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Research Letters |

Clinical and Laboratory Findings in Individuals With Acute Norovirus Disease FREE

Catherine Yu, MD; Stephen Baker, MScPH, PhD; Leonard J. Morse, MD; James Gardiner; Marcia Meehan, LRN; Anthony Esposito, MD; Regina Roberto, MSN, APRN-BC; Richard T. Ellison III, MD
Arch Intern Med. 2007;167(17):1903-1905. doi:10.1001/archinte.167.17.1903.
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Published online

Noroviruses are a major cause of foodborne disease outbreaks.1 Our primary understanding of norovirus disease manifestations stems from volunteer studies, but a norovirus outbreak at a small college provided the opportunity to delineate findings in naturally occurring illness.

On April 19, 2005, students at Worcester Polytechnic Institute (WPI), Worcester, Massachusetts, began developing gastroenteritis symptoms. During the next 48 hours, more students became ill, with most reporting symptoms the evening of April 20, 2005, after the student health clinic had closed. Ultimately, 39 students were referred to 3 local hospital emergency departments (Figure).

Place holder to copy figure label and caption
Figure.

Epidemiologic curve of symptom onset for gastroenteritis-like symptoms from April 19, 2005, to May 1, 2005. Those individuals whose symptoms began before April 20, 2005, or after midnight on April 21, 2005, were excluded from this study.

Graphic Jump Location

A systematic review of available medical records was undertaken with the Worcester Division of Public Health and approved by the institutional review boards of WPI, St Vincent Hospital, and University of Massachusetts Medical School. Inclusion criteria for the study included the following: (1) symptom onset between 6 AM April 20 and midnight April 21, 2005; (2) on-campus residence; (3) symptoms of nausea, vomiting, diarrhea, or abdominal pain; and (4) the absence of another likely cause of their symptoms. Available stool specimens from students and food handlers were tested for norovirus by reverse transcription–polymerase chain reaction (RT-PCR) at the Massachusetts Department of Public Health, Boston.2

No common food source was identified, but norovirus genogroup II was detected by RT-PCR in 4 of 9 students' stool specimens and in 1 food handler specimen. Ninety students reported possible gastroenteritis, but 6 cases occurred outside of the time criteria. Two students had other, more probable, causes of illness. A total of 82 students met inclusion criteria, and 55 clinical profiles were available from questionnaires and medical charts. Sixty individuals (73%) were male, with a mean age of 19.1 years (range, 18-23 years). Predominant symptoms were abdominal pain (n = 79; 96%), vomiting (n = 75; 91%), and diarrhea (n = 67; 82%); 34 (41%) of students seen in emergency departments had a fever (temperature ≥ 38°C).

Nonbloody, nonbilious vomiting varied in frequency (1 to 8 episodes) and lasted up to 12 hours. Within 17 hours of symptom onset, all treated individuals were able to tolerate oral fluid intake. A few students reported illness persistence for 72 hours.

Clinical laboratory results were most notable for leukocytosis with a neutrophil predominance; the mean absolute neutrophil count was 11 414 cells/μL (Table). For 10 of 11 students, results from a manual differential cell count demonstrated increased immature band forms. Other test results were essentially normal except for mild hyperbilirubinemia. All other stool microbiologic study results were negative. All stool samples tested (n = 7) had fecal leukocytes (rare to 6-20 cells per high-power field), including those in which norovirus was detected.

Table Graphic Jump LocationTable. Laboratory Data for Individuals Evaluated in Local Emergency Departments During the Outbreaka

Medical textbooks have traditionally stated that leukocytosis is rare with norovirus gastroenteritis and that “[r]ed and white cells are not found in the stool.”3 In contrast, we found a high frequency of both leukocytosis and fecal leukocytes. One prior study in volunteers and another natural norovirus outbreak description also document leukocytosis, but neither assessed for fecal leukocytes.4,5 In addition, jejunal biopsy specimens in symptomatic volunteers exposed to Norwalk virus have shown a polymorphonuclear and mononuclear cell infiltration into the lamina propria, indicating a neutrophilic response to this agent.6

The presence of hyperbilirubinemia has uncertain significance, since dehydration can elevate bilirubin levels mildly. Further assessment for hyperbilirubinemia should be considered in future norovirus investigations.

This study fulfills published guidelines to identify a norovirus outbreak: RT-PCR detection and a consistent clinical syndrome.1 However, there are several limitations. The sample size was small, norovirus disease was not confirmed in all cases, a control population of unaffected students was not available for comparison, and laboratory testing was likely skewed to the most affected students. Overall, these outbreak findings suggest that elevated neutrophil counts and fecal leukocytes should be considered consistent with norovirus disease.

Correspondence: Dr Yu, Division of Infectious Diseases, One Boston Medical Center Place, Dowling 3 N, Boston Medical Center, Boston, MA 02118 (Catherine.Yu@bmc.org).

Author Contributions:Study concept and design: Yu and Ellison. Acquisition of data: Yu, Morse, Gardiner, Meehan, Esposito, Roberto, and Ellison. Analysis and interpretation of data: Yu, Baker, and Ellison. Drafting of the manuscript: Yu and Ellison. Critical revision of the manuscript for important intellectual content: Baker, Morse, Gardiner, Meehan, Esposito, Roberto, and Ellison. Statistical analysis: Yu and Baker. Administrative, technical, and material support: Yu, Morse, Gardiner, Meehan, Esposito, Roberto, and Ellison. Study supervision: Ellison.

Financial Disclosure: Dr Ellison has been a consultant to Boehringer Ingelheim and Microbiotix Inc.

Additional Contributions: The following individuals also contributed to this investigation: Steven Lamontagne, Egal Gudal, Courtney Carpenter, Charles Daniel, and Marc Restuccia, MD (medical director), Department of Emergency Medicine, Worcester Emergency Medical Services, Worcester, Massachusetts; Octavio Diaz, MD (director), Department of Emergency Medicine, Saint Vincent Hospital, Worcester; and Rosemarie Erlichman (infection control practitioner), UMass Memorial Medical Center, Worcester.

Lynch  MPainter  JWoodruff  RBraden  C Surveillance for foodborne-disease outbreaks—United States, 1998-2002. MMWR Surveill Summ 2006;55 (10) ((SS10)) 1- 42
PubMed
Ando  TMonroe  SSGentsch  JRJin  QLewis  DCGlass  RI Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and southern hybridization. J Clin Microbiol 1995;33 (1) 64- 71
PubMed
Greenberg  HB Viral gastroenteritis. Braunwald  EFauci  ASKasper  DLHauser  SLLongo  DLJameson  JLHarrison's Principles of Internal Medicine. 15th ed. New York, NY McGraw-Hill2001;1135- 1138
Dolin  RBlacklow  NRDuPont  H  et al.  Transmission of acute infectious nonbacterial gastroenteritis to volunteers by oral administration of stool filtrates. J Infect Dis 1971;123 (3) 307- 312
PubMed Link to Article
Alexander  WJHolmes  JRShaw  JFERiley  WERoper  WL Norwalk virus outbreak at a college campus. South Med J 1986;79 (1) 33- 36
PubMed Link to Article
Schreiber  DSBlacklow  NRTrier  JS The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N Engl J Med 1973;288 (25) 1318- 1323
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Epidemiologic curve of symptom onset for gastroenteritis-like symptoms from April 19, 2005, to May 1, 2005. Those individuals whose symptoms began before April 20, 2005, or after midnight on April 21, 2005, were excluded from this study.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. Laboratory Data for Individuals Evaluated in Local Emergency Departments During the Outbreaka

References

Lynch  MPainter  JWoodruff  RBraden  C Surveillance for foodborne-disease outbreaks—United States, 1998-2002. MMWR Surveill Summ 2006;55 (10) ((SS10)) 1- 42
PubMed
Ando  TMonroe  SSGentsch  JRJin  QLewis  DCGlass  RI Detection and differentiation of antigenically distinct small round-structured viruses (Norwalk-like viruses) by reverse transcription-PCR and southern hybridization. J Clin Microbiol 1995;33 (1) 64- 71
PubMed
Greenberg  HB Viral gastroenteritis. Braunwald  EFauci  ASKasper  DLHauser  SLLongo  DLJameson  JLHarrison's Principles of Internal Medicine. 15th ed. New York, NY McGraw-Hill2001;1135- 1138
Dolin  RBlacklow  NRDuPont  H  et al.  Transmission of acute infectious nonbacterial gastroenteritis to volunteers by oral administration of stool filtrates. J Infect Dis 1971;123 (3) 307- 312
PubMed Link to Article
Alexander  WJHolmes  JRShaw  JFERiley  WERoper  WL Norwalk virus outbreak at a college campus. South Med J 1986;79 (1) 33- 36
PubMed Link to Article
Schreiber  DSBlacklow  NRTrier  JS The mucosal lesion of the proximal small intestine in acute infectious nonbacterial gastroenteritis. N Engl J Med 1973;288 (25) 1318- 1323
PubMed Link to Article

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