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► Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals was assessed. ► Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. ► Immunogenicity and safety of HRV vaccine in transmission cases was assessed. ► Transmission rate was 18.8%; however, they were not associated with increased risk of gastroenteritis. Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts. This randomized (1:1), double-blind study evaluated the potential for transmission of human rotavirus vaccine strain, HRV (Rotarix™) from vaccine recipients to unvaccinated close contacts (twins). 100 pairs of healthy twins aged 6–14 weeks at the time of Dose 1 of HRV vaccine/placebo were enrolled and one randomly selected twin from each pair received two vaccine doses and the other received placebo doses (at 2 and 4 months of age). Presence of vaccine strain in the stool samples of placebo recipients was an indicator of transmission. Serial stool samples were tested for rotavirus using ELISA at pre-determined time points; rotavirus positive stool samples were tested with RT-PCR and reverse hybridization assay to identify G1P[8] vaccine strain. If G1P[8] vaccine strain was detected, the complete genome was sequenced to assess the similarity between viral isolates. Immunogenicity and safety of HRV vaccine in transmission cases was assessed. 15 transmission cases were reported in 80 evaluable twins who received placebo and the transmission rate was 18.8% (95% CI: 10.9–29.0%). None of the transmission cases was associated with gastroenteritis symptoms. Anti-rotavirus IgA seroconversion was 62.5% (95% CI: 51.0–73.1%) (HRV) and 21.3% (95% CI: 12.9–31.8%) (placebo) 7-weeks post-Dose 2; seroconversion in transmission cases was 26.7% (95% CI: 7.8–55.1%). Genetic variations or amino acid substitutions in transmission cases were similar to that seen in corresponding vaccine recipients. Transmission of HRV vaccine strain to unvaccinated twins living in close contact occurred, however, they were not associated with increased of gastroenteritis. Whether transmission leads to indirect protection among unvaccinated individuals remains unknown at this stage.

Rotavirus diarrhea is a public health problem throughout the world, and it takes its greatest toll on infants and young children less than 24 months of age. Development of a rotavirus vaccine to prevent severe diarrhea is a high priority. 1 , 2 Although rotavirus infections occur with nearly equal frequency in developed and developing countries, the consequences are quite different. More than 870,000 children under five years of age are estimated to die annually from rotavirus infections in developing countries, and only 75 to 150 in the United States. 3 , 4 However, more than 100,000 infants and young children are hospitalized annually . . .

Rotavirus A (RVA) is a leading cause of severe diarrhoea in children, and interspecies transmission significantly drives the genomic diversity of human RVAs. Cats represent a key host species, requiring in-depth analysis regarding RVA transmission to humans. This review evaluated the literature on the complex genotype constellations of feline RVAs in relation to relevant canine and human RVAs to define the role of feline RVAs in the evolutionary history of human strains. The review traces the methodological shift from genogrouping by RNA-RNA hybridisation to the current genotype constellation system enabled by whole-genome sequencing. While early methods identified a shared genomic closeness between human AU-1 and feline FRV-1, whole-genome sequencing indicated that several human RVA strains, including AU-1, HCR3A, and Ro1845, likely resulted from direct transmission of feline/canine strains, due to shared genotype constellations and high sequence identity with animal strains like feline FRV-1, Cat97 and canine CU-1. Evidence of reassortment—such as the emergence of G1P[9] and G9P[9] strains after the feline-derived G3P[9] crossed into the human population—suggests these feline-like strains have successfully overcome the host-species barrier and are capable of onward human-to-human transmission, not just dead-end spillover events. However, definitive confirmation of sustained transmission or contemporary spillover requires stringent phylogenetic criteria: multiple human strains with >99% identical sequences in a monophyletic lineage for sustained transmission, or an identical human–feline pair across all genome segments for contemporary spillover. Confirming the status of the AU-1-like constellation as a third, low-frequency human RVA type requires future studies applying these strict criteria.

Norovirus and rotavirus are the dominant pathogens causing acute gastroenteritis in children. To quantify their natural disease burden and transmission, we prospectively monitored households in an endemic setting in the Netherlands, a high-income country that does not have a rotavirus vaccination programme. We did a prospective, household survey-based cohort study in the Netherlands. Randomly selected households from the Dutch Population Register were invited to participate if they had at least three household members, including a child younger than 2 years. A member of each household was asked to record the gastrointestinal symptoms of all household members every day for 10 consecutie weeks using an interactive smartphone application. Real-time detection of acute gastroenteritis onset on the basis of entered symptoms activated requests for the case and one other household member to complete disease questionnaires and provide stool samples. Stool samples were analysed by real-time PCR for norovirus, rotavirus, adenovirus 40/41, and astrovirus. We calculated the per-pathogen proportion of households with at least one secondary acute gastroenteritis episode (epidemiologically but not microbiologically linked), the probability of a secondary episode in household members at risk (secondary attack rate), and the microbiologically confirmed symptomatic and asymptomatic transmission rates. During two seasons (January to March) in 2016 and 2017, 30 660 households were invited to participate, of which 604 households including 2298 individuals were enrolled. 697 acute gastroenteritis episodes were detected in 358 households, with samples obtained from 609 (87%) of 697 episodes. Norovirus (150 [25%] of 609 cases) and rotavirus (91 [15%] cases) were most frequently detected. Astrovirus was detected in 50 (8%) samples and adenovirus 40/41 in 24 (4%) samples. Overall disease severity was higher in patients with rotavirus-positive acute gastroenteritis than those with norovirus-positive acute gastroenteritis. Norovirus led to higher disease burden in adults than did rotavirus. Following an index case, a secondary acute gastroenteritis episode occurred in 34 (35%) of 96 households for norovirus and 26 (46%) of 56 households for rotavirus. Secondary attack rates were 15% (37 of 244 participants) for norovirus and 28% (33 of 120 participants) for rotavirus and asymptomatic transmission rates were 51% (52 of 102 household members) for norovirus and 22% (12 of 55 household members) for rotavirus. The microbiologically confirmed symptomatic transmission rate for norovirus was 10% (25 of 254 household members) and 18% for rotavirus (21 of 119 household members). In households with young family members in a setting without rotavirus vaccination, norovirus is the dominant acute gastroenteritis pathogen, but rotavirus is associated with more severe disease. There was substantial within-household transmission, both symptomatic and asymptomatic. The study provides key quantities on transmission, which can inform vaccine policy decisions and act as a baseline for impact evaluations in high-income settings. The Netherlands Organisation for Health Research and Development (grant 91616158).

The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses. IMPORTANCE The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents sheds light on the vast genetic diversity of rotaviruses and also hints at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.

Rotavirus is the leading cause of severe diarrhea in infants and young children. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains leading to clinical disease was not well evaluated in the pivotal clinical trials, and only a few case reports have been described in the literature. We performed a systematic literature review to investigate secondary transmission of RV5 strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers, and other resources (i.e., conference papers with full text) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles based on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 strain transmission as outcomes. Other study or publication types were excluded, such as pre-clinical studies, interventional studies and case reports. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used, and study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess the risk of bias. The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of the NOS or JBI checklist, respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms, but all symptoms were attributed to other clinical conditions. We found no evidence of horizontal transmission of RV5 strains to unvaccinated infants in a context of a limited amount and the descriptive nature of the identified studies.

Rotavirus infection is the major cause of acute gastroenteritis among children globally. Sub-Saharan Africa including Ethiopia is disproportionally affected by the disease. The aims of this review were to determine the pooled prevalence of rotavirus infection among children under-five and to identify the dominant rotavirus genotypes in Ethiopia. Twelve studies were included to estimate the pooled prevalence of rotavirus acute gastroenteritis and five studies were used to determine predominantly circulating genotypes of rotavirus. The pooled prevalence of rotavirus infection was 23% (95% CI = 22%–24%). G3 (27.1%) and P[8] (49%) were the dominant G and P types, respectively. The G8 G-type uncommon in humans but highly prevalent in cattle was also reported accounting for 1% of all cases. The major G/P combinations were G12P[8] (15.4%), G3P[6] (14.2%), G1P[8] (13.6%) and G3P[8] (12.9%) collectively accounting for 56.1% of rotavirus strains. Similar to other parts of the world, the dominance of G1, G3, P[6] and P[8] genotypes was noted in Ethiopia. The increased prevalence of G12P[8] strains observed in Ethiopia was similar to observations in other geographic regions in the post-vaccine introduction period. Thus, further studies are required on the vaccine effectiveness, genotype distribution and inter-species transmission potential of rotaviruses in Ethiopia.

Probiotics have been proposed for the management and prevention of acute diarrhoea in infants. A double-blind, randomised, placebo controlled study was carried out in 224 Chinese infants 6 to 36 months of age with severe acute diarrhoea and free from moderate or severe malnutrition. After oral or parenteral rehydration, they were allocated to one of three groups: a lactose-free formula (Control); the same formula but with viable 108CFU B. lactis Bb12 and 5x107CFU St. thermophilus TH4 per gram of powder and, the same formula with the same microorganisms, but with 109CFU/g and 5x108CFU, respectively. Anthropometric parameters, duration of the diarrhoea and rotavirus shedding were evaluated. Eighty seven percent of the episodes were associated with rotavirus infection. The duration of the diarrhoea was not influenced by the intake of probiotics. However, a decrease of rotavirus shedding was observed in infants fed the formula with 109 Bb12/g, a finding of probable epidemiological importance in the transmission of this agent.

Rotaviruses (RVs) are responsible for more than 600,000 child deaths each year. The worldwide introduction of two life oral vaccines RotaTeq and Rotarix is believed to reduce this number significantly. Before the licensing of both vaccines, two new genotypes, G9 and G12, emerged in the human population and were able to spread across the entire globe in a very short time span. To quantify the VP7 mutation rates of these G9 and G12 genotypes and to estimate their most recent common ancestors, we used a Bayesian Markov chain Monte Carlo framework. Based on 356 sequences for G9 and 140 sequences for G12, we estimated mutation rates (nt substitutions/site/year) of 1.87 × 10−3 (1.45–2.27 × 10−3) for G9 and 1.66 × 10−3 (1.13–2.32 × 10−3) for G12. For both the G9 and G12 strains, one particular (sub) lineage was able to disseminate and cause disease across the world. The most recent common ancestors of these particular lineages were dated back to 1989 (1986–1992) and 1995 (1992–1998) for the G9 and G12 genotypes, respectively. These estimates suggest that a single novel RV (e.g., a vaccine escape mutant) can spread worldwide in little more than a decade. These results re-emphasize the need for thorough and continued RV surveillance in order to detect such potential spreading events at an early stage.

Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1–2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06–1·30) and disease (1·28 [1·08–1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16–57). Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.