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

BackgroundThe 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. MethodsFrom 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. ResultsOverall, 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. ConclusionsThe 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.