Rotavirus Vaccine Effectiveness Research Articles

VP8 Mosaic Nanoparticles Elicit Cross-Neutralizing Immune Responses and Provide Protection Against Heterotypic Rotavirus Challenge in Mice.

Group A rotaviruses (RVA) remain one of the dominant pathogens causing diarrhea in children under 5 years of age worldwide, despite a sharp decrease of RVA-associated diarrhea and mortality since the introduction of rotavirus vaccines. The decreased effectiveness of live attenuated rotavirus vaccines, coupled with the emergence of new rotavirus genotypes and the risk of cross-species virus transmission, underscores the necessity to develop more effective and broad-spectrum rotavirus vaccines. In this study, we utilized nanoparticles coupled with the SpyCatcher-SpyTag system to effectively display the truncated VP8-1 protein. The modular display of the monovalent VP8-1 proteins markedly increased the immunogenicity of VP8-1. Furthermore, the bivalent display of VP8-1 proteins from simian rotavirus SA11 and lamb rotavirus LLR on the same particle not only increased immunogenicity against homotypic antigens but also elicited robust heterotypic immune responses and conferred effective protection against a distant heterotypic rotavirus with sequence identities of only 62%-66% in an adult mouse model. Therefore, mosaic VP8 nanoparticles could be considered as a viable strategy for the development of the next-generation broad-spectrum rotavirus vaccine.

Virus-like Particles vaccine based on co-expression of G5 Porcine rotavirus VP2-VP6-VP7 induces a powerful immune protective response in mice

Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40μg of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.

Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study.

The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited. We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2months to 5years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) -58.1-85.3%]) for one dose, 37.6% (95% CI -58.5-75.4%) for two doses, and 64.1% (95% CI 38.0-79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7-60.2%) for one dose, 74.6% (95% CI 35.3-90.0%) for two doses, and 58.8% (95% CI -217.6-94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI -144.7-95.6%) for one dose, 74.0% (95% CI -92.1-96.5%) for two doses, and 86.6% (95% CI 56.8-95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3-77.6%) for one dose, 73.4% (95% CI 11.9-92.0%) for two doses, and -27.8% (95% CI -949.7-84.4%) for three doses. Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection.

Rotavirus Vaccine Effectiveness Against Severe Acute Gastroenteritis: 2009-2022.

Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children.

Effectiveness and impact of monovalent rotavirus vaccination in Afghanistan: a test-negative case–control analysis

Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan. We used a test-negative case-control design embedded in an active sentinel surveillance platform to evaluate vaccine effectiveness. Children born on or after Jan 1, 2018, who had documentation of their rotavirus vaccination status and who were admitted for acute gastroenteritis at one of four sentinel hospitals from May, 2018 to December, 2021 were eligible to be included. We used an unconditional logistic regression model to estimate vaccine effectiveness and 95% CIs for a complete series of doses compared with no rotavirus vaccine doses among patients admitted with acute gastroenteritis. Vaccine effectiveness against hospitalisation was calculated as (1 - [odds of being vaccinated in cases] / [odds of being vaccinated in controls]) × 100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact. The vaccine effectiveness analysis included 1172 cases and 2173 controls. Approximately 2108 (63·0%) of 3345 cases and controls were male, 1237 (37·0%) were female, and 2171 (65·0%) were aged 6-11 months. Two doses of Rotarix were 45% (95% CI 22-62) effective against rotavirus hospitalisation in children aged 6-59 months, adjusting for age, severity, admission year, and rotavirus season. Rotavirus positivity decreased from 51% pre-vaccine to 39% post-vaccine, resulting in a 39% adjusted reduction in rotavirus positivity among children younger than 5 years admitted with acute gastroenteritis. Rotarix showed moderate effectiveness in preventing rotavirus gastroenteritis hospitalisations, consistent with findings in other low-income countries. These findings support the continued administration of the rotavirus vaccine in Afghanistan. Gavi, the Vaccine Alliance. For the Dari translation of the abstract see Supplementary Materials section.

Generation of Recombinant Authentic Live Attenuated Human Rotavirus Vaccine Strain RIX4414 (Rotarix®) from Cloned cDNAs Using Reverse Genetics.

The live attenuated human rotavirus vaccine strain RIX4414 (Rotarix®) is used worldwide to prevent severe rotavirus-induced diarrhea in infants. This strain was attenuated through the cell culture passaging of its predecessor, human strain 89-12, which resulted in multiple genomic mutations. However, the specific molecular reasons underlying its attenuation have remained elusive, primarily due to the absence of a suitable reverse genetics system enabling precise genetic manipulations. Therefore, we first completed the sequencing of its genome and then developed a reverse genetics system for the authentic RIX4414 virus. Our experimental results demonstrate that the rescued recombinant RIX4414 virus exhibits biological characteristics similar to those of the parental RIX4414 virus, both in vitro and in vivo. This novel reverse genetics system provides a powerful tool for investigating the molecular basis of RIX4414 attenuation and may facilitate the rational design of safer and more effective human rotavirus vaccines.

Effectiveness of self-financed rotavirus vaccines on acute gastroenteritis primary care episodes using real-world data in Spain: a propensity score-matched analysis of cohort study.

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. • 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. • 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.

Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6.

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.

Impact of rotavirus vaccination in Malawi from 2012 to 2022 compared to model predictions before, during, and after the COVID-19 pandemic.

Rotarix® rotavirus vaccine was introduced into the Malawi national immunization program in October 2012. We used a previously developed mathematical models to estimate overall vaccine effectiveness over a 10-year period following rotavirus vaccine introduction. We analyzed data on children <5 years old hospitalized with acute gastroenteritis in Blantyre, Malawi from January 2012 to June 2022, compared to pre-vaccination data. We estimated vaccine coverage before, during, and after the COVID-19 pandemic using data from rotavirus-negative children. We compared model predictions for the weekly number of rotavirus-associated gastroenteritis (RVGE) cases to the observed number by age to validate model predictions and estimate overall vaccine effectiveness. The number of RVGE and rotavirus-negative acute gastroenteritis cases declined substantially following vaccine introduction. Vaccine coverage among rotavirus-negative controls was >90% with two doses by July 2014, and declined to a low of ~80% in October 2020, before returning to pre-pandemic levels by July 2021. Our models captured the post-vaccination trends in RVGE incidence, with 5.4% to 19.4% of observed weekly RVGE cases falling outside of the 95% prediction intervals. Comparing observed RVGE cases to the model-predicted incidence without vaccination, overall vaccine effectiveness was estimated to be 36.0% (95% prediction interval: 33.6%, 39.9%) peaking in 2014 and was highest in infants (52.5%; 95% prediction interval: 50.1%, 54.9%). Overall effectiveness of rotavirus vaccination in Malawi is modest despite high vaccine coverage and has plateaued since 2016. Our mathematical models provide a validated platform for assessing strategies to improve rotavirus vaccine impact.

Characteristics of acute diarrhea under the sentinel surveillance system at the Vietnam National Children’s Hospital from 2018 to 2022

The study describes a sentinel diarrhea surveillance system at the Vietnam National Children’s Hospital from 2018 - 2022, characterizing the epidemiology of acute diarrhea (AD) due to rotavirus (RV) and identifying circulating RV strains. Of 4,765 AD cases, 861 were positive for RV, accounting for 18.07%. The disease appeared in all months, peaking in the winter-spring months (from October to March of the following year). The groups of children aged 6 - 11 months, 12 - 23 months, and 6 weeks-6 months had the highest number of cases, but the highest positive rate is 24 - 47 months old. About 24% of RV patients under 2 years of age have already been vaccinated, while this proportion among 3 - 5 years of age patients is 41%. Dehydration and no dehydration account for 96,7%, while severe dehydration only accounts for 3.3%, the prevalent RV types identified were G3P[8], G8P[8], G1P[8], G9P[8], which account for 50.7%, 20.6%, 11.4%, and 9%, respectively and changed annually. It is necessary to implement RV vaccines in the Expanded Program on Immunization. Meanwhile maintaining an RV sentinel surveillance system and continuing research on the effectiveness of RV vaccines in Viet Nam are also critical for controlling RV in Vietnam.

Effectiveness and Safety of Bovine Human Pentavalent Rotavirus Vaccine (BRV-PV) in Preventing Severe Acute Rotavirus Gastroenteritis (SRVGE): A systematic review of the experience in developing countries

Background: Severe acute rotavirus gastroenteritis (SRVGE) is the world's highest cause of children mortality, with symptoms of severe dehydrating diarrhea due to rotavirus (RV) infection. SRVGE provides a high economic burden, mostly in developing countries. Currently, three RV vaccines (Rotarix, RotaTeq, Rotavac) are licensed internationally by the World Health Organization (WHO) and are not yet applicable in developing countries. Hence, research shows the potential of BRV-PV in preventing RV infection in pediatrics, especially in developing countries. Objective: This review aims to analyze the effectiveness and safety of BRV-PV in developing countries. Methods: This systematic review includes studies from the ScienceDirect, PubMed, Elsevier, and Cochrane databases that met the inclusion and exclusion criteria. The search method uses the Boolean operator with the articles from the last ten years. Eight articles with a total of 9088 children were reviewed to analyze the effectiveness and safety of BRV-PV. Results and Discussion: Of all the studies involved, BRV-PV has effectively reduced the incidence of hospitalization and emergency cases due to SRVGE. Furthermore, BRV-PV is also safe for children in developing countries, proven by increased anti-RV IgA concentrations and minimal side effects. Conclusion: BRV-PV is more effective, safe, heat-stable, and affordable than the previous three RV vaccines in developing countries Keyword: BRV-PV, Gastroenteritis, Rotavirus, Rotavirus Vaccine Latar Belakang: Severe acute rotavirus gastroenteritis (SRVGE) merupakan penyebab kematian anak tertinggi di dunia dengan gejala diare dehidrasi parah akibat infeksi rotavirus (RV). SRVGE memberikan beban ekonomi yang tinggi, terutama di negara-negara berkembang. Saat ini, tiga vaksin RV (Rotarix, RotaTeq, Rotavac) dilisensikan secara internasional oleh World Health Organization (WHO) dan belum dapat diterapkan di negara-negara berkembang. Oleh karena itu, penelitian menunjukkan potensi BRV-PV dalam mencegah infeksi RV pada anak-anak, khususnya di negara berkembang. Tujuan: Ulasan ini bertujuan untuk menganalisis efektivitas dan keamanan BRV-PV dalam mencegah SRVGE. Metode: Tinjauan sistematis ini mencakup studi dari database ScienceDirect, PubMed, Elsevier, dan Cochrane yang memenuhi kriteria inklusi dan eksklusi. Metode pencariannya menggunakan operator boolean dengan artikel sepuluh tahun terakhir. Delapan artikel dengan total 9088 pediatri ditinjau untuk menganalisis efektivitas dan keamanan BRV-PV. Hasil dan Pembahasan: Dari semua penelitian yang terlibat, BRV-PV telah secara efektif mengurangi kejadian rawat inap dan kasus darurat akibat SRVGE. Selain itu, BRV-PV juga aman untuk anak-anak di negara berkembang, terbukti dengan peningkatan konsentrasi IgA anti-RV dan efek samping yang minimal. Kesimpulan: BRV-PV lebih efektif, aman, tahan panas, dan terjangkau dibandingkan tiga vaksin RV sebelumnya di negara berkembang.. Kata Kunci: BRV-PV, Gastroenteritis, Rotavirus, Vaksin Rotavirus

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.

Results and prospects of rotavirus immunisation in the Russian Federation

Scientific relevance. Rotavirus disease and its consequences remain a leading vaccine-preventable cause of mortality in young children. Russia has not yet included rotavirus immunisation in the national vaccination schedule, but paediatric rotavirus vaccines are provided under several regional immunisation programmes.Aim. The authors aimed to review literature covering Russian clinical evidence of the safety and effectiveness of rotavirus vaccines and to analyse the prospects for the development of the national immunisation programme for young children using the available rotavirus vaccines and considering promising pipeline ones.Discussion. Local epidemiological studies on a range of pathogens suggest that rotaviruses are the most common cause of acute intestinal infections, especially in children under 3 years of age. Since Russia’s first rotavirus vaccine approval in 2012, the healthcare system has acquired sufficient experience with rotavirus vaccines to evaluate the safety and effectiveness of rotavirus immunisation. Long-term monitoring of the rotavirus A genotypes circulating in the country shows that currently available rotavirus vaccines cover the majority of identified rotavirus isolates. Local observational studies confirm the favourable safety profile of rotavirus vaccines and demonstrate notable effectiveness of vaccination. In the regions with high immunisation coverage, the overall morbidity has declined dramatically in vaccinated children compared to unvaccinated children; some of these regions have reported only individual hospital visits or admissions for acute intestinal infections.Conclusion. This review demonstrates that rotavirus immunisation should be included in the Russian National Immunisation Schedule.

Increased bacterial taxonomic and functional diversity is associated with impaired rotavirus vaccine immunogenicity in infants from India and Malawi

The immunogenicity and effectiveness of oral rotavirus vaccines (ORVs) against severe rotavirus-associated gastroenteritis are impaired in low- and middle-income countries (LMICs) where the burden of disease is highest. Determining risk factors for impaired ORV response may help identify strategies to enhance vaccine effectiveness. In this study, we use metagenomic sequencing to provide a high-resolution taxonomic analysis of stool samples collected at 6 weeks of age (coinciding with the first ORV dose) during a prospective study of ORV immunogenicity in India and Malawi. We then analyse the functional capacity of the developing microbiome in these cohorts. Microbiome composition differed significantly between countries, although functional capacity was more similar than taxonomic composition. Our results confirm previously reported findings that the developing microbiome is more diverse in taxonomic composition in ORV non-seroconverters compared with seroconverters, and we additionally demonstrate a similar pattern in functional capacity. Although taxonomic or functional feature abundances are poor predictors of ORV response, we show that skews in the direction of associations within these microbiome data can be used to identify consistent markers of ORV response across LMIC infant cohorts. We also highlight the systemic under-representation of reference genes from LMICs that limit functional annotation in our study (7% and 13% annotation at pathway and enzyme commission level, respectively). Overall, higher microbiome diversity in early life may act as marker for impaired ORV response in India and Malawi, whilst a holistic perspective of functional capacity may be hidden in the “dark matter” of the microbiome.

Rotavirus Genotypes in the Postvaccine Era: A Systematic Review and Meta-analysis of Global, Regional, and Temporal Trends by Rotavirus Vaccine Introduction.

Even moderate differences in rotavirus vaccine effectiveness against nonvaccine genotypes may exert selective pressures on circulating rotaviruses. Whether this vaccine effect or natural temporal fluctuations underlie observed changes in genotype distributions is unclear. We systematically reviewed studies reporting rotavirus genotypes from children <5 years of age globally between 2005 and 2023. We compared rotavirus genotypes between vaccine-introducing and nonintroducing settings globally and by World Health Organization (WHO) region, calendar time, and time since vaccine introduction. Crude pooling of genotype data from 361 studies indicated higher G2P[4], a nonvaccine genotype, prevalence in vaccine-introducing settings, both globally and by WHO region. This difference did not emerge when examining genotypes over time in the Americas, the only region with robust longitudinal data. Relative to nonintroducing settings, G2P[4] detections were more likely in settings with recent introduction (eg, 1-2 years postintroduction adjusted odds ratio [aOR], 4.39; 95% confidence interval [CI], 2.87-6.72) but were similarly likely in settings with more time elapsed since introduction, (eg, 7 or more years aOR, 1.62; 95% CI, .49-5.37). When accounting for both regional and temporal trends, there was no substantial evidence of long-term vaccine-related selective pressures on circulating genotypes. Increased prevalence of G2P[4] may be transient after rotavirus vaccine introduction.

Meta-Analysis the Effects of Rotavirus Vaccine, Exclusive Breastfeeding, and Maternal Education on Diarrhea in Children Under Five

Background: Diarrhea is an infectious disease that can cause death in children under five years. Diarrheal disease is a disease with the highest mortality and morbidity after pneumonia. The purpose of this study was to analyze and estimate the effect of rotavirus vaccine, exclusive breastfeeding, and mother's education level on the incidence of diarrhea in toddlers, with a meta-analysis based on previously conducted primary studies. Subjects and Method: This article was prepared using a systematic review and meta-analytic study. This research was conducted using the PICO model. Meta-analytic studies were conducted by searching for articles from databases in electronic form using PubMed, Google Scholar, Sciencedirect, and Springer Link. Article searches were conducted from 1-28 February 2023. The keywords used were “Vacinnation” OR “Exclusive breastfeeding” OR “Educational Mother” OR “Infection” OR “Diarrhea Childhood”. The inclusion criteria for this study were complete articles using cross-sectional research, published years from 2013-2022. Analysis of the articles used RevMan 5.3 software. Results: A total of 24 cross-sectional studies from Africa and Asia were selected for systematic review and meta-analysis. The results of the meta-analysis showed that not given rotavirus vaccine had a 3.60 times the risk of experiencing diarrhea compared to those given rotavirus vaccine (aOR= 3.60; 95% CI= 2.31 to 5.64; p&lt;0.001), not given exclusive breastfeeding had a risk of experiencing diarrhea 3.28 times compared with those who were given exclusive breastfeeding (aOR= 3.28; 95% CI= 2.24 to 4.80; p&lt;0.001), and children who had mothers with low education levels had a 2.08 times higher risk of experiencing diarrhea compared to children who had mothers with low education levels which is higher (aOR= 2.08; 95% CI= 1.71 to 2.54; p&lt;0.001). Conclusion: Not being given the rotavirus vaccine, not being given exclusive breastfeeding, and the mother's low education level are at risk of increasing the incidence of diarrhea in toddlers. Keywords: rotavirus vaccine, exclusive breastfeeding, mother's level of education, child diarrhea Correspondence: Genn Andrean Pratama. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java, Indonesia. Email: andreanpratama0077@gmail.com. Mobile: +6282278467441.

Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico

ABSTRACT Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer’s perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

The Impact of Rotavirus Vaccination on Discharges for Pediatric Gastroenteritis in Italy: An Eleven Year (2009-2019) Nationwide Analysis.

In Italy, despite the documented positive effects of rotavirus (RV) vaccination on reducing the burden of RV disease, an updated national assessment of its impact on clinical outcomes is still lacking. This study aims to analyze the implementation of RV vaccination in Italy, evaluating its impact on discharges for acute pediatric gastroenteritis (AGE). A retrospective analysis, including hospital discharge records and data on vaccination coverage for children aged 0-71 months from 2009 to 2019, was conducted. We examined trends in hospital discharge standardized incidence before and after vaccine introduction using a negative binomial mixture model with fixed effects to evaluate the impact of universal vaccination. The percentage of vaccination coverage increased over the years, from <5% between 2009 and 2013 to 26% in 2017, reaching 70% in 2019. The standardized incidence of discharges decreased over the period from 16.6/100,000 inhabitants in 2009-2013 to 9.9/100,000 inhabitants in 2018-2019. In this phase, about 15% of the estimated hospital discharges were avoided compared with those estimated in the first phase. The implementation of RV vaccination reduced AGE incidence discharges in children aged 0-71 months. Further efforts are needed to continue monitoring the vaccination effect over time and to increase vaccination coverage.

A health surveillance data-based assessment of the impact of routine paediatric rotavirus vaccination on all-cause acute childhood diarrhoea

Background: To improve the fight against faecal-orally transmitted rotavirus infection, which is the leading cause of severe diarrhoea among children aged &lt; 5 years, Ghana has incorporated rotavirus vaccination into its expanded programme of immunization. Rotavirus diarrhoea constitutes a significant portion of all-cause acute childhood diarrhoea (ACD) in children. Objective: This study was designed to investigate the impact of routine rotavirus vaccination on ACD cases. Methods: The study was completed through a cross-sectional review of health institutional childhood diarrhoea surveillance data from 2012 to 2021, which includes the year when rotavirus vaccination was introduced. The study dataset was abstracted from the DHIMS-2 internet-based health data repository and was descriptively analyzed by administrative regions using Epi InfoTM version 3.5.1(CDC, USA). Results: The burden of ACD in terms of both absolute and mean values remained the lowest among infants aged under 28 days across all regions, as they had not yet received rotavirus vaccination. In contrast, children aged 1 to 4 years, who are typically exposed to rotavirus serotypes 1 and 2, consistently experienced the highest burden of ACD. With increasing rotavirus vaccination coverage, children aged 1 month to 4 years recorded a marginal, but sustained decline in mean ACD cases from 2016 to 2021. The ACD also similarly declined slowly among the rotavirus vaccine naïve infants aged &lt; 28 days. Despite a spike in 2017, the burden of ACD was low in the Ahafo administrative region. However, increasing rotavirus vaccination coverage did not appear to have a significant impact on reducing ACD in the Ashanti, Bono, Bono East, Eastern, and Northeast administrative regions. From 2012 to 2021, the Central, Greater Accra, Oti, Upper East, Volta, and Western administrative regions recorded a marginal decline in the burden of ACD among children aged 1 to 4 years, and this was accompanied by an increase in rotavirus vaccination coverage. The ACD cases rose as rotavirus vaccination coverage decreased in the Western North Region between 2015 and 2019. Conclusion: Routine rotavirus vaccination may have contributed to a reduction in severe childhood ACD cases even though this study cannot exclude the impact of other anti-diarrhoeal interventions. To evaluate the population effectiveness of rotavirus vaccines, it is recommended to widely promote routine rotavirus disease surveys, which can be nested within ACD surveillance.

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

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. 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. 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≤4years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to≤2years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. 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.