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.
Study Type
OBSERVATIONAL
Enrollment
1,796
International Centre for Diarrheal Disease Research, Bangladesh
Dhaka, Bangladesh
Universidade Federal do Ceará
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Vaccine response will be recorded at 24 months of age.
Gut inflammation
Stool biomarkers will be evaluated to detect gut and systemic inflammation.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Gut integritywill be recorded at at 15 months of age.
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