High Prevalence of Coinfecting Enteropathogens in Suspected Rotavirus Vaccine Breakthrough Cases.

Despite the global use of rotavirus vaccines, vaccine breakthrough cases remain a pediatric health problem. In this study, we investigated suspected rotavirus vaccine breakthrough cases using next-generation sequencing (NGS)-based viral metagenomics (n = 102) and a panel of semiquantitative reverse transcription-PCR (RT-qPCR) (n = 92) targeting known enteric pathogens. Overall, we identified coinfections in 80% of the cases. Enteropathogens such as adenovirus (32%), enterovirus (15%), diarrheagenic Escherichia coli (1 to 14%), astrovirus (10%), Blastocystis spp. (10%), parechovirus (9%), norovirus (9%), Clostridioides (formerly Clostridium) difficile (9%), Dientamoeba fragilis (9%), sapovirus (8%), Campylobacter jejuni (4%), and Giardia lamblia (4%) were detected. Except for a few reassortant rotavirus strains, unusual genotypes or genotype combinations were not present. However, in addition to well-known enteric viruses, divergent variants of enteroviruses and nonclassic astroviruses were identified using NGS. We estimated that in 31.5% of the patients, rotavirus was likely not the cause of gastroenteritis, and in 14.1% of the patients, it contributed together with another pathogen(s) to disease. The remaining 54.4% of the patients likely had a true vaccine breakthrough infection. The high prevalence of alternative enteropathogens in the suspected rotavirus vaccine breakthrough cases suggests that gastroenteritis is often the result of a coinfection and that rotavirus vaccine effectiveness might be underestimated in clinical and epidemiological studies.

Gut Virome Analysis of Cameroonians Reveals High Diversity of Enteric Viruses, Including Potential Interspecies Transmitted Viruses.

Diarrhea remains one of the most common causes of deaths in children. A limited number of studies have investigated the prevalence of enteric pathogens in Cameroon, and as in many other African countries, the cause of many diarrheal episodes remains unexplained. A proportion of these unknown cases of diarrhea are likely caused by yet-unidentified viral agents, some of which could be the result of (recent) interspecies transmission from animal reservoirs, like bats. Using viral metagenomics, we screened fecal samples of 221 humans (almost all with gastroenteritis symptoms) between 0 and 89 years of age with different degrees of bat contact. We identified viruses belonging to families that are known to cause gastroenteritis such as Adenoviridae, Astroviridae, Caliciviridae, Picornaviridae, and Reoviridae Interestingly, a mammalian orthoreovirus, picobirnaviruses, a smacovirus, and a pecovirus were also found. Although there was no evidence of interspecies transmission of the most common human gastroenteritis-related viruses (Astroviridae, Caliciviridae, and Reoviridae), the phylogenies of the identified orthoreovirus, picobirnavirus, and smacovirus indicate a genetic relatedness of these viruses identified in stools of humans and those of bats and/or other animals. These findings points out the possibility of interspecies transmission or simply a shared host of these viruses (bacterial, fungal, parasitic, …) present in both animals (bats) and humans. Further screening of bat viruses in humans or vice versa will elucidate the epidemiological potential threats of animal viruses to human health. Furthermore, this study showed a huge diversity of highly divergent novel phages, thereby expanding the existing phageome considerably.IMPORTANCE Despite the availability of diagnostic tools for different enteric viral pathogens, a large fraction of human cases of gastroenteritis remains unexplained. This could be due to pathogens not tested for or novel divergent viruses of potential animal origin. Fecal virome analyses of Cameroonians showed a very diverse group of viruses, some of which are genetically related to those identified in animals. This is the first attempt to describe the gut virome of humans from Cameroon. Therefore, the data represent a baseline for future studies on enteric viral pathogens in this area and contribute to our knowledge of the world's virome. The studies also highlight the fact that more viruses may be associated with diarrhea than the typical known ones. Hence, it provides meaningful epidemiological information on diarrhea-related viruses in this area.