title: Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh.
abstract: BACKGROUND
  Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh.
  
  
  METHODS
  We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647.
  
  
  RESULTS
  EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < - 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix® IgA positive individuals can be attributed to the selected biomarkers.
  
  
  CONCLUSIONS
  EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention.
  
  
  BACKGROUND
  The Bill and Melinda Gates Foundation (OPP1017093).
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Caitlin
authors: C
authors: Naylor
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Miao
authors: M
authors: Lu
authors: The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
authors: Rashidul
authors: R
authors: Haque
authors: The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
authors: Dinesh
authors: D
authors: Mondal
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Erica
authors: E
authors: Buonomo
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Uma
authors: U
authors: Nayak
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Josyf C
authors: JC
authors: Mychaleckyj
authors: The University of Vermont, Burlington, VT, USA.
authors: Beth
authors: B
authors: Kirkpatrick
authors: The University of Vermont, Burlington, VT, USA.
authors: Ross
authors: R
authors: Colgate
authors: The University of Vermont, Burlington, VT, USA.
authors: Marya
authors: M
authors: Carmolli
authors: The University of Vermont, Burlington, VT, USA.
authors: Dorothy
authors: D
authors: Dickson
authors: Netherlands National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors: Fiona
authors: F
authors: van der Klis
authors: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: William
authors: W
authors: Weldon
authors: Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: M
authors: M
authors: Steven Oberste
authors: The University of Virginia, Charlottesville, VA, USA.
authors: Jennie Z
authors: JZ
authors: Ma
authors: The University of Virginia, Charlottesville, VA, USA.
authors: William A
authors: WA
authors: Petri
mesh_terms: D000284:Administration, Oral; D001459:Bangladesh / Q000453:epidemiology; D015415:Biomarkers; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007228:Infant Nutrition Disorders / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism; D007231:Infant, Newborn; D007410:Intestinal Diseases / Q000453:epidemiology* / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D017063:Outcome Assessment, Health Care; D062486:Public Health Surveillance; D012959:Socioeconomic Factors; D014505:Urban Population; D014611:Vaccination / Q000379:methods / Q000706:statistics & numerical data*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015415:Biomarkers; D014612:Vaccines
keywords: Environmental enteropathy; Malnutrition; Oral vaccine failure