Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.
Campylobacter is the leading bacterial cause of diarrheal disease worldwide and poultry remains the primary vehicle of its transmission to humans. Due to the rapid increase in antibiotic resistance among Campylobacter strains, the World Health Organization (WHO) added Campylobacter fluoroquinolone resistance to the WHO list of antibiotic-resistant “priority pathogens”. This study aimed to investigate the occurrence and antibiotic resistance of Campylobacter spp. in meat samples from chickens reared in different production systems: (a) conventional, (b) free-range and (c) backyard farming. Campylobacter spp. was detected in all samples from conventionally reared and free-range broilers and in 72.7% of backyard chicken samples. Levels of contamination were on average 2.7 × 103 colony forming units (CFU)/g, 4.4 × 102 CFU/g and 4.2 × 104 CFU/g in conventionally reared, free-range and backyard chickens, respectively. Campylobacter jejuni and Campylobacter coli were the only species isolated. Distribution of these species does not seem to be affected by the production system. The overall prevalence of Campylobacter isolates exhibiting resistance to at least one antimicrobial was 98.4%. All the C. coli isolates showed resistance to ciprofloxacin and to nalidixic acid, and 79.5 and 97.4% to ampicillin and tetracycline, respectively. In total, 96.2% of C. jejuni isolates displayed a resistant phenotype to ciprofloxacin and to nalidixic acid, and 92.3% to ampicillin and tetracycline. Of the 130 Campylobacter isolates tested, 97.7% were classified as multidrug resistant (MDR).
Campylobacter spp. are the most common bacterial pathogens associated with human gastroenteritis in industrialized countries. Contaminated chicken is the food vehicle associated with the majority of reported cases of campylobacteriosis, either by the consumption of undercooked meat or via cross- contamination of ready-to-eat (RTE) foods during the handling of contaminated raw chicken parts and carcasses. Our results indicate that cooking salt (used for seasoning) is a potential vehicle for Campylobacter spp. cross-contamination from raw chicken to lettuce, through unwashed hands after handling contaminated chicken. Cross-contamination events were observed even when the chicken skin was contaminated with low levels of Campylobacter spp. (ca. 1.48 Log CFU/g). The pathogen was recovered from seasoned lettuce samples when raw chicken was contaminated with levels ≥ 2.34 Log CFU/g. We also demonstrated that, once introduced into cooking salt, Campylobacter spp. are able to survive in a culturable state up to 4 hours. After six hours, although not detected following an enrichment period in culture medium, intact cells were observed by transmission electron microscopy. These findings reveal a “novel” indirect cross-contamination route of Campylobacter in domestic settings, and a putative contamination source to RTE foods that are seasoned with salt, that might occur if basic food hygiene practices are not adopted by consumers when preparing and cooking poultry dishes.
Enteroviruses are a leading cause of upper respiratory tract, gastrointestinal, and neurological infections. Management of enterovirus-related diseases has been hindered by the lack of specific antiviral treatment. The pre-clinical and clinical development of such antivirals has been challenging, calling for novel model systems and strategies to identify suitable pre-clinical candidates. Organoids represent a new and outstanding opportunity to test antiviral agents in a more physiologically relevant system. However, dedicated studies addressing the validation and direct comparison of organoids versus commonly used cell lines are lacking. Here, we described the use of human small intestinal organoids (HIOs) as a model to study antiviral treatment against human enterovirus 71 (EV-A71) infection and compared this model to EV-A71-infected RD cells. We used reference antiviral compounds such as enviroxime, rupintrivir, and 2′-C-methylcytidine (2′CMC) to assess their effects on cell viability, virus-induced cytopathic effect, and viral RNA yield in EV-A71-infected HIOs and cell line. The results indicated a difference in the activity of the tested compounds between the two models, with HIOs being more sensitive to infection and drug treatment. In conclusion, the outcome reveals the value added by using the organoid model in virus and antiviral studies.