title: Environmental enteric dysfunction: pathogenesis, diagnosis, and clinical consequences.
abstract: Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection.
authors.affiliation: Boston University, Massachusetts.
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Keusch
authors.affiliation: University of Washington, Seattle.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Denno
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Black
authors.affiliation: Boston Children's Hospital, Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
authors.affiliation: University of Virginia, Charlottesville.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.affiliation: St Michael's Hospital, Toronto, Canada.
authors.forename: James V
authors.initials: JV
authors.lastname: Lavery
authors.affiliation: University of Virginia, Charlottesville.
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.affiliation: Tufts University.
authors.forename: Irwin H
authors.initials: IH
authors.lastname: Rosenberg
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
authors.affiliation: Washington University, St Louis.
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
authors.affiliation: Tufts University.
authors.forename: Honorine
authors.initials: H
authors.lastname: Ward
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
authors.affiliation: University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Hoosen
authors.initials: H
authors.lastname: Coovadia
authors.affiliation: Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Aldo
authors.initials: A
authors.lastname: Lima
authors.affiliation: Christian Medical College, Vellore, India.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Ramakrishna
authors.affiliation: Aga Khan University, Karachi, Pakistan Bill & Melinda Gates Foundation, Seattle, Washington.
authors.forename: Anita K M
authors.initials: AK
authors.lastname: Zaidi
authors.affiliation: Bill & Melinda Gates Foundation, Seattle, Washington.
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Hay Burgess
authors.affiliation: Bill & Melinda Gates Foundation, Seattle, Washington.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brewer
mesh_terms: D015415:Biomarkers; D002648:Child; D015362:Child Nutrition Disorders; D002675:Child, Preschool; D003906:Developing Countries; D006801:Humans; D007410:Intestinal Diseases; D008286:Malabsorption Syndromes; D044342:Malnutrition
chemical_list: D015415:Biomarkers
keywords: biomarkers; developing countries; enteropathy; malabsorption; stunting