High Levels of Co-detection of Norovirus and Other Enteric Pathogens in Hospitalized Patients with and without Acute Gastroenteritis in Bangladesh

Background: The contribution of various enteropathogens to the occurrence of acute gastroenteritis (AGE) remains uncertain in highly endemic settings. We describe the frequency of norovirus-only detections and norovirus co -detections in hospitalized patients in Bangladesh and compare their clinical severity and viral load. Methods: From March 2018--October 2021, 1,250 AGE cases and 1,250 non-AGE controls of all ages were enrolled at 10 tertiary care hospitals in Bangladesh. All norovirus-positive AGE cases (n=111) and non-AGE controls (n=182), and a randomly selected subset of 126 norovirus-negative AGE cases, were tested for other enteric viral, bacterial, and parasitic co-pathogens with quantitative real-time PCR assays. We used cycle threshold (Ct) values as a proxy for viral load and the Vesikari scale to assess disease severity. Results: Overall, 92% (218/237) of AGE cases had [≥]1 enteropathogen detected. Among 293 norovirus-positive AGE cases and non-AGE controls, 88 (30%) were norovirus-only detections and 205 (70%) were norovirus co-detections. Norovirus-rotavirus was the predominant co-detection, found in 140 (68%) of 205 norovirus co-detections. No differences in clinical severity were observed among AGE cases with norovirus-only versus norovirus co-detections. The median (interquartile range) Ct values among genogroup II norovirus-only AGE cases, norovirus co-detection AGE cases, and norovirus-positive non-AGE controls were 26 (21-31), 25 (20-29), and 25 (21-30), respectively. Conclusions: The frequent co-detection of norovirus with other enteropathogens, especially rotavirus, along with overlapping Ct-values in patients with and without AGE, and between norovirus-only and norovirus co-detections, complicates attributing norovirus as a primary cause of AGE in hospitalized patients in Bangladesh.