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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)

Objective Preterm birth can have short-term and long-term complications for a child. Socioeconomic factors and pregnancy-related morbidities may be important to predict and prevent preterm births in low-resource settings. The objective of our study was to find prevalence and predictors of spontaneous preterm birth in rural Nepal.Design This is a secondary observational analysis of trial data (registration number NCT01177111).Setting Rural Sarlahi district, Nepal.Participants 40 119 pregnant women enrolled from 9 September 2010 to 16 January 2017.Outcome measures The outcome variable is spontaneous preterm birth. Generalized Estimating Equations Poisson regression with robust variance was fitted to present effect estimates as risk ratios.Result The prevalence of spontaneous preterm birth was 14.5% (0.5% non-spontaneous). Characteristics not varying in pregnancy associated with increased risk of preterm birth were maternal age less than 18 years (adjusted risk ratio=1.13, 95% CI: 1.02 to 1.26); being Muslim (1.53, 1.16 to 2.01); first pregnancy (1.15, 1.04 to 1.28); multiple births (4.91, 4.20 to 5.75) and male child (1.10, 1.02 to 1.17). Those associated with decreased risk were maternal education >5 years (0.81, 0.73 to 0.90); maternal height ≥150 cm (0.89, 0.81 to 0.98) and being from wealthier families (0.83, 0.74 to 0.93). Pregnancy-related morbidities associated with increased risk of preterm birth were vaginal bleeding (1.53, 1.08 to 2.18); swelling (1.37, 1.17 to 1.60); high systolic blood pressure (BP) (1.47, 1.08 to 2.01) and high diastolic BP (1.41, 1.17 to 1.70) in the third trimester. Those associated with decreased risk were respiratory problem in the third trimester (0.86, 0.79 to 0.94); having poor appetite, nausea and vomiting in the second trimester (0.86, 0.80 to 0.92) and third trimester (0.86, 0.79 to 0.94); and higher weight gain from second to third trimester (0.89, 0.87 to 0.90).Conclusion The prevalence of preterm birth is high in rural Nepal. Interventions that increase maternal education may play a role. Monitoring morbidities during antenatal care to intervene to reduce them through an effective health system may help reduce preterm birth.

Summary: Background: Stunting during childhood has long-term consequences on human capital, including decreased physical growth, and lower educational attainment, cognition, workforce productivity and wages. Previous research has quantified the costs of stunting to national economies however beyond a few single-country datasets there has been a limited number of which have used diverse datasets and have had a dedicated focus on the private sector, which employs nearly 90% of the workforce in many low- and middle-income countries (LMICs). We aimed to examine (i) the impact of childhood stunting on income loss of private sector workforce in LMICs; (ii) to quantify losses in sales to private firms in LMICs due to childhood stunting; and (iii) to estimate potential gains (benefit-cost ratios) if stunting levels are reduced in select high prevalence countries. Methods: This multiple-methods study engaged multi-disciplinary technical advisers, executed several literature reviews, used innovative statistical methods, and implemented health and labor economic models. We analyzed data from seven longitudinal datasets (up to 30+ years of follow-up; 1982–2016; Peru, Ethiopia, India, Vietnam, Philippines, Tanzania, Brazil), 108 private firm datasets (spanning 2008–2020), and many global datasets including Joint Malnutrition Estimates, and World Development Indicators to produce estimates for 120+ LMICs (with estimates up to 2021). We studied the impact of childhood stunting on adult cognition, education, and height as pathways to wages/productivity in adulthood. We employed cloud-based artificial intelligence (AI) platforms, and conducted comparative analyses using three analytic approaches: traditional frequentist statistics, Bayesian inferential statistics and machine learning. We employed labour and health economic models to estimate wage losses to the private sector worker and firm revenue losses due to stunting. We also estimated benefit-cost ratios for countries investing in nutrition-specific interventions to prevent stunting. Findings: Across 95 LMICs, childhood stunting costs the private sector at least US$135.4 billion in sales annually. Firms from countries in Latin America and the Caribbean and East Asia and Pacific regions had the greatest losses. Totals sales losses to the private sector accumulated to 0.01% to 1.2% of national GDP across countries. Sectors most affected by childhood stunting were manufacturing (non-metallic mineral, fabricated metal, other), garments and food sectors. Sale losses were highest for larger sized private firms. Across regions (representing 123 LMICs), US$700 million (Middle East and North Africa) to US$16.5 billion (East Asia and Pacific) monthly income was lost among private sector workers. Investing in stunting reduction interventions yields gains from US$2 to US$81 per $1 invested annually (or 100% to 8000% across countries). Across sectors, the highest returns were in elementary occupations (US$46) and the lowest were among agricultural workers (US$8). By gender, women incurred a higher income penalty from childhood stunting and earned less than men; due to their relatively higher earnings, the returns for investing in stunting reduction were consistently higher for men across most countries studied. Interpretation: Childhood stunting costs the private sector in LMICs billions of dollars in sales and earnings for the workforce annually. Returns to nutrition interventions show that there is an economic case to be made for investing in childhood nutrition, alongside a moral one for both the public and private sector. This research could be used to motivate strong public-private sector partnerships to invest in childhood undernutrition for benefits in the short and long-term.

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.

Summary: Background: The population effects of armed conflict on non-combatant vulnerable populations are incompletely understood. We aimed to study the effects of conflict on mortality among women of childbearing age (15–49 years) and on orphanhood among children younger than 15 years in Africa. Methods: We tested the extent to which mortality among women aged 15–49 years, and orphanhood among children younger than 15 years, increased in response to nearby armed conflict in Africa. Data on location, timing, and intensity of armed conflicts were obtained from the Uppsala Conflict Data Program, and data on the location, timing, and outcomes of women and children from Demographic and Health Surveys done in 35 African countries from 1990 to 2016. Mortality among women was obtained from sibling survival data. We used cluster-area fixed-effects regression models to compare survival of women during periods of nearby conflict (within 50 km) to survival of women in the same area during times without conflict. We used similar methods to examine the extent to which children living near armed conflicts are at increased risk of becoming orphans. We examined the effects of varying conflict intensity using number of direct battle deaths and duration of consecutive conflict exposure. Findings: We analysed data on 1 629 352 women (19 286 387 person-years), of which 103 011 (6·3%) died (534·1 deaths per 100 000 women-years), and 2 354 041 children younger than 15 years, of which 204 276 (8·7%) had lost a parent. On average, conflict within 50 km increased women's mortality by 112 deaths per 100 000 person-years (95% CI 97–128; a 21% increase above baseline), and the probability that a child has lost at least one parent by 6·0% (95% CI 3–8). This effect was driven by high-intensity conflicts: exposure to the highest (tenth) decile conflict in terms of conflict-related deaths increased the probability of female mortality by 202% (187–218) and increased the likelihood of orphanhood by 42% compared with a conflict-free period. Among the conflict-attributed deaths, 10% were due to maternal mortality. Interpretation: African women of childbearing age are at a substantially increased risk of death from nearby high-intensity armed conflicts. Children exposed to conflict are analogously at increased risk of becoming orphans. This work fills gaps in literature on the harmful effects of armed conflict on non-combatants and highlights the need for humanitarian interventions to protect vulnerable populations. Funding: Bill & Melinda Gates Foundation to the BRANCH Consortium.

Summary: Background: Low birthweight (LBW) of less than 2500 g is an important marker of maternal and fetal health, predicting mortality, stunting, and adult-onset chronic conditions. Global nutrition targets set at the World Health Assembly in 2012 include an ambitious 30% reduction in LBW prevalence between 2012 and 2025. Estimates to track progress towards this target are lacking; with this analysis, we aim to assist in setting a baseline against which to assess progress towards the achievement of the World Health Assembly targets. Methods: We sought to identify all available LBW input data for livebirths for the years 2000–16. We considered population-based national or nationally representative datasets for inclusion if they contained information on birthweight or LBW prevalence for livebirths. A new method for survey adjustment was developed and used. For 57 countries with higher quality time-series data, we smoothed country-reported trends in birthweight data by use of B-spline regression. For all other countries, we estimated LBW prevalence and trends by use of a restricted maximum likelihood approach with country-level random effects. Uncertainty ranges were obtained through bootstrapping. Results were summed at the regional and worldwide level. Findings: We collated 1447 country-years of birthweight data (281 million births) for 148 countries of 195 UN member states (47 countries had no data meeting inclusion criteria). The estimated worldwide LBW prevalence in 2015 was 14·6% (uncertainty range [UR] 12·4–17·1) compared with 17·5% (14·1–21·3) in 2000 (average annual reduction rate [AARR] 1·23%). In 2015, an estimated 20·5 million (UR 17·4–24·0 million) livebirths were LBW, 91% from low-and-middle income countries, mainly southern Asia (48%) and sub-Saharan Africa (24%). Interpretation: Although these estimates suggest some progress in reducing LBW between 2000 and 2015, achieving the 2·74% AARR required between 2012 and 2025 to meet the global nutrition target will require more than doubling progress, involving both improved measurement and programme investments to address the causes of LBW throughout the lifecycle. Funding: Bill & Melinda Gates Foundation, The Children's Investment Fund Foundation, United Nations Children's Fund (UNICEF), and WHO.

Summary: Background: Climate change threatens to undermine recent progress in reducing global deaths from diarrhoeal disease in children. However, the scarcity of evidence about how individual environmental factors affect transmission of specific pathogens makes prediction of trends under different climate scenarios challenging. We aimed to model associations between daily estimates of a suite of hydrometeorological variables and rotavirus infection status ascertained through community-based surveillance. Methods: For this analysis of multisite cohort data, rotavirus infection status was ascertained through community-based surveillance of infants in the eight-site MAL-ED cohort study, and matched by date with earth observation estimates of nine hydrometeorological variables from the Global Land Data Assimilation System: daily total precipitation volume (mm), daily total surface runoff (mm), surface pressure (mbar), wind speed (m/s), relative humidity (%), soil moisture (%), solar radiation (W/m2), specific humidity (kg/kg), and average daily temperatures (°C). Lag relationships, independent effects, and interactions were characterised by use of modified Poisson models and compared with and without adjustment for seasonality and between-site variation. Final models were created with stepwise selection of main effects and interactions and their validity assessed by excluding each site in turn and calculating Tjur's Coefficients of Determination. Findings: All nine hydrometeorological variables were significantly associated with rotavirus infection after adjusting for seasonality and between-site variation over multiple consecutive or non-consecutive lags, showing complex, often non-linear associations that differed by symptom status and showed considerable mutual interaction. The final models explained 5·9% to 6·2% of the variability in rotavirus infection in the pooled data and their predictions explained between 0·0% and 14·1% of the variability at individual study sites. Interpretation: These results suggest that the effect of climate on rotavirus transmission was mediated by four independent mechanisms: waterborne dispersal, airborne dispersal, virus survival on soil and surfaces, and host factors. Earth observation data products available at a global scale and at subdaily resolution can be combined with longitudinal surveillance data to test hypotheses about routes and drivers of transmission but showed little potential for making predictions in this setting. Funding: Bill & Melinda Gates Foundation; Foundation for the National Institutes of Health, National Institutes of Health, Fogarty International Center; Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases, Johns Hopkins School of Medicine; and NASA's Group on Earth Observations Work Programme.

Summary: Background: India had the largest number of under-5 deaths of all countries in 2015, with substantial subnational disparities. We estimated national and subnational all-cause and cause-specific mortality among children younger than 5 years annually in 2000–15 in India to understand progress made and to consider implications for achieving the Sustainable Development Goal (SDG) child survival targets. Methods: We used a multicause model to estimate cause-specific mortality proportions in neonates and children aged 1–59 months at the state level, with causes of death grouped into pneumonia, diarrhoea, meningitis, injury, measles, congenital abnormalities, preterm birth complications, intrapartum-related events, and other causes. AIDS and malaria were estimated separately. The model was based on verbal autopsy studies representing more than 100 000 neonatal deaths globally and 16 962 deaths among children aged 1–59 months at the subnational level in India. By applying these proportions to all-cause deaths by state, we estimated cause-specific numbers of deaths and mortality rates at the state, regional, and national levels. Findings: In 2015, there were 25·121 million livebirths in India and 1·201 million under-5 deaths (under-5 mortality rate 47·81 per 1000 livebirths). 0·696 million (57·9%) of these deaths occurred in neonates. There were disparities in child mortality across states (from 9·7 deaths [Goa] to 73·1 deaths [Assam] per 1000 livebirths) and regions (from 29·7 deaths [the south] to 63·8 deaths [the northeast] per 1000 livebirths). Overall, the leading causes of under-5 deaths were preterm birth complications (0·330 million [95% uncertainty range 0·279–0·367]; 27·5% of under-5 deaths), pneumonia (0·191 million [0·168–0·219]; 15·9%), and intrapartum-related events (0·139 million [0·116–0·165]; 11·6%), with cause-of-death distributions varying across states and regions. In states with very high under-5 mortality, infectious-disease-related causes (pneumonia and diarrhoea) were among the three leading causes, whereas the three leading causes were all non-communicable in states with very low mortality. Most states had a slower decline in neonatal mortality than in mortality among children aged 1–59 months. Ten major states must accelerate progress to achieve the SDG under-5 mortality target, while 17 are not on track to meet the neonatal mortality target. Interpretation: Efforts to reduce vaccine-preventable deaths and to reduce geographical disparities should continue to maintain progress achieved in 2000–15. Enhanced policies and programmes are needed to accelerate mortality reduction in high-burden states and among neonates to achieve the SDG child survival targets in India by 2030. Funding: Bill & Melinda Gates Foundation.

Summary: Background: Global child mortality reduced substantially during the Millennium Development Goal period (2000–15). We aimed to estimate morbidity, mortality, and prevalence of risk factors for child pneumonia at the global, regional, and national level for developing countries for the Millennium Development Goal period. Methods: We estimated the incidence, number of hospital admissions, and in-hospital mortality due to all-cause clinical pneumonia in children younger than 5 years in developing countries at 5-year intervals during the Millennium Development Goal period (2000–15) using data from a systematic review and Poisson regression. We estimated the incidence and number of cases of clinical pneumonia, and the pneumonia burden attributable to HIV for 132 developing countries using a risk-factor-based model that used Demographic and Health Survey data on prevalence of the various risk factors for child pneumonia. We also estimated pneumonia mortality in young children using data from multicause models based on vital registration and verbal autopsy. Findings: Globally, the number of episodes of clinical pneumonia in young children decreased by 22% from 178 million (95% uncertainty interval [UI] 110–289) in 2000 to 138 million (86–226) in 2015. In 2015, India, Nigeria, Indonesia, Pakistan, and China contributed to more than 54% of all global pneumonia cases, with 32% of the global burden from India alone. Between 2000 and 2015, the burden of clinical pneumonia attributable to HIV decreased by 45%. Between 2000 and 2015, global hospital admissions for child pneumonia increased by 2·9 times with a more rapid increase observed in the WHO South-East Asia Region than the African Region. Pneumonia deaths in this age group decreased from 1·7 million (95% UI 1·7–2·0) in 2000 to 0·9 million (0·8–1·1) in 2015. In 2015, 49% of global pneumonia deaths occurred in India, Nigeria, Pakistan, Democratic Republic of the Congo, and Ethiopia collectively. All key risk factors for child pneumonia (non-exclusive breastfeeding, crowding, malnutrition, indoor air pollution, incomplete immunisation, and paediatric HIV), with the exception of low birthweight, decreased across all regions between 2000 and 2015. Interpretation: Globally, the incidence of child pneumonia decreased by 30% and mortality decreased by 51% during the Millennium Development Goal period. These reductions are consistent with the decrease in the prevalence of some of the key risk factors for pneumonia, increasing socioeconomic development and preventive interventions, improved access to care, and quality of care in hospitals. However, intersectoral action is required to improve socioeconomic conditions and increase coverage of interventions targeting risk factors for child pneumonia to accelerate decline in pneumonia mortality and achieve the Sustainable Development Goals for health by 2030. Funding: Bill & Melinda Gates Foundation.

Summary: Background: Undernutrition is a pervasive condition in Afghanistan, and prevalence is among the highest in the world. We aimed to comprehensively assess district-level geographical disparities and determinants of nutritional status (stunting, wasting, or underweight) among women and children in Afghanistan. Methods: The study used individualised data from the recent Afghanistan National Nutrition Survey 2013. Outcome variables were based on growth and weight anthropometry data, which we analysed linearly as Z scores and as dichotomous categories. We analysed data from a total of almost 14 000 index mother–child pairs using Bayesian spatial and generalised least squares regression models accounting for the complex survey design. Findings: We noted that childhood stunting, underweight, and combined stunting and wasting were consistently highest in districts in Farah, Nangarhar, Nuristan, Kunar, Paktia, and Badakhshan provinces. District prevalence ranged from 4% to 84% for childhood stunting and 5% to 66% for underweight. Child wasting exceeded 20% in central and high-conflict regions that bordered Pakistan including east, southeast, and south. Among mothers, dual burden of underweight and overweight or obesity existed in districts of north, northeast, central, and central highlands (prevalence of 15–20%). Linear growth and weight of children were independently associated with household wealth, maternal literacy, maternal anthropometry, child age, food security, geography, and improved hygiene and sanitation conditions. The mother's body-mass index was determined by many of the same factors, in addition to ethnolinguistic status and parity. Younger mothers (

Reducing neonatal and child mortality is a key component of the health-related sustainable development goal (SDG), but most low and middle income countries lack data to monitor child mortality on an annual basis. We tested a mortality monitoring system based on the continuous recording of pregnancies, births and deaths by trained community-based volunteers (CBV).This project was implemented in 96 clusters located in three districts of the Northern Region of Ghana. Community-based volunteers (CBVs) were selected from these clusters and were trained in recording all pregnancies, births, and deaths among children under 5 in their catchment areas. Data collection lasted from January 2012 through September 2013. All CBVs transmitted tallies of recorded births and deaths to the Ghana Birth and deaths registry each month, except in one of the study districts (approximately 80% reporting). Some events were reported only several months after they had occurred. We assessed the completeness and accuracy of CBV data by comparing them to retrospective full pregnancy histories (FPH) collected during a census of the same clusters conducted in October-December 2013. We conducted all analyses separately by district, as well as for the combined sample of all districts. During the 21-month implementation period, the CBVs reported a total of 2,819 births and 137 under-five deaths. Among the latter, there were 84 infant deaths (55 neonatal deaths and 29 post-neonatal deaths). Comparison of the CBV data with FPH data suggested that CBVs significantly under-estimated child mortality: the estimated under-5 mortality rate according to CBV data was only 2/3 of the rate estimated from FPH data (95% Confidence Interval for the ratio of the two rates = 51.7 to 81.4). The discrepancies between the CBV and FPH estimates of infant and neonatal mortality were more limited, but varied significantly across districts.In northern Ghana, a community-based data collection systems relying on volunteers did not yield accurate estimates of child mortality rates. Additional implementation research is needed to improve the timeliness, completeness and accuracy of such systems. Enhancing pregnancy monitoring, in particular, may be an essential step to improve the measurement of neonatal mortality.

Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever, caused by Salmonella Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance network but does not monitor enteric fever. We evaluated the feasibility and sustainability of integrating enteric fever surveillance into the ongoing IB-VPD platform.The IB-VPD surveillance system uses WHO definitions to enroll 2-59 month children hospitalized with possible pneumonia, sepsis or meningitis. We expanded this surveillance system to additionally capture suspect enteric fever cases during 2012-2016, in two WHO sentinel hospitals of Bangladesh, by adding inclusion criteria of fever ≥102°F for ≥3 days, irrespective of other manifestations. Culture-positive enteric fever cases from in-patient departments (IPD) detected in the hospital laboratories but missed by the expanded surveillance, were also enrolled to assess completion. Costs for this integration were calculated for the additional personnel and resources required.In the IB-VPD surveillance, 5,185 cases were enrolled; 3% (N = 171/5185) were positive for microbiological growth, of which 55% (94/171) were culture-confirmed cases of enteric fever (85 Typhi and 9 Paratyphi A). The added inclusion criteria for enteric fever enrolled an additional 1,699 cases; 22% (358/1699) were positive, of which 85% (349/358) were enteric fever cases (305 Typhi and 44 Paratyphi A). Laboratory surveillance of in-patients of all ages enrolled 311 additional enteric fever cases (263 Typhi and 48 Paratyphi A); 9% (28/311) were 2-59 m and 91% (283/311) >59 m. Altogether, 754 (94+349+311) culture-confirmed enteric fever cases were found, of which 471 were 2-59 m. Of these 471 cases, 94% (443/471) were identified through the hospital surveillances and 6% (28/471) through laboratory results. Twenty-three percent (170/754) of all cases were children

BACKGROUND:Millions of children worldwide suffer and die from conditions for which effective interventions exist. While there is ample evidence regarding these diseases, there is a dearth of information on the social factors associated with child mortality. METHODS:The 2014 Verbal and Social Autopsy Study was conducted based on a nationally representative sample of 3,254 deaths that occurred in children under the age of five and were reported on the birth history component of the 2013 Nigerian Demographic and Health Survey. We conducted a descriptive analysis of the preventive and curative care sought and obtained for the 2,057 children aged 1-59 months who died in Nigeria and performed regional (North vs. South) comparisons. RESULTS:A total of 1,616 children died in the northern region, while 441 children died in the South. The majority (72.5%) of deceased children in the northern region were born to mothers who had no education, married at a young age, and lived in the poorest two quintiles of households. When caregivers first noticed that their child was ill, a median of 2 days passed before they sought or attempted to seek healthcare for their children. The proportion of children who reached and departed from their first formal healthcare provider alive was greater in the North (30.6%) than in the South (17.9%) (p

Nigeria's under-five mortality rate is the eighth highest in the world. Identifying the causes of under-five deaths is crucial to achieving Sustainable Development Goal 3 by 2030 and improving child survival. National and international bodies collaborated in this study to provide the first ever direct estimates of the causes of under-five mortality in Nigeria. Verbal autopsy interviews were conducted of a representative sample of 986 neonatal and 2,268 1-59 month old deaths from 2008 to 2013 identified by the 2013 Nigeria Demographic and Health Survey. Cause of death was assigned by physician coding and computerized expert algorithms arranged in a hierarchy. National and regional estimates of age distributions, mortality rates and cause proportions, and zonal- and age-specific mortality fractions and rates for leading causes of death were evaluated. More under-fives and 1-59 month olds in the South, respectively, died as neonates (N = 24.1%, S = 32.5%, p

[This corrects the article DOI: 10.1371/journal.pmed.1002056.].

Gretchen Stevens and colleagues present the GATHER statement, which seeks to promote good practice in the reporting of global health estimates.

Under the Global Forum for Health Research, the Child Health and Nutrition Research Initiative (CHNRI) began its operations in 1999 and became a Swiss foundation in 2006. The vision of CHNRI was to improve child health and nutrition of all children in low– and middle–income countries (LMIC) through research that informs health policy and practice. Specific objectives included expanding global knowledge on childhood disease burden and cost-effectiveness of interventions, promoting priority setting in research, ensuring inclusion of institutions and scientists in LMIC in setting priorities, promoting capacity development in LMIC and stimulating donors and countries to increase resources for research. CHNRI created a knowledge network, funded research through multiple rounds of a global competitive process and published research papers and policy briefs. A signature effort was to develop a systematic methodology for prioritizing health and nutrition research investments. The “CHNRI method” has been extensively applied to global health problems and is now the most commonly used method for prioritizing health research questions.

In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013–2025.

This study was one of a set of verbal/social autopsy (VASA) investigations undertaken by the WHO/UNICEF–supported Child Health Epidemiology Reference Group to estimate the causes and determinants of neonatal and child deaths in high priority countries. The study objective was to help explain the lack of decrease in neonatal mortality in Niger from 2007 to 2010, a period during which child mortality was decreasing.

Physician assessment historically has been the most common method of analyzing verbal autopsy (VA) data. Recently, the World Health Organization endorsed two automated methods, Tariff 2.0 and InterVA–4, which promise greater objectivity and lower cost. A disadvantage of the Tariff method is that it requires a training data set from a prior validation study, while InterVA relies on clinically specified conditional probabilities. We undertook to validate the hierarchical expert algorithm analysis of VA data, an automated, intuitive, deterministic method that does not require a training data set.

The World Health Organization (WHO) currently coordinates rotavirus diarrhea and invasive bacterial disease (IBD) surveillance at 178 sentinel sites in 60 countries. However, only 78 sites participate in both surveillance systems using a common sentinel site. Here, we explored the feasibility of extending a WHO-IBD surveillance platform to generate data on the burden of rotaviral diarrhea and its epidemiological characteristics to prepare the countries to measure the impact of rotaviral vaccine. A six-month (July to December, 2012) surveillance, managed by IBD team, collected stool samples and clinical data from under-five children with acute watery diarrhea at an IBD sentinel site. Samples were tested for rotavirus antigen by ELISA and genotyped by PCR at the regional reference laboratory (RRL). Specimens were collected from 79% (n=297) of eligible cases (n=375); 100% of which were tested for rotavirus by ELISA and 54% (159/297) of them were positive. At RRL, all the cases were confirmed by PCR and genotyped (99%; 158/159). The typing results revealed the predominance of G12 (40%; 64/159) genotype, followed by G1 (31%; 50/159) and G9 (19%; 31/159). All in all, this exploratory surveillance collected the desired demographic and epidemiological data and achieved almost all the benchmark indicators of WHO, starting from enrollment number to quality assurance through a number of case detection, collection, and testing of specimens and genotyping of strains at RRL. The success of this WHO-IBD site in achieving these benchmark indicators of WHO can be used by WHO as a proof-of-concept for considering integration of rotavirus surveillance with WHO-IBD platforms, specifically in countries with well performing IBD site and no ongoing rotavirus surveillance.

Improving the counting of stillbirths and neonatal deaths is important to tracking Sustainable Development Goal 3.2 and improving vital statistics in low- and middle-income countries (LMICs). However, the validity of self-reported stillbirths and neonatal deaths in surveys is often threatened by misclassification errors between the two birth outcomes. We assessed the extent and correlates of stillbirths being misclassified as neonatal deaths by comparing two recent and linked population surveys conducted in Malawi, one being a full birth history (FBH) survey, and the other a follow-up verbal/social autopsy (VASA) survey. We found that one-fifth of 365 neonatal deaths identified in the FBH survey were classified as stillbirths in the VASA survey. Neonatal deaths with signs of movements in the last few days before delivery reported were less likely to be misclassified stillbirths (OR = 0.08, p

BackgroundFoodborne diseases are important worldwide, resulting in considerable morbidity and mortality. To our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases.Methods and findingsWe synthesized data on the number of foodborne illnesses, sequelae, deaths, and Disability Adjusted Life Years (DALYs), for all diseases with sufficient data to support global and regional estimates, by age and region. The data sources included varied by pathogen and included systematic reviews, cohort studies, surveillance studies and other burden of disease assessments. We sought relevant data circa 2010, and included sources from 1990-2012. The number of studies per pathogen ranged from as few as 5 studies for bacterial intoxications through to 494 studies for diarrheal pathogens. To estimate mortality for Mycobacterium bovis infections and morbidity and mortality for invasive non-typhoidal Salmonella enterica infections, we excluded cases attributed to HIV infection. We excluded stillbirths in our estimates. We estimate that the 22 diseases included in our study resulted in two billion (95% uncertainty interval [UI] 1.5-2.9 billion) cases, over one million (95% UI 0.89-1.4 million) deaths, and 78.7 million (95% UI 65.0-97.7 million) DALYs in 2010. To estimate the burden due to contaminated food, we then applied proportions of infections that were estimated to be foodborne from a global expert elicitation. Waterborne transmission of disease was not included. We estimate that 29% (95% UI 23-36%) of cases caused by diseases in our study, or 582 million (95% UI 401-922 million), were transmitted by contaminated food, resulting in 25.2 million (95% UI 17.5-37.0 million) DALYs. Norovirus was the leading cause of foodborne illness causing 125 million (95% UI 70-251 million) cases, while Campylobacter spp. caused 96 million (95% UI 52-177 million) foodborne illnesses. Of all foodborne diseases, diarrheal and invasive infections due to non-typhoidal S. enterica infections resulted in the highest burden, causing 4.07 million (95% UI 2.49-6.27 million) DALYs. Regionally, DALYs per 100,000 population were highest in the African region followed by the South East Asian region. Considerable burden of foodborne disease is borne by children less than five years of age. Major limitations of our study include data gaps, particularly in middle- and high-mortality countries, and uncertainty around the proportion of diseases that were foodborne.ConclusionsFoodborne diseases result in a large disease burden, particularly in children. Although it is known that diarrheal diseases are a major burden in children, we have demonstrated for the first time the importance of contaminated food as a cause. There is a need to focus food safety interventions on preventing foodborne diseases, particularly in low- and middle-income settings.

To address inadequate coverage of oral rehydration salts (ORS) and zinc supplements for the treatment of diarrhea among children under–five, the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program was carried out from 2011–2013 in Gujarat and from 2011–2014 in Uttar Pradesh (UP), India. The program focused on improving the diarrhea treatment practices of public and private sector providers. We conducted cross–sectional household surveys in program districts at baseline and endline and constructed state–specific logistic regression models with generalized estimating equations to assess changes in ORS and zinc treatment during the program period. Between baseline and endline, zinc coverage increased from 2.5% to 22.4% in Gujarat and from 3.1% to 7.0% in UP; ORS coverage increased from 15.3% to 39.6% in Gujarat but did not change in UP. In comparison to baseline, children with diarrhea in the two–weeks preceding the endline survey had higher odds of receiving zinc treatment in both Gujarat (odds ratio, OR = 11.2; 95% confidence interval (CI) 6.4–19.3) and UP (OR = 2.4; 95% CI 1.4–3.9), but the odds of receiving ORS only increased in Gujarat (OR = 3.6; 95% CI 2.7–4.8; UP OR = 0.9; 95% CI 0.7–1.2). Seeking care outside the home, especially from a public sector source, was associated with higher odds of receiving ORS and zinc. Conclusions During the duration of the DAZT program, there were modest improvements in the treatment of diarrhea among young children. Future programs should build upon and accelerate this trend with continued investment in public and private sector provider training and supply chain sustainability, in addition to targeted care–giver demand generation activities.

There is limited evidence on adherence to the recommended dose and duration of zinc supplementation for diarrheal episodes in children under five years of age. In selected districts of Uttar Pradesh, India, we sought to assess adherence to the nationally advised zinc treatment regimen (ie, 10 mg/day for ages 2–6 months and 20 mg/day for ages 7–59 months for 14 days) among caregivers of zinc–prescribed children. We identified and conducted follow–up visits to children advised zinc for the treatment of diarrhea. At the initial visit, we collected data on the treatment instructions received from providers. Caregivers were asked to record treatments administered on a pictorial tracking form and were asked to retain all packaging for collection at follow–up. We quantified the average dose and duration of zinc therapy and built logistic regression models to assess the factors associated with caregiver adherence to national guidelines. Caregivers administered zinc for an average of 10.7 days (standard deviation (SD) = 3.9 days; median = 13 days), and 47.8% continued treatment for the complete 14 days. Among children receiving zinc syrups and tablets respectively, the age appropriate dose was received by 30.8% and 67.3%. Adherence to age appropriate dose and continuation of zinc for 14 days were highly associated with having received appropriate provider instructions. Our results indicate moderate–to–good adherence to national zinc treatment guidelines for diarrhea among caregivers in rural India. Our findings also highlight the importance of provider guidance in ensuring adherence to zinc dose and duration. Programs aiming to scale–up zinc treatment for childhood diarrhea should train providers to successfully communicate dosing instructions to caregivers, while also addressing the tendency of caregivers to terminate treatment once a child appears to have recovered from an acute diarrheal episode.

Recent studies, partly based on murine models, suggest childhood immunization and vitamin A supplements may confer protection against malaria infection, although strong evidence to support these theories in humans has so far been lacking. We analyzed national survey data from children aged 6–59 months in four sub-Saharan African countries over an 18-month time period, to determine the risk of Plasmodium spp. parasitemia (n=8390) and Plasmodium falciparum HRP-2 (PfHRP-2)-related antigenemia (n=6121) following vitamin A supplementation and standard vaccination. Bacille Calmette Guerin-vaccinated children were more likely to be PfHRP-2 positive (relative risk [RR]=4.06, 95% confidence interval [CI]=2.00–8.28). No association was identified with parasitemia. Measles and polio vaccination were not associated with malaria. Children receiving vitamin A were less likely to present with parasitemia (RR=0.46, 95% CI=0.39–0.54) and antigenemia (RR=0.23, 95% CI=0.17–0.29). Future studies focusing on climate seasonality, placental malaria and HIV are needed to characterize better the association between vitamin A and malaria infection in different settings.

Diarrhoeal diseases are major contributors to the global burden of disease, particularly in children. However, comprehensive estimates of the incidence and mortality due to specific aetiologies of diarrhoeal diseases are not available. The objective of this study is to provide estimates of the global and regional incidence and mortality of diarrhoeal diseases caused by nine pathogens that are commonly transmitted through foods.We abstracted data from systematic reviews and, depending on the overall mortality rates of the country, applied either a national incidence estimate approach or a modified Child Health Epidemiology Reference Group (CHERG) approach to estimate the aetiology-specific incidence and mortality of diarrhoeal diseases, by age and region. The nine diarrhoeal diseases assessed caused an estimated 1.8 billion (95% uncertainty interval [UI] 1.1-3.3 billion) cases and 599,000 (95% UI 472,000-802,000) deaths worldwide in 2010. The largest number of cases were caused by norovirus (677 million; 95% UI 468-1,153 million), enterotoxigenic Escherichia coli (ETEC) (233 million; 95% UI 154-380 million), Shigella spp. (188 million; 95% UI 94-379 million) and Giardia lamblia (179 million; 95% UI 125-263); the largest number of deaths were caused by norovirus (213,515; 95% UI 171,783-266,561), enteropathogenic E. coli (121,455; 95% UI 103,657-143,348), ETEC (73,041; 95% UI 55,474-96,984) and Shigella (64,993; 95% UI 48,966-92,357). There were marked regional differences in incidence and mortality for these nine diseases. Nearly 40% of cases and 43% of deaths caused by these nine diarrhoeal diseases occurred in children under five years of age.Diarrhoeal diseases caused by these nine pathogens are responsible for a large disease burden, particularly in children. These aetiology-specific burden estimates can inform efforts to reduce diarrhoeal diseases caused by these nine pathogens commonly transmitted through foods.

BACKGROUND:Deficiencies in essential vitamins and minerals-also termed hidden hunger-are pervasive and hold negative consequences for the cognitive and physical development of children. METHODS:This analysis evaluates the change in hidden hunger over time in the form of one composite indicator-the Hidden Hunger Index (HHI)-using an unweighted average of prevalence estimates from the Nutrition Impact Model Study for anemia due to iron deficiency, vitamin A deficiency, and stunting (used as a proxy indicator for zinc deficiency). Net changes from 1995-2011 and population weighted regional means for various time periods are measured. FINDINGS:Globally, hidden hunger improved (-6.7 net change in HHI) from 1995-2011. Africa was the only region to see a deterioration in hidden hunger (+1.9) over the studied time period; East Asia and the Pacific performed exceptionally well (-13.0), while other regions improved only slightly. Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anemia due to iron deficiency persisted and even increased. INTERPRETATION:This analysis is critical for informing and tracking the impact of policy and programmatic efforts to reduce micronutrient deficiencies, to advance the global nutrition agenda, and to achieve the Millennium Development Goals (MDGs). However, there remains an unmet need to invest in gathering frequent, nationally representative, high-quality micronutrient data as we renew our efforts to scale up nutrition, and as we enter the post-2015 development agenda. FUNDING:Preparation of this manuscript was funded by Sight and Life. There was no funding involved in the study design, data collection, analysis, or decision to publish.

As community case management of childhood illness expands in low-income countries, there is a need to assess the quality of care provided by community health workers. This study had the following objectives: 1) examine methods of recruitment of sick children for assessment of quality of care, 2) assess the validity of register review (RR) and direct observation only (DO) compared to direct observation with re-examination (DO+RE), and 3) assess the effect of observation on community health worker performance.We conducted a survey to assess the quality of care provided by Ethiopian Health Extension Workers (HEWs). The sample of children was obtained through spontaneous consultation, HEW mobilization, or recruitment by the survey team. We assessed patient characteristics by recruitment method. Estimates of indicators of quality of care obtained using RR and DO were compared to gold standard estimates obtained through DO+RE. Sensitivity, specificity, and the area under receiver operator characteristic curve (AUC) were calculated to assess the validity of RR and DO. To assess the Hawthorne effect, we compared estimates from RR for children who were observed by the survey team to estimates from RR for children who were not observed by the survey team.Participants included 137 HEWs and 257 sick children in 103 health posts, plus 544 children from patient registers. Children mobilized by HEWs had the highest proportion of severe illness (27%). Indicators of quality of care from RR and DO had high sensitivity for most indicators, but specificity was low. The AUC for different indicators from RR ranged from 0.47 to 0.76, with only one indicator above 0.75. The AUC of indicators from DO ranged from 0.54 to 1.0, with three indicators above 0.75. The differences between estimates of correct care for observed versus not observed children were small.Mobilization by HEWs and recruitment by the survey teams were feasible, but potentially biased, methods of obtaining sick children. Register review and DO underestimated performance errors. Our data suggest that being observed had only a small positive effect on the performance of HEWs.

Programs aimed at reducing the burden of diarrhea among children under-five in low-resource settings typically allocate resources to training community-level health workers, but studies have suggested that provider knowledge does not necessarily translate into adequate practice. A diarrhea management program implemented in Bihar, Gujarat and Uttar Pradesh, India trained private sector rural medical practitioners (RMPs) and public sector Accredited Social Health Activists (ASHAs) and Anganwadi workers (AWWs) in adequate treatment of childhood diarrhea with oral rehydration salts (ORS) and zinc. We used cross-sectional program evaluation data to determine the association between observed diarrhea treatment practices and reported knowledge of ORS and zinc among each provider cadre.We conducted principal components analysis on providers' responses to diarrhea treatment questions in order to generate a novel scale assessing ORS/zinc knowledge. We subsequently regressed a binary indicator of whether ORS/zinc was prescribed during direct observation onto the resulting knowledge scores, controlling for other relevant knowledge predictors.There was a positive association between ORS/zinc knowledge score and prescribing ORS and zinc to young children with diarrhea among private sector RMPs (aOR: 2.32; 95% CI: 1.29-4.17) and public sector ASHAs and AWWs (aOR 2.48; 95% CI: 1.90-3.24). Controlling for knowledge score, receipt of training in the preceding 6 months was a good predictor of adequate prescribing in the public but not the private sector. In the public sector, direct access to ORS and zinc supplies was also highly associated with prescribing.To enhance the management of childhood diarrhea in India, programmatic activities should center on increasing knowledge of ORS and zinc among public and private sector providers through biannual trainings but should also focus on ensuring sustained access to an adequate supply chain.

Ethiopia has scaled up its community-based programs over the past decade by training and deploying health extension workers (HEWs) in rural communities throughout the country. Consequently, child mortality has declined substantially, placing Ethiopia among the few countries that have achieved the United Nations' fourth Millennium Development Goal. As Ethiopia continues its efforts, results must be assessed regularly to provide timely feedback for improvement and to generate further support for programs. More specifically the expansion of HEWs at the community level provides a unique opportunity to build a system for real-time monitoring of births and deaths, linked to a civil registration and vital statistics system that Ethiopia is also developing. We tested the accuracy and completeness of births and deaths reported by trained HEWs for monitoring child mortality over 15 -month periods.HEWs were trained in 93 randomly selected rural kebeles in Jimma and West Hararghe zones of the Oromia region to report births and deaths over a 15-month period from January, 2012 to March, 2013. Completeness of number of births and deaths, age distribution of deaths, and accuracy of resulting under-five, infant, and neonatal mortality rates were assessed against data from a large household survey with full birth history from women aged 15-49. Although, in general HEWs, were able to accurately report events that they identified, the completeness of number of births and deaths reported over twelve-month periods was very low and variable across the two zones. Compared to household survey estimates, HEWs reported only about 30% of births and 21% of under-five deaths occurring in their communities over a twelve-month period. The under-five mortality rate was under-estimated by around 30%, infant mortality rate by 23% and neonatal mortality by 17%. HEWs reported disproportionately higher number of deaths among the very young infants than among the older children.Birth and death data reported by HEWs are not complete enough to support the monitoring of changes in childhood mortality. HEWs can significantly contribute to the success of a CRVS in Ethiopia, but cannot be relied upon as the sole source for identification of vital events. Further studies are needed to understand how to increase the level of completeness.