A Clinical Epidemiology and Molecular Attribution Evaluation of Adenoviruses in Pediatric Acute Gastroenteritis: a Case-Control Study

Abstract

The objective of this study was to characterize the etiological role of human adenovirus (HAdV) serotypes in pediatric gastroenteritis. Using a case-control design, we compared the frequencies of HAdV serotypes between children with ≥3 episodes of vomiting or diarrhea within 24 h and <7 days of symptoms (i.e., cases) and those with no infectious symptoms (i.e., controls). Stool samples and/or rectal swabs underwent molecular serotyping with cycle threshold (Ct) values provided by multiplex real-time reverse transcription-PCR testing. Cases without respiratory symptoms were analyzed to calculate the proportion of disease attributed to individual HAdV serotypes (i.e., attributable fraction). Between December 2014 and August 2018, adenoviruses were detected in 18.8% (629/3,347) of cases and 7.2% (97/1,355) of controls, a difference of 11.6% (95% confidence interval [CI], 9.6%, 13.5%). In 96% (95% CI, 92 to 98%) of HAdV F40/41 detections, the symptoms could be attributed to the identified serotype; when serotypes C1, C2, C5, and C6 were detected, they were responsible for symptoms in 52% (95% CI, 12 to 73%). Ct values were lower among cases than among controls (P < 0.001). HAdV F40/41, C2, and C1 accounted for 59.7% (279/467), 17.6% (82/467), and 12.0% (56/467) of all typed cases, respectively. Among cases, Ct values were lower for F40/41 serotypes than for non-F40/41 serotypes (P < 0.001). HAdV F40/41 serotypes account for the majority of HAdV-positive gastroenteritis cases, and when detected, disease is almost always attributed to infection with these pathogens. Non-F40/41 HAdV species have a higher frequency of asymptomatic infection and may not necessarily explain gastroenteritis symptoms. Real-time quantitative PCR may be useful in differentiating asymptomatic shedding from active infection.