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Showing papers by "Jim Gray published in 2008"


Journal ArticleDOI
TL;DR: The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection, and their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting.
Abstract: The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.

221 citations


Journal ArticleDOI
TL;DR: This study highlights the importance of a constant reconsideration of primer sequences employed for the molecular typing of rotaviruses, and design and evaluate a new VP4 consensus oligonucleotide primer pair that provides increased sensitivity and allows typing of strains that were untypeable using available methods.

165 citations


Journal ArticleDOI
23 Jan 2008-PLOS ONE
TL;DR: The diversity of amino acid sequences of the highly variable P2 region in the major capsid protein, VP1, of the GII-4 human noroviruses strains are described using sequence analysis and homology modelling techniques and suggest that norovirus follow a neutral network pattern of evolution.
Abstract: Background Human noroviruses are a highly diverse group of viruses classified into three of the five currently recognised Norovirus genogroups, and contain numerous genotypes or genetic clusters. Noroviruses are the major aetiological agent of endemic gastroenteritis in all age groups, as well as the cause of periodic epidemic gastroenteritis. The noroviruses most commonly associated with outbreaks of gastroenteritis are genogroup II genotype 4 (GII-4) strains. The relationship between genotypes of noroviruses with their phenotypes and antigenic profile remains poorly understood through an inability to culture these viruses and the lack of a suitable animal model.

136 citations


Journal ArticleDOI
TL;DR: The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory andintestinal illnesses.
Abstract: Objective: To establish incidence rates, clinic referrals, hospitalisations, mortality rates and baseline determinants of morbidity among infants in an Indian slum. Design: A community-based birth cohort with twice-weekly surveillance. Setting: Vellore, South India. Subjects: 452 newborns recruited over 18 months, followed through infancy. Main outcome measures: Incidence rates of gastrointestinal illness, respiratory illness, undifferentiated fever, other infections and non-infectious morbidity; rates of community-based diagnoses, clinic visits and hospitalisation; and rate ratios of baseline factors for morbidity. Results: Infants experienced 12 episodes (95% confidence interval (CI) 11 to 13) of illness, spending about one fifth of their infancy with an illness. Respiratory and gastrointestinal symptoms were most common with incidence rates (95% CI) of 7.4 (6.9 to 7.9) and 3.6 (3.3 to 3.9) episodes per child-year. Factors independently associated with a higher incidence of respiratory and gastrointestinal illness were age (3-5 months), male sex, cold/wet season and household involved in beedi work. The rate (95% CI) of hospitalisation, mainly for respiratory and gastrointestinal illness, was 0.28 (0.22 to 0.35) per child-year. Conclusions: The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory and gastrointestinal illnesses. The risk factors identified were younger age, male sex, cold/wet season and household involvement in beedi work.

81 citations


Journal ArticleDOI
TL;DR: Analysis of the questionnaires indicated that rotavirus infections were likely to be more severe than any other virus infection, and children from whom a viral pathogen was identified were more likely to require rehydration therapy.
Abstract: The aim of this study was to investigate the burden of disease associated with gastroenteric viruses (rotavirus, norovirus, sapovirus, astrovirus and enteric adenovirus) using structured surveillance of children aged <6 years in the community. Faecal samples were collected between 2000 and 2003 from 685 children with symptoms of gastroenteritis. The children comprised three groups; 223 in the structured surveillance cohort, 203 in a community cohort and 259 in a cohort of hospitalized children. All samples were tested for the presence of viral pathogens using molecular methods. Questionnaires were sent to the parents/carers of the children recruited to the structured surveillance cohort in order to collect data that would allow an estimation of the severity of illness by means of the Vesikari score, and of the cost associated with gastrointestinal disease in this age group. A viral aetiological agent was detected in 53·5% of samples tested. Rotavirus was the most common pathogen found in all three cohorts followed by norovirus and enteric adenoviruses. Multiple viruses were found in 8% of the samples, and commonly involved rotavirus and any other virus. G1P[8] was the most commonly detected rotavirus strain and there was no significant difference in the distribution of rotavirus genotypes among the three cohorts. Analysis of the questionnaires indicated that rotavirus infections were likely to be more severe than any other virus infection, and children from whom a viral pathogen was identified were more likely to require rehydration therapy.

69 citations


Journal ArticleDOI
TL;DR: Overall, changes to cleaning protocols were deemed to have reduced the level of environmental contamination with gastroenteric viruses, but contamination still occurred due to a breakdown in infection control procedures indicated by contamination in areas frequented by parents but used only occasionally by staff.
Abstract: The aims of this study were to examine the extent of gastroenteric virus contamination in a pediatric primary immunodeficiency (PPI) ward and a general pediatric ward over a winter season and to determine whether changes to hospital infection control interventions would have an impact on environmental contamination levels within pediatric units. Environmental swabs were collected weekly from 11 sites in both wards from 15 December 2005 to 3 March 2006 and examined for the presence of norovirus (NoV), astrovirus, and rotavirus (RV) by reverse transcriptase PCR. Viruses were detected in 17% and 19% of swabs from both wards. Virus contamination for NoV and RV decreased from 20% to 6% and 15% to 10% of swabs, respectively, in the PPI ward from the 2004 study by Gallimore et al. (C. I. Gallimore, C. Taylor, A. R. Gennery, A. J. Cant, A. Galloway, M. Iturriza-Gomara, and J. J. Gray, J. Clin. Microbiol. 44:395-399, 2006). Overall, changes to cleaning protocols were deemed to have reduced the level of environmental contamination with gastroenteric viruses, but contamination still occurred due to a breakdown in infection control procedures indicated by contamination in areas frequented by parents but used only occasionally by staff.

66 citations


Journal ArticleDOI
TL;DR: The outbreaks reported to the FBVE reflect the lack of standardization of surveillance systems across Europe, making direct comparison of data between countries difficult, but trends in reported outbreaks per country, distribution of NoV genotypes, and detection of diffuse international outbreaks were used as background data in acute questions about NoV illness and the changing genotype distribution during the 5-year period.
Abstract: Background The food-borne viruses in Europe (FBVE) network database was established in 1999 to monitor trends in outbreaks of gastroenteritisdue to noroviruses (NoVs), to identify major transmission routes of NoV infections within and between participating countries and to detectdiffuse international food-borne outbreaks.Methods We reviewed the total of 9430 NoVoutbreak reports from 13 countries with date of onset between 1 January 2002 and 1 January2007 for representativeness, completeness and timeliness against these objectives.Results Rates of reporting ranged from a yearly average of 1.8 in 2003 to 11.6 in 2006. Completeness of reporting of an agreed minimumdataset improved over the years, both for epidemiological and virological data. For the 10 countries that provided integrated (epidemiological ANDvirological) reporting over the 5-year period, the completeness of the minimum dataset rose from 15% in 2003 to 48% in 2006. Two countrieshave not been able to combine both data types due to the structure of the national surveillance system (England and Wales and Germany).Timeliness of reporting (median days between the onset of an outbreak and the date of reporting to the FBVE database) differed greatly betweencountries, but gradually improved to 47 days in 2006.Conclusion The outbreaks reported to the FBVE reflect the lack of standardization of surveillance systems across Europe, making directcomparison of data between countries difficult. However, trends in reported outbreaks per country, distribution of NoV genotypes, and detectionof diffuse international outbreaks were used as background data in acute questions about NoV illness and the changing genotype distributionduring the 5-year period, shown to be of added value. Integrated reporting is essential for these objectives, but could be limited to sentinelcountries with surveillance systems that allow this integration. For successful intervention in case of diffuse international outbreaks, completenessand timeliness of reporting would need to be improved and expanded to countries that presently do not participate.Keywords Epidemiology, Food safety, Public health

66 citations


Journal ArticleDOI
TL;DR: The results suggest that some of the health sector costs, and all of the societal costs, of rotavirus gastroenteritis in children can be avoided by an immunization programme.
Abstract: Rotavirus is the most common cause of gastroenteritis in children aged <5 years old, two new vaccines have recently been developed which can prevent associated morbidity and mortality. While apparently safe and efficacious, it is also important to establish whether rotavirus immunization is cost effective. A decision analytical model which employs data from a review of published evidence is used to determine the cost effectiveness of a rotavirus vaccine. The results suggest that some of the health sector costs, and all of the societal costs, of rotavirus gastroenteritis in children can be avoided by an immunization programme. The additional cost to the health sector may be considered worthwhile if there is a sufficient improvement in the quality-of-life of children and parents affected by gastroenteritis; this study did not find any evidence of research which has measured the utility gains from vaccination.

61 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used sequence analysis of regions of the genes encoding the RNA-dependent RNA polymerase and the S domain of the capsid to track the spread of norovirus during outbreaks of gastroenteritis.
Abstract: Tracking the spread of noroviruses during outbreaks of gastroenteritis is hampered by the lack of sequence diversity in those regions of the genome chosen for virus detection and characterization. Sequence analysis of regions of the genes encoding the RNA-dependent RNA polymerase and the S domain of the capsid does not provide sufficient discrimination between genotypically related strains of different outbreaks. However, analysis of sequences derived from the region encoding the P2 domain showed 100% similarity among strains from the same outbreak and <100% similarity among strains of different outbreaks. The prolonged nature of some hospital outbreaks, links between hospitals, and the introduction of multiple strains of a single genotype associated with an outbreak aboard a cruise ship were determined using this method. This provides a powerful tool for tracking outbreak strains and the subsequent analysis and validation of interventions in a background of multiple introductions of virus strains of the same genotype or genetic cluster.

56 citations


Journal ArticleDOI
TL;DR: The results of a cost-of-illness study which was conducted alongside a structured community surveillance study found that forty-eight percent of the sample was found to have rotavirus acute gastroenteritis, and the average total cost of a child presenting with rotav virus gastroenteropathy ranged between £59 and £143 per episode.
Abstract: Rotavirus infections are the main cause of gastroenteritis in infants and children and it is expected that by the age of 5 years, nearly every child will have experienced at least one episode of rotavirus gastroenteritis. While severe cases are hospitalized, milder disease is either treated at home or by the GP, and as such the true prevalence of rotavirus infection in the community, and the burden of disease, is unknown. This paper reports the results of a cost-of-illness study which was conducted alongside a structured community surveillance study. Forty-eight percent of our sample was found to have rotavirus acute gastroenteritis; and the average total cost of a child presenting with rotavirus gastroenteritis ranged between pound sterling 59 and pound sterling 143 per episode, depending on the perspective. Given the prevalence and severity of the disease, the estimated burden of rotavirus gastroenteritis to society is pound sterling 11.5 million per year.

44 citations


Journal ArticleDOI
TL;DR: The Loopamp GII detection kit is a sensitive method for detecting all the commonly circulating GII-4 strains included in the evaluation panel and performed well compared to genogroup-specific real-time RT-PCR.

Journal ArticleDOI
TL;DR: Findings can help to predict future viral gastroenteritis outbreaks and target improved prevention strategies appropriately, however, more systematic studies are now required.
Abstract: Objectives The aim of this study was to see what lessons could be learnt from the suspected viral gastroenteritis outbreaks that have occurred in deployed British troops during 2002-7. Method Epidemiological and laboratory data from identifiable outbreaks were reviewed, including epidemic curves and the results of PCR testing for enteropathic viruses. Results The epidemic curves of outbreaks varied predictably in accordance with the size of the population at risk and whether this population was constant or expanding. Of 11 outbreaks identified, 10 (91%) had a proven viral cause and 10 (91%) occurred in Iraq. Of 84 enteropathic viruses identified, 61 (73%) were noroviruses and these included both unknown strains and those that were common in the UK and Europe. Of the 10 viral outbreaks, 3 (30%) occurred in medical units, 5 (50%) were associated with large-scale relief in place (RiP) deployments and 5 (50%) involved >3 different viruses, which is strongly suggestive of food or water contamination. Conclusion These findings can help to predict future viral gastroenteritis outbreaks and target improved prevention strategies appropriately. However, more systematic studies are now required.

Journal ArticleDOI
TL;DR: The use of reverse transcription–polymerase chain reaction (RT–PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in an south Indian urban slum is reported.
Abstract: Asymptomatic enteric infections are important where sequelae or protection from subsequent illness is an outcome measure. The use of reverse transcription-polymerase chain reaction (RT-PCR) to identify asymptomatic enteric infections in a birth cohort followed for rotaviral infections in a south Indian urban slum is reported. Of 1191 non-diarrhoeal samples from 371 children collected in May-June 2003, 22 (1.9%) were positive by ELISA. A total of 147 (40.6%) of 362 samples tested by VP6 RT-PCR were positive. In those samples that could be typed, a high diversity of G types including G1, G2, G4, G8, G9 and G10, and a high proportion (34.4%) of mixed infections were detected. Noroviruses were identified in 6/28 (21.4%) samples tested. The identification of infections undetectable by conventional techniques indicates the importance of the use of sensitive diagnostic techniques in research studies. Asymptomatically infected children may also act as a source of infection for other susceptible hosts.

Journal ArticleDOI
TL;DR: This study is the first to use phylogenetic analysis to study the intrafamilial spread of rotavirus infection in a birth cohort of children based in an urban slum in Vellore and their familial contacts, and demonstrated a high degree of similarity in all these pairs.
Abstract: 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.