Symptomatic Rotavirus Infection Research Articles

Infant Non-Secretor Histoblood Group Antigen Phenotype Reduces Susceptibility to Both Symptomatic and Asymptomatic Rotavirus Infection.

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case-control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity.

The Association between Symptomatic Rotavirus Infection and Histo-Blood Group Antigens in Young Children with Diarrhea in Pretoria, South Africa.

Recently, histo-blood group antigens (HBGAs) have been identified as receptors or attachment factors of several viral pathogens. Among rotaviruses, HBGAs interact with the outer viral protein, VP4, which has been identified as a potential susceptibility factor, although the findings are inconsistent throughout populations due to HBGA polymorphisms. We investigated the association between HBGA phenotypes and rotavirus infection in children with acute gastroenteritis in northern Pretoria, South Africa. Paired diarrheal stool and saliva samples were collected from children aged ≤ 59 months (n = 342) with acute moderate to severe diarrhea, attending two health care facilities. Rotaviruses in the stool samples were detected by commercial EIA and the rotavirus strains were characterized by RT-PCR targeting the outer capsid VP7 (G-type) and VP4 (P-type) antigens for genotyping. Saliva-based ELISAs were performed to determine A, B, H, and Lewis antigens for blood group typing. Blood type O was the most common blood group (62.5%) in this population, followed by groups A (26.0%), B (9.3%), and AB (2.2%). The H1-based secretors were common (82.7%) compared to the non-secretors (17.3%), and the Lewis antigen positive phenotypes (Le(a+b+)) were predominant (54.5%). Blood type A children were more likely to be infected by rotavirus (38.8%) than any other blood types. P[4] rotaviruses (21/49; 42.9%) infected only secretor individuals, whereas P[6] rotaviruses (3/49; 6.1%) only infected Le(a-b-), although the numbers were very low. On the contrary, P[8] rotaviruses infected children with a wide range of blood group phenotypes, including Le(a-b-) and non-secretors. Our findings demonstrated that Lewis antigens, or the lack thereof, may serve as susceptibility factors to rotaviral infection by specific VP4 genotypes as observed elsewhere. Potentially, the P[8] strains remain the predominant human VP4 genotype due to their ability to bind to a variety of HBGA phenotypes.

Diversity of Rotavirus Strains in Children; Results From a Community-Based Study in Nepal.

Objective: The objectives of this study were to describe the incidence and genetic diversity of Rotavirus (RV) infection among children up to 3 years of age in a community in Nepal.Methods: We investigated community-acquired cases of asymptomatic and symptomatic RV infections in children from birth to 36 months of age in a community-based birth cohort in Bhaktapur, Nepal. Monthly surveillance and diarrheal stool samples were collected from 240 children enrolled at birth, of which 238 completed the 3 years of follow-up. Samples were screened for rotavirus by Enzyme Immuno Assay (EIA). All RV screened positives were further genotyped by reverse transcription-polymerase chain reaction for the capsid genes VP7 and VP4.Results: In total, 5,224 stool samples were collected from 238 children, followed from birth to 36 months of age. Diarrhea occurred in 92.4% (230/238) of all children in the cohort. During the 3 years study period, RV was more frequently seen in children with symptoms (7.6%) than in non-symptomatic children (0.8%). The highest RV detection rate was found in younger children between 3 and 21 months of age. Although rotavirus is known as winter diarrhea, it was detected throughout the year except in August. The highest positivity rate was observed in the months between December and March, with a peak in January. Four common G types were seen: G2 (30%), G1 (29%), G12 (19%), and G9 (16%). The most predominant genotypes seen were G2P[4] (30%), followed by G1P[8] (27.0%), G12P[6] (14.0%), G9P[8] (10%), and remaining were mixed, partial, and untyped.Conclusion: Our study confirms that rotavirus is a common cause of gastroenteritis in young children in the community. The prevalence and pathogenicity of rotavirus infection differed by age. There was substantial variability in circulating strains in the community samples compared to samples collected from hospitals. This shows the importance of including community-based surveillance systems to monitor the diversity of circulating rotavirus strains in Nepal.

Does Having Rotavirus Infection in Early Childhood Increase the Risk of Celiac Disease?

Abstract Objective With the increasing prevalence of celiac disease (CD) in the population, possible risk factors are under investigation. Environmental and genetic factors that trigger the immune response have been analyzed for many years. This study investigates the presence of CD in children with rotavirus infection. Rotavirus infection is thought to be a risk factor for CD. Methods Included in the study were 105 of 160 pediatric patients hospitalized due to symptomatic rotavirus infection between 2012 and 2018. These children were screened for CD 45.6 ± 18.2 (14–90) months following the rotavirus infection diagnosed with CD as per ESPGHAN guidelines. Results A total of 105 pediatric patients who had rotavirus gastroenteritis were included in the study. The age of the children with rotavirus infection was 3.98 ± 1 (2–6) months. In terms of CD, it was 45.6 ± 18.2 months. Around 14 to 90 months later, patients were called for control. CD developed in four (3.8%) of the children with rotavirus, whereas none of the children in the control group developed CD. Conclusion Rotavirus infection may be a risk factor for CD through immune mechanisms. There are genetic and various environmental factors for the development of CD. Although the CD's occurrence on children who had rotavirus gastroenteritis in our study also supported this situation, there was no statistically significant difference.

The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam: A study protocol for an open single-arm interventional trial

Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018.

Rotavirus symptomatic infection among unvaccinated and vaccinated children in Valencia, Spain

BackgroundHuman group A rotavirus is the leading cause of severe acute gastroenteritis in young children worldwide. Immunization programs have reduced the disease burden in many countries. Vaccination coverage in the Autonomous Region of Valencia, Spain, is around 40%, as the rotavirus vaccine is not funded by the National Health System. Despite this low-medium vaccine coverage, rotavirus vaccination has substantially reduced hospitalizations due to rotavirus infection and hospital-related costs. However, there are very few studies evaluating symptomatic rotavirus infections not requiring hospitalization in vaccinated children. The objective of this study was to investigate symptomatic rotavirus infections among vaccinated children in the health area served by the Hospital Clínico Universitario of Valencia, Spain, from 2013 to 2015.MethodsA total of 133 children younger than 5 years of age with rotavirus infection were studied. Demographic and epidemiological data were collected and informed consent from their caretakers obtained. Rotavirus infection was detected by immunological methods and G/P rotavirus genotypes were determined by RT-PCR, following standard procedures from the EuroRotaNet network.ResultsForty infants (30.1%; 95% CI: 22.3–37.9) out of 133 were diagnosed with symptomatic rotavirus infection despite having been previously vaccinated, either with RotaTeq (85%) or with Rotarix (15%). Children fully vaccinated against rotavirus (24.8%), partially vaccinated (5.3%) and unvaccinated (69.9%) were found. The infecting genotypes showed high G-type diversity, although no significant differences were found between the G/P genotypes infecting vaccinated and unvaccinated children during the same time period. G9P[8], G12P[8] and G1P[8] were the most prevalent genotypes. Severity of gastroenteritis symptoms required 28 (66.6%) vaccinated and 67 (73.6%) unvaccinated children to be attended at the Emergency Room.ConclusionRotavirus vaccine efficacy in reducing the incidence of severe rotavirus infection has been well documented, but symptomatic rotavirus infection can sometimes occur in vaccinees.

Histo-Blood Group Antigens in Children with Symptomatic Rotavirus Infection.

Group A rotaviruses are a major cause of acute gastroenteritis in children. The diversity and unequal geographical prevalence of rotavirus genotypes have been linked to histo-blood group antigens (HBGAs) in different human populations. In order to evaluate the role of HBGAs in rotavirus infections in our population, secretor status (FUT2+), ABO blood group, and Lewis antigens were determined in children attended for rotavirus gastroenteritis in Valencia, Spain. During three consecutive years (2013–2015), stool and saliva samples were collected from 133 children with rotavirus infection. Infecting viral genotypes and HBGAs were determined in patients and compared to a control group and data from blood donors. Rotavirus G9P[8] was the most prevalent strain (49.6%), followed by G1P[8] (20.3%) and G12P[8] (14.3%). Rotavirus infected predominantly secretor (99%) and Lewis b positive (91.7%) children. Children with blood group A and AB were significantly more prone to rotavirus gastroenteritis than those with blood group O. Our results confirm that a HBGA genetic background is linked to rotavirus P[8] susceptibility. Rotavirus P[8] symptomatic infection is manifestly more frequent in secretor-positive (FUT2+) than in non-secretor individuals, although no differences between rotavirus G genotypes were found.

Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis.

BackgroundCurrently, Indian officials are incorporating a domestically manufactured rotavirus vaccine (based on the 116E rotavirus strain) into the country’s universal immunization program; this vaccine will cost significantly less than western rotavirus vaccines. Here, we examine the public health impact, cost, and cost-effectiveness of universal vaccination in India using the 116E vaccine. This work will allow comparison of universal 116E vaccination with other approaches to child mortality reduction, shed light on the future burden of rotavirus disease in India, and help stakeholders understand future resource needs.MethodsUsing information from published literature, we developed a dynamic simulation model of rotavirus transmission, natural history, and related utilization among Indian infants followed until age five. Infection risk depended on the degree of viral shedding in the population. Infection risk and severity were influenced by age, number of previous infections, and vaccination history. Probabilities of inpatient and outpatient health services utilization depended on symptom severity. With the model, we compared a strategy of nationwide 116E vaccination to one of no vaccination. Costs were considered from the perspective of all payers (including families) and from the societal perspective.ResultsWe estimated that an established 116E vaccination program would reduce symptomatic rotavirus infection by 13.0%, while reducing population-wide rotavirus mortality by 34.6% (over 34,000 lives annually). Rotavirus outpatient visits would decline by 21.3%, and hospitalization would decline by 28.1%. The cost per disability-adjusted life year (DALY) averted was estimated at 3,429 Rupees (approximately $56). Predicted mortality reduction in children born during the first five years of vaccination implementation was nearly identical to that in children born in later years (34.4% versus 34.6%).Conclusions116E vaccination of Indian infants would likely substantially reduce rotavirus-related morbidity, mortality, and utilization at a cost considered highly cost-effective by standard criteria. Nearly the entire mortality reduction benefit of vaccination was attributable to direct protection of those vaccinated, as opposed to indirect “herd immunity” effects.

Malnutrition Is Associated with Protection from Rotavirus Diarrhea: Evidence from a Longitudinal Birth Cohort Study in Bangladesh

Rotavirus is a leading cause of dehydrating diarrhea and death among infants and children globally, particularly in communities of the developing world. While numerous studies have described the complex relationships among infectious diarrhea, growth faltering, and poverty, the impact of nutritional status on susceptibility to rotavirus diarrhea is not well understood. In a longitudinal study conducted over the first 3 years of life among 626 slum-dwelling infants enrolled at birth in Dhaka, Bangladesh, we observed that common measures of healthy growth and development were positively associated with a risk of symptomatic rotavirus infection. This finding runs counter to the idea that improving childhood nutrition will implicitly decrease the incidence of symptomatic infection by enteric pathogens. As childhood nutrition improves worldwide, rotavirus infection may remain a public health challenge, making universal vaccination of even greater importance.

Identification of Equine Lactadherin-derived Peptides That Inhibit Rotavirus Infection via Integrin Receptor Competition

Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants against symptomatic rotavirus infections. To explore the potential antiviral activity of lactadherin sourced by equines, we undertook a proteomic analysis of milk fat globule membrane proteins from donkey milk and elucidated its amino acid sequence. Alignment of the human, bovine, and donkey lactadherin sequences revealed the presence of an Asp-Gly-Glu (DGE) α2β1 integrin-binding motif in the N-terminal domain of donkey sequence only. Because integrin α2β1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a minilibrary of donkey lactadherin-derived peptides containing DGE sequence for anti-rotavirus activity. A 20-amino acid peptide containing both DGE and RGD motifs (named pDGE-RGD) showed the greatest activity, and its mechanism of antiviral action was characterized; pDGE-RGD binds to integrin α2β1 by means of the DGE motif and inhibits rotavirus attachment to the cell surface. These findings suggest the potential anti-rotavirus activity of equine lactadherin and support the feasibility of developing an anti-rotavirus peptide that acts by hindering virus-receptor binding.

Determination of a Viral Load Threshold To Distinguish Symptomatic versus Asymptomatic Rotavirus Infection in a High-Disease-Burden African Population.

We evaluated quantitative real-time PCR to establish the diagnosis of rotavirus gastroenteritis in a high-disease-burden population in Malawi using enzyme immunoassay as the gold standard diagnostic test. In 146 children with acute gastroenteritis and 65 asymptomatic children, we defined a cutoff point in the threshold cycle value (26.7) that predicts rotavirus-attributable gastroenteritis in this population. These data will inform the evaluation of direct and indirect rotavirus vaccine effects in Africa.

Rotavirus infections in a community based cohort in Vellore, India

IntroductionThe burden of infection in communities determines the spread of rotavirus infection and disease in susceptible populations. This study reports rotavirus infection and disease in a community based birth cohort in Vellore. MethodsBimonthly surveillance and diarrheal stool were collected from 452 children enrolled at birth, of whom 373 completed three years of follow up. Samples were screened for rotavirus by an ELISA and genotyped by reverse transcription polymerase chain reaction for VP7 and VP4 genes. Rotavirus incidence rates were calculated using Poisson regression equations. Risk factors associated with symptomatic and asymptomatic rotavirus infections were compared using multiple logistic regression. ResultsA total of 1149 episodes of rotavirus infections occurred in 94.4% children in the cohort. Incidence of rotavirus infection was 1.04 (0.97–1.1) per child-year with 0.75 asymptomatic and 0.29 symptomatic infections per child-year. About 18% of the children were infected in the first month, mainly with the G10P[11] strain. Rotavirus infections were more prevalent during October–March, but seasonality was not as marked in rotavirus disease. Rotavirus was associated with 15.1% of mild diarrhea, 38.9% of moderate/severe diarrhea and 66.7% of very severe diarrhea. Four common G types – G1 (26.8%), G2 (16%), G10 (11.2%) and G9 (9.6%) were seen, with high rates of mixed infections and untypable samples. Male gender, presence of siblings and low maternal education were associated with rotavirus disease. ConclusionThis study demonstrates that rotavirus is the most common cause of gastroenteritis in the community, and indicates that since rotavirus caused the greatest proportion of moderate and severe disease, targeted interventions such as vaccines are needed for rotavirus, in addition to health education, sanitation and appropriate treatment to decrease diarrheal disease in communities.

Diarrhea incidence and intestinal infections among rotavirus vaccinated infants from a poor area in Brazil: a spatial analysis.

BackgroundAcute diarrhea is the second leading cause of mortality among children under 5 years of age in developing countries. The pathogen most strongly associated with diarrhea is rotavirus followed by enteric pathogens such as bacteria, helminthes and protozoan. Adequate sanitation and water supply contribute to decrease acute diarrhea incidence of most etiologic agents, although vaccination remains the most important intervention to control rotavirus acute diarrhea. This study aimed to describe environmental conditions and analyze spatially the acute diarrhea and intestinal infection among rotavirus vaccinated infants from Laranjeiras-Sergipe, Brazil.MethodsChildren were enrolled between 2 and 11 months of age and followed through 12 months. Demographic, socioeconomic and environmental data were obtained from a questionnaire, and immunization data were obtained from children vaccination card. Children stool samples were collected each month in order to run laboratory analyses. The household spatial localization was obtained by using a Global Positioning System (GPS). Spatial analysis was performed using the TerraView computer program and Kernel intensity estimation.ResultsA total of 1,113 stool samples were collected with 80 being diarrhea associated. Diarrhea incidence rate was 0.5 ± 1.0 episodes/child/year. The overall infection rates by Ascaris lumbricoides, Endolimax nana, Giardia lamblia and rotavirus were 5.1%, 3.0%, 0.9% and 2.6%, respectively. 3.8% of diarrhea-associated stool samples were positive for rotavirus and 11.3% were positive for helminths and protozoans. There were some changes on spatial distribution of intestinal infections and diarrhea episodes along the four trimesters evaluated.ConclusionsThe studied infants live equally in precarious conditions of sanitation which probably explain the significant rates of parasitic infections appearing in early life. The low acute diarrhea incidence in the studied rotavirus vaccinated population and the low number of symptomatic rotavirus infection may indicate vaccination efficacy to prevent acute diarrhea among young children in a poor environmental sanitary setting.

Factors associated with diarrhoea in young children and incidence of symptomatic rotavirus infection in rural West Bengal, India

Socio-behavioural factors and pathogens associated with childhood diarrhoea are of global public health concern. Our survey in 696 children aged ⩽2 years in rural West Bengal detected rotavirus as sole pathogen in 8% (17/199) of diarrhoeic stool specimens. Other organisms were detected along with rotavirus in 11% of faecal specimens. A third of the children with rotavirus diarrhoea, according to Vesikari score, had severe illness. The top four rotavirus genotypes were G9P[4] (28%), G1P[8] (19%), G2P[4] (14%) and G8P[4] (8%). In the multivariate model, the practice of 'drawing drinking water by dipping a pot in the storage vessel' [adjusted odds ratio (aOR) 2·21, 95% confidence interval (CI) 1·03-4·74, P = 0·041], and 'children aged ⩽6 months with non-exclusive breastfeeding' (aOR 2·07, 95% CI 1·1-3·82, P = 0·024) had twice the odds of having diarrhoea. Incidence of rotavirus diarrhoea was 24/100 child-years in children aged >6-18 months, 19/100 child-years in children aged >18-24 months and 5/100 child-years in those aged ⩽6 months. Results have translational implications for future interventions including vaccine development.

Rotavirus shedding in symptomatic and asymptomatic children using reverse transcription-quantitative PCR.

Reverse transcription-real-time polymerase chain reaction (RT-qPCR) for the VP6 gene was used to study group A rotavirus shedding in children with symptomatic and asymptomatic rotavirus infection. Sequential stool samples (n = 345) from 10 children with rotavirus associated diarrhea and from five children (n = 161) with asymptomatic rotavirus infection were collected over a period of 2 months. A RT-qPCR assay on the samples using a rotavirus VP6 plasmid standard demonstrated high reproducibility, with an inter-assay coefficient of variation (CV) of 1.40-2.97% and an intra-assay CV of 0.03-3.03%. The median duration of shedding was longer in children with diarrhea compared to asymptomatic children (24 days vs. 18 days; P = 0.066). The median quantitation cycle (C(q)) at presentation in symptomatic children was 17.21 compared to 30.98 in asymptomatic children (P = 0.086). The temporal pattern in symptomatic children consisted of a high initial viral shedding coinciding with the duration of diarrhea, followed by a rapid fall, and then a small increase in secondary shedding 21 days later. Compared to children with rotavirus diarrhea, those with asymptomatic infection shed lower quantities of virus throughout the observation period. No difference was noted between the G and P genotypes of samples collected at onset of infection and during the shedding period. Shedding was intermittent in a subset of children in both groups. RT-qPCR is a useful method to characterize shedding patterns.

Comparison of viral load and duration of virus shedding in symptomatic and asymptomatic neonatal rotavirus infections

A single rotavirus strain causing asymptomatic infections as well as severe gastrointestinal disease has been described in the neonatal nurseries of the Christian Medical College, Vellore. In this study, quantitative real-time RT-PCR was used to determine the association of viral load with the presence of gastrointestinal symptoms in neonates. Viral load was estimated in terms of the crossing point [C(t) value] at which the amplicon could be detected in the real-time PCR assay. The study was carried out on 103 neonates, including 33 asymptomatic neonates and 70 neonates with different gastrointestinal symptoms. The duration of virus shedding was also compared between five symptomatic and four asymptomatic neonates using real-time RT-PCR. There was no significant difference in viral load between symptomatic and asymptomatic neonates (P = 0.087). Among neonates with different gastrointestinal symptoms, those presenting with feed intolerance and abdominal distension had a significantly higher viral load than those with other gastrointestinal symptoms (P = 0.02). For the study on virus shedding, nine neonates were followed up for a median duration of 53 days, with a median of 31 samples tested per child. Extended shedding of low copies of rotavirus was found, with no significant differences in pattern of shedding between symptomatic and asymptomatic neonates. The lack of correlation between viral load and gastrointestinal disease demonstrates yet another difference between neonatal rotavirus infection and infection in older children where higher viral load correlates with severe disease.

Symptomatic and Asymptomatic Rotavirus and Norovirus Infections During Infancy in a Chilean Birth Cohort

Rotavirus and more recently norovirus have been recognized as 2 of the most common causes of acute diarrhea in children. Comparative analysis of these infections in a birth cohort has not been performed and can provide relevant insight on clinical and viral behaviors. Mother-infant pairs from middle-low socioeconomic background living in the Metropolitan Region of Chile are being followed for 18 months in 2 outpatient clinics. Infants are evaluated monthly for asymptomatic excretion of rotavirus and norovirus and during acute diarrhea episodes (ADE) for rotavirus, norovirus, and bacterial enteropathogens. Severity of ADE is evaluated using the Vesikari score. Between July 1, 2006 and September 1, 2008 a total of 198 children were followed for a mean of 15.7 months. Asymptomatic rotavirus and norovirus infections were detected in 1.3% and 8% of 2278 stool samples compromising 14% and 57% of infants, respectively. Incidence of ADE was approximately 0.8 for the first year of life and approximately 0.6 for the 13 to 18 month age group. Rotavirus and norovirus were detected in 15% and 18% of 145 ADE evaluated. Mean Vesikari score was 10.4 and 7.4 for rotavirus and norovirus respectively (P = 0.01) and severity was not associated with age of patients for either virus. Reinfections were more common for norovirus asymptomatic episodes: 44% versus 19% (P = 0.01) and borderline for symptomatic episodes: 40% versus 11% (P = 0.08). Rotavirus genotype G9P8 and norovirus genogroup II (GII) predominated although most asymptomatic episodes for both viruses were nontypable. None of 19 symptomatic GII norovirus infections had a previous documented GII infection compared with 10 of 31 asymptomatic GII infections (OR = 0. 95% CL = 0, 0.59; P = 0.008). Children had suffered a mean of approximately 1.4 ADE by 18 months of age of which 15% and 18% were caused by rotavirus and norovirus, respectively. In general rotavirus infections were more severe than norovirus infections and for both viruses severity was not related to age. Norovirus reinfections were significantly more common than rotavirus reinfections but for GII norovirus a primary infection seems to confer protection against clinically significant reinfections.

Estimating the incidence of symptomatic rotavirus infections: a systematic review and meta-analysis.

BackgroundWe conducted for the first time a systematic review, including a meta-analysis, of the incidence of symptomatic rotavirus (RV) infections, because (1) it was shown to be an influential factor in estimating the cost-effectiveness of RV vaccination, (2) multiple community-based studies assessed it prospectively, (3) previous studies indicated, inconclusively, it might be similar around the world.MethodologyPubmed (which includes Medline) was searched for surveys assessing prospectively symptomatic (diarrheal) episodes in a general population and situation, which also reported on the number of the episodes being tested RV+ and on the persons and the time period observed. A bias assessment tool was developed and used according to Cochrane guidelines by 4 researchers with different backgrounds. Heterogeneity was explored graphically and by comparing fits of study-homogenous ‘fixed effects’ and -heterogeneous ‘random effects’ models. Data were synthesized using these models. Sensitivity analysis for uncertainty regarding data abstraction, bias assessment and included studies was performed.Principal FindingsVariability between the incidences obtained from 20 studies is unlikely to be due to study groups living in different environments (tropical versus temperate climate, slums versus middle-class suburban populations), nor due to the year the study was conducted (from 1967 to 2003). A random effects model was used to incorporate unexplained heterogeneity and resulted in a global incidence estimate of 0.31 [0.19; 0.50] symptomatic RV infections per personyear of observation for children below 2 years of age, and of 0.24 [0.17; 0.34] when excluding the extreme high value of 0.84 reported for Mayan Indians in Guatemala. Apart from the inclusion/exclusion of the latter study, results were robust.Conclusions/SignificanceRather than assumptions based on an ad-hoc selection of one or two studies, these pooled estimates (together with the measure for variability between populations) should be used as an input in future cost-effectiveness analyses of RV vaccination.

Whole genome characterization of reassortant G10P[11] strain (N155) from a neonate with symptomatic rotavirus infection: Identification of genes of human and animal rotavirus origin

BackgroundRotavirus G10P[11] strains have long been associated with asymptomatic neonatal infections in some parts of India. We have previously reported G10P[11] strains associated with both asymptomatic infections and severe gastrointestinal disease in neonates from Vellore in southern India, with >90% partial nucleotide and amino acid identity to the VP4, VP6, VP7 and NSP4 genes of the exclusively asymptomatic G10P[11] strain I321. ObjectivesIn this study, the whole genome of a G10P[11] isolate (N155) from a neonate with severe gastrointestinal disease was characterized to determine whether there were significant differences in its genetic makeup in comparison to G10P[11] strain I321 and to establish the origin of the G10P[11] strains in Vellore. Study designPCR amplification and complete genome sequencing was carried out for all 11 gene segments of symptomatic G10P[11] rotavirus isolate N155. Nucleotide and amino acid sequence similarity with I321, other human and bovine strains for each gene segment were determined. The origin of each gene was determined based on the degree of identity to bovine or human rotavirus strains. ResultsN155 was found to be a reassortant between human and bovine rotaviruses. With the exception of NSP2, gene sequences of strain N155 showed >90% identity to published sequences of I321. Gene segments encoding NSP1, 2 and 3 were of human rotavirus origin for both strains; however, phylogenetic analysis of NSP2 sequences indicated that the human parental strain that led to the origin of these bovine-human reassortant strains was different. There were no significant differences between NSP2 sequences of strains from symptomatic and asymptomatic neonates in the same setting. ConclusionsThe study shows that the difference in clinical presentations in neonates may not be due to the limited variability in the genome sequence of G10P[11] strains and that G10P[11] strains in different parts of India could have evolved through reassortment of different parental strains.

Evidence of intrafamilial transmission of rotavirus in a birth cohort in South India

Transmission of rotavirus infection was studied in a birth cohort of children based in an urban slum in Vellore and their familial contacts. Contemporaneous samples from index patients and their familial contacts were collected for analysis in three different settings. Firstly, samples were collected from familial contacts during a period of rotavirus infection in children from the cohort. Secondly, on occasions when a family member had rotavirus diarrhea, samples from the cohort child were taken for analysis. Lastly, asymptomatic surveillance samples collected at predetermined time points from both the cohort child and familial contacts were analyzed. From 560 samples collected from family members during symptomatic and asymptomatic rotavirus infections in these children, three rotavirus transmissions were identified, accounting for a secondary attack rate of 0.54%. In four instances of rotavirus diarrhea in a family member, one infection was transmitted to the cohort child. Nucleotide sequence and phylogenetic analysis demonstrated a high degree of similarity in all these pairs ranging between 99% and 100% at both the nucleotide and the deduced amino acid levels, highly suggestive of person-to-person transmission of rotavirus infection. There was complete concordance of rotavirus genotyping between these pairs. No transmission events were noted from 14 asymptomatic rotavirus infections identified during routine surveillance of family members. This study is the first to use phylogenetic analysis to study the intrafamilial spread of rotavirus infection.