Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 14, Number 8—August 2008
CME ACTIVITY - Research

Systematic Literature Review of Role of Noroviruses in Sporadic Gastroenteritis

Author affiliations: *Centers for Disease Control and Prevention, Atlanta, Georgia, USA; †National Institutes of Health, Bethesda, Maryland, USA; ‡Chigasaki Tokushukai Medical Center, Kanagawa, Japan;

Cite This Article

Introduction

CME Logo

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation at http://www.medscape.com/cme/eid; (4) view/print certificate.

Learning Objectives

Upon completion of this activity, participants will be able to:

  • Describe the frequency of norovirus (NoV) infection worldwide.
  • Describe the prevalence of NoV infection among mild-to-moderate community-acquired diarrhea cases.
  • Describe the morbidity associated with severe diarrhea due to NoV infection.
  • Identify the most common virulent strains of NoV.
  • Describe the morbidity and mortality attributed to NoV infection worldwide.

Editor

Anne Mather, Technical Writer-Editor, Emerging Infectious Diseases. Disclosure: Anne Mather has disclosed no relevant financial relationships.

CME Author

Désirée Lie, MD, MSEd, Clinical Professor, Family Medicine, University of California, Orange; Director, Division of Faculty Development, UCI Medical Center, Orange, California. Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Authors

Disclosures: Manish M. Patel, MD; Marc-Alain Widdowson, VetMB, MSc; Roger I. Glass, MD, PhD; Kenichiro Akazawa; Jan Vinjé, PhD; and Umesh D. Parashar, MBBS, MPH, have disclosed no relevant financial relationships.

Top

Abstract

We conducted a systematic review of studies that used reverse transcription–PCR to diagnose norovirus (NoV) infections in patients with mild or moderate (outpatient) and severe (hospitalized) diarrhea. NoVs accounted for 12% (95% confidence interval [CI] 10%–15%) of severe gastroenteritis cases among children <5 years of age and 12% (95% CI 9%–15%) of mild and moderate diarrhea cases among persons of all ages. Of 19 studies among children <5 years of age, 7 were in developing countries where pooled prevalence of severe NoV disease (12%) was comparable to that for industrialized countries (12%). We estimate that each year NoVs cause 64,000 episodes of diarrhea requiring hospitalization and 900,000 clinic visits among children in industrialized countries, and up to 200,000 deaths of children <5 years of age in developing countries. Future efforts should focus on developing targeted strategies, possibly even vaccines, for preventing NoV disease and better documenting their impact among children living in developing countries, where >95% of the deaths from diarrhea occur.

Despite improved safety of food, water, and sanitation and aggressive promotion of noninvasive interventions (e.g., oral rehydration therapy) and prevention strategies (e.g., increased breastfeeding), diarrhea remains a common cause of illness worldwide. It accounts for ≈1.8 million annual deaths in children <5 years of age (1). Reduction of this disease will require targeted prevention and treatment strategies against the common agents causing severe diarrhea.

Noroviruses (NoVs) and sapoviruses are genetically and antigenically diverse single-stranded RNA viruses that belong to 2 different genera (Norovirus and Sapovirus) in the family Caliciviridae and are collectively referred to as human caliciviruses (2). The prototype virus of the NoVs, Norwalk virus, was identified in 1972. However, the inability to cultivate these viruses in routine cell culture and the consequent challenges in developing sensitive nonmolecular diagnostic assays hindered initial efforts to define the epidemiology and assess the impact of disease associated with NoV infection. In the past 15 years, the availability of sensitive molecular diagnostic methods based on reverse transcription–PCR (RT-PCR) has allowed broader examination of the etiologic role of NoVs in epidemic and sporadic gastroenteritis (3,4).

Since the application of molecular assays, NoVs have been well-documented as the leading cause of epidemic gastroenteritis in all age groups, causing >90% of nonbacterial and ≈50% of all-cause epidemic gastroenteritis worldwide (5). Recent studies that used improved diagnostics have demonstrated that NoVs may also fill in the “diagnostic gap” in severe sporadic gastroenteritis among all age groups worldwide (6). Much of the misconception of NoV as an infrequent cause of severe sporadic diarrhea might also stem from studies undertaken before the mid-1990s that found low rates of NoV infection because available diagnostics such as electron microscopy and antigen detection assays had poor sensitivity. Recent data are emerging that are debunking these misconceptions, suggesting that the impact of NoV disease may be much greater than previously suspected and the disease may be more severe in some populations (4,68). However, because these novel assays are not typically available outside of reference laboratories, the true global prevalence and potential economic impact of NoV disease remain unrecognized (3). To further understand the etiologic role of NoVs in sporadic diarrhea, we conducted a systematic review to identify studies that used similar inclusion criteria and molecular assays based on RT-PCR to detect NoVs in fecal specimens from patients with diarrhea.

Methods

We searched MEDLINE, EMBASE, and Google Scholar to identify studies published in English between January 1990 and February 2008. We used the following keywords: Norwalk, norovirus,Norwalk-like virus,human calicivirus,calicivirus,NLV,small round virus, and small round structured virus. We reviewed all abstracts to identify articles that assessed the prevalence of NoV among sporadic cases of diarrhea. To ensure complete capture of all relevant studies, we cross-referenced all articles from the bibliography of the selected articles. After reviewing each article, we selected studies that met the following inclusion criteria: 1) study duration was >1 year, and 2) study used RT-PCR to diagnose caliciviruses (NoV and sapovirus) or NoV in patients with diarrhea. We included studies that tested for caliciviruses, even when they did not differentiate between NoV and sapovirus. For these studies, we multiplied the proportion of caliciviruses detected in each study by the mean proportion of caliciviruses that were NoV among studies that differentiated between NoVs and sapoviruses to yield the estimated NoV prevalence in each study. We excluded studies that did not provide a denominator (i.e., the total number of patients with diarrhea in the study population) or that only conducted molecular analysis using a fraction of the fecal samples (Technical Appendix 1). If the authors presented the data again in another study, only 1 study was included. See Technical Appendix 2, for a list of all references used in the review but not cited in this article.

We stratified studies into 2 settings: community or clinic-based (mild or moderate diarrhea) and hospital-based including emergency department and inpatients (severe diarrhea). We counted cases in which NoV was detected in the presence of >1 other pathogens (i.e., mixed infection) as NoV infection; however, we also present data on mixed infections, when available. Pooled proportions and 95% confidence intervals (CIs) of NoV-positive cases were calculated by using the random effects models (DerSimonnian and Laird method, StatsDirect Ltd, Cheshire, UK). For the studies that included fecal testing on concurrent diarrhea-free controls, the pooled proportions were based on absolute difference in NoV detection rate between cases and controls, thus only including the fraction of cases attributable to NoVs. The Cochran Q statistic and degrees of freedom (df) are presented as a measure of heterogeneity among studies. Analyses were conducted with StatsDirect version 2.5.7 (StatsDirect Ltd).

To calculate the number of outpatient NoV episodes and hospitalizations for children living in industrialized countries (where 23 of 31 studies in our review were conducted), we multiplied the total number of estimated diarrhea episodes in each clinical setting by the pooled proportion attributable to NoV based on the studies we reviewed to yield the number of NoV cases in each setting (9). No data exist on estimates of total diarrhea episodes in industrialized countries. Thus, we divided the estimates of outpatient and inpatient rotavirus episodes for industrialized countries, provided by Parashar et al. (9), by the proportion of diarrhea episodes attributable to rotavirus (23% and 42%, respectively) in the United States (10) and Europe (11) to yield the annual number of total diarrhea episodes in industrialized countries. To estimate the proportion of outpatient (23%) and inpatient (42%) diarrhea episodes attributable to rotavirus, we assumed the midpoint of the proportion of gastroenteritis visits attributable to rotavirus in the United States (19% and 35%, respectively) and 7 European countries (27% and 50% respectively) for each setting, respectively.

To estimate NoV-associated deaths and hospitalizations among children in developing countries, we multiplied global estimates of diarrhea deaths (1) and hospitalizations (9) by the pooled proportion of NoV among children <5 years of age hospitalized with diarrhea. Data from developing countries were sparse on fraction of NoV-associated diarrhea episodes in the outpatient setting.

Results

Overall, we reviewed 235 studies and identified 31 original studies that met our inclusion criteria (Tables 1, 2) (6,1241). Of these 31 studies, 20 were conducted in high-income countries, 2 were high-middle-income countries, 5 were low-middle income, and 4 were low-income countries, based on World Bank classification of economies. The duration of these studies was 1–5 years. Fourteen studies tested only for NoV (13,14,19,21,22,27,29,30,35,3741); 17 tested for NoV and sapovirus (6,12,1518,20,2326,28,3134,36). Among 13 of 17 studies that tested for and presented separate detection rates on both caliciviruses, NoV was detected in 84.5% and 88.5% of the community- and hospital-based studies, respectively (6,15,16,20,2326,3134,36). In these 13 studies, 69%–90% of the outpatient cases and 61%–100% of the hospital cases with caliciviruses were identified as NoV.

Illness by Age and Setting
Community- or Clinic-based Cases (i.e., Mild and Moderate Diarrhea)

Figure 1

Thumbnail of Figure 1&nbsp;-&nbsp;Summary of studies assessing proportion of norovirus (NoV)-positive fecal samples among persons with community and outpatient cases of sporadic diarrhea (all ages). *Lau et al. (13), O’Ryan et al. (18), Monica et al. (33), and Sdiri-Loulizi et al. (34) included outpatient and emergency department/hospital patients, but only outpatient data are included in this figure. †Pooled proportion calculated by using the random effects model (DerSimonian and Laird method,

Figure 1. Summary of studies assessing proportion of norovirus (NoV)-positive fecal samples among persons with community and outpatient cases of sporadic diarrhea (all ages). *Lau et al. (13), O’Ryan et al....

Among the 13 studies of community- or clinic-based diarrhea cases, NoVs were detected in 5%–36% of cases; pooled proportion was 12% (95% CI 9%–15%; Cochran Q 335; df 12) (Figure 1). Five studies enrolled both adults and children, and 8 studies focused only on children, each with varying age ranges (overall range 0–13 years). In the 8 studies that assessed mixed infections, 0.4%–6.5% (median 1.1%) of the gastroenteritis cases were also positive for another viral or bacterial pathogen (Table 1).

Hospitalizations (i.e., Severe Diarrhea)

Figure 2

Thumbnail of Figure 2&nbsp;-&nbsp;Summary of studies assessing proportion of norovirus (NoV)-positive fecal samples among hospitalized and emergency department cases of children &lt;5 years of age who had sporadic diarrhea. *Lau et al. (13), O’Ryan et al. (18), Monica et al. (33), and Sdiri-Loulizi et al. (34) included outpatient and emergency department/hospital patients, but only inpatient data are included in this figure. †Oh et al. (27), 98% (213 of 217) of the case-patients were &lt;5 years

Figure 2. Summary of studies assessing proportion of norovirus (NoV)-positive fecal samples among hospitalized and emergency department cases of children <5 years of age who had sporadic diarrhea. *Lau et al. (

Twenty-three studies [hospital-based (n = 21); emergency department–based (n = 1); both (n = 1)] evaluated NoV disease among hospitalized diarrhea case-patients in whom the proportion of NoV disease ranged from 3% to 31%; pooled proportion was 11% (95% CI 8%–14%). Most (n = 19) of these studies of severe diarrhea cases focused on children <5 years of age, and the pooled proportion of NoV disease in these studies was 12% (95% CI 10%–15%) (Figure 2). In the 5 studies that assessed for multiple enteric pathogens, mixed infections were detected in 0%–24% (median 3.7%) of the gastroenteritis cases (Table 2).

Most (>95%) of the world’s diarrheal deaths occur in low-middle– and low-income countries. In our review, 7 of 19 studies assessing prevalence of severe NoV disease among children <5 years of age were conducted in these countries (23,25,28,33,34,36,39). Pooled proportions for NoV-associated childhood hospitalization were 12% (95%CI 8%–17%) among low-middle and low income in comparison to 12% (95% CI 9%–16%) for high- and high-middle–income countries.

Studies with Concurrent Controls

Concurrent diarrhea-free controls were enrolled in 9 of 31 studies, and NoVs were detected in 0%–16% (median 4%) of the controls (6,12,1518,27,28,33). On the basis of the difference in detection rate between cases and controls in these studies, we estimate that the fraction of cases attributable to NoV in these studies was 4%–20% (median 12%) for mild to moderate diarrhea and 2%–26% (median 11%) for severe diarrhea.

Strain Characterization

Overall, 19 studies characterized the NoV strains by using nucleotide sequencing (13,14,17,1921,23,24,26,27,3236,3841). Among NoV cases, strains belonging to NoV genogroup (G) II were the most common (range 75%–100%). With the exception of 2 studies, the overwhelming majority of the NoV strains belonged to the GII.4 cluster (21,23). In Malawi (1 of the 4 low-income countries in our analysis), GII.3 strains were detected in 69% of the samples that were sequenced (23). Similarly, in 2006, novel GII.3 strains were identified in 44% of the samples in a clinic-based study in Japan (21). Through genetic characterization, the authors demonstrated that these GII.3 strains likely were recombinant strains that appeared over a period of 4 months.

Estimated Prevalence of NoV Disease in Children

We estimate that each year NoVs cause ≈900,000 episodes of gastroenteritis that require a clinic visit and ≈64,000 hospitalizations among children <5 years of age residing in high-income countries (Table 3). If one assumes that the proportion of annual childhood diarrhea-associated hospitalizations (≈124 million) and deaths (≈1.8 million) in developing countries approximates the overall proportion of children (12.1%) with severe NoV illness in our review, NoVs may cause up to 1.1 million hospitalizations and 218,000 deaths each year in children in developing countries.

Discussion

This systematic review of studies that used RT-PCR for detection of NoVs in fecal specimens clearly indicates that these viruses play an important role in the cause of both mild and severe gastroenteritis worldwide. In 1979, Greenberg et al. demonstrated that virtually all children in various countries worldwide acquired antibodies to NoVs by 5–15 years of age (Technical Appendix 2). However, despite strong evidence that NoV infection was ubiquitous, detection rates in children hospitalized with diarrhea were low in early studies that used electron microscopy and antigen assays (4). The advent of conventional RT-PCR for the diagnosis of NoVs has substantially changed our understanding of their epidemiology. Among all reported studies that used conventional RT-PCR, NoVs were detected in ≈12% of children <5 years of age with severe diarrhea, which suggests that these viruses are the second most common cause of severe childhood gastroenteritis, following rotavirus. In addition, although some studies suggest that NoV infections in the community are slightly less severe than rotavirus infections, data also exist to suggest that these childhood infections may be similar in severity, which may particularly apply to hospitalized children (Technical Appendix 2). On the basis of the pooled detection rates of NoV in our review, we would estimate that in the United States alone NoVs may account for >235,000 clinic visits, 91,000 emergency room visits, and 23,000 hospitalizations among children <5 years of age (10). Limited data from developing countries are available to make firm estimates, but NoV disease may cause >1 million hospitalizations and 200,000 deaths each year among children <5 years of age.

Although these figures provide a preliminary indication of the substantial magnitude of illness from NoV disease, they may underestimate the true extent of disease. Evidence suggests that detection of NoVs in fecal specimens by conventional RT-PCRs may be limited by factors such as low virus concentrations in feces, improper specimen storage, inefficient viral RNA extraction, presence of fecal reverse transcriptase inhibitors, and use of different primers (Technical Appendix 2). In addition, NoVs are extremely genetically diverse and none of the reported conventional RT-PCR assays is able to detect all strains (Technical Appendix 2). These hypotheses are supported by the findings of an evaluation of children with gastroenteritis in Peru in which both RT-PCR testing of fecal specimens and serologic assays were used to assess NoV infection, and serologic testing was found to increase the rates of NoV detection from 35% with fecal testing alone to 55% by use of either assay (28). A recent validation study comparing state-of-the-art real-time RT-PCR with conventional RT-PCR found that the sensitivity of real-time RT-PCR was greater than that of the conventional method, especially for samples containing low NoV concentrations or RT-PCR inhibitors (Technical Appendix 2). The broader application of real-time RT-PCR assays to diagnose NoV among children hospitalized with gastroenteritis should provide better estimates of the true prevalence of disease.

Some factors could have led us to overestimate the extent of sporadic NoV disease. Our estimates of sporadic NoV disease prevalence are based on a review of active surveillance data of all diarrhea cases and do not exclude cases originating from an outbreak. In a few studies, NoVs were detected in patients who were co-infected with another pathogen, and only a limited number of studies enrolled concurrent healthy controls, thus making it difficult to determine the fraction of diarrhea cases truly attributable to NoV. Among all studies testing for co-infections, however, the median rate of detecting another pathogen in addition to NoV was low (2%). This finding, combined with the fact that most studies only assessed for NoV among samples that previously tested negative for other bacterial and viral pathogens, suggests that our overall pooled proportion attributable to NoVs is unlikely to be much lower. In addition, for the studies that enrolled diarrhea-free controls, we subtracted control prevalence from the case prevalence of NoV disease when calculating the overall pooled estimate. Lastly, other unmeasured factors underestimating disease prevalence that could not be accounted for, such as inefficient primers, low virus shedding, delays in specimen collection, and lack of a sensitive case-definition are also likely to exist in these studies.

The heterogeneity in the NoV literature is evident and should be considered when interpreting the results of this review. Our systematic approach and strict inclusion criteria likely reduced heterogeneity but do not eliminate biases in the original studies, diversity in study design and population, and publication bias. Nonetheless, the findings of this review suggest that NoVs are a frequent cause of mild and severe sporadic gastroenteritis among children in high- and middle-income countries. In addition, hospital studies in our review only assessed patients admitted with diarrhea. Because of the highly infectious nature of NoVs, substantial additional health and economic effects would also occur from nosocomial disease and outbreaks in healthcare facilities, as previously identified by Lopman et al (7). NoVs are also a frequent cause of severe illness and death from diarrhea among children in developing countries, although firm conclusions cannot be made because of limited data. Systematic evaluations that use broadly reactive, state-of-the-art diagnostic assays, with concurrent evaluation of healthy controls and examination of potential co-infection, are needed to fully understand the role of NoVs in the etiology of sporadic childhood gastroenteritis. These evaluations are especially necessary in developing countries, where diarrhea remains a leading cause of childhood death, causing >1.8 million annual deaths (1).

The increasing evidence documenting the magnitude of the NoV disease prevalence provides support for considering targeted interventions, such as vaccines, for reducing the extent of this illness among young children. However, if one considers that NoV frequently causes both sporadic and epidemic gastroenteritis and can affect all age groups, some other potential targets for vaccination may include elderly persons in nursing homes, who are vulnerable to severe complications, and military recruits, in whom sporadic and epidemic NoV disease is known to incur substantial illness and financial costs from work disruption (7; Technical Appendix 2). The development of vaccines against NoVs will likely be challenging because the immunity to these viruses and the diversity and evolution of circulating strains are incompletely understood (Technical Appendix 2). However, genotype II, cluster 4 NoV strains appeared to be by far the most prevalent strains among the studies we reviewed, and these strains may be the primary targets for vaccine development.

Carefully designed epidemiologic studies that evaluate NoV prevalence in children with diarrhea and a suitable comparison group and that use sensitive molecular assays will help further define target groups that would benefit from vaccines and other interventions. A particularly pressing need exists for better quantifying the extent of severe norovirus disease among children in developing countries and identifying prevention strategies to help reduce the prevalence of deaths from diarrhea in the poorest countries.

Dr Patel is a medical epidemiologist with the Epidemiology Branch, Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention. His research focuses on the epidemiology of viral gastroenteritis and methods for its prevention and control.

Top

References

  1. Bryce J, Boschi-Pinto C, Shibuya K, Black RE; WHO Child Health Epidemiology Reference Group.WHO estimates of the causes of death in children.Lancet. 2005;365:114752. DOIPubMedGoogle Scholar
  2. Green KY. Caliciviridae: the noroviruses. In: Knipe DM, Howley PM, editors. Fields virology, 5th ed., vol. 1. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 949–78.
  3. Lopman B. Noroviruses: simple detection for complex epidemiology.Clin Infect Dis. 2006;42:9701. DOIPubMedGoogle Scholar
  4. Glass RI, Noel J, Ando T, Fankhauser R, Belliot G, Mounts A, The epidemiology of enteric caliciviruses from humans: a reassessment using new diagnostics.J Infect Dis. 2000;181(Suppl 2):S25461. DOIPubMedGoogle Scholar
  5. Widdowson MA, Monroe SS, Glass RI. Are noroviruses emerging?Emerg Infect Dis. 2005;11:7357.PubMedGoogle Scholar
  6. Amar CF, East CL, Gray J, Iturriza-Gomara M, Maclure EA, McLauchlin J. Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re-examination of the English case-control Infectious Intestinal Disease Study (1993–1996).Eur J Clin Microbiol Infect Dis. 2007;26:31123. DOIPubMedGoogle Scholar
  7. Lopman BA, Reacher MH, Vipond IB, Hill D, Perry C, Halladay T, Epidemiology and cost of nosocomial gastroenteritis, Avon, England, 2002–2003.Emerg Infect Dis. 2004;10:182734.PubMedGoogle Scholar
  8. Lopman BA, Reacher MH, Vipond IB, Sarangi J, Brown DW. Clinical manifestation of norovirus gastroenteritis in health care settings.Clin Infect Dis. 2004;39:31824. DOIPubMedGoogle Scholar
  9. Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children.Emerg Infect Dis. 2003;9:56572.PubMedGoogle Scholar
  10. Widdowson MA, Meltzer MI, Zhang X, Bresee JS, Parashar UD, Glass RI. Cost-effectiveness and potential impact of rotavirus vaccination in the United States.Pediatrics. 2007;119:68497. DOIPubMedGoogle Scholar
  11. Van Damme P, Giaquinto C, Huet F, Gothefors L, Maxwell M, Van der Wielen M, Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAL study.J Infect Dis. 2007;195(Suppl 1):S416. DOIPubMedGoogle Scholar
  12. Bon F, Fascia P, Dauvergne M, Tenenbaum D, Planson H, Petion AM, Prevalence of group A rotavirus, human calicivirus, astrovirus, and adenovirus type 40 and 41 infections among children with acute gastroenteritis in Dijon, France.J Clin Microbiol. 1999;37:30558.PubMedGoogle Scholar
  13. Lau CS, Wong DA, Tong LK, Lo JY, Ma AM, Cheng PK, High rate and changing molecular epidemiology pattern of norovirus infections in sporadic cases and outbreaks of gastroenteritis in Hong Kong.J Med Virol. 2004;73:1137. DOIPubMedGoogle Scholar
  14. Marshall JA, Hellard ME, Sinclair MI, Fairley CK, Cox BJ, Catton MG, Incidence and characteristics of endemic Norwalk-like virus-associated gastroenteritis.J Med Virol. 2003;69:56878. DOIPubMedGoogle Scholar
  15. de Wit MA, Koopmans MP, Kortbeek LM, Wannet WJ, Vinjé J, van Leusden F, Sensor, a population-based cohort study on gastroenteritis in the Netherlands: incidence and etiology.Am J Epidemiol. 2001;154:66674. DOIPubMedGoogle Scholar
  16. de Wit MA, Koopmans MP, Kortbeek LM, van Leeuwen NJ, Bartelds AI, van Duynhoven YT. Gastroenteritis in sentinel general practices, the Netherlands.Emerg Infect Dis. 2001;7:8291.PubMedGoogle Scholar
  17. 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;18:4206. DOIPubMedGoogle Scholar
  18. O’Ryan ML, Mamani N, Gaggero A, Avendaño LF, Prieto S, Peña A, Human caliciviruses are a significant pathogen of acute sporadic diarrhea in children of Santiago, Chile.J Infect Dis. 2000;182:151922. DOIPubMedGoogle Scholar
  19. Phan TG, Takanashi S, Kaneshi K, Ueda Y, Nakaya S, Nishimura S, Detection and genetic characterization of norovirus strains circulating among infants and children with acute gastroenteritis in Japan during 2004–2005.Clin Lab (Zaragoza). 2006;52:51925.
  20. Phan TG, Nguyen TA, Kuroiwa T, Kaneshi K, Ueda Y, Nakaya S, Viral diarrhea in Japanese children: results from a one-year epidemiologic study.Clin Lab (Zaragoza). 2005;51:18391.
  21. Phan TG, Kuroiwa T, Kaneshi K, Ueda Y, Nakaya S, Nishimura S, Changing distribution of norovirus genotypes and genetic analysis of recombinant GIIb among infants and children with diarrhea in Japan.J Med Virol. 2006;78:9718. DOIPubMedGoogle Scholar
  22. Boga JA, Melon S, Nicieza I, De Diego I, Villar M, Parra F, Etiology of sporadic cases of pediatric acute gastroenteritis in asturias, Spain, and genotyping and characterization of norovirus strains involved.J Clin Microbiol. 2004;42:266874. DOIPubMedGoogle Scholar
  23. Dove W, Cunliffe NA, Gondwe JS, Broadhead RL, Molyneux ME, Nakagomi O, Detection and characterization of human caliciviruses in hospitalized children with acute gastroenteritis in Blantyre, Malawi.J Med Virol. 2005;77:5227. DOIPubMedGoogle Scholar
  24. Hansman GS, Doan LT, Kguyen TA, Okitsu S, Katayama K, Ogawa S, Detection of norovirus and sapovirus infection among children with gastroenteritis in Ho Chi Minh City, Vietnam.Arch Virol. 2004;149:167388. DOIPubMedGoogle Scholar
  25. Hansman GS, Katayama K, Maneekarn N, Peerakome S, Khamrin P, Tonusin S, Genetic diversity of norovirus and sapovirus in hospitalized infants with sporadic cases of acute gastroenteritis in Chiang Mai, Thailand.J Clin Microbiol. 2004;42:13057. DOIPubMedGoogle Scholar
  26. Kirkwood CD, Clark R, Bogdanovic-Sakran N, Bishop RF. A 5-year study of the prevalence and genetic diversity of human caliciviruses associated with sporadic cases of acute gastroenteritis in young children admitted to hospital in Melbourne, Australia (1998-2002).J Med Virol. 2005;77:96101. DOIPubMedGoogle Scholar
  27. Oh DY, Gaedicke G, Schreier E. Viral agents of acute gastroenteritis in German children: prevalence and molecular diversity.J Med Virol. 2003;71:8293. DOIPubMedGoogle Scholar
  28. Parashar UD, Li JF, Cama R, DeZalia M, Monroe SS, Taylor DN, Human caliciviruses as a cause of severe gastroenteritis in Peruvian children.J Infect Dis. 2004;190:108892. DOIPubMedGoogle Scholar
  29. Sanchez-Fauquier A, Montero V, Moreno S, Solé M, Colomina J, Iturriza-Gomara M, Human rotavirus G9 and G3 as major cause of diarrhea in hospitalized children, Spain.Emerg Infect Dis. 2006;12:153641.PubMedGoogle Scholar
  30. Schnagl RD, Barton N, Patrikis M, Tizzard J, Erlich J, Morey F. Prevalence and genomic variation of Norwalk-like viruses in central Australia in 1995-1997.Acta Virol. 2000;44:26571.PubMedGoogle Scholar
  31. Wolfaardt M, Taylor MB, Booysen HF, Engelbrecht L, Grabow WO, Jiang X. Incidence of human calicivirus and rotavirus infection in patients with gastroenteritis in South Africa.J Med Virol. 1997;51:2906. DOIPubMedGoogle Scholar
  32. Zintz C, Bok K, Parada E, Barnes-Eley M, Berke T, Staat MA, Prevalence and genetic characterization of caliciviruses among children hospitalized for acute gastroenteritis in the United States.Infect Genet Evol. 2005;5:28190. DOIPubMedGoogle Scholar
  33. Monica B, Ramani S, Banerjee I, Primrose B, Iturriza-Gomara M, Gallimore CI, Human caliciviruses in symptomatic and asymptomatic infections in children in Vellore, South India.J Med Virol. 2007;79:54451. DOIPubMedGoogle Scholar
  34. Sdiri-Loulizi K, Gharbi-Khelifi H, de Rougemont A, Chouchane S, Sakly N, Ambert-Balay K, Acute infantile gastroenteritis associated with human enteric viruses in Tunisia.J Clin Microbiol. 2008;46:134955. Epub 2008 Feb 20. DOIPubMedGoogle Scholar
  35. Colomba C, Saporito L, Giammanco GM, De Grazia S, Ramirez S, Arista S, Norovirus and gastroenteritis in hospitalized children, Italy.Emerg Infect Dis. 2007;13:138991.PubMedGoogle Scholar
  36. Khamrin P, Maneekarn N, Peerakome S, Tonusin S, Malasao R, Mizuguchi M, Genetic diversity of noroviruses and sapoviruses in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand.J Med Virol. 2007;79:19216. DOIPubMedGoogle Scholar
  37. Lee JI, Chung JY, Han TH, Song MO, Hwang ES. Detection of human bocavirus in children hospitalized because of acute gastroenteritis.J Infect Dis. 2007;196:9947. DOIPubMedGoogle Scholar
  38. Onishi N, Hosoya M, Matsumoto A, Imamura T, Katayose M, Kawasaki Y, Molecular epidemiology of norovirus gastroenteritis in Soma, Japan, 2001-2003.Pediatr Int. 2008;50:659. DOIPubMedGoogle Scholar
  39. Papaventsis DC, Dove W, Cunliffe NA, Nakagomi O, Combe P, Grosjean P, Norovirus infection in children with acute gastroenteritis, Madagascar, 2004–2005.Emerg Infect Dis. 2007;13:90811.PubMedGoogle Scholar
  40. Victoria M, Carvalho-Costa FA, Heinemann MB, Leite JP, Miagostovich M. Prevalence and molecular epidemiology of noroviruses in hospitalized children with acute gastroenteritis in Rio de Janeiro, Brazil, 2004.Pediatr Infect Dis J. 2007;26:6026. DOIPubMedGoogle Scholar
  41. Yoon JS, Lee SG, Hong SK, Lee SA, Jheong WH, Oh SS, Molecular epidemiology of norovirus infections in children with acute gastroenteritis in South Korea, November 2005 through November 2006.J Clin Microbiol. 2008;46:14747. Epub 2008 Feb 13. DOIPubMedGoogle Scholar

Top

Figures
Tables

Top

Follow Up

Earning CME Credit

To obtain credit, you should first read the journal article. After reading the article, you should be able to answer the following, related, multiple-choice questions. To complete the questions and earn continuing medical education (CME) credit, please go to http://www.medscape.com/cme/eid. Credit cannot be obtained for tests completed on paper, although you may use the worksheet below to keep a record of your answers. You must be a registered user on Medscape.com. If you are not registered on Medscape.com, please click on the New Users: Free Registration link on the left hand side of the website to register. Only one answer is correct for each question. Once you successfully answer all post-test questions you will be able to view and/or print your certificate. For questions regarding the content of this activity, contact the accredited provider, CME@medscape.net. For technical assistance, contact CME@webmd.net. American Medical Association's Physician's Recognition Award (AMA PRA) credits are accepted in the US as evidence of participation in CME activities. For further information on this award, please refer to http://www.ama-assn.org/ama/pub/category/2922.html. The AMA has determined that physicians not licensed in the US who participate in this CME activity are eligible for AMA PRA Category 1 Credits™. Through agreements that the AMA has made with agencies in some countries, AMA PRA credit is acceptable as evidence of participation in CME activities. If you are not licensed in the US and want to obtain an AMA PRA CME credit, please complete the questions online, print the certificate and present it to your national medical association.

Systematic Literature Review of Role of Noroviruses in Sporadic Gastroenteritis

CME Questions

1. Norovirus (NoV) has been documented to cause what percentage of all-cause epidemic gastroenteritis worldwide?

A. 30%

B. 50%

C. 75%

D. 90%

2. Among 13 studies of community- or clinic-based mild-to-moderate diarrhea cases, what was the most likely pooled proportion attributed to NoV infection?

A. 5%

B. 12%

C. 40%

D. 65%

3. For severe diarrhea seen in emergency departments and/or resulting in hospitalizations, which of the following best describes the pooled proportion of cases attributable to NoV infection as reported in 23 studies?

A. 2%

B. 11%

C. 23%

D. 35%

4. Which of the following is considered the most common strain of NoV causing diarrhea among NoV cases?

A. GII.4 cluster

B. GII.1 cluster

C. GI.1 cluster

D. GIII.2 cluster

5. The worldwide morbidity and mortality from NoV among children in developing countries is best described by which of the following estimations?

A. 5 million hospitalizations

B. 400,000 deaths

C. 216,000 deaths

D. 2.5 million hospitalizations

Activity Evaluation

1. The activity supported the learning objectives.
Strongly Disagree      
Strongly Agree
1 2 3 4 5
2. The material was organized clearly for learning to occur.
Strongly Disagree      
Strongly Agree
1 2 3 4 5
3. The content learned from this activity will impact my practice.
Strongly Disagree      
Strongly Agree
1 2 3 4 5
4. The activity was presented objectively and free of commercial bias.
Strongly Disagree      
Strongly Agree
1 2 3 4 5

Top

Cite This Article

DOI: 10.3201/eid1408.071114

Related Links

Table of Contents – Volume 14, Number 8—August 2008

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.

Top

Comments

Please use the form below to submit correspondence to the authors or contact them at the following address:

Manish M. Patel, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Mailstop A47, Atlanta, GA 30333, USA;

Send To

10000 character(s) remaining.

Top

Page created: July 12, 2010
Page updated: July 12, 2010
Page reviewed: July 12, 2010
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external