Rotaviruses (RVs) are major causative agents of diarrhea in both humans and animals worldwide. Despite the successful development of live attenuated vaccines, the efficacy of these vaccines remains low in developing countries and RV infections still result in more than 200,000 deaths in children under 5 years old globally each year. These viruses are also an enteric pathogen for agricultural animals and have caused substantial economic losses annually to the animal livestock industry. Frequent reassortment and the emergence of new RV strains continue to pose a significant challenge to human and agricultural animal health. Attachment to susceptible cells by recognizing cell surface glycans is the first step of the RV lifecycle, which is directed by the RV spike protein VP8∗. VP8∗-host glycan receptor interactions are thought to be strain-specific and play an important role in RV replication fitness, tropism, and cross-species transmission. This review will summarize the current understanding of the roles of VP8∗ in engagement of glycan receptors and its functional consequences in impacting RV replication fitness and host ranges. The current progress towards developing a VP8∗-based RV vaccine is also discussed in the review.

Group A rotavirus (RVA) is the primary causative agent of acute gastroenteritis (AGE) in children under five years of age, resulting in over 120,000 deaths annually. In previous studies, we identified truncated VP4∗ as a potentially more promising vaccine candidate compared to VP8∗ and VP5∗. This study aimed to compare the immunogenicity and protective efficacy of VP4∗ and P2-VP8, the most advanced recombinant rotavirus vaccine undergoing phase 3 clinical trial in various animal models, including mice, guinea pigs, rabbits, and piglets. The results indicated that the binding antibodies and neutralizing antibodies induced by VP4∗ were significantly higher levels compared to P2-VP8. Immunization with VP4∗ provided 100 % protection for mice against challenges with EDIM and LLR strains. Additionally, we were intrigued to discover that the VP4∗ antibody not only inhibited virus adsorption but also prevented the virus from entering cells following pre-adsorption. In summary, VP4∗ demonstrates greater immunogenicity and protective efficacy compared to P2-VP8, making it a more promising candidate antigen for recombinant rotavirus vaccines.

This study aimed to examine the association between fecal viral load and peripheral blood Th1/Th2 cytokines in children with rotavirus (RV) infection enteritis. A total of 102 children with RV enteritis and 102 healthy infants were enrolled between April 2022 and April 2024. Fecal viral load was assessed using real-time polymerase chain reaction (RT-PCR), while T lymphocyte subsets and Th1/Th2 cytokines were measured using flow cytometry and ELISA, respectively. Pearson correlation analysis was employed to explore the relationship between RV load and Th1/Th2 cytokines. The RV enteritis group exhibited significantly higher fecal viral load than the control group (P<0.05). Moreover, levels of peripheral blood CD3+, CD4+, and CD4+/CD8+ were significantly lower in the RV enteritis group compared to the control group (P<0.05). Additionally, the levels of IL-6, IL-10, TNF-α, and IFN-γ were significantly elevated in the RV enteritis group (P<0.05). Correlation analysis revealed a negative association between viral load and CD3+, CD4+, and CD4+/CD8+ levels, and a positive association with IL-6, IL-10, TNF-α, and IFN-γ levels (P<0.05). Notably, no significant correlation was found between viral load and CD8+ levels (P>0.05). These findings suggest that viral load correlates with Th1/Th2 cytokines in children with RV infection enteritis, providing potential targets for early diagnosis and treatment.

Group A rotavirus (RVA) associated gastroenteritis is a major cause of infantile morbidity and mortality, globally. Pakistan had the highest rates of gastroenteritis among kids, every year. Our study aimed to assess the RVA disease burden and circulating genotypes in Rawalpindi, before the vaccine's introduction in Pakistan. Stool samples were collected from children < 5 years of age admitted at Benazir Bhutto Hospital, Rawalpindi, from November 2014 to May 2015. Of the 300 stool samples, 47% of children were found positive for RVA antigen on ELISA, with the highest prevalence (52%) in infants less than 7 months of age. Rotavirus positive cases through real-time PCR were 65.5%. Fever and diarrhea were significantly related to RVA infection when compared to RVA-negative cases (P = 0.02). It is the first report on an upsurge of G12P[6] (17.24%) along with the rise of previously declining G3 in the current epidemiological area. The other prevalent types were G1P[8] (12.07%), G1P[4] (6.90%), G1P[6] (5.17%), G3P[6] (5.17%), followed by G2P[6], G3P[4], G9P[4], and G12P[8] each found with a prevalence of (3.45%). This study reports G3P[4], G3P[6] and G12P[4] for the first time in Pakistan. Mixed genotype infections were found in 21% of cases. G12P[6], which was the predominant genotype in this study, was found to be significantly associated with fever (P = 0.03). This study provides valuable data on the significantly highest prevalence of RVA-associated gastroenteritis in kids of Rawalpindi, Pakistan, and elucidates the vast diversity of circulating RVA genotypes. The reported disease burden, genotypes, and clinical symptoms would enable public health dealers to cope with the severity of the disease. It also provides an evolutionary trend of changing genotypes in the country.

The pathogenesis of enteric viral infections is attributed to both viral replication and the resultant immune-inflammatory response. To recapitulate this complex pathophysiology, we engineer macrophage-augmented organoids (MaugOs) by integrating human macrophages into primary intestinal organoids. Echovirus 1, echovirus 6, rotavirus, seasonal coronavirus OC43 and SARS-CoV-2- known to directly invade the intestine- are used as disease modalities. We demonstrate that these viruses efficiently propagate in MaugOs and stimulate the host antiviral response. However, rotavirus, coronavirus OC43 and SARS-CoV-2, but not the two echoviruses, trigger inflammatory responses. Acetate, a microbial metabolite abundantly present in the intestine, potently inhibits virus-induced inflammatory responses in MaugOs, while differentially affecting viral replication in macrophages and organoids. Furthermore, we provide a proof-of-concept of combining antiviral agent with either anti-inflammatory regimen or acetate to simultaneously inhibit viral infection and inflammatory response in MaugOs. Collectively, these findings demonstrate that MaugOs are innovative tools for studying the complex virus-host interactions and advancing therapeutic development.

Rotavirus (RV) is the most common cause of severe acute gastroenteritis (AGE) in children under five years of age. This review summarizes current knowledge on RV infections, with a particular focus on viral structure, pathophysiological mechanisms, and age-dependent clinical presentation. Special attention is given to systemic manifestations, including central nervous system involvement, autoimmune responses such as type 1 diabetes and celiac disease, and rare associations with biliary atresia. The mechanisms of RV-induced diarrhea and vomiting are discussed in detail. Clinical severity scoring systems-such as the Vesikari and Clark scales-and dehydration assessment tools-the Clinical Dehydration Scale (CDS) and the Dehydration: Assessing Kids Accurately (DHAKA) score-are compared. The review highlights differences in disease course between children under and over five years, emphasizing that RV is not limited to early childhood. A major section addresses the global effectiveness of vaccination programs, their role in reducing disease burden, coverage challenges, and decreased efficacy in low-income countries. Particular focus is placed on high-risk groups, including preterm and immunocompromised infants.

Group A rotavirus continues to be a leading global etiological agent of severe gastroenteritis in young children under 5 years of age. The replication of this virus in the host is associated with the occurrence of Lewis antigens and the secretor condition. Moreover, histo-blood group antigens (HBGAs) act as attachment factors to the outer viral protein of VP4 for rotavirus. Therefore, in this study, we employed a metabolomic approach to reveal potential signature metabolic molecules and metabolic pathways specific to rotavirus P[8] strain infection (VP4 genotype), which is associated with the expression of HBGA combined secretor and Lewis (Le) phenotypes, specifically secretor/Le(a+b+). Further integration of the achieved metabolomics results with lipidomic and proteomics metadata analyses was performed. Saliva samples were collected from children diagnosed as negative or positive for rotavirus P[8] strain infection (VP4 genotype), which is associated with the HBGA combined secretor/Le(a+b+). A total of 22 signature metabolic molecules that were downregulated include butyrate, putrescine, lactic acid, and 7 analytes. The upregulated metabolic molecule was 2,3-Butanediol. Significant pathway alterations were also specifically observed in various metabolism processes, including galactose and butanoate metabolisms. Butyrate played a significant role in viral infection and was revealed to exhibit different reactions with glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, and fatty acyls. Moreover, butyrate might interact with protein receptors of free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). The revealed metabolic pathways and molecule might provide fundamental insight into the status of rotavirus P[8] strain infection for monitoring its effects on humans.

Rotavirus infection, the most common cause of infant infectious diarrhoea and related deaths worldwide, has imposed a high disease burden in China, especially in Zhejiang Province. This study described the overall epidemiological characteristics and trends of reported rotavirus infections in Zhejiang Province from 2005 to 2022 and evaluated the effectiveness of rotavirus vaccines on the incidence of rotavirus infection.

Data on reported cases of rotavirus infection from 2005 to 2022 were extracted from the China Disease Prevention and Control Information System. Information on rotavirus vaccination was obtained from the Zhejiang Provincial Viral Diarrhoea Surveillance Site in 2022. Join-point regression, spatial and temporal aggregation analysis, and an age-period-cohort model were used to explore the epidemiological trends of rotavirus infection. Interrupted time series analysis and an overdispersed Poisson model were used to quantify the effectiveness of rotavirus vaccines.

The average age-standardized reporting incidence rate (ASRIR) of rotavirus infection in Zhejiang Province was 38.58/100,000, particularly in children aged 0-2 years, who had the highest average annual incidence of 951.63/100,000. The annual ASRIR of all ages showed a significant upward trend before 2017 (average percentage change [APC] = 21.64%) and then decreased significantly (APC = -23.02%). However, in children aged 6-19 years, the annual incidence presented a sustained and significant upward trend over time. The rotavirus infection peak showed a seasonal drift in Zhejiang Province, shifting from November before 2014 to January after 2014. Spatiotemporal aggregation revealed two clusters. The spatio-temporal scanning found two spatio-temporal aggregation areas, the first level spatio-temporal aggregation area was distributed in Hangzhou, Jiaxing and Huzhou, and the second level spatio-temporal aggregation area was Lishui. The age-period-cohort model indicated that the risk of rotavirus infection was primarily concentrated in children aged 0-4 years. The vaccine effectiveness (VE) of rotavirus vaccines was 71.62% (95% confidence interval [CI]: 45.21-86.05%) in children aged 2-59 months, in which the VE of the human-bovine reassortant pentavalent vaccine (RV5) was 91.31% (95% CI: 74.39-97.97%). Since the implementation of RV5 vaccination in September 2018, the number of cases of rotavirus infection per month has decreased by 3,061 (65.27%) in Zhejiang Province.

The disease burden of rotavirus infection in Zhejiang Province was high, especially in children. Rotavirus vaccination have significantly reduced the incidence rate of rotavirus infection. Therefore, the prevention of infectious diarrhoea should be further strengthened, especially through increased coverage with the rotavirus vaccine.

Background/Objective: Rotavirus is a major cause of acute gastroenteritis (AGE) in children <5 years. While rotavirus vaccines are effective in reducing AGE, limited data on their indirect effects exist. The aim of our narrative systematic review was to summarise the indirect effects of rotavirus vaccines on unvaccinated children and adults (PROSPERO: CRD42023418015). Methods: Peer-reviewed articles and conference abstracts were searched through Medline, Embase and PubMed on 8 December 2024. Observational studies of national/regional vaccine introduction were included. We included five outcomes: rotavirus-AGE inpatient admissions, rotavirus-AGE outpatient attendances, all-cause AGE inpatient admissions, all-cause AGE outpatient attendances, and stool rotavirus positivity. Outcome measures reported as percent reduction or individual incidence rates for the pre- and post-introduction periods were transformed to incidence rate ratios (IRRs). Median IRRs and interquartile ranges (IQRs) were calculated for each outcome by age group (<5, 5-19, and >18 years). Results: From an initial 757 articles, 44 studies including 9,327,974 participants were included. In unvaccinated children <5 years, there were reductions in rotavirus-AGE admissions (median IRR: 0.62, IQR: 0.40-0.82), rotavirus-AGE outpatient attendances (0.74, 0.16-0.98), all-cause AGE admissions (0.70, 0.56-0.86), and stool rotavirus positivity (0.42, 0.31-0.57), but not all-cause AGE outpatient attendances (0.92, 0.78-1.17). Few studies reported these outcomes for children and adolescents aged 5-19 years and adults >18 years. Indirect effects appeared to be greater in higher income and lower under-five mortality settings. Conclusions: Understanding these indirect benefits is crucial for evaluating the broader impact and cost-effectiveness of rotavirus immunisation programs.

While acute gastroenteritis (AGE) occurs year-round, norovirus has a winter seasonality in the United States.

We analyzed norovirus seasonality within a US integrated healthcare delivery system from 2016-2019.

Electronic medical records were collected for acute gastroenteritis (AGE) encounters with specific ICD-9/10 codes or clinical stool testing. Norovirus percent positivity was calculated as the 8-week centered rolling average. Temperature and absolute humidity data were measured via weather station. The relationship between these factors and weekly norovirus episodes were modeled via negative binomial models.

From 2016-2019, there were 198,181 AGE episodes reported; among the 18,998 episodes tested, 892 (5%) were norovirus positive. Norovirus percent positivity peaked in epidemiologic week 7 at 9%. Two negative binomial models showed significant inverse relationships between weekly number of norovirus episodes and both temperature and absolute humidity.

Norovirus AGE exhibited winter seasonality from 2016-2019, associated with lower temperatures and humidity. Understanding this seasonality may help predict peak transmission periods and their impact on healthcare resources.

Rotavirus (RV) is a leading cause of severe diarrhea among children under five years of age in China. In this meta-analysis, we assessed the disease burden of RV-related diarrhea by analyzing 73 studies retrieved from the PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases (2013-2023). The incidence of RV-related diarrhea ranged from 0.637 /1000 to 31.46/1000 persons. The pooled RV positivity rate for the under-5 age group was 24.7% (95% confidence interval: 22.1-27.4), with higher positivity rates observed among inpatients compared to outpatients (24.1% vs. 22.2%). Notably, the RV positivity rate declined from 27.3 to 21.5% pre- and post- the RotaTeq® licensure and 28.8-22.5% following the COVID-19 pandemic. The G9P[8] genotype was predominant, accounting for 71.7% of the RV cases in the under-5 age group. Given the dynamic nature of the incidence rate of RV-related diarrhea and the prevalence of the G9P[8] genotype, it is imperative to enhance surveillance efforts targeting incidence of RV-related diarrhea and the circulating genotypes of rotavirus.

Background/Objectives: Rotavirus gastroenteritis is a vaccine-preventable disease that leads to hospitalization in children less than 5 years of age. Immunizations to prevent rotavirus have greatly altered the epidemiology of significant diarrheal illness. It has been reported that routine immunization rates in children were impacted during the COVID-19 pandemic. Contrary to this fact, rates of many childhood illnesses also decreased. Methods: The Military Health System Data Repository (MDR) contains the health records of all military beneficiaries. We queried the MDR before and during the COVID-19 pandemic to assess for alterations in immunization rates and hospitalization rates and to assess for risk factors for significant (hospitalizations) rotavirus disease. Results: Our study included a cohort of 1.27 million children under the age of 5 years old. There were 186 unique cases of rotavirus-related hospitalizations over the 5-year study period. During COVID-19 Years 1 and 2, there was a decrease in rotavirus-related hospitalizations compared to the pre-pandemic period. During Year 3, there was a return to the pre-pandemic level of rotavirus hospitalization rates. Patients in the northern United States were less likely to be hospitalized from rotavirus when compared to those in the south. The patients at greatest risk were the youngest beneficiaries. Rotavirus vaccination rates declined in this age group during all three years of the pandemic. Conclusions: As the pandemic resulted in less frequent rotavirus immunizations in the Military Health System (MHS), there was not an increase in rotavirus-related hospitalizations above the pre-pandemic baseline.

The majority of people with enterically transmitted viruses excrete significant amounts of the virus in their feces for several days or weeks. Therefore, viruses causing diarrhea could be detected in the feces of infected persons and wastewater. In this study, the presence of human astrovirus (AstV), norovirus (NoV), rotavirus (RV), and enterovirus (EntV) was analyzed by real-time RT-PCR in raw sewage (n = 96), treated sewage (n = 96) and diarrheal stool samples (n = 200). Overall, 92.7% (89/96) of raw sewage samples and 48% (46/96) of treated sewage tested positive for at least one virus. The highest detection rates of the four viruses in raw sewage were observed in the winter season. Overall, the mean concentration of the four viruses was 7.3 log10 in raw and 4.8 log10 in treated wastewater, for a total removal of 34% of viral loads. In clinical samples, the most commonly detected virus was EntV followed by RV, NoV, and AstV. The mean concentrations of the four viruses in clinical samples ranged between 2.5 × 101 and 9.86 × 107 GC/g. The results presented here demonstrated that the environmental surveillance of entric viruses in sewage is a useful tool for the study of their transmission dynamics in humans and their molecular epidemiology.

In this study, VP6 protein of rotavirus A (RVA) was expressed in the prokaryotic system for the development of indigenous Latex Agglutination Test for diagnosis of RVA gastroenteritis in animals. Polyclonal anti-rVP6 IgG were raised in rabbits; purified and conjugated to carboxylated beads via covalent coupling for development of in-house LAT. Clinical utility of in-house developed LAT was evaluated on 313 stool samples collected from calves, children and piglets of Bareilly, Uttar Pradesh, India. In-house LAT yielded consistent results at weekly intervals for 2 months. Best visual perception of agglutination was observed when 5 μL beads coupled with 200 μg anti-rVP6 IgG and 10 μL of antigen reacted within reaction time of 2 minutes. Relative sensitivity and specificity of in-house LAT w.r.t RT-PCR was 65.45 % and 95.73 %, respectively; w.r.t commercial LFA was 75.55 % and 95.14 %, respectively and w.r.t RNA-PAGE was 70.27 % and 92.39 %, respectively. The kappa agreement between LAT and RT-PCR was 0.65 (substantial); between LAT and LFA was 0.7 (substantial) and between LAT and RNA-PAGE was 0.56 (moderate). Overall RVA stool positivity from children, calves and piglets with 4 assays was found to be 40 % (40/100), 9 % (9/100) and 16.81 % (19/113), respectively. Higher positivity was recorded in male (45.90 %, 28/61) than in female (30.76 %, 12/39) children. Developed LAT has fulfilled the WHO criteria for point-of-care testing with satisfactory efficacy for detection of RVA. This may serve as a preliminary assay for epidemiological surveillance of RVA antigen in determining rotavirus outbreaks in animal herds under resource-poor settings.

Two live attenuated rotavirus vaccines (RVs) were licensed in China. Passive surveillance for adverse events following immunization (AEFI) provides valuable evidence for potential safety signal detection of RV in China.

We obtained data on RV doses administered and RV AEFI reports from the Chinese National Immunization Information System (CNIIS) during January 2013 to December 2023. We conducted a descriptive analysis of RV AEFI characteristics and estimated incidences of RV AEFI.

During the study period, 77.36 million doses of RV were administered, and 20,556 RV AEFI reports were made, yielding an overall incidence of 26.57 AEFI per 100,000 doses administered; incidences were 26.42 for RV1 and 26.85 for RV5. Among all RV AEFI, 20,334 (98.92%) were non-serious. Vaccine product-related reactions accounted for 95.68% of AEFI reports, including 18,192 (88.50%) common and 1,476 (7.18%) rare vaccine reactions. Among common vaccine reactions, case reports per 100,000 doses administered were 16.85 (13,031 reports) for fever, 5.84 (4,520 reports) for gastrointestinal disorders, and 1.28 (988 reports) for rash. Among rare vaccine reactions, case reports per 100,000 doses were 1.43 (1,104 reports) for allergic rash, 0.07 (56 reports) for thrombocytopenic purpura, 0.03 (26 reports) for febrile convulsion, and 0.01 (5 reports) for intussusception.

Most RV AEFIs were mild and non-serious, and the incidence of rare vaccine reactions was very low. RVs have reasonable safety surveillance profiles and AEFI evaluation should be continued.

Australia was one of the first countries to include rotavirus vaccines in its National Immunisation Program, in 2007. We compared trends in acute gastroenteritis (AGE) and intussusception-coded hospitalisations over 13-year post-vaccine period against five-year pre-vaccine baseline.

In a descriptive before-after study, incidence of hospitalisations with ICD-code of rotavirus AGE (A08.0), other AGE (K52, A01-A09 excluding A08.0) or intussusception (K56.1) between 2002 and 2020 was calculated using population denominators by age and Indigenous status. We used 2002-2006 as pre-vaccine baseline and calculated Incidence Rate Ratios [IRRs] for 2008-2019 and 2020.

In children aged <5 years, mean annual hospitalisation rate/100,000 decreased by 85% for rotavirus-coded AGE, from 248.3 in 2002-2006 to 37.6 (IRR 0.15; 95% CI 0.15-0.16) in 2008-2019 (61.4% for Indigenous children, from 680.2 to 262.2), and 46% for other AGE, from 1274.5 to 689.1 (IRR 0.54; CI 0.54-0.55), decreasing further in 2020 to 6.3 (rotavirus-coded) and 445.0 (other AGE). Rates for rotavirus-coded and other AGE declined in 2008-2019 in those aged 5-<20 years (IRR 0.52; CI 0.49-0.56 and 0.86; CI 0.85-0.87, respectively), but increased in 20-<65 years (IRR 2.38; CI 2.01-2.83 and 1.15; CI 1.15-1.16) and ≥65 years (IRR 2.24; CI 1.91-2.62 and 1.24; CI 1.23-1.25). Average annual hospitalisation rate for intussusception in infants was similar in pre-vaccine and post-vaccine periods (IRR 0.97; CI 0.90-1.04).

Over a 13-year period post-rotavirus vaccine introduction we document major sustained declines in hospitalisations coded as rotavirus and other AGE in age groups <20 years, with no change in intussusception hospitalisation rates in infants. Despite small increases in AGE hospitalisations in adults, likely due to increased PCR testing, our findings are consistent with highly favourable risk benefit ratio at whole-of-population level in Australia.

Rotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy to prevent rotavirus, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to identify the optimal rotavirus vaccination strategy for Malawi by modeling vaccine impact and cost-effectiveness, comparing the current two-dose Rotarix vaccine schedule to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a transmission dynamic model of rotavirus and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose Rotarix strategy is predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) compared to no vaccination and is cost-effective at willingness-to-pay (WTP) thresholds above $105 per DALY averted from the government perspective. Adding a third dose at 14 weeks could avert an additional 1 million cases and 38,000 DALYs, while switching to the neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs compared to the current strategy. Whereas adding a third dose of Rotarix would cost $4.1-4.9 million, switching to the neonatal vaccine is expected to save $3.7 million compared to the current strategy. Considering the neonatal vaccine is not yet available, adding a third dose of Rotarix at 14 weeks of age is cost-effective at WTP thresholds above $138 per DALY averted. The neonatal vaccine offers a more cost-effective alternative to Malawi's current rotavirus vaccine, while adding a third dose to the current strategy also provides substantial benefits.

Rotavirus remains the leading cause of diarrhea among children under five years of age, with an incidence of 31.1-90.9% in Indonesia. Initially, a rotavirus vaccination program was introduced in several provinces of Indonesia in 2022, which would be conducted nationally. This review provides information on the rotavirus genotype distribution in Indonesia, efficacy and effectiveness data of the rotavirus vaccine, and an update on the status of rotavirus vaccine implementation worldwide. The results show a varied distribution of G and P genotypes from 1978 to 2018, with G1-G3, G9, P[4], P[6], and P[8] as the prevalent genotypes, followed by a small proportion of G4, P[9], P[10], and P[11]. Three rotavirus vaccines, which are prequalified by the World Health Organization (WHO) and available in Indonesia, showed an efficacy of 17.6-76.9% in high-mortality countries. The Indonesian government procured ROTAVAC with a G9P[11] genotype for the national immunization program, which showed 31.3-69.1% protective efficacy against severe gastroenteritis caused by other strains. This review suggested that the decision to choose the rotavirus vaccine for the national program should take into account the country's prevalent circulating genotype and the vaccine's efficacy against severe diarrhea. The use of a pentavalent rotavirus vaccine with high efficacy in high-mortality countries can be regarded as the prime choice for the program. Another alternative is the rotavirus vaccine, which showed efficacy data in multiple high-mortality countries. In addition, regular surveillance of the rotavirus genotypes and the clinical manifestations of diarrhea are necessary to design vaccination strategies in Indonesia.

As an emerging genotype, the G9 genotype rotaviruses (RVs) are widespread among humans and pigs, and have been reported in many countries and regions in the recent years. Moreover, porcine G9 strains could cross the interspecies barrier to infect human. To investigate the epidemic trends of porcine G9 strains as well as the cross-immunoreactivity among different isolates, an epidemiological investigation about porcine G9 genotype RVs (PoRVs) was performed during the period 2020-2023 in multiple provinces of China. A total of nine representative strains were identified. The phylogenetic analysis based on viral VP7 gene showed that these strains mainly clustered with lineages III and VI, which revealed the predominant G9 PoRVs in China. Moreover, a new lineage, lineage VII, was identified, and strains of this lineage were found to be circulating in Guangdong and Taiwan. Except lineages I and IV, some isolates from other lineages could co-circulate in pigs and humans. Three G9 strains, namely 923H, 923E, and 923X, which belonged to the largest sub-lineage III, were isolated. Then, the significant cross-reactivity was observed among strains of the same or different lineages. This study is the first to systematically investigate the genetic and immunogenetic characteristics of porcine G9 genotype rotavirus in China, as well as the potential cross-species transmission between pigs and humans, providing a valuable direction for the effective prevention of porcine rotavirus.

Rotavirus is the leading cause of diarrhoea worldwide, particularly affecting young children. While national rotavirus immunization programs have reduced rotavirus morbidity and mortality, vaccine performance varies considerably between high-income and low-income settings.

We updated a previous systematic review of studies reporting rotavirus vaccine efficacy and vaccine effectiveness against severe rotavirus-associated gastroenteritis (RVGE) by performing a rapid review from July 1, 2020 through October 16, 2024. We included randomized controlled trials reporting vaccine efficacy against severe RVGE and case-control and cohort studies reporting vaccine effectiveness against hospitalization with RVGE in children <5 years old for current internationally licensed vaccines. We developed a meta-regression model for vaccine efficacy and effectiveness using widely available country-specific predictors of rotavirus vaccine performance and simultaneously estimated the relationship between vaccine efficacy and effectiveness. We used the model to predict vaccine efficacy and effectiveness for all countries and assessed its predictive accuracy using a modified leave-one-country-out validation approach.

Predicted vaccine efficacy ranged from 69.6% to 94.3% across countries in the Americas, European, and Western Pacific Regions, with a decreased efficacy ranging from 18.6% to 85.3% in the African, South-East Asian, and Eastern Mediterranean regions. Estimates of vaccine effectiveness were generally lower than vaccine efficacy when efficacy was greater than 60%, but effectiveness was predicted to be higher when vaccine efficacy was low. A strong correlation (r = 0.63) was found between the observed and predicted vaccine efficacy and effectiveness, with 98.2% of observed efficacy and effectiveness estimates falling within the 95% prediction intervals.

Our approach enhances the understanding of global variation in rotavirus vaccine performance and can be used to inform predictions of the potential impact of rotavirus vaccines for countries that have yet to introduce them. Higher-quality data on predictor variables and broader regional representation in vaccine trials are required for more robust vaccine performance estimates.

National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01AI112970) and the Bill & Melinda Gates Foundation (INV-17940).

In the post-rotavirus (RVA) vaccination era, uncommon and zoonotic strains have emerged as causative agents of acute gastroenteritis in humans, including the equine-like G3P[8] strains. First identified in 2013, this strain has quickly spread worldwide, reaching the position of the most prevalent genotype in many countries, including Brazil. Here, we report full genotype characterization and phylogenetic analysis of two equine-like G3P[8] strains detected in Goiás, a state in the Cerrado biome of the Brazilian Midwestern region, during the year of 2019. The strains were detected in different socioeconomic and demographic contexts: GO-MR from an asymptomatic adult living in a rural traditional community and GO-H5 from a symptomatic child from the state capital, with access to safe drinking water and essential sanitation services. These strains also displayed different backbone constellations considering the NSP2 gene segment (G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 for GO-MR and G3-P[8]-I2-R2-C2-M2-A2-N1-T2-E2-H2 for GO-H5). Furthermore, significant mutations in the main epitope sites of the VP7 and VP8* proteins of the detected strains, and other Brazilian G3P[8] viruses, were found with the comparison to RV1 and RV5 vaccine proteins, indicating a potential ability of these viruses to evade vaccine protection, which may contribute to their prevalence both nationally and globally. In summary, this study corroborates the genetic diversity of equine-like G3P[8] DS-1-like strains circulating worldwide, highlights the epidemiological importance of adults as reservoirs of RVA and shows the substantial differences between these emerging strains and the currently used anti-RVA vaccines, which may partially explain their predominance due to potential evasion of vaccine-induced protection.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern due to its resistance to conventional antibiotics. This study evaluated the efficacy of liposome-encapsulated vancomycin against MRSA using phospholipids extracted from egg yolk. Liposomes were prepared via the freeze-thaw method, yielding vesicles with an average diameter of 157.01 ± 33.04 nm and a polydispersity index (PDI) of 0.0442, indicating uniformity and stability. Antibacterial activity was assessed using the microdilution method. Liposome-encapsulated vancomycin demonstrated complete bacterial growth inhibition (100%) against MRSA ATCC 2758 at dilutions of 101 and 102, compared to only 50% inhibition by free vancomycin at 101. At higher dilutions (103), liposome-encapsulated vancomycin maintained 70% inhibition, whereas free vancomycin was ineffective. In vivo studies using a murine wound infection model revealed that wounds treated with liposome-encapsulated vancomycin achieved superior healing, with complete tissue regeneration observed by day 14. Histological analysis showed reduced inflammation and enhanced tissue recovery in liposome-encapsulated vancomycin-treated groups, compared to fibrosis and persistent necrosis in free vancomycin-treated groups. By enabling sustained drug release and improved bioavailability, liposomal formulations minimized required dosages and systemic toxicity, reducing the risk of resistance development. This study highlights the clinical potential of liposome-encapsulated vancomycin as a scalable, cost-effective treatment for MRSA, particularly in resource-limited settings.

Histo-blood group antigen (HBGA) phenotypes may contribute to poor oral rotavirus vaccine (RVV) immunogenicity, since rotavirus binds intestinal epithelial HBGA glycans, while maternal HBGA status shapes breastmilk composition, which influences the composition of the infant microbiome. We investigated associations between maternal/infant HBGA phenotypes and RVV immunogenicity in rural Zimbabwe.

We undertook salivary FUT2/FUT3 phenotyping in mother-infant pairs. Serum anti-rotavirus immunoglobulin A was measured by enzyme-linked immunosorbent assay. We explored adjusted associations between FUT2/FUT3 status and RVV seroconversion (primary outcome, n = 322) and seropositivity and geometric mean titer (secondary outcomes, n = 776).

Infants of FUT2- or FUT3-positive women were less likely to seroconvert post-RVV than infants of FUT2- or FUT3-negative women (FUT2 positive [20.1%] vs FUT2 negative [27.5%]: adjusted relative risk [aRR], 0.47; 95% CI, .26-.82; P = .008; FUT3 positive [18.1%] vs FUT3 negative [30.0%]: aRR, 0.45; 95% CI, .25-.78; P = .005). When compared with FUT2-positive infants with FUT2-positive mothers, FUT2-positive infants with FUT2-negative mothers were twice as likely to seroconvert (36.8% vs 21.9%; aRR, 2.12; 95% CI, 1.23-3.63; P = .006). When compared with FUT3-positive infants with FUT3-positive mothers, FUT3-positive infants with FUT3-negative mothers were 3 times as likely to seroconvert (48.3% vs 18.2%; aRR, 2.99; 95% CI, 1.82-4.90; P < .001).

Maternal and infant FUT2 and FUT3 status influences infant RVV immunogenicity.

Groundwater is one of the main sources of drinking water, thus, human enteric viruses in groundwater could pose safety risks. Many enteric viruses enter drinking water sources through irrigation or recharge of contaminated water. It is therefore advised to test the potential transport risk with harmless surrogates before wastewater or recycled water is used for irrigation or groundwater recharge. An ideal virus surrogate should be able to mimic the particle size, the surface properties and the inactivation rate of its target virus and should be easy to detect. Particle size should be the first consideration when selecting a suitable virus surrogate in soil and aquifer. The natural bacteriophages could only mimic the viruses that are inherently similar to themselves, and there is only a limited number of readily available bacteriophages. Therefore, once a certain bacteriophage is chosen for study, its particle size, surface properties and inactivation rate are set and unmodifiable for the experiment. Fluorescent microspheres <200 nm could surrogate target viruses in fast-flow subsurface systems, where inactivation can be neglected. However, the current detection limit of fluorescent nanospheres cannot support the detection of small-sized fluorescent microspheres (∼20 nm) through porous media without macropores. Newly emerging DNA tracers not only allow controlling the size and surface properties, but also offer a low detection limit (ideally 1 copy of DNA). Investigating new types of DNA tracers that could either simulate or mimic the inactivation rate of target viruses could widen the use of virus surrogates to study groundwater contamination and drinking water supply safety.

Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.

Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric pathogen infections and diarrhea are highly seasonal and climate-sensitive, which could explain heterogeneous findings. Understanding how season influences the effectiveness of WASH interventions is critical for informing intervention approaches that will be resistant under the varying weather conditions that climate change will bring.

We conducted a systematic review of the literature and meta-analysis to test whether and to what extent the impact of WASH interventions on diarrhea differs by season. We searched the literature for randomized and nonrandomized controlled WASH intervention trials and identified the season in which data were collected-rainy, dry, or both-for each study using proximate land station weather datasets. We compared the relative risk (RR) estimates for the impact of interventions on diarrhea for each study, stratified by season, and analyzed estimates using meta-analysis and meta-regression. This study is registered with PROSPERO, CRD42021231137.

A total of 50 studies met the inclusion criteria, resulting in 34 drinking water intervention estimates, 8 sanitation intervention estimates, and 14 handwashing intervention estimates. Of the total studies, 60% (n = 30 ) spanned more than one season, with most single-season studies (75%, n = 15 ) occurring exclusively in the dry season. The effect of WASH interventions was stronger in dry seasons than in rainy seasons, with a 33% [95% confidence interval (CI): 24%, 41%] and 18% reduction (95% CI: 5%, 29%) in diarrhea risk, respectively. When stratified by type of intervention, the stronger effect size in dry seasons was consistent for water and handwashing interventions but not for sanitation interventions.

Estimates of the seasonal impact of WASH interventions revealed larger effects in the dry season than in the rainy season overall and for water and handwashing interventions in particular. These patterns likely affected previous estimates of intervention effectiveness, which included more dry season estimates. These findings suggest the need to collect data across seasons and report seasonally stratified results to allow for more accurate estimates of the burden of disease impacted by WASH investments and to improve projections of potential impacts of these interventions under future climate conditions. These findings also underscore the need for robust WASH interventions designed to be resistant to seasonal variations in temperature and rainfall now and under future climate change scenarios. https://doi.org/10.1289/EHP14502.

Rotavirus (RV) is the primary cause of gastroenteritis in children worldwide, contributing significantly to morbidity and mortality, particularly among children under five years of age. The introduction of Rotavirus vaccines (RVV) has markedly reduced RV-related childhood deaths, especially in Europe, where substantial reductions in hospitalizations and disease prevalence have been observed. Despite these advances, RVV uptake in Italy remains below the desired targets, with notable regional disparities. In Sicily, vaccination rates have fluctuated, with current coverage failing to meet national goals. Safety concerns and insufficient parental awareness are major barriers to RVV acceptance.

This case-control study was conducted in Southern Italy to identify factors influencing parental acceptance of RVV. Data were collected from parents using a structured questionnaire that assessed socio-demographic factors, vaccine knowledge, and attitudes based on the Health Belief Model (HBM).

Overall, 226 parents were enrolled. Higher perceived benefit of RVV was significantly associated with increased vaccine adherence (Odds Ratio = 13.65; 95% Confidence Interval = 6.88-27.09; p < 0.001).

These results highlight the need for targeted interventions to improve vaccine coverage and address regional and socio-economic barriers to RVV acceptance. Furthermore, tailored educational campaigns and univocal information from healthcare providers could play pivotal roles in achieving higher vaccine uptake.

Rotavirus is a leading cause of severe diarrheal disease in infants and young children worldwide. Vaccination offers the best protection against this disease, and two rotavirus vaccines were developed in India and included in its routine immunization program. The Government of India's decision to adopt this intervention was supported by a solid base of evidence from clinical trials, as well as substantial research regarding rotavirus disease burden and the potential health and economic value of immunization. Following program implementation, multiple studies were initiated, including three evaluations of effectiveness and several investigations regarding intussusception. These additional data regarding vaccine impact, safety, and delivery from post-introduction evaluations in conditions of real-world use will further strengthen and sustain the immunization program. This manuscript evaluates the status of existing and forthcoming evidence regarding rotavirus vaccination in India through a literature review and consultation with relevant stakeholders. Studies evaluating vaccine impact, effectiveness, safety, health economics, and acceptability, as well as operational and programmatic research, were included in the review. Overall, we found that the evidence base did not contain any major gaps. Nevertheless, additional smaller-scale research studies would be valuable in providing a more complete picture of rotavirus vaccine performance and benefit. Documentation of India's experience with rotavirus vaccines may provide lessons learned for other countries in the Asia region, where rotavirus disease burden remains high, yet vaccine adoption has been slow, as well as for countries worldwide that may be considering implementation of the Indian-made rotavirus vaccines.

Many neonatal intensive care units (NICUs) do not give rotavirus vaccines to inpatients due to a theoretical risk of horizontal transmission of vaccine strains. We aimed to determine incidence and clinical significance of vaccine-strain transmission to unvaccinated infants in a NICU that routinely administers pentavalent rotavirus vaccine (RV5).

This prospective cohort study included all patients admitted to a 100-bed NICU for 1 year. Stool specimens were collected weekly; real-time quantitative reverse-transcription polymerase chain reaction was used to detect any RV5 strain. Incidence of transmission to unvaccinated infants was calculated assuming each unvaccinated patient's stool contributed 1 patient-day at risk for transmission. Investigations and geospatial analyses were conducted for suspected transmission events.

Of 1238 infants admitted, 560 (45%) were premature and 322 (26%) had gastrointestinal pathology. During observation, 226 RV5 doses were administered. Overall, 3448 stool samples were tested, including 2252 from 686 unvaccinated patients. Most (681, 99.3%) unvaccinated patients never tested positive for RV5 strain. Five (<1%) tested RV5 strain positive. The estimated rate of transmission to unvaccinated infants was 5/2252 stools or 2.2/1000 patient-days at risk (95% CI: 0.7-5.2). No gastroenteritis symptoms were identified in transmission cases within 7 days of collection of RV5-positive stool. Of 126 patients for whom the RV5 series was initiated before the discharge date, 55% would have become age-ineligible to start the series if vaccination was allowed only at discharge.

Transmission of RV5 strain was infrequent and without clinical consequences. Benefits of allowing vaccine-induced protection against rotavirus disease in infants through in-NICU RV5 vaccination appear to have outweighed risks from vaccine-strain transmission.

Rotavirus (RV) remains the most common cause of morbidity and mortality due to acute gastroenteritis (AGE) in children under five. In Indonesia, RV is responsible for 60 % of severe AGE and 40 % of non-severe AGE in these children. This study assessed the cost-effectiveness of introduction of rotavirus vaccines (RVV) into the National Immunization Program in Indonesia.

We conducted a cost-effectiveness analysis (CEA) of RVV introduction in Indonesia, assuming a three-dose vaccine schedule based on the planned introduction proposed by the Strategic Advisory Group of Experts on Immunization. The analysis involved an initial introduction of an imported RVV (Rotavac®, Bharat Biotech, India) followed by a staged implementation of the locally produced RVV (Bio Farma, Indonesia) from both health system and societal perspectives. The primary outcome measure was the incremental cost (2019 USD) per disability-adjusted life year (DALY) averted, compared to no vaccination. We took model inputs from an Indonesian cost-of-illness study, national information systems and scientific literature, covering disease incidence, hospitalization, mortality, healthcare costs, and vaccine related factors. Our analyses included univariate and probabilitistic sensitivity analyses to assess various parameters.

The cost of a 10-year vaccination program is 82.6 million USD and can potentially prevent 7.3 million cases of rotavirus and 0.42 million DALYs. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the staged program is 464 USD per DALY averted (12 % of Indonesia's gross domestic product (GDP) per capita). From a healthcare sector perspective, ICER is similar at 479 USD (13 % GDP per capita).

The introduction of RVV into the National Immunization Program is likely to be highly cost-effective in Indonesia.

This work was supported by funding agreement with the Murdoch Children's Research Institute (MCRI), PATH, and the Indonesian Technical Advisory Group on Immunization (ITAGI).

Rotavirus (RV) causes severe gastroenteritis in infants and young children worldwide. Fresh produce has been reported as a source of RV infection during production and harvesting, leading to foodborne illness. Cases of contamination from contact surfaces have also been reported. Therefore, this study applied chemical methods (chlorine dioxide [ClO2], peracetic acid [PAA]), physical methods (gamma irradiation), and a combination of methods (disinfectants + gamma irradiation) to inactivate RV on food contact surfaces (stainless steel) and food (lettuce). Furthermore, the changes in food quality after the combined treatments were assessed. The results of the chemical treatment showed that RV was reduced below the detection limit after treatment for 1 min with 20 ppm ClO2 or 120 ppm PAA in RV suspension. On stainless steel, treatment with 200 ppm ClO2 or 2,000 ppm PAA reduced contaminated RV by more than 4 log. A 5 min treatment with 50 ppm ClO2 or 80 ppm PAA on lettuce reduced the RV by 1.79 and 0.75 log, respectively. Treatment with 4 kGy of gamma irradiation resulted in more than 5 log reduction in suspensions and 3.27 log reduction on food. The sequential treatments, including 30 ppm ClO2 followed by 1.5 kGy gamma irradiation and 80 ppm PAA followed by 1.5 kGy gamma irradiation, showed additional inactivation effects (p < 0.05) compared to each single treatment. No changes in food quality (color difference and texture) were observed after any treatments, suggesting that the combined treatment of both ClO2 and gamma irradiation and PAA and gamma irradiation can be applied in the fresh food industry to reduce RV contamination.

This study investigated the survival of human rotavirus (HRV) on fresh beef, chicken, and lettuce stored at various temperatures, as well as the effect of UV-C exposure on HRV viability on these food surfaces. At 20 °C, the survival rate of three HRV strains (WA, 89-12C2, and DS-1) on beef, chicken, and lettuce decreased within 3 days, with the most significant reduction observed on beef. When stored at 4 °C, a significant reduction in HRV viability was observed by day 7, with the greatest decrease observed on beef, followed by chicken and lettuce. Conversely, storage at -20 °C for up to 28 days did not significantly reduce HRV viability on any of the food surfaces. Exposure to UV-C irradiation at a dosage of 100 mJ/cm2 reduced the viral titers on beef and chicken surfaces by approximately 1 log10 PFU/mL, while those on the surfaces of lettuce were more than 4 log10 PFU/mL. These findings indicate that HRV strains exhibit strong viability on beef, chicken, and lettuce surfaces, enduring extended periods at low temperatures, but display varying susceptibility to UV-C irradiation. Due to the persistence of HRV on contaminated food, implementing effective measures to prevent food contamination is crucial. The findings of this study contribute to the development of a robust sanitation strategy utilizing UV-C to mitigate foodborne HRV transmission.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.