for wasting and stunting at 6 and 24 months of age and the relationship between episodes of wasting, stunting and concurrent wasting-stunting were assessed using general estimating equations., Results: Half of children (50%) were female, and 8.3% were born low birthweight (< 2500 g). Overall, at 24 months of age, 14% of children were wasted, 80% were stunted and 12% were concurrently wasted-stunted. We found that maternal short stature, male sex, and low birthweight were risk factors for wasting and stunting at 6 and 24 months, whereas higher maternal body mass index and household wealth were protective factors. Wasting at 6 and 24 months was predicted by a prior episodes of wasting, stunting, and concurrent wasting-stunting. Stunting at 6 and 24 months was similarly predicted by prior episodes of stunting and concurrent wasting-stunting at any prior age but only by prior episodes of wasting after 6 months of age., Conclusions: These data support a complex and dynamic bi-directional relationship between wasting and stunting in young children in rural Niger and an important burden of concurrent wasting-stunting in this setting. Further research to better understand the inter-relationships and mechanisms between these two conditions is needed in order to develop and target interventions to promote child growth., Trial Registration: ClinicalTrials.gov Identifier: NCT02145000 ., (© 2021. The Author(s).)

Background: The World Health Organization recommends the use of a weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC) as anthropometric criteria for the admission and discharge of young children for the community-based management of severe acute malnutrition. However, using MUAC as a single anthropometric criterion for admission and discharge in therapeutic nutritional programs may offer operational advantages to simplify admission processes at therapeutic nutritional centers and improve program coverage., Methods: This pragmatic, non-randomized, intervention study compared a standard outpatient nutritional program (n = 824) for the treatment of uncomplicated severe acute malnutrition using WHZ < - 3 and/or MUAC< 115 mm and/or bipedal edema for admission and discharge to a program (n = 1019) using MUAC as the sole anthropometric criterion for admission (MUAC< 120 mm) and discharge (MUAC ≥125 mm at two consecutive visits) in the Tahoua Region of Niger., Results: Compared to the standard program, the MUAC-only program discharged more children as recovered (70.1% vs. 51.6%; aOR 2.31, 95%CI 1.79-2.98) and fewer children as non-respondent or defaulters, based on respective program definitions. The risk of non-response was high in both programs. Three months post-discharge, children who were discharged after recovery in the MUAC-only program had lower WHZ and MUAC measures. Sixty-three children ineligible for the MUAC-only program but eligible for a standard program (MUAC ≥120 mm and WHZ < -3) were followed for twelve weeks and the anthropometric status of 69.8% of these children did not deteriorate (i.e. MUAC ≥120 mm) despite not immediately receiving treatment in the MUAC-only program., Conclusions: The results from this study share the first operational experience of using MUAC as sole anthropometric criterion for admission and discharge in Niger and overall support the consideration for MUAC-only programming: the MUAC-only model of care was associated with a higher recovery and a lower defaulter rate than the standard program with very few children found to be excluded from treatment with an admission criterion of MUAC < 120 mm. Further consideration of the appropriate MUAC-based discharge criterion as it relates to an increased risk of non-response and adverse post-discharge outcomes would be prudent., (© 2021. The Author(s).)

Background: Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine., Methods and Findings: We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear., Conclusions: This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings., Trial Registration: ClinicalTrials.gov NCT02145000., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RFG is an Academic Editor on PLOS Medicine’s editorial board. BP is the sole member of BioStat Consulting LLC. MMM received institutional grants from PATH, Merck and Sanofi to provide laboratory service for rotavirus vaccine studies.

Background: The risk of healthcare-associated infections is exacerbated by poor hygiene practices in health care facilities and can contribute to increased patient morbidity and mortality. In low-income settings, caregivers play a key role in maintaining proper hygiene during inpatient stays. We aimed to explore caregivers' knowledge, perceptions and practices related to hospital hygiene in a rural, sub-Saharan African setting., Methods: We conducted an exploratory qualitative study among caregivers of children admitted to an inpatient therapeutic feeding center in Madarounfa, Niger. Individual interviews with 28 caregivers of hospitalized children were conducted to explore their knowledge, perceptions and practices of hygiene in the health facility., Findings: Caregivers described a broad understanding of hygiene and reported knowledge of its importance in the hospital, particularly to prevent disease transmission and protect child health. Hygiene was perceived as a collective rather than individual responsibility. Caregivers reported on the poor hygiene practice of others and cited a lack of space and hygiene materials as barriers to correct hygiene practice. Caregivers described educational sessions and informal sharing with other caregivers as tools to gain knowledge and improve practice., Conclusion: This exploratory study is unique in describing the perspective of caregivers in a low-resource hospital setting, a group often underrepresented when designing health interventions to improve hospital hygiene. Our findings suggest a strong knowledge of hospital hygiene among caregivers in this setting, with positive perception of its importance in health promotion. Poor individual practice was reported but may be improved through additional education and provision of hygiene materials., (© 2021 The Authors.)

Background: Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger., Methods and Findings: From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy., Conclusions: Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development., Trial Registration: ClinicalTrials.gov NCT02145000., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RFG is an Academic Editor on PLOS Medicine’s editorial board. BP is the sole member of BioStat Consulting LLC.

Growth faltering in early childhood is prevalent in many low resource countries. Poor maternal dietary diversity during pregnancy has been linked with increased risk of fetal growth failure and adverse birth outcomes but may also influence subsequent infant growth. Our aim is to assess the role of prenatal maternal dietary diversity in infant growth in rural Uganda. Data from 3291 women and infant pairs enrolled in a birth cohort from 2014 to 2016 were analysed (NCT04233944). Maternal diets were assessed using dietary recall in the second or third trimesters of pregnancy. Maternal dietary diversity scores (DDS) were calculated using the FAO Minimum Dietary Diversity for Women (MDD-W). Cox regression models were used to evaluate associations of the DDS with the incidence of underweight, stunting and wasting in infants from 3 to 12 months, adjusting for confounding factors. The median DDS for women was low, at 3.0 (interquartile range 3.0-4.0), relative to the threshold of consuming five or more food groups daily. Infants of women in highest quartile of DDS (diverse diets) were less likely to be underweight (adjusted hazard ratio: 0.70, 95% confidence interval: 0.61, 0.80) compared with infants of women in Quartile 1 (p for trend <0.001) in models controlling for maternal factors. There was no significant association between DDS and stunting or wasting. Our findings suggest a relationship between higher maternal dietary diversity and lower risk of underweight in infancy. These findings suggest that programmes to improve infant growth could additionally consider strengthening prenatal dietary diversity to improve child outcomes globally., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Balanced energy protein (BEP) supplementation for pregnant and lactating women in low- and middle-income countries is a promising strategy to improve birth outcomes and child growth. The objective of this study was to assess and compare the acceptability of new formulations of two fortified BEP supplements, a lipid-based peanut paste and a vanilla biscuit, among 80 pregnant women in rural Burkina Faso, prior to an efficacy trial. A 10-week individually randomized cross-over study was designed, in which women received a weekly supply of each supplement for 4 weeks, and a daily choice between the supplements in the last 2 weeks. Questionnaires to assess daily consumption and supplement acceptability (n = 80) and home observations (n = 20) were combined with focus group discussions (n = 6) and in-depth interviews with women (n = 80) and stakeholders (n = 24). Results showed that the two supplements were well accepted. Quantitative findings indicated high compliance (>99.6%) and high overall appreciation (Likert score >6 out of 7) of both supplements. The assessment of preferred choice in Weeks 9 and 10 indicated a slight preference for the vanilla biscuit. Qualitative findings indicated that perceived health benefits, support from household members and educational messages from health professionals were important drivers for acceptance and compliance. Sharing was not often reported but was identified during interviews as a possible risk. We recommend that future studies use a combination of methods to identify appropriate food supplements and context-specific factors that influence acceptability, compliance and subsequent impact of nutritious food supplements., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Introduction: Estimates of incident cases of severe wasting among young children are not available for most settings but are needed for optimal planning of treatment programmes and burden estimation. To improve programme planning, global guidance recommends a single 'incidence correction factor' of 1.6 be applied to available prevalence estimates to account for incident cases. This study aimed to update estimates of the incidence correction factor to improve programme planning and inform the approach to burden estimation for severe wasting., Methods: A global call was issued for secondary data from severe wasting treatment programmes including prevalence, population size, programme admission and programme coverage through a UNICEF-led effort. Site-specific incidence correction factors were calculated as the number of incident cases (annual programme admissions/programme coverage) divided by the number of prevalent cases (prevalence*population size). Estimates were aggregated by country, region and overall using inverse-variance weighted random-effects meta-analysis., Results: We estimated incidence correction factors from 352 sites in 20 countries. Estimates aggregated by country ranged from 1.3 (Nigeria) to 30.1 (Burundi). Excluding implausible values, the overall incidence correction factor was 3.6 (95% CI 3.4 to 3.9)., Conclusion: Our results suggest that incidence correction factors vary between sites and that the burden of severe wasting will often be underestimated using the currently recommended incidence correction factor of 1.6. Application of updated incidence correction factors represents a simple way to improve programme planning when incidence data are not available and could inform the approach to burden estimation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Poor maternal nutrition contributes to poor birth outcomes, including low birth weight and small for gestational age births. Fortified balanced energy protein (BEP) supplements may be beneficial, although evidence is limited. This mixed method study, conducted among pregnant women in Burkina Faso, is part of a larger clinical trial that seeks to understand the impact of fortified BEP supplements on pregnancy outcomes and child growth. The formative research reported here, a single-meal rapid assessment of 12 product formulations, sought to understand product preferences for provision of BEP supplements and contextual factors that might affect product acceptability and use. Results indicate a preference for products perceived as sweet rather than salty/savoury and for products perceived as familiar, as well as a sensitivity to product odours. Women expressed a willingness and intention to use the products even if they did not like them, because of the health benefits for their babies. Data also indicate that household food sharing practices may impact supplement use, although most women denied any intention to share the products. Sharing behaviour should therefore be monitored, and strategies to avoid sharing should be developed during the succeeding parts of the research., (© 2020 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Analysis of immunogenicity data is a critical component of vaccine development, providing a biological basis to support any observed protection from vaccination. Conventional methods for analyzing immunogenicity data use either post-vaccination titer or change in titer, often defined as a binary variable using a threshold. These methods are simple to implement but can be limited especially in populations experiencing natural exposure to the pathogen. A mixture model can overcome the limitations of the conventional approaches by jointly modeling the probability of an immune response and the level of the immune marker among those who respond. We apply a mixture model to analyze the immunogenicity of an oral, pentavalent rotavirus vaccine in a cohort of children enrolled into a placebo-controlled vaccine efficacy trial in Niger. Among children with undetectable immunoglobulin A (IgA) at baseline, vaccinated children had 5.2-fold (95% credible interval (CrI) 3.7, 8.3) higher odds of having an IgA response than placebo children, but the mean log IgA among vaccinated responders was 0.9-log lower (95% CrI 0.6, 1.3) than among placebo responders. This result implies that the IgA response generated by vaccination is weaker than that generated by natural infection. Multivariate logistic regression of seroconversion defined by ≥ 3-fold rise in IgA similarly found increased seroconversion among vaccinated children, but could not demonstrate lower IgA among those who seroresponded. In addition, we found that the vaccine was less immunogenic among children with detectable IgA pre-vaccination, and that pre-vaccination infant serum IgG and mother's breast milk IgA modified the vaccine immunogenicity. Increased maternal antibodies were associated with weaker IgA response in placebo and vaccinated children, with the association being stronger among vaccinated children. The mixture model is a powerful and flexible method for analyzing immunogenicity data and identifying modifiers of vaccine response and independent predictors of immune response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)