Multiplex PCR Pathogen Detection in Acute Gastroenteritis Among Hospitalized US Children Compared With Healthy Controls During 2011–2016 in the Post–Rotavirus Vaccine Era

Abstract

Background Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post-RV-vaccine era. Methods From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from two NVSN sites (Kansas City; Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms. Results For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HC), overall organism detection was 51.2% and 20.6% respectively, p <0.001. Among AGE subjects, GPP PCR detected >1 virus in 39% and >1 bacteria in 14% of specimens. Detection frequencies for AGE subjects vs. HC were: norovirus (NoV) 18.5% vs 6.6%, rotavirus (RV) 16.1% vs 9.8%, adenovirus 7.7% vs 1.4%, Shigella 4.8% vs 1.0%, Salmonella 3.1% vs 0.1%, Clostridioides difficile in ≥2-year olds 4.4% vs 2.4%. More co-detections occurred among AGE (37/660, 5.6%) than HC (14/624, 2.2%), p=0.0024. Per logistic regression analysis, ill contacts increased risk for NoV, RV and Shigella, p<0.001. More vomiting episodes occurred with NoV and RV, and more diarrheal episodes with Shigella and Salmonella. Modified Vesikari scores were highest for Shigella and lowest for C. difficile. Conclusion NoV detection was most frequent, however RV remained important in hospitalized AGE in the post-RV-vaccine era. Continued active surveillance is important to document ongoing vaccine effects, pathogen emergence and baseline disease burden for new vaccines.

Differences in epidemiology of enteropathogens in children pre- and post-rotavirus vaccine introduction in Kilifi, coastal Kenya

“…Further, despite introduction of childhood rotavirus vaccination, RVA was the fourth most detected and we did not observe a significant difference in RVA positivity rate between pre- and post-vaccination introduction periods following TAC analysis. There have been few studies focused on illuminating on changes in multiple enteropathogen presentation post-rotavirus vaccination [ 26 – 31 ]. Our findings here align with previous research in low-middle income countries (LMIC) settings, such as Global Enteric Multicenter Study (GEMS) [ 25 ] and Malnutrition and Enteric Disease Study (MAL-ED) study [ 32 ], which also found high rates of enteropathogen co-infections.…”

Variation in stool testing for children with acute gastrointestinal infections

“…[1][2][3][4] While viruses are the most frequent cause in the United States, bacteria and parasites are important to identify as they may warrant different management, including infection prevention interventions for school or childcare. [5][6][7][8][9][10][11] The Centers for Disease Control and Prevention guidelines for the management of acute gastrointestinal infections advocate for limited use of diagnostic tests such as stool cultures. 12 The guidelines have not been updated since publication in 2003 and do not address molecular tests (e.g., multiplex polymerase chain reaction [PCR] testing).…”

“…[13][14][15] Within the last decade, many hospitals across the United States have transitioned away from conventional diagnostic studies for gastroenteritis (e.g., culture, serology, and immunofluorescence assays) in favor of multiplex PCRs for the detection of multiple enteric organisms from a single specimen. 11,16 Multiplex PCR tests have advantages over conventional tests, including speed and increased sensitivity to identify gastrointestinal pathogens. 11,[16][17][18] While these tests may contribute to earlier targeting and discontinuation of antimicrobials, 19 they may also lead to overidentification of nonpathogenic bacteria in healthy patients, contributing to inappropriate antibiotic use.…”

“…11,16 Multiplex PCR tests have advantages over conventional tests, including speed and increased sensitivity to identify gastrointestinal pathogens. 11,[16][17][18] While these tests may contribute to earlier targeting and discontinuation of antimicrobials, 19 they may also lead to overidentification of nonpathogenic bacteria in healthy patients, contributing to inappropriate antibiotic use. 10,20 Recent studies highlight low-value care practices for children hospitalized with acute gastrointestinal infections, including high rates of electrolyte testing and intravenous fluid administration among hospitalized children and increased multiplex PCR testing with minimal impact on patient outcomes.…”

“…Children with gastrointestinal infections often require an emergency department (ED) evaluation or hospitalization 1–4 . While viruses are the most frequent cause in the United States, bacteria and parasites are important to identify as they may warrant different management, including infection prevention interventions for school or childcare 5–11 . The Centers for Disease Control and Prevention guidelines for the management of acute gastrointestinal infections advocate for limited use of diagnostic tests such as stool cultures 12 .…”