Background
Rotavirus infection is the leading cause of acute gastroenteritis in infants and young children worldwide [
1], and is estimated to cause over 146,000 hospital admissions per year in children aged <5 years in the World Health Organization (WHO) European region [
2]. In the 23.6 million children aged <5 years in the European Union (EU) countries, 3.6 million episodes of rotavirus illness are estimated to occur annually, resulting in almost 700,000 outpatient visits, over 87,000 hospitalisations and 231 deaths per year [
3].
Vaccination against rotavirus is recommended in guidelines issued by the European Society for Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology, and Nutrition [
4,
5], and by the WHO Strategic Advisory Group of Experts [
6]. Two rotavirus vaccines have demonstrated good clinical efficacy and safety in large clinical trials and are currently available in Europe, a two-dose live attenuated monovalent human vaccine (GSK Biologicals, Rixensart, Belgium) [
7,
8] and a three-dose live human-bovine reassortant vaccine (Sanofi Pasteur MSD) [
9].
Rotavirus gastroenteritis is associated more frequently with severe symptoms and increased hospital admissions, compared with acute gastroenteritis due to other infectious causes [
10]. The severity of symptoms may cause worry, anxiety and distress in the affected child’s parents, as well as distress to the child. Family life may also be disrupted, for example if parents have to take time away from work to look after a child with rotavirus gastroenteritis or to travel to healthcare facilities, or if parents’ other daily activities are curtailed. Information about the emotional impact of rotavirus gastroenteritis on the family is important for a fuller understanding of the burden of rotavirus disease. We conducted a quality of life study as part of the
Surveillance for
Practitioner/Paediatrician for
Rotavirus
Infections in
Kids (
SPRIK) epidemiological study assessing the disease burden of rotavirus among children seen by primary care physicians, to investigate the impact of a child’s rotavirus gastroenteritis on the quality of life of parents and children in three European countries, namely Spain, Italy and Poland. To our knowledge, this is the first multicentre study to investigate this issue using the same validated questionnaire in multiple countries.
Discussion
In this paper we present results from a questionnaire designed to be completed by parents to assess the impact of childhood rotavirus gastroenteritis on affected children and their parents as a quality of life measurement. The questionnaire was validated and used as part of a multinational observational prospective study of children aged <5 years presenting to a general practitioner or paediatrician for acute rotavirus gastroenteritis. To our knowledge, this is the first multicentre multinational study to investigate this issue using the same validated questionnaire in a range of different countries.
Two hundred and sixty-four children with PCR-confirmed rotavirus infection were included in the main analysis. The responses to the self-administered questionnaire showed that PCR-confirmed rotavirus gastroenteritis was associated with changes in the child’s behaviour, parental distress, parental worry and impact on parents’ daily activities. This is consistent with results from previous studies that have found rotavirus gastroenteritis to be associated with particularly severe symptoms [
10][
16]. The validity of the questionnaire was supported by parents reporting a greater change in their child’s behaviour and more worry due to symptoms when the child had clinically severe rotavirus gastroenteritis than when the child had clinically mild rotavirus gastroenteritis (as assessed by the Vesikari scale).
The five scales showed subtly different patterns of variation in relation to demographic parameters. Parents’ perceptions of symptom severity and their worries due to the symptoms unexpectedly increased with the child’s age up to 35 months and then declined. Conversely, the Child’s Behaviour score was lower for children aged under 6 months than for the older age groups. This may reflect the generally lower level of activity in children aged under 6 months, which could make it more difficult to identify a change in behaviour compared with older children. The impact on parents’ daily activities showed a trend to lower scores in children aged under 6 months compared with the older age groups, possibly because parents of children aged under 6 months are likely to be on parental leave, or possibly because a child aged under 6 months requires a great deal of parental attention regardless of health status, and therefore the change in response to illness may be correspondingly less than in older age groups. Another possibility is that parents of children aged under 6 months may be more likely to visit hospitals or emergency rooms if the child has acute severe rotavirus gastroenteritis symptoms, rather than presenting to general practice. As our study was conducted in a general practice setting, it may thus have tended to include less severe cases in very young children, which in turn may have influenced parents’ assessments of the child’s behaviour and impact on the parents’ daily activities.
Rotavirus gastroenteritis confirmed by PCR testing was associated with significantly greater change in the child’s behaviour (p < 0.05), parental distress (p < 0.01) and impact on the parents’ daily activities (p < 0.05), compared with cases that initially tested positive on the rapid test but were negative on PCR. The rapid test is known to have a lower sensitivity than PCR testing (sensitivity around 87%, specificity around 80% [GlaxoSmithKline Biologicals, unpublished data]). The relatively low specificity would be expected to produce some false-positive results (around 20%), and thus the RotaStrip® rapid test was used as a screen with positive results confirmed using PCR as a reference assay. Most of the cases reported in this analysis (n = 264) were positive on both PCR and the rapid test, and 34 cases that were initially positive on the rapid test were negative on PCR (PCR data were missing in 4 cases). The study was conducted before widespread introduction of rotavirus vaccination, and therefore represents the situation in an unvaccinated population.
Parents in all three countries in the study perceived similar changes in their child’s behaviour and similar symptom severity, but there appeared to be subtle country variations in the parents’ perceptions of worry, distress or disruption to daily activities. Polish parents reported greater levels of worry due to their child’s symptoms and a more severe impact on their daily activities compared with Spanish or Italian parents, and there was a trend to greater parents’ distress in Poland and Spain than in Italy. This did not appear to be explained by differences in clinical severity between countries, as Poland did not have a higher percentage of severe cases than Spain or Italy (Table
1). These differences may indicate cultural or social differences, which could be explored in further research.
These variations in the results between the different scales indicate that the five scales provide complementary information. Thus, we elected not to calculate a global score, as the five individual scores provide a more complete picture of the impact of rotavirus gastroenteritis than a global score could achieve.
Among the study’s strengths are its laboratory confirmation of rotavirus infection using PCR, its assessment of case severity using an objective medical evaluation (the Vesikari score), and its use of a questionnaire validated by recognised methods (as described in
Additional file 1). Another key strength of the study is its inclusion of participants from three different countries, applying the same study protocol and design. Participants in all three countries were assessed using the same psychometrically validated questionnaire containing the same items, thereby allowing exploration of similarities and differences in the impact of rotavirus across the different countries and providing a broad perspective on the burden of rotavirus gastroenteritis in Europe.
One limitation of our study is that it was not designed or powered to compare scores according to demographic or risk factors. Thus, although the results indicate that the questionnaire is able to discriminate between different groups of patients, which is encouraging for the future use of the questionnaire in further research, the differences reported here should be interpreted with caution. Another limitation is that the number of respondents in Italy was small. The lower response rate in Italy compared with the other two countries may be due to differences in follow-up, as not all the participating centres in Italy followed up parents who had not returned the questionnaire. It was not possible to determine whether patients enrolled in the study had a previous history of rotavirus gastroenteritis, because testing for rotavirus infection was not part of routine clinical practice when the study was conducted, so we could not assess whether the quality of life impact varied between first and subsequent episodes.
Another limitation of our study is that it did not include a control group of rotavirus-negative patients, as all cases enrolled in the study tested positive for rotavirus on the rapid test. The PCR-negative cases in the study were analysed as a comparison group. However, the comparison should be interpreted with caution, as the PCR-negative cases were few (n = 34). A full comparison of the impact of rotavirus gastroenteritis with that of non-rotavirus gastroenteritis would require a different study design with a rotavirus-negative control group. Our results suggest that the questionnaire described here would be a suitable instrument for such a study.
Our results are broadly consistent with those of other published studies that have investigated the impact of rotavirus gastroenteritis on families. In Canada, a prospective study in children aged under 3 years presenting in outpatient settings with rotavirus gastroenteritis (the MIRAGE study) found that over half (53.8%) of parents of children with rotavirus gastroenteritis had to take time off work as a result of their child’s illness [
17]. A sub-analysis of the same study used the EuroQol 5D (EQ-5D) to assess the parents’ quality of life, and reported adverse effects of the child’s rotavirus gastroenteritis on the parents’ EQ-5D scores on the dimensions of anxiety/depression, pain/discomfort and usual activities [
18]. These studies are consistent with our findings of adverse effects of childhood rotavirus gastroenteritis on parental worry, distress and impact on daily activities. The EQ-5D scale is widely used [
19] and can be converted into utility values using a country-specific algorithm [
20], but it is a generic quality of life instrument rather than a disease-specific measure. A smaller study of children aged 2–36 months presenting with rotavirus gastroenteritis at outpatient clinics or emergency rooms in North Carolina, USA, used qualitative interviews with 17 parents to explore the emotional impact of the child’s illness on the family [
21]. The parents were frightened and worried by the severity of the symptoms, and reported that the child’s illness caused loss of sleep, missed work and difficulty in completing normal household tasks [
21]. Although this study did not attempt to quantify these adverse emotional and practical effects using a scoring system, the issues reported are consistent with those addressed by our questionnaire.
In Europe, a study in 25 hospitals and five primary care centres in Spain found that rotavirus-positive gastroenteritis in children aged under 2 years was associated with more severe parental worry and more disruption to household tasks than rotavirus-negative gastroenteritis [
22]. The multi-country REVEAL study conducted in Belgium, France, Germany, Italy, Spain, Sweden and the UK in 2004–2005 found high levels of self-reported parental stress among parents of children with rotavirus gastroenteritis aged under 5 years, with mean stress levels of 4.5 to 8.99 on a visual analogue scale from 1 (no stress) to 10 (extremely stressed) [
23]. A large survey conducted in 69 paediatric practices in Germany in 2005–2006 used a questionnaire developed for the study (the Parental Appraisal of the Morbidity of Diarrhea in Infants and toddlers [PAMODI]) to assess clinical and behavioural symptoms, treatment and parental feelings in 2023 parents of children aged under 2 years presenting with diarrhoea [
24]. Parents’ feelings were characterised by sympathy and anxiety for the child, followed by feelings of helplessness, stress and exhaustion. Over half (53.6%)of parents of children with severe gastroenteritis reported restrictions on their normal daily activities [
24]. The validity of the PAMODI questionnaire was supported by the finding that clinically more severe disease (measured by a modified Vesikari score) was associated with a higher perceived disease burden, but the psychometric properties of the PAMODI questionnaire were not formally investigated. Our study builds on the earlier results by using a fully validated questionnaire specifically designed for use with parents of children experiencing rotavirus gastroenteritis.
Acknowledgements
The SPRIK Rotavirus Study Group in the countries in this study included: Julia Colomer (Spain), Isabel Ubeda (Spain), Trinidad Alvarez-Laviada (Spain), Mercedes Garcia (Spain), Angels Jubert (Spain), María Garcés (Spain), Carmen Peidró (Spain), Victoria Planelles (Spain), Carmen Casani (Spain), Giacomo Toffol (Italy), Silvia Carnazza (Italy).
Other contributors to the SPRIK study were: Manuel Martínez-Pons (Spain), Jose Villaroya (Spain), Luis Blesa (Spain), Inmaculada Latorre (Spain), Pilar Albors-Esteve (Spain), Anton Crespo (Spain), Mª Dolores Gallego (Spain), Mª Mercedes Garcia-Ballesta (Spain),Mª Desamparados Gil-Mary (Spain), Marta Graullera-Millas (Spain), Teresa Margarit-Vercher (Spain), Mª Jesus Muñoz (Spain), Amelia Peris-Vidal (Spain), Pedro Polo-Martin (Spain), Alesandra Puertes-Almenar (Spain), Mª José Sanz (Spain), Ignacio Sorribes-Monrabal (Spain), Pilar García-Corbeira (GSK Spain), Eduardo Fernández (GSK Spain), Sandra Sistiaga (GSK Spain), Saúl Robles (GSK Spain), Silvia Della Coletta (GSK Italy), Federico Marchetti (GSK Italy), Alicja Ksiazek (GSK Poland).
The authors would like to thank Khadra Benmedjahed from Mapi Values for her help in the questionnaire development, as well as Muriel Viala-Danten from Mapi Values for her advice in the statistical analyses. The authors would also like to thank Carlo Giaquinto, an independent expert contracted by GlaxoSmithKline Biologicals to act as lead editorial advisor, for assistance with data review and manuscript preparation including critical reviewing. Medical writing assistance was provided by Carole Nadin, and publication co-ordination and editorial assistance by Uta Gomes, funded by GlaxoSmithKline Biologicals, Rixensart, Belgium.
RotaStrip is a registered trademark of Coris BioConcept.
Competing interests
Dr J Diez Domingo is a member of advisory boards and speaker bureaus for GlaxoSmithKline, SPMSD and Pfizer for which he receives payment. He is also a principal investigator in clinical trials for GlaxoSmithKline and SPMSD.
Dr L Cantarutti does not have any conflicts of interest to declare.
Dr M Patrzalek received payment for services on lecture bureaus for GlaxoSmithKline, Polpharma, and Pfizer.
Dr Benoit Arnould and Juliette Meunier work for MAPI Values who receive grants and payment from GlaxoSmithKline Group of Companies to conduct statistical analyses and research.
Nadia Meyer, Jean-Yves Pircon and Katsiaryna Holl are employed by the GlaxoSmithKline Group of Companies. Montse Soriano Gabarro was an employee of GlaxoSmithKline Group of Companies at commencement of this study.
This study, including preparation of the manuscript, was funded by GlaxoSmithKline Biologicals, Rixensart, Belgium. The study sponsor was involved in the design and conduct of the trial, and in data collection and analysis. All authors had full access to the clinical trial report and reviewed all drafts of the manuscript. The corresponding author had final responsibility for the decision to submit for publication.
Authors’ contributions
JDD, LC, MP, MSG, NM and JYP, took part in the design of the study and collection of the data. JYP, JM and BA performed the data analyses. All authors reviewed and commented on the draft manuscript, and all authors read and approved the final manuscript.