RESUMEN
Rotavirus (RV) vaccines have demonstrated substantial effectiveness in reducing the healthcare burden caused by gastroenteritis (RVGE) worldwide. This study aims to understand the differential impact of RV vaccination in reducing RVGE burden in children under 7 years old in China. A Markov Model was used to investigate the health impact of introducing two different RV vaccines into the Chinese population. The analysis was conducted for RV5, a live pentavalent human-bovine reassortant vaccine, and Lanzhou Lamb RV (LLR), a live-attenuated monovalent RV vaccine, separately, by comparing the strategy of each vaccine to no vaccination within a Chinese birth cohort, including 100,000 children modeled until 7 years of age. The vaccination scenario assumed a vaccination coverage of 2.5%, 2.5%, 90% and 5% for doses one, two, three and no vaccine, respectively, for both vaccines. Strategies with RV5, LLR, and no vaccination were associated with 9,895, 49,069, and 64,746 symptomatic RV infections, respectively. RV5 and LLR were associated with an 85% and 24% reduction in the total symptomatic RV infections, respectively, suggesting that the health benefits of RV5 are at least three-fold greater than those associated with the LLR. Further, strategies with RV5 and LLR resulted in an estimated 206 and 59-year increase in quality-adjusted life years (QALYs), respectively. Sensitivity and scenario analyses supported the robustness of the base-case findings. Use of RV vaccine is expected to improve RV-associated health outcomes and its adoption will help alleviate the burden of RVGE in China. RV5 use will result in significantly better health outcomes.
Asunto(s)
Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Vacunación , Humanos , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , China/epidemiología , Lactante , Preescolar , Vacunación/estadística & datos numéricos , Niño , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/epidemiología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Cobertura de Vacunación/estadística & datos numéricos , Cadenas de Markov , Recién Nacido , Masculino , Rotavirus/inmunología , FemeninoRESUMEN
Rotavirus, a dsRNA virus in the Reoviridae family, shows a segmented genome. The VP1 gene encodes the RNA-dependent RNA polymerase (RdRp). This study aims to develop a multiepitope-based vaccine targeting RdRp using immunoinformatic approaches. In this study, 100 available nucleotide sequences of VP1-Rotavirus belonging to different strains across the world were retrieved from NCBI database. The selected sequences were aligned, and a global consensus sequence was developed by using CLC work bench. The study involved immunoinformatic approaches and molecular docking studies to reveal the promiscuous epitopes that can be eventually used as active vaccine candidates for Rotavirus. In total, 27 highly immunogenic, antigenic, and non-allergenic T-cell and B-cell epitopes were predicted for the Multiepitope vaccine (MEV) against rotavirus. It was also observed that MEV can prove to be effective worldwide due to its high population coverage, demonstrating the consistency of this vaccine. Moreover, there is a high docking interaction and immunological response with a binding score of -50.2 kcal/mol, suggesting the vaccine's efficacy. Toll-like receptors (TLRs) also suggest that the vaccine is physiologically and immunologically effective. Collectively, our data point to an effective MEV against rotavirus that can effectively reduce viral infections and improve the health status worldwide.
Asunto(s)
Simulación del Acoplamiento Molecular , Vacunas contra Rotavirus , Rotavirus , Vacunas de Subunidad , Rotavirus/inmunología , Rotavirus/genética , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/genética , Vacunas contra Rotavirus/inmunología , ARN Polimerasa Dependiente del ARN/inmunología , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/química , Biología Computacional , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Humanos , Epítopos/inmunología , Epítopos/genética , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Inmunoinformática , Vacunas de Subunidades ProteicasRESUMEN
Evidence on unnecessary antibiotic use in children with acute viral gastroenteritis (AGE) is scarce. We characterized the extent and correlates of antibiotic use among children hospitalized with viral AGE. A single-center study enrolled children aged 0-59 months hospitalized for AGE between 2008 and 2015 in Israel. Information was collected on laboratory tests, diagnoses, antibiotic treatment, and rotavirus vaccination. Stool samples were tested for rotavirus antigen, GII-norovirus, and stool cultures were performed for bacterial enteropathogens. Data from 2240 children were analyzed. Rotavirus vaccine was given to 79% of eligible children. Rotavirus test was performed on 1419 (63.3%) children. Before the introduction of universal rotavirus vaccination (2008-2010), rotavirus positivity in stool samples was 37.0%, which declined to 17.3% during the universal vaccination years (2011-2015). Overall, 1395 participants had viral AGE. Of those, 253 (18.1% [95% CI 16.1-20.2]) had unnecessary antibiotic treatment, mostly penicillin 46.6%, ceftriaxone 34.0% and azithromycin 21.7%. A multivariable analysis showed an inverse association between rotavirus vaccination and unnecessary antibiotic treatment (odds ratio = 0.53 [95% CI 0.31-0.91]), while positive associations were found with performing chest-X-ray test (3.00 [1.73-5.23]), blood (3.29 [95% CI 1.85-5.86]) and urine cultures (7.12 [3.77-13.43]), levels of C-reactive protein (1.02 [1.01-1.02]) and leukocytes (1.05 [1.01-1.09]). The results were consistent in an analysis of children with laboratory-confirmed rotavirus or norovirus AGE, or after excluding children with CRP > 50 mg/L. In conclusion, antibiotic prescription was common among hospitalized children with viral AGE, which was inversely related to rotavirus vaccination, possibly due to less severe illness in the vaccinated children.
Asunto(s)
Antibacterianos , Gastroenteritis , Hospitalización , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Gastroenteritis/virología , Gastroenteritis/prevención & control , Gastroenteritis/tratamiento farmacológico , Lactante , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Preescolar , Masculino , Femenino , Antibacterianos/uso terapéutico , Infecciones por Rotavirus/prevención & control , Hospitalización/estadística & datos numéricos , Israel/epidemiología , Recién Nacido , Heces/virología , Heces/microbiología , Rotavirus/inmunología , Rotavirus/aislamiento & purificación , Vacunación/estadística & datos numéricos , Norovirus/inmunologíaRESUMEN
BACKGROUND: Kenya introduced a monovalent rotavirus vaccine administered orally at 6 and 10 weeks of age into her National Immunization Program in July 2014. The study evaluated the long-term impact of the vaccine on hospitalization for all-cause and rotavirus-specific acute gastroenteritis (AGE) and strain epidemiology in Kenya. METHODS: Data on all-cause and rotavirus-specific AGE and strain distribution were derived from an eleven-year hospital-based surveillance of AGE among children aged <5 years at Kiambu County Teaching and Referral Hospital (KCTRH) in Central Kenya between 2009 and 2020. Fecal samples were screened for group A rotavirus using ELISA and genotyped using multiplex semi-nested RT-PCR. Trends in all-cause and rotavirus-related AGE and strain distribution were compared between the pre-vaccine (July 2009-June 2014), early post-vaccine (July 2014-June 2016) and late post-vaccine (February 2019-October 2020) periods. RESULTS: Rotavirus-specific AGE was detected at 27.5% (429/1546, 95% CI: 25.5-30.1%) in the pre-vaccine period; 13.8% (91/658, 95% CI: 11.3-16.6%) in the early post-vaccine period (July 2014-June 2016); and 12.0% (229/1916, 95% CI: 10.6-13.5%) in the late post-vaccine period (February 2019-October 2020). This amounted to a decline of 49.8% (95% CI: 34.6%-63.7%) in rotavirus-specific AGE in the early post-vaccine period and 53.4% (95% CI: 41.5-70.3%) in the late post-vaccine period when compared to the pre-vaccine period. All-cause AGE hospitalizations declined by 40.2% (95% CI: 30.8%-50.2%) and 75.3% (95% CI: 65.9-83.1%) in the early post-vaccine and late post-vaccine periods, respectively, when compared to the pre-vaccine period. G3P [8] was the predominant strain in the late post-vaccine period, replacing G1P[8] which had predominated in the pre-vaccine and early post-vaccine periods. Additionally, we detected considerable proportions of uncommon strains G3P[6] (4.8%) and G12P[6] (3.5%) in the post-vaccine era. CONCLUSION: Rotavirus vaccination has resulted in a significant decline in all-cause and rotavirus-specific AGE, and thus, provides strong evidence for public health policy makers in Kenya to support the sustained use of the rotavirus vaccine in routine immunization. However, the shift in strain dominance and age distribution of rotavirus AGE in the post-vaccine era underscores the need for continued surveillance to assess any possible vaccine-induced selective pressure that could diminish the vaccine effectiveness over time.
Asunto(s)
Gastroenteritis , Programas de Inmunización , Análisis de Series de Tiempo Interrumpido , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunación , Humanos , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Gastroenteritis/epidemiología , Gastroenteritis/virología , Gastroenteritis/prevención & control , Kenia/epidemiología , Preescolar , Rotavirus/inmunología , Rotavirus/genética , Lactante , Vacunación/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Femenino , Heces/virología , Masculino , Genotipo , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificaciónRESUMEN
Age-stratified path analyses modeled associations between enteric pathogen reservoirs, transmission pathways and height-for-age z-scores (HAZ) to identify determinants of childhood growth in the Kolkata, India site of the Global Enteric Multicenter Study (GEMS). Models tested direct associations of potential pathogen reservoirs with HAZ at 60-day follow-up in separate moderate and severe diarrhea (MSD) case and control cohorts or indirectly when mediated by enteric infections. In the MSD cohort, rotavirus and typical EPEC (tEPEC) infections among children 0-11 months of age and ST-ETEC infections among children 12-23 months of age were associated with lower HAZ. Handwashing after defecating and before cooking reduced impaired growth through reductions in rotavirus and tEPEC infections. Water storage increased rotavirus and ST-ETEC infection risks, resulting in increased impaired growth, but was reduced with reported child feces disposal. The GII norovirus variant was inversely associated with HAZ among children 12-59 months of age in the control cohort. Reported handwashing before the handling of children reduced GII infections and impaired growth. Boiling water and the disposal of children's feces mediated by stored water were positively associated with HAZ. The targeting of pathogen-specific reservoirs and transmission pathways may more effectively improve childhood linear growth in South Asian urban communities.
Asunto(s)
Diarrea , Humanos , India/epidemiología , Lactante , Masculino , Preescolar , Femenino , Diarrea/virología , Diarrea/epidemiología , Recién Nacido , Trastornos del Crecimiento/epidemiología , Trastornos del Crecimiento/virología , Estatura , Estudios de Casos y Controles , Infecciones por Rotavirus/transmisión , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Heces/virología , Heces/microbiología , Desinfección de las Manos , Rotavirus/aislamiento & purificación , Reservorios de Enfermedades/virologíaRESUMEN
INTRODUCTION: Rotavirus vaccines may provide indirect protection by reducing transmission in the population and thus reducing disease burden. METHODS: This systematic review summarizes estimates of indirect protection from rotavirus vaccines and the methods used to obtain these estimates. RESULTS: We identified 71 studies published between 2009 and 2022 that provided 399 estimates of indirect protection from rotavirus vaccine. Most estimates (73%) evaluated hospitalizations due to rotavirus gastroenteritis as the outcome and unvaccinated children <5 years old as the agegroup (64%), but there was considerable variability in methods to evaluate indirect protection. For hospitalizations due to rotavirus gastroenteritis among unvaccinated children <5 years old, the median incidence rate ratio was 0.60 (IQR: 0.40-0.87, n = 110 estimates), the median relative percent change in percent positivity was 25% (IQR: 13-44%, n = 49 estimates), and the median relative percent change in absolute number of rotavirus positive tests or rotavirus-specific International Classification of Diseases codes was 42% (IQR: 16-66%, n = 40 estimates). CONCLUSIONS: These findings broadly suggest rotavirus vaccines provide some indirect protection. There is a need to standardize measurement of indirect rotavirus vaccine protection, particularly using consistent outcomes and metrics, and stratifying results by standardized age groups and years since vaccine introduction.
Asunto(s)
Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Preescolar , Humanos , Lactante , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/epidemiología , Gastroenteritis/inmunología , Hospitalización/estadística & datos numéricos , Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunologíaRESUMEN
BACKGROUND: Rotavirus is a leading cause of diarrhea in infants and young children in many low- and middle-income countries. India launched a childhood immunization program for rotavirus in 2016, starting with four states and expanding it to cover all states by 2019. The objective of this study was to estimate the effects of the rotavirus vaccination program in India on disease burden and antibiotic misuse. METHODS: We built a dynamic agent-based model of rotavirus progression in children under five within each district in India. Simulations were run for various scenarios of vaccination coverage in the context of India's Universal Immunization Programme. Population data were obtained from the National Family Household Surveys and used to calibrate the models. Disease parameters were obtained from published studies. We estimated past and projected future reduction of disease burden and antibiotic misuse due to full vaccination nationwide, by state, and by wealth quintile. RESULTS: We estimate that rotavirus vaccination in India has reduced the prevalence of rotavirus cases by 33.7% (prediction interval: 30.7-36.0%), total antibiotic misuse due to rotavirus by 21.8% (18.6-25.1%), and total deaths due to rotavirus by 38.3% (31.3-44.4%) for children under five. We estimate total antibiotic misuse due to rotavirus infection to be 7.6% (7.5-7.9%) of total antibiotic consumption in this demographic versus 9.6% (9.4-9.9%) in the absence of vaccination. We project rotaviral prevalence to drop to below one case for every 100,000 individuals in those below five if vaccination coverage is increased by 50.3% (45.2-58.5%) to 68.1% (63.1-76.4) nationwide. CONCLUSION: Universal coverage of childhood rotavirus vaccination can substantially reduce inappropriate antibiotic use in India.
Asunto(s)
Antibacterianos , Programas de Inmunización , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , India/epidemiología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/uso terapéutico , Vacunas contra Rotavirus/inmunología , Lactante , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Preescolar , Cobertura de Vacunación/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Rotavirus/inmunología , Costo de Enfermedad , Prevalencia , Diarrea/prevención & control , Diarrea/epidemiología , Recién Nacido , Masculino , FemeninoRESUMEN
BACKGROUND: Rotavirus infections are a significant cause of severe diarrhea and related illness and death in children under five worldwide. Despite the global introduction of vaccinations for rotavirus over a decade ago, rotavirus infections still result in high deaths annually, mainly in low-income countries, including Ethiopia, and need special attention. This system review and meta-analysis aimed to comprehensively explore the positive proportion of rotavirus at pre- and post-vaccine introduction periods and genotype distribution in children under five with diarrhea in Ethiopia. METHODS: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Database sources included PubMed, Scopus, EMBASE, and Epistemonikos, focusing on studies published before November 30, 2023. The search targeted rotavirus infection and genotype distribution in Ethiopia before and after the introduction of the Rota vaccine. Data was managed using EndNote 2020 software and stored in an Excel 2010 sheet. A random-effects model determined the pooled estimate of the rotavirus infection rate at 95% confidence intervals. The Q-and I² statistics were used to assess the study heterogeneity, and a funnel plot (Egger test) was used to determine the possibility of publication bias. RESULTS: The analysis included data from nine studies conducted in different regions of Ethiopia. The overall prevalence of rotavirus infection was significant, with a prevalence rate of approximately 22.63% (1362/6039). The most common genotypes identified before the Rota vacation introduction were G1, G2, G3, G12, P [4], P [6], P [8], P [9], and P [10]. Meanwhile, G3 and P [8] genotypes were particularly prevalent after the Rota vaccine introduction. These findings highlight the importance of implementing preventive measures, such as vaccination, to reduce the burden of rotavirus infection in this population. The identified genotypes provide valuable insights for vaccine development and targeted interventions. CONCLUSION: This study contributes to the evidence base for public health interventions and strategies to reduce the impact of rotavirus infection in children under five in Ethiopia. Despite the rollout of the Rota vaccination in Ethiopia, rotavirus heterogeneity is still high, and thus, enhancing vaccination and immunization is essential.
Asunto(s)
Diarrea , Genotipo , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Preescolar , Humanos , Lactante , Diarrea/epidemiología , Diarrea/prevención & control , Diarrea/virología , Etiopía/epidemiología , Prevalencia , Rotavirus/clasificación , Rotavirus/genética , Rotavirus/inmunología , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/administración & dosificación , Vacunación/estadística & datos numéricosRESUMEN
Two vaccines against rotavirus diseases, Rotarix® and RotaTeq®, are being marketed in Spain; but rotavirus is not presently among the diseases covered by universal vaccination in Spain. The aim of this study was to assess the efficiency of extending Spain's current targeted rotavirus vaccination strategy including only preterm babies, to a policy of universal vaccination. A de novo cohort-based Markov model was built to evaluate the efficiency of three compared rotavirus vaccination strategies in Spain: targeted, universal, and no vaccination. Using Rotarix® or RotaTeq®, we compared the cost-utility of these strategies from both a societal perspective and Spanish National Health System (SNHS) perspective. The model represents the most important clinical events conceivably linked to rotavirus infection. Efficacy, effectiveness, safety, costs, and utilities were identified by systematic reviews. Incremental cost-utility ratio (ICUR) is EUR 23,638/QALY (Quality-Adjusted Life Year) for targeted vaccination with Rotarix® compared with no vaccination. The ICUR for the rest of the strategies evaluated are above EUR 30,000/QALY. The sensitivity analysis shows price as the only parameter that could make the universal vaccination strategy efficient. Considering a threshold of EUR 25,000/QALY, only targeted vaccination with Rotarix® would be efficient from societal perspective. Price drops of 36.9% for Rotarix® and 44.6% for RotaTeq® would make universal vaccination efficient.
Asunto(s)
Análisis Costo-Beneficio , Años de Vida Ajustados por Calidad de Vida , Infecciones por Rotavirus , Vacunas contra Rotavirus , Vacunación , Vacunas Atenuadas , Vacunas contra Rotavirus/economía , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , España , Humanos , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/economía , Vacunación/economía , Vacunas Atenuadas/economía , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Lactante , Rotavirus/inmunología , Cadenas de Markov , Preescolar , Recién Nacido , PresupuestosRESUMEN
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.
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ADN Complementario , Genética Inversa , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunas Atenuadas , Vacunas contra Rotavirus/genética , Vacunas contra Rotavirus/inmunología , Genética Inversa/métodos , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Rotavirus/genética , Rotavirus/inmunología , Humanos , Animales , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , ADN Complementario/genética , Genoma Viral , Ratones , Línea CelularRESUMEN
We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011-2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage <40% (e.g., for coverage >80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83-0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.
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Gastroenteritis , Hospitalización , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Cobertura de Vacunación , Humanos , Gastroenteritis/epidemiología , Gastroenteritis/virología , Gastroenteritis/prevención & control , Lactante , Japón/epidemiología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Vacunas contra Rotavirus/administración & dosificación , Hospitalización/estadística & datos numéricos , Preescolar , Cobertura de Vacunación/estadística & datos numéricos , Masculino , Femenino , Rotavirus/inmunología , Adulto , Niño , Adolescente , Recién Nacido , Persona de Mediana Edad , Adulto Joven , Anciano , Incidencia , Vacunación/estadística & datos numéricos , Historia del Siglo XXIRESUMEN
OBJECTIVE: In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination. MATERIALS AND METHODS: A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3. RESULTS: Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively. CONCLUSIONS: Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.
Asunto(s)
Gastroenteritis , Programas de Inmunización , Salud Pública , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Francia/epidemiología , Lactante , Preescolar , Programas de Inmunización/estadística & datos numéricos , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/epidemiología , Hospitalización/estadística & datos numéricos , Vacunación/estadística & datos numéricos , Cobertura de Vacunación/estadística & datos numéricos , Rotavirus/inmunología , Recién Nacido , Inmunidad ColectivaRESUMEN
BACKGROUND: 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. METHODS: 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 (1â-â[odds of being vaccinated in cases]â/â[odds of being vaccinated in controls])â×â100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Gavi, the Vaccine Alliance. TRANSLATION: For the Dari translation of the abstract see Supplementary Materials section.
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Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Eficacia de las Vacunas , Humanos , Vacunas contra Rotavirus/administración & dosificación , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Afganistán/epidemiología , Estudios de Casos y Controles , Lactante , Masculino , Femenino , Preescolar , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/epidemiología , Eficacia de las Vacunas/estadística & datos numéricos , Vacunas Atenuadas/administración & dosificación , Hospitalización/estadística & datos numéricos , Vigilancia de Guardia , Vacunación/estadística & datos numéricosRESUMEN
Enteric viruses are the leading cause of diarrhoea in children <5 years. Despite existing studies describing rotavirus diarrhoea in Mozambique, data on other enteric viruses remains scarce, especially after rotavirus vaccine introduction. We explored the prevalence of norovirus GI and GII, adenovirus 40/41, astrovirus, and sapovirus in children <5 years with moderate-to-severe (MSD), less severe (LSD) diarrhoea and community healthy controls, before (2008-2012) and after (2016-2019) rotavirus vaccine introduction in Manhiça District, Mozambique. The viruses were detected using ELISA and conventional reverse transcription PCR from stool samples. Overall, all of the viruses except norovirus GI were significantly more detected after rotavirus vaccine introduction compared to the period before vaccine introduction: norovirus GII in MSD (13/195, 6.7% vs. 24/886, 2.7%, respectively; p = 0.006) and LSD (25/268, 9.3% vs. 9/430, 2.1%, p < 0.001); adenovirus 40/41 in MSD (7.2% vs. 1.8%, p < 0.001); astrovirus in LSD (7.5% vs. 2.6%, p = 0.002); and sapovirus in MSD (7.1% vs. 1.4%, p = 0.047) and controls (21/475, 4.4% vs. 51/2380, 2.1%, p = 0.004). Norovirus GII, adenovirus 40/41, astrovirus, and sapovirus detection increased in MSD and LSD cases after rotavirus vaccine introduction, supporting the need for continued molecular surveillance for the implementation of appropriate control and prevention measures.
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Diarrea , Heces , Vacunas contra Rotavirus , Humanos , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Mozambique/epidemiología , Preescolar , Lactante , Femenino , Diarrea/virología , Diarrea/epidemiología , Diarrea/prevención & control , Heces/virología , Masculino , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/virología , Prevalencia , Gastroenteritis/virología , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Norovirus/genética , Norovirus/inmunología , Norovirus/aislamiento & purificación , Rotavirus/genética , Rotavirus/aislamiento & purificación , Rotavirus/inmunología , Sapovirus/genética , Sapovirus/aislamiento & purificación , Recién NacidoRESUMEN
Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine's antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.
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Antígenos Virales , Biología Computacional , Epítopos de Linfocito B , Epítopos de Linfocito T , Simulación de Dinámica Molecular , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunas de Subunidad , Animales , Porcinos , Rotavirus/inmunología , Rotavirus/genética , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/química , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/química , Vacunas contra Rotavirus/genética , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Infecciones por Rotavirus/virología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/genética , Vacunas de Subunidad/química , Antígenos Virales/inmunología , Antígenos Virales/genética , Antígenos Virales/química , Simulación del Acoplamiento Molecular , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/virología , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/química , Desarrollo de Vacunas , Inmunogenicidad VacunalRESUMEN
To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = -0.59 log copies per gram of stool; 95% confidence interval [CI], -.99 to -.19). Duration of illness was on average 0.47 days (95% CI, -.23 to 1.17 days) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of rotavirus gastroenteritis. Clinical Trials Registration . NCT01375647.
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Heces , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunas Atenuadas , Esparcimiento de Virus , Humanos , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Lactante , Bangladesh/epidemiología , Rotavirus/inmunología , Heces/virología , Femenino , Masculino , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Gastroenteritis/virología , Gastroenteritis/prevención & control , Gastroenteritis/epidemiología , Vacunación , Diarrea/virología , Diarrea/prevención & control , Diarrea/epidemiología , Administración OralRESUMEN
Rotavirus, a primary contributor to severe cases of infantile gastroenteritis on a global scale, results in significant morbidity and mortality in the under-five population, particularly in middle to low-income countries, including India. WHO-approved live-attenuated vaccines are linked to a heightened susceptibility to intussusception and exhibit low efficacy, primarily attributed to the high genetic diversity of rotavirus, varying over time and across different geographic regions. Herein, molecular data on Indian rotavirus A (RVA) has been reviewed through phylogenetic analysis, revealing G1P[8] to be the prevalent strain of RVA in India. The conserved capsid protein sequences of VP7, VP4 and VP6 were used to examine helper T lymphocyte, cytotoxic T lymphocyte and linear B-cell epitopes. Twenty epitopes were identified after evaluation of factors such as antigenicity, non-allergenicity, non-toxicity, and stability. These epitopes were then interconnected using suitable linkers and an N-terminal beta defensin adjuvant. The in silico designed vaccine exhibited structural stability and interactions with integrins (αvß3 and αIIbß3) and toll-like receptors (TLR2 and TLR4) indicated by docking and normal mode analyses. The immune simulation profile of the designed RVA multiepitope vaccine exhibited its potential to trigger humoral as well as cell-mediated immunity, indicating that it is a promising immunogen. These computational findings indicate potential efficacy of the designed vaccine against rotavirus infection.
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Antígenos Virales , Proteínas de la Cápside , Epítopos de Linfocito T , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Rotavirus/inmunología , Rotavirus/genética , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/genética , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/química , Antígenos Virales/inmunología , Antígenos Virales/genética , Humanos , India , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Vacunología/métodos , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/genética , Filogenia , Simulación del Acoplamiento Molecular , Epítopos/inmunología , Epítopos/genética , Desarrollo de VacunasRESUMEN
Rotavirus remains a significant public health threat, especially in low-income countries, where it is the leading cause of severe acute childhood gastroenteritis, contributing to over 128,500 deaths annually. Although the introduction of the Rotarix and RotaTeq vaccines in 2006 marked a milestone in reducing mortality rates, approximately 83,158 preventable deaths persisted, showing ongoing challenges in vaccine accessibility and effectiveness. To address these issues, a novel subcutaneous vaccine formulation targeting multiple rotavirus genotypes has been developed. This vaccine consists of nine VP8* proteins from nine distinct rotavirus genotypes and sub-genotypes (P[4], P[6], P[8]LI, P[8]LIII, P[8]LIV, P[9], P[11], P[14], and P[25]) expressed in E. coli. Two groups of mice were immunized either with a single immunogen, the VP8* from the rotavirus Wa strain (P[8]LI), or with the nonavalent formulation. Preliminary results from mouse immunization studies showed promising outcomes, eliciting antibody responses against six of the nine immunogens. Notably, significantly higher antibody titers against VP8* P[8]LI were observed in the group immunized with the nonavalent vaccine compared to mice specifically immunized against this genotype alone. Overall, the development of parenteral vaccines targeting multiple rotavirus genotypes represents a promising strategy in mitigating the global burden of rotavirus-related morbidity and mortality, offering new avenues for disease prevention and control.
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Anticuerpos Antivirales , Infecciones por Rotavirus , Vacunas contra Rotavirus , Rotavirus , Vacunas de Subunidad , Animales , Vacunas contra Rotavirus/inmunología , Vacunas contra Rotavirus/administración & dosificación , Ratones , Rotavirus/inmunología , Rotavirus/genética , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/genética , Infecciones por Rotavirus/prevención & control , Infecciones por Rotavirus/inmunología , Infecciones por Rotavirus/virología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Femenino , Ratones Endogámicos BALB C , Proteínas no Estructurales Virales/inmunología , Proteínas no Estructurales Virales/genética , Inmunogenicidad Vacunal , Genotipo , Proteínas de la Cápside/inmunología , Proteínas de la Cápside/genética , Proteínas de Unión al ARN/inmunología , Proteínas de Unión al ARN/genéticaRESUMEN
Mozambique introduced the Rotarix® vaccine into the National Immunization Program in September 2015. Following vaccine introduction, rotavirus A (RVA) genotypes, G9P[4] and G9P[6], were detected for the first time since rotavirus surveillance programs were implemented in the country. To understand the emergence of these strains, the whole genomes of 47 ELISA RVA positive strains detected between 2015 and 2018 were characterized using an Illumina MiSeq-based sequencing pipeline. Of the 29 G9 strains characterized, 14 exhibited a typical Wa-like genome constellation and 15 a DS-1-like genome constellation. Mostly, the G9P[4] and G9P[6] strains clustered consistently for most of the genome segments, except the G- and P-genotypes. For the G9 genotype, the strains formed three different conserved clades, separated by the P type (P[4], P[6] and P[8]), suggesting different origins for this genotype. Analysis of the VP6-encoding gene revealed that seven G9P[6] strains clustered close to antelope and bovine strains. A rare E6 NSP4 genotype was detected for strain RVA/Human-wt/MOZ/HCN1595/2017/G9P[4] and a genetically distinct lineage IV or OP354-like P[8] was identified for RVA/Human-wt/MOZ/HGJM0644/2015/G9P[8] strain. These results highlight the need for genomic surveillance of RVA strains detected in Mozambique and the importance of following a One Health approach to identify and characterize potential zoonotic strains causing acute gastroenteritis in Mozambican children.