title: Methods of analysis of enteropathogen infection in the MAL-ED Cohort Study.
abstract: Studies of diarrheal etiology in low- and middle-income countries have typically focused on children presenting with severe symptoms to health centers and thus are best equipped to describe the pathogens capable of leading to severe diarrheal disease. The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study was designed to evaluate, via intensive community surveillance, the hypothesis that repeated exposure to enteropathogens has a detrimental effect on growth, vaccine response, and cognitive development, which are the primary outcome measures for this study. In the setting of multiple outcomes of interest, a longitudinal cohort design was chosen. Because many or even the majority of enteric infections are asymptomatic, the collection of asymptomatic surveillance stools was a critical element. However, capturing diarrheal stools additionally allowed for the determination of the principle causes of diarrhea at the community level as well as for a comparison between those enteropathogens associated with diarrhea and those that are associated with poor growth, diminished vaccine response, and impaired cognitive development. Here, we discuss the analytical methods proposed for the MAL-ED study to determine the principal causes of diarrhea at the community level and describe the complex interplay between recurrent exposure to enteropathogens and these critical long-term outcomes.
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.
authors.forename: James A
authors.initials: JA
authors.lastname: Platts-Mills
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, and.
authors.forename: Benjamin J J
authors.initials: BJ
authors.lastname: McCormick
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Biomedical Research, Asociación Benéfica PRISMA, Iquitos, Peru.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kosek
authors.affiliation: Duke Global Health Institute, Duke University, Durham, North Carolina.
authors.forename: William K
authors.initials: WK
authors.lastname: Pan
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Checkley
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Houpt
mesh_terms: D002648:Child; D002675:Child, Preschool; D003906:Developing Countries; D003967:Diarrhea; D004756:Enterobacteriaceae Infections; D015340:Epidemiologic Research Design; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D044342:Malnutrition
keywords: MAL-ED; birth cohort study; diarrhea etiology; enteropathogens; growth