Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development

Conditions

Cognitive Development, Diarrhea, Immune Response, Malnutrition, Stunting, Wasting

Keywords

Cognitive development, Diarrheal disease, Enteric infections, Malnutrition, Vaccine Response, Enteropathy, Antibiotic use, Micronutrients, Breast feeding, Gut inflammation

Brief summary

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: * which micro-organisms or mixed infections are most frequently associated with growth faltering and poor development; and * at what age specific infections cause the most disruption to growth and development and impair immune response.

Kambiz Nemati, Y Michael, Bernadetha P Hhando, Samwel Jatosh, Eric R. Houpt et al. (7 authors)

BMJ Open2025-08-01

10.1136/bmjopen-2025-100955

Plasma Fibroblast Growth Factor 21 Is Associated with Subsequent Growth in a Cohort of Underweight Children in Bangladesh.

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.

2019-03-308 citations

10.1093/cdn/nzz024

A methodologic framework for modeling and assessing biomarkers of environmental enteropathy as predictors of growth in infants: an example from a Peruvian birth cohort.

Colston JM, Peñataro Yori P, Colantuoni E, Moulton LH, Ambikapathi R, Lee G, Rengifo Trigoso D, Siguas Salas M, Kosek MN.

2017-06-0723 citations

10.3945/ajcn.116.151886

Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study.

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.

2017-04-0571 citations

10.3945/ajcn.116.138800

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

1 Minutes to 17 Days

Healthy volunteers

Yes

Inclusion criteria

* Less than 17 days old.

Exclusion criteria

* Mother is less than 16 years of age. * Mother has another child inthe MAL-ED study. * Pregnancy resulted in multiple birth (e.g., twins). * Child has a severe disease requiring hospitalization for something other than for a typical healthy birth. * Child has a severe or chronic condition diagnosed by a medical doctor (e.g., neonatal disease, renal disease, chronic heart failure, liver disease, cystic fibrosis, congenital conditions). * Child has enteropathies diagnosed by medical doctor. * Mother is living and unable to provide informed consent.

Design outcomes

Primary

Measure	Time frame	Description
Cognitive development	Cognitive development will be recorded at 6 months of age.	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.
Vaccine response	Vaccine response will be recorded at 7 months of age.	Antibody titers will be determined following immunization against rotavirus, polio virus, tetanus toxoid, pertussis toxin and measles vaccines.
Diarrhea	Each diarrheal episode willbe recorded for up to 24 months of age.	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.
Anthropometry	Anthropomentry will be recorded each month for up to 24 months of age.	Head Circumference, length, and weight are measured monthly on the anniversary of the child's birth.

Secondary

Measure	Time frame	Description
Gut inflammation	Gut inflammation will be recorded each month for up to 24 months of age.	Stool biomarkers will be evaluated to detect gut and systemic inflammation.
Gut integrity	Gut integritywill be recorded at at 3 months of age.	Intestinal absorptive capacity and barrier function will be assessed by dual sugar permeability test.

Countries

Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa, Tanzania

Outcome results