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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.

Abstract 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.

Abstract 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)

Abstract 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.

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.

Abstract 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

Abstract 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

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.

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

Abstract Background Low birthweight (LBW) (

Abstract 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

Abstract 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

Abstract 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.

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 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. Christopher R. Sudfeld and colleagues evaluate the benefit of multiple micronutrient supplementation and medium‐quantity lipid‐based nutrient supplementation in pregnancy on child development in rural Niger. Author summary Why was this study done? It is estimated that over 250 million children under 5 years of age do not reach their developmental potential in low- and middle-income country (LMIC) settings. Observational studies suggest that poor diet, anemia, and micronutrient deficiencies in pregnancy are associated with poor child development outcomes; however, the effect of macronutrient and micronutrient supplementation in pregnancy on child development outcomes remains inconclusive due to a limited number of randomized trials that have assessed developmental outcomes. What did the researchers do and find? We conducted a cluster-randomized controlled trial of prenatal multiple micronutrient supplementation (MMS) and lipid-based nutrient supplementation (LNS) as compared to routine iron–folic acid (IFA) supplementation among pregnant women in rural Niger and evaluated the effect on child development outcomes during the first 2 years of life. There was no benefit of prenatal MMS on child Bayley Scales of Infant and Toddler Development III (BSID-III) scores or on time to achievement of motor milestones as compared to IFA. There was no effect of prenatal LNS on BSID-III scores at 24 months of age as compared to IFA; however, the trajectory of child development differed between groups, with children in the prenatal LNS group having higher cognitive scores at 18 and 21 months of age as compared to IFA. Children whose mothers received prenatal LNS also had earlier achievement of sitting alone and walking alone as compared to children whose mothers received prenatal IFA. What do these findings mean? Prenatal supplementation with LNS appeared to support the achievement of selected motor milestones and improve cognitive development trajectory; however, there was no evidence of benefit of MMS over routine IFA on developmental outcomes in the context of rural Niger. Nevertheless, the apparent beneficial effects of prenatal LNS were limited, and, therefore, integrated interventions that consider maternal and child nutritional support along with parenting interventions and other components to support an enabling environment may provide larger effects on child development outcomes.

Abstract 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.

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. Matt D.T. Hitchings and colleagues investigate the effectiveness of a monthly schedule of follow-up for the management of uncomplicated severe acute malnutrition in children aged 6-59 months in Nigeria. Author summary Why was this study done? Severe acute malnutrition (SAM) affects at least 13.6 million children under 5 worldwide each year and is associated with significant increase in mortality and morbidity. Despite improvements in the management of SAM, coverage of treatment programs remains low. Distance to outpatient clinics and high opportunity costs for caregivers represent major barriers to access. New models are needed to increase coverage and access to lifesaving treatment for SAM. What did the researchers do and find? We conducted a cluster randomized crossover trial to assess the effectiveness of a monthly follow-up schedule compared to a weekly schedule in terms of nutritional recovery and secondary outcomes including nonresponse, default, hospitalization, and death, and weight gain, length of stay, and relapse among recovered children. Study outcomes were assessed at the end of treatment and at 3 months postdischarge. Noninferiority of the monthly follow-up group in terms of nutritional recovery was not demonstrated. However, we found lower rates of default with monthly follow-up implying greater acceptability among caregivers. There was no statistical difference in weight velocity between groups at 4 and 8 weeks, but time to recovery was longer with monthly follow-up and relapse at 3 months postdischarge was less likely to occur in the monthly group. Finally, the mortality risk between admission and 3 months postdischarge was significantly higher in the monthly follow-up group. What do these findings mean? Where possible, a weekly schedule of clinic visits should be preferred for treatment of SAM. Although this study did not demonstrate noninferiority of a monthly schedule of follow-up for nutritional recovery, monthly follow-up may be considered in specific settings where more frequent follow-up is infeasible.

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.

Abstract 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.

Abstract Background Coverage is an important indicator to assess both the performance and effectiveness of public health programs. Recommended methods for coverage estimation for the treatment of severe acute malnutrition (SAM) can involve active and adaptive case finding (AACF), an informant-driven sampling procedure, for the identification of cases. However, as this procedure can yield a non-representative sample, exhaustive or near exhaustive case identification is needed for valid coverage estimation with AACF. Important uncertainty remains as to whether an adequate level of exhaustivity for valid coverage estimation can be ensured by AACF. Methods We assessed the sensitivity of AACF and a census method using a capture-recapture design in northwestern Nigeria. Program coverage was estimated for each case finding procedure. Results The sensitivity of AACF was 69.5% (95% CI: 59.8, 79.2) and 91.9% (95% CI: 85.1, 98.8) with census case finding. Program coverage was estimated to be 40.3% (95% CI 28.6, 52.0) using AACF, compared to 34.9% (95% CI 24.7, 45.2) using the census. Depending on the distribution of coverage among missed cases, AACF sensitivity of at least ≥70% was generally required for coverage estimation to remain within ±10% of the census estimate. Conclusion Given the impact incomplete case finding and low sensitivity can have on coverage estimation in potentially non-representative samples, adequate attention and resources should be committed to ensure exhaustive or near exhaustive case finding. Trial registration ClinicalTrials.gov ID NCT03140904. Registered on May 3, 2017.

S U M M A R Y: 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.

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. Sheila Isanaka and co-workers study nutrient supplementation and infants’ immune responses to rotavirus vaccination. Author summary Why was this study done? The World Health Organization recommends that all children be vaccinated against rotavirus, the most common cause of severe childhood diarrhea and a major cause of morbidity and mortality worldwide. Two oral rotavirus vaccines have been shown to be highly efficacious against childhood diarrhea in high- and middle-income countries (85%–98%), but, virtually, all trials in sub-Saharan Africa and South Asia have shown lower immune response and much lower efficacy (40%–64%), leaving many children unprotected. As the development of the immune cells that support vaccine response specifically depend on an adequate supply of micronutrients, nutritional supplementation has been considered as a potential adjunctive intervention to improve oral vaccine performance. What did the researchers do and find? 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. This study found no effect of the type of prenatal nutrient supplementation on immune response in this setting; however, the immune response appeared to vary by previous exposure to rotavirus. What do these findings mean? To improve the oral vaccine immunogenicity gap between low- and high-income countries, a more complete understanding of the factors influencing immunogenicity and a reliable correlate of protection are needed. Without improvement in oral vaccine performance, alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings.

Abstract 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.

Abstract 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

BackgroundRotavirus 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 findingsFrom 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.ConclusionsRotasiil 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 registrationClinicalTrials.gov NCT02145000.

Abstract Background In food insecure settings, it may be difficult for pregnant women to meet increased nutritional needs through traditional diets. A promising new strategy to fill nutrient gaps in pregnancy involves the provision of lipid-based nutrient supplements (LNS). We aimed to assess the acceptability and utilization of a 40 g LNS formulation (Epi-E) with increased micronutrient content relative to the recommended daily allowance among pregnant women in rural Niger. Methods We conducted a two-part, multi-methods study among pregnant women presenting to antenatal care in Madarounfa, Niger during two periods (Ramadan and non-Ramadan). Part 1 included two LNS test meals provided at the health center, and Part 2 included a 14-day home trial to simulate more realistic conditions outside of the health center. Open- and closed-ended questions were used to assess organoleptic properties of Epi-E using a 5-point hedonic scale after the test meals, as well as utilization and willingness to pay for Epi-E after the 14-day home trial. Results Participants consumed more than 90% of the test meal in both periods. Epi-E was rated highly in terms of overall liking, color, taste and smell during test meals in both periods (median 5/5 for all); only time, mode and frequency of consumption varied between Ramadan and non-Ramadan periods in observance of daily fasting during the holy month. Conclusion Epi- E, a 40 g LNS formulation with increased micronutrient content, was highly acceptable among pregnant women in rural Niger, and utilization was guided by household and individual considerations that varied by time period. This formulation can be further tested as a potential strategy to improve the nutritional status of pregnant women in this context. Trial registration ClinicalTrials.gov Identifier: NCT02145000. Registered 22 May 2014.

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.

Abstract Outpatient therapeutic feeding protocols for the treatment of uncomplicated severe acute malnutrition in children were initially based on weight gain data from inpatient settings and expert knowledge of the physiological requirements during recovery. However, weight gain and energy requirements from historic inpatient settings may differ from modern outpatient settings and therefore may not be appropriate to guide current therapeutic feeding protocols. We calculated the weight gain and average estimated total daily energy requirement of children successfully treated for uncomplicated severe acute malnutrition as outpatients in Niger (n = 790). Mean energy provided by six therapeutic feeding protocols was calculated and compared with average estimated energy requirements in the study population. Overall weight gain was 5.5 g·kg−1·day−1 among recovered children. Average energy requirements ranged from 92 to 110 kcal·kg−1·day−1 depending on the estimation approach. Two current therapeutic feeding protocols were found to provide an excess of energy after the first week of treatment in our study population, whereas four research protocols tended to provide less energy than the estimated requirement after the first week of treatment. Alternative feeding protocols have the potential to simplify and lead to important savings for programmes but should be evaluated to show adequacy to meet the energy needs of children under treatment, as well as feasibility and cost efficiency. Our findings rely on theoretical calculations based on several assumptions and should be confirmed in field studies.

BACKGROUND:An estimated 49.5 million children under five years of age are wasted. There is a lack of robust studies on effective interventions to prevent wasting. The aim of this study was to identify and prioritise the main outstanding research questions in relation to wasting prevention to inform future research agendas. METHOD:A research prioritisation exercise was conducted following the Child Health and Nutrition Research Initiative method. Identified research gaps were compiled from multiple sources, categorised into themes and streamlined into forty research questions by an expert group. A survey was then widely circulated to assess research questions according to four criteria. An overall research priority score was calculated to rank questions. FINDINGS:The prioritised questions have a strong focus on interventions. The importance of the early stages of life in determining later experiences of wasting was highlighted. Other important themes included the identification of at-risk infants and young children early in the progression of wasting and the roles of existing interventions and the health system in prevention. DISCUSSION:These results indicate consensus to support more research on the pathways to wasting encompassing the in-utero environment, on the early period of infancy and on the process of wasting and its early identification. They also reinforce how little is known about impactful interventions for the prevention of wasting. CONCLUSION:This exercise provides a five-year investment case for research that could most effectively improve on-the-ground programmes to prevent child wasting and inform supportive policy change.

Abstract Background Community-based treatment of severe acute malnutrition (SAM) has proven to be safe and cost-effective, although identifying additional factors that can increase recovery and decrease treatment failure may improve program effectiveness. We examine the association of dietary diversity and clinical and program treatment outcomes among children treated for uncomplicated SAM in Niger. Methods Two thousand four hundred twelve children were enrolled in a randomized trial of routine amoxicillin in the treatment of uncomplicated SAM from 2012 to 2014. All children received ready to use therapeutic food (RUTF) and standard clinical care. Child dietary diversity was assessed using a 7-day food frequency questionnaire and 8-food group diet diversity score. We assessed the association of dietary diversity at admission with nutritional recovery, hospitalization, and death at program discharge and 12 weeks, and weight and height gain. Results Food groups most commonly consumed by children in seven days preceding SAM treatment were cereals, roots and tubers (N = 2364, 99.5%) and vitamin A rich fruits and vegetables (N = 2253, 94.8%). Egg (N = 472, 19.9%) and dairy (N = 659, 27.7%) consumption was low. Mean (SD) diet diversity score was significantly lower in the lean vs. non-lean season [2.7 (1.1) vs. 2.9 (1.0)]. There was no evidence that dietary diversity increased nutritional recovery at discharge (RR: 1.02, 95% CI: 1.00, 1.04) or 12 weeks (RR: 0.98, 95%CI: 0.94, 1.02). No significant association was found with risk of hospitalization or death, or weight and height gain. Egg consumption was protective against death at discharge (RR: 0.53, 95% CI: 0.39, 0.70) and 12 weeks (RR: 0.66, 95% CI: 0.45, 0.96). Vitamin A rich fruits and vegetable consumption was associated with greater risk of mortality in children at discharge (RR: 1.30, 95% CI: 1.08, 1.56) and 12 weeks (RR: 1.19, 95% CI: 1.03, 1.36). Conclusions We did not find evidence that dietary diversity influenced nutrition recovery or response to treatment for children with uncomplicated SAM in Niger. It is feasible consumption of nutrient-dense foods like eggs may be important for recovery from SAM. There is need for continued research to further elucidate drivers of nutritional recovery from acute malnutrition in different settings. Trial registration Trial registration number: ClinicalTrials.gov NCT01613547. Registered May 26, 2012.

Abstract Background Many health programs can assess coverage using standardized cluster survey methods, but estimating the coverage of nutrition programs presents a special challenge due to low disease prevalence. Used since 2012, the Semi-Quantitative Evaluation of Access and Coverage (SQUEAC) employs both qualitative and quantitative methods to identify key barriers to access and estimate coverage of therapeutic feeding programs. While the tool has been increasingly used in programs, the validity of certain methodological elements has been the subject of debate. Methods We conducted a study comparing a SQUEAC conjugate Bayesian analysis to a two-stage cluster survey estimating the coverage of a therapeutic feeding program in Niger in 2016. Results We found that the coverage estimate from the conjugate Bayesian analysis was sensitive to the prior estimation. With the exception of prior estimates produced by an external support team, all prior estimates resulted in a conflict with the likelihood result, excluding interpretation of the final coverage estimate. Allowing for increased uncertainty around the prior estimate did not materially affect conclusions. Conclusion SQUEAC is a demanding analytical method requiring both qualitative and quantitative data collection and synthesis to identify program barriers and estimate coverage. If the necessary technical capacity is not available to objectively specify an accurate prior for a conjugate Bayesian analysis, alternatives, such as a two-stage cluster survey or a larger likelihood survey, may be considered to ensure valid coverage estimation. Trial registration NCT03280082. Retrospectively registered on September 12, 2017.

Dietary diversity scores (DDS) are considered as metrics for monitoring the implementation of the UN's Sustainable Development Goals, but they need to be rigorously evaluated.To examine two DDS, the Food Groups Index (FGI), and the Minimum Dietary Diversity-Women (MDD-W), alongside two dietary quality scores, the Alternate Healthy Eating Index (AHEI-2010) and the Prime Diet Quality Score (PDQS), with risks of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDPs).The analysis included 21,312 (GDM) and 19,917 (HDPs) singleton births reported in the Nurses' Health Study II cohort (1991-2001), among women without major chronic disease or GDM/HDPs. Scores were derived using prepregnancy diet collected by a comprehensive food frequency questionnaire. Multivariable models were utilized to calculate relative risks (RR) and confidence intervals (95%CIs).Incident GDM (n = 916) and HDPs (n = 1,421) were reported. The MDD-W and FGI were not associated with risk of GDM or HDPs, but the AHEI-2010 and PDQS were associated with a lower risk of GDM and marginally lower risk of HDP. The RR's of GDM comparing the highest vs. lowest quintiles were 1.00 (95%CI: 0.79, 1.27; p-trend = 0.82) for MDD-W, 0.96 (95%CI: 0.76, 1.22; p-trend = 0.88) for FGI, 0.63 (95%CI: 0.50, 0.81; p-trend

Nutritional status in pregnancy is a key determinant of birth outcomes. In low-income countries, maternal diets are often limited, and daily nutrient supplements are recommended to fill nutrient gaps. As a result, it is important to understand the factors influencing acceptability and utilization of nutrient supplements in these settings. Qualitative data (individual interviews and focus group discussions with pregnant women, household members, and study staff) and quantitative data (unannounced household spot checks) were collected in 24 villages in the Maradi region of south-central Niger. Each village was randomly assigned to one of three study arms, with pregnant women receiving either iron and folic acid (IFA) supplements, multiple micronutrient (MMN) supplements, or medium-quantity lipid-based nutrient supplements (MQ-LNS) for daily consumption during pregnancy. Data were collected longitudinally to capture changes in perspective as women progressed through their pregnancy. Participants accepted all three supplement types, and perceived a wide range of health benefits attributed to supplement consumption. However, several important barriers to appropriate consumption were reported, and rumors about the supplements leading to childbirth complications also decreased utilization. The household spot checks suggested that IFA had the highest level of correct consumption. Overall, despite a stated high level of acceptance and enthusiasm for the supplements among participants and their household members, certain fears, side effects, and organoleptic factors led to decreased utilization. The effectiveness of future programs to improve maternal nutritional status through supplementation may be improved by understanding perceived barriers and facilitating factors among participants and tailoring communication efforts appropriately.

OBJECTIVES/SPECIFIC AIMS: A course of oral broad-spectrum antibiotics frequently has a positive effect on morbidity and mortality in severe acute malnutrition (SAM), but the actual mechanism for this effect is unknown. This mechanism is especially important to find and quantify because of the possibility that using antibiotics prophylactically may accelerate the danger from antibiotic resistant infections. This study aims to answer (1) how antibiotic therapy improves the nutritional recovery and (2) how much it affects the prevalence of resistance genes in the microbiome. METHODS/STUDY POPULATION: Stool samples were collected from children with SAM between 6 and 60 weeks of age who received either one week of amoxicillin or placebo (n=164). The children were followed for 12 weeks with longitudinal sampling, and a subset were followed out to 2 years. All samples were frozen at −80°C and prepared for metagenome shotgun sequencing via the Illumina Nextera platform. RESULTS/ANTICIPATED RESULTS: Antibiotic treatment at the start of the nutritional program is associated with significant improvements in weight gain, mid-upper-arm circumference, and graduation from the treatment program. It is also associated with qualitative decreases in early-life fermenter Lactobacillus and known enteropathogen Campylobacter. Two years after the use of amoxicillin, the Shannon diversity index is significantly higher than that of malnourished children (effect size 0.507, 95% CI: 0.204–0.630, p=0.0007), while children who received placebo are not distinguishable from malnourished children by the same metric (effect size 0.147, 95% CI: −0.311, 0.630, p=0.5878). Sustained antibiotic resistance gene enrichment within the microbiota did not occur, as the enrichment effects disappears by week 4 of follow-up. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of amoxicillin to treat uncomplicated SAM has therapeutic benefits visible by anthropometry and by content of the gut microbiota. The main concern with the use of prophylactic antibiotics for this purpose is the effect on antibiotic resistance gene enrichment in the children’s microbiota. This concern was not supported here. The benefit/cost ratio for the use of prophylactic antibiotics for individuals in this cohort is positive when weighing effects on anthropometry, microbiome, and antibiotic resistance. The results of this study impact the treatment of millions of children each year at nutritional therapy clinics around the world.

Debate for a greater role of mid-upper arm circumference (MUAC) measures in nutritional programming continues, but a shift from therapeutic feeding programs admitting children using MUAC and/or weight-for-height Z (WHZ) to a new model admitting children using MUAC only remains complicated by limited information regarding the clinical profile and response to treatment of children selected by MUAC vs. WHZ. To broaden our understanding of how children identified for therapeutic feeding by MUAC and/or WHZ may differ, we aimed to investigate differences between children identified for therapeutic feeding by MUAC and/or WHZ in terms of demographic, anthropometric, clinical, and laboratory and treatment response characteristics.Using secondary data from a randomized trial in rural Niger among children with uncomplicated severe acute malnutrition, we compared children that would be admitted to a therapeutic feeding program that used a single anthropometric criterion of MUAC< 115 mm vs. children that are admitted under current admission criteria (WHZ< -3 and/or MUAC< 115 mm) but would be excluded from a program that used a single MUAC< 115 mm admission criterion. We assessed differences between groups using multivariate regression, employing linear regression for continuous outcomes and log-binomial regression for dichotomous outcomes.We found no difference in terms of clinical and laboratory characteristics and discharge outcomes evaluated between children that would be included in a MUAC< 115 mm therapeutic feeding program vs. children that are currently eligible for therapeutic feeding but would be excluded from a MUAC-only program.A single anthropometric admission criterion of MUAC < 115 mm did not differentiate well between children in terms of clinical or laboratory measures or program outcomes in this context. If nutritional programming is to use a single MUAC-based criterion for admission to treatment, further research and program experience can help to identify the most appropriate criterion in a broad range of contexts to target children in most urgent need of treatment.

Experimental data suggest a role for iron in the course of tuberculosis (TB) infection, but there is limited evidence on the potential effects of iron deficiency or iron overload on the progression of TB disease in humans. The aim of the present analysis was to examine the association of iron status with the risk of TB progression and death.We analyzed plasma samples and data collected as part a randomized micronutrient supplementation trial (not including iron) among HIV-infected and HIV-uninfected TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV-uninfected) to the risk of treatment failure at one month after initiation, TB recurrence and death using binomial and Cox regression analyses. Overall, low (plasma ferritin150 µg/L for women and>200 µg/L for men) iron status were seen in 9% and 48% of patients, respectively. Compared with normal levels, low plasma ferritin predicted an independent increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to 3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95% CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein concentrations, was associated with an increased risk of overall mortality (adjusted RR = 3.02, 95% CI: 1.95 to 4.67).Both iron deficiency and overload exist in TB patients and may contribute to disease progression and poor clinical outcomes. Strategies to maintain normal iron status in TB patients could be helpful to reduce TB morbidity and mortality.

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 Χ2 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).