Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Causal Pathways from Enteropathogens to Environmental Enteropathy: Findings from the MAL-ED Birth Cohort Study
EBioMedicine, Volume 18, Year 2017
Notification
URL copied to clipboard!
Description
Background Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Methods Non-diarrheal stool samples (N = 22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N = 6363) and plasma alpha-1-acid glycoprotein (AGP) (N = 2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0–2 years of age. Findings Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. Interpretation The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Funding Bill & Melinda Gates Foundation. © 2017 The Authors
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC5405169/bin/mmc1.docx
Authors & Co-Authors
Kosek, Margaret N.
United States, Baltimore
Johns Hopkins University
Ahmed, Tahmeed J.
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Bhutta, Zulfiqar A.
Pakistan, Karachi
The Aga Khan University
Caulfield, Laura E.
United States, Baltimore
Johns Hopkins University
Guerrant, Richard Littleton
United States, Charlottesville
University of Virginia
Houpt, Eric R.
United States, Charlottesville
University of Virginia
Kang, Gagandeep
India, Vellore
Christian Medical College, Vellore
Lee, Gwenyth O.Neill
United States, Baltimore
Johns Hopkins University
Moreira Lima, Aldo Ângelo
Brazil, Fortaleza
Universidade Federal do Ceará
McCormick, Benjamin J.J.
United States, Bethesda
Fogarty International Center
Platts-Mills, James A.
United States, Charlottesville
University of Virginia
Seidman, Jessica C.
United States, Bethesda
Fogarty International Center
Blank, Rebecca R.
United States, Bethesda
National Institutes of Health Nih
Gottlieb, Michael
United States, Bethesda
National Institutes of Health Nih
Knobler, Stacey L.
United States, Bethesda
Fogarty International Center
Lang, Dennis R.
United States, Bethesda
Fogarty International Center
United States, Bethesda
National Institutes of Health Nih
Miller, Mark A.
United States, Bethesda
Fogarty International Center
Tountas, Karen H.
United States, Bethesda
National Institutes of Health Nih
Checkley, William N.
United States, Bethesda
Fogarty International Center
United States, Baltimore
Johns Hopkins University
Mason, Carl Jeffries
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Murray-Kolb, Laura E.
United States, University Park
Pennsylvania State University
Petri, William A.
United States, Charlottesville
University of Virginia
Bessong, Pascal Obong
South Africa, Thohoyandou
University of Venda
Haque, Rashidul
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
John, Sushil Mathew
India, Vellore
Christian Medical College, Vellore
Mduma, Estomih R.
Tanzania, Mbulu
Haydom Lutheran Hospital
Oriá, Reinaldo B.
Brazil, Fortaleza
Universidade Federal do Ceará
Shrestha, Prakash Sunder
Nepal, Kathmandu
Tribhuvan University
Shrestha, Sanjaya Kumar
Nepal, Kathmandu
Walter Reed/afrims Research Unit
Svensen, Erling
Tanzania, Mbulu
Haydom Lutheran Hospital
Norway, Bergen
Haukeland Universitetssjukehus
Zaidi, Anita Kaniz Mehdi
Pakistan, Karachi
The Aga Khan University
Abreu, Claúdia B.
Brazil, Fortaleza
Universidade Federal do Ceará
Acosta, Angel Mendez
Peru, Lima
Asociacion Benefica Prisma Lima
Ahmed, Imran
Pakistan, Karachi
The Aga Khan University
Shamsir Ahmed, Abul Mansur
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Ali, Asad S.
Pakistan, Karachi
The Aga Khan University
Ambikapathi, Ramya
United States, Bethesda
Fogarty International Center
Barrett, Leah J.
United States, Charlottesville
University of Virginia
Bauck, Aubrey
United States, Baltimore
Johns Hopkins University
Bayyo, Eliwaza B.
Tanzania, Mbulu
Haydom Lutheran Hospital
Bodhidatta, Ladaporn
Thailand, Bangkok
Armed Forces Research Institute of Medical Sciences, Thailand
Bose, Anuradha
India, Vellore
Christian Medical College, Vellore
Daniel Carreon, J.
United States, Bethesda
Fogarty International Center
Chandyo, Ram Krishna
Nepal, Kathmandu
Tribhuvan University
Charu, Vivek
United States, Bethesda
Fogarty International Center
Costa, Hilda
Brazil, Fortaleza
Universidade Federal do Ceará
Dillingham, Rebecca Anne
United States, Charlottesville
University of Virginia
Moura, Alessandra Di
Brazil, Fortaleza
Universidade Federal do Ceará
Doan, Viyada
United States, Bethesda
Fogarty International Center
Filho, José Quirino S.
United States, Bethesda
Fogarty International Center
Brazil, Fortaleza
Universidade Federal do Ceará
Graham, Jhanelle
United States, Bethesda
Fogarty International Center
Hoest, Christel
United States, Bethesda
Fogarty International Center
Hossain, Iqbal
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Islam, Mohammad Munirul
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Jennifer, Mats Steffi
India, Vellore
Christian Medical College, Vellore
Kaki, Shiny
India, Vellore
Christian Medical College, Vellore
Koshy, Beena
India, Vellore
Christian Medical College, Vellore
Leite, Álvaro Jorge Madeiro
Brazil, Fortaleza
Universidade Federal do Ceará
Lima, Noélia Leal
Brazil, Fortaleza
Universidade Federal do Ceará
MacIel, Bruna Leal Lima
Brazil, Fortaleza
Universidade Federal do Ceará
Mahfuz, Mustafa U.
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Mahopo, Cloupas
South Africa, Thohoyandou
University of Venda
Maphula, Angelina
South Africa, Thohoyandou
University of Venda
McGrath, Monica
United States, Bethesda
Fogarty International Center
Mohale, Archana
United States, Bethesda
Fogarty International Center
Moraes, Milena L.
Brazil, Fortaleza
Universidade Federal do Ceará
Mota, Francisco Suetônio Bastos
Brazil, Fortaleza
Universidade Federal do Ceará
Muliyil, Jayaprakash
India, Vellore
Christian Medical College, Vellore
Mvungi, Regisiana
Tanzania, Mbulu
Haydom Lutheran Hospital
Nayyar, Gaurvika M.L.
United States, Bethesda
Fogarty International Center
Nyathi, Emanuel
South Africa, Thohoyandou
University of Venda
Paredes Olórtegui, Maribel
Peru, Lima
Asociacion Benefica Prisma Lima
Vasquez, Angel Orbe
Peru, Lima
Asociacion Benefica Prisma Lima
Pan, William K.Y.
United States, Durham
Duke University
United States, Bethesda
Fogarty International Center
Pascal, John
Tanzania, Mbulu
Haydom Lutheran Hospital
Patil, Crystal L.
United States, Chicago
University of Illinois at Chicago
Pendergast, Laura L.
United States, Philadelphia
Temple University
Pinedo, Silvia Rengifo
Peru, Lima
Asociacion Benefica Prisma Lima
Psaki, Stephanie R.
United States, Bethesda
Fogarty International Center
Mohan, Venkata Raghava
India, Vellore
Christian Medical College, Vellore
Ramanujam, Karthikeyan
India, Vellore
Christian Medical College, Vellore
Rasheed, Muneera Abdul
Pakistan, Karachi
The Aga Khan University
Rasmussen, Zeba A.
United States, Bethesda
Fogarty International Center
Richard, Stephanie A.
United States, Bethesda
Fogarty International Center
Rose, Anuradha R.
India, Vellore
Christian Medical College, Vellore
Roshan, Reeba
India, Vellore
Christian Medical College, Vellore
Schaefer, Barbara A.
United States, Bethesda
Fogarty International Center
United States, University Park
Pennsylvania State University
Scharf, Rebecca J.
United States, Charlottesville
University of Virginia
Sharma, Srujan Lam
India, Vellore
Christian Medical College, Vellore
Shrestha, Binob
Nepal, Kathmandu
Walter Reed/afrims Research Unit
Shrestha, Rita
Nepal, Kathmandu
Tribhuvan University
Simons, Suzanne
United States, University Park
Pennsylvania State University
Soares, Alberto Melo
Brazil, Fortaleza
Universidade Federal do Ceará
Mota, Rosa Maria Salani
Brazil, Fortaleza
Universidade Federal do Ceará
Soofi, Sajid Bashir
Pakistan, Karachi
The Aga Khan University
Strand, Tor A.
Norway, Bergen
Universitetet I Bergen
Nepal, Kathmandu
Walter Reed/afrims Research Unit
Tofail, Fahmida
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Thomas, Rahul Jacob
India, Vellore
Christian Medical College, Vellore
Turab, Ali
Pakistan, Karachi
The Aga Khan University
Ulak, Manjeswori
Nepal, Kathmandu
Tribhuvan University
Wang, Vivian Ota
United States, Bethesda
Fogarty International Center
Yarrot, Ladislaus Blacy
Tanzania, Mbulu
Haydom Lutheran Hospital
Peñataro Yori, Pablo
United States, Baltimore
Johns Hopkins University
Alam, Didar
Pakistan, Karachi
The Aga Khan University
Amour, Caroline
Tanzania, Mbulu
Haydom Lutheran Hospital
Chávez, Cesar Banda
Peru, Lima
Asociacion Benefica Prisma Lima
Babji, Sudhir
India, Vellore
Christian Medical College, Vellore
de Burga, Rosa Rios
Peru, Lima
Asociacion Benefica Prisma Lima
Flores, Julian Torres
Peru, Lima
Asociacion Benefica Prisma Lima
Gratz, Jean C.
United States, Charlottesville
University of Virginia
George, Ajila T.
India, Vellore
Christian Medical College, Vellore
Hariraju, Dinesh
India, Vellore
Christian Medical College, Vellore
Havt, Alexandre
Brazil, Fortaleza
Universidade Federal do Ceará
Karunakaran, Priyadarshani
India, Vellore
Christian Medical College, Vellore
Lazarus, Robin Penugula
India, Vellore
Christian Medical College, Vellore
Lima, Ila Fernanda Nunes
Brazil, Fortaleza
Universidade Federal do Ceará
Mondal, Dinesh K.
Bangladesh, Dhaka
International Centre for Diarrhoeal Disease Research Bangladesh
Medeiros, Pedro Henrique Quintela Soares
Brazil, Fortaleza
Universidade Federal do Ceará
Nshama, Rosemary P.
Tanzania, Mbulu
Haydom Lutheran Hospital
Quetz, Josiane S.
Brazil, Fortaleza
Universidade Federal do Ceará
Qureshi, Shahida Mumtaz
Pakistan, Karachi
The Aga Khan University
Raju, Sophy
India, Vellore
Christian Medical College, Vellore
Ramachandran, Anup
India, Vellore
Christian Medical College, Vellore
Ramadas, Rakhi
India, Vellore
Christian Medical College, Vellore
Ross, A. Catharine
United States, University Park
Pennsylvania State University
Salas, Mery Siguas
Peru, Lima
Asociacion Benefica Prisma Lima
Samie, Amidou
South Africa, Thohoyandou
University of Venda
Schulze, Kerry J.
United States, Baltimore
Johns Hopkins University
Shanmuga Sundaram, E.
India, Vellore
Christian Medical College, Vellore
Swema, Buliga Mujaga
Tanzania, Mbulu
Haydom Lutheran Hospital
Trigoso, Dixner Rengifo
Peru, Lima
Asociacion Benefica Prisma Lima
Statistics
Citations: 186
Authors: 131
Affiliations: 20
Identifiers
Doi:
10.1016/j.ebiom.2017.02.024
ISSN:
23523964
Research Areas
Food Security
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Approach
Quantitative