Acute intestinal infections cause high morbidity and frequent complications, especially in young children. These issues are relevant all over the world. In young children, the most frequent agents of infection are intestinal viruses, which are known to be involved in sporadic cases as well as in epidemic outbreaks (1–4). Rotavirus and norovirus (previously known as Norwalk virus) were discovered about 30 years ago. Literature sources show that norovirus infection commonly was associated with gastroenteritis in all age groups in the community (2,5,6).
A laboratory assay for detection of rotavirus was introduced in Lithuania 20 years ago, and official statistics have been available for 8 years. The peak of morbidity was recorded in 2003, and the virus mostly affected children younger than 3 years old. The microbiology laboratory of Vilnius University Children's Hospital first provided the detection of norovirus antigen in faeces in October 2004. Norovirus antigen was found in >1000 stool specimens of hospitalised children during 2005.
Symptoms of viral infection of the intestine are not specific. In practice, there is a common assumption that all symptomatic infections appear as gastroenteritis (vomiting with diarrhoea); however, infection can manifest as only vomiting or only fever. The symptoms and syndromes of children with rotavirus infection are widely described in the medical literature (7,8); however, clinical syndromes of norovirus infection are less readily available.
Our aim was to identify clinical characteristics of norovirus in young children, to establish main clinical syndromes, and to compare norovirus and rotavirus infections.
PATIENTS AND METHODS
Random selection and retrospective analysis was done for 140 cases of norovirus and rotavirus infections in children younger than 3 years old. All of the children were treated in Vilnius University Children's Hospital from January 2005 to September 2005. Everyone who was admitted with intestinal infection symptoms or had epidemiological anamnesis was tested for norovirus, rotavirus, adenovirus, and bacterial agents in the faeces. The norovirus antigen was detected using enzyme-linked immunosorbent assay (Ridascreen Norovirus, R-Biopharm, Darmstadt, Germany). Rotavirus and adenovirus antigens were found using an immunochromatography diagnostic assay (Ridaquick Rotavirus and Adenovirus, R-Biopharm).
Inclusion criteria for our analysis were age <3 years, duration of illness before hospitalisation <3 days, laboratory-verified mono (norovirus or rotavirus) infection, no concomitant diseases, and no underlying disorders. The cases with mixed intestinal infections, concomitant diseases (pneumonia, acute upper respiratory tract infection, or urinary tract infection), or any other underlying disorder were excluded.
The research evaluated the epidemiological data, signs, and symptoms, as well as their duration before admission. Other symptoms such as nausea, abdominal pain, myalgia, and headache were not assessed because of the difficulty in quantifying these symptoms in young children.
Enteritis was defined as loose stools 3 times or more daily, gastritis as vomiting, gastroenteritis as vomiting with watery diarrhoea, and fever as an axillary temperature above 37°C. The severity of dehydration was determined by the Centers for Disease Control and Prevention 1992 recommendation and the American Academy of Paediatrics 1996 guidelines based on clinical signs that correspond to the water expressed as a percentage of the body weight (mild dehydration, 3–5%; moderate, 6–9%; severe, ≥10%).
The statistical analysis was made using the SPSS programme (SPSS, Chicago, IL). The results were analysed using Student t test, with chi-square tests for group comparison. The results were presented as mean values with standard deviation or percentage. Data were considered as statistically significant if P < 0.05.
The characteristics of patients are shown in Table 1. Both groups of children (those infected with norovirus or rotavirus) were similar in age, sex, and duration of symptoms before hospitalisation. In this study, 36% (25) of children infected with norovirus and 34% (24) infected with rotavirus were <1 year old. Of all of the patients, 46% with norovirus infection and 52% with rotavirus infection had a family member (parent or sibling) who had symptoms of intestinal infection.
Frequency of symptoms is displayed in Table 2. In young children, norovirus infection manifested as vomiting (94%), diarrhoea (81%), and fever (66%). Fever in both groups of patients lasted between 1 and 3 days. High-grade fever (>38°C) was more common among children infected with rotavirus than norovirus (P < 0.0001). The majority of children experienced vomiting, which lasted from 1 to 5 days, but it was more severe in the norovirus group. Enteritis in both groups of children lasted 1 to 7 days; however, in the rotavirus group, diarrhoea was more intense and lasted longer. Moderate or severe dehydration was diagnosed in three fourths of all patients in both groups.
While comparing the clinical presentation of norovirus and rotavirus infections, there were statistically significant differences between the 2 groups in the degree of fever, intensity of diarrhoea, vomiting, and duration of the disease. Norovirus infection lasted on average 2.3 days and rotavirus infection 3.4 days. Children infected with norovirus had an average hospital stay of 3.6 days and with rotavirus 4.1 days.
Syndromes in norovirus and rotavirus infections are shown in Figures 1 and 2. In young children, norovirus infection manifested as gastroenteritis with fever (47%) or without fever (30%), whereas surprisingly 19% of cases were without diarrhoea. The majority of children had fever and vomiting, and only a few had just vomiting or raised temperature.
Rotavirus infection for the majority of children manifested as gastroenteritis with fever, and rarely as gastroenteritis without fever, enteritis, or gastritis. Rotavirus infection without diarrhoea was noticed in just 4% of children, compared with 19% in norovirus infection (P < 0.05). Norovirus and rotavirus infections had a statistically significant difference in frequency of predominant syndromes—gastroenteritis with and without fever (P < 0.0001).
To our knowledge, this is the first study to have evaluated the predominant syndromes of norovirus infection in young hospitalised children. We compared the frequency of symptoms, signs, and syndromes of norovirus and rotavirus infections.
In young children, norovirus infection manifested as vomiting (94%), diarrhoea (81%), and fever (66%). Further analysis showed that norovirus infection presented with more intense vomiting but less severe diarrhoea. High-grade fever was less common compared with rotavirus infection. Moderate and severe dehydration was diagnosed in >70% of all of the patients and was similar in both groups. The dehydration associated with calicivirus infection is less common and less severe than with rotavirus infection (9). Vomiting as a prominent feature of norovirus infection has been described by other authors (1,6,8,10). Götz et al (10) found that 40% of cases had vomiting without diarrhoea in his research. In this study, diarrhoea was absent in 19% of cases. We believe that the real percentage in our hospital would be closer to Götz's findings if more children presenting with vomiting were tested for norovirus in their stools. According to other authors (6,7,10), enteritis in norovirus infection was less frequent than in our study (52%–79% cases), but the duration of symptoms was similar. In some studies (6,10), fever during norovirus infection was present in 24% to 40% of patients, and high-grade fever (>38°C) in just 21% of cases. It was noted in the study by Bresee et al (11) that fever usually lasts 1 day. Comparing our data with these studies, fever was more frequent and more intense and lasted 2 days on average. This could be explained by the fact that our patients were hospitalised because of severe presentation of the illness. In contrast, patients in other studies had milder symptoms and just 1.4% of them required hospitalisation (8).
We were unable to find scientific studies that have investigated clinical syndromes in norovirus infection. We have established a spectrum of possible syndromes (see above). In this study, 77% of patients had gastroenteritis, yet 30% of those were not accompanied by fever. Gastritis with or without fever was diagnosed in 17% of children. In this group, the diagnosis was frequently delayed.
According to our results, rotavirus infection in young children manifested with fever (97%), diarrhoea (96%), and vomiting (93%). Staat et al (7) investigated 234 children younger than 6 years old with rotavirus infection in the United States. They found fever in 77%, diarrhoea in 91%, and vomiting in 89% of cases. Gastroenteritis with or without fever was present in 84% of children in the study. This syndrome was encountered in 89% of our cases. Rotavirus infection without diarrhoea is rare: in our study, it was found in 4% of cases, and in other studies 9% (7). Having compared the clinical presentation of norovirus and rotavirus infection, we estimated that intensity and length of diarrhoea, fever (including high grade), and gastroenteritis with fever would be statistically significantly more frequently during rotavirus than norovirus infection. The duration of illness was longer in patients with rotavirus than in patients with norovirus infection. Lopman et al (12) reported that the median duration of norovirus infection for hospital patients was 3 days in children <5 years old, but only 1 day in children ages 5 to 14 years. Other authors agree that norovirus infection is usually milder than rotavirus infection (8,9).
According to several sources in the literature and our findings, we suggest that in practice naming a viral intestinal infection gastroenteritis is inappropriate because the syndrome of gastroenteritis appeared in just 60% to 77% of cases. In sporadic cases, in which viral intestinal infection presents as gastritis, particularly without fever, or just as fever alone, it may be difficult to make the correct preliminary diagnosis and exclude other noninfective causes. The primary diagnosis should be a syndrome (eg, gastroenteritis, enteritis, gastritis, fever), but not gastroenteritis for all cases. A physician who is aware of the incidence of a specific virus based on the presenting syndrome (especially in cases without diarrhoea) may suspect intestinal infection early. The physician can send stools for viral antigen detection, reduce the amount of errors, treat rationally, and organise appropriate epidemiological care. However, detection of virus in a patient with fever does not always mean that he or she has norovirus infection. There are some studies suggesting prolonged (≥40 days) norovirus shedding after symptomatic or asymptomatic infection in young children (13,14).
In conclusion, this study provides the first representative information on the clinical features of norovirus infection in hospitalised young children. Our results show that norovirus infection can present as gastroenteritis with or without fever. Diarrhoea was absent in almost one fifth of all of the patients with norovirus. Norovirus and rotavirus infections in young children had statistically significant differences in the degree of fever and intensity of diarrhoea and vomiting, as well as the frequency of syndromes.
We are grateful to Dr Genovaite Bernatoniene in the Microbiology Laboratory at the Vilnius University Children's Hospital for laboratorial values. We thank Ms Rasa Potiejuniene for technical assistance.
1. Phan TG, Nguyen TA, Kuroiwa T, et al
. Viral diarrhea in Japanese children: results from a one-year epidemiologic study. Clin Lab 2005; 51:183–191.
2. de Wit MA, Koopmans MP, 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.
3. Sakai Y, Nakata S, Honma S, et al
. Clinical severity of Norwalk virus and Sapporo virus gastroenteritis in children in Hokkaido, Japan. Pediatr Infect Dis J 2001; 20:849–853.
4. Widdowson M-A, Sulka A, Bulens S, et al
. The role of norovirus (NoV) in outbreaks of foodborne disease—United States, 1991–2000. Emerg Infect Dis 2005; 11:95–102.
5. Pang XL, Honma S, Nakata S, et al
. Human caliciviruses in acute gastroenteritis of young children in community. J Infect Dis 2000; 181:S288–S294.
6. 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.
7. Staat MA, Azimi PH, Berke T, et al
. Clinical presentations of rotavirus infection among hospitalized children. Pediatr Infect Dis J 2002; 21:221–227.
8. Pang XL, Joensuu J, Vesikari T. Human calicivirus–associated sporadic gastroenteritis in Finnish children less than two years of age followed prospectively during a rotavirus vaccine trial. Pediatr Infect Dis J 1999; 18:420–426.
9. Marie-Cardine A, Gourlain K, Mouterde O, et al
. Epidemiology of acute viral gastroenteritis in children hospitalized in Rouen, France. Clin Infect Dis 2002; 34:1170–1178.
10. Götz H, Ekdahl K, Lindbäck J, et al
. 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.
11. Bresee JS, Widdowson M-A, Monroe SS, et al
. Foodborne viral gastroenteritis: challenges and opportunities. Clin Infect Dis 2002; 35:748–753.
12. Lopman BA, Reacher MH, Vipond IB, et al
. Clinical manifestation of norovirus gastroenteritis in health care setting. Clin Infect Dis 2004; 39:318–324.
13. Garcia C, DuPont HL, Long KZ, et al
. Asymptomatic norovirus infection in Mexican children. J Clin Microbiol 2006; 44:2997–3000.
14. Murata T, Katsushima N, Mizuta K, et al
. Prolonged norovirus shedding in infants <6 months of age with gastroenteritis. Pediatr Infect Dis J 2007; 26:46–49.
© 2008 Lippincott Williams & Wilkins, Inc.