Search

Background Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage. Methods and findings We performed a randomized, 2 x 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania. Mother-child dyads were enrolled by age 14 days and followed with monthly home visits and every 3-month anthropometry assessments through 18 months. Those randomized to the antimicrobial arm received 2 medications (versus corresponding placebos): azithromycin (single dose of 20 mg/kg) at months 6, 9, 12, and 15 and nitazoxanide (3-day course of 100 mg twice daily) at months 12 and 15. Those randomized to nicotinamide arm received daily nicotinamide to the mother (250 mg pills months 0 to 6) and to the child (100 mg sachets months 6 to 18). Primary outcome was length-for-age z-score (LAZ) at 18 months in the modified intention-to-treat group. Between September 5, 2017 and August 31, 2018, 1,188 children were randomized, of whom 1,084 (n = 277 placebo/placebo, 273 antimicrobial/placebo, 274 placebo/nicotinamide, and 260 antimicrobial/nicotinamide) were included in the modified intention-to-treat analysis. The study was suspended for a 3-month period by the Tanzanian National Institute for Medical Research (NIMR) because of concerns related to the timing of laboratory testing and the total number of serious adverse events (SAEs); this resulted in some participants receiving their final study assessment late. There was a high prevalence of stunting overall (533/1,084, 49.2%). Mean 18-month LAZ did not differ between groups for either intervention (mean LAZ with 95% confidence interval [CI]: antimicrobial: -2.05 CI -2.13, -1.96, placebo: -2.05 CI -2.14, -1.97; mean difference: 0.01 CI -0.13, 0.11, p = 0.91; nicotinamide: -2.06 CI -2.13, -1.95, placebo: -2.04 CI -2.14, -1.98, mean difference 0.03 CI -0.15, 0.09, p = 0.66). There was no difference in LAZ for either intervention after adjusting for possible confounders (baseline LAZ, age in days at 18-month measurement, ward, hospital birth, birth month, years of maternal education, socioeconomic status (SES) quartile category, sex, whether the mother was a member of the Datoga tribe, and mother's height). Adverse events (AEs) and SAEs were overall similar between treatment groups for both the nicotinamide and antimicrobial interventions. Key limitations include the absence of laboratory measures of pathogen carriage and nicotinamide metabolism to provide context for the negative findings. Conclusions In this study, we observed that neither scheduled administration of azithromycin and nitazoxanide nor daily provision of nicotinamide was associated with improved growth in this resource-poor setting with a high force of enteric infections. Further research remains critical to identify interventions toward improved early childhood growth in challenging conditions. Trial registration ClinicalTrials.gov NCT03268902., Author(s): Mark D. DeBoer 1,*, James A. Platts-Mills 2, Sarah E. Elwood 2, Rebecca J. Scharf 1,2, Joann M. McDermid 2, Anne W. Wanjuhi 2, Samwel Jatosh 3, Siphael Katengu [...]

Objective To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics. Methods Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers' reports at twice-weekly visits over the children's first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class. Findings Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an Incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites. Conclusion Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non- specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest. Objectif Decrire la frequence et les facteurs associes a l'utilisation d'antibiotiques chez les jeunes enfants et estimer la proportion d'episodes de diarrhee et de maladies respiratoires traites avec des antibiotiques. Methodes De 2009 a 2014, nous avons suivi 2134 enfants qui participaient a l'etude de cohorte de naissance MAL-ED sur huit sites en Afrique du Sud, au Bangladesh, au Bresil, en Inde, au Nepal, au Pakistan, au Perou et en Republique-Unie de Tanzanie. Nous avons note l'utilisation de tous les antibiotiques declares par les meres lors de consultations bi-hebdomadalres pendant les deux premieres annees de vie des enfants. Nous avons estime l'Incidence du recours aux antibiotiques ainsi que les associations entre utilisation d'antibiotiques et caracteristiques des enfants et des foyers. Nous avons decrit les habitudes de traitement de la diarrhee et des maladies respiratoires et avons Identifie les facteurs associes aux traitements et aux classes d'antibiotiques. Resultats Sur 1 346 388 jours d'observation au total, 16 913 traitements aux antibiotiques ont ete enregistres (Incidence de 4,9 traitements par enfant et par an), la plus forte utilisation ayant ete observee en Asie du Sud. Un traitement antibiotique a ete administre pour 375/499 (75,2%) episodes de diarrhee sanglante et pour 4274/9661 (44,2%) episodes de diarrhee sans presence de sang dans les selles. Des antibiotiques ont ete utilises pour 2384/3943 (60,5%) episodes de maladie aigue des voies respiratoires inferieures confirmee par un professionnel sur le terrain ainsi que pour 6608/16 742 (39,5%) episodes de maladie des voies respiratoires superieures. Les penicillines etaient les plus frequemment utilisees pour combattre les maladies respiratoires, tandis que les classes d'antibiotiques utilisees pour traiter la diarrhee variaient selon les sites et au sein d'un meme site. Conclusion L'exposition repetee aux antibiotiques a un jeune age etait courante et le traitement de la diarrhee sans presence de sang dans les selles et de maladies respiratoires non specifiques ne respectait pas les recommandations internationales. C'est en Asie du Sud, oU l'usage des antibiotiques etait le plus important, que les programmes d'utilisation rationnelle des antibiotiques pourraient avoir le plus fort impact. Objetivo Describir la frecuencia y los-factores relacionados con el uso de antibioticos en la primera infancia y estimar la proporcion de los episodios de diarrea y enfermedades respiratorias tratados con antibioticos. Metodos Entre 2009 y 2014, se realizo el seguimiento de 2 134 ninos de ocho lugares en Bangladesh, Brasil, India, Nepal, Pakistan, Peru, la Republica Unida de Tanzania y Sudafrica inscritos en el estudio de cohortes en el nacimiento MAL-ED. Se documento el uso de todos los antibioticos de los informes de las madres en las visitas dos veces por semana a lo largo de los dos primeros anos de vida de los ninos. Se estimo la incidencia del uso de antibioticos y las asociaciones del uso de antibioticos con caracteristicas familiares y con ninos. Se describieron los patrones de tratamiento para la diarrea y las enfermedades respiratorias, y se identificaron los factores relacionados con las clases de tratamientos y de antibioticos. Resultados De un total de 1 346 388 dias de observacion, se registraron 16 913 tratamientos con antibioticos (una incidencia de 4,9 tratamientos por nino al ano), siendo el mayor uso en el sur de Asia. Se empleo tratamiento con antibioticos en 375/499 (75,2%) episodios de diarrea hemorragica y en 4 274/9 661 (44,2%) episodios de diarrea sin deposiciones hemorragicas. Se usaron antibioticos en 2 384/3 943 (60,5%) episodios de enfermedad respiratoria aguda de las vias bajas confirmadas por los investigadores, asi como en 6 608/16 742 (39,5%) episodios de enfermedad respiratoria de las vias altas. Las penicilinas se usaron mas frecuentemente para las enfermedades respiratorias, mientras que los antibioticos para el tratamiento de la diarrea variaron entre los distintos lugares. Conclusion La exposicion repetida a antibioticos fue comun en los primeros anos de vida, y el tratamiento de diarrea no hemorragica y de enfermedades respiratorias no especificas no fue coherente con las recomendaciones internacionales. Los programas de uso racional de antibioticos pueden tener el mayor efecto en el sur de Asia, donde el uso de antibioticos fue el mas alto., Introduction Antibiotics can be a lifesaving treatment for children with bacterial infections and are the most commonly prescribed therapy among all medications given to children. (1) However, antibiotics can also [...]

Since its discovery in 1976 (1), Ebola virus has caused small sporadic outbreaks with high case-fatality rates (CFRs), mostly in rural areas in central and eastern Africa (2). The outbreak [...]

Abstract Background Stunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites. Methods We administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites. Results Average age of study children was 41 months. Mean food access insecurity score (range: 0–27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17). Conclusions Our study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition.

Background: Poor growth in early childhood has been considered irreversible after 2-3 years of age and has been associated with morbidity and mortality over the short-term and with poor economic and cognitive outcomes over the long-term. The MAL-ED cohort study was performed in eight low-income settings with the goal of evaluating relationships between the child's environment and experience (dietary, illness, and pathogen exposure, among others) and their growth and development. The goal of this analysis is to determine whether there are differences in the factors associated with growth from 24 to 60 months using two different metrics.Methods: Across six MAL-ED sites, 942 children had anthropometry data at 24 and 60 months, as well as information about socioeconomic status, maternal height, gut permeability (lactulose-mannitol z-score (LMZ)), dietary intake from 9 to 24 months, and micronutrient status. Anthropometric changes were in height- or weight-for-age z-score (HAZ, WAZ), their absolute difference from the growth standard median (HAD (cm), WAD (kg)), as well as recovery from stunting/underweight. Outcomes were modeled using multivariate regression.Results: At 24 months, almost half of the cohort was stunted (45%) and 21% were underweight. Among those who were stunted at 24 months (n = 426), 185 (43%) were no longer stunted at 60 months. Most children increased their HAZ from 24 to 60 months (81%), whereas fewer (33%) had positive changes in their HAD. Linear regression models indicate that girls improved less than boys from 24 to 60 months (HAZ: -0.21 (95% CI -0.27, -0.15); HAD: -0.75 (-1.07, -0.43)). Greater intestinal permeability (higher LMZ) at 0-24 months was associated with lower relative and absolute changes from 24 to 60 months (HAZ: -0.10 (-0.16, -0.04); HAD: -0.47 (-0.73, -0.21)). Maternal height (per 10 cm) was positively associated with changes (HAZ: 0.09 (0.03, 0.15); HAD: 0.45 (0.15, 0.75)). Similar relationships were identified for changes in WAZ and WAD.Conclusions: The study children demonstrated improved growth from 24 to 60 months of age, but only a subset had positive changes in HAD and WAD. The same environmental factors were associated with growth from 24 to 60 months regardless of metric used (change in HAZ or HAD, or WAZ and WAD). [ABSTRACT FROM AUTHOR]

Abstract: Although many studies around the world hope to measure or improve developmental progress in children to promote community flourishing and productivity, growth is sometimes used as a surrogate because cognitive skills are more difficult to measure. Our objective was to assess how childhood measures of anthropometry correlate with measures of child development in low‐income settings with high prevalence of poor nutrition and enteric disease, to inform studies considering growth outcomes in the absence of direct child developmental skill assessment. Children from the MAL‐ED study were followed from birth to 24 months of age in field sites in 8 low‐ and middle‐income countries across 3 continents. Monthly weight, length, and head circumference measurements were performed. At 24 months, the Bayley Scales of Infant and Toddler Development was administered. We correlated cognitive measures at 24 months with anthropometric measurements from birth to 2 years comparing 3 constructs: absolute attained monthly measures, summative difference in measures from the mean growth curve, and rate of change in measures. Growth faltering at multiple time periods is related to Bayley cognitive outcomes at 24 months. Birthweight, overall growth by 18–24 months, and rate of growth in the 6‐ to 18‐month period were most associated with 24‐month developmental scores. In this study, head circumference measurements, compared with length, was more closely linked to cognitive scores at 24 months. Notably, all studies between growth and cognitive outcomes exhibited low r2 values (0.001–0.049). Anthropometric measures, particularly head circumference, were related to cognitive development, although explaining a low percent of variance. When feasible, direct measures of child development may be more useful. [ABSTRACT FROM AUTHOR]

Introduction As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam). [ABSTRACT FROM AUTHOR]

Background. Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study. Methods. From 2089 children, 34 916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. Results. The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years. Conclusions. Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestinal permeability and stunted growth. [ABSTRACT FROM AUTHOR]

Introduction: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods of neurodevelopment. Methods and analysis In this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12 supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12 daily for at least 6 months. Vitamin B12 was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12 supplementation in different periods during early life and measure the outcomes later in childhood. Ethics and dissemination The study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access. Trial registration number NCT00641862 (Bangalore); NCT00717730, updated CTRI/2016/11/007494 (Delhi); NCT00197548 and NCT00421668 (Dar es Salaam).

Although many studies around the world hope to measure or improve developmental progress in children to promote community flourishing and productivity, growth is sometimes used as a surrogate because cognitive skills are more difficult to measure. Our objective was to assess how childhood measures of anthropometry correlate with measures of child development in low-income settings with high prevalence of poor nutrition and enteric disease, to inform studies considering growth outcomes in the absence of direct child developmental skill assessment. Children from the MAL-ED study were followed from birth to 24 months of age in field sites in 8 low- and middle-income countries across 3 continents. Monthly weight, length, and head circumference measurements were performed. At 24 months, the Bayley Scales of Infant and Toddler Development was administered. We correlated cognitive measures at 24 months with anthropometric measurements from birth to 2 years comparing 3 constructs: absolute attained monthly measures, summative difference in measures from the mean growth curve, and rate of change in measures. Growth faltering at multiple time periods is related to Bayley cognitive outcomes at 24 months. Birthweight, overall growth by 18-24 months, and rate of growth in the 6- to 18-month period were most associated with 24-month developmental scores. In this study, head circumference measurements, compared with length, was more closely linked to cognitive scores at 24 months. Notably, all studies between growth and cognitive outcomes exhibited low r 2 values (0.001-0.049). Anthropometric measures, particularly head circumference, were related to cognitive development, although explaining a low percent of variance. When feasible, direct measures of child development may be more useful., (© 2018 John Wiley & Sons Ltd.)

Background: There is no standardized approach to comparing socioeconomic status (SES) across multiple sites in epidemiological studies. This is particularly problematic when cross-country comparisons are of interest. We sought to develop a simple measure of SES that would perform well across diverse, resource-limited settings., Methods: A cross-sectional study was conducted with 800 children aged 24 to 60 months across eight resource-limited settings. Parents were asked to respond to a household SES questionnaire, and the height of each child was measured. A statistical analysis was done in two phases. First, the best approach for selecting and weighting household assets as a proxy for wealth was identified. We compared four approaches to measuring wealth: maternal education, principal components analysis, Multidimensional Poverty Index, and a novel variable selection approach based on the use of random forests. Second, the selected wealth measure was combined with other relevant variables to form a more complete measure of household SES. We used child height-for-age Z-score (HAZ) as the outcome of interest., Results: Mean age of study children was 41 months, 52% were boys, and 42% were stunted. Using cross-validation, we found that random forests yielded the lowest prediction error when selecting assets as a measure of household wealth. The final SES index included access to improved water and sanitation, eight selected assets, maternal education, and household income (the WAMI index). A 25% difference in the WAMI index was positively associated with a difference of 0.38 standard deviations in HAZ (95% CI 0.22 to 0.55)., Conclusions: Statistical learning methods such as random forests provide an alternative to principal components analysis in the development of SES scores. Results from this multicountry study demonstrate the validity of a simplified SES index. With further validation, this simplified index may provide a standard approach for SES adjustment across resource-limited settings.