BACKGROUND: Rotavirus infections are a significant cause of severe diarrhea and related illness and death in children under five worldwide. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in high deaths annually, mainly in low-income countries, including Ethiopia, and need special attention. This system review and meta-analysis aimed to comprehensively explore the positive proportion of rotavirus at pre- and post-vaccine introduction periods and genotype distribution in children under five with diarrhea in Ethiopia.
METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Database sources included PubMed, Scopus, EMBASE, and Epistemonikos, focusing on studies published before November 30, 2023. The search targeted rotavirus infection and genotype distribution in Ethiopia before and after the introduction of the Rota vaccine. Data was managed using EndNote 2020 software and stored in an Excel 2010 sheet. A random-effects model determined the pooled estimate of the rotavirus infection rate at 95% confidence intervals. The Q-and I² statistics were used to assess the study heterogeneity, and a funnel plot (Egger test) was used to determine the possibility of publication bias.
RESULTS: The analysis included data from nine studies conducted in different regions of Ethiopia. The overall prevalence of rotavirus infection was significant, with a prevalence rate of approximately 22.63% (1362/6039). The most common genotypes identified before the Rota vacation introduction were G1, G2, G3, G12, P [4], P [6], P [8], P [9], and P [10]. Meanwhile, G3 and P [8] genotypes were particularly prevalent after the Rota vaccine introduction. These findings highlight the importance of implementing preventive measures, such as vaccination, to reduce the burden of rotavirus infection in this population. The identified genotypes provide valuable insights for vaccine development and targeted interventions.
CONCLUSIONS: This study contributes to the evidence base for public health interventions and strategies to reduce the impact of rotavirus infection in children under five in Ethiopia. Despite the rollout of the Rota vaccination in Ethiopia, rotavirus heterogeneity is still high, and thus, enhancing vaccination and immunization is essential.

The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA- like substances (HBGA+) capable of binding RV particles in vitro. We hypothesized that HBGA+ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA+ or HBGA- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA+ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA+ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA+ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.

The objective of this study was to estimate, by a novel spatiotemporal approach in an environment of non-funded rotavirus (RV) vaccines, the RV vaccine effectiveness (VE) to prevent acute gastroenteritis primary care (AGE-PC)-attended episodes, demonstrating how indirect protection leads to underestimation of direct VE under high vaccine coverage (VC). This population-based retrospective cohort study used electronic healthcare registries including all children 2 months-5 years old, born from 2009 to 2018 in the Valencia Region (Spain). Direct RV VE preventing AGE-PC episodes was estimated using propensity score matching and Poisson regressions stratified by VC, adjusted by age and calendar season. Indirect VE was estimated by Poisson regression comparing AGE-PC rates in unvaccinated children among the different VC levels. A total of 563,442 children were included for the RV VC estimation; of them, 360,576 were included in the birth-cohort for VE analysis. RV VC showed strong variability among districts and seasons, rising on average from 21% in 2009/2010 to 55% in 2017/2018. The highest direct VE was found in vaccinated children from districts with 0-30% RV VC (16.4%) and the lowest in those from districts with ≥ 70% RV VC (9.7%). The indirect protection in unvaccinated children raised from 6 to 16.6% for those living with 20-30% and ≥ 70% VC, respectively.
CONCLUSIONS: Considering that RV is the causative agent in 20% of AGE cases, a direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with VC over 70% because of indirect protection.
BACKGROUND: • The effectiveness of RV vaccines preventing hospitalizations due to RV-acute gastroenteritis (RV-AGE) has been extensively studied. However, RV also burdens the primary care (PC) setting, and data on vaccine effectiveness (VE) in preventing AGE-PC visits are scarce. • The RV vaccine distribution in Spain (non-funded), with large differences in vaccine coverage (VC) among healthcare districts, provides an ideal scenario to assess the actual VE in preventing AGE-PC consultations, including the direct and indirect protection.
BACKGROUND: • A direct effectiveness of 82% preventing AGE-PC episodes due to RV could be deduced using a novel spatiotemporal approach. A reduction of 17% of AGE-PC episodes in unvaccinated was observed in areas with high VC because of indirect protection. • These findings, together with existing data on the impact on hospitalizations due to RV-AGE, offer valuable insights for implementing vaccination initiatives in countries that have not yet commenced such programs.

Probiotics represent viable microorganisms which are found within the normal gut microbiota, that exert strain-specific benefits in the management of several gastrointestinal disorders in children, including acute gastroenteritis. This review aims to evaluate the pathogen-specific role of probiotic supplementation in childhood diarrhea. A search of scientific databases was conducted to identify studies which investigated efficacy of probiotics and synbiotics in influencing outcome of acute gastroenteritis of known etiology. We identified 32 studies, most of which analyzed impact of probiotic supplementation in rotavirus gastroenteritis, while a very limited number of these conducted a separate analysis on bacterial diarrhea. Lactobacillus rhamnosus (L. rhamnosus), L. reuteri and S. boulardii still remain the most researched strains, with a proven role in decreasing diarrhea and hospitalization duration, especially in the setting of rotavirus infection. Combined products containing at least one of the aforementioned strains also performed similarly and might also influence rotavirus fecal shedding. Rotavirus immunization status has also been proposed as a significant influencing factor of probiotic use impact. The paucity of research focusing on bacterial etiologies, as well as of clinical trials conducted within ambulatory care units leaves room for further research on the matter, which needs to include larger cohort studies.

UNASSIGNED: To investigate the prevalence of rotavirus infection and acute diarrhea after immunization and further assess the quality of nursing care provided by the nurses to such patients.
UNASSIGNED: A total of 432 children aged 3-36 months with acute diarrhea between February 2019 and March 2022 were enrolled, and rotavirus testing was performed within 24 h using a rotavirus enzyme immunoassay kit. Clinical characteristics were evaluated, and regression analysis was performed.
UNASSIGNED: Eighty vaccinated children (18.5%) were confirmed to have rotavirus infection out of 432 children. The prevalence of rotavirus positivity was the highest at 20-28 months (22 cases, 24.44%) and 11-19 months age group (27 cases, 22.50%). There is a significant association between rotavirus infection and hygiene score (p = 0.009). Based on the association with quality of nursing care, rotavirus infection was association with \"appropriate care\" (p = 0.001).
UNASSIGNED: Rotavirus infection was strongly associated with poor hygiene score which may be due to the hygienic nature of the mother and her family. Nursing care assessments revealed a huge gap between nurses and the guardians, which reflects the behavior of Chinese nurses. Thus, an intervention is required by the policymakers for implementing effective strategies of quality nursing for the improvement of the pediatric patients with rotavirus gastroenteritis.

No study has ever investigated how ambient temperature and PM2.5 mediate rotavirus infection (RvI) in children. We used insurance claims data from Taiwan in 2006-2012 to evaluate the RvI characteristics in children aged ≤ 9. The RvI incidence rates were higher in colder months, reaching the highest in March (117.0/100 days), and then declining to the lowest in July (29.2/100 days). The age-sex-specific average incident cases were all higher in boys than in girls. Stratified analysis by temperature (<20, 20-24, and ≥25 °C) and PM2.5 (<17.5, 17.5-31.4, 31.5-41.9, and ≥42.0 μg/m3) showed that the highest incidence was 16.4/100 days at average temperatures of <20 °C and PM2.5 of 31.5-41.9 μg/m3, with Poisson regression analysis estimating an adjusted relative risk (aRR) of 1.26 (95% confidence interval (CI) = 1.11-1.43), compared to the incidence at the reference condition (<20 °C and PM2.5 < 17.5 μg/m3). As the temperature increased, the incident RvI cases reduced to 4.84 cases/100 days (aRR = 0.40, 95% CI = 0.35-0.45) when it was >25 °C with PM2.5 < 17.5 μg/m3, or to 9.84/100 days (aRR = 0.81, 95% CI = 0.77-0.93) when it was >25 °C with PM2.5 > 42 μg/m3. The seasonal RvI is associated with frequent indoor personal contact among children in the cold months. The association with PM2.5 could be an alternative assessment due to temperature inversion.

Neonatal rotavirus infections are predominantly caused by distinct genotypes restricted to this age-group and are mostly asymptomatic.
Stool samples from neonates admitted for >48 h in neonatal intensive care units (NICUs) in Vellore (2014-2015) and Chennai (2015-2016) in southern India, and from neonates born at hospitals in Vellore but not admitted to NICUs (2015-2016) were tested for rotavirus by ELISA and genotyped by hemi-nested RT-PCR.
Of 791 neonates, 150 and 336 were recruited from Vellore and Chennai NICUs, and 305 were born in five hospitals in Vellore. Positivity rates in the three settings were 49.3% (74/150), 29.5% (99/336) and 54% (164/305), respectively. G10P[11] was the commonly identified genotype in 87.8% (65/74), 94.9% (94/99) and 98.2% (161/164) of the neonates in Vellore and Chennai NICUs, and those born at Vellore hospitals, respectively. Neonates delivered by lower segment cesarian section (LSCS) at Vellore hospitals, not admitted to NICUs, had a significantly higher odds of acquiring rotavirus infection compared to those delivered vaginally [p = 0.002, OR = 2.4 (1.4-4.3)].
This report demonstrates the persistence of G10P[11] strain in Vellore and Chennai, indicating widespread neonatal G10P[11] strain in southern India and their persistence over two decades, leading to interesting questions about strain stability.

UNASSIGNED: 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid saponin metabolite of glycyrrhizin, exhibits several biological activities.
UNASSIGNED: We investigated the effects of 18β-GA on MA104 cells infected with rotavirus (RV) and its potential mechanism of action.
UNASSIGNED: Cell Counting Kit-8 was used to assess tissue culture infective dose 50 (TCID50) and 50% cellular cytotoxicity (CC50) concentration. MA104 cells infected with RV SA11 were treated with 18β-GA (1, 2, 4, and 8 μg/mL, respectively). Cytopathic effects were observed. The virus inhibition rate, concentration for 50% of maximal effect (EC50), and selection index (SI) were calculated. Cell cycle, cell apoptosis, and mRNA and protein expression related to the Fas/FasL pathway were detected.
UNASSIGNED: TCID50 of RV SA11 was 10-4.47/100 µL; the CC50 of 18β-GA on MA104 cells was 86.92 µg/mL. 18β-GA showed significant antiviral activity; EC50 was 3.14 μg/mL, and SI was 27.68. The ratio of MA104 cells infected with RV SA11 in the G0/G1 phase and the G2/M phase decreased and increased, respectively, after 18β-GA treatment. 18β-GA significantly induced apoptosis in the infected cells. Furthermore, after 18β-GA treatment, the mRNA and protein expression levels of Fas, FasL, caspase 3, and Bcl-2 decreased, whereas the expression levels of Bax increased.
UNASSIGNED: The study demonstrates that 18β-GA may be a promising candidate for the treatment of RV SA11 infection and provides theoretical support for the clinical development of glycyrrhizic acid compounds for the treatment of RV infection.

Rotavirus is the most common cause of severe diarrhea among infants and young children and is responsible for more than 200,000 pediatric deaths per year. There is currently no pharmacological treatment for rotavirus infection in clinical activity. Although cholesterol synthesis has been proven to play a key role in the infections of multiple viruses, little is known about the relationship between cholesterol biosynthesis and rotavirus replication. The models of rotavirus infected two cell lines and a human small intestinal organoid were used. We investigated the effects of cholesterol biosynthesis, including inhibition, enhancement, and their combinations on rotavirus replication on these models. The knockdown of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was built by small hairpin RNAs in Caco2 cells. In all these models, inhibition of cholesterol synthesis by statins or HMGCR knockdown had a significant inhibitory effect on rotavirus replication. The result was further confirmed by the other inhibitors: 6-fluoromevalonate, Zaragozic acid A and U18666A, in the cholesterol biosynthesis pathway. Conversely, enhancement of cholesterol production increased rotavirus replication, suggesting that cholesterol homeostasis is relevant for rotavirus replication. The effects of all these compounds toward rotavirus were further confirmed with a clinical rotavirus isolate. We concluded that rotavirus replication is dependent on cholesterol biosynthesis. To be specific, inhibition of cholesterol synthesis can downregulate rotavirus replication; on the contrary, rotavirus replication is upregulated. Statin treatment is potentially an effective novel clinical anti-rotavirus strategy.

Rotavirus infections cause severe gastroenteritis in small children, with both high morbidity and mortality. The rotavirus vaccine has been recommended by the World Health Organization since 2009 and was being used by 108 countries by 2019. It joined Sweden\'s national immunisation programme that year, after 5 years of selective regional use. This review summarises the baseline facts and evidence, the most common vaccines and the global direct and indirect effects, with a special focus on Sweden. CONCLUSION: The vaccine has had a considerable impact on global and Swedish morbidity and mortality, but some indirect effects and socioeconomic differentials need research.