Scandinavian Journal of Infectious Diseases
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden Malin Rinder, Anh Nhi Tran, Rutger Bennet, Maria Brytting, Tobias Cassel, Margareta Eriksson, Deborah Frithiof, Leif Gothefors, Jann Storsaeter, Birger Trollfors, Sindri Valdimarsson, Martin Wennerström & Kari Johansen To cite this article: Malin Rinder, Anh Nhi Tran, Rutger Bennet, Maria Brytting, Tobias Cassel, Margareta Eriksson, Deborah Frithiof, Leif Gothefors, Jann Storsaeter, Birger Trollfors, Sindri Valdimarsson, Martin Wennerström & Kari Johansen (2014) Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden, Scandinavian Journal of Infectious Diseases, 46:4, 294-302 To link to this article: http://dx.doi.org/10.3109/00365548.2013.876511
Published online: 03 Feb 2014.
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Date: 24 September 2015, At: 20:47
Scandinavian Journal of Infectious Diseases, 2014; 46: 294–302
ORIGINAL ARTICLE
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden
MALIN RINDER1*, ANH NHI TRAN2,3*, RUTGER BENNET4, MARIA BRYTTING2**, TOBIAS CASSEL5, MARGARETA ERIKSSON4, DEBORAH FRITHIOF6, LEIF GOTHEFORS6, JANN STORSAETER7,8, BIRGER TROLLFORS9, SINDRI VALDIMARSSON9, MARTIN WENNERSTRÖM9 & KARI JOHANSEN2,3 From the 1Sachs’ Children’s Hospital, Stockholm South General Hospital, Stockholm, Sweden, 2Department of Virology, Swedish Institute for Communicable Disease Control, Stockholm, Sweden, 3Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden, 4Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden, 5Sanofi Pasteur, Solna, Sweden, 6Department of Clinical Sciences, Paediatrics, Umeå University Hospital, Umeå, Sweden, 7GlaxoSmithKline, Sweden, 8Vaccine Department, National Public Health Institute, Oslo, Norway, and 9Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
Abstract Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirusinduced gastroenteritis in Swedish children aged ⬍ 5 y. Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged ⬍ 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February–April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature ⬎ 38.5°C upon admission. Complications occurred in ⬎ 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in ⬎ 10% of hospitalized children.
Keywords: Rotavirus, incidence, hospitalization, complication, genotype
Introduction Rotaviruses are the most common causes of severe acute gastroenteritis in young children, and in the pre-vaccine era were estimated to cause around 2 million hospitalizations and up to 453,000 deaths in children aged ⬍ 5 y worldwide annually [1]. Five genotypes are globally known to cause ⬎ 80% of all rotavirus infections: G1[P8], G2[P4], G3[P8], G4[P8], and G9[P8] [2].
In most European countries, Germany being an exception, rotavirus disease is not a notifiable infectious disease, which is why no comprehensive epidemiological surveillance data exist for the region. A network of laboratories collaborate to genotype and collect information on circulating rotavirus genotypes in Europe in a standardized way [3]. In addition, circulating rotavirus strains, including new emerging genotypes, have been monitored by the World Health
*These two authors contributed equally to this study. **Project leader from 1 December, 2008. Correspondence: M. Rinder, Sachs’ Children Hospital, Stockholm South General Hospital, SE-118 83 Stockholm, Sweden. E-mail: malin.ryd-rinder@ sodersjukhuset.se (Received 30 October 2013 ; accepted 28 November 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.876511
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Burden of severe rotavirus disease in Sweden Organization (WHO) since 2002, in a global surveillance system to which 64 countries report today. The burden and severity of rotavirus disease in Sweden have been evaluated in 4 previous studies [4–7]. Already in 1986, the first study showed that almost 50% of hospitalized children with acute gastroenteritis suffered from rotavirus-induced gastroenteritis [4]. Extrapolating retrospective data from 2 large children’s hospitals, available national laboratory data, and national hospitalization data for children with acute diarrhoea under 4 y of age collected by the Swedish National Board of Health in the y 1993–1996, suggested an annual incidence of 370 hospitalizations/100,000 children [5]. A prospective observational multicenter study (REVEAL) was performed in 2004–2005 by one of the vaccine manufacturers in 7 European countries, including 1 Swedish hospital situated in Umeå in northern Sweden. Data obtained in that study suggested an incidence of 770 hospitalizations per 100,000 children [6]. Finally, significant complications attributable to rotavirus-induced gastroenteritis in a Swedish paediatric population were identified in an observational study conducted over 11 y [7]. The WHO has recommended rotavirus vaccination for all children since 2009 [8]. The introduction of rotavirus vaccination in countries with similar socioeconomic conditions to Sweden has led to a significant reduction in hospitalizations due to rotavirus-induced gastroenteritis [9–23]. With growing interest in the possible introduction of vaccination against rotavirus-induced gastroenteritis in the routine programme, the need for baseline data to enable future evaluation of vaccination impact on hospitalizations and rotavirus genotype patterns was identified. The aims of this prospective cohort study were to determine the incidence of severe disease leading to hospitalization due to rotavirus-induced gastroenteritis, the age and gender distribution of cases, seasonality, the proportion of nosocomial and community-acquired cases, and the genotype pattern of circulating rotavirus strains in children under 5 y of age. In addition, the clinical course and treatment of the disease were analysed, as was the contribution of underlying medical conditions to hospitalizations.
295
coordinated by the Swedish Institute for Communicable Disease Control and involved 4 study hospitals: (1) the Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg with 47,053 children ⬍ 5 y of age in western Sweden, (2) the Astrid Lindgren Children’s Hospital, Karolinska University Hospital with 66,222 children ⬍ 5 y of age and (3) Sachs’ Children’s Hospital, South General Hospital with 34,435 children ⬍ 5 y of age, both located in Stockholm in eastern Sweden, and (4) the Department of Clinical Sciences, Paediatrics, Umeå University Hospital with 8128 children ⬍ 5 y of age located in northern Sweden. Study subjects Children under 5 y of age and hospitalized for acute gastroenteritis (vomiting and/or ⱖ 3 loose stools/day) were considered eligible for the study and were tested upon admission for the excretion of rotavirus. Testpositive children were offered inclusion in the study following the provision of informed consent. Rotavirus diagnosis and genotyping Following hospital admission, faecal samples from all children with acute gastroenteritis were first tested with the rapid VIKIA ROTA-ADENO test (BioMérieux Clinical Diagnostics) available 24/7. VIKIA ROTA-ADENO-negative samples were further tested by ELISA (IDEIA™ Rotavirus, DakoCytomation Ltd, UK; cut-off 0.7 OD). Faecal samples from all rapid-test positive cases were confirmed by PCR. Using identified PCR products, rotavirus strains were further genotyped by multiplex PCR (http:// www.eurorota.net/docs.php). Nosocomial versus community-derived infections Each case of rotavirus-induced gastroenteritis was evaluated as being nosocomial or communityderived. The case definition used for a nosocomial case was the development of acute rotavirus-induced gastroenteritis during or within 72 h following hospitalization for another diagnosis. Duration of hospitalization
Materials and methods Study design The burden of severe rotavirus-induced gastroenteritis leading to hospitalization was assessed in a prospective cohort study including study hospitals serving approximately 30% of all Swedish children younger than 5 y of age. The study was conducted over a 12-month period from October 2007 to October 2008. The study was
The study protocol stipulated calculation of the duration of hospitalization using the following formula: discharge date – date of admission ⫹ 1 day. Results obtained were validated through chart review at study centre 3. Structured interviews with the affected families All families were interviewed by study nurses, available daytime Monday through Friday and most
296
M. Rinder et al.
weekends. Data were collected in a standardized case report form.
Clinical symptoms and complications Clinical symptoms, complications, laboratory results, and treatment provided were recorded.
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Evaluation of dehydration Blood samples were obtained as part of routine care for the analysis of sodium (S-Na; normal value 135– 147 mmol/l), potassium (S-K; normal value 3.5– 4.5 mmol/l), and chloride (S-Cl; normal value 98–107 mmol/l). Serum samples for electrolyte evaluation were available from 551/604 children. Using the laboratory results obtained and clinical information such as weight loss and general clinical appearance, the clinician responsible at each study centre judged the level of dehydration. Mild dehydration was defined as weight loss ⬍ 5%, moderate dehydration as 5–10%, and severe dehydration as ⬎ 10% weight loss. Hypertonic dehydration was defined as S-Na ⬎ 150 mmol/l. Evaluation of transaminases As part of the cohort study, serum samples from a subset of children were evaluated for serum transaminases by the laboratories in the respective hospitals: alanine aminotransferase (S-ALT; normal value ⬍ 1.0 μkat/l) and aspartate aminotransferase (S-AST; normal value ⬍ 0.8 μkat/l). Underlying medical conditions Underlying medical conditions were recorded. Follow-up Following discharge, families were contacted approximately 14 days later by the study nurse and a structured follow-up interview was performed. Questions were posed on the total duration of diarrhoea, the persistence of fever and vomiting, and changes in feeding and general behaviour. Ethical approval The study was approved by the Karolinska Institute Ethics Committee (Dnr 2007/578-31/4). The study was conducted in accordance with Good Clinical Practice and the 1996 version of the Declaration of Helsinki.
Statistics All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC, USA). Continuous variables were described with the number of observations available (n), the mean, standard deviation, median, minimum, maximum, and missing. Categorical variables were described with frequency tables; absolute numbers and percentages were computed for each level. All confidence intervals (CI) were 2-sided 95% CI. To estimate the confidence limit of the incidence rate, the exact confidence limit was used. The exact 95% CIs for a proportion within a group were calculated from ProcStatXact. Associations were calculated using the Chi-square test and Cochran–Armitage trend test.
Results Study cohort Of a total 1549 children aged ⬍ 5 y admitted with acute gastroenteritis, 642 rapid test rotavirus-positive children were initially included (Figure 1). A total 38 children were later excluded due to protocol violations or a rotavirus infection that could not be confirmed by PCR (rapid test false-positive). Altogether, 604 children were included in the study cohort and were used for the data analysis. In the whole study cohort, 49 children (8.1%) fulfilled the criteria for a nosocomial infection (range 4.6–15.9% in the different study hospitals). Age and gender distribution The median age of included cases was 14 months and only 15/604 (2.5%) of the children were younger than 3 months of age (Figure 2). The median age of children with community-derived infections was 15 months, while for nosocomial infections it was 9 months. Two hundred and eighty-nine (47.8%) of the cases were females and 315 (52.2%) were males. Seasonality The rotavirus season started at different time-points in the 3 regions, with the first cases observed in the eastern region in the month of October, followed by cases observed in the western region in November and then cases in the northern region first in December. However, at least 1 case of rotavirus occurred in every month of the year, suggesting that the rotaviruses circulate all year round (June–September, n ⫽ 31), with cases diagnosed in all of the summer months. The peak was observed in February–April in all regions (Figure 3).
Burden of severe rotavirus disease in Sweden All children
ISSN: 0036-5548 (Print) 1651-1980 (Online) Journal homepage: http://www.tandfonline.com/loi/infd19
Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden Malin Rinder, Anh Nhi Tran, Rutger Bennet, Maria Brytting, Tobias Cassel, Margareta Eriksson, Deborah Frithiof, Leif Gothefors, Jann Storsaeter, Birger Trollfors, Sindri Valdimarsson, Martin Wennerström & Kari Johansen To cite this article: Malin Rinder, Anh Nhi Tran, Rutger Bennet, Maria Brytting, Tobias Cassel, Margareta Eriksson, Deborah Frithiof, Leif Gothefors, Jann Storsaeter, Birger Trollfors, Sindri Valdimarsson, Martin Wennerström & Kari Johansen (2014) Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden, Scandinavian Journal of Infectious Diseases, 46:4, 294-302 To link to this article: http://dx.doi.org/10.3109/00365548.2013.876511
Published online: 03 Feb 2014.
Submit your article to this journal
Article views: 212
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd19 Download by: [University of Lethbridge]
Date: 24 September 2015, At: 20:47
Scandinavian Journal of Infectious Diseases, 2014; 46: 294–302
ORIGINAL ARTICLE
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden
MALIN RINDER1*, ANH NHI TRAN2,3*, RUTGER BENNET4, MARIA BRYTTING2**, TOBIAS CASSEL5, MARGARETA ERIKSSON4, DEBORAH FRITHIOF6, LEIF GOTHEFORS6, JANN STORSAETER7,8, BIRGER TROLLFORS9, SINDRI VALDIMARSSON9, MARTIN WENNERSTRÖM9 & KARI JOHANSEN2,3 From the 1Sachs’ Children’s Hospital, Stockholm South General Hospital, Stockholm, Sweden, 2Department of Virology, Swedish Institute for Communicable Disease Control, Stockholm, Sweden, 3Department of Microbiology, Tumour and Cell Biology, Karolinska Institute, Stockholm, Sweden, 4Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden, 5Sanofi Pasteur, Solna, Sweden, 6Department of Clinical Sciences, Paediatrics, Umeå University Hospital, Umeå, Sweden, 7GlaxoSmithKline, Sweden, 8Vaccine Department, National Public Health Institute, Oslo, Norway, and 9Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
Abstract Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirusinduced gastroenteritis in Swedish children aged ⬍ 5 y. Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged ⬍ 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February–April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature ⬎ 38.5°C upon admission. Complications occurred in ⬎ 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in ⬎ 10% of hospitalized children.
Keywords: Rotavirus, incidence, hospitalization, complication, genotype
Introduction Rotaviruses are the most common causes of severe acute gastroenteritis in young children, and in the pre-vaccine era were estimated to cause around 2 million hospitalizations and up to 453,000 deaths in children aged ⬍ 5 y worldwide annually [1]. Five genotypes are globally known to cause ⬎ 80% of all rotavirus infections: G1[P8], G2[P4], G3[P8], G4[P8], and G9[P8] [2].
In most European countries, Germany being an exception, rotavirus disease is not a notifiable infectious disease, which is why no comprehensive epidemiological surveillance data exist for the region. A network of laboratories collaborate to genotype and collect information on circulating rotavirus genotypes in Europe in a standardized way [3]. In addition, circulating rotavirus strains, including new emerging genotypes, have been monitored by the World Health
*These two authors contributed equally to this study. **Project leader from 1 December, 2008. Correspondence: M. Rinder, Sachs’ Children Hospital, Stockholm South General Hospital, SE-118 83 Stockholm, Sweden. E-mail: malin.ryd-rinder@ sodersjukhuset.se (Received 30 October 2013 ; accepted 28 November 2013) ISSN 0036-5548 print/ISSN 1651-1980 online © 2014 Informa Healthcare DOI: 10.3109/00365548.2013.876511
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Burden of severe rotavirus disease in Sweden Organization (WHO) since 2002, in a global surveillance system to which 64 countries report today. The burden and severity of rotavirus disease in Sweden have been evaluated in 4 previous studies [4–7]. Already in 1986, the first study showed that almost 50% of hospitalized children with acute gastroenteritis suffered from rotavirus-induced gastroenteritis [4]. Extrapolating retrospective data from 2 large children’s hospitals, available national laboratory data, and national hospitalization data for children with acute diarrhoea under 4 y of age collected by the Swedish National Board of Health in the y 1993–1996, suggested an annual incidence of 370 hospitalizations/100,000 children [5]. A prospective observational multicenter study (REVEAL) was performed in 2004–2005 by one of the vaccine manufacturers in 7 European countries, including 1 Swedish hospital situated in Umeå in northern Sweden. Data obtained in that study suggested an incidence of 770 hospitalizations per 100,000 children [6]. Finally, significant complications attributable to rotavirus-induced gastroenteritis in a Swedish paediatric population were identified in an observational study conducted over 11 y [7]. The WHO has recommended rotavirus vaccination for all children since 2009 [8]. The introduction of rotavirus vaccination in countries with similar socioeconomic conditions to Sweden has led to a significant reduction in hospitalizations due to rotavirus-induced gastroenteritis [9–23]. With growing interest in the possible introduction of vaccination against rotavirus-induced gastroenteritis in the routine programme, the need for baseline data to enable future evaluation of vaccination impact on hospitalizations and rotavirus genotype patterns was identified. The aims of this prospective cohort study were to determine the incidence of severe disease leading to hospitalization due to rotavirus-induced gastroenteritis, the age and gender distribution of cases, seasonality, the proportion of nosocomial and community-acquired cases, and the genotype pattern of circulating rotavirus strains in children under 5 y of age. In addition, the clinical course and treatment of the disease were analysed, as was the contribution of underlying medical conditions to hospitalizations.
295
coordinated by the Swedish Institute for Communicable Disease Control and involved 4 study hospitals: (1) the Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg with 47,053 children ⬍ 5 y of age in western Sweden, (2) the Astrid Lindgren Children’s Hospital, Karolinska University Hospital with 66,222 children ⬍ 5 y of age and (3) Sachs’ Children’s Hospital, South General Hospital with 34,435 children ⬍ 5 y of age, both located in Stockholm in eastern Sweden, and (4) the Department of Clinical Sciences, Paediatrics, Umeå University Hospital with 8128 children ⬍ 5 y of age located in northern Sweden. Study subjects Children under 5 y of age and hospitalized for acute gastroenteritis (vomiting and/or ⱖ 3 loose stools/day) were considered eligible for the study and were tested upon admission for the excretion of rotavirus. Testpositive children were offered inclusion in the study following the provision of informed consent. Rotavirus diagnosis and genotyping Following hospital admission, faecal samples from all children with acute gastroenteritis were first tested with the rapid VIKIA ROTA-ADENO test (BioMérieux Clinical Diagnostics) available 24/7. VIKIA ROTA-ADENO-negative samples were further tested by ELISA (IDEIA™ Rotavirus, DakoCytomation Ltd, UK; cut-off 0.7 OD). Faecal samples from all rapid-test positive cases were confirmed by PCR. Using identified PCR products, rotavirus strains were further genotyped by multiplex PCR (http:// www.eurorota.net/docs.php). Nosocomial versus community-derived infections Each case of rotavirus-induced gastroenteritis was evaluated as being nosocomial or communityderived. The case definition used for a nosocomial case was the development of acute rotavirus-induced gastroenteritis during or within 72 h following hospitalization for another diagnosis. Duration of hospitalization
Materials and methods Study design The burden of severe rotavirus-induced gastroenteritis leading to hospitalization was assessed in a prospective cohort study including study hospitals serving approximately 30% of all Swedish children younger than 5 y of age. The study was conducted over a 12-month period from October 2007 to October 2008. The study was
The study protocol stipulated calculation of the duration of hospitalization using the following formula: discharge date – date of admission ⫹ 1 day. Results obtained were validated through chart review at study centre 3. Structured interviews with the affected families All families were interviewed by study nurses, available daytime Monday through Friday and most
296
M. Rinder et al.
weekends. Data were collected in a standardized case report form.
Clinical symptoms and complications Clinical symptoms, complications, laboratory results, and treatment provided were recorded.
Downloaded by [University of Lethbridge] at 20:47 24 September 2015
Evaluation of dehydration Blood samples were obtained as part of routine care for the analysis of sodium (S-Na; normal value 135– 147 mmol/l), potassium (S-K; normal value 3.5– 4.5 mmol/l), and chloride (S-Cl; normal value 98–107 mmol/l). Serum samples for electrolyte evaluation were available from 551/604 children. Using the laboratory results obtained and clinical information such as weight loss and general clinical appearance, the clinician responsible at each study centre judged the level of dehydration. Mild dehydration was defined as weight loss ⬍ 5%, moderate dehydration as 5–10%, and severe dehydration as ⬎ 10% weight loss. Hypertonic dehydration was defined as S-Na ⬎ 150 mmol/l. Evaluation of transaminases As part of the cohort study, serum samples from a subset of children were evaluated for serum transaminases by the laboratories in the respective hospitals: alanine aminotransferase (S-ALT; normal value ⬍ 1.0 μkat/l) and aspartate aminotransferase (S-AST; normal value ⬍ 0.8 μkat/l). Underlying medical conditions Underlying medical conditions were recorded. Follow-up Following discharge, families were contacted approximately 14 days later by the study nurse and a structured follow-up interview was performed. Questions were posed on the total duration of diarrhoea, the persistence of fever and vomiting, and changes in feeding and general behaviour. Ethical approval The study was approved by the Karolinska Institute Ethics Committee (Dnr 2007/578-31/4). The study was conducted in accordance with Good Clinical Practice and the 1996 version of the Declaration of Helsinki.
Statistics All statistical analyses were performed using SAS version 9.1 (SAS Institute, Cary, NC, USA). Continuous variables were described with the number of observations available (n), the mean, standard deviation, median, minimum, maximum, and missing. Categorical variables were described with frequency tables; absolute numbers and percentages were computed for each level. All confidence intervals (CI) were 2-sided 95% CI. To estimate the confidence limit of the incidence rate, the exact confidence limit was used. The exact 95% CIs for a proportion within a group were calculated from ProcStatXact. Associations were calculated using the Chi-square test and Cochran–Armitage trend test.
Results Study cohort Of a total 1549 children aged ⬍ 5 y admitted with acute gastroenteritis, 642 rapid test rotavirus-positive children were initially included (Figure 1). A total 38 children were later excluded due to protocol violations or a rotavirus infection that could not be confirmed by PCR (rapid test false-positive). Altogether, 604 children were included in the study cohort and were used for the data analysis. In the whole study cohort, 49 children (8.1%) fulfilled the criteria for a nosocomial infection (range 4.6–15.9% in the different study hospitals). Age and gender distribution The median age of included cases was 14 months and only 15/604 (2.5%) of the children were younger than 3 months of age (Figure 2). The median age of children with community-derived infections was 15 months, while for nosocomial infections it was 9 months. Two hundred and eighty-nine (47.8%) of the cases were females and 315 (52.2%) were males. Seasonality The rotavirus season started at different time-points in the 3 regions, with the first cases observed in the eastern region in the month of October, followed by cases observed in the western region in November and then cases in the northern region first in December. However, at least 1 case of rotavirus occurred in every month of the year, suggesting that the rotaviruses circulate all year round (June–September, n ⫽ 31), with cases diagnosed in all of the summer months. The peak was observed in February–April in all regions (Figure 3).
Burden of severe rotavirus disease in Sweden All children
