Pathogen-specifi c burdens of community diarrhoea in developing countries: a multisite birth cohort study (MAL-ED)

Background Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specifi c diarrhoea burdens in the community. Methods We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defi ned as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identifi ed through twice-weekly home visits by fi eldworkers over a follow-up period of 24 months. Non-diarrhoeal stool specimens were also collected for surveillance for months 1–12, 15, 18, 21, and 24. Stools were analysed for a broad range of enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted attributable fraction (AF) to estimate pathogen-specifi c burdens of diarrhoea. Findings Between Nov 26, 2009, and Feb 25, 2014, we tested 7318 diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0–24 months. Pathogen detection was common in non-diarrhoeal stools but was higher with diarrhoea. Norovirus GII (AF 5·2%, 95% CI 3·0–7·1), rotavirus (4·8%, 4·5–5·0), Campylobacter spp (3·5%, 0·4–6·3), astrovirus (2·7%, 2·2–3·1), and Cryptosporidium spp (2·0%, 1·3–2·6) exhibited the highest attributable burdens of diarrhoea in the fi rst year of life. The major pathogens associated with diarrhoea in the second year of life were Campylobacter spp (7·9%, 3·1–12·1), norovirus GII (5·4%, 2·1–7·8), rotavirus (4·9%, 4·4–5·2), astrovirus (4·2%, 3·5–4·7), and Shigella spp (4·0%, 3·6–4·3). Rotavirus had the highest AF for sites without rotavirus vaccination and the fi fth highest AF for sites with the vaccination. There was substantial variation in pathogens according to geography, diarrhoea severity, and season. Bloody diarrhoea was primarily associated with Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and vomiting with norovirus GII. Interpretation There was substantial heterogeneity in pathogen-specifi c burdens of diarrhoea, with important determinants including age, geography, season, rotavirus vaccine usage, and symptoms. These fi ndings suggest that although single-pathogen strategies have an important role in the reduction of the burden of severe diarrhoeal disease, the eff ect of such interventions on total diarrhoeal incidence at the community level might be limited

Gut microbiota features associated with Campylobacter burden and postnatal linear growth deficits in a Peruvian birth cohort

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru. METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition were investigated using multiple linear regression adjusting for within-child correlations, age, and breastfeeding. Indicator species analyses identified taxa specifically associated with Campylobacter burden. RESULTS: Ninety-three percent (251) of children had Campylobacter present in asymptomatic fecal samples during the follow-up period. A 10% increase in the proportion of stools infected was associated with mean reductions of 0.02 length-for-age z scores (LAZ) at 3, 6, and 9 months thereafter (P \u3c .01). We identified 13 bacterial taxa indicative of cumulative Campylobacter burden and 14 taxa significantly associated with high or low burden of enteroaggregative Escherichia coli, norovirus, or Giardia. CONCLUSIONS: Campylobacter infection is common in this cohort and associated with changes in microbial community composition. These results support the notion that disruptions to the fecal microbiota may help explain the observed effects of asymptomatic infections on growth in early life

Diarrhea as a potential cause and consequence of reduced gut microbial diversity among undernourished children in Peru

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon. METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S rRNA genes in fecal samples collected at 6, 12, 18, and 24 months. Linear and generalized linear models were used to determine whether diarrhea was associated with altered microbiota and, in turn, if features of the microbiota were associated with the subsequent risk of diarrhea. RESULTS: Diarrheal frequency, duration, and severity were negatively associated with bacterial diversity and richness (P \u3c .05). Children born stunted (length-for-age z-score [LAZ] ≤ -2) who were also severely stunted (LAZ ≤ -3) at the time of sampling exhibited the greatest degree of diarrhea-associated reductions in bacterial diversity and the slowest recovery of bacterial diversity after episodes of diarrhea. Increased bacterial diversity was predictive of reduced subsequent diarrhea from age 6 to 18 months. CONCLUSIONS: Persistent, severe growth faltering may reduce the gut microbiota\u27s resistance and resilience to diarrhea, leading to greater losses of diversity and longer recovery times. This phenotype, in turn, denotes an increased risk of future diarrheal disease and growth faltering

Characteristics associated with the transition to partial breastfeeding prior to 6 months of age : Data from seven sites in a birth cohort study

ACKNOWLEDGMENTS The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) was carried out as a collaborative project supported by the Bill & Melinda Gates Foundation, the Foundation for the NIH and the NIH/Fogarty International Center.Peer reviewedPublisher PD

Early interruption of exclusive breastfeeding: results from the eight-country MAL-ED study

We report the infant feeding experiences in the first month of life for 2,053 infants participating in \u201cMalnutrition and Enteric Infections: Consequences for Child Health and Development\u201d (MAL-ED). Eight sites (in Bangladesh, India, Nepal, Pakistan, Brazil, Peru, South Africa, Tanzania), each followed a cohort of children from birth (by day 17), collecting detailed information on infant feeding practices, diet and illness episodes. Mothers were queried twice weekly regarding health status, breastfeeding and the introduction (or no) of non-breast milk liquids and foods. Here, our goal is to describe the early infant feeding practices in the cohort and evaluate factors associated with termination of exclusive breastfeeding in the first month of life. With data from enrollment to a visit at 28-33 days of life, we characterized exclusive, predominant or partial breastfeeding (using a median of 6-9 visits per child across the sites). Only 6 of 2,053 infants were never breastfed. By one month, the prevalences of exclusive breastfeeding were < 60% in 6 of 8 sites, and of partial breastfeeding (or no) were > 20% in 6 of 8 sites. Logistic regression revealed that prelacteal feeding (given to 4-63% of infants) increased the likelihood of partial breastfeeding (Odds Ratio (OR): 1.48 (95% confidence interval (CI): 1.04, 2.10), as did the withholding of colostrum (2-16% of infants) (OR: 1.63:1.01, 2.62), and being a first-time mother (OR: 1.38:1.10, 1.75). Our results reveal diversity across these sites, but an overall trend of early transition away from exclusive breastfeeding in the first month of life. Interventions which introduce or reinforce the WHO/UNICEF Ten Steps for Successful Breastfeeding are needed in these sites to improve breastfeeding initiation, to reinforce exclusive breastfeeding and delay introduction of non-breast milk foods and/or liquids

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study—a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella­-associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6–35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior

Infant feeding practices in the Peruvian Amazon: implications for programs to improve feeding

OBJECTIVE: To characterize feeding practices in a community in the Peruvian Amazon and to consider how this information could be used to strengthen programs and policies designed to improve nutrition and reduce child malnutrition in vulnerable communities METHODS: Data from three structured questionnaires were combined to produce a comprehensive depiction of feeding in a sample of 246 infants from birth through 8 months of life in the community of Santa Clara de Nanay near Iquitos, Peru. Breastfeeding initiation practices, exclusive breastfeeding in the first 180 days of life, the introduction of solids, and complementary feeding practices from 6-8 months, were described and related to maternal, infant, and household characteristics, including food insecurity RESULTS: The median duration of exclusive breastfeeding was 19 days. However, over the first 180 days of life, children were exclusively breastfed on 46.1% of days. Overall, 68.3% of infants received some semi-solid or solid food between 0-6 months and all had received semi-solids by the end of 8 months of age. The proportion of infants consuming a minimally acceptable (frequent and diverse) complementary diet was 2.9%, 7.9%, and 16.1% at 6, 7, and 8 months respectively CONCLUSIONS: Although breastfeeding is nearly universal, promotion programs are needed in Santa Clara to 1) delay the introduction of plain water, other non-breast milk liquids, and semi-solid foods; 2) extend the period of exclusive breastfeeding; and 3) increase food diversity and the frequency of feeding during the period of complementary feeding. These results can be used to guide programs and policies to improve nutrition and reduce child malnutrition