Incidence of Asymptomatic Shigella Infection and Association with the Composite Index of Anthropometric Failure among Children Aged 1-24 Months in Low-Resource Settings.

Asymptomatic or subclinical infection by diarrheal enteropathogens during childhood has been linked to poor health and nutritional outcomes. In this study, we aimed to assess the impact of asymptomatic Shigella infection on different forms of childhood malnutrition including the composite index of anthropometric failure (CIAF). We used data from 1715 children enrolled in the multi-country birth cohort study, MAL-ED, from November 2009 to February 2012. Monthly non-diarrheal stools were collected and assessed using TaqMan Array Cards (TAC). Poisson regression was used to calculate incidence rates of asymptomatic Shigella infection. Generalized estimating equations (GEE) were used to assess the association between asymptomatic Shigella infection and nutritional indicators after adjusting for relevant covariates. Incidence rates per 100 child-months were higher in Tanzania, Bangladesh and Peru. Overall, after adjusting for relevant covariates, asymptomatic Shigella infection was significantly associated with stunting (aOR 1.60; 95% CI: 1.50, 1.70), wasting (aOR 1.26; 95% CI: 1.09, 1.46), underweight (aOR 1.45; 95% CI: 1.35, 1.56), and CIAF (aOR 1.55; 95% CI: 1.46, 1.65) in all the study sites except for Brazil. The high incidence rates of asymptomatic Shigella infection underscore the immediate need for Shigella vaccines to avert the long-term sequelae involving childhood growth.

Inadequate Vitamin C Intake and Intestinal Inflammation Are Associated with Multiple Micronutrient Deficiency in Young Children: Results from a Multi-Country Birth Cohort Study.

Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex [OR: 0.72, 95% CI: 0.54, 0.92]. A greater risk of MMD was associated with lower vitamin C intake [OR: 0.70, 95% CI: 0.48, 0.94] and increased fecal concentrations of MPO [OR: 1.31, 95% CI: 1.08, 1.51]. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.

Effect of early life antibiotic use on serologic responses to oral rotavirus vaccine in the MAL-ED birth cohort study.

BACKGROUND: Oral rotavirus vaccine efficacy is lower in low- and middle-income countries (LMICs) than in high-income countries. The degree to which antibiotic use impacts rotavirus vaccine immunogenicity in LMICs is unknown. Using data from a multisite prospective birth cohort study of malnutrition and enteric disease, MAL-ED, we examined the effect of early life antibiotic use on the immune response to rotavirus vaccine. METHODS: We assessed whether antibiotic use from birth up to 7 days following rotavirus vaccine series completion was associated with rotavirus seropositivity at 7 months of age in Brazil, Peru, and South Africa using a modified Poisson regression. We then used parametric g-computation to estimate the impact of hypothetical interventions that treated all children and alternatively prevented inappropriate antibiotic treatments on seropositivity. RESULTS: Of 537 children, 178 (33%) received at least one antibiotic course during the exposure window. Probability of seropositivity was 40% higher among children who had at least one course of antibiotics compared with those with no antibiotic exposure (PR: 1.40, 95% CI: 1.04, 1.89). There was no significant difference by the number of antibiotic courses received or total duration of antibiotics. Treating all children with antibiotics would be associated with a 19% (95% CI: 18%, 21%) absolute increase in seropositivity at 7 months. In contrast, removing inappropriate antibiotics would result in a 4% absolute reduction (95% CI: -5%, -2%) in seropositivity. CONCLUSIONS: Early life antibiotic use was associated with increased seropositivity. However, a hypothetical intervention to remove inappropriate antibiotics would have little effect on overall seropositivity. Further investigation into the underlying mechanisms of antibiotic use on the infant gut microbiome and immune response are needed.

Full breastfeeding protection against common enteric bacteria and viruses: results from the MAL-ED cohort study.

BACKGROUND: Breastfeeding is known to reduce the risk of enteropathogen infections, but protection from specific enteropathogens is not well characterized. OBJECTIVE: The aim was to estimate the association between full breastfeeding (days fed breast milk exclusively or with nonnutritive liquids) and enteropathogen detection. METHODS: A total of 2145 newborns were enrolled at 8 sites, of whom 1712 had breastfeeding and key enteropathogen data through 6 mo. We focused on 11 enteropathogens: adenovirus 40/41, norovirus, sapovirus, astrovirus, and rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter spp., and typical enteropathogenic E. coli as well as entero-aggregative E. coli, Shigella and Cryptosporidium. Logistic regression was used to estimate the risk of enteropathogen detection in stools and survival analysis was used to estimate the timing of first detection of an enteropathogen. RESULTS: Infants with 10% more days of full breastfeeding within the preceding 30 d of a stool sample were less likely to have the 3 E. coli and Campylobacter spp. detected in their stool (mean odds: 0.92-0.99) but equally likely (0.99-1.02) to have the viral pathogens detected in their stool. A 10% longer period of full breastfeeding from birth was associated with later first detection of the 3 E. coli, Campylobacter, adenovirus, astrovirus, and rotavirus (mean HRs of 0.52-0.75). The hazards declined and point estimates were not statistically significant at 3 mo. CONCLUSIONS: In this large multicenter cohort study, full breastfeeding was associated with lower likelihood of detecting 4 important enteric pathogens in the first 6 mo of life. These results also show that full breastfeeding is related to delays in the first detection of some bacterial and viral pathogens in the stool. As several of these pathogens are risk factors for poor growth during childhood, this work underscores the importance of exclusive or full breastfeeding during the first 6 mo of life to optimize early health.

Evaluating association of vaccine response to low serum zinc and vitamin D levels in children of a birth cohort study in Dhaka.

BACKGROUND: Vaccine-preventable infectious diseases are often responsible for childhood morbidity and high rates of mortality. Immune response to the vaccine is associated with multiple factors in early childhood and measured by antibody titers. Among them, micronutrient deficiencies such as vitamin D and zinc deficiencies are the most important in resource-limited settings like Bangladesh. OBJECTIVE: We aimed to evaluate the association of vaccine response to low serum zinc and vitamin D levels in children. METHODS: We evaluated vaccine response for measles and poliovirus, tetanus and pertussis toxoid, and Ig A antibody levels to rotavirus by ELISA and serum vitamin D and zinc at 7 and 15 months in the MAL-ED birth cohort of the Bangladesh site. By using population-specific generalized estimating equations (GEE), the association between each explanatory variable and the binary outcome variable was examined longitudinally where the dependent variable was vaccine titers and the independent variables were low serum vitamin D and zinc levels. RESULTS: The GEE multivariable model identified a positive association between serum zinc level and tetanus vaccine titer (OR: 1.84; 95% CI: 1.07-3.17 and p value = 0.028) after adjusting for age, gender, birth weight, WAMI score, diarrhea, ALRI, exclusive breastfeeding, serum ferritin, serum retinol and undernutrition (stunting, wasting, underweight). No association was found between the rest of the vaccine titers with serum vitamin D and zinc level (p > 0.05). CONCLUSION: In the MAL-ED birth cohort, where children were followed for five years, serum zinc level had a positive impact on tetanus vaccine titers.

Natural Infection with Giardia Is Associated with Altered Community Structure of the Human and Canine Gut Microbiome.

Enteric parasitic infections are among the most prevalent infections in lower- and middle-income countries (LMICs) and have a profound impact on global public health. While the microbiome is increasingly recognized as a key determinant of gut health and human development, the impact of naturally acquired parasite infections on microbial community structure in the gut, and the extent to which parasite-induced changes in the microbiome may contribute to gastrointestinal symptoms, is poorly understood. Enteric parasites are routinely identified in companion animals in the United States, presenting a unique opportunity to leverage this animal model to investigate the impact of naturally acquired parasite infections on the microbiome. Clinical, parasitological, and microbiome profiling of a cohort of 258 dogs revealed a significant correlation between parasite infection and composition of the bacterial community in the gut. Relative to other enteric parasites, Giardia was associated with a more pronounced perturbation of the microbiome. To compare our findings to large-scale epidemiological studies of enteric diseases in humans, a database mining approach was employed to integrate clinical and microbiome data. Substantial and consistent alterations to microbiome structure were observed in Giardia-infected children. Importantly, infection was associated with a reduction in the relative abundance of potential pathobionts, including Gammaproteobacteria, and an increase in Prevotella-a profile often associated with gut health. Taken together, these data show that widespread Giardia infection in young animals and humans is associated with significant remodeling of the gut microbiome and provide a possible explanation for the high prevalence of asymptomatic Giardia infections observed across host species.IMPORTANCE While enteric parasitic infections are among the most important infections in lower- and middle-income countries, their impact on gut microbiota is poorly understood. We reasoned that clinical symptoms associated with these infections may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate to severe diarrhea.

Introducing a drift and diffusion framework for childhood growth research.

Background: Growth trajectories are highly variable between children, making epidemiological analyses challenging both to the identification of malnutrition interventions at the population level and also risk assessment at individual level. We introduce stochastic differential equation (SDE) models into child growth research. SDEs describe flexible dynamic processes comprising: drift - gradual smooth changes - such as physiology or gut microbiome, and diffusion - sudden perturbations, such as illness or infection. Methods: We present a case study applying SDE models to child growth trajectory data from the Haydom, Tanzania and Venda, South Africa sites within the MAL-ED cohort. These data comprise n=460 children aged 0-24 months. A comparison with classical curve fitting (linear mixed models) is also presented. Results: The SDE models offered a wide range of new flexible shapes and parameterizations compared to classical additive models, with performance as good or better than standard approaches. The predictions from the SDE models suggest distinct longitudinal clusters that form distinct 'streams' hidden by the large between-child variability. Conclusions: Using SDE models to predict future growth trajectories revealed new insights in the observed data, where trajectories appear to cluster together in bands, which may have a future risk assessment application. SDEs offer an attractive approach for child growth modelling and potentially offer new insights.

Early childhood development and stunting: Findings from the MAL-ED birth cohort study in Bangladesh.

Information on the association between stunting and child development is limited from low-income settings including Bangladesh where 36% of children under- 5 are stunted. This study aimed to explore differences in early childhood development (ECD) between stunted (length-for-age z-score [LAZ] < -2) and nonstunted (LAZ ≥ -2) children in Bangladesh. Children (n = 265) aged 6-24 months who participated in the MAL-ED birth cohort study were evaluated by trained psychologists at 6, 15, and 24 months of age using the Bayley Scales of Infant and Toddler Development-III; child length and weight were measured using standard procedures. ECD scores (z-scores derived from cognitive, motor, language and socio-emotional skills) were compared between stunted, underweight (weight-for-age z-score < -2), and wasted (weight-for-length z-score < -2) children, controlling for child age and sex and maternal age, education, body mass index (BMI), and depressive symptoms. Stunted children had significantly lower ECD scores than their nonstunted peers on cognitive (P = .049), motor (P < .001), language (P < .001) and social-emotional (P = .038) scales where boys had significantly lower fine motor skills compared with girls (P = .027). Mother's schooling and BMI were significant predictors of ECD. Similar to stunting, underweight children had developmental deficits in all domains (cognitive: P = .001; fine motor: P = .039, and P < .001 for both gross motor and total motor; expressive communication: P = .032; total language: P = .013; social-emotional development: P = .017). Wasted children had poor motor skills (P = .006 for the fine motor; P < .001 for both gross motor and total motor development) compared with the nonwasted peers. Early childhood stunting and underweight were associated with poor developmental outcomes in Bangladesh.

Daily Supplementation With Egg, Cow Milk, and Multiple Micronutrients Increases Linear Growth of Young Children with Short Stature.

BACKGROUND: Childhood stunting is the most prevalent public health nutrition problem in low- and middle-income countries. OBJECTIVE: This study aimed to determine whether daily supplementation in 12-18-mo-old undernourished Bangladeshi children with egg, cow milk, and multiple micronutrients improves linear growth. METHODS: In the Bangladesh Environmental Enteric Dysfunction (BEED) study, a community-based intervention study, 12-18-mo-old children with length-for-age z score (LAZ) <1 were supplemented daily with an egg and 150 mL of milk for 90 feeding days, and 1 sachet of multiple micronutrient powder was provided daily for 60 feeding days. The change in LAZ over this period was compared with that in children of the same age and same baseline LAZ who were enrolled in the recently completed Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Dhaka birth cohort study conducted in the same community where no nutrition intervention was provided. Difference-in-difference (DID) analysis was done and the effect size was adjusted for other possible covariates using a generalized estimating equation in a regression model. RESULTS: A total of 472 children with LAZ <1 completed the intervention and data were available for 174 children in the comparison group. Compared with the comparison group, adjusted DID analysis revealed a change in LAZ in the intervention group of +0.23 (95% CI: 0.18, 0.29; P < 0.05). In a subgroup analysis, the changes were +0.27 (95% CI: 0.18, 0.35; P < 0.05) in stunted (LAZ <2) children and +0.19 (95% CI: 0.12, 0.27; P < 0.05) in children at risk of stunting (LAZ -1 to -2). No allergic reactions or other adverse events related to milk and egg consumption were observed. CONCLUSIONS: Daily directly observed milk, egg, and multiple micronutrient supplementation may improve linear growth of stunted children. A randomized controlled trial with longer duration of supplementation coupled with an additional intervention aimed at reducing pathogen burden is warranted to confirm these results. This trial was registered at clinicaltrials.gov as NCT02812615.

Aflatoxin exposure in children living in Mirpur, Dhaka: data from MAL-ED companion study.

Dietary exposure to aflatoxin is implicated in growth faltering of children. Despite the high burden of childhood stunting in urban Bangladesh, there are no data on long-term exposure to aflatoxin. This study aimed to explore aflatoxin exposure levels in a group of children followed longitudinally. The current study used data and biospecimens collected during 2010-2014 as part of the MAL-ED birth cohort study in an urban slum of Mirpur, Dhaka where children were followed from birth to 36 months. AFB1-lysine adduct concentrations were determined by isotope dilution mass spectrometry from plasma samples collected at 7, 15, 24, and 36 months of age. The limit of detection was 0.5 pg of AFB1-lys/mg albumin. In 744 plasma samples, the geometric mean of AFB1-lysine/mg albumin was 1.07 pg (range 0.04-123.5 pg/mg albumin). The proportion of children with detectable aflatoxin exposure was 10.1, 20.9, 17.9, and 61.7% for 7, 15, 24, and 36 months, respectively. Reduction in breastfeeding prevalence (80% at 24 months vs. 38% in 36 months) corresponded with the high-level detection of AFB1-lysine at the age of 36 months. AFB1-lysine concentrations were the highest at the end of monsoon. This study reveals that 62% of children in slum settlement were exposed to aflatoxin by the end of the third year of life. High aflatoxin exposure was detected at the end of rainy season and with the introduction of family food. These findings suggest interventions to ameliorate the problem of chronic aflatoxin exposure including childhood stunting.

Antibiotic Resistance of Campylobacter Species in a Pediatric Cohort Study.

The objective of this study was to determine the phenotypic patterns of antibiotic resistance and the epidemiology of drug-resistant Campylobacter spp. from a low-resource setting. A birth cohort of 303 patients was followed until 5 years of age. Stool samples from asymptomatic children (n = 10,008) and those with diarrhea (n = 3,175) were cultured for Campylobacter Disk diffusion for ciprofloxacin (CIP), nalidixic acid (NAL), erythromycin (ERY), azithromycin (AZM), tetracycline (TE), gentamicin (GM), ampicillin (AMP), amoxicillin and clavulanic acid (AMC), ceftriaxone (CRO), chloramphenicol (C), and trimethoprim-sulfamethoxazole (TMS) was determined. Antibiotic resistances in Campylobacter jejuni and non-C. jejuni isolates from surveillance and diarrhea samples were compared, and the association between personal macrolide exposure and subsequent occurrence of a macrolide-resistant Campylobacter spp. was assessed. Of 917 Campylobacter isolates, 77.4% of C. jejuni isolates and 79.8% of non-C. jejuni isolates were resistant to ciprofloxacin, while 4.9% of C. jejuni isolates and 24.8% of non-C. jejuni isolates were not susceptible to azithromycin. Of the 303 children, 33.1% had been diagnosed with a Campylobacter strain nonsusceptible to both azithromycin and ciprofloxacin. Personal macrolide exposure did not affect the risk of macrolide-resistant Campylobacter Amoxicillin and clavulanic acid (94.0%) was one of the antibiotics with the highest rates of susceptibility. There is a high incidence of quinolone- and macrolide-resistant Campylobacter infections in infants under 24 months of age. Given the lack of association between personal exposure to macrolides and a subsequent Campylobacter infection resistant to macrolides, there is a need to evaluate the source of multidrug-resistant (MDR) Campylobacter This study provides compelling evidence to propose amoxicillin/clavulanic acid as a treatment for campylobacteriosis.

Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings.

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide. Routine norovirus diagnosis requires stool collection. The goal of this study was to develop and validate a noninvasive method to diagnose norovirus to complement stool diagnostics and to facilitate studies on transmission. METHODS: A multiplex immunoassay to measure salivary immunoglobulin G (IgG) responses to 5 common norovirus genotypes (GI.1, GII.2, GII.4, GII.6, and GII.17) was developed. The assay was validated using acute and convalescent saliva samples collected from Peruvian children <5 years of age with polymerase chain reaction (PCR)-diagnosed norovirus infections (n = 175) and controls (n = 32). The assay sensitivity and specificity were calculated to determine infection status based on fold rise of salivary norovirus genotype-specific IgG using norovirus genotype from stool as reference. RESULTS: The salivary assay detected recent norovirus infections and correctly assigned the infecting genotype. Sensitivity was 71% and specificity was 96% across the evaluated genotypes compared to PCR-diagnosed norovirus infection. CONCLUSIONS: This saliva-based assay will be a useful tool to monitor norovirus transmission in high-risk settings such as daycare centers or hospitals. Cross-reactivity is limited between the tested genotypes, which represent the most commonly circulating genotypes.

Associations of land, cattle and food security with infant feeding practices among a rural population living in Manyara, Tanzania.

BACKGROUND: Livelihoods strategies and food security experiences can positively and negatively affect infant and young child feeding (IYCF) practices. This study contributes to this literature by exploring how variation in household economics among rural farmers in Tanzania relates to IYCF patterns over the first 8 months of an infant's life. METHODS: These data were produced from a longitudinal study in which a cohort of mother-infant dyads was followed from birth to 24 months. In addition to baseline maternal, infant, and household characteristics, mothers were queried twice weekly and monthly about infant feeding practices and diet. Weekly and monthly datasets were merged and analyzed to assess infant feeding patterns through the first 8 months. Standard statistical methods including survival and logistic regression analyses were used. RESULTS: Aside from breastfeeding initiation, all other IYCF practices were suboptimal in this cohort. Land and cattle ownership were associated with the early introduction of non-breastmilk food items. Food insecurity also played a role in patterning and inadequate complementary feeding was commonplace. CONCLUSIONS: Health promotion programs are needed to delay the introduction of animal milks and grain-based porridge, and to achieve a minimum acceptable diet after 6 months of age among smallholder farmers in rural Tanzania. Results highlight that livelihoods-based health promotion interventions, built from a flexible and integrated design, may be an important strategy to address community-level variation in infant feeding practices and promote optimal IYCF practices.

Tracking of infant and young child feeding practices among 9- to 24-month-old children in Nepal: the MAL-ED Birth Cohort Study.

OBJECTIVE: The present study aimed to assess infant and young child feeding (IYCF) practices and the tracking of dietary diversity score (DDS), intakes of Fe- and vitamin A-rich foods and meal frequency in a peri-urban area in Nepal. Furthermore, to explore whether sociodemographic factors were associated with tracking patterns of these IYCF practices. DESIGN: Longitudinal study. Monthly food intake was measured by 24 h recall. Four time slots were used (9-12, 13-16, 17-20 and 21-24 months). Tracking of IYCF practices was investigated using generalized estimating equations (GEE) models and Cohen's weighted kappa. Multinominal logistic regression was used to identify determinants for tracking of the IYCF practices. SETTING: Bhaktapur municipality, Nepal. SUBJECTS: Children (n 229) aged 9-24 months, randomly selected. RESULTS: Prevalence of minimum meal frequency was higher than for minimum dietary diversity at all time slots. Tracking based on absolute measures (GEE models) was moderate for DDS (0·48) and meal frequency (0·53), and low for intakes of Fe- (0·23) and vitamin A-rich (0·35) foods. Tracking based on rank measured was moderate for DDS and meal frequency, and fair for Fe- and vitamin A-rich foods. Low socio-economic status significantly increased the odds (OR; 95 % CI) of tracking of low v. high DDS (3·31; 1·44, 7·60) and meal frequency (3·46; 1·54, 7·76). CONCLUSIONS: Low tracking for intakes of Fe- and vitamin A-rich foods implies that interventions to improve these IYCF practices must address underlying causes for irregular intake to have sustainable effects.

Recommendations for Infant Feeding Policy and Programs in Dzimauli Region, South Africa: Results From the MAL-ED Birth Cohort.

BACKGROUND: There is strong evidence that exclusive breastfeeding (EBF) in the first 6 months of life reduces the risk of diseases in infancy and in later life. OBJECTIVE: To understand the maternal reasoning that influences optimum infant feeding practices of caregivers in semirural communities of Limpopo province. METHODS: Nested qualitative study among mothers in an ongoing birth cohort study was conducted; structured and semi-structured interviews were used to collect data. Data from 234 infants after 6 months of follow-up was included for quantitative analysis. Four focus discussion groups comprising 7 to 10 caregivers were used to obtain perception of mothers on breastfeeding. A semi-structured interview guide was used to stimulate discussions. Thematic content analyses were conducted to identify the main themes that influence breastfeeding practices of caregivers. RESULTS: Over 90% of the caregivers initiated breastfeeding after delivery. However, less than 1% of mothers practiced EBF by 3 months, and none of the children were exclusively breastfed for up to 6 months. All caregivers introduced non-breast milk liquids and solids by the second month of child's life. Common reasons for introducing non-breast milk foods included insufficiency of breast milk production, going back to work or school, and influence by elderly women (mothers/mothers-in-law) and church members. CONCLUSION: Exclusive breastfeeding was not practiced in this community due to cultural and religious beliefs and misinformation. The involvement of elderly women and church members in infant feeding education and promotion programs and the dissemination of breastfeeding information through mobile phones to younger mothers are recommended.

Measuring home environments across cultures: Invariance of the HOME scale across eight international sites from the MAL-ED study.

The home environment provides the context for much of a child's early development. Examples of important aspects of the home environment include safety, cleanliness, and opportunities for cognitive stimulation. This study sought to examine the psychometric properties of an adapted form of the Home Observation for the Measurement of the Environment (HOME; Caldwell & Bradley, 1984, 2003) across the eight international sites of the MAL-ED project (Dhaka, Bangladesh; Vellore, India; Bhakatapur, Nepal; Naushahro Feroze, Pakistan; Fortaleza, Brazil; Loreto, Peru; Venda, South Africa; Haydom, Tanzania), to identify a factor structure that fit the data at all sites, and to derive a subset of items that could be used to examine home environmental characteristics across sites. A three-factor structure (i.e., Emotional and Verbal Responsivity; Clean and Safe Environment; Child Cleanliness) was identified, and partial measurement equivalence/invariance across sites was supported. Overall, these findings lend support for the use of portions of this abbreviated and adapted version of the HOME for use among heterogeneous, cross-cultural groups in low- and middle-income nations.

A methodologic framework for modeling and assessing biomarkers of environmental enteropathy as predictors of growth in infants: an example from a Peruvian birth cohort.

Background: Environmental enteropathy (EE) impairs the gut's absorptive capacity and immune function and causes decelerations in statural growth that manifest gradually over time.Objective: To illustrate an approach for assessing emerging biomarkers of EE, we separately assessed the associations between 3 such markers and subsequent nutritional status.Design: Stool samples were routinely collected between January 2010 and November 2014 from a cohort of 303 Peruvian infants and analyzed for concentrations of the biomarkers α-1-antitrypsin (AAT), myeloperoxidase, and neopterin. For each marker, a mixed-effects linear regression model was fitted for length-for-age z scores (LAZs) obtained from anthropometric assessments that incorporated covariate predictors, polynomial terms for age, and product interaction terms to test associations over varying lag lengths. The biomarkers' contribution to the models was assessed with the use of the likelihood ratio test and partial R2 statistics.Results: Test statistics for the combined inclusion of the 4-model terms that involved the biomarker were highly statistically significant for AAT (28.71; P < 0.0001) and myeloperoxidase (62.79; P < 0.0001) over a 3-mo lag and moderately so for neopterin (13.97; P = 0.0074). AAT and myeloperoxidase seemed to interact strongly with age, with the magnitude and direction of the effect varying considerably over the first 3 y of life. The largest proportion of the variance explained by any biomarker (2.8%) and the largest difference in LAZ predicted between the 5th and 95th percentile (0.25) was by myeloperoxidase over a 2-mo lag.Conclusions: Of the 3 fecal biomarkers studied, 2 that related to intestinal function-AAT and myeloperoxidase-were associated with small but highly statistically significant differences in future statural growth trajectories in infants in this cohort, lending further evidence to the EE hypothesis that increased gut permeability and inflammation adversely affects subsequent nutritional status. This association exhibited a complex interaction with age. This trial was registered at clinicaltrials.gov as NCT02441426.

Perceptions of community-based field workers on the effect of a longitudinal biomedical research project on their sustainable livelihoods.

BACKGROUND: Researchers involved in biomedical community-based projects rarely seek the perspectives of community fieldworkers, who are the 'foot soldiers' in such projects. Understanding the effect of biomedical research on community-based field workers could identify benefits and shortfalls that may be crucial to the success of community-based studies. The present study explored the perceptions of community-based field workers on the effect of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project" (MAL-ED) South Africa on their tangible and intangible capital which together comprise sustainable livelihoods. METHODS: The study was conducted in Dzimauli community in Limpopo Province of South Africa between January-February 2016. The sustainable livelihoods framework was used to query community-based field workers' perspectives of both tangible assets such as income and physical assets and intangible assets such as social capital, confidence, and skills. Data were collected through twenty one individual in-depth interviews and one focus group discussion. Data were analysed using the Thematic Content Analysis approach supported by ATLAS.ti, version 7.5.10 software. RESULTS: All the field workers indicated that they benefitted from the MAL-ED South Africa project. The benefits included intangible assets such as acquisition of knowledge and skills, stronger social capital and personal development. Additionally, all indicated that MAL-ED South Africa provided them with the tangible assets of increased income and physical assets. Observations obtained from the focus group discussion and the community-based leaders concurred with the findings from the in-depth interviews. Additionally, some field workers expressed the desire for training in public relations, communication, problem solving and confidence building. CONCLUSIONS: The MAL-ED South Africa, biomedical research project, had positive effects on tangible and intangible assets that compose the sustainable livelihoods of community-based fieldworkers. However, the field workers expressed the need to acquire social skills to enable them carry out their duties more efficiently.

How multiple episodes of exclusive breastfeeding impact estimates of exclusive breastfeeding duration: report from the eight-site MAL-ED birth cohort study.

The duration of exclusive breastfeeding (EBF) is often defined as the time from birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated by calculating the proportion of women at a given infant age who EBF in the previous 24 h (EBFDHS). Others have measured the total days or personal prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur, EBF can be re-initiated for extended periods. We compared breastfeeding metrics in the MAL-ED study; infants' breastfeeding trajectories were characterized from enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice-weekly surveillance, caretakers were queried about infant feeding the prior day. Overall, 101 833 visits and 356 764 child days of data were collected from 1957 infants. Median duration of EBFLONG was 33 days (95% CI: 32-36), compared to 49 days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62-70). Differences were because of the return to EBF after a non-EBF period. The median number of returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode), infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days (SD: 18.1) (third episode). In settings where women report short gaps in EBF, programmes should work with women to return to EBF. Interventions could positively influence the duration of these additional periods of EBF and their quantification should be considered in impact evaluation studies. © 2016 John Wiley & Sons Ltd.

The MAL-ED study: a multinational and multidisciplinary approach to understand the relationship between enteric pathogens, malnutrition, gut physiology, physical growth, cognitive development, and immune responses in infants and children up to 2 years of age in resource-poor environments.

Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community-rather than the relatively rarer circumstances that lead to hospitalization-during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.