Rotavirus infections and their genotype distribution pre- and post-vaccine introduction in Ethiopia: a systemic review and meta-analysis.

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.

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.

The objective of this study was to estimate, by a novel spatiotemporal approach in an environment of non-funded rotavirus (RV) vaccines, the RV vaccine effectiveness (VE) to prevent acute gastroenteritis primary care (AGE-PC)-attended episodes, demonstrating how indirect protection leads to underestimation of direct VE under high vaccine coverage (VC). This population-based retrospective cohort study used electronic healthcare registries including all children 2 months-5 years old, born from 2009 to 2018 in the Valencia Region (Spain). Direct RV VE preventing AGE-PC episodes was estimated using propensity score matching and Poisson regressions stratified by VC, adjusted by age and calendar season. Indirect VE was estimated by Poisson regression comparing AGE-PC rates in unvaccinated children among the different VC levels. A total of 563,442 children were included for the RV VC estimation; of them, 360,576 were included in the birth-cohort for VE analysis. RV VC showed strong variability among districts and seasons, rising on average from 21% in 2009/2010 to 55% in 2017/2018. The highest direct VE was found in vaccinated children from districts with 0-30% RV VC (16.4%) and the lowest in those from districts with ≥ 70% RV VC (9.7%). The indirect protection in unvaccinated children raised from 6 to 16.6% for those living with 20-30% and ≥ 70% VC, respectively. CONCLUSION: 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. WHAT IS KNOWN: • 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. WHAT IS NEW: • 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.

Global and Swedish review of rotavirus vaccines showed considerable reductions in morbidity and mortality.

Rotavirus infections cause severe gastroenteritis in small children, with both high morbidity and mortality. The rotavirus vaccine has been recommended by the World Health Organization since 2009 and was being used by 108 countries by 2019. It joined Sweden's national immunisation programme that year, after 5 years of selective regional use. This review summarises the baseline facts and evidence, the most common vaccines and the global direct and indirect effects, with a special focus on Sweden. CONCLUSION: The vaccine has had a considerable impact on global and Swedish morbidity and mortality, but some indirect effects and socioeconomic differentials need research.

18ß-Glycyrrhetinic acid inhibits the apoptosis of cells infected with rotavirus SA11 via the Fas/FasL pathway.

CONTEXT: 18ß-Glycyrrhetinic acid (18ß-GA), a pentacyclic triterpenoid saponin metabolite of glycyrrhizin, exhibits several biological activities. OBJECTIVE: We investigated the effects of 18ß-GA on MA104 cells infected with rotavirus (RV) and its potential mechanism of action. MATERIALS AND METHODS: Cell Counting Kit-8 was used to assess tissue culture infective dose 50 (TCID50) and 50% cellular cytotoxicity (CC50) concentration. MA104 cells infected with RV SA11 were treated with 18ß-GA (1, 2, 4, and 8 µg/mL, respectively). Cytopathic effects were observed. The virus inhibition rate, concentration for 50% of maximal effect (EC50), and selection index (SI) were calculated. Cell cycle, cell apoptosis, and mRNA and protein expression related to the Fas/FasL pathway were detected. RESULTS: TCID50 of RV SA11 was 10-4.47/100 µL; the CC50 of 18ß-GA on MA104 cells was 86.92 µg/mL. 18ß-GA showed significant antiviral activity; EC50 was 3.14 µg/mL, and SI was 27.68. The ratio of MA104 cells infected with RV SA11 in the G0/G1 phase and the G2/M phase decreased and increased, respectively, after 18ß-GA treatment. 18ß-GA significantly induced apoptosis in the infected cells. Furthermore, after 18ß-GA treatment, the mRNA and protein expression levels of Fas, FasL, caspase 3, and Bcl-2 decreased, whereas the expression levels of Bax increased. DISCUSSION AND CONCLUSIONS: The study demonstrates that 18ß-GA may be a promising candidate for the treatment of RV SA11 infection and provides theoretical support for the clinical development of glycyrrhizic acid compounds for the treatment of RV infection.

[A Recombinant Rotavirus Antigen Based on the Coat Protein of Alternanthera Mosaic Virus].

Thanks to their strong immunostimulating properties and safety for humans, plant viruses represent an appropriate basis for the design of novel vaccines. The coat protein of Alternanthera mosaic virus can form virus-like particles that are stable under physiological conditions and have adjuvant properties. This work presents a recombinant human rotavirus A antigen based on the epitope of rotavirus structural protein VP6, using Alternanthera mosaic virus coat protein as a carrier. An expression vector containing the gene of Alternanthera mosaic virus (MU strain) coat protein fused to the epitope of rotavirus protein VP6 was designed. Immunoblot analysis showed that the chimeric protein was effectively recognized by commercial polyclonal antibodies to rotavirus and therefore is a suitable candidate for development of a vaccine prototype. Interaction of the chimeric recombinant protein with the native coat protein of Alternanthera mosaic virus and its RNA resulted in the formation of ribonucleoprotein complexes that were recognized by anti-rotavirus antibodies.

A cost minimization analysis of α2b-interferon supplementation in complex pharmacotherapy of rotavirus infection in newborns.

Rotavirus is one of the most important causative agents of gastroenteritis in both infants and children worldwide, resulting in high mortality and morbidity, mainly in low-income, developing countries. Respective analysis of medical records of newborns hospitalized with acute gastroenteritis showed that the use of α2b-interferon in complex pharmacotherapy was characterized by faster reverse development of clinical manifestations of the disease than in patients who did not receive interferon. In our study, we also aimed to estimate the effectiveness of α2b-interferon supplementation in combination pharmacotherapy of newborns with suspected rotavirus infection. Achievement of this goal was possible with the construction of a decision tree model and determination of decision rules for inclusion of α2b-interferon supplementation into the complex pharmacotherapy. The input parameters of the model were hospitalization days of patients stratified by such signs as the presence or absence of rotavirus infection, as well as the additional inclusion of α2b-interferon supplementation in complex pharmacotherapy. The criterion for prediction and decision-making was global retrospective rotavirus prevalence. The feature of the simulation was that the costs were expressed as relative to each other, which allowed unifying the proposed methodology. Retrospective analysis of the clinical database of Ukrainian newborns with acute diarrhea has proved that the decision of α2b-interferon supplementation as additional treatment could be cost-saving under 7.4 times its lower price.

Group A rotavirus surveillance before vaccine introduction in Italy, September 2014 to August 2017.

IntroductionGroup A rotaviruses (RVA) are the leading cause of acute gastroenteritis (AGE) in young children, causing ca 250,000 deaths worldwide, mainly in low-income countries. Two proteins, VP7 (glycoprotein, G genotype) and VP4 (protease-sensitive protein, P genotype), are the basis for the binary RVA nomenclature. Although 36 G types and 51 P types are presently known, most RVA infections in humans worldwide are related to five G/P combinations: G1P[8], G2P[4], G3P[8], G4P[8], G9P[8].AimThis study aimed to characterise the RVA strains circulating in Italy in the pre-vaccination era, to define the trends of circulation of genotypes in the Italian paediatric population.MethodsBetween September 2014 and August 2017, after routine screening in hospital by commercial antigen detection kit, 2,202 rotavirus-positive samples were collected in Italy from children hospitalised with AGE; the viruses were genotyped following standard European protocols.ResultsThis 3-year study revealed an overall predominance of the G12P[8] genotype (544 of 2,202 cases; 24.70%), followed by G9P[8] (535/2,202; 24.30%), G1P[8] (459/2,202; 20.84%) and G4P[8] (371/2,202; 16.85%). G2P[4] and G3P[8] genotypes were detected at low rates (3.32% and 3.09%, respectively). Mixed infections accounted for 6.49% of cases (143/2,202), uncommon RVA strains for 0.41% of cases (9/2,202).ConclusionsThe emergence of G12P[8] rotavirus in Italy, as in other countries, marks this genotype as the sixth most common human genotype. Continuous surveillance of RVA strains and monitoring of circulating genotypes are important for a better understanding of rotavirus evolution and genotype distribution, particularly regarding strains that may emerge from reassortment events.

Pharmacoeconomic and epidemiological bases of optimal rotavirus vaccine supply for Ukrainian population.

OBJECTIVE: Introduction: Several studies has shown that rotaviruses play a leading role in the structure of acute intestinal infections (AII) of viral etiology in children. In the National vaccination calendar of Ukraine, vaccination against rotavirus infection (RVI) is classified as recommended, with the expected goal of reducing the number of severe RVI cases among under five-year-old children. Nevertheless, despite the positive epidemiological and clinical effects of vaccination against RVI, it remains unclear how appropriate the introduction of rotavirus vaccines is in terms of potential costs and benefits, as well as determining the optimal level of subsidy required to cover part of the costs of voluntary vaccination of the population. The aim: Study of optimal subsidy level of rotavirus vaccine in Ukraine using epidemiological and pharmacoeconomic modeling. PATIENTS AND METHODS: Materials and methods: The retrospective epidemiological data of the monthly RVI incidence in Ukraine as well as the population number from 2010 to 2016 formed the information basis for determining the transmission parameter of the viral agent. The scenario of RVI epidemic process as an acute intestinal infection from the point of view of mathematical epidemiology is best described by developed mathematical model. Cost-benefit of rotavirus vaccination was studied with the use of developed pharmacoeconomic criteria. RESULTS: Results and conclusions: Prediction of possible implications of RVI vaccination and finding optimal level of vaccine supply involves a comprehensive study of the epidemic process peculiarities of this infection with development of an adequate epidemiological model. We have proposed a model of RVI epidemiological process in Ukraine, determining its main parameters with the use of available retrospective data of anual number of RVI cases for the period from 2010 to 2016. The developed model was used as an analytical tool for analyzing influence of different levels of vaccine supply on vaccination cost-benefit. The results of research showed that the use of epidemiological modeling in pharmacoeconomic analysis of rotavirus vaccination made it possible to determine analytically optimal level of vaccination subsidy level.

Relationship between asymptomatic rotavirus infection and jaundice in neonates: a retrospective study.

BACKGROUND: Rotavirus (RV) infection in neonates can be mild or even asymptomatic. In RV infection, jaundice is often reported, but the relationship between jaundice and RV infection has not been studied. This study aimed to determine the importance of asymptomatic RV screening in neonates with jaundice. METHODS: Neonates from the neonatal intensive care unit (NICU) of Chonbuk National University Hospital, those transferred from local obstetrics and gynecology hospitals and outpatient clinics were selected from 2014 to 2017. The study included only infants aged between 3 and 28 days. Jaundice was defined according to gestational age and birth age, in accordance with the American Academy of Pediatrics guidelines criteria. RV infection was confirmed by a stool test, and RV screening and laboratory tests were performed at admission. RESULTS: Among 596 patients, 166 patients had jaundice. RV infection was observed in 70 (42%) jaundice patients. There were 36 (22%) jaundice patients with asymptomatic RV infection. Patients with onset of jaundice 3-7 days after birth had a high incidence of RV infection. When the RV test was positive, the risk of jaundice was significantly high [odds ratio (OR) 1.89; 95% confidence interval (CI), 1.20-2.98; p = 0.006]. CONCLUSIONS: Infants with the onset of jaundice > 3 days after birth were likely to have RV infection. Therefore, we suggest that screening tests for RV infection be included as part of the evaluation of jaundiced infants presenting to NICU.

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection.

BACKGROUND: The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. METHODS: We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. RESULTS: Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r2 = -0.63). CONCLUSIONS: The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

Rotavirus infection in children as of today (literature review).

INTRODUCTION: Urgency of the issue of rotavirus infection (RV) is stipulated by a special place in the structure of morbidity and mortality among young children. According to the data provided by WHO, 180 million diarrheal diseases with rotavirus etiology are registered every year. The aim of this article is to examine of current views on diagnosis and management of rotavirus infection in children. MATERIAL AND METHODS: The data of scientific literatures with the use of bibliosemantic method of study became the material for research. REVIEW: The urgent approaches to diagnosis and management of rotavirus infection in children is reflected in the article. CONCLUSIONS: The specific prophylaxis is recommended in order to prevent these infection. Apply monovalent vaccine, which has cross protection against different strains (G1, G2, G3, G4 and G9), and use pentavalent liquid vaccine containing G serotypes are recommended. It has cross-protection against different strains.

A case-control study of risk factors for rotavirus infections in adults, Denmark, 2005-2009.

Rotavirus (RV) infections affect young children, but can also occur in adults. We sought to identify risk factors for RV infections in adults aged ⩾18 years in Denmark, and to describe illness and genotyping characteristics. From March 2005 to February 2009, we recruited consecutive cases of laboratory-confirmed RV infection and compared them with healthy controls matched by age, gender and municipality of residence. We collected information on illness characteristics and exposures using postal questionnaires. We calculated univariable and multivariable matched odds ratios (mOR) with conditional logistic regression. The study comprised 65 cases and 246 controls. Illness exceeded 10 days in 31% of cases; 22% were hospitalized. Cases were more likely than controls to suffer serious underlying health conditions [mOR 5·6, 95% confidence interval (CI) 1·7-18], and to report having had close contact with persons with gastrointestinal symptoms (mOR 9·4, 95% CI 3·6-24), in particular young children aged 18 years. Close contact with young children or adults with gastrointestinal symptoms is the main risk factor for RV infection in adults in Denmark. RV vaccination assessments should consider that RV vaccination in children may indirectly reduce the burden of disease in adults.

In-season and out-of-season variation of rotavirus genotype distribution and age of infection across 12 European countries before the introduction of routine vaccination, 2007/08 to 2012/13.

The EuroRotaNet surveillance network has conducted rotavirus genotype surveillance since 2007 in 16 European countries. Using epidemiological and microbiological data from 39,786 genotyped rotavirus-positive specimens collected between September 2007 and August 2013, we assessed genotype distribution and age distribution of rotavirus gastroenteritis (RVGE) cases in and out of peak season in 12 countries which were yet to implement routine rotavirus vaccination. In multinomial multivariate logistic regression, adjusting for year, country and age, the odds of infection caused by genotype-constellation 2 DS-1-like stains (adjusted multinomial odds ratio (aM-OR) = 1.25; 95% confidence interval (CI): 1.13-1.37; p < 0.001), mixed or untypable genotypes (aM-OR = 1.55; 95% CI: 1.40-1.72; p < 0.001) and less common genotypes (aM-OR = 2.11; 95% CI:1.78-2.51; p < 0.001) increased out of season relative to G1P[8]. Age varied significantly between seasons; the proportion of RVGE cases younger than 12 months in the United Kingdom increased from 34% in season to 39% out of season (aM-OR = 1.66; 95% CI: 1.20-2.30), and the proportion five years and older increased from 9% in season to 17% out of season (aM-OR = 2.53; 95% CI: 1.67-3.82). This study provides further understanding of the rotavirus ecology before vaccine introduction, which will help interpret epidemiological changes in countries introducing or expanding rotavirus vaccination programmes.

Marked Elevation of Excitatory Amino Acids in Cerebrospinal Fluid Obtained From Patients With Rotavirus-Associated Encephalopathy.

Rotavirus is the most common cause of severe gastroenteritis in young children; however, its pathogenesis and immunity are not completely understood. Even less well recognized is rotavirus-induced central nervous system (CNS) involvement, which has been associated with seizure, encephalopathy and death, among others. To elucidate the host response to rotavirus infection, we retrospectively examined neurotransmitter amino acids in the cerebrospinal fluid (CSF) of 19 children with CNS involvement associated with rotavirus infection. Subjects were classified into two groups: those with encephalopathy followed by prolonged seizure (encephalopathy group) and those who had experienced afebrile, brief cluster of seizures without encephalopathy (cluster group). The levels of glutamate, glycine, and taurine in the encephalopathy group were significantly higher than those in the cluster group. Increased levels of excitatory amino acids in the CSF may induce neurological disorders and be related to disorder severity. To the best of our knowledge, this is the first report regarding amino acids in the CSF obtained from patients with rotavirus-induced CNS involvement. Further study is necessary to elucidate the role of CSF amino acid levels in rotavirus-induced CNS involvement.

Assessing the impacts of the first year of rotavirus vaccination in the United Kingdom.

The United Kingdom (UK) added rotavirus (RV) vaccine (Rotarix GlaxoSmithKline) to the national vaccine schedule in July 2013. During the 2012-2014 rotavirus seasons, children presenting to the Bristol Royal Hospital for Children Emergency Department with gastroenteritis symptoms had stool virology analysis (real-time PCR) and clinical outcome recorded. Nosocomial cases were identified as patients with non-gastroenteritis diagnosis testing positive for rotavirus > 48h after admission. In comparison to average pre-vaccine seasons, in the first year after vaccine introduction there were 48% fewer attendances diagnosed with gastroenteritis, 53% reduction in gastroenteritis admissions and a total saving of 330 bed-days occupancy. There was an overall reduction in number of rotavirus-positive stool samples with 94% reduction in children aged under one year and a 65% reduction in those too old to have been vaccinated. In the first year after the introduction of universal vaccination against rotavirus we observed a profound reduction in gastroenteritis presentations and admissions with a substantial possible herd effect seen in older children. Extrapolating these findings to the UK population we estimate secondary healthcare savings in the first year of ca £7.5 (€10.5) million. Ongoing surveillance will be required to determine the long-term impact of the RV immunisation programme.

Histo-Blood Group Antigen-Producing Bacterial Cocktail Reduces Rotavirus A, B, and C Infection and Disease in Gnotobiotic Piglets.

The suboptimal performance of rotavirus (RV) vaccines in developing countries and in animals necessitates further research on the development of novel therapeutics and control strategies. To initiate infection, RV interacts with cell-surface O-glycans, including histo-blood group antigens (HBGAs). We have previously demonstrated that certain non-pathogenic bacteria express HBGA- like substances (HBGA+) capable of binding RV particles in vitro. We hypothesized that HBGA+ bacteria can bind RV particles in the gut lumen protecting against RV species A (RVA), B (RVB), and C (RVC) infection in vivo. In this study, germ-free piglets were colonized with HBGA+ or HBGA- bacterial cocktail and infected with RVA/RVB/RVC of different genotypes. Diarrhea severity, virus shedding, immunoglobulin A (IgA) Ab titers, and cytokine levels were evaluated. Overall, colonization with HBGA+ bacteria resulted in reduced diarrhea severity and virus shedding compared to the HBGA- bacteria. Consistent with our hypothesis, the reduced severity of RV disease and infection was not associated with significant alterations in immune responses. Additionally, colonization with HBGA+ bacteria conferred beneficial effects irrespective of the piglet HBGA phenotype. These findings are the first experimental evidence that probiotic performance in vivo can be improved by including HBGA+ bacteria, providing decoy epitopes for broader/more consistent protection against diverse RVs.

Pathogen-Specific Benefits of Probiotic and Synbiotic Use in Childhood Acute Gastroenteritis: An Updated Review of the Literature.

Probiotics represent viable microorganisms which are found within the normal gut microbiota, that exert strain-specific benefits in the management of several gastrointestinal disorders in children, including acute gastroenteritis. This review aims to evaluate the pathogen-specific role of probiotic supplementation in childhood diarrhea. A search of scientific databases was conducted to identify studies which investigated efficacy of probiotics and synbiotics in influencing outcome of acute gastroenteritis of known etiology. We identified 32 studies, most of which analyzed impact of probiotic supplementation in rotavirus gastroenteritis, while a very limited number of these conducted a separate analysis on bacterial diarrhea. Lactobacillus rhamnosus (L. rhamnosus), L. reuteri and S. boulardii still remain the most researched strains, with a proven role in decreasing diarrhea and hospitalization duration, especially in the setting of rotavirus infection. Combined products containing at least one of the aforementioned strains also performed similarly and might also influence rotavirus fecal shedding. Rotavirus immunization status has also been proposed as a significant influencing factor of probiotic use impact. The paucity of research focusing on bacterial etiologies, as well as of clinical trials conducted within ambulatory care units leaves room for further research on the matter, which needs to include larger cohort studies.

A Clinical Nursing Care Study on the Prevalence of Rotavirus Infection and Acute Diarrhea in Vaccinated Chinese Pediatric Population from 2019-2022.

Purpose: To investigate the prevalence of rotavirus infection and acute diarrhea after immunization and further assess the quality of nursing care provided by the nurses to such patients. Methods: A total of 432 children aged 3-36 months with acute diarrhea between February 2019 and March 2022 were enrolled, and rotavirus testing was performed within 24 h using a rotavirus enzyme immunoassay kit. Clinical characteristics were evaluated, and regression analysis was performed. Results: Eighty vaccinated children (18.5%) were confirmed to have rotavirus infection out of 432 children. The prevalence of rotavirus positivity was the highest at 20-28 months (22 cases, 24.44%) and 11-19 months age group (27 cases, 22.50%). There is a significant association between rotavirus infection and hygiene score (p = 0.009). Based on the association with quality of nursing care, rotavirus infection was association with "appropriate care" (p = 0.001). Conclusion: Rotavirus infection was strongly associated with poor hygiene score which may be due to the hygienic nature of the mother and her family. Nursing care assessments revealed a huge gap between nurses and the guardians, which reflects the behavior of Chinese nurses. Thus, an intervention is required by the policymakers for implementing effective strategies of quality nursing for the improvement of the pediatric patients with rotavirus gastroenteritis.

Escherichia coli Nissle 1917 Enhances Efficacy of Oral Attenuated Human Rotavirus Vaccine in a Gnotobiotic Piglet Model.

Human rotavirus (HRV) infection is a major cause of viral gastroenteritis in young children worldwide. Current oral vaccines perform poorly in developing countries where efficacious vaccines are needed the most. Therefore, an alternative affordable strategy to enhance efficacy of the current RV vaccines is necessary. This study evaluated the effects of colonization of neonatal gnotobiotic (Gn) pigs with Escherichia coli Nissle (EcN) 1917 and Lacticaseibacillus rhamnosus GG (LGG) probiotics on immunogenicity and protective efficacy of oral attenuated (Att) HRV vaccine. EcN-colonized pigs had reduced virulent HRV (VirHRV) shedding and decreased diarrhea severity compared with the LGG-colonized group. They also had enhanced HRV-specific IgA antibody titers in serum and antibody secreting cell numbers in tissues pre/post VirHRV challenge, HRV-specific IgA antibody titers in intestinal contents, and B-cell subpopulations in tissues post VirHRV challenge. EcN colonization also enhanced T-cell immune response, promoted dendritic cells and NK cell function, reduced production of proinflammatory cytokines/Toll like receptor (TLR), and increased production of immunoregulatory cytokines/TLR expression in various tissues pre/post VirHRV challenge. Thus, EcN probiotic adjuvant with AttHRV vaccine enhances the immunogenicity and protective efficacy of AttHRV to a greater extent than LGG and it can be used as a safe and economical oral vaccine adjuvant.

The Combined Escherichia coli Nissle 1917 and Tryptophan Treatment Modulates Immune and Metabolome Responses to Human Rotavirus Infection in a Human Infant Fecal Microbiota-Transplanted Malnourished Gnotobiotic Pig Model.

Human rotavirus (HRV) is a major cause of childhood diarrhea in developing countries where widespread malnutrition contributes to the decreased oral vaccine efficacy and increased prevalence of other enteric infections, which are major concerns for global health. Neonatal gnotobiotic (Gn) piglets closely resemble human infants in their anatomy, physiology, and outbred status, providing a unique model to investigate malnutrition, supplementations, and HRV infection. To understand the molecular signatures associated with immune enhancement and reduced diarrheal severity by Escherichia coli Nissle 1917 (EcN) and tryptophan (TRP), immunological responses and global nontargeted metabolomics and lipidomics approaches were investigated on the plasma and fecal contents of malnourished pigs transplanted with human infant fecal microbiota and infected with virulent (Vir) HRV. Overall, EcN + TRP combined (rather than individual supplement action) promoted greater and balanced immunoregulatory/immunostimulatory responses associated with greater protection against HRV infection and disease in malnourished humanized piglets. Moreover, EcN + TRP treatment upregulated the production of several metabolites with immunoregulatory/immunostimulatory properties: amino acids (N-acetylserotonin, methylacetoacetyl-CoA), lipids (gamma-butyrobetaine, eicosanoids, cholesterol-sulfate, sphinganine/phytosphingosine, leukotriene), organic compound (biliverdin), benzenoids (gentisic acid, aminobenzoic acid), and nucleotides (hypoxathine/inosine/xanthine, cytidine-5'-monophosphate). Additionally, the levels of several proinflammatory metabolites of organic compounds (adenosylhomocysteine, phenylacetylglycine, urobilinogen/coproporphyrinogen) and amino acid (phenylalanine) were reduced following EcN + TRP treatment. These results suggest that the EcN + TRP effects on reducing HRV diarrhea in neonatal Gn pigs were at least in part due to altered metabolites, those involved in lipid, amino acid, benzenoids, organic compounds, and nucleotide metabolism. Identification of these important mechanisms of EcN/TRP prevention of HRV diarrhea provides novel targets for therapeutics development. IMPORTANCE Human rotavirus (HRV) is the most common cause of viral gastroenteritis in children, especially in developing countries, where the efficacy of oral HRV vaccines is reduced. Escherichia coli Nissle 1917 (EcN) is used to treat enteric infections and ulcerative colitis while tryptophan (TRP) is a biomarker of malnutrition, and its supplementation can alleviate intestinal inflammation and normalize intestinal microbiota in malnourished hosts. Supplementation of EcN + TRP to malnourished humanized gnotobiotic piglets enhanced immune responses and resulted in greater protection against HRV infection and diarrhea. Moreover, EcN + TRP supplementation increased the levels of immunoregulatory/immunostimulatory metabolites while decreasing the production of proinflammatory metabolites in plasma and fecal samples. Profiling of immunoregulatory and proinflammatory biomarkers associated with HRV perturbations will aid in the identification of treatments against HRV and other enteric diseases in malnourished children.