title: Case-Control Assessment of the Roles of Noroviruses, Human Bocaviruses 2, 3, and 4, and Novel Polyomaviruses and Astroviruses in Acute Childhood Diarrhea.
abstract: BACKGROUND
  The etiology of acute childhood diarrhea often eludes identification. We used a case-control study-stool archive to determine if nucleic acid tests for established and newly identified viruses diminish our previously published 32% rate of microbiologically unexplained episodes.
  
  
  METHODS
  Using polymerase chain reaction, we sought to detect noroviruses GI and GII, classic and novel astroviruses, and human bocaviruses (HBoVs) 2, 3, and 4 among 178 case and 178 matched control stool samples and St. Louis and Malawi polyomaviruses among a subset of 98 case and control stool samples. We calculated adjusted odds ratios and 95% confidence intervals using conditional logistic regression.
  
  
  RESULTS
  Noroviruses were more common in cases (GI, 2.2%; GII, 16.9%) than in controls (GI, 0%; GII, 4.5%) (adjusted odds ratio, 5.2 [95% confidence interval, 2.5-11.3]). Astroviruses and HBoVs 2, 3, and 4 were overrepresented among the cases, although this difference was not statistically significant. Malawi polyomavirus was not associated with case status, and St. Louis polyomavirus was identified in only 1 subject (a control). When identified in cases, HBoVs 2, 3, and 4 were frequently (77%) found in conjunction with a bona fide diarrheagenic pathogen. Thirty-five (20%) case and 3 (2%) control stool samples contained more than 1 organism of interest. Overall, a bona fide or plausible pathogen was identified in 79% of the case stool samples. Preceding antibiotic use was more common among cases (adjusted odds ratio, 4.5 [95% confidence interval, 2.3-8.5]).
  
  
  CONCLUSIONS
  Noroviruses were found to cause one-third of the diarrhea cases that previously had no identified etiology. Future work should attempt to ascertain etiologic agents in the approximately one-fifth of cases without a plausible microbial cause, understand the significance of multiple agents in stools, and guide interpretation of nonculture diagnostics.
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Rimma
authors.initials: R
authors.lastname: Melamed
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Storch
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Lori R
authors.initials: LR
authors.lastname: Holtz
authors.affiliation: Departments of Pediatrics.|Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: Klein
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Brittany
authors.initials: B
authors.lastname: Herrin
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
authors.affiliation: Departments of Pediatrics.|Global Health, University of Washington School of Medicine, Seattle, Washington.|Department of Pediatrics, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Denno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019350:Astroviridae Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D001424:Bacterial Infections / Q000453:epidemiology / Q000382:microbiology; D017250:Caliciviridae Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016022:Case-Control Studies; D002648:Child; D003967:Diarrhea / Q000453:epidemiology* / Q000209:etiology* / Q000821:virology*; D005243:Feces / Q000821:virology; D005260:Female; D056661:Human bocavirus / Q000472:pathogenicity*; D006801:Humans; D016015:Logistic Models; D008297:Male; D001257:Mamastrovirus / Q000472:pathogenicity*; D008875:Middle Aged; D029322:Norovirus / Q000145:classification / Q000472:pathogenicity*; D016017:Odds Ratio; D010322:Parvoviridae Infections / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000472:pathogenicity*; D015995:Prevalence; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents
keywords: antibiotics; children; diarrhea; human bocaviruses; viruses