title: Delayed Dosing of Oral Rotavirus Vaccine Demonstrates Decreased Risk of Rotavirus Gastroenteritis Associated With Serum Zinc: A Randomized Controlled Trial.
abstract: BACKGROUND
  Rotavirus is the world's leading cause of childhood diarrheal death. Despite successes, oral rotavirus vaccines are less effective in developing countries. In an urban slum of Dhaka, we performed active diarrhea surveillance to evaluate monovalent G1P[8] rotavirus vaccine (RV1) efficacy and understand variables contributing to risk of rotavirus diarrhea (RVD).
  
  
  METHODS
  We performed a randomized controlled trial of monovalent oral rotavirus vaccine (RV1). Seven hundred healthy infants received RV1 or no RV1 (1:1) using delayed dosing (10 and 17 weeks) and were followed for 1 year. Intensive diarrhea surveillance was performed. The primary outcome was ≥1 episode of RVD. Nutritional, socioeconomic, and immunologic factors were assessed by logistic regression best-subsets analysis for association with risk of RVD and interactions with vaccine arm.
  
  
  RESULTS
  Incidence of all RVD was 38.3 cases per 100 person-years. Per-protocol RV1 efficacy was 73.5% (95% confidence interval [CI], 45.8%-87.0%) against severe RVD and 51% (95% CI, 33.8%-63.7%) against all RVD. Serum zinc level (odds ratio [OR], 0.77; P = .002) and lack of rotavirus immunoglobulin A (IgA) seroconversion (OR, 1.95; P = .018) were associated with risk of RVD, independent of vaccination status. Water treatment and exclusive breastfeeding were of borderline significance. Factors not associated with RVD included height for age at 10 weeks, vitamin D, retinol binding protein, maternal education, household income, and sex.
  
  
  CONCLUSIONS
  In an urban slum with high incidence of RVD, the efficacy of RV1 against severe RVD was higher than anticipated in the setting of delayed dosing. Lower serum zinc level and lack of IgA seroconversion were associated with increased risk of RVD independent of vaccination.
  
  
  BACKGROUND
  NCT01375647.
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: E Ross
authors.initials: ER
authors.lastname: Colgate
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Dickson
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: Marya P
authors.initials: MP
authors.lastname: Carmolli
authors.affiliation: Department of Public Health Sciences Center for Public Health Genomics, University of Virginia.
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.affiliation: Center for Public Health Genomics, University of Virginia.
authors.forename: Uma
authors.initials: U
authors.lastname: Nayak
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
authors.forename: Masud
authors.initials: M
authors.lastname: Alam
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: Mary Claire
authors.initials: MC
authors.lastname: Walsh
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Diehl
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka.
authors.forename: K
authors.initials: K
authors.lastname: Zaman
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
authors.affiliation: Department of Medicine, Vaccine Testing Center and Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
mesh_terms: D000284:Administration, Oral; D001459:Bangladesh / Q000453:epidemiology; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D012307:Risk Factors; D012401:Rotavirus; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D015032:Zinc / Q000097:blood*
chemical_list: D022243:Rotavirus Vaccines; D015032:Zinc
keywords: developing countries; oral vaccine; rotavirus diarrhea; underperformance; zinc