Pierre Van Damme

Multicenter Prospective Study of the Burden of Rotavirus Acute Gastroenteritis in Europe, 2004–2005: The Reveal Study

BACKGROUNDnRotavirus is recognized as a significant cause of pediatric gastroenteritis worldwide. Comprehensive data on the burden of rotavirus disease in Europe were lacking.nnnMETHODSnA prospective, multicenter, observational study was conducted during the 2004-2005 season in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom, to estimate the incidence of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children <5 years of age who require medical care in primary care, emergency department, and hospital settings.nnnRESULTSnA total of 2846 children with AGE were included in the study, and, of the 2712 children for whom ELISA results were available, 1102 (40.6%) were found to be rotavirus positive. The estimated annual incidence of RVGE was 2.07-4.97 cases/100 children <5 years of age, and it was highest among children 6-23 months of age, with 56.7%-74.2% of all RVGE cases occurring in children in this age group. Overall, RVGE was estimated to account for 27.8%-52.0% of AGE cases, and it was responsible for up to two-thirds of hospitalizations and emergency department consultations, as well as one-third of primary care consultations for AGE.nnnCONCLUSIONSnRotavirus infections account for a significant proportion of AGE cases in children <5 years of age in Europe, many of whom require frequent primary care consultations or care in emergency department and/or hospital settings. The results of the present study suggest that routine rotavirus vaccination for infants <6 months of age could significantly reduce the substantial burden of this potentially serious childhood disease.

Costs of Community-Acquired Pediatric Rotavirus Gastroenteritis in 7 European Countries: The Reveal Study

BACKGROUNDnMorbidity and resource use due to rotavirus gastroenteritis (RVGE) are substantial in Europe, although comprehensive data on the economic impact of the disease are lacking.nnnMETHODSnA cost study was conducted to assess health care resource use data collected during a prospective epidemiologic study of acute gastroenteritis in children <5 years of age in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. We calculated the average cost (direct and indirect) per episode of confirmed RVGE in primary care, emergency department, and hospital settings.nnnRESULTSnThe total societal cost (including direct medical, direct nonmedical, and indirect costs) per episode of RVGE ranged from 166 euros to 473 euros in the primary care setting, from 334 euros to 770 euros in the emergency department setting, and from 1525 euros to 2101 euros in the hospital setting. The majority of hospital-related costs were reimbursed by national health care payers, but the percentage of reimbursed costs declined progressively in the emergency department and primary care settings. The mean number of workdays lost by parents and other relatives varied between study areas and settings, ranging from 2.3 to 7.5 days, and this represented the major cost not reimbursed by national health care payers.nnnCONCLUSIONSnRVGE incurs considerable resource utilization in all health care settings and substantial costs for national health care payers, families of patients, and employers. Routine rotavirus vaccination in infants could significantly reduce the health and economic burden of pediatric RVGE.

Distribution of Rotavirus Genotypes in Europe, 2004–2005: The REVEAL Study

BACKGROUNDnRotavirus gastroenteritis (RVGE) constitutes a significant burden of pediatric disease. Knowledge of currently cocirculating rotavirus genotypes is required to help guide immunization strategies.nnnMETHODSnDuring the 2004-2005 RVGE season, a prospective, multicenter, observational study of RVGE was conducted in children <5 years of age seeking health care in primary care, emergency department, and hospital settings in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. Rotavirus was identified by enzyme-linked immunosorbent assay (ELISA), and genotypes were determined by reverse-transcription polymerase chain reaction (RT-PCR) analysis of stool samples for which ELISA results were positive.nnnRESULTSnELISA results were available for 2712 of the 2846 children with acute gastroenteritis who were recruited for the study; of these 2712 children, 1102 (40.6%) were rotavirus positive. RT-PCR results were available for 1031 children with ELISA-positive samples. G1-G4 and G9 were the most prevalent genotypes identified: G1 was identified in Spain, Sweden, and the United Kingdom; G9 in Italy, France, and Belgium; and G4 in Germany. Only the G4 and G9 genotypes were identified in all study areas. Rotavirus infections showed seasonal variation, with different patterns noted among the genotypes.nnnCONCLUSIONSnRotavirus genotypes G1-G4 and G9 are associated with the majority of RVGE infections in the areas studied, with geographic and seasonal variation in the distributions of rotavirus strains. Rotavirus vaccines should, therefore, provide protection against all major genotypes to decrease effectively the RVGE disease burden in Europe.

Clinical Consequences of Rotavirus Acute Gastroenteritis in Europe, 2004-2005: The REVEAL Study

BACKGROUNDnThe availability of comprehensive, up-to-date epidemiologic data would improve the understanding of the disease burden and clinical consequences of rotavirus gastroenteritis (RVGE) in Europe.nnnMETHODSnDuring the 2004-2005 season, a prospective, multicenter, observational study was conducted in children <5 years of age in primary care, emergency department, and hospital settings in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. The clinical consequences of acute gastroenteritis (AGE) and RVGE were estimated.nnnRESULTSnThe estimated percentage of children with rotavirus-positive AGE admitted to a hospital was 10.4%-36.0%, compared with 2.1%-23.5% of children with rotavirus-negative AGE. In France, Germany, Italy, Spain, and the United Kingdom, the relative risk of hospitalization was statistically significantly higher for children with rotavirus-positive AGE than for those with rotavirus-negative AGE. Children with rotavirus-positive AGE were more likely to have lethargy, fever, vomiting, and dehydration, and, therefore, more severe disease than were children with rotavirus-negative AGE. Dehydration was up to 5.5 times more likely in children with rotavirus-positive AGE than in those with rotavirus-negative AGE.nnnCONCLUSIONSnRotavirus-positive AGE is more severe, causes more dehydration, and results in more emergency department consultations and hospitalizations than does rotavirus-negative AGE. Variations in the management of RVGE seen across study areas could be explained by differences in health care systems. Routine rotavirus vaccination of infants could significantly reduce the substantial burden of RVGE and would have major benefits for potential patients, their families, and health care providers.

RotaTeq, a pentavalent rotavirus vaccine: efficacy and safety among infants in Europe

A pentavalent human-bovine reassortant oral rotavirus vaccine, RotaTeq, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort (N=2686) in Finland. RotaTeq was 98.3% (95% CI, 90.2-100%) and 68.0% (95% CI 60.3-74.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.3-96.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq and placebo for any of the safety outcomes. In Europe, RotaTeq was highly efficacious and well tolerated.

Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5)

BackgroundThe Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance.MethodsData on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses.ResultsIn the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable = 4,451) and every 6 weeks (number evaluable = 52,683) respectively.ConclusionsOur analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published.Trial RegistrationClinicalTrials.gov number, NCT00090233