Evaluating Associations Between Vaccine Response and Malnutrition, Gut Function, and Enteric Infections in the MAL-ED Cohort Study: Methods and Challenges

Hoest, Christel; Seidman, Jessica C.; Pan, William; Ambikapathi, Ramya; Kang, Gagandeep; Kosek, Margaret; Knobler, Stacey; Mason, Carl J.; Miller, Mark A.

doi:10.1093/cid/ciu611

Cited by 33 publications

(21 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differential nutritional status can modulate intestinal microbiome, metabolome, and immune responses ( 29 – 31 ), although these effects are currently being defined only in the context of enteric infections. Furthermore, undernourished children in low-resource settings are associated with poor vaccine responses but the mechanisms of the responses are not fully understood ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea

et al. 2018

View full text Add to dashboard Cite

Enterotoxigenic Escherichia coli (ETEC) is a major cause of traveler's diarrhea as well as of endemic diarrhea and stunting in children in developing areas. However, a small-mammal model has been badly needed to better understand and assess mechanisms, vaccines, and interventions. We report a murine model of ETEC diarrhea, weight loss, and enteropathy and investigate the role of zinc in the outcomes. ETEC strains producing heat-labile toxins (LT) and heat-stable toxins (ST) that were given to weaned C57BL/6 mice after antibiotic disruption of normal microbiota caused growth impairment, watery diarrhea, heavy stool shedding, and mild to moderate intestinal inflammation, the latter being worse with zinc deficiency. Zinc treatment promoted growth in zinc-deficient infected mice, and subinhibitory levels of zinc reduced expression of ETEC virulence genes cfa1, cexE, sta2, and degP but not of eltA in vitro. Zinc supplementation increased shedding and the ileal burden of wild-type (WT) ETEC but decreased shedding and the tissue burden of LT knockout (LTKO) ETEC. LTKO ETEC-infected mice had delayed disease onset and also had less inflammation by fecal myeloperoxidase (MPO) assessment. These findings provide a new murine model of ETEC infection that can help elucidate mechanisms of growth, diarrhea, and inflammatory responses as well as potential vaccines and interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Data collection methods have been previously described [16]. Briefly, the MAL-ED cohorts consisted of approximately 200 children per site followed from birth to 24 months of age [7].…”

Section: Methodsmentioning

confidence: 99%

Vaccine coverage and adherence to EPI schedules in eight resource poor settings in the MAL-ED cohort study

Hoest

Seidman

Lee

et al. 2017

Vaccine

Self Cite

View full text Add to dashboard Cite

BackgroundLaunched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings.MethodsThe Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained monthly from vaccination cards, local clinic records and/or caregiver reports. Vaccination histories were compared against the prescribed EPI schedules for each country, and coverage rates were examined in relation to the timing of vaccination. The influence of socioeconomic factors on vaccine timing and coverage was also considered.ResultsCoverage rates for EPI vaccines varied between sites and by type of vaccine; overall, coverage was highest in the Nepal and Bangladesh sites and lowest in the Tanzania and Brazil sites. Bacillus Calmette-Guérin coverage was high across all sites, 87–100%, whereas measles vaccination rates ranged widely, 73–100%. Significant delays between the scheduled administration age and actual vaccination date were present in all sites, especially for measles vaccine where less than 40% were administered on schedule. A range of socioeconomic factors were significantly associated with vaccination status in study children but these results were largely site-specific.ConclusionsOur findings highlight the need to improve measles vaccination rates and reduce delayed vaccination to achieve EPI targets related to the establishment of herd immunity and reduction in disease transmission.

show abstract

“…Malnutrition is associated with dysfunctions of innate and adaptive immunity [ 41 ] and therefore is a major factor negatively affecting vaccine efficacy and effectiveness in low- and middle-income countries [ 42 ]. Malnutrition has long been recognized as a determinant of adverse patient outcome in hospital [ 43 ].…”

Section: Differences In Rotavirus Vaccine Effectiveness: Causes Anmentioning

confidence: 99%

Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

2017

View full text Add to dashboard Cite

Rotaviruses are a major cause of acute gastroenteritis in infants and young children worldwide and in many other mammalian and avian host species. Since 2006, two live-attenuated rotavirus vaccines, Rotarix® and RotaTeq®, have been licensed in >100 countries and are applied as part of extended program of vaccination (EPI) schemes of childhood vaccinations. Whereas the vaccines have been highly effective in high-income countries, they were shown to be considerably less potent in low- and middle-income countries. Rotavirus-associated disease was still the cause of death in >200,000 children of <5 years of age worldwide in 2013, and the mortality is concentrated in countries of sub-Saharan Africa and S.E. Asia. Various factors that have been identified or suggested as being involved in the differences of rotavirus vaccine effectiveness are reviewed here. Recognition of these factors will help to achieve gradual worldwide improvement of rotavirus vaccine effectiveness.

show abstract

Evaluating Associations Between Vaccine Response and Malnutrition, Gut Function, and Enteric Infections in the MAL-ED Cohort Study: Methods and Challenges

Cited by 33 publications

References 41 publications

Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea

Critical Role of Zinc in a New Murine Model of Enterotoxigenic Escherichia coli Diarrhea

Vaccine coverage and adherence to EPI schedules in eight resource poor settings in the MAL-ED cohort study

Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors

Contact Info

Product

Resources

About