Health economic evaluation of 2-dose and 3-dose rotavirus vaccines in children below 5 years of age in Morocco.

Following the introduction of rotavirus vaccination into the Moroccan National Immunization Program, the prevalence of the disease has decreased by nearly 50%. However, evidence on the economic value of rotavirus vaccinations in Morocco is limited. This health economic analysis evaluated, from both country payer and societal perspectives, the costs and the cost-effectiveness of three rotavirus vaccines using a static, deterministic, population model in children aged < 5 years in Morocco. Included vaccines were HRV (2-dose schedule), HBRV (3-dose schedule) and BRV-PV 1-dose vial (3-dose schedule). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty in model inputs. The model predicted that vaccination with HRV was estimated to result in fewer rotavirus gastroenteritis events (-194 homecare events, -57 medical visits, -8 hospitalizations) versus the 3-dose vaccines, translating into 7 discounted quality-adjusted life years gained over the model time horizon. HRV was associated with lower costs versus HBRV from both the country payer (-$1.8 M) and societal (-$4.1 M) perspectives, and versus BRV-PV 1-dose vial from the societal perspective (-$187,000), dominating those options in the cost-effectiveness analysis. However, costs of BRV-PV 1-dose vial were lower than HRV from the payer perspective, resulting in an ICER of approximately $328,376 per QALY, above the assumed cost effectiveness threshold of $3,500. Vaccination with a 2-dose schedule of HRV may be a cost-saving option and could lead to better health outcomes for children in Morocco versus 3-dose schedule rotavirus vaccines.

Trends in the detection of viruses causing gastroenteritis over a 10-year period and impact of nonpharmaceutical interventions.

BACKGROUND: Viral gastroenteritis continues to be a leading cause of death in low-income countries. The impact of nonpharmaceutical interventions (NPIs) on the transmission of gastroenteritis-causing viruses during the COVID-19 pandemic is understudied. OBJECTIVES: To investigate the 10-year trends of enteric viruses and estimate the impact of implementing and mitigating NPIs. STUDY DESIGN: Data regarding norovirus, rotavirus, adenovirus, astrovirus, and sapovirus detection were collected from five Korean hospitals between January 2013 and April 2023. We compared positivity between the pre-pandemic, pandemic, and post-pandemic periods. The causal effects of implementing and mitigating NPIs were quantified using the Bayesian Structural Time Series (BSTS) model. RESULTS: Norovirus was most frequently detected (9.9 %), followed by rotavirus (6.7 %), adenovirus (3.3 %), astrovirus (1.4 %), and sapovirus (0.6 %). During the pandemic, the positivity of all five viruses decreased, ranging from -1.0 % to -8.1 %, with rotavirus showing the greatest decrease. In the post-pandemic period, positivity rebounded for all viruses except for rotavirus. The BSTS model revealed that NPI implementation negatively affected the detection of all five viruses, resulting in reductions ranging from -73.0 % to -91.0 % compared to the prediction, with rotavirus being the least affected. Conversely, NPI mitigation positively affected the detection of all viruses, ranging from 79.0 % to 200.0 %, except for rotavirus. CONCLUSIONS: Trends observed over 10 years show that NPIs have had a major impact on changes in enteric virus detection. The effect of vaccines, in addition to NPIs, on rotavirus detection requires further investigation. Our findings emphasize the importance of NPIs in infection control and prevention.

Epidemiological Features of Human Norovirus Genotypes before and after COVID-19 Countermeasures in Osaka, Japan.

We investigated the molecular epidemiology of human norovirus (HuNoV) in all age groups using samples from April 2019 to March 2023, before and after the COVID-19 countermeasures were implemented. GII.2[P16] and GII.4[P31], the prevalent strains in Japan before COVID-19 countermeasures, remained prevalent during the COVID-19 pandemic, except from April to November 2020; in 2021, the prevalence of GII.2[P16] increased among children. Furthermore, there was an increase in the prevalence of GII.4[P16] after December 2022. Phylogenetic analysis of GII.P31 RdRp showed that some strains detected in 2022 belonged to a different cluster of other strains obtained during the present study period, suggesting that HuNoV strains will evolve differently even if they have the same type of RdRp. An analysis of the amino acid sequence of VP1 showed that some antigenic sites of GII.4[P16] were different from those of GII.4[P31]. The present study showed high infectivity of HuNoV despite the COVID-19 countermeasures and revealed changes in the prevalent genotypes and mutations of each genotype. In the future, we will investigate whether GII.4[P16] becomes more prevalent, providing new insights by comparing the new data with those analyzed in the present study.

Production of OSU G5P[7] Porcine Rotavirus Expressing a Fluorescent Reporter via Reverse Genetics.

Rotaviruses are a significant cause of severe, potentially life-threatening gastroenteritis in infants and the young of many economically important animals. Although vaccines against porcine rotavirus exist, both live oral and inactivated, their effectiveness in preventing gastroenteritis is less than ideal. Thus, there is a need for the development of new generations of porcine rotavirus vaccines. The Ohio State University (OSU) rotavirus strain represents a Rotavirus A species with a G5P[7] genotype, the genotype most frequently associated with rotavirus disease in piglets. Using complete genome sequences that were determined via Nanopore sequencing, we developed a robust reverse genetics system enabling the recovery of recombinant (r)OSU rotavirus. Although rOSU grew to high titers (~107 plaque-forming units/mL), its growth kinetics were modestly decreased in comparison to the laboratory-adapted OSU virus. The reverse genetics system was used to generate the rOSU rotavirus, which served as an expression vector for a foreign protein. Specifically, by engineering a fused NSP3-2A-UnaG open reading frame into the segment 7 RNA, we produced a genetically stable rOSU virus that expressed the fluorescent UnaG protein as a functional separate product. Together, these findings raise the possibility of producing improved live oral porcine rotavirus vaccines through reverse-genetics-based modification or combination porcine rotavirus vaccines that can express neutralizing antigens for other porcine enteric diseases.

Systematic literature review and meta-analysis on preventing and controlling norovirus outbreaks on cruise ships, 1990 to 2020: calling for behaviour change strategies of travellers.

BackgroundOutbreaks of norovirus gastroenteritis aboard cruise ships may affect a large number of people, debilitate vulnerable travellers, disrupt vacations and cause economic losses to the cruise ship industry.AimWe aimed to identify risk factors for norovirus outbreaks on cruise ships and assess the effectiveness of prevention and control measures.MethodsWe conducted a systematic literature review searching PubMed and Scopus databases as well as grey literature for articles and reports describing norovirus outbreaks on cruise ships between 1990 and 2020. We also performed a meta-analysis of norovirus prevalence in passengers and crew members.ResultsData from 45 outbreaks on 26 cruise ships from 1990 to 2020 were identified in 13 articles and five reports, with a weighted average of prevalence (attack rate) for passengers of 7% (95% confidence interval (CI): 5.00-9.00) and for crew of 2% (95% CI: 0.00-3.00). Person-to-person was the most frequent mode of transmission in 35 of the 45 outbreaks (in 14 the only mode and in 21 as part of multiple transmission routes). Having an ill cabin mate (OR = 38.70; 95% CI: 13.51-110.86) was the most common risk factor. Six outbreak investigations reported poor hygiene, while four reported satisfactory hygiene in the cruise setting. Behavioural risk factors among travellers were investigated in three of the 13 studies.ConclusionsThe findings indicate a need for behavioural interventions to improve personal hygiene, symptom reporting and compliance with isolation measures, and for reconsidering current isolation policies where symptomatic and healthy individuals are isolated in the same cabin.

Changes in vaccine coverage and incidence of acute gastroenteritis and severe rotavirus gastroenteritis in children <5 years in Shibata City, Niigata Prefecture, Japan.

Rotavirus (RV) vaccines were first introduced in 2011 and adopted for universal vaccination in 2020 in Japan. However, the effectiveness of RV vaccines after being adopted for universal vaccination in 2020 has not been reported. Because of the easy accessibility of clinics in Japan, many children are not usually hospitalized for RV gastroenteritis (RVGE). Therefore, in order to evaluate the impact of the RV vaccine since 2008, we investigated the incidence of hospitalization for RVGE as well as the frequency of children aged < 5 years who received medical treatment for severe RVGE at clinics in Shibata City, Japan. The RV vaccine coverage rate was 94.0% (1,046/1,113) in Shibata City after universal vaccination in 2020; this was a significant increase from previous rates. The incidence per 1000 person - years for RVGE hospitalization and severe RVGE at clinics were significantly higher among children aged < 3 years than in previous time periods. The incidence in children with all acute gastroenteritis (AGE) decreased significantly after universal vaccination during the COVID-19 pandemic. The proportion of severe RVGE among all AGE cases also decreased significantly after universal vaccination among children aged < 3 years (0.0%) and those aged 3-4 years (0.6%). There were significant differences in the distribution of RV genotypes isolated from the feces of children with RVGE between different eras divided by RV vaccination rates, especially G1P[8], which was the major genotype before it recently almost disappeared. Further studies are warranted to assess the impact of the COVID-19 pandemic.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Novel Universal Recombinant Rotavirus A Vaccine Candidate: Evaluation of Immunological Properties.

Rotavirus infection is a leading cause of severe dehydrating gastroenteritis in children under 5 years of age. Although rotavirus-associated mortality has decreased considerably because of the introduction of the worldwide rotavirus vaccination, the global burden of rotavirus-associated gastroenteritis remains high. Current vaccines have a number of disadvantages; therefore, there is a need for innovative approaches in rotavirus vaccine development. In the current study, a universal recombinant rotavirus antigen (URRA) for a novel recombinant vaccine candidate against rotavirus A was obtained and characterised. This antigen included sequences of the VP8* subunit of rotavirus spike protein VP4. For the URRA, for the first time, two approaches were implemented simultaneously-the application of a highly conserved neutralising epitope and the use of the consensus of the extended protein's fragment. The recognition of URRA by antisera to patient-derived field rotavirus isolates was proven. Plant virus-based spherical particles (SPs), a novel, effective and safe adjuvant, considerably enhanced the immunogenicity of the URRA in a mouse model. Given these facts, a URRA + SPs vaccine candidate is regarded as a prospective basis for a universal vaccine against rotavirus.

Rotavirus and adenovirus infections in children with acute gastroenteritis after introducing the Rotasiil® vaccine in Kisangani, Democratic Republic of the Congo.

BACKGROUND: Although rotavirus vaccination has reduced the global burden of the virus, morbidity and mortality from rotavirus infection remain high in Sub-Saharan Africa. This study aimed to determine the prevalence of rotavirus and adenovirus infections in children under five years with acute gastroenteritis and to identify factors associated with rotavirus infection after the introduction of the Rotasiil® vaccine in 2019 in Kisangani, Democratic Republic of the Congo (DRC). METHODS: This study consisted of a cross-sectional hospital-based survey conducted from May 2022 to April 2023 in four health facilities in Kisangani, using a fecal-based test (rapid antigenic immuno-chromatographic diagnostic test, BYOSYNEX adenovirus/rotavirus BSS, Biosynex SA, Illkirch-Graffenstaden, France) of rotavirus and adenovirus infections among children under five years of age with acute gastroenteritis. RESULTS: A total of 320 children under five years of age with acute gastroenteritis were included. The prevalence of rotavirus infection was 34.4%, that of adenovirus was 6.3%, and that of both rotavirus and adenovirus coinfection was 1.3%. The prevalence of rotavirus was significantly higher in unvaccinated children than in vaccinated children (55.4% versus 23.1%; P < 0.001). This difference was observed only in children who received all three vaccine doses. Multivariate logistic regression analysis shows that the rate of rotavirus infection was significantly reduced in vaccinated children (adjusted OR: 0.31 [95% confidence intervals (CI): 0.19-0.56]; P < 0.001) and those whose mothers had an average (adjusted OR: 0.51 [95% CI: 0.25-0.91]; P = 0.018) or high level (adjusted OR: 0.34 [95% CI: 0.20-0.64]; P < 0.001) of knowledge about the rotavirus vaccine. CONCLUSIONS: The prevalence of rotavirus infection remains high in Kisangani despite vaccination. However, the prevalence of adenovirus infections was low in our series. Complete vaccination with three doses and mothers' average and high level of knowledge about the rotavirus vaccine significantly reduces the rate of rotavirus infection. It is, therefore, essential to strengthen the mothers' health education, continue with the Rotasiil® vaccine, and ensure epidemiological surveillance of rotavirus infection.

Prediction of effectiveness of universal rotavirus vaccination in Southwestern Vietnam based on a dynamic mathematical model.

Vaccinating young children against rotavirus (RV) is a promising preventive strategy against rotavirus gastroenteritis (RVGE). We evaluated the relative risk reduction of RVGE induced by universal vaccination in Vietnam through dynamic model analysis. We developed an age-stratified dynamic Vaccinated-Susceptible-Infectious-Recovered-Susceptible model to analyze RV transmission and assess vaccine effectiveness (VE). We assumed 3 different vaccine efficacies: 55%, 70%, and 85%. For model calibration, we used a database of patients under 5 years of age admitted to Ho Chi Minh No.1 Hospital with RVGE between January 2013 and December 2018. Assuming a vaccination rate of 95%, the number of RVGE hospitalizations after 5 years from universal RV vaccination decreased from 92,502 cases to 45,626 with 85% efficacy, to 54,576 cases with 70% efficacy, and to 63,209 cases with 55% efficacy. Additionally, RVGE hospitalizations after 10 years decreased from 177,950 to 89,517 with 85% efficacy and to 121,832 cases with 55% efficacy. The relative risk reductions of RVGE after 10 years were 49.7% with 85% efficacy, 40.6% with 70% efficacy, and 31.5% with 55% efficacy. The VE was 1.10 times (95% CI, 1.01-1.22) higher in the 4-months to 1-year-old age group than in the other age groups (P = 0.038), when applying 85% efficacy with 95% coverage. In conclusion, despite its relatively lower efficacy compared to high-income countries, RV vaccination remains an effective intervention in Southwestern Vietnam. In particular, implementing universal RV vaccination with higher coverage would result in a decrease in RVGE hospitalizations among Vietnamese children under 5 years of age.

Prevalence and Characterization of Gastroenteritis Viruses among Hospitalized Children during a Pilot Rotavirus Vaccine Introduction in Vietnam.

Rotavirus (RV), norovirus (NoV), sapovirus (SaV), and human astrovirus (HAstV) are the most common viral causes of gastroenteritis in children worldwide. From 2016 to 2021, we conducted a cross-sectional descriptive study to determine the prevalence of these viruses in hospitalized children under five years old in Nam Dinh and Thua Thien Hue provinces in Vietnam during the pilot introduction of the RV vaccine, Rotavin-M1 (POLYVAC, Hanoi, Vietnam). We randomly selected 2317/6718 (34%) acute diarrheal samples from children <5 years of age enrolled at seven sentinel hospitals from December 2016 to May 2021; this period included one year surveillance pre-vaccination from December 2016 to November 2017. An ELISA kit (Premier Rotaclone®, Meridian Bioscience, Inc., Cincinnati, OH, USA) was used to detect RV, and two multiplex real-time RT-PCR assays were used for the detection of NoV, SaV and HAstV. The prevalence of RV (single infection) was reduced from 41.6% to 22.7% (p < 0.0001) between pre- and post-vaccination periods, while the single NoV infection prevalence more than doubled from 8.8% to 21.8% (p < 0.0001). The SaV and HAstV prevalences slightly increased from 1.9% to 3.4% (p = 0.03) and 2.1% to 3.3% (p = 0.09), respectively, during the same period. Viral co-infections decreased from 7.2% to 6.0% (p = 0.24), mainly due to a reduction in RV infection. Among the genotypeable samples, NoV GII.4, SaV GI.1, and HAstV-1 were the dominant types, representing 57.3%, 32.1%, and 55.0% among the individual viral groups, respectively. As the prevalence of RV decreases following the national RV vaccine introduction in Vietnam, other viral pathogens account for a larger proportion of the remaining diarrhea burden and require continuing close monitoring.

Cost-of-illness of gastroenteritis caused by rotavirus in Chinese children less than 5 years.

Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.

Rotavirus vaccination as a public health strategy to reduce the burden of hospitalization: The field experience of Italy (2008-2018).

Rotavirus (RV) infection is a leading cause of severe diarrhea among children younger than 5 years old and a considerable cause of RV gastroenteritis (RVGE) hospitalization. This study aimed to evaluate the impact of vaccination in Italy in the reduction of the burden of RV-related disease, estimating the relation between vaccination coverage and hospitalization rates. RVGE-related hospitalizations that occurred in Italy from 2008 to 2018 among children aged 0-35 months were assessed by consulting the Hospital Discharge Record database and including records whose ICD-9-CM diagnosis code was 008.61 in the first or in any diagnosis position. In the 2008-2018 period, a total of 17 535 791 at-risk person-years were considered and 74 211 (423.2 cases × 100 000 per year) RVGE hospitalizations were observed. Higher hospitalization rates occurred in males (456.6 vs. 387.9 × 100 000 per year) and in children aged 1 year (507.8 × 100 000 per year). Poisson regression analysis showed a decrease of -1.25% in hospitalization rates (-1.19% to -1.31%, p < 0.001) per unit increase in vaccination coverage. This is the first study that correlates hospitalization rate reduction with a percentage increase in vaccination coverage. Our findings strongly support RV vaccination as an effective public health strategy for reducing RVGE-related hospitalizations.

Investigating association between inflammatory bowel disease and rotavirus vaccination in a paediatric cohort in the UK.

In the UK, the incidence and prevalence of inflammatory bowel disease (IBD) is increasing in paediatric populations. Environmental factors including acute gastroenteritis episodes (AGE) may impact IBD development. Infant rotavirus vaccination has been shown to significantly reduce AGE. This study aims to explore the association between vaccination with live oral rotavirus vaccines and IBD development. A population-based cohort study was used, analysing primary care data from the Clinical Practice Research Datalink Aurum. Participants included children born in the UK from 2010 to 2015, followed from a minimum of 6 months old to a maximum of 7 years old. The primary outcome was IBD, and the primary exposure was rotavirus vaccination. Cox regression analysis with random intercepts for general practices was undertaken, with adjustment for potential confounding factors. In a cohort of 907,477 children, IBD was recorded for 96 participants with an incidence rate of 2.1 per 100,000 person-years at risk. The univariable analysis hazard ratio (HR) for rotavirus vaccination was 1.45 (95% confidence interval (CI) 0.93-2.28). Adjustment in the multivariable model attenuated the HR to 1.19 (95% CI 0.53-2.69). This study shows no statistically significant association between rotavirus vaccination and development of IBD. However, it provides further evidence for the safety of live rotavirus vaccination.

Comparison of IgA Antibody Titer Induced by Human-Bovine Rotavirus Candidate Vaccine with Bovine Rotavirus and Rotarix.

Rotavirus (RV) is the most common cause of acute gastroenteritis in early childhood worldwide. Gastroenteritis is a preventable disease by the vaccine, and vigorous efforts were made to produce attenuated oral rotavirus vaccines. In recent years, despite the existence of three types of live attenuated rotavirus vaccines, several countries, such as China and Vietnam, have intended to produce indigenous vaccines based on rotavirus serotypes circulating among their population. In this study, the immunogenicity of homemade human-bovine reassortant RV candidate vaccine was tested in an animal model. Rabbits were randomly distributed into eight experimental groups with three animals per group. Afterward, three rabbits in each test group designated as P1, P2, and P3 were experimentally inoculated with the 106, 107, and 108 tissue culture infectious dose 50 (TCID50) of the reassortant virus, respectively. The N1 group received the reassortant rotavirus vaccine containing 107 TCID50+zinc. The N2, N3, and N4 groups received rotavirus vaccine strain, RV4 human rotavirus, and bovine rotavirus strain, respectively, and the control group received phosphate-buffered saline. It is noteworthy that three rabbits have been included in each group. The IgA total antibody titer was measured and evaluated by non-parametric Mann-Whitney and Kruskal-Wallis tests. The antibody titer produced in the studied groups did not significantly differ. The candidate vaccine showed immunogenicity, protectivity, stability, and safety. The findings of this study indicated a critical role of IgA production, which can induce immunity against a gastroenteritis viral pathogen. Regardless of purification, candidate reassortant vaccine and cell adapted animal strains could be used as a vaccine candidate for production.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study.

OBJECTIVE: To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. STUDY DESIGN: We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. RESULTS: A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to ≤4 years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to ≤2 years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. CONCLUSIONS: A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Advances in the development of antivirals for rotavirus infection.

Rotavirus (RV) causes 200,000 deaths per year and imposes a serious burden to public health and livestock farming worldwide. Currently, rehydration (oral and intravenous) remains the main strategy for the treatment of rotavirus gastroenteritis (RVGE), and no specific drugs are available. This review discusses the viral replication cycle in detail and outlines possible therapeutic approaches including immunotherapy, probiotic-assisted therapy, anti-enteric secretory drugs, Chinese medicine, and natural compounds. We present the latest advances in the field of rotavirus antivirals and highlights the potential use of Chinese medicine and natural compounds as therapeutic agents. This review provides an important reference for rotavirus prevention and treatment.

The economic impact of the introduction of universal rotavirus vaccination on rotavirus gastroenteritis related hospitalisations in children in Ireland.

BACKGROUND: Rotavirus gastroenteritis (RVGE), a vaccine preventable disease, remains a common cause of severe gastroenteritis in children globally. Ireland introduced the universal rotavirus vaccination to the national immunisation programme in 2016. In this paper the economic impact on RVGE related hospitalisations amongst children under 5 years is examined. METHODS: Using national data from all Irish public hospitals, an Interrupted Times Series Analysis (ITSA) compares RVGE hospitalisations amongst children under 5 years, pre- and post-vaccine introduction. Costs are estimated and ITSA results are compared to the counterfactual to estimate the economic impact of the vaccine. A probit model examines patient characteristics pre- and post-vaccine introduction. RESULTS: Vaccine introduction coincided with lowered RVGE related hospitalisations. While this effect was delayed (1 year) there is evidence of a sustained impact. RVGE patients' post-vaccine introduction were likely to be over 2 years (p = 0.001) and length of stay was lower on average (p = 0.095). The counterfactual analysis revealed 492 RVGE hospitalisations were avoided on average annually since the introduction of the vaccine. This has an estimated economic value of €0.92 million per annum. CONCLUSIONS: Following the introduction of the rotavirus vaccine in Ireland, hospitalisations for RVGE decreased significantly and those hospitalised were older and with a reduced length of stay on average. This has the potential for significant cost savings for the Irish healthcare system.

Transporting monovalent rotavirus vaccine efficacy estimates to an external target population: a secondary analysis of data from a randomised controlled trial in Malawi.

Oral rotavirus vaccine efficacy estimates from randomised controlled trials are highly variable across settings. Although the randomised study design increases the likelihood of internal validity of findings, results from trials may not always apply outside the context of the study due to differences between trial participants and the target population. Here, we used a weight-based method to transport results from a monovalent rotavirus vaccine clinical trial conducted in Malawi between 2005 and 2008 to a target population of all trial-eligible children in Malawi, represented by data from the 2015-2016 Malawi Demographic and Health Survey (DHS). We reweighted trial participants to reflect the population characteristics described by the Malawi DHS. Vaccine efficacy was estimated for 1008 trial participants after applying these weights such that they represented trial-eligible children in Malawi. We also conducted subgroup analyses to examine the heterogeneous treatment effects by stunting and tuberculosis vaccination status at enrolment. In the original trial, the estimates of one-year vaccine efficacy against severe rotavirus gastroenteritis and any-severity rotavirus gastroenteritis in Malawi were 49.2% (95% CI 15.6%-70.3%) and 32.1% (95% CI 2.5%-53.1%), respectively. After weighting trial participants to represent all trial-eligible children in Malawi, vaccine efficacy increased to 62.2% (95% CI 35.5%-79.0%) against severe rotavirus gastroenteritis and 38.9% (95% CI 11.4%-58.5%) against any-severity rotavirus gastroenteritis. Rotavirus vaccine efficacy may differ between trial participants and target populations when these two populations differ. Differences in tuberculosis vaccination status between the trial sample and DHS population contributed to varying trial and target population vaccine efficacy estimates.