In 2002, British Columbia witnessed an unprecedented number of outbreaks of gastroenteritis. The causative agent in over half of these outbreaks was the Norwalk-like virus, which has become a household word. The virus causes a self-limiting illness including vomiting, diarrhea, cramping, and fever, which generally resolves within 24 to 48 hours.
The first human gastroenteritis virus was identified 30 years ago in Norwalk, Ohio, and was designated the Norwalk virus. Investigating this virus proved challenging since it could not be propagated in cell culture, and initial studies, which established that this was a causative agent of gastroenteritis, were limited to electron microscopic observations on specimens from infected human volunteers. Subsequently Norwalk virus was found to be only one of a number of morphologically and antigenically related gastroenteritis viruses, collectively referred to as Norwalk-like viruses. These were also shown to be related to classical enteric caliciviruses, (Sapporo-like viruses).
The comparison of the RNA sequences of the genomes of these viruses demonstrated that they were related, and on this basis they have now been classified into the family Caliciviridae of which the genus Norovirus embodies the Norwalk-like viruses. From the genome sequences, primers and probes were designed for reverse transcriptase-polymerase chain reaction (RT-PCR) assays, which can detect these viruses in stool specimens with greatly increased sensitivity (100 viruses per gram for RT-PCR compared to 1 000 000 for EM). Moreover, by analyzing the sequence of the RT-PCR products, the viruses can be identified at the level of the specific group, subtype, and clade or sequevar. Viral antigens for investigation of the sero-epidemiology of these viruses can now be produced by expressing the structural genes of the respective subtypes as recombinant proteins.
These developments have greatly enhanced our understanding of the role of these viruses in gastroenteritis. The duration of shedding has now been documented to be 7 to 14 days compared to 1 to 3 days based on EM methodology, although it remains unclear whether virus shedding beyond 2 days after resolution of illness contributes significantly to its spread. The prevalence of caliciviruses in children with sporadic diarrhea is now documented to be over 20% from less than 5% by previous estimates, implicating children as a source of Norovirus infections. Lastly, Noroviruses are now considered to be responsible for up to 90% of all outbreaks of acute nonbacterial gastroenteritis.
Noroviruses have been definitively identified in food handlers and from food and water specimens associated with gastroenteritis outbreaks. Infected foods include shellfish harvested from contaminated environments, fruits exposed to partially treated waste water, and foods prepared by infected handlers. The viruses are infectious at very low doses, which potentially allows for their spread through infected airborne droplets produced when patients vomit. They are resistant to freezing, withstand heating to 60°C, and survive for prolonged time periods in stool kept at 4°C. This resistant nature, along with prolonged excretion from infected individuals and the wide genetic diversity of these viruses—which precludes the development of broad-spectrum host immunity—accounts for why these viruses are the most prevalent etiological agents of acute, nonbacterial gastroenteritis.
During 2002, Laboratory Services at BCCDC tested specimens from 189 gastroenteritis outbreaks investigated throughout the province. In over half of these, Noroviruses were detected by RT-PCR. Most of the viruses belonged to a sequevar provisionally designated as BC02-007, first recognized at the BCCDC in May 2002. Viruses of this sequevar have also been detected by the BCCDC from specimens from other parts of Canada.
To date, there is no valid explanation for the increase of Norovirus gastroenteritis witnessed over the past year. Hypotheses to explain this include an increased winter activity superimposed on an already high activity throughout the year, a more virulent strain of the Norovirus, or a new antigenic variant that is circulating in the community (and perhaps worldwide). While sporadic cases in a family setting resolve spontaneously, institutional cases must be followed up with appropriate monitoring, management of potentially debilitated patients, preventing the spread of the virus by infection control measures, and decontamination of the environment. Further details are available at www.bccdc.org.
—M. Petric, PhD, FCCM
—B. Gamage, BSN, CIC
—L. McIntyre, BSc
—A. McNabb, BSc, RT
—J. Isaac-Renton, MD, FRCPC
BC Centre for Disease Control
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