Vesikari Score Research Articles

Multispecies Cocirculation of Adenoviruses Identified by Next-Generation Sequencing During an Acute Gastroenteritis Outbreak in Coastal Kenya in 2023.

Although 7 human adenovirus (HAdV) species are known to exist, only F (types 40 and 41) and G are identified as diarrheal disease agents. The role of other HAdV species in diarrheal disease remains unclear, and data on their prevalence are limited. We describe HAdV species and types in hospitalized children with diarrhea in coastal Kenya. Three hundred twenty-nine stool samples collected between June 2022 and August 2023 from children aged <13 years were screened for HAdV using quantitative polymerase chain reaction (qPCR). Positive HAdV cases were genotyped by adenovirus primers from the RespiCoV panel by amplification, next-generation sequencing, and phylogenetic analysis. Sixty-five samples (20%) tested HadV positive, of which 5 HAdV species were identified. Other than HAdV F, other species included A, B, C, and D; these were detected as either mono-detections or coinfections. Six HAdV F identified by NGS had been missed by our qPCR typing method. This appeared to be as a result of a 133-nucleotide deletion in the long fiber protein, which abrogated a primer and probe binding site. Based on grading of diarrheal disease severity using VESIKARI scores, 93% of the HAdV cases presented with severe disease. One child with an HAdV F infection died. Our study shows the enormous diversity and clinical characteristics of HAdV species in children with diarrhea in coastal Kenya. These data offer an opportunity to improve current diagnostic assays and increase knowledge of HAdV in Africa for control of outbreaks in the future.

Evaluating Acute Viral Gastroenteritis Severity: Modified Vesikari and Clark Scoring Systems.

Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.

Clinical Severity of Enteric Viruses Detected Using a Quantitative Molecular Assay Compared With Conventional Assays in the Global Enteric Multicenter Study.

Quantitative molecular assays are increasingly used for detection of enteric viruses. We compared the clinical severity using the modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIAs] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (Ct) cutoffs. Using conventional assays, the median mVS (interquartile range) was 10 (8-11) for rotavirus, 9 (7-11) for adenovirus 40/41, 8 (6-10) for astrovirus, sapovirus, and norovirus GII, and 7 (6-9) for norovirus GI. Compared with rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with Ct <32.6 or Ct ≥32.6 and <35, respectively (P < .001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of Ct cutoff. Quantitative molecular assays compared with conventional assays, such as EIA, may influence the severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

Epidemiology of group A rotavirus in children under five years of age with gastroenteritis in N'Djamena, Chad.

Group A Rotaviruses (RVA) is one of the most common causes of severe diarrhoea in infants and children under 5 years of age. Unlike many countries in the world where RVA surveillance/control is active, in Chad , there is currently no applied RVA immunization program and surveillance strategy. The present study aims to determine the prevalence and associated risk factors of RVA gastroenteritis among children under five years of age in N'Djamena. This study comprised two parts: (1) A cross-sectional study carried in four hospitals in N'Djamena between August and November 2019, to determine infection risk factors and evidence of RVA infection among children aged five and below, consulted or hospitalized for diarrhea. An ELISA based RVA VP6 protein detection was used to determine RVA infection prevalence. Infection results and sociodemographic data were statistically analysed to determine RVA infection risk factors. (2) A retrospective study that consisted of analysing the records of stool examinations of the period from January 2016 to December 2018, to determine the prevalence of infectious gastroenteritis among the target population. For the cross-sectional study, RVA infection prevalence was 12.76% (18/141) with males (61.11%) being more affected (sex ratio: 1.57). Children below 12 months were the most affected age group (44.44%) and 44.4% were malnourished. The mean Vesikari score shows that 38.8% of children have a high severity level and 41.1% have a moderate level. For the retrospective study, 2,592 cases of gastroenteritis hospitalization were analysed; 980 out of 2,592 cases (37.81%) of hospitalization due to diarrhoea were due to diarrhoeagenic pathogens including Emtamoeba hystolitica, Gardia lamblia, Trichomonas hominis, Hymenolepis nana, Escherichia coli, Shigella spp, Proteus mirabilis, and Klebsiella oxytoca. Cases of diarrhoea with negative pathogen search were 1,612 cases (62.19%). The diarrhoea peak was observed during the dry seasons, and the age group under 11 months was the most affected was (57.3%). This study describes the evidence of RVA infection among diarrhoeic children below five years of age in N'Djamena, thus indicates a serious health burden. Malnourishment younger age was the higher risk factor. Further studies are needed to determine the circulating strains prior to considering introduction of RVA vaccine and setup a routine rotavirus surveillance in Chad.

Genomic and clinical characteristics of campylobacteriosis in Australia.

Campylobacter spp. are a common cause of bacterial gastroenteritis in Australia, primarily acquired from contaminated meat. We investigated the relationship between genomic virulence characteristics and the severity of campylobacteriosis, hospitalisation, and other host factors.We recruited 571 campylobacteriosis cases from three Australian states and territories (2018-2019). We collected demographic, health status, risk factors, and self-reported disease data. We whole genome sequenced 422 C. jejuni and 84 C. coli case isolates along with 616 retail meat isolates. We classified case illness severity using a modified Vesikari scoring system, performed phylogenomic analysis, and explored risk factors for hospitalisation and illness severity.On average, cases experienced a 7.5 day diarrhoeal illness with additional symptoms including stomach cramps (87.1 %), fever (75.6 %), and nausea (72.0 %). Cases aged ≥75 years had milder symptoms, lower Vesikari scores, and higher odds of hospitalisation compared to younger cases. Chronic gastrointestinal illnesses also increased odds of hospitalisation. We observed significant diversity among isolates, with 65 C. jejuni and 21 C. coli sequence types. Antimicrobial resistance genes were detected in 20.4 % of isolates, but multidrug resistance was rare (0.04 %). Key virulence genes such as cdtABC (C. jejuni) and cadF were prevalent (>90 % presence) but did not correlate with disease severity or hospitalisation. However, certain genes (e.g. fliK, Cj1136, and Cj1138) appeared to distinguish human C. jejuni cases from food source isolates.Campylobacteriosis generally presents similarly across cases, though some are more severe. Genotypic virulence factors identified in the literature to-date do not predict disease severity but may differentiate human C. jejuni cases from food source isolates. Host factors like age and comorbidities have a greater influence on health outcomes than virulence factors.

Эффективность регидратирующей терапии при вирусных гастроэнтеритах у детей

Aim: to compare the efficacy of reduced osmolarity oral rehydration solution (ORS) with zinc and infusion therapy with salt and sugar-salt solutions in children suffering from viral gastroenteritis (VGE) complicated by dehydration syndrome of I-II stage and II stage. Patients and Methods: a prospective open-ended comparative randomized clinical trial was conducted The children were divided into two groups: the main group (n=45) with therapy used reduced osmolarity ORS (carbohydrates 2.84 g, glucose 2.82 g, chlorides 0.453 g, zink 0.003 g, osmolarity: 245 mOsm/L, per 1 sachet), and the comparison group (n=34), receiving standard infusion therapy with salt-sugar solutions. The severity of acute gastroenteritis was assessed using a modified Vesikari score. Comprehensive clinical and laboratory examination of children was performed before and after treatment Results: the mean severity of the patients' condition on the modified Vesikari score was 13.26±0.7 points for VGE, which corresponds to the moderate severity. In 42 (93.3±4.5%) patients of the main group, the condition stabilization and reduction of pathological losses were achieved during the first 6 hours, and therefore oral rehydration was continued. In this case, the active use of ORS was conducted for 24–48 hours with an assessment of the trend in general and topical symptoms, as well as laboratory parameters of the fluid and electrolyte balance and renal excretion of nitrogenous compounds. 3 patients (6.66±3.7%) who required further parenteral fluid administration were excluded from the study due to the lack of proper oral rehydration effect associated with the vomiting and the impossibility of further therapeutic manipulations. During oral rehydration in the main group, the febrile reaction duration was comparable in the lasting with the comparison group. Normalization of general well-being in the form of the fatigue disappearance was noted in the compared groups at the same time, while the vomiting cessation was recorded in a significantly shorter time in the main group. Exicosis and diarrhea were managed to be stopped in the main and comparison groups at almost comparable time. Conclusion: rehydration with low-osmolar ORS helps to avoid possible complications of parenteral fluid administration and a traumatic situation for a child KEYWORDS: exicosis, dehydration syndrome, viral gastroenteritis, acute intestinal infection, oral rehydration, oral rehydration therapy, oral rehydration solution, zinc, low-osmolar oral rehydration solution, children. FOR CITATION: Bekhtereva M.K., Komarova A.M. Rehydration therapy efficacy of viral gastroenteritis in children. Russian Journal of Woman and Child Health. 2024;7(2):177–183 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-14.

Comparing single versusmultiple virus detection in pediatric acute gastroenteritis postimplementation of routine multiplex RT-PCR diagnostic testing.

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.

Assessment of Acute Gastroenteritis in Children Under Five Years of Age by Vesikari Score; A Comparative Analysis of the Efficacy of the Rota-Virus Vaccine

Objective: To assess the severity of acute gastroenteritis by Vesikari score in children under five years of age and compare the severity in children vaccinated for Rotavirus with those who have not been vaccinated. Study Design: Comparative Prospective study. Place and Duration of Study: Paediatrics Department, Pak Emirates Military Hospital, and Combined Military Hospital, Rawalpindi Pakistan, from Oct 2019 to Oct 2020. Methodology: Children aged 1-5 years presenting with acute gastroenteritis to the Outpatient Department were included in the study. Vesikari scoring was carried out in all of them at the presentation time. They were divided into two groups based on their Rotavirus vaccination status. The presence of hyponatremia, hypoglycemia, duration of admission and severity of Vesikari score were compared in both groups. Results: Out of 250 children presenting with acute gastroenteritis, 135(54%) patients were male and 115(46%) were female. The mean age of the patients was 3.144±2.75 years. 165(66%) were vaccinated for Rotavirus, while 85(34%) were not vaccinated. Based on the Vesikari score, 154(61.6%) had mild, 70(28%) had moderate and 26(10.4%) had severe illness. Hyponatremia, hypoglycemia, longer duration of admission and severe forms of illness were found significantly more in the non-vaccinated group (p-value&lt;0.05). Conclusion: Vesikari score revealed that many children with acute gastroenteritis had moderate to severe illness. Children not vaccinated with the Rotavirus had more chances of having severe illness.

Norovirus-Associated Gastroenteritis Vesikari Score and Pre-Existing Salivary IgA in Young Children from Rural South Africa.

Norovirus (NoV) is the leading cause of viral gastroenteritis, mostly affecting young children worldwide. However, limited data are available to determine the severity of norovirus-associated AGE (acute gastroenteritis) and to correlate it with the NoV-specific IgA antibodies' level. Between October 2019 and September 2021, two hundred stool samples were randomly collected from symptomatic cases for the vesikari score and NoV-specific IgA assessment in young children from rural South Africa. Additionally, one hundred saliva specimens were concomitantly sampled within the same cohort to evaluate the NoV-specific salivary IgA levels. In addition, 50 paired saliva and stool samples were simultaneously collected from asymptomatic children to serve as controls. NoV strains in stool samples were detected using real-time RT-PCR, amplified, and genotyped with RT-PCR and Sanger sequencing. ELISA using NoV VLP (virus-like particles) GII.4 as antigens was performed on the saliva specimens. Dehydrated children were predominantly those with NoV infections (65/74, 88%; p < 0.0001). NoV-positive infections were significantly associated with the severe diarrhea cases having a high vesikari score (55%, 33/60) when compared to the non-severe diarrheal score (29.3%, 41/140; p < 0.0308). NoV of the GII genogroup was mainly detected in severe diarrhea cases (50.9%, 30/59; p = 0.0036). The geometric means of the NoV-specific IgA level were higher in the asymptomatic NoV-infected group (0.286) as compared to the symptomatic group (0.174). This finding suggests that mucosal immunity may not protect the children from the NoV infection. However, the findings indicated the contribution of the pre-existing NoV-specific IgA immune response in reducing the severity of diarrheal disease. A high vesikari score of AGE associated with the NoV GII genogroup circulating in the study area underscores the need for an appropriate treatment of AGE based on the severity level of NoV-associated clinical symptoms in young children.

Quantification of fecal adenovirus viral load and correlation with Vesikari Score in children with acute gastroenteritis

Quantification of fecal adenovirus viral load and correlation with Vesikari Score in children with acute gastroenteritis

Effect of the coronavirus disease 2019 pandemic on pediatric emergency department visits for acute gastroenteritis evaluated using a validated clinical severity score.

The coronavirus disease 2019 (COVID-19) outbreak that began in late 2019 has significantly affected quality of life and healthcare. Approaches to prevent the spread of COVID-19 have also affected the prevalence of other diseases. This retrospective review evaluated pediatric emergency department (PED) volume, in terms of children with acute gastroenteritis (AGE), and changes in AGE severity before versus during the COVID-19 pandemic in a tertiary medical center in Taiwan. Patients who visited the PED and were diagnosed with AGE during the 70-day COVID-19 lockdown in 2021, or the identical period in 2020, were compared using a clinically validated AGE severity score, the modified Vesikari score (MVS), and additional parameters. During the COVID-19 outbreak, there was a 61.4% reduction in the number of children with AGE visiting the PED. In that period, the AGE severity score was similar compared to the pre-pandemic period (9.00 vs. 8.57, p=0.273). The mean C-reactive protein (CRP) level (55.7 vs. 40.6mg/L, p<0.001) and rate of antibiotics use (48% vs. 23.5%, p<0.001) were higher during the outbreak than the pre-pandemic period. The number of children with AGE visiting the PED decreased during the COVID-19 outbreak, while disease severity was unchanged compared to the pre-pandemic period. The use of antibiotics during the COVID-19 pandemic warrants further investigation.

Clinical profile of children under 5 years of age with rotavirus diarrhoea in a hospital setting in Kisangani, DRC, after the introduction of the rotavirus vaccine, a cross-sectional study

BackgroundThe Democratic Republic of the Congo (DRC) is one of the countries with the highest rotavirus mortality rate in the world. The aim of this study was to describe the clinical features of rotavirus infection after the introduction of rotavirus vaccination of children in the city of Kisangani, DRC.MethodsWe conducted a cross-sectional study of acute diarrhoea in children under 5 years of age admitted to 4 hospitals in Kisangani, DRC. Rotavirus was detected in children’s stools by an immuno-chromatographic antigenic rapid diagnostic test.ResultsA total of 165 children under 5 years of age were included in the study. We obtained 59 cases of rotavirus infection, or 36% CI95 [27, 45]. The majority of children with rotavirus infection were unvaccinated (36 cases) and had watery diarrhoea (47 cases), of high frequency per day/per admission 9.6 ± 3.4 and accompanied by severe dehydration (30 cases). A statistically significant difference in mean Vesikari score was observed between unvaccinated and vaccinated children (12.7 vs 10.7 p-value 0.024).ConclusionRotavirus infection in hospitalized children under 5 years of age is characterized by a severe clinical manifestation. Epidemiological surveillance is needed to identify risk factors associated with the infection.

Prevalence, Clinical Severity, and Seasonality of Adenovirus 40/41, Astrovirus, Sapovirus, and Rotavirus Among Young Children With Moderate-to-Severe Diarrhea: Results From the Vaccine Impact on Diarrhea in Africa (VIDA) Study

While rotavirus causes severe diarrheal disease in children aged <5 years, data on other viral causes in sub-Saharan Africa are limited. In the Vaccine Impact on Diarrhea in Africa study (2015-2018), we analyzed stool from children aged 0-59 months with moderate-to-severe diarrhea (MSD) and without diarrhea (controls) in Kenya, Mali, and The Gambia using quantitative polymerase chain reaction. We derived the attributable fraction (AFe) based on the association between MSD and the pathogen, accounting for other pathogens, site, and age. A pathogen was attributable if the AFe was ≥0.5.The severity of attributable MSD was defined by a modified Vesikari score (mVS). Monthly cases were plotted against temperature and rainfall to assess seasonality. Among 4840 MSD cases, proportions attributed to rotavirus, adenovirus 40/41, astrovirus, and sapovirus were 12.6%, 2.7%, 2.9%, and 1.9%, respectively. Attributable rotavirus, adenovirus 40/41, and astrovirus MSD cases occurred at all sites, with mVS of 11, 10, and 7, respectively. MSD cases attributable to sapovirus occurred in Kenya, with mVS of 9. Astrovirus and adenovirus 40/41 peaked during the rainy season in The Gambia, while rotavirus peaked during the dry season in Mali and The Gambia. In sub-Saharan Africa, rotavirus was the most common cause of MSD; adenovirus 40/41, astrovirus, and sapovirus contributed to a lesser extent among children aged <5 years. Rotavirus- and adenovirus 40/41-attributable MSD were most severe. Seasonality varied by pathogen and location. Efforts to increase the coverage of rotavirus vaccines and to improve prevention and treatment for childhood diarrhea should continue.

Norovirus acute gastroenteritis amongst US and European travellers to areas of moderate to high risk of travellers' diarrhoea: a prospective cohort study.

Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited. Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms whilst travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14days of return. Samples were tested for NoV by RT-qPCR, genotyped if positive and tested for other common enteric pathogens by Luminex xTAG GPP. Of the 1109 participants included, 437 (39.4%) developed AGE symptoms resulting in an overall AGE incidence of 24.7 per 100 person-weeks [95% confidence interval (CI): 22.4; 27.1]. In total, 20 NoV-positive AGE cases (5.2% of those tested) were identified at an incidence of 1.1 per 100 person-weeks (95% CI: 0.7; 1.7). NoV-positive samples belonged mostly to genogroup GII (18, 85.7%); None of the 13 samples sequenced belonged to genotype GII.4. Clinical severity of AGE was higher for NoV-positive than for NoV-negative cases (mean modified Vesikari Score 6.8 vs 4.9) with more cases classified as severe or moderate (25% vs 6.8%). In total, 80% of NoV-positive participants (vs 38.9% in NoV-negative) reported at least moderate impact on travel plans. AGE is a prevalent disease amongst travellers with a small proportion associated with NoV. Post-travel stool sample collection timing might have influenced the low number of NoV cases detected; however, NoV infections resulted in high clinical severity and impact on travel plans. These results may contribute to targeted vaccine development and the design of future studies on NoV epidemiology.

Norovirus Disease Among Children &amp;lt;5 Years in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015–2018

To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0-59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6-8 months with majority (61.2%) aged 6-11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. Infants aged 6-11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.

Genomic epidemiology of human adenovirus F40 and F41 in coastal Kenya: A retrospective hospital-based surveillance study (2013-2022).

Human enteric adenovirus species F (HAdV-F) is a leading cause of childhood diarrhoeal deaths. The genomic analysis would be key to understanding transmission dynamics, potential drivers of disease severity, and vaccine development. However, currently, there are limited HAdV-F genomic data globally. Here, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in coastal Kenya from children <13 years of age who reported a history of three or more loose stools in the previous 24 hours. The genomes were analysed together with the data from the rest of the world by phylogenetic analysis and mutational profiling. Types and lineages were assigned based on phylogenetic clustering consistent with the previously described criteria and nomenclature. Participant clinical and demographic data were linked to genotypic data. Of ninety-one cases identified using real-time Polymerase Chain Reaction, eighty-eight near-complete genomes were assembled, and these were classified into HAdV-F40 (n = 41) and HAdV-F41 (n = 47). These types co-circulated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineages 1-3) and HAdV-F41 (Lineages 1, 2A, 3A, 3C, and 3D). Types F40 and F41 coinfections were observed in five samples and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe diseases as defined using the Vesikari Scoring System, respectively. Intratypic recombination was found in four HAdV-F40 sequences occurring between Lineages 1 and 3. None of the HAdV-F41 cases had jaundice. This study provides evidence of extensive genetic diversity, coinfections, and recombination within HAdV-F40 in a rural coastal Kenya that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.

581. Monovalent rotavirus vaccine efficacy against different rotavirus genotypes: a pooled analysis of Phase II and III trial data

Abstract Background Rotavirus vaccine effects appear lower in countries with high child mortality rates and high diversity of rotavirus genotypes. Some evidence suggests diminished vaccine efficacy (VE) against the G2P[4] genotype, which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. Methods We pooled individual-level data from ten Phase II and III clinical trials of monovalent rotavirus vaccine containing G1 and P[8] antigens (RV1). We estimated VE against any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for three types of VE: non-specific VE against any RVGE; genotype-specific VE against specific genotypes; and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with the RV1 G1 and P[8] antigens. Models were adjusted for oral poliovirus vaccination concomitant with RV1 vaccination and the country’s child mortality stratum. Results A total of 87,644 infants from 22 countries in the Americas, Europe, Africa, and Asia were included in analysis. VE against severe RVGE was 91% (95% confidence interval (CI): 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against homotypic G1P[8] to 71% (95% CI: 43-85%) against fully-heterotypic G2P[4]. VE against severe RVGE caused by partially heterotypic genotypes (92% (95% CI: 84-96%)) was similar to VE against the homotypic genotype, but VE against fully heterotypic genotypes was lower (83% (95% CI: 67-91%)). VE against any-severity RVGE was 82% (95% CI: 75-87%). Genotype-specific VE estimates against any-severity RVGE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (95% CI: 41-77%) against G2P[4]. VE against any-severity RVGE was lower (83% (95% CI: 72-90%) against partially heterotypic genotypes, but lowest (63% (95% CI: 40-77%)) against fully heterotypic genotypes. Conclusion RV1 VE is diminished against fully heterotypic genotypes including G2P[4]. Disclosures Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant.

1540. Clinical severity across five viral diarrheal pathogens in infants and young children Global Enteric Multicenter Study (GEMS)

Abstract Background Viruses are a leading cause of pediatric diarrheal illness, resulting in over 200,000 childhood deaths annually worldwide. Rotavirus is the most common viral cause of moderate-to-severe diarrhea in low to middle-income countries, but adenovirus 40/41, norovirus, sapovirus, and astrovirus are increasingly recognized as important contributors to the global viral gastroenteritis burden. Comparisons of clinical severity between these five viruses among infants and young children are currently limited. Methods The objective of this analysis was to describe the clinical severity of rotavirus, adenovirus 40/41, norovirus, sapovirus, and astrovirus among children enrolled in the Global Enteric Multicenter Study (GEMS). Stool samples from children younger than 5 years of age with moderate-to-severe diarrhea at four sites in Africa and three in Asia were tested by enzyme immunoassays (rotavirus, adenovirus) and multiplex reverse transcriptase polymerase chain reaction (norovirus, sapovirus, astrovirus). A modified Vesikari score (MVS) to assess clinical severity was calculated based on symptoms and clinical characteristics. Results Among 3,305 viral diarrhea cases, rotavirus had the highest median MVS (9 [interquartile range [IQR: 7,11]) followed by adenovirus 40/41 (8 [IQR]: 6,10]); sapovirus and astrovirus had a similar MVS distribution to norovirus (7 [IQR: 6, 9]). The proportion of patients experiencing &amp;gt; 3 episodes of vomiting was high for those with rotavirus (66.3%) and adenovirus 40/41 (55.7%); astrovirus (40.8%), sapovirus (40.0%), and norovirus (35.9%) patients also experienced substantial episodes of vomiting. A high proportion of cases with adenovirus 40/41 (54.0%) and rotavirus (46.3%) experienced ≥ 7 episodes of diarrhea within 24 hours. While hospitalization or intravenous fluids were required most frequently for patients with rotavirus (42.1%), the proportion was also high in those with adenovirus 40/41 (30.6%). Conclusion These findings demonstrate the clinical severity of viral diarrheal pathogens besides rotavirus, in particular adenovirus 40/41, warranting the continued development of vaccines and therapeutics to prevent morbidity and mortality due to viral enteric pathogens. Disclosures All Authors: No reported disclosures.

Monovalent Rotavirus Vaccine Efficacy Against Different Rotavirus Genotypes: A Pooled Analysis of Phase II and III Trial Data.

Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. We pooled individual-level data from 10 Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's designated child mortality stratum. Analysis included 87 644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval [CI]: 87-94%). Genotype-specific VE ranged from 96% (95% CI: 89-98%) against G1P[8] to 71% (43-85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84-96%) against partially heterotypic genotypes but 83% (67-91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75-87%). Genotype-specific VE ranged from 94% (95% CI: 86-97%) against G1P[8] to 63% (41-77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72-90%) against partially heterotypic genotypes but 63% (40-77%) against fully heterotypic genotypes. RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4].

Risk Factors for Acute Gastroenteritis Among Patients Hospitalized in 5 Veterans Affairs Medical Centers, 2016-2019.

In the United States, ∼179 million acute gastroenteritis (AGE) episodes occur annually. We aimed to identify risk factors for all-cause AGE, norovirus-associated vs non-norovirus AGE, and severe vs mild/moderate AGE among hospitalized adults. We enrolled 1029 AGE cases and 624 non-AGE controls from December 1, 2016, to November 30, 2019, at 5 Veterans Affairs Medical Centers. Patient interviews and medical chart abstractions were conducted, and participant stool samples were tested using the BioFire Gastrointestinal Panel. Severe AGE was defined as a modified Vesikari score of ≥11. Multivariate logistic regression was performed to assess associations between potential risk factors and outcomes; univariate analysis was conducted for norovirus-associated AGE due to limited sample size. Among 1029 AGE cases, 551 (54%) had severe AGE and 44 (4%) were norovirus positive. Risk factors for all-cause AGE included immunosuppressive therapy (adjusted odds ratio [aOR], 5.6; 95% CI, 2.7-11.7), HIV infection (aOR, 3.9; 95% CI, 1.8-8.5), severe renal disease (aOR, 3.1; 95% CI, 1.8-5.2), and household contact with a person with AGE (aOR, 2.9; 95% CI, 1.3-6.7). Household (OR, 4.4; 95% CI, 1.6-12.0) and non-household contact (OR, 5.0; 95% CI, 2.2-11.5) with AGE was associated with norovirus-associated AGE. Norovirus positivity (aOR, 3.4; 95% CI, 1.3-8.8) was significantly associated with severe AGE. Patients with immunosuppressive therapy, HIV, and severe renal disease should be monitored for AGE and may benefit from targeted public health messaging regarding AGE prevention. These results may also direct future public health interventions, such as norovirus vaccines, to specific high-risk populations.