The Changing Landscape of Pediatric Viral Enteropathogens in the Post-Rotavirus Vaccine Era

Abstract

Background: Acute gastroenteritis (AGE) is a common reason for children to receive medical care. However, the viral etiology of AGE illness is not well described in the post-rotavirus vaccine era, particularly in the outpatient (OP) setting.

Methods: Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children's Hospital, Nashville, Tennessee, with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings, and stool specimens were collected. Healthy controls (HCs) were enrolled and frequency matched for period, age group, race, and ethnicity. Stool specimens were tested by means of reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by polymerase chain reaction verification of antigen detection.

Results: A total of 3705 AGE case patients and 1563 HCs were enrolled, among whom 2885 case patients (78%) and 1110 HCs (71%) provided stool specimens that were tested. All 4 viruses were more frequently detected in AGE case patients than in HCs (norovirus, 22% vs 8%, respectively; rotavirus, 10% vs 1%; sapovirus, 10% vs 5%; and astrovirus, 5% vs 2%; P < .001 for each virus). In the OP setting, rates of AGE due to norovirus were higher than rate for the other 3 viruses. Children <5 years old had higher OP AGE rates than older children for all viruses.

Conclusions: Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, norovirus, sapovirus, rotavirus, and astrovirus were associated with almost half of all AGE visits and therefore are an important reason for children to receive medical care.

Keywords: acute gastroenteritis; healthy controls; outpatient; rotavirus; viral detection.

Figure 1.

Study enrollment algorithm and results of viral testing. Abbreviations: AGE, acute gastroenteritis; HCs, healthy controls.

Figure 2.

A, Viral pathogens detected in acute gastroenteritis (AGE) case patients. Total numbers of AGE case patients with astrovirus, rotavirus, sapovirus, norovirus, or codetections are shown. B, Viral codetections, with combinations represented by colors below bars. C, Seasonal monthly distribution of AGE viruses detected in case patients over the study period. Abbreviation: AGE, acute gastroenteritis.

Figure 3.

A, Viral loads of norovirus, astrovirus, and sapovirus in stool specimens in acute gastroenteritis (AGE) case patients and healthy controls (HCs), shown as cycle threshold (Ct) values. B, Viral loads of norovirus, astrovirus, and sapovirus in stool specimens by singly detected and codetected viruses. C, Comparison of Ct values between subjects by age groups. D, Viral loads of norovirus, astrovirus, and sapovirus in stool specimens by clinical setting. Data are shown as medians with 95% confidence intervals, and P values were calculated using the Wilcoxon rank sum test (NS, not significant). Note that Ct values were missing for 1 norovirus-positive and 1 sapovirus–positive case patient (both <5 years old). Abbreviations: AGE, acute gastroenteritis; Ct, cycle threshold; ED, emergency department; HCs, healthy controls.

Figure 4.

Rates of outpatient (OP) visits by age group, for acute gastroenteritis due to laboratory-confirmed norovirus (A), rotavirus (B), sapovirus (C), and astrovirus (D). Rates are shown as expected values with 95% posterior credible intervals; data are reported as rate credible intervals. Abbreviations: mo, month; OP, outpatient.

Figure 5.

Frequency of fever, diarrhea, and vomiting according to viral pathogen detection in acute gastroenteritis (AGE) case patients. A, Rotavirus only. B, Norovirus only. C, Astrovirus only. D, Sapovirus only. E, More than 1 pathogen. Abbreviation: AGE, acute gastroenteritis.