- Email: [email protected]
Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study
ORIGINAL ARTICLE
10.1111/j.1469-0691.2009.02831.x
Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study C. Arias1, M. R. Sala1, A. Domı´nguez2,3,4, N. Torner3,4, L. Ruı´z4, A. Martı´nez4, R. Bartolome´5, M. de Simo´n6 and J. Buesa7 1) Epidemiological Surveillance Unit of the Central Region of Catalonia, Department of Health, Generalitat of Catalonia, Terrassa, 2) Department of Public Health, University of Barcelona, 3) CIBER Epidemiologı´a y Salud Pu´blica (CIBERESP), 4) Department of Health, Generalitat of Catalonia, 5) Microbiology Department, Hospital Universitari Vall d’Hebron and 6) Laboratory of the Public Health Agency, Barcelona and 7) Microbiology Department, University of Valencia, Valencia, Spain
Abstract Noroviruses are the most frequent cause of acute gastroenteritis in the community. In Catalonia, it is not clear how this type of viral gastroenteritis is evolving, and the objective of this prospective population-based study was to describe the incidence and epidemiological and clinical features of outbreaks of acute gastroenteritis due to norovirus in Catalonia between October 2004 and October 2005. Incidence rates were calculated using the estimated population of Catalonia in 2005. For each outbreak, the mode of transmission, the number of persons affected, demographic variables, clinical presentation, the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. Sixty viral outbreaks affecting 1791 people were identified, with no distinct seasonality. The mean number of outbreaks per month was 4.6. The global incidence was 24.6 per 100 000 person-years. The incidence was higher in women (25.7 per 100 000 person-years) and in the 5–11 years (52.4 per 100 000 person-years) and ‡65 years (42.4 per 100 000 person-years) age groups. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. These results suggest that norovirus infection has an important public health impact in Catalonia and that prevention strategies should be designed and implemented. Keywords: Clinical features, norovirus; outbreak; incidence, population-based study Original Submission: 18 November 2008; Revised Submission: 13 January 2009; Accepted: 16 January 2009 Editor: D. Raoult Article published online: 22 June 2009 Clin Microbiol Infect 2010; 16: 39–44 Corresponding author and reprint requests: C. Arias, Epidemiological Surveillance Unit of the Central Region, Carretera de Torrebonica s/n, 08227, Terrassa, Spain E-mail: [email protected]
Introduction Gastrointestinal tract infections are common in both developing and developed countries [1] and are produced by a wide variety of enteropathogens including bacteria, viruses and parasites. The main causes of viral gastroenteritis include adenoviruses, astroviruses, noroviruses (NV) and rotaviruses [2]. Since the original outbreak of Norwalk virus gastroenteritis in an elementary school in Norwalk (OH, USA) in the fall of 1968, studies have shown that viral infections, especially those due to NV, are the most frequent cause of acute gastroenteritis in the community [3–7]. NV infects all age groups, with particularly severe disease occurring in young children, the elderly, and persons with chronic illness [8].
NV infections have historically been described as mild and self-limiting. Studies in the 1970s were the basis for the criteria used by Kaplan et al. to discern outbreaks with a viral aetiology, which include stool culture negative for bacterial pathogens, mean (or median) duration of illness 12–60 h, vomiting in ‡50% of cases, and, if known, mean (or median) incubation period of 24–48 h [9]. NV have emerged as an important cause of human viral gastroenteritis and cause outbreaks in a wide range of settings, including nursing homes, hospitals, retirement centres, summer camps, schools, restaurants and events with catered meals and cruise ships. The mode of transmission may be foodborne, waterborne or person-to-person contact [9–12]. There are many reports of NV outbreaks that include details on the mode of transmission and setting and, in some cases, the molecular epidemiology of circulating NV strains [3– 5,7,9,13–16]. However, there are fewer reports on the clinical manifestations of NV infections in the community [11,17]. The objective of this study was to describe the epidemiological and clinical features of outbreaks of acute gastroenteritis
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases
40
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
CMI
due to NV in Catalonia between October 2004 and October 2005.
The level of statistical significance was established as a = 0.05.
Materials and Methods
Results
In Catalonia, a region of seven million inhabitants in the northeast of Spain, reporting of epidemic outbreaks of gastroenteritis by public and private physicians to the Department of Health is mandatory. Between 15 October 2004 and 30 October 2005, information on all reported viral outbreaks of gastroenteritis was systematically compiled and epidemiological and clinical data of cases involved in the outbreaks were collected on a standardized form using a protocol designed specifically for the study. For each outbreak, the mode of transmission, the number of persons affected, the age and sex, clinical presentation (including diarrhoea, vomiting, abdominal pain, nausea, fever, headache, myalgia, general malaise and chills), the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. The case definition of viral gastroenteritis used was two or more loose stools in 24 h and/or vomiting twice or more in 24 h, with additional symptoms including nausea, fever, abdominal pain, headache, myalgia, general malaise and chills. The incidence rates of cases associated with outbreaks occurring during the study period were calculated using the estimated population of Catalonia in 2005 and the 95% CIs were calculated assuming Poisson distribution. Stool samples were collected using the following norms: (i) samples were collected during the acute phase (first 3–5 days) of the infection; (ii) a minimum of 1 g of faeces was collected in a sterile, preferably plastic, container; (iii) no faeces mixed with urine were collected; (iv) only faeces without preservative were collected; and (v) no samples were collected using rectal swabs. Samples were kept at room temperature for 2 h followed by refrigeration at 4C for 2 days and freezing at )20C until microbiological analysis, which was carried out by the reference laboratories. Samples were transported to the laboratory in a refrigerated state by courier. Samples were pre-screened using standard microbiological tests to rule out bacteria and parasites. Viruses were identified by RT-PCR according to previously described methods [18–20]. In the statistical analysis, the v2 test was used to measure qualitative variables and Student’s t-test to measure quantitative variables. All statistical analyses were carried out using the SPSS V12 statistical program (SPSS Inc., Chicago, IL, USA).
During the study period, 60 viral outbreaks affecting 1791 people were identified. The outbreaks occurred mainly in restaurants (37%), nursing homes (18.3%), private residences (18.3%), hospital or long-term care facilities (10%), and holiday camps (10%). Incidence rates were calculated using the 1791 cases identified. Two hundred and forty-seven cases were excluded from the analysis of the onset of symptoms, disease duration and symptoms presented due to lack of information on these variables. Therefore the remaining analyses were made in 1544 cases. Stool samples were analysed in 534 patients. In six patients infected by norovirus, co-infection by Salmonella typhimurium or Vibrio parahaemolyticus was detected. Viruses were found in 277 patients, of which 273 corresponded to NV. The genotype was determined in 217/273 samples positive for NV. Because the samples were pre-screened using standard microbiological tests to rule out bacteria and parasites, these enteropathogens were not determined in our investigation. The outbreaks occurred predominantly between October and March (excepting January) with an increase from July onwards, although outbreaks occurred during all the months studied (Fig. 1). The mean number of outbreaks per month was 4.6 (SD ± 2.2). The global incidence rate was 24.6/100 000 person-years (95% CI 23.4–25.7), with rates of 25.7/100 000 person-years in women and 18.2/100 000 person-years in men. The incidence rates were highest in the 5–11 years and ‡65 years age groups (Table 1). Persons of all ages, from 14 months to 100 years, were affected (mean age 44.7 years). A total of 24.1% of cases occurred in the <15 years age group and 75.9% in the
No of outbreaks
10 8 6 4 2 0 Oct
Nov Dec Jan Feb Mar 2004
Apr May Jun
Jul
Aug Sept Oct
2005
FIG. 1. Monthly distribution of the 60 outbreaks included in the study. N.B. When setting figure, use the powerpoint version, which has the axes correctly labelled.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
CMI
Arias et al.
TABLE 1. Incidence rates and rates ratio of cases according
TABLE 2. Distribution of symptoms according to sex in
to age and sex
1544 cases
Incidence rates per 100 000 person-years (95% CI)
Global Sexa Male Female
24.6 (23.4–25.7) 18.2 (16.8–19.6) 25.7 (24.1–27.3)
41
Sex Rates ratio (95% CI)
Symptoms
Reference 1.41 (1.28–1.56)
Ageb <1 year 1–4 years 5–11 years 12–17 years 18–64 years ‡65 years
No cases 20.6 (15.4–25.8) 52.4 (45.8–59.0) 30.2 (24.8–35.6) 13.0 (12.0–14.0) 42.4 (38.7–46.1)
– Reference 2.54 (1.92–3.37) 1.46 (1.08–2.00) 0.63 (0.48–0.82) 2.06 (1.58–2.68)
– 1.58 (1.22–2.06) 4.03 (3.48–4.68) 2.32 (1.91–2.82) Reference 3.26 (2.90–3.66)
Ageb <1 year 1–4 years 5–14 years 15–24 years 25–39 years 40–64 years ‡65 years
No cases 20.6 (15.4–25.8) 50.1 (44.6–55.5) 18.1 (15.6–21.0) 12.9 (11.3–14.5) 11.5 (10.1–12.9) 42.4 (38.7–46.1)
– Reference 2.43 (1.85–3.19) 0.88 (0.65–1.18) 0.63 (0.47–0.83) 0.56 (0.42–0.74) 2.06 (1.58–2.68)
– 1.79 (1.35–2.36) 4.34 (3.69–5.02) 1.57 (1.28–1.92) 1.12 (0.94–1.33) Reference 3.68 (3.17–4.27)
a
Population-based study of gastroenteritis
In 189/1791 cases, sex was unknown. In 230/1791 cases, age was unknown.
b
‡15 years age group (15–64 years, 42.8%; ‡65 years, 33.1%). Forty-one percent of cases occurred in male subjects (mean age 38.6 years, SD ± 27.8) and 59% in female subjects (mean age 49.1 years, SD ± 30.1) (p <0.001), of which 30.4% occurred in male subjects aged <15 years, compared with 19.7% in female subjects (p <0.001). The first symptom to appear was diarrhoea in 23.1% of cases, vomiting in 19.6% and abdominal pain in 15.9%. Diarrhoea and vomiting coexisted in 45.2% of cases, and there was diarrhoea without vomiting in 34.9% of cases and vomiting without diarrhoea in 19.9%. The mean number of defaecations in 24 h was 4.5 (SD ± 3.5); the mean number of episodes of vomiting in 24 h was 3.7 (SD ± 2.5); in patients with fever, the mean maximum temperature was 37.8C (SD ± 0.6C). Abdominal pain and fever were more frequent in men than in women (70.8% vs. 64.4%, p 0.013; and 34.5% vs. 28.9%, p 0.022, respectively). No differences were found between sexes for the other symptoms studied (Table 2). Diarrhoea occurred more frequently in people aged >18 years, whereas vomiting and abdominal pain were more frequent in people aged <18 years (Table 3). Malaise was more frequent in children aged <11 years. The other symptoms studied were more frequent in the 12–64 years age group. In the ‡65 years age group, the predominant symptom was diarrhoea (87.9%) followed by vomiting (52.9%). The risk of diarrhoea was greater in people aged >65 than in people aged <65 years (OR 2.61; 95% CI 1.93–3.55),
All cases (total 1544)
Male
Female
Cases %
Cases %
Cases %
OR (95% CI)
483 390 402 289 203 172 128 77 56
703 574 543 439 247 254 185 107 61
0.96 0.94 1.34 0.94 1.30 1.04 1.01 1.10 1.35
Diarrhoea 1186 Vomiting 964 Abdominal pain 945 Nausea 728 Fever 453 Headache 426 Myalgia 313 Chills 184 General malaise 117
78.8 64.9 67.0 51.6 31.2 31.0 24.1 15.4 7.6
78.4 64.0 70.8 50.6 34.5 31.5 24.2 16.1 8.8
79.0 65.5 64.4 52.3 28.9 30.7 24.1 14.9 6.7
(0.75–1.24) (0.76–1.16) (1.06–1.68) (0.76–1.16) (1.04–1.63) (0.82–1.31) (0.78–1.30) (0.80–1.51) (0.93–1.97)
whereas the other clinical manifestations were associated with age <65 years (Table 4). Vomiting and abdominal pain were more frequent in children aged <5 years (74.6% and 91.5%, respectively) compared with people aged ‡5 years, although diarrhoea presented practically equally in both groups (77.2% in people aged <5 years and 78.5% in those aged ‡5 years). There was a statistically significant difference between the two age groups with respect to abdominal pain, but not with respect to diarrhoea and vomiting. The mean disease duration was 49 h (SD ± 39.9 h, 80th percentile, 3 days) and was longer in women than in men (52 h vs. 46 h; p 0.016). The mean disease duration was 38 h in the <5 years age group compared with 50 h in the >5 years age group (p 0.093); 35 h in the <15 years age group compared with 54 h in the >15 years age group (p <0.001) and 45 h in the <65 years age group compared with 57 h in the ‡65 years age group (p <0.001). The norovirus genotype was sequenced in 63.3% of the outbreaks, with both GI and GII strains being found. The most frequently isolated genotype was GGII.4, followed by GGII.2, GGIIb, GGI.1 and GGI.6. The GGII.4 genotype predominated in persons aged ‡15 years, the GGII.2 genotype in persons aged <15 years and the GGI.6 genotype was isolated only in persons aged <15 years.
Discussion We studied the incidence rates and clinical and epidemiological characteristics of cases of gastroenteritis associated with community outbreaks of NV infection reported to the epidemiological surveillance services in Catalonia. Isolated cases of gastroenteritis due to NV and unreported outbreaks were not included.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
42
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
CMI
TABLE 3. Distribution of symptoms according to age group in 1544 cases Age group All casesa
1–4 years
5–11 years
12–17 years
‡65 years
18–64 years
Symptoms
Cases
%
Cases
%
Cases
%
Cases
%
Cases
%
Cases
%
Diarrhoea Vomiting Abdominal pain Nausea Fever Headache Myalgia Chills General malaise
1150 940 922 712 448 417 303 181 117
78.4 65.1 67.2 51.9 31.7 31.3 24.1 15.7 7.8
44 44 54 17 19 11 10 3 10
77.2 74.6 91.5 30.4 32.2 20.4 18.5 7.7 16.7
108 180 180 110 71 81 13 17 45
49.8 82.2 86.1 54.7 33.3 40.1 6.8 12.8 20.1
57 91 73 66 42 49 17 24 5
53.8 84.3 83.0 75.0 40.0 57.0 22.1 30.0 4.5
504 369 416 362 230 221 203 107 44
85.6 64.2 74.4 64.0 41.5 41.5 39.4 22.2 7.2
437 256 199 157 86 55 60 30 13
87.9 52.9 43.5 34.1 17.8 12.0 14.2 7.1 2.6
a
In 40/1544 cases, age was unknown.
TABLE 4. Symptoms presented by Children (<5 years)
Elderly (‡65 years)
Symptoms
5–100 years (%)
<5 years (%)
OR (95% CI)
‡65 years (%)
1–64 years (%)
OR (95% CI)
Diarrhoea Vomiting Abdominal pain Nausea Fever Headache Myalgia Chills General malaise
78.5 64.6 66.1 52.8 31.7 31.7 24.3 15.9 7.4
77.2 74.6 91.5 30.4 32.2 20.4 18.5 7.7 16.7
1.08 0.62 0.18 2.57 0.98 1.82 1.41 2.27 0.40
87.9 52.9 43.5 34.1 17.8 12.0 14.2 7.1 2.6
73.6 71.2 79.0 60.9 38.9 41.4 29.1 20.5 10.3
2.61 0.45 0.20 0.33 0.34 0.19 0.40 0.30 0.23
(0.57–2.03) (0.34–1.13) (0.07–0.45) (1.44–4.58) (0.56–1.71) (0.93–3.56) (0.70–2.84) (0.69–7.47) (0.20–0.81)
In addition, there may have been under-detection of cases in outbreaks mainly due to non-detection of secondary cases; this should be taken into account when interpreting the incidence rates found, which undoubtedly underestimate the magnitude of community NV infections. Mead et al. [21] used a variety of sources to estimate that 23 million cases of NV infection occur in the USA each year, a rate higher than 8000 cases/100 000 person-years. Within the limited 12.5-month surveillance period, no distinct seasonality of outbreaks was observed, in contrast to longer studies [5,12,22], which found seasonal differences. Some investigations where the study period of 12–18 months was similar to ours [23,24] found that outbreaks appeared to have winter–spring seasonality or that norovirus-associated outbreaks showed a peak in the January–March period. Only one 3-year study found no distinct seasonality of outbreaks [25]. As in other studies, we found that NV infections occurred in all age groups [6,11,26–28], with the highest incidence rates occurring in the 5–14 years and ‡65 years age group. Rockx et al. [11] found that 88% of cases occurred in children aged <12 years compared with 18.9% in our study. We found that 25.4% of cases occurred in people aged 70–90 years, compared with 60% in the study by Hedlund et al. [22], although in this study 76% of outbreaks occurred
two different age groups
(1.93–3.55) (0.36–0.57) (0.16–0.26) (0.26–0.42) (0.26–0.45) (0.14–0.26) (0.29–0.55) (0.20–0.45) (0.13–0.42)
in general hospitals (median age 78 years) and nursing homes (median age 84 years). The mean age of cases in our study was 44.7 years, very similar to that found by other investigators [22,23,25]. Fiftynine percent of cases occurred in women, similar to the results found by Marshall et al. [24] and Fankhauser et al. [25]. It has been suggested that hormonal factors could affect the physiology of the digestive tract and favour infection in women [29], but further research is needed to confirm this. In our study, the crude incidence rates show that no cases occurred in infants aged <1 year and that the incidence was 20.6 cases/100 000 person-years in the 1–4 years age group, substantially different from the crude incidence rates found in two studies by Witt et al. [6,7], in which higher levels were found in these age groups. There may be two reasons for this. First, the studies by Witt et al. refer to gastroenteritis of any aetiology, although NV represented 5% and 11%, respectively, and it would be necessary to know the specific rates for NV infection. Second, a possible limitation of our study could be the underreporting of secondary cases, especially in infants aged <1 year, who do not share adult meals and therefore are not exposed to risk from collective catering or other areas in which outbreaks are common in Catalonia [30]. The highest incidence rate was found in the 5–11 years group (52.4 cases/100 000 person-years) and the lowest in
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
CMI
Arias et al.
the 18–64 years age group. In persons aged ‡65 years the rates increased to 42.4 cases/100 000 person-years, a rise not seen in the studies by Witt et al. [6,7]. The predominant clinical manifestations observed, as in other studies [11,27,28,31], were diarrhoea, vomiting, abdominal pain and nausea and, to a lesser extent, fever, headache, myalgia, chills and general malaise. Children and adolescents are likely to experience vomiting more frequently than diarrhoea, whereas adults experience diarrhoea more usually than vomiting. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. Go¨tz et al. [27] also observed a greater prevalence of diarrhoea and myalgia in adults and a greater prevalence of vomiting in children; the main difference between the two studies was that we found a predominance of headache in children and not in adults. Rockx et al. [11] found that diarrhoea was more frequent in patients aged <5 years and vomiting and abdominal pain were most frequent in patients aged >5 years, unlike our study, where the frequency of diarrhoea was slightly greater in patients aged ‡5 years and the frequency of vomiting and abdominal pain was greater in patients aged <5 years. The mean disease duration was 49 h, much lower than the mean of 5 days found by Rockx et al. [11] and comparable to other studies where the disease duration ranged between 12 and 60 h [31,32]. Like Rockx et al., we found multiple circulation of NV genotypes, which were not associated with particular clinical manifestations. In conclusion, this study presents the natural history, duration and symptoms of NV infection in the community. Our results were fairly close to the criteria of Kaplan et al. [9], with a high frequency of vomiting, a short infection duration and stool cultures negative for bacterial pathogens. However, one main difference with respect to the study by Rockx et al. [11] was the disease duration, suggesting that the burden of illness may be underestimated when findings are based on historic data on the duration of illness. Our prospective study detects this difference and more closely resembles Kaplan’s criteria. However, like Rockx et al., we also consider that community studies to evaluate the real incidence of NV infections are essential to determinate the characteristics of NV gastroenteritis.
Public Health Agency of Barcelona. Other members of the Catalan Viral Gastroenteritis Study Group: G. Carmona, N. Carden˜osa (Department of Health, Barcelona, Spain), I. Barrabeig, A. Rovira, J. Alvarez, I. Parro´n, C. Planas (Department of Health, Territorial Service of Barcelona, Barcelona, Spain), N. Camps, N. Fullia, M. Company (Department of Health, Territorial Service of Girona, Girona, Spain), P. Godoy, M. Alseda, J. Torres, A. Artigues (Department of Health, Territorial Service of Lleida), S. Minguell, P. J. Balan˜a (Department of Health, Territorial Service of Tarragona, Tarragona, Spain), D. Ferrer (Laboratory of the Public Health Agency, Barcelona, Spain), R. M. Pinto´, A. Bosch (Enteric Virus Laboratory, University of Barcelona, Barcelona, Spain), G. Codina (Microbiology Service, Vall d’Hebron Hospital, Barcelona Spain), R. Montaba, J. Rodrı´guez (Microbiology Department, University of Valencia, Valencia, Spain).
Acknowledgements We thank the physicians reporting outbreaks and the technicians of the Epidemiological Surveillance Units of the Department of Health of the Generalitat of Catalonia and the
Population-based study of gastroenteritis
43
Transparency Declaration This work was supported by a grant from the Fondo de Investigaciones Sanitarias Instituto de Salud Carlos III, Madrid, Spain (Project no. PI 030 877). All authors declare no conflicts of interest.
References 1. Guerrant RL, Hughes JM, Lima NL, Crane J. Diarrhea in developed and developing countries: magnitude, special settings and etiologies. Rev Infect Dis 1990; 12: S41–S50. 2. Guerrant RL, Bobak DA. Nausea, vomiting, and noninflammatory diarrhea. In: Mandell GL, Bennett JE, Dolin R, eds. , 6th edn. Philadelphia: Elsevier Inc, 2005; 1236–1249. 3. Fretz R, Svoboda P, Lu¨thi TN, Tanner M, Baumgartner A. Outbreak of gastroenteritis due to infections with Norovirus in Switzerland, 2001–2003. Epidemiol Infect 2005; 133: 429–437. 4. Lopman BA, Reacher MH, Van Duijnhoven Y, Hanon FX, Brown D, Koopmans M. Viral gastroenteritis outbreaks in Europe, 1995–2000. Emerg Infect Dis 2003; 9: 90–96. 5. Lopman BA, Adak GK, Reacher MH, Brown DW. Two epidemiologic patterns of norovirus outbreaks: surveillance in England and Wales, 1992–2000. Emerg Infect Dis 2003; 9: 71–77. 6. de Wit MAS, Koopamns MPG, Kortbeek LM, van Leeuwen WJ, Bartelds AIM, van Duynhoven YTHP. Gastroenteritis in sentinel general practices, the Netherlands. Emerg Infect Dis 2001; 7: 82–91. 7. de Wit MAS, Koopamns MPG, Kortbeek LM et al. Sensor, a population-based cohort study on gastroenteritis in the Netherlands: incidence and etiology. Am J Epidemiol 2001; 154: 666–674. 8. Estes MK, Verkataram BV, Atmar RL. Noroviruses everywhere: has something changed? Curr Opin Infect Dis 2006; 19: 467–474. 9. Kaplan JE, Feldman R, Campbell DS, Lookabaugh C, Gary GW. The frequency of a Norwalk-like pattern of illness in outbreaks of acute gastroenteritis. Am J Public Health 1982; 72: 1329–1332. 10. Hedberg CW, Osterholm MT. Outbreaks of food-borne and waterborne viral gastroenteritis. Clin Microbiol Rev 1993; 6: 199–210.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
44
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
11. Rockx B, de Wit M, Vennema H et al. Natural history of human Calicivirus infection: a prospective cohort study. Clin Infect Dis 2002; 35: 246–253. 12. Blanton LH, Adams SM, Beard RS et al. Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000–2004. J Infect Dis 2006; 193: 413– 421. 13. Buesa J, Collado B, Lo´pez-Andu´jar P et al. Molecular epidemiology of caliciviruses causing outbreaks and sporadic cases of acute gastroenteritis in Spain. J Clin Microbiol 2002; 40: 2854–2859. 14. Waters A, Coughlan S, Dunford L, Hall WW. Molecular epidemiology of norovirus strains circulating in Ireland from 2003 to 2004. Epidemiol Infect 2006; 134: 917–925. 15. Ike AC, Brockmann SO, Harlelt K, Marschang RE, Contzen M, Oehme RM. Molecular epidemiology of norovirus in outbreaks of gastroenteritis in southwest Germany from 2001 to 2004. J Clin Microbiol 2006; 44: 1262–1267. 16. Vainio K, Myrmel M. Molecular epidemiology of norovirus outbreaks in Norway during 2000 to 2005 and comparison of four norovirus real-time reverse transcriptase PCR assays. J Clin Microbiol 2006; 44: 3695–3702. 17. Pang XL, Honma S, Nakata S, Vesikari T. Human caliciviruses in acute gastroenteritis of young children in the community. J Infect Dis 2000; 181: S288–S294. 18. Allard A, Albisson B, Wadell G. Detection of adenovirus in stools from healthy persons and patients with diarrhea by two-step polymerase chain reaction. J Med Virol 1992; 37: 149–157. 19. Guix S, Caballero S, Villena C et al. Molecular epidemiology of astrovirus infection in Barcelona, Spain. J Clin Microbiol 2002; 40: 133–139. 20. Vinje J, Koopmans MP. Molecular detection and epidemiology of small round-structured viruses in outbreaks of gastroenteritis in the Netherlands. J Infect Dis 1996; 174: 610–615. 21. Mead PS, Slutsker L, Dietz V et al. Food-related illness and death in the United States. Emerg Infect Dis 1999; 5: 607–625.
CMI
22. Hedlund KO, Rubilar-Abreu E, Svennson L. Epidemiology of calicivirus infections in Sweden, 1994–1998. J Infect Dis 2000; 181 (suppl 2): S275–S280. 23. Fankhauser RL, Noel JS, Monroe SS, Ando T, Glass RI. Molecular epidemiology of ‘‘Norwalk-like viruses’’ in outbreaks of gastroenteritis in the United States. J Infect Dis 1998; 178: 1571–1578. 24. Marshall JA, Dimitriadis A, Wright PJ. Molecular and epidemiological features of norovirus-associated gastroenteritis outbreaks in Victoria, Australia in 2001. J Med Virol 2005; 75: 321–331. 25. Fankhauser RL, Monroe SS, Noel JS et al. Epidemiologic and molecular trends or ‘‘Norwalk-like viruses’’ associated with outbreaks of gsatroenteritis in the United States. J Infect Dis 2002; 186: 1–7. 26. Koopmans M, Vinje´ J, de Witt M, Leenen I, van der Poel W, van Duynhoven Y. Molecular epidemiology of human enteric caliciviruses in the Netherlands. J Infect Dis 2000; 181 (suppl 2): S262–S269. 27. Go¨tz H, Ekdahl K, Lindba¨ck J, de Jong B, Hedlund KO, Giesecke J. Clinical spectrum and transmission characteristics of infection with Norwalk-like virus: findings from a large community outbreak in Sweden. Clin Infect Dis 2001; 33: 622–628. 28. Lopman BA, Reacher MH, Vipond IB, Sarangi J, Brown DWG. Clinical manifestation of norovirus gastroenteritis in health care settings. Clin Infect Dis 2004; 39: 318–324. 29. McMichael AJ, Potter JD. Do intrinsic sex differences in lower alimentary tract physiology influence the sex-specific risk in bowel cancer and other biliary and intestinal diseases? Am J Epidemiol 1983; 118: 620–627. 30. Dominguez A, Torner N, Ruiz L et al. Aetiology and epidemiology of viral gastroenteritis outbreaks in Catalonia (Spain) in 2004–2005. J Clin Virol 2008; 43: 126–131. 31. Kaplan JE, Gary GW, Baron RC et al. Epidemiology of Norwalk gastroenteritis and the role of Norwalk virus in outbreaks of acute nonbacterial gastroenteritis. Ann Intern Med 1982; 96: 756–761. 32. Graham DY, Jiang X, Tanaka T, Openkun AR, Madore HP, Estes MK. Norwalk virus infection of volunteers: new insights based on improved assays. J Infect Dis 1994; 170: 34–43.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
10.1111/j.1469-0691.2009.02831.x
Epidemiological and clinical features of norovirus gastroenteritis in outbreaks: a population-based study C. Arias1, M. R. Sala1, A. Domı´nguez2,3,4, N. Torner3,4, L. Ruı´z4, A. Martı´nez4, R. Bartolome´5, M. de Simo´n6 and J. Buesa7 1) Epidemiological Surveillance Unit of the Central Region of Catalonia, Department of Health, Generalitat of Catalonia, Terrassa, 2) Department of Public Health, University of Barcelona, 3) CIBER Epidemiologı´a y Salud Pu´blica (CIBERESP), 4) Department of Health, Generalitat of Catalonia, 5) Microbiology Department, Hospital Universitari Vall d’Hebron and 6) Laboratory of the Public Health Agency, Barcelona and 7) Microbiology Department, University of Valencia, Valencia, Spain
Abstract Noroviruses are the most frequent cause of acute gastroenteritis in the community. In Catalonia, it is not clear how this type of viral gastroenteritis is evolving, and the objective of this prospective population-based study was to describe the incidence and epidemiological and clinical features of outbreaks of acute gastroenteritis due to norovirus in Catalonia between October 2004 and October 2005. Incidence rates were calculated using the estimated population of Catalonia in 2005. For each outbreak, the mode of transmission, the number of persons affected, demographic variables, clinical presentation, the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. Sixty viral outbreaks affecting 1791 people were identified, with no distinct seasonality. The mean number of outbreaks per month was 4.6. The global incidence was 24.6 per 100 000 person-years. The incidence was higher in women (25.7 per 100 000 person-years) and in the 5–11 years (52.4 per 100 000 person-years) and ‡65 years (42.4 per 100 000 person-years) age groups. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. These results suggest that norovirus infection has an important public health impact in Catalonia and that prevention strategies should be designed and implemented. Keywords: Clinical features, norovirus; outbreak; incidence, population-based study Original Submission: 18 November 2008; Revised Submission: 13 January 2009; Accepted: 16 January 2009 Editor: D. Raoult Article published online: 22 June 2009 Clin Microbiol Infect 2010; 16: 39–44 Corresponding author and reprint requests: C. Arias, Epidemiological Surveillance Unit of the Central Region, Carretera de Torrebonica s/n, 08227, Terrassa, Spain E-mail: [email protected]
Introduction Gastrointestinal tract infections are common in both developing and developed countries [1] and are produced by a wide variety of enteropathogens including bacteria, viruses and parasites. The main causes of viral gastroenteritis include adenoviruses, astroviruses, noroviruses (NV) and rotaviruses [2]. Since the original outbreak of Norwalk virus gastroenteritis in an elementary school in Norwalk (OH, USA) in the fall of 1968, studies have shown that viral infections, especially those due to NV, are the most frequent cause of acute gastroenteritis in the community [3–7]. NV infects all age groups, with particularly severe disease occurring in young children, the elderly, and persons with chronic illness [8].
NV infections have historically been described as mild and self-limiting. Studies in the 1970s were the basis for the criteria used by Kaplan et al. to discern outbreaks with a viral aetiology, which include stool culture negative for bacterial pathogens, mean (or median) duration of illness 12–60 h, vomiting in ‡50% of cases, and, if known, mean (or median) incubation period of 24–48 h [9]. NV have emerged as an important cause of human viral gastroenteritis and cause outbreaks in a wide range of settings, including nursing homes, hospitals, retirement centres, summer camps, schools, restaurants and events with catered meals and cruise ships. The mode of transmission may be foodborne, waterborne or person-to-person contact [9–12]. There are many reports of NV outbreaks that include details on the mode of transmission and setting and, in some cases, the molecular epidemiology of circulating NV strains [3– 5,7,9,13–16]. However, there are fewer reports on the clinical manifestations of NV infections in the community [11,17]. The objective of this study was to describe the epidemiological and clinical features of outbreaks of acute gastroenteritis
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases
40
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
CMI
due to NV in Catalonia between October 2004 and October 2005.
The level of statistical significance was established as a = 0.05.
Materials and Methods
Results
In Catalonia, a region of seven million inhabitants in the northeast of Spain, reporting of epidemic outbreaks of gastroenteritis by public and private physicians to the Department of Health is mandatory. Between 15 October 2004 and 30 October 2005, information on all reported viral outbreaks of gastroenteritis was systematically compiled and epidemiological and clinical data of cases involved in the outbreaks were collected on a standardized form using a protocol designed specifically for the study. For each outbreak, the mode of transmission, the number of persons affected, the age and sex, clinical presentation (including diarrhoea, vomiting, abdominal pain, nausea, fever, headache, myalgia, general malaise and chills), the date and time of onset of symptoms and the duration of symptoms, physician visits and hospitalizations were collected. The case definition of viral gastroenteritis used was two or more loose stools in 24 h and/or vomiting twice or more in 24 h, with additional symptoms including nausea, fever, abdominal pain, headache, myalgia, general malaise and chills. The incidence rates of cases associated with outbreaks occurring during the study period were calculated using the estimated population of Catalonia in 2005 and the 95% CIs were calculated assuming Poisson distribution. Stool samples were collected using the following norms: (i) samples were collected during the acute phase (first 3–5 days) of the infection; (ii) a minimum of 1 g of faeces was collected in a sterile, preferably plastic, container; (iii) no faeces mixed with urine were collected; (iv) only faeces without preservative were collected; and (v) no samples were collected using rectal swabs. Samples were kept at room temperature for 2 h followed by refrigeration at 4C for 2 days and freezing at )20C until microbiological analysis, which was carried out by the reference laboratories. Samples were transported to the laboratory in a refrigerated state by courier. Samples were pre-screened using standard microbiological tests to rule out bacteria and parasites. Viruses were identified by RT-PCR according to previously described methods [18–20]. In the statistical analysis, the v2 test was used to measure qualitative variables and Student’s t-test to measure quantitative variables. All statistical analyses were carried out using the SPSS V12 statistical program (SPSS Inc., Chicago, IL, USA).
During the study period, 60 viral outbreaks affecting 1791 people were identified. The outbreaks occurred mainly in restaurants (37%), nursing homes (18.3%), private residences (18.3%), hospital or long-term care facilities (10%), and holiday camps (10%). Incidence rates were calculated using the 1791 cases identified. Two hundred and forty-seven cases were excluded from the analysis of the onset of symptoms, disease duration and symptoms presented due to lack of information on these variables. Therefore the remaining analyses were made in 1544 cases. Stool samples were analysed in 534 patients. In six patients infected by norovirus, co-infection by Salmonella typhimurium or Vibrio parahaemolyticus was detected. Viruses were found in 277 patients, of which 273 corresponded to NV. The genotype was determined in 217/273 samples positive for NV. Because the samples were pre-screened using standard microbiological tests to rule out bacteria and parasites, these enteropathogens were not determined in our investigation. The outbreaks occurred predominantly between October and March (excepting January) with an increase from July onwards, although outbreaks occurred during all the months studied (Fig. 1). The mean number of outbreaks per month was 4.6 (SD ± 2.2). The global incidence rate was 24.6/100 000 person-years (95% CI 23.4–25.7), with rates of 25.7/100 000 person-years in women and 18.2/100 000 person-years in men. The incidence rates were highest in the 5–11 years and ‡65 years age groups (Table 1). Persons of all ages, from 14 months to 100 years, were affected (mean age 44.7 years). A total of 24.1% of cases occurred in the <15 years age group and 75.9% in the
No of outbreaks
10 8 6 4 2 0 Oct
Nov Dec Jan Feb Mar 2004
Apr May Jun
Jul
Aug Sept Oct
2005
FIG. 1. Monthly distribution of the 60 outbreaks included in the study. N.B. When setting figure, use the powerpoint version, which has the axes correctly labelled.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
CMI
Arias et al.
TABLE 1. Incidence rates and rates ratio of cases according
TABLE 2. Distribution of symptoms according to sex in
to age and sex
1544 cases
Incidence rates per 100 000 person-years (95% CI)
Global Sexa Male Female
24.6 (23.4–25.7) 18.2 (16.8–19.6) 25.7 (24.1–27.3)
41
Sex Rates ratio (95% CI)
Symptoms
Reference 1.41 (1.28–1.56)
Ageb <1 year 1–4 years 5–11 years 12–17 years 18–64 years ‡65 years
No cases 20.6 (15.4–25.8) 52.4 (45.8–59.0) 30.2 (24.8–35.6) 13.0 (12.0–14.0) 42.4 (38.7–46.1)
– Reference 2.54 (1.92–3.37) 1.46 (1.08–2.00) 0.63 (0.48–0.82) 2.06 (1.58–2.68)
– 1.58 (1.22–2.06) 4.03 (3.48–4.68) 2.32 (1.91–2.82) Reference 3.26 (2.90–3.66)
Ageb <1 year 1–4 years 5–14 years 15–24 years 25–39 years 40–64 years ‡65 years
No cases 20.6 (15.4–25.8) 50.1 (44.6–55.5) 18.1 (15.6–21.0) 12.9 (11.3–14.5) 11.5 (10.1–12.9) 42.4 (38.7–46.1)
– Reference 2.43 (1.85–3.19) 0.88 (0.65–1.18) 0.63 (0.47–0.83) 0.56 (0.42–0.74) 2.06 (1.58–2.68)
– 1.79 (1.35–2.36) 4.34 (3.69–5.02) 1.57 (1.28–1.92) 1.12 (0.94–1.33) Reference 3.68 (3.17–4.27)
a
Population-based study of gastroenteritis
In 189/1791 cases, sex was unknown. In 230/1791 cases, age was unknown.
b
‡15 years age group (15–64 years, 42.8%; ‡65 years, 33.1%). Forty-one percent of cases occurred in male subjects (mean age 38.6 years, SD ± 27.8) and 59% in female subjects (mean age 49.1 years, SD ± 30.1) (p <0.001), of which 30.4% occurred in male subjects aged <15 years, compared with 19.7% in female subjects (p <0.001). The first symptom to appear was diarrhoea in 23.1% of cases, vomiting in 19.6% and abdominal pain in 15.9%. Diarrhoea and vomiting coexisted in 45.2% of cases, and there was diarrhoea without vomiting in 34.9% of cases and vomiting without diarrhoea in 19.9%. The mean number of defaecations in 24 h was 4.5 (SD ± 3.5); the mean number of episodes of vomiting in 24 h was 3.7 (SD ± 2.5); in patients with fever, the mean maximum temperature was 37.8C (SD ± 0.6C). Abdominal pain and fever were more frequent in men than in women (70.8% vs. 64.4%, p 0.013; and 34.5% vs. 28.9%, p 0.022, respectively). No differences were found between sexes for the other symptoms studied (Table 2). Diarrhoea occurred more frequently in people aged >18 years, whereas vomiting and abdominal pain were more frequent in people aged <18 years (Table 3). Malaise was more frequent in children aged <11 years. The other symptoms studied were more frequent in the 12–64 years age group. In the ‡65 years age group, the predominant symptom was diarrhoea (87.9%) followed by vomiting (52.9%). The risk of diarrhoea was greater in people aged >65 than in people aged <65 years (OR 2.61; 95% CI 1.93–3.55),
All cases (total 1544)
Male
Female
Cases %
Cases %
Cases %
OR (95% CI)
483 390 402 289 203 172 128 77 56
703 574 543 439 247 254 185 107 61
0.96 0.94 1.34 0.94 1.30 1.04 1.01 1.10 1.35
Diarrhoea 1186 Vomiting 964 Abdominal pain 945 Nausea 728 Fever 453 Headache 426 Myalgia 313 Chills 184 General malaise 117
78.8 64.9 67.0 51.6 31.2 31.0 24.1 15.4 7.6
78.4 64.0 70.8 50.6 34.5 31.5 24.2 16.1 8.8
79.0 65.5 64.4 52.3 28.9 30.7 24.1 14.9 6.7
(0.75–1.24) (0.76–1.16) (1.06–1.68) (0.76–1.16) (1.04–1.63) (0.82–1.31) (0.78–1.30) (0.80–1.51) (0.93–1.97)
whereas the other clinical manifestations were associated with age <65 years (Table 4). Vomiting and abdominal pain were more frequent in children aged <5 years (74.6% and 91.5%, respectively) compared with people aged ‡5 years, although diarrhoea presented practically equally in both groups (77.2% in people aged <5 years and 78.5% in those aged ‡5 years). There was a statistically significant difference between the two age groups with respect to abdominal pain, but not with respect to diarrhoea and vomiting. The mean disease duration was 49 h (SD ± 39.9 h, 80th percentile, 3 days) and was longer in women than in men (52 h vs. 46 h; p 0.016). The mean disease duration was 38 h in the <5 years age group compared with 50 h in the >5 years age group (p 0.093); 35 h in the <15 years age group compared with 54 h in the >15 years age group (p <0.001) and 45 h in the <65 years age group compared with 57 h in the ‡65 years age group (p <0.001). The norovirus genotype was sequenced in 63.3% of the outbreaks, with both GI and GII strains being found. The most frequently isolated genotype was GGII.4, followed by GGII.2, GGIIb, GGI.1 and GGI.6. The GGII.4 genotype predominated in persons aged ‡15 years, the GGII.2 genotype in persons aged <15 years and the GGI.6 genotype was isolated only in persons aged <15 years.
Discussion We studied the incidence rates and clinical and epidemiological characteristics of cases of gastroenteritis associated with community outbreaks of NV infection reported to the epidemiological surveillance services in Catalonia. Isolated cases of gastroenteritis due to NV and unreported outbreaks were not included.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
42
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
CMI
TABLE 3. Distribution of symptoms according to age group in 1544 cases Age group All casesa
1–4 years
5–11 years
12–17 years
‡65 years
18–64 years
Symptoms
Cases
%
Cases
%
Cases
%
Cases
%
Cases
%
Cases
%
Diarrhoea Vomiting Abdominal pain Nausea Fever Headache Myalgia Chills General malaise
1150 940 922 712 448 417 303 181 117
78.4 65.1 67.2 51.9 31.7 31.3 24.1 15.7 7.8
44 44 54 17 19 11 10 3 10
77.2 74.6 91.5 30.4 32.2 20.4 18.5 7.7 16.7
108 180 180 110 71 81 13 17 45
49.8 82.2 86.1 54.7 33.3 40.1 6.8 12.8 20.1
57 91 73 66 42 49 17 24 5
53.8 84.3 83.0 75.0 40.0 57.0 22.1 30.0 4.5
504 369 416 362 230 221 203 107 44
85.6 64.2 74.4 64.0 41.5 41.5 39.4 22.2 7.2
437 256 199 157 86 55 60 30 13
87.9 52.9 43.5 34.1 17.8 12.0 14.2 7.1 2.6
a
In 40/1544 cases, age was unknown.
TABLE 4. Symptoms presented by Children (<5 years)
Elderly (‡65 years)
Symptoms
5–100 years (%)
<5 years (%)
OR (95% CI)
‡65 years (%)
1–64 years (%)
OR (95% CI)
Diarrhoea Vomiting Abdominal pain Nausea Fever Headache Myalgia Chills General malaise
78.5 64.6 66.1 52.8 31.7 31.7 24.3 15.9 7.4
77.2 74.6 91.5 30.4 32.2 20.4 18.5 7.7 16.7
1.08 0.62 0.18 2.57 0.98 1.82 1.41 2.27 0.40
87.9 52.9 43.5 34.1 17.8 12.0 14.2 7.1 2.6
73.6 71.2 79.0 60.9 38.9 41.4 29.1 20.5 10.3
2.61 0.45 0.20 0.33 0.34 0.19 0.40 0.30 0.23
(0.57–2.03) (0.34–1.13) (0.07–0.45) (1.44–4.58) (0.56–1.71) (0.93–3.56) (0.70–2.84) (0.69–7.47) (0.20–0.81)
In addition, there may have been under-detection of cases in outbreaks mainly due to non-detection of secondary cases; this should be taken into account when interpreting the incidence rates found, which undoubtedly underestimate the magnitude of community NV infections. Mead et al. [21] used a variety of sources to estimate that 23 million cases of NV infection occur in the USA each year, a rate higher than 8000 cases/100 000 person-years. Within the limited 12.5-month surveillance period, no distinct seasonality of outbreaks was observed, in contrast to longer studies [5,12,22], which found seasonal differences. Some investigations where the study period of 12–18 months was similar to ours [23,24] found that outbreaks appeared to have winter–spring seasonality or that norovirus-associated outbreaks showed a peak in the January–March period. Only one 3-year study found no distinct seasonality of outbreaks [25]. As in other studies, we found that NV infections occurred in all age groups [6,11,26–28], with the highest incidence rates occurring in the 5–14 years and ‡65 years age group. Rockx et al. [11] found that 88% of cases occurred in children aged <12 years compared with 18.9% in our study. We found that 25.4% of cases occurred in people aged 70–90 years, compared with 60% in the study by Hedlund et al. [22], although in this study 76% of outbreaks occurred
two different age groups
(1.93–3.55) (0.36–0.57) (0.16–0.26) (0.26–0.42) (0.26–0.45) (0.14–0.26) (0.29–0.55) (0.20–0.45) (0.13–0.42)
in general hospitals (median age 78 years) and nursing homes (median age 84 years). The mean age of cases in our study was 44.7 years, very similar to that found by other investigators [22,23,25]. Fiftynine percent of cases occurred in women, similar to the results found by Marshall et al. [24] and Fankhauser et al. [25]. It has been suggested that hormonal factors could affect the physiology of the digestive tract and favour infection in women [29], but further research is needed to confirm this. In our study, the crude incidence rates show that no cases occurred in infants aged <1 year and that the incidence was 20.6 cases/100 000 person-years in the 1–4 years age group, substantially different from the crude incidence rates found in two studies by Witt et al. [6,7], in which higher levels were found in these age groups. There may be two reasons for this. First, the studies by Witt et al. refer to gastroenteritis of any aetiology, although NV represented 5% and 11%, respectively, and it would be necessary to know the specific rates for NV infection. Second, a possible limitation of our study could be the underreporting of secondary cases, especially in infants aged <1 year, who do not share adult meals and therefore are not exposed to risk from collective catering or other areas in which outbreaks are common in Catalonia [30]. The highest incidence rate was found in the 5–11 years group (52.4 cases/100 000 person-years) and the lowest in
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
CMI
Arias et al.
the 18–64 years age group. In persons aged ‡65 years the rates increased to 42.4 cases/100 000 person-years, a rise not seen in the studies by Witt et al. [6,7]. The predominant clinical manifestations observed, as in other studies [11,27,28,31], were diarrhoea, vomiting, abdominal pain and nausea and, to a lesser extent, fever, headache, myalgia, chills and general malaise. Children and adolescents are likely to experience vomiting more frequently than diarrhoea, whereas adults experience diarrhoea more usually than vomiting. The prevalence of vomiting, abdominal pain and general malaise was higher in children and adolescents, whereas the prevalence of diarrhoea and myalgia was higher in adults. Go¨tz et al. [27] also observed a greater prevalence of diarrhoea and myalgia in adults and a greater prevalence of vomiting in children; the main difference between the two studies was that we found a predominance of headache in children and not in adults. Rockx et al. [11] found that diarrhoea was more frequent in patients aged <5 years and vomiting and abdominal pain were most frequent in patients aged >5 years, unlike our study, where the frequency of diarrhoea was slightly greater in patients aged ‡5 years and the frequency of vomiting and abdominal pain was greater in patients aged <5 years. The mean disease duration was 49 h, much lower than the mean of 5 days found by Rockx et al. [11] and comparable to other studies where the disease duration ranged between 12 and 60 h [31,32]. Like Rockx et al., we found multiple circulation of NV genotypes, which were not associated with particular clinical manifestations. In conclusion, this study presents the natural history, duration and symptoms of NV infection in the community. Our results were fairly close to the criteria of Kaplan et al. [9], with a high frequency of vomiting, a short infection duration and stool cultures negative for bacterial pathogens. However, one main difference with respect to the study by Rockx et al. [11] was the disease duration, suggesting that the burden of illness may be underestimated when findings are based on historic data on the duration of illness. Our prospective study detects this difference and more closely resembles Kaplan’s criteria. However, like Rockx et al., we also consider that community studies to evaluate the real incidence of NV infections are essential to determinate the characteristics of NV gastroenteritis.
Public Health Agency of Barcelona. Other members of the Catalan Viral Gastroenteritis Study Group: G. Carmona, N. Carden˜osa (Department of Health, Barcelona, Spain), I. Barrabeig, A. Rovira, J. Alvarez, I. Parro´n, C. Planas (Department of Health, Territorial Service of Barcelona, Barcelona, Spain), N. Camps, N. Fullia, M. Company (Department of Health, Territorial Service of Girona, Girona, Spain), P. Godoy, M. Alseda, J. Torres, A. Artigues (Department of Health, Territorial Service of Lleida), S. Minguell, P. J. Balan˜a (Department of Health, Territorial Service of Tarragona, Tarragona, Spain), D. Ferrer (Laboratory of the Public Health Agency, Barcelona, Spain), R. M. Pinto´, A. Bosch (Enteric Virus Laboratory, University of Barcelona, Barcelona, Spain), G. Codina (Microbiology Service, Vall d’Hebron Hospital, Barcelona Spain), R. Montaba, J. Rodrı´guez (Microbiology Department, University of Valencia, Valencia, Spain).
Acknowledgements We thank the physicians reporting outbreaks and the technicians of the Epidemiological Surveillance Units of the Department of Health of the Generalitat of Catalonia and the
Population-based study of gastroenteritis
43
Transparency Declaration This work was supported by a grant from the Fondo de Investigaciones Sanitarias Instituto de Salud Carlos III, Madrid, Spain (Project no. PI 030 877). All authors declare no conflicts of interest.
References 1. Guerrant RL, Hughes JM, Lima NL, Crane J. Diarrhea in developed and developing countries: magnitude, special settings and etiologies. Rev Infect Dis 1990; 12: S41–S50. 2. Guerrant RL, Bobak DA. Nausea, vomiting, and noninflammatory diarrhea. In: Mandell GL, Bennett JE, Dolin R, eds. , 6th edn. Philadelphia: Elsevier Inc, 2005; 1236–1249. 3. Fretz R, Svoboda P, Lu¨thi TN, Tanner M, Baumgartner A. Outbreak of gastroenteritis due to infections with Norovirus in Switzerland, 2001–2003. Epidemiol Infect 2005; 133: 429–437. 4. Lopman BA, Reacher MH, Van Duijnhoven Y, Hanon FX, Brown D, Koopmans M. Viral gastroenteritis outbreaks in Europe, 1995–2000. Emerg Infect Dis 2003; 9: 90–96. 5. Lopman BA, Adak GK, Reacher MH, Brown DW. Two epidemiologic patterns of norovirus outbreaks: surveillance in England and Wales, 1992–2000. Emerg Infect Dis 2003; 9: 71–77. 6. de Wit MAS, Koopamns MPG, Kortbeek LM, van Leeuwen WJ, Bartelds AIM, van Duynhoven YTHP. Gastroenteritis in sentinel general practices, the Netherlands. Emerg Infect Dis 2001; 7: 82–91. 7. de Wit MAS, Koopamns MPG, Kortbeek LM et al. Sensor, a population-based cohort study on gastroenteritis in the Netherlands: incidence and etiology. Am J Epidemiol 2001; 154: 666–674. 8. Estes MK, Verkataram BV, Atmar RL. Noroviruses everywhere: has something changed? Curr Opin Infect Dis 2006; 19: 467–474. 9. Kaplan JE, Feldman R, Campbell DS, Lookabaugh C, Gary GW. The frequency of a Norwalk-like pattern of illness in outbreaks of acute gastroenteritis. Am J Public Health 1982; 72: 1329–1332. 10. Hedberg CW, Osterholm MT. Outbreaks of food-borne and waterborne viral gastroenteritis. Clin Microbiol Rev 1993; 6: 199–210.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44
44
Clinical Microbiology and Infection, Volume 16 Number 1, January 2010
11. Rockx B, de Wit M, Vennema H et al. Natural history of human Calicivirus infection: a prospective cohort study. Clin Infect Dis 2002; 35: 246–253. 12. Blanton LH, Adams SM, Beard RS et al. Molecular and epidemiologic trends of caliciviruses associated with outbreaks of acute gastroenteritis in the United States, 2000–2004. J Infect Dis 2006; 193: 413– 421. 13. Buesa J, Collado B, Lo´pez-Andu´jar P et al. Molecular epidemiology of caliciviruses causing outbreaks and sporadic cases of acute gastroenteritis in Spain. J Clin Microbiol 2002; 40: 2854–2859. 14. Waters A, Coughlan S, Dunford L, Hall WW. Molecular epidemiology of norovirus strains circulating in Ireland from 2003 to 2004. Epidemiol Infect 2006; 134: 917–925. 15. Ike AC, Brockmann SO, Harlelt K, Marschang RE, Contzen M, Oehme RM. Molecular epidemiology of norovirus in outbreaks of gastroenteritis in southwest Germany from 2001 to 2004. J Clin Microbiol 2006; 44: 1262–1267. 16. Vainio K, Myrmel M. Molecular epidemiology of norovirus outbreaks in Norway during 2000 to 2005 and comparison of four norovirus real-time reverse transcriptase PCR assays. J Clin Microbiol 2006; 44: 3695–3702. 17. Pang XL, Honma S, Nakata S, Vesikari T. Human caliciviruses in acute gastroenteritis of young children in the community. J Infect Dis 2000; 181: S288–S294. 18. Allard A, Albisson B, Wadell G. Detection of adenovirus in stools from healthy persons and patients with diarrhea by two-step polymerase chain reaction. J Med Virol 1992; 37: 149–157. 19. Guix S, Caballero S, Villena C et al. Molecular epidemiology of astrovirus infection in Barcelona, Spain. J Clin Microbiol 2002; 40: 133–139. 20. Vinje J, Koopmans MP. Molecular detection and epidemiology of small round-structured viruses in outbreaks of gastroenteritis in the Netherlands. J Infect Dis 1996; 174: 610–615. 21. Mead PS, Slutsker L, Dietz V et al. Food-related illness and death in the United States. Emerg Infect Dis 1999; 5: 607–625.
CMI
22. Hedlund KO, Rubilar-Abreu E, Svennson L. Epidemiology of calicivirus infections in Sweden, 1994–1998. J Infect Dis 2000; 181 (suppl 2): S275–S280. 23. Fankhauser RL, Noel JS, Monroe SS, Ando T, Glass RI. Molecular epidemiology of ‘‘Norwalk-like viruses’’ in outbreaks of gastroenteritis in the United States. J Infect Dis 1998; 178: 1571–1578. 24. Marshall JA, Dimitriadis A, Wright PJ. Molecular and epidemiological features of norovirus-associated gastroenteritis outbreaks in Victoria, Australia in 2001. J Med Virol 2005; 75: 321–331. 25. Fankhauser RL, Monroe SS, Noel JS et al. Epidemiologic and molecular trends or ‘‘Norwalk-like viruses’’ associated with outbreaks of gsatroenteritis in the United States. J Infect Dis 2002; 186: 1–7. 26. Koopmans M, Vinje´ J, de Witt M, Leenen I, van der Poel W, van Duynhoven Y. Molecular epidemiology of human enteric caliciviruses in the Netherlands. J Infect Dis 2000; 181 (suppl 2): S262–S269. 27. Go¨tz H, Ekdahl K, Lindba¨ck J, de Jong B, Hedlund KO, Giesecke J. Clinical spectrum and transmission characteristics of infection with Norwalk-like virus: findings from a large community outbreak in Sweden. Clin Infect Dis 2001; 33: 622–628. 28. Lopman BA, Reacher MH, Vipond IB, Sarangi J, Brown DWG. Clinical manifestation of norovirus gastroenteritis in health care settings. Clin Infect Dis 2004; 39: 318–324. 29. McMichael AJ, Potter JD. Do intrinsic sex differences in lower alimentary tract physiology influence the sex-specific risk in bowel cancer and other biliary and intestinal diseases? Am J Epidemiol 1983; 118: 620–627. 30. Dominguez A, Torner N, Ruiz L et al. Aetiology and epidemiology of viral gastroenteritis outbreaks in Catalonia (Spain) in 2004–2005. J Clin Virol 2008; 43: 126–131. 31. Kaplan JE, Gary GW, Baron RC et al. Epidemiology of Norwalk gastroenteritis and the role of Norwalk virus in outbreaks of acute nonbacterial gastroenteritis. Ann Intern Med 1982; 96: 756–761. 32. Graham DY, Jiang X, Tanaka T, Openkun AR, Madore HP, Estes MK. Norwalk virus infection of volunteers: new insights based on improved assays. J Infect Dis 1994; 170: 34–43.
ª2009 The Authors Journal Compilation ª2009 European Society of Clinical Microbiology and Infectious Diseases, CMI, 16, 39–44