Summary

Objectives
Primary: 
To evaluate the following in children below the age of 5 years in 7 European countries: 
-Yearly hospital admissions due to acute rotavirus gastroenteritis (RVGE) 
-Yearly emergency department consultations due to RVGE 
-Frequency of family paediatrician consultations due to RVGE. 

Secondary: 
-Estimate the incidence of RVGE in 
a) children hospitalised 
b) seen in emergency departments 
c) seen by family paediatricians at different ages 
-Compare the clinical and management issues of children with RVGE with those of other causes of gastroenteritis (severity, symptoms, treatment, lost working days, etc) 
-Estimate direct and indirect costs of RVGE 
-Describe the seasonal variance in RVGE incidence in the different European countries 
-Study the prevalence of rotavirus subtypes causing RVGE in the various countries (and various groups) studied 

Study design
Prospective, observational multicentre study 

Methods
An area of about 250,000 inhabitants in which there is one (or more) paediatric referral hospital, an emergency department and a diffuse family medical system will be identified for each country taking part (Italy, Germany, France, Great Britain, Sweden, Spain and Belgium). 
The area will be selected bearing in mind the following: 
-Paediatric referral department catering for about 14,000 children under the age of 5 years 
-Paediatric emergency department with a similar catchment area 
-10-12 doctors of family paediatricians who look after about 5000 children under the age of 5 years 
In Italy the selected town was Padua. 

Study period
February 2004 – June 2005 

Inclusion Criteria
All children below the age of 5 years with acute gastroenteritis who presented during the study period to the selected referral structures/doctors involved whose parents had given written consent. 

Case definition
Child below the age of 5 years presenting with the following symptoms occurring in a 24 hour period (maximum 7 days before presentation): 
- At least 3 episodes of watery diarrhoea with or without vomiting in the absence of known chronic gastrointestinal pathology (e.g. celiac disease, Hirschsprung) 

Exclusion Criteria
-Age greater than 5 years 
-Chronic gastrointestinal disease 
-Lack of informed consent 
-Not able to speak the language of country in which recruited 
-Recruitment into a rotavirus vaccine trial 
-Nosocomial RVGE 

Procedures

Hospital Paediatric Ward or Emergency Department
All children recruited had a stool sample taken within 14 days of the symptoms starting, to look for rotavirus using immunochromatography (VIKIA, Biomerieux). 
The sample was taken by the doctor (or medical personnel) during the consultation or parents brought the sample in at a later time. From the moment the sample was collected to the moment it was analyzed the sample was kept in a fridge at + 4° C for a maximum of 48 hours. 
The rotavirus antigen was tested for using immunochromatography (VIKIA, Biomerieux) [optical reading, very simple and quick (about 10 min)]which was carried out by the doctor or medical personnel in charge in the department. Once analysed the sample was frozen at – 20° C and sent to the lab in the United States (Ward Lab, Cincinnati) for typing. 
Questionnaires were used to gather information about each child recruited. The following information was gathered from the parents by the doctors: 
-Date of birth, sex, socioeconomic status 
-Clinical information (signs and symptoms, start of symptoms, information on stool, dehydration, etc) 
-Clinical management: drugs given, consultations undertaken 
-Work days lost to look after child 
The information was gathered using a questionnaire at recruitment and at discharge, administered to the parents and the medical personnel looking after the child. 
All information was collected and treated anonymously according to laws in the various countries (Italy: L 675-676/96). Each patient was given a numbered i.d. which allowed the patient to be identified only by the doctor looking after the child. 

Paediatrician's ambulatory
All children recruited had a stool sample taken within 14 days of the symptoms starting to look for rotavirus using immunochromatography (VIKIA, Biomerieux). 
The sample was taken by the doctor (or medical personnel) during the consultation or parents brought the sample in at a later time. From the moment the sample was collected to the moment it was analysed the sample was kept in a fridge at + 4° C for a maximum of 48 hours. 
The rotavirus antigen was tested for using immunochromatography (VIKIA, Biomerieux) [optical reading, very simple and quick (about 10 min)] which was carried out by the doctor or medical personnel in charge in the department. Once analysed the sample was frozen at – 20° C and sent to the lab in the United States (Ward Lab, Cincinnati) for typing. 
Questionnaires were used to gather the following information about each child recruited. The information was gathered by the doctors from the parents: 
-Date of birth, sex, socioeconomic status 
-Clinical information (signs and symptoms, start of symptoms, information on stool, dehydration,etc) 
-Clinical management: drugs given, consultations undertaken 
-Work days lost to look after child 
The information was gathered using a questionnaire at recruitment and at discharge, administered to the parents and the medical personnel looking after the child. 
All information was collected and treated anonymously according to laws in the various countries (Italy: L 675-676/96). Each patient was given a numbered i.d which allowed the patient to be identified only by the doctor looking after the child. 

Organization
The study was sponsored by Sanofi Pasteur MSD. Società Servizi Telematici (PEDIANET project) coordinated the logistic and administrative aspects of the research in Padua. An international scientific committee assured the scientific validity of the study, validated the final results and prepared the final write-up. 
The logistics (data collection, monitoring data analysis, etc) of the study was coordinated by Quintiles. 

Results
2846 children with acute gastroenteritis were recruited into the study. Of these 1102 (40.6%) tested positive for Rotavirus. Italy, along with Spain, recruited the largest number of children, 757 in all with 83 hospital patients, 266 emergency department patients and 408 family paediatrician cases. 
For more detailed results see publications.

Partecipants and Collaborations

Coordinators

Luigi Cantarutti 
Coordinamento Pedianet, PLS, Padova 
Liviana Da Dalt 
Dipartimento di Pediatria, Padova 
Carlo Giaquinto 
Dipartimento di Pediatria, Padova

Partecipants

Pediatri di libera scelta: 
M. Bernuzzi, L. Cantarutti, S. Drago, A. De Marchi, P. Falconi, M. Felice, G. Giancola, C. Lista, C. Manni, M. Perin, F. Pisetta, M.P. Sidran, 

Dipartimento di Pediatria, Padova: 
B.Andreola, S. Callegaro, M. Perin, L. Da Dalt, R. D’Elia.

Collaborations

Data Monitor (in collaboration with Quintiles)

Antonio Scamarcia 
Società Servizi Telematici, Padova

Pubblications

Financing

The study was financed by Sanofi Pasteur MSD, Lione, France