Assessing the burden of viral co-infections in acute gastroenteritis in children: An eleven-year-long investigation

Background: Acute gastroenteritis is an important cause of childhood morbidity and mortality worldwide. A number of pathogens are responsible for human acute gastroenteritis. The recent introduction of syndromic assays for the diagnosis of enteric infections, including a wide panel of enteric pathogens, has unveiled the frequency of mixed infections. This study was carried out to assess the burden of viral co-infections and the genetic diversity of the viruses detected in children hospitalized with acute gastroenteritis in Italy. Methods: A total of 4161 stool samples collected from diarrheic children over 11 years, from January 2008 to December 2018, were investigated for the presence of four enteric viruses, i.e. group A rotavirus, norovirus, astrovirus and adenovirus. The samples were initially screened by either molecular or immunochromatographic assays and subsequently confirmed by Real-time PCR and sequence analyses. Results: At least one viral agent was detected in 48.6 %of specimens. Rotavirus was the most prevalent virus (24.7 %) followed by norovirus (19.6 %), adenovirus (5.3 %) and astrovirus (3%). Co-infections were detected in 8.3 % of virus-positive patients, with common viral combination being rotavirus with norovirus (70.6 % of co-infections) or with astrovirus (9.6 %). A variety of viral genotypes was detected in co-infections and in single infections. Using Real-time PCR cycle thresholds as a proxy measure of fecal viral load, rotavirus was generally detected at higher levels in co-infected patients. Conclusions: Combining and deciphering measurable indicators of viral load and epidemiological information could be useful for an accurate interpretation of viral co-infections.