Rotavirus Infection Research Articles

Nucleolin-RNA interaction modulates rotavirus replication.

Rotavirus infection is a leading cause of gastroenteritis in children worldwide; the genome of this virus is composed of 11 segments of dsRNA packed in a triple-layered protein capsid. Here, we investigated the role of nucleolin, a protein with diverse RNA-binding domains, in rotavirus infection. Knocking down the expression of nucleolin in MA104 cells by RNA interference resulted in a remarkable 6.3-fold increase in the production of infectious rhesus rotavirus (RRV) progeny, accompanied by an elevated synthesis of viral mRNA and genome copies. Further analysis unveiled an interaction between rotavirus segment 10 (S10) and nucleolin, potentially mediated by G-quadruplex domains on the viral genome. To determine whether the nucleolin-RNA interaction regulates RRV replication, MA104 cells were transfected with AGRO100, a compound that forms G4 structures and selectively inhibits nucleolin-RNA interactions by blocking the RNA-binding domains. Under these conditions, viral production increased by 1.5-fold, indicating the inhibitory role of nucleolin on the yield of infectious viral particles. Furthermore, G4 sequences were identified in all 11 RRV dsRNA segments, and transfection of oligonucleotides representing G4 sequences in RRV S10 induced a significant increase in viral production. These findings show that rotavirus replication is negatively regulated by nucleolin through the direct interaction with the viral RNAs by sequences forming G4 structures.IMPORTANCEViruses rely on cellular proteins to carry out their replicative cycle. In the case of rotavirus, the involvement of cellular RNA-binding proteins during the replicative cycle is a poorly studied field. In this work, we demonstrate for the first time the interaction between nucleolin and viral RNA of rotavirus RRV. Nucleolin is a cellular protein that has a role in the metabolism of ribosomal rRNA and ribosome biogenesis, which seems to have regulatory effects on the quantity of viral particles and viral RNA copies of rotavirus RRV. Our study adds a new component to the current model of rotavirus replication, where cellular proteins can have a negative regulation on rotavirus replication.

Microbiota-Derived Extracellular Vesicles as a Postbiotic Strategy to Alleviate Diarrhea and Enhance Immunity in Rotavirus-Infected Neonatal Rats.

Rotavirus (RV) infection is a major cause of acute gastroenteritis in children under 5 years old, resulting in elevated mortality rates in low-income countries. The efficacy of anti-RV vaccines is limited in underdeveloped countries, emphasizing the need for novel strategies to boost immunity and alleviate RV-induced diarrhea. This study explores the effectiveness of interventions involving extracellular vesicles (EVs) from probiotic and commensal E. coli in mitigating diarrhea and enhancing immunity in a preclinical model of RV infection in suckling rats. On days 8 and 16 of life, variables related to humoral and cellular immunity and intestinal function/architecture were assessed. Both interventions enhanced humoral (serum immunoglobulins) and cellular (splenic natural killer (NK), cytotoxic T (Tc) and positive T-cell receptor γδ (TCRγδ) cells) immunity against viral infections and downregulated the intestinal serotonin receptor-3 (HTR3). However, certain effects were strain-specific. EcoR12 EVs activated intestinal CD68, TLR2 and IL-12 expression, whereas EcN EVs improved intestinal maturation, barrier properties (goblet cell numbers/mucin 2 expression) and absorptive function (villus length). In conclusion, interventions involving probiotic/microbiota EVs may serve as a safe postbiotic strategy to improve clinical symptoms and immune responses during RV infection in the neonatal period. Furthermore, they could be used as adjuvants to enhance the immunogenicity and efficacy of anti-RV vaccines.

Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus

ABSTRACT Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. Cryptosporidium infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.

A Cross-sectional Study on the Role of Rotavirus and Microbial Co-infection in Children with Acute Diarrhea in Vietnam

Background: Rotavirus is the leading cause of acute diarrhea in children. Understanding co-infections with other bacterial or viral microorganisms alongside Rotavirus is crucial. Objectives: This study aimed to determine the frequency distribution of Rotavirus infections and related co-infections in children with acute diarrhea. Additionally, it sought to compare 2 groups: Those with Rotavirus mono-infection and those with microbial co-infections in terms of clinical and laboratory characteristics. Methods: In this cross-sectional study, we collected a total of 171 rectal swabs at Can Tho Children′s Hospital, Can Tho City, Vietnam, from November 2022 to April 2023. We used real-time polymerase chain reaction (PCR) to detect infectious agents. Patients underwent examinations and tests to assess clinical features and laboratory data. Results: Rotavirus was the most commonly detected agent (42.7%). The incidence of co-infection with other bacterial or viral microorganisms alongside Rotavirus was 45.2%. Acute diarrhea caused by Rotavirus significantly increased the percentage of children with watery stools (P = 0.004) and vomiting (P < 0.001) and led to a greater number of loose stools per day (P = 0.007) compared to cases without Rotavirus. However, there were no significant differences in clinical features or laboratory data between cases with Rotavirus mono-infection and those with co-infections involving other bacterial or viral microorganisms. Conclusions: This study sheds light on the prevalence of Rotavirus and co-infections in Vietnam. Among these findings, identifying Rotavirus in children with acute diarrhea is more critical than detecting co-infecting agents.

Solução intravenosa poliiônica com concentração elevada de lactato (84 mEq/L) é eficaz para o tratamento de bezerros com diarreia

ABSTRACT This study aimed to evaluate the effectiveness of an electrolyte solution with a high lactate concentration (84mEq/L; L84) in correcting imbalances in diarrheal calves. Another solution with similar electrolyte composition, containing 84mEq/L of bicarbonate (B84) was used for comparison. Diarrhea was induced in neonatal calves by rotavirus infection, sucrose ingestion and furosemide administration. When a moderate degree of metabolic acidosis was reached, the calves were treated with intravenous infusion of L84 (n=10) or B84 (n=10) solutions. Venous blood and urine samples were collected before starting the infusion (0 h), in the middle (2.5 h), at the end (5.0 h) and 2.5 hours later. Total plasma protein concentration, blood and urine pH, blood pCO2, HCO3 -, and BE, plasma and urine concentration of L-lactate, and serum and urine concentrations of Na+, K+, and Cl- were measured. Strong ion difference, total concentration of non-volatile weak acids, anion gap, strong ion gap, percentage change in plasma volume, and urinary fractional clearances of Na+, K+, Cl-, and L-lactate were calculated. The calves demonstrated moderate dehydration, hypernatremia, hyperchloremia, metabolic acidosis, and unmeasured anion accumulation. These changes were completely corrected with the L84 solution, and the effects did not differ from those observed with B84 solution. The calves recovered without further therapeutic procedures, demonstrating that the L84 solution was effective for treating diarrheal calves.

Герпетические инфекции и воспалительные заболевания кишечника

It is well known that herpes viruses are pantropic; therefore, herpes infections have a varied clinical picture. There are studies establishing a connection between the course of inflammatory bowel diseases, the effectiveness of their treatment, and the detection of herpesvirus DNA in the mucous membrane of the colon. The article examines a case of reactivation of a chronic herpetic infection with a predominant clinical picture of colitis against the background of immunosuppression after successive coronavirus SARS-Cov-2 and rotavirus infections. Against the background of antiviral therapy, clinical improvement was noted, laboratory parameters and histological analyzes were normalized.

CONTENT OF COLOSTRAL ANTIBODIES IN CALVES WITH APPLIED ASSOCIATED VACCINE BAKTOVIR-6

The article presents the results on serological studies of cattle blood serum after immunization with associated vaccines against infectious rhinotracheitis, viral diarrhea, rotavirus and coronavirus infections, colibacillosis and salmonellosis in calves. Immunization of animals led to a pronounced immune response in vaccinated pregnant cows, with the accumulation of specific antibodies in values from 4.0 log2 to 10.4 log2. High levels of specific antibodies in the blood serum of calves born from cows vaccinated against the most common dried period infectious diseases were determined in values from 4.0 log2 to 10.0 log2.

Caracterización microbiológica y análisis genético de bacterias aisladas de hemocultivos y muestras fecales en terneros con síntomas de septicemia y diarrea

Diarrhea in calves can be caused by bacteria, viruses, and parasites. Among bacteria, Escherichia coli is considered responsible for the appearance of enteric diarrhea and septicemia in these animals, conditions that require immediate attention. Among E. coli infections of calves, more focus is placed on intestinal pathogenic (InPEC) infections, and extra – intestinal pathogenic (ExPEC) infections are ignored. This study aims to reveal which E. coli pathotype causes the infection as molecular and serotype and to reveal the differences according to the age groups of the factors in the herd. Blood and fecal samples of 10 calves aged 3 – 15 d with diarrhea were analyzed. The primary agent causing enteritis was determined by examining the stool samples with BoviD – 5 Ag. Then, samples were subjected to culture and identification processes. It was determined that the stool samples had 2/10 with E. coli K99, 4/10 with rotavirus, and 4/10 with mixed rotavirus infections and Cryptosporidium spp. E. coli was detected from all blood samples by hemoculture. The study isolated only the SepEC and ETEC groups from samples. All SepEC isolates were determined to carry type 1 pilus responsible for adhesion. In addition, it was determined that 9/10 of the SepEC group carried the colicin V gene responsible for pathogenicity. Also, all E. coli isolated from calves aged 3 – 15 d were found to be resistant to antibiotics. In conclusion, primary enteritis is caused by rotavirus Cryptosporidium spp. and ETEC. However, it was determined that SepEC group E. coli causing septicemia showed different antigenic and genetic features than E. coli in the intestinal tract. The virulence factors of the SepEC group may vary due to genomic plasticity, and their antigenic structures should be more closely examined and added to vaccine test studies.

Antirotaviral activity of dairy byproducts enriched in fractions from hyperimmune bovine colostrum: the effect of thermal and high hydrostatic pressure treatments.

Nowadays, rotaviruses remain a major health burden, especially in developing countries, and strategies complementary to vaccination are needed. In this view, dairy fractions have attracted great scientific interest, due to their high content of bioactive compounds. The objective of this study was to evaluate the antiviral activity of whey and buttermilk enriched in proteins from hyperimmune bovine colostrum (HBC) against rotavirus. The enriched fractions were spray-dried and subsequently tested for their neutralizing activity against the bovine rotavirus WC3 strain in vitro, using differentiated Caco-2/TC7 cells. The highest antirotaviral activity was observed when whey and buttermilk were enriched in purified immunoglobulin G (IgG), showing complete rotavirus neutralization at concentrations of 3 and 6 mg mL-1 for whey and buttermilk, respectively. Additionally, the use of a crude immunoglobulin fraction also gave satisfactory results. The inhibitory activities of all samples significantly decreased after the application of heat, except for the IgG-enriched buttermilk which showed a slight increase of activity following the application of short-time treatments (75 or 85 °C for 20 s). This sample also showed a significant increase of activity (13%) after the application of low-intensity high hydrostatic pressure treatment (400 MPa for 5 min). The maximum loss of bioactivity was observed at 600 MPa for 10 min (31 and 20% for whey- and buttermilk-based formulas, respectively). This study provides relevant information on the potential of whey, buttermilk, and HBC to be part of functional products as complementary strategies to combat rotavirus infections.

Association between Rotavirus Infection and Irritable Bowel Syndrome: A Case-Control Study in Kerman, Iran

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease of unknown etiology. Researchers have recently drawn attention to the possible role of viruses in the development of IBS and provided evidence in this regard. In this study, it was decided to investigate the possible role of rotavirus infection in the onset of IBS. Methods: Stool and serum samples were collected from 40 patients with IBS and 40 healthy individuals. To evaluate the previous exposure to rotavirus we checked the presence and concentration of anti-rotavirus IgG by ELISA. ELISA test was performed on the serum samples. A real-time polymerase chain reaction (PCR) test was also used to measure the viral load in the stool. Finally, the data were analyzed by SPSS version 22 software. Results: No significant relationship was found between anti-rotavirus IgG presence and its level in the serum of case and healthy individuals (P value>0.05). Moreover, there was no significant difference between the viral genome load in the stool samples of the two groups (P value>0.05). Conclusion: According to the results, it seems unlikely that a link exists between rotavirus infection and the onset of IBS, but the possible role of other gastrointestinal viruses, including coronavirus, remains.

Evidence-based comparism of conventional sandwich enzyme-linked immunosorbent assay (ELISA) and lateral flow (LAT) method in the detection of human rotavirus pathogen for prompt monitoring and robust surveillance outcome

Introduction: Rotavirus has been known to be the causative agent of some cases of gastroenteritis across the world. A disease common in infants and young children ≤5 years of age, mostly in developing countries. This study was aimed at comparing the effectiveness of the sandwich ELISA and lateral flow method for the detection of rotavirus infection. Materials and methods: The human rotavirus sample (Code Number: BO218) at a concentration of 1x108/ml) was obtained from Dako A/S, Denmark and subsequently, a 1/4 serial dilution was performed to obtain varying concentrations. The already confirmed positive rotavirus samples obtained from the Nimi Briggs Hospital of the Rivers State University, Port Harcourt were used to evaluate and validate the sensitivity of both methods. Data obtained from ELISA method were analysed statistically using Microsoft excel and the spearman test to analyse the linear relationship between the absorbance and concentration of rotavirus expressed in number of rotavirus particles per ml. Results: The evidence-based results outcome showed that the ELISA approach was more sensitive to detecting the presence of rotavirus in the samples at the concentration of 381.5 rotavirus particle per ml, while that of LAT detected the presence of rotavirus at the concentration of 1,562,500 rotavirus particle per ml. The plot of absorbance and rotavirus particles following the serial dilution was plotted using Microsoft excel and the relationship between concentration and rotavirus was established. The result of the plot of the mean absorbance values against the rotavirus concentration (number of rotavirus per ml) showed an exponential increase in the absorbance value until a plateau was established as the concentration approached 1.0 × 108/ml of rotavirus in the solution. Also, the correlation of the absorbance and rotavirus concentration and a straight-line graph was plotted showing a correlation value of R2 =0.4505 with an intercept at 1.4236. Discussion: However, the ELISA is more robust, though very expensive for monitoring and surveillance of diarrhoea cases unlike the LAT method which is very cheap, with less expertise required, thus would be recommended for health care facilities in our remote communities.

Postbiotic Activities of Bifidobacterium adolescentis: Impacts on Viability, Structural Integrity, and Cell Death Markers in Human Intestinal C2BBe1 Cells.

Acute diarrheal disease (ADD) caused by rotavirus (RV) contributes significantly to morbidity and mortality in children under five years of age. Currently, there are no specific drugs for the treatment of RV infections. Previously, we reported the anti-rotaviral activity of the protein metabolites derived from Bifidobacterium adolescentis. In this study, our aim was to assess the impact of B. adolescentis-secreted proteins (BaSP), with anti-rotaviral activity on the human intestinal C2BBe1 cell line. We initiated the production of BaSP and subsequently confirmed its anti-rotaviral activity by counting the infectious foci using immunocytochemistry. We then exposed the C2BBe1 cells to various concentrations of BaSP (≤250 µg/mL) for 72 h. Cell viability was assessed using the MTT assay, cell monolayer integrity was monitored through transepithelial electrical resistance (TEER), and cytoskeleton architecture and tight junctions (TJs) were examined using confocal microscopy with F-actin and occludin staining. Finally, we utilized a commercial kit to detect markers of apoptosis and necrosis after 24 h of treatment. The results demonstrated that BaSP does not have adverse effects on C2BBe1 cells. These findings confirm that BaSP inhibits rotavirus infectivity and has the potential to strengthen intestinal defense against viral and bacterial infections via the paracellular route.

In Vitro Antiviral Potential of Cucurbitaceae Ecballium elaterium and Its Extract Containing Protease Inhibitors against Bovine Rotavirus

Bovine rotaviruses (BRVs) are significant causative agents of severe diarrhea in newborn calves, resulting in substantial economic losses in the livestock industry. Inhibition of bovine rotavirus using extracts prepared from a Cucurbitaceae plant, which contains trypsin protease inhibitors, might offer a potential anti-rotaviral effect in vitro. Ecballium elaterium (E. elaterium) belongs to the Cucurbitaceae family, indigenous to the Mediterranean, contains E. elaterium trypsin isoinhibitors (EETIso), and has been used in traditional medicine. This study aimed to evaluate the in vitro efficacy of E. elaterium extract against bovine rotavirus infections. Ethanol extracts were prepared from E. elaterium seeds and fruit juice, and their non-toxic concentrations were determined using MA-104 cells. The cells were infected with bovine rotavirus in the presence of E. elaterium extract. The results demonstrated a significant decrease in the rotavirus titer in vitro upon treatment with the E. elaterium extract, suggesting its potential as a therapeutic agent against bovine rotavirus-induced diarrhea in calves. The utilization of E. elaterium extract may contribute to reduced calf mortality, lower medication costs, and improved economic value in cattle farming.

Improving utilization of rotavirus vaccination among children in Kuwait: an intervention study

Vaccination against rotavirus is an effective strategy to overcome the consequences of rotavirus infection. This study aims to raise the knowledge, attitude, and practice (KAP) of both parents or caregivers and healthcare providers towards the rotavirus vaccination. The design of the study was an interventional pre-test and post-test. The type of intervention used in this study is an educational intervention. The intervention consisted of a health education message delivered to the participants including both parents or caregivers and healthcare providers. It included three phases, the first one was carried out to assess the KAP of mothers and caregivers before the intervention, the second phase involved the evaluation of participants’ post-intervention, and the third phase involved the assessment of healthcare providers. The study used a survey to assess the demographics, KAP of the participants. The collected data was analyzed using the SPSS program. The overall KAP among mothers were high (11.6%). After the intervention, the level of KAP of mothers toward the rotavirus vaccine was improved significantly (p=0.0001). Also, after the health education message, the level of KAP of the healthcare providers was significantly improved (p=0.0001). The levels of KAP of mothers and healthcare providers were improved after the educational intervention and the health educational message, reflecting the important role of educational intervention in raising the awareness of both mothers and healthcare providers.

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

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

Oxidative stress enhances rotavirus oncolysis in breast cancer and leukemia, except in melanoma with abundant matrix

ObjectivesThis study aimed to explore the impact of oxidative stress and extracellular matrix integrity on rotavirus infection in various cancer cells, including breast cancer, acute lymphoblastic leukemia, and melanoma. MethodsWe induced oxidative stress using ROS-inducing drugs (cisplatin, metronidazole, melatonin, valproic acid, doxorubicin, losartan, nitrofurantoin, and DHA) and investigated the effects on viral infection in MCF-7, Reh, A375, B16-F1, and SK-MEL-28 cells and the generation of virions from infected cells by harvesting the supernatants every two hours, reinfecting other cells, and analyzing cell viability and DNA fragmentation. FindingsIn MCF-7 and Reh cells, rotavirus Wt1–5 infection led to increased ROS generation, virion production, membrane permeability, mitochondrial dysfunction, DNA damage, and cell death. These effects were amplified by ROS-inducing drugs. Conversely, melanoma cells (SK-MEL-28 and A375) with a robust extracellular matrix network showed limited sensitivity to the drugs. Notably, losartan, which modulates the extracellular matrix, enhanced viral infection in melanoma cells (99 %). ConclusionsOxidative stress promotes oncolytic rotavirus infection in breast cancer and acute lymphoblastic leukemia cells, suggesting potential utility in combination with radiotherapy or chemotherapy due to their shared induction of intracellular oxidative stress.

Distribution of group a Rotavirus circulating in Mashhad, Iran.

Group A Rotavirus (RVA) is the most important causative agent of acute diarrheal disease in pediatrics 5 years and below. This study aimed to determine the distribution of circulating RVA in Mashhad, Iran to develop health improvement strategies and vaccine decision making. A total of 106 fecal specimens were collected from children admitted to Akbar and Dr. Sheikh referral pediatric hospitals of Mashhad City during the December 2020 to March 2021 and December 2021 to March 2022. All specimens were tested for specific bacterial, parasitic, and amoebic infections. Negative samples were analyzed for RVA infections using the RT-PCR method. RVA was detected in 31.3% of the specimens, indicating no statistical significance in gender distribution or between fall and winter positivity rates. The number of RVA-positive specimens increased following age increasing in the range of 1 to 60 months. Today, acute diarrheal disease (ADD) is still caused mostly by Rotavirus infections in pediatrics in Mashhad. Comprehensive studies are needed to determine the genetic diversity of circulating Rotavirus strains in this era.

A 7-Year Survey (2015-2021) in One Pediatric Hospital (Brasov, Romania) on Rotavirus Gastroenteritis Specified as Community- or Hospital-Acquired Infection in Young Children.

This project is an observational, descriptive study evaluating frequencies of rotavirus disease in hospitalized children aged less than 5 years old between 2015 and 2021 in the Pediatric Hospital of Brasov, Central Romania. The study compares socio-demographic (age, sex, place of living and ethnicity), clinical, and treatment aspects between community-acquired rotavirus gastroenteritis (CARG) and hospital-acquired rotavirus gastroenteritis (HARG). During that period, 1913 hospitalized children had a rapid positive immunichromatographic rotavirus test from stool specimens. Among them, 1620 (84.6%) were CARG and 293 (15.4%) were HARG. CARG conditions represented 28.5% of all acute hospitalized gastroenteritis (n = 5673) whereas HARG represented 5.2%. Around the same percentage of urban children were seen in CARG as in HARG (58.5% (n = 948) for CARG and 56.3% (n = 164) for HARG). About 64.9% (n = 1052) of CARG cases were from Roma population, and 66.5% (n = 195) in HARG. The age group with the highest frequency of the disease was 12 to 24 months old for both CARG and HARG. The average hospital duration was 5.09 days for CARG and 7.62 days for HARG. Diarrhea was the principal symptom in both CARG and HARG (92.6% (n = 1500) for CARG and 93.9% (n = 275) for HARG). Most CARG patients (61% (n = 989)) were treated for symptomatic management with iv fluids. Most HARG (60.4% (n = 177)) were treated for symptomatic management with iv fluids and antibiotics. A significant seasonal shift to a later period in the year was observed during the last registration year of 2021, possibly due to the COVID-19 epidemic. The seasonal disease burden of rotavirus infection in children remains high in hospital care in Romania, which may justify the systematic introduction of rotavirus vaccination across the whole country.

660. Pediatric Rotavirus Hospitalization Rates in the Military Health System Before and During the COVID-19 Pandemic

Abstract Background Rotavirus, a vaccine preventable disease, causes significant morbidity and mortality in children < 5 years of age. Globally, the COVID-19 pandemic reduced the rates of pediatric vaccinations, and the Military Health System (MHS) was no different (Figure 1). This gap in immunizations left many children vulnerable to preventable illnesses, including rotavirus. We hypothesized that the reduction in rotavirus vaccine administration during the pandemic would lead to an increase in rotavirus related hospitalizations within the MHS. Methods A repeated monthly cross-sectional study was performed using inpatient data from the MHS to observe differences in rotavirus rates and risk factors before and during the COVID-19 pandemic. Data from March 2018 to February 2020 was considered pre-pandemic, while the following two years (until February 2022), were divided into COVID Year 1 and Year 2. Children included in the study were between 0-59 months of age and those with rotavirus were identified using ICD-10 codes. Poisson regression calculated rate ratios of rotavirus, adjusting for several demographic variables and time period at diagnosis. Monthly counts and rates of rotavirus were also documented. Results Across the cohort of 1.14 million MHS beneficiaries, there were 3,503 unique cases of rotavirus infections in hospitalized children < 5 years old (Table 1). During both Years 1 and 2 of COVID-19, there was a significant decrease in rotavirus related hospitalizations compared to the pre-pandemic period (Figure 2). Younger age was associated with increased risk. Patient sex, parent military rank, and region were not statistically significant (Table 2). Conclusion Despite the reduction in routine immunization administration to children in the MHS after the COVID-19 pandemic started, there was not an increase in rotavirus related hospitalizations. In the two years following the start of the pandemic, there was a statistically significant decrease in hospitalizations related to rotavirus in our cohort. Social distancing to include daycare closures, increased hygiene measures, and catch-up immunizations may explain this finding. Continued research into this topic will help determine if rotavirus related hospitalizations return to pre-pandemic levels. Disclosures All Authors: No reported disclosures

Characterization of Rotavirus Strains Responsible for Breakthrough Diarrheal Diseases among Zambian Children Using Whole Genome Sequencing.

The occurrence of rotavirus (RV) infection among vaccinated children in high-burden settings poses a threat to further disease burden reduction. Genetically altered viruses have the potential to evade both natural infection and vaccine-induced immune responses, leading to diarrheal diseases among vaccinated children. Studies characterizing RV strains responsible for breakthrough infections in resource-limited countries where RV-associated diarrheal diseases are endemic are limited. We aimed to characterize RV strains detected in fully vaccinated children residing in Zambia using next-generation sequencing. We conducted whole genome sequencing on Illumina MiSeq. Whole genome assembly was performed using Geneious Prime 2023.1.2. A total of 76 diarrheal stool specimens were screened for RV, and 4/76 (5.2%) were RV-positive. Whole genome analysis revealed RVA/Human-wt/ZMB/CIDRZ-RV2088/2020/G1P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and RVA/Human-wt/ZMB/CIDRZ-RV2106/2020/G12P[4]-I1-R2-C2-M2-A2-N1-T2-E1-H2 strains were mono and multiple reassortant (exchanged genes in bold) respectively, whilst RVA/Human-wt/ZMB/CIDRZ-RV2150/2020/G12P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1 was a typical Wa-like strain. Comparison of VP7 and VP4 antigenic epitope of breakthrough strains and Rotarix strain revealed several amino acid differences. Variations in amino acids in antigenic epitope suggested they played a role in immune evasion of neutralizing antibodies elicited by vaccination. Findings from this study have the potential to inform national RV vaccination strategies and the design of highly efficacious universal RV vaccines.