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| Name | Class |
|---|---|
| University of Virginia | OTHER |
| Johns Hopkins University | OTHER |
| Aga Khan University | OTHER |
| Christian Medical College, Vellore, India |
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Malnutrition is considered one of the most prevalent risk factors for morbidity and mortality in children under five. An estimated 20% of children in the developing world are malnourished [1] and poor nutrition is linked to more than half of all child deaths worldwide [2]. Malnutrition in early childhood may lead to cognitive and physical deficits and may cause similar deficits in future generations as malnourished mothers give birth to low birth weight children [3]. In addition, malnutrition increases susceptibility and incidence of infections and is associated with diminished response to vaccines.
The MAL-ED Project is designed to determine the impact of enteric infections/diarrhea that alter gut function and impair children's nutrition, growth and development to help develop new intervention strategies that can break the vicious enteric infection-malnutrition cycle and reduce its global burden.
The overall objective of the MAL-ED Project is to quantify the associations of specific enteric pathogens, measures of physical and mental development, micronutrient malnutrition, gut function biomarkers, the gut microbiome, and immune responses in very young children in resource-limited settings across eight sites that vary by culture, economics, geography, and climate.
The central hypothesis of the MAL-ED Project is that infection (and co-infection) with specific enteropathogens leads to impaired growth and development and to diminished immune response to orally administered vaccines by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. Data analyses will test for associations between enteropathogen infections and growth/development to help illuminate:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bangladesh | Birth cohort study community in Bangladesh is urban, and located in the Mirpur neighborhood of Dhaka. Case control study is being conducted in the same catchment area. Cases defined as children 6-24 months of age with <-2WAZ (weight for age) score, controls are age and community matched with >-1WAZ. | ||
| Brazil | Birth cohort study community in Brazil is urban, and located within the Papoco area of Fortaleza. Case control study is being conducted in the same area as the cohort study. Cases are children 6 - 24 months of age, with <-2 WAZ (weight for age) score, controls are age and community matched children with >-1 WAZ. | ||
| India | Birth cohort study community in India is urban, and located in the southern state of Tamil Nadu, specifically in Vellore. | ||
| Nepal | Birth cohort study community in Nepal is semi-urban, and located in Bhaktapur, approximately 25km from Kathmandu. | ||
| Pakistan | Birth cohort study community in Pakistan is rural, and located in Naushero Feroze, Sindh. | ||
| Peru | Birth cohort study community in Peru is rural, and located approximately 15km from Iquitos in Loreto. |
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| Measure | Description | Time Frame |
|---|---|---|
| Diarrhea | All diarrheal samples are analyzed for the presence of bacterial, viral, and parasitic pathogens. Normal stool is collected monthly and analyzed for the same list of 57 different pathogens. | Each diarrheal episode willbe recorded for up to 24 months of age. |
| Anthropometry | Head Circumference, length, and weight are measured monthly on the anniversary of the child's birth. | Anthropomentry will be recorded each month for up to 24 months of age. |
| Cognitive development | A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices. | Cognitive development will be recorded at 6 months of age. |
| Vaccine response | Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines. | Vaccine response will be recorded at 7 months of age. |
| Cognitive development | A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices. | Cognitive development will be recorded at 8 months of age. |
| Cognitive development | A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices. |
| Measure | Description | Time Frame |
|---|---|---|
| Gut inflammation | Stool biomarkers will be evaluated to detect gut and systemic inflammation. | Gut inflammation will be recorded each month for up to 24 months of age. |
| Gut integrity | Intestinal absorptive capacity and barrier function will be assessed by dual sugar permeability test. |
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Inclusion Criteria:
Exclusion Criteria:
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The study population for the MAL-ED Project is a birth cohort. Pregnant women were identified from their communities, consented and the child will be enrolled.
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| Name | Affiliation | Role |
|---|---|---|
| Michael Gottlieb, Ph.D. | Fountation for the National Institutes of Health | Principal Investigator |
| Roger Glass, M.D. | Fogarty International Center of the National Institute of Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| International Centre for Diarrheal Disease Research, Bangladesh | Dhaka | Bangladesh | ||||
| Universidade Federal do Ceará |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40840991 | Derived | Nemati K, Michael YZ, Hhando BP, Jatosh S, Houpt ER, Mduma E, DeBoer MD. Catch-up growth following early-life stunting in a low-resource area in rural Tanzania: the MAL-ED Metabolic study. BMJ Open. 2025 Aug 21;15(8):e100955. doi: 10.1136/bmjopen-2025-100955. | |
| 31093598 | Derived | Arndt MB, Richardson BA, Mahfuz M, Ahmed T, Haque R, Gazi MA, John-Stewart GC, Denno DM, Scarlett JM, Walson JL; coordination with The Interactions of Malnutrition & Enteric Infections: Consequences for Child Health and Development Project Network. Plasma Fibroblast Growth Factor 21 Is Associated with Subsequent Growth in a Cohort of Underweight Children in Bangladesh. Curr Dev Nutr. 2019 Mar 30;3(5):nzz024. doi: 10.1093/cdn/nzz024. eCollection 2019 May. |
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| OTHER |
| Henry M. Jackson Foundation for the Advancement of Military Medicine | OTHER |
| Fogarty International Center of the National Institute of Health | NIH |
| Penn State University | OTHER |
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plasma, stool, urine, saliva
| South Africa | Birth cohort study community in South Africa is rural/peri-urban, and comprised of nine settlements within Limpopo Province. |
| Tanzania | Birth cohort study community in Tanzania is rural, and located within Haydom. |
| Cognitive development will be recorded at 15 months of age. |
| Vaccine response | Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines. | Vaccine response will be recorded at 15 months of age. |
| Cognitive development | A battery of tests include the Bayley Scales of Infant Development, MacArthur Words and Gestures, Infant Temperament Scale, HOME inventory, SRQ-20 and Raven's Combined Progressive Matrices. | Cognitive development will be recorded 24 months of age. |
| Vaccine response | Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines. | Vaccine response will be recorded at 24 months of age. |
| Gut integritywill be recorded at at 3 months of age. |
| Gut integrity | Intestinal absorptive capacity and barrier function will be assessed by dual sugar permeability test. | Gut integritywill be recorded at at 6 months of age. |
| Gut integrity | Intestinal absorptive capacity and barrier function will be assessed by dual sugar permeability test. | Gut integritywill be recorded at at 9 months of age. |
| Gut integrity | Intestinal absorptive capacity and barrier function will be assessed by dual sugar permeability test. | Gut integritywill be recorded at at 15 months of age. |
| Fortaleza |
| Brazil |
| Christian Medical College | Vellore | India |
| Institute of Medicine | Kathmandu | Nepal |
| Aga Khan University | Karachi | Pakistan |
| JHSPH Satellite Laboratory | Iquitos | Peru |
| University of Venda | Limpopo | South Africa |
| Haydom Lutheran Hospital | Haydom | Tanzania |
| 29684739 | Derived | Colston JM, Ahmed T, Mahopo C, Kang G, Kosek M, de Sousa Junior F, Shrestha PS, Svensen E, Turab A, Zaitchik B; MAL-ED Network. Evaluating meteorological data from weather stations, and from satellites and global models for a multi-site epidemiological study. Environ Res. 2018 Aug;165:91-109. doi: 10.1016/j.envres.2018.02.027. Epub 2018 Apr 21. |
| 28592604 | Derived | Colston JM, Penataro Yori P, Colantuoni E, Moulton LH, Ambikapathi R, Lee G, Rengifo Trigoso D, Siguas Salas M, Kosek MN. A methodologic framework for modeling and assessing biomarkers of environmental enteropathy as predictors of growth in infants: an example from a Peruvian birth cohort. Am J Clin Nutr. 2017 Jul;106(1):245-255. doi: 10.3945/ajcn.116.151886. Epub 2017 Jun 7. |
| 28381477 | Derived | Platts-Mills JA, Taniuchi M, Uddin MJ, Sobuz SU, Mahfuz M, Gaffar SA, Mondal D, Hossain MI, Islam MM, Ahmed AS, Petri WA, Haque R, Houpt ER, Ahmed T. Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study. Am J Clin Nutr. 2017 May;105(5):1132-1138. doi: 10.3945/ajcn.116.138800. Epub 2017 Apr 5. |
| ID | Term |
|---|---|
| D003967 | Diarrhea |
| D044342 | Malnutrition |
| D006130 | Growth Disorders |
| D002100 | Cachexia |
| D007410 | Intestinal Diseases |
| D001942 | Breast Feeding |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D010335 | Pathologic Processes |
| D015431 | Weight Loss |
| D001836 | Body Weight Changes |
| D001835 | Body Weight |
| D013851 | Thinness |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D005247 | Feeding Behavior |
| D001519 | Behavior |
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