Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED)

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One in every five children in low and middle income countries (LMICs) is undernourished. Poor nutrition, not all of which is due to food insecurity, is associated with nearly half of child deaths under the age of five. Early childhood malnutrition is considered one of the most prevalent risk factors for morbidity and mortality in children under five and may lead to cognitive and physical deficits later in life.

For children living in resource-constrained areas in LMICs, malnutrition, frequently identified by a severe shortfall in physical growth (i.e. stunting), is associated with the chronic exposure to infectious disease-causing enteric pathogens. These pathogens may alter gut integrity and impair absorption of nutrients resulting in further malnutrition and increased susceptibility to and incidence of infection and disease and in diminished immune responses to childhood vaccines. Moreover, the effects of these pathogens may also lead to cognitive and related developmental deficits. The cumulative effects of high rates of disease, malnutrition, and impaired child development place an enormous and disproportionate social and economic burden on poor families and the societies in which they reside.

Increased understanding of the complex inter-relationship between enteric infections and malnutrition in the context of poor socioeconomic conditions is needed to design and implement better intervention strategies to reduce childhood morbidity and mortality.

An international network of investigators collaborated on a project entitled Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development to gain a comprehensive understanding of environmental factors affecting child development. For this project, abbreviated as MAL-ED, investigators conducted research at eight geographically distinct sites, within populations known to have high rates of malnutrition and enteric infections. Children were closely monitored beginning in each child’s first month of life in an effort to determine those early life exposures that pose the greatest risk.

Investigators working at institutions and sites, identified below, in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa, Tanzania, along with investigators at institutions in the United States designed and executed the first-of-its-kind comprehensive study of early child growth and development.

The study was implemented using shared and harmonized protocols across the eight sites to gather an enormous amount of data (physical, cognitive assessments, diet, illness and enteric infection, socio-economic status, etc.) to enable identification and characterization of factors associated with negative impacts on a child’s growth, development and vaccine response early in life.

With approval from institutional ethical review committees, the children were recruited within the first 17 days of life for this study in order to establish a birth cohort at each of eight sites. Each site enrolled at least 200 children over the course of two years. As per the protocol, each child and caregiver pair was visited twice weekly by field workers who collected survey and health data as well as biospecimens for further testing.

A central hypothesis of the project was that enteric infections and poor nutrition result in changes in gut function (e.g. malabsorption of nutrients, inflammation) that are detrimental to healthy child growth and development.

The MAL-ED study generated a large-scale, high-quality data set, possibly the largest of its kind. Analyses both on individual site and multisite basis have evaluated, and will continue to evaluate data obtained for various research areas including infectious etiology of diarrheal disease, cognitive abilities, gut functioning, nutritional status, and socio-economic and educational status as well as immunological responses. It is anticipated that the data will be used far into the future to further improve scientific understanding, to promote intervention strategy development and to test research hypotheses as a catalyst for new research projects.

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Goals

  • Identify those environmental exposures (infection, symptomatic diseases, nutrition, socioeconomic) early in a child’s life that are associated with shortfalls in physical growth, cognitive development and immunity.
  • Characterize a series of gut function biomarkers that are on the causal pathway from environmental exposure to growth and development deficits.
  • Assess diversity across the sites with respect to exposures and child health and development.

Results & Accomplishments

Media

FNIH Announcement (Oct. 11, 2017): Q&A with Michael Gottlieb, Ph.D., FNIH Deputy Director of Science: The Significant Role of Malnutrition, Intestinal Infection and Disease on Child Development

Selected Publications

Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study. MAL-ED Network Investigators PLoS Med 2017. 14(10): e1002408.

The Malnutrition and Enteric Disease Study (MAL-ED): Understanding the Consequences for Child Health and Development. The MAL-ED Network Investigators. CID. 2014. 59, suppl. #4.

Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study. The MAL-ED Network Investigators. Ebiomedicine. 2017. 18:109-117

Childhood stunting in relation to the pre- and post-natal environment during the first two years of life: The MAL-ED longitudinal birth cohort study. The MAL-ED Network Investigators PLoS Medicine. Accepted August 2017

The relationship between growth and illness, enteropathogens, and dietary intakes in the first two years of life: findings from the MAL-ED birth cohort study. The MAL-ED Network Investigators. BMJ Global Health. Accepted Sept 2017.

View more papers through a PubMed Search for MAL-ED.

Data Access

An interactive platform that will include data visualization and analysis tools is in development to facilitate interrogation of the MAL-ED study data. This platform will be made publicly available sometime in 2018.

Partners

Armed Forces Research Institute of Medical Sciences
Aga Khan University, Karachi, Pakistan
Bill & Melinda Gates Foundation
Christian Medical College, Vellore, India
Federal University of Ceará, Fortaleza, Ceará, Brazil
Haydom Lutheran Hospital, Haydom, Tanzania
Henry M Jackson Foundation
icddr,b, Dhaka, Bangladesh
Institute of Medicine, Kathmandu, Nepal
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
NIH, Fogarty International Center
Pennsylvania State University
University of Venda, Limpopo, South Africa
University of Virginia

Contact

Karen H. Tountas, Ph.D., Scientific Program Manager, ktountas@fnih.org