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INTRODUCTION: 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. METHODS: We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2 months to 5 years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. RESULTS: 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. CONCLUSIONS: 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 is a common cause of severe diarrhea in young children, and vaccines are crucial in preventing this illness. This study looked at how well two rotavirus vaccines, Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5), protect children against rotavirus gastroenteritis (RVGE), including infections caused by a new strain called G8P[8]. We analyzed data from children aged 2 months to 5 years who were hospitalized between 2020 and 2023. We compared children who tested positive for rotavirus (cases) with those who tested negative (controls) to determine how well the vaccines worked. Our results showed that both RV5 and LLR vaccines provided protection against RVGE. For RV5, three doses provided strong protection, while for LLR, two doses provided good protection. Against severe RVGE, three doses of RV5 were effective, while two doses of LLR also showed good protection.
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Previous systematic literature reviews of rotavirus genotype circulation in Europe and the Middle East are limited because they do not include country-specific prevalence data. This study documents country-specific evidence on the prevalence of rotavirus genotypes in Europe and the Middle East to enable more precise epidemiological modeling and contribute to the evidence-base about circulating rotavirus genotypes in the post-vaccination era. This study systematically searched PubMed, Embase and Scopus for all empirical epidemiological studies that presented genotype-specific surveillance data for countries in Europe and the Middle East published between 2006 and 2021. The STROBE checklist was used to assess the quality of included studies. Proportional meta-analysis was conducted using the generic inverse variance method with arcsine transformation and generalized linear-mixed models to summarize genotype prevalence. Our analysis estimated the genotype prevalence by country across three date categories corresponding with rotavirus seasons: 2006-2010, 2011-2015, 2016-2021. A total of 7601 deduplicated papers were identified of which 88 studies were included in the final review. Rotavirus genotypes exhibited significant variability across regions and time periods, with G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and, to a lesser extent G12P[8], being the most prevalent genotypes through different regions and time-periods. Uncommon genotypes included G3P[9] in Poland, G2P[6] in Iraq, G4P[4] in Qatar, and G9P[4] as reported by the European Rotavirus Network. There was high genotype diversity with routinely identified genotypes being G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]; there was high variability across time periods and regions. Continued surveillance at the national and regional levels is relevant to support further research and inform public health decision-making.
This study synthesizes data from rotavirus surveillance studies to characterize genotype-specific prevalence of rotavirus in Europe and the Middle East following the licensure of rotavirus vaccines in 2006. In line with previous pan-European studies, results highlight the lack of a single dominant genotype across this time period. There was high genotype diversity with G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] being the most commonly identified genotypes through different regions and time-periods.
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Genotipo , Infecciones por Rotavirus , Rotavirus , Humanos , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Rotavirus/genética , Rotavirus/clasificación , Europa (Continente)/epidemiología , Prevalencia , Medio Oriente/epidemiología , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunologíaRESUMEN
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.
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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
The inner capsid protein of rotavirus, VP6, emerges as a promising candidate for next-generation vaccines against rotaviruses owing to its abundance in virion particles and high conservation. However, the formation of inclusion bodies during prokaryotic VP6 expression poses a significant hurdle to rotavirus research and applications. Here, we employed experimental and computational approaches to investigate inclusion body formation and aggregation-prone regions (APRs). Heterologous recombinant VP6 expression in Escherichia coli BL21(DE3) cells resulted in inclusion body formation, confirmed by transmission electron microscopy revealing amorphous aggregates. Thioflavin T assay demonstrated incubation temperature-dependent aggregation of VP6 inclusion bodies. Computational predictions of APRs in rotavirus A VP6 protein were performed using sequence-based tools (TANGO, AGGRESCAN, Zyggregator, Waltz, FoldAmyloid, ANuPP, Camsol intrinsic) and structure-based tools (SolubiS, CamSol structurally corrected, Aggrescan3D). A total of 24 consensus APRs were identified, with 21 of them being surface-exposed in VP6. All identified APRs display a predominance of hydrophobic amino acids, ranging from 33 to 100%. Computational identification of these APRs corroborates our experimental observation of VP6 inclusion body or aggregate formation. Characterization of VP6's aggregation propensity facilitates understanding of its behaviour during prokaryotic expression and opens avenues for protein engineering of soluble variants, advancing research on rotavirus VP6 in pathology, therapy, and diagnostics.
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Antígenos Virales , Proteínas de la Cápside , Escherichia coli , Cuerpos de Inclusión , Rotavirus , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Antígenos Virales/genética , Antígenos Virales/metabolismo , Cuerpos de Inclusión/metabolismo , Rotavirus/genética , Rotavirus/metabolismo , Agregado de Proteínas , Simulación por Computador , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Post-translational modifications (PTMs), as epigenetic modifications, are significant in the interaction between virus and its host. However, it is unclear whether rotavirus (RV) causes changes in both the host cell epigenetic protein modification and the regulatory mechanism of viral replication. Here, we analyzed the proteome of Caco-2 cells to determine if acetylation modification occurred within the cells after RV infection. We found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein involved in glycolysis, was deacetylated at lysine 219 via histone deacetylase 9 (HDAC9) in 50 h after the RV infection. Remarkably, the deacetylation of GAPDH promoted RV replication. Finally, we found that glycolysis was alterable in Caco-2 cells by RV or the deacetylation of GAPDH lysine 219, using the Seahorse XF Glycolysis Stress Test. In conclusion, our results demonstrate for the first time that RV infection promoted deacetylation of GAPDH at lysine 219 in order to increase its own viral replication in Caco-2 cells.
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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 65â¯nm. 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 40⯵g 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.
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BACKGROUND: Monovalent rotavirus vaccine substantially reduced rotavirus disease burden after introduction (May 2014) in Madagascar. We examined the effectiveness and long-term impact on acute watery diarrhea and rotavirus-related hospitalizations among children <5 years old at two hospitals in Antananarivo, Madagascar (2010-2022). METHODS: We used a test-negative case-control design to estimate monovalent rotavirus vaccine effectiveness (VE) against laboratory-confirmed rotavirus hospitalizations among children age 6-23 months with documented vaccination status adjusted for year of symptom onset, rotavirus season, age group, nutritional status, and clinical severity. To evaluate the impact, we expanded to children age 0-59 months with acute watery diarrhea. First, we used admission logbook data to compare the proportion of all hospitalizations attributed to diarrhea in the pre-vaccine (January 2010-December 2013), transition period (January 2014-December 2014), and post-vaccine (January 2015-December 2022) periods. Second, we used active surveillance data (June 2013-May 2022) to describe rotavirus positivity and detected genotypes by vaccine introduction period and surveillance year (1 June-31 May). RESULT: Adjusted VE of at least one dose against hospitalization due to rotavirus diarrhea among children age 6-23 months was 61 % (95 % CI: -39 %-89 %). The annual median proportion of hospitalizations attributed to diarrhea declined from 28 % in the pre-vaccine to 10 % in the post-vaccine period. Rotavirus positivity among hospitalized children age 0-59 months with acute watery diarrhea was substantially higher during the pre-vaccine (59 %) than the post-vaccine (23 %) period. In the pre-vaccine period, G3P[8] (76 %) and G2P[4] (12 %) were the dominant genotypes detected. Although genotypes varied by surveillance year, G1P[8] and G2P[4] represented >50 % of the genotypes detected post-introduction. CONCLUSIONS: Rotavirus vaccine has been successfully implemented in Madagascar's routine childhood immunization program and had a large impact on rotavirus disease burden, supporting continued use of rotavirus vaccines in Madagascar.
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The causes of diarrhea after ten years of rotavirus vaccination in Rwanda were investigated in 496 children with and 298 without diarrhea using a real-time PCR. Rotavirus was detected in 11% of children with diarrhea (OR 2.48, P=0.002). Comparison of population attributable fractions (PAF) show that Shigella (PAF=11%) and ETEC-eltB (PAF=12%) have replaced rotavirus as the main causative agents. The PAF for rotavirus had declined from 41% pre-vaccination to 6.5%, indicating that rotavirus has become one among several similarly important causes of childhood diarrhea in Rwanda. A rotavirus genotype shift to G3P[8] points at the importance of continued genotype surveillance.
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BACKGROUND: Calf diarrhea is a major cause of morbidity and mortality in the livestock sector worldwide and it can be caused by multiple infectious agents. In Ethiopia, cattle are the most economically important species within the livestock sector, but at the same time the young animals suffer from high rates of morbidity and mortality due to calf diarrhea. However, studies including both screening and molecular characterization of bovine enteric pathogens are lacking. Therefore, we aimed to both detect and molecularly characterize four of the major enteric pathogens in calf diarrhea, Enterotoxigenic Escherichia coli (E. coli K99 +), Cryptosporidium spp., rotavirus A (RVA), and bovine coronavirus (BCoV) in calves from central Ethiopia. Diarrheic and non-diarrheic calves were included in the study and fecal samples were analyzed with antigen-ELISA and quantitative real-time PCR (qPCR). Positive samples were further characterized by genotyping PCRs. RESULTS: All four pathogens were detected in both diarrheic and non-diarrheic calves using qPCR and further characterization showed the presence of three Cryptosporidium species, C. andersoni, C. bovis and C. ryanae. Furthermore, genotyping of RVA-positive samples found a common bovine genotype G10P[11], as well as a more unusual G-type, G24. To our knowledge this is the first detection of the G24 RVA genotype in Ethiopia as well as in Africa. Lastly, investigation of the spike gene revealed two distinct BCoV strains, one classical BCoV strain and one bovine-like CoV strain. CONCLUSIONS: Our results show that Cryptosporidium spp., E. coli K99 + , RVA and BCoV circulate in calves from central Ethiopia. Furthermore, our findings of the rare RVA G-type G24 and a bovine-like CoV demonstrates the importance of genetic characterization.
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Enfermedades de los Bovinos , Coronavirus Bovino , Cryptosporidium , Diarrea , Heces , Rotavirus , Animales , Bovinos , Etiopía/epidemiología , Diarrea/veterinaria , Diarrea/virología , Diarrea/microbiología , Diarrea/parasitología , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/microbiología , Enfermedades de los Bovinos/parasitología , Heces/virología , Heces/parasitología , Heces/microbiología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Rotavirus/clasificación , Cryptosporidium/aislamiento & purificación , Cryptosporidium/genética , Cryptosporidium/clasificación , Coronavirus Bovino/genética , Coronavirus Bovino/aislamiento & purificación , Escherichia coli Enterotoxigénica/aislamiento & purificación , Escherichia coli Enterotoxigénica/genética , Genotipo , Criptosporidiosis/epidemiología , Infecciones por Rotavirus/veterinaria , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiologíaRESUMEN
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.
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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
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.
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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
Rotaviruses (RVs) are classified into nine species, A-D and F-J, with species A being the most studied. In rotavirus of species A (RVA), replication occurs in viroplasms, which are cytosolic globular inclusions composed of main building block proteins NSP5, NSP2, and VP2. The co-expression of NSP5 with either NSP2 or VP2 in uninfected cells leads to the formation of viroplasm-like structures (VLSs). Although morphologically identical to viroplasms, VLSs do not produce viral progeny but serve as excellent tools for studying complex viroplasms. A knowledge gap exists regarding non-RVA viroplasms due to the lack of specific antibodies and suitable cell culture systems. In this study, we explored the ability of NSP5 and NSP2 from non-RVA species to form VLSs. The co-expression of these two proteins led to globular VLSs in RV species A, B, D, F, G, and I, while RVC formed filamentous VLSs. The co-expression of NSP5 and NSP2 of RV species H and J did not result in VLS formation. Interestingly, NSP5 of all RV species self-oligomerizes, with the ordered C-terminal region, termed the tail, being necessary for self-oligomerization of RV species A-C and G-J. Except for NSP5 from RVJ, all NSP5 interacted with their cognate NSP2. We also found that interspecies VLS are formed between closely related RV species B with G and D with F. Additionally, VLS from RVH and RVJ formed when the tail of NSP5 RVH and RVJ was replaced by the tail of NSP5 from RVA and co-expressed with their respective NSP2. IMPORTANCE: Rotaviruses (RVs) are classified into nine species, A-D and F-J, infecting mammals and birds. Due to the lack of research tools, all cumulative knowledge on RV replication is based on RV species A (RVA). The RV replication compartments are globular cytosolic structures named viroplasms, which have only been identified in RV species A. In this study, we examined the formation of viroplasm-like structures (VLSs) by the co-expression of NSP5 with NSP2 across RV species A to J. Globular VLSs formed for RV species A, B, D, F, G, and I, while RV species C formed filamentous structures. The RV species H and J did not form VLS with their cognates NSP5 and NSP2. Similar to RVA, NSP5 self-oligomerizes in all RV species, which is required for VLS formation. This study provides basic knowledge of the non-RVA replication mechanisms, which could help develop strategies to halt virus infection across RV species.
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Rotavirus , Proteínas no Estructurales Virales , Replicación Viral , Rotavirus/genética , Rotavirus/metabolismo , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/genética , Animales , Humanos , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Línea Celular , ARN Polimerasa Dependiente del ARN/metabolismo , ARN Polimerasa Dependiente del ARN/genética , Infecciones por Rotavirus/virología , Proteínas de Unión al ARNRESUMEN
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.
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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
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.
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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
Equine rotavirus species A (ERVA) G3P[12] and G14P[12] are two dominant genotypes that cause foal diarrhoea with a significant economic impact on the global equine industry. ERVA can also serve as a source of novel (equine-like) rotavirus species A (RVA) reassortants with zoonotic potential as those identified previously in 2013-2019 when equine G3-like RVA was responsible for worldwide outbreaks of severe gastroenteritis and hospitalizations in children. One hurdle to ERVA research is that the standard cell culture system optimized for human rotavirus replication is not efficient for isolating ERVA. Here, using an engineered cell line defective in antiviral innate immunity, we showed that both equine G3P[12] and G14P[12] strains can be rapidly isolated from diarrhoeic foals. The genome sequence analysis revealed that both G3P[12] and G14P[12] strains share the identical genotypic constellation except for VP7 and VP6 segments in which G3P[12] possessed VP7 of genotype G3 and VP6 of genotype I6 and G14P[12] had the combination of VP7 of genotype G14 and VP6 of genotype I2. Further characterization demonstrated that two ERVA genotypes have a limited cross-neutralization. The lack of an in vitro broad cross-protection between both genotypes supported the increased recent diarrhoea outbreaks due to equine G14P[12] in foals born to dams immunized with the inactivated monovalent equine G3P[12] vaccine. Finally, using the structural modelling approach, we provided the genetic basis of the antigenic divergence between ERVA G3P[12] and G14P[12] strains. The results of this study will provide a framework for further investigation of infection biology, pathogenesis and cross-protection of equine rotaviruses.
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Antígenos Virales , Diarrea , Genotipo , Enfermedades de los Caballos , Infecciones por Rotavirus , Rotavirus , Animales , Caballos , Rotavirus/genética , Rotavirus/inmunología , Rotavirus/aislamiento & purificación , Rotavirus/clasificación , Infecciones por Rotavirus/veterinaria , Infecciones por Rotavirus/virología , Infecciones por Rotavirus/inmunología , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/inmunología , Diarrea/virología , Diarrea/veterinaria , Antígenos Virales/genética , Antígenos Virales/inmunología , Genoma Viral/genética , Filogenia , Línea CelularRESUMEN
Background: Rotavirus is globally recognized as an important cause of acute gastroenteritis in young children. Whereas previous studies focused more on sporadic diarrhea, the epidemiological characteristics of rotavirus outbreaks have not been systematically understood. Methods: This systematic review was carried out according to the Preferred Reporting Items for Systematic Review and Meta-Analysis standards, WANFANG, China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science databases were searched from database inception to February 20, 2022. We used SPSS 21.0 statistical software for data analysis, RStudio1.4.1717, and ArcGIS trial version for plotting bar graphs and maps. Results: Among 1,596 articles, 78 were included, with 92 rotavirus outbreaks and 96,128 cases. Most outbreaks (67.39%, 62/92) occurred in winter and spring. The number of rotavirus outbreaks reported in the eastern region was more than that in the western region. Outbreaks were most commonly reported in villages (33/92, 35.87%), followed by hospitals (19, 20.65%). The outbreak duration was longer in factories and workers' living places, and villages, while it was shorter in hospitals. Waterborne transmission was the main transmission mode, with the longest duration and the largest number of cases. Rotavirus groups were identified in 66 outbreaks, with 40 outbreaks (60.61%) caused by Group B rotaviruses and 26 outbreaks (39.39%) caused by Group A rotaviruses. Significant differences were found in duration, number of cases, settings, population distribution, and transmission modes between Groups A and B rotavirus outbreaks. Conclusion: Rotavirus is an important cause of acute gastroenteritis outbreaks in China. It should also be considered in the investigation of acute gastroenteritis outbreaks, especially norovirus-negative outbreaks.
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Brotes de Enfermedades , Infecciones por Rotavirus , Humanos , Infecciones por Rotavirus/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , China/epidemiología , Rotavirus , Gastroenteritis/epidemiología , Gastroenteritis/virología , Estaciones del AñoRESUMEN
A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.
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COVID-19 , Síndrome de Liberación de Citoquinas , Humanos , Síndrome de Liberación de Citoquinas/inmunología , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/terapia , COVID-19/virología , Linfohistiocitosis Hemofagocítica/terapia , Linfohistiocitosis Hemofagocítica/inmunología , Linfohistiocitosis Hemofagocítica/virología , SARS-CoV-2 , Fiebres Hemorrágicas Virales/virologíaRESUMEN
Introduction: approximately over 80% of mortalities due to rotavirus occur in countries that have limited resources, especially in sub-Saharan Africa and South Asia. The study was intended to determine the genetic characteristics of rotavirus A in children exhibiting gastroenteritis at Kericho County Referral Hospital. Methods: the study design was cross-sectional. Consecutive sampling was engaged obtaining a sample size of 200 stool samples. Genetic characterization of group A rotavirus strains was done using Enzyme-Linked Immunosorbent Assay. Positive samples underwent Sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Afterwards viewing of the RNA double strands of the rotavirus genome in gels was done using Silver Nitrate. The positive samples underwent RT-PCR amplification followed by sequencing on the pieces of the VP7 or VP4 gene obtained. Results: one hundred and six (53%) samples from males and 94 (47%) from females. Twenty-three samples were positive hence a prevalence of 11.5%. The most affected demographics were children of guardians with secondary school education (51%). The most affected social economic status was housewives (46.5%). The most affected age was 21-30 months at 26.5%. Long electropherotypes were in 22 samples (96%). The G3 genotype of rotavirus A was prevalent 16/23 (69.57%). Conclusion: rotavirus prevalence was 11.5%. The G3 genotype was the most prevalent in circulation. The occurrence of non-typable strains indicated that the strains may be diversified emphasizing the need to include emerging strains within the vaccines in use. Hence the need to continuously monitor the effects in older children.
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Heces , Gastroenteritis , Genotipo , Infecciones por Rotavirus , Rotavirus , Humanos , Gastroenteritis/virología , Gastroenteritis/epidemiología , Rotavirus/genética , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Femenino , Preescolar , Estudios Transversales , Masculino , Lactante , Enfermedad Aguda , Prevalencia , Heces/virología , Kenia/epidemiología , Niño , Ensayo de Inmunoadsorción Enzimática , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
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.
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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
Background: The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have led to substantial decreases in case numbers of infectious diseases in several countries worldwide. As NPIs were gradually lifted, intense or out-of-season outbreaks of respiratory and gastrointestinal diseases were reported, raising the hypothesis of a potential catch-up effect of infections. By analysing surveillance data from the federal reporting system for notifiable infectious diseases, we aimed to assess the potential impact of lifting COVID-19 associated NPIs on notifications of selected infectious diseases in Bavaria, 2022. Methods: We compared influenza, chickenpox, norovirus gastroenteritis, rotavirus gastroenteritis weekly case numbers in a pre-pandemic period (2016-2019) and 2022 using two time series analyses approaches: (i) a predictive model forecasting weekly case numbers for the pandemic years 2020-2022, based on 2016-2019 data, (ii) interrupted time series model, based on 2016-2022 data, including a term per pandemic period. Results: In 2022, incidence rates were higher compared to pre-pandemic period for influenza (IRR = 3.47, 95%CI: 1.49-7.94) and rotavirus gastroenteritis (IRR = 1.36, 95%CI: 0.95-1.93), though not significant for rotavirus gastroenteritis. Conversely, case numbers remained significantly below pre-pandemic levels for chickenpox (IRR = 0.52, 95%CI: 0.41-0.65) and norovirus gastroenteritis (IRR = 0.59, 95%CI: 0.42-0.82). Seasonality changed notably for influenza, showing an earlier influenza wave compared to pre-pandemic periods. Conclusion: The lifting of NPIs was associated with heterogenic epidemiological patterns depending on the selected disease. The full impact of NPIs and their discontinuation may only become clear with continued monitoring and assessment of potential additional contributing factors.