Volume 29-08
15 April 2003

[Table of Contents]

EPIDEMIOLOGY, CLINICAL PRESENTATION AND LABORATORY INVESTIGATION OF SEVERE ACUTE RESPIRATORY SYNDROME (SARS) IN CANADA, MARCH 2003

On 12 March, 2003, the World Health Organization (WHO) issued a global alert in relation to clusters of severe acute respiratory syndrome (SARS) in Hong Kong Special Administrative Region (SAR), China and Vietnam (Hanoi City), which appeared to be spreading among health care workers. In issuing the global alert, WHO recommended that health authorities increase vigilance for the recognition and reporting of any suspected cases of SARS, including atypical pneumonia. In response, Health Canada recommended enhanced surveillance to detect any possible cases of SARS in Canada. This report summarizes information received for the first 11 cases of SARS identified in Canada.

Canada Overview

As of 23 March, 2003, a total of 11 adults with SARS have been reported in Ontario and British Columbia, including three deaths. All cases were people who had travelled to China, including Hong Kong SAR, or contacts of cases in household or health care settings (see Figure 1 for SARS case definition). There has been no evidence of transmission in the general community.

Ontario has reported a total of 10 cases of SARS. Five of these cases (A to E) occurred in a single extended family (Figure 2). The index case had recently returned from Hong Kong SAR. An additional case (F) occurred in a family physician who had close contact with three of the ill family members. A person (G) who occupied an emergency room bed next to one family member also became ill. The final two cases included in this summary (H and I) are a family member of G and an individual who is thought to have developed SARS as a result of close contact with one of the hospitalized cases.

Outside of the family cluster, a case of SARS (J) was identified in an individual who had recently returned from travel in south-east Asia.

British Columbia (BC) also reported a single case of SARS (K) in an individual returning from travel in south-east Asia. This person became ill at the end of February 2003.

On 19 March, 2003, the Hong Kong Department of Health reported that seven people with SARS had stayed at or visited the Metropole Hotel in Kowloon, Hong Kong SAR, between 12 February and 2 March⁽¹⁾. Epidemiologic investigations have revealed that both the Ontario index case (A) and the BC case (K) stayed in this hotel during the identified risk period. Another Canadian case, who remains hospitalized in Hong Kong SAR, also stayed at the hotel.

Clinical Characteristics

The following summary of the clinical characteristics of SARS cases is based on the first seven Ontario cases and the one BC case. The age of these cases ranged from 24 to 78 years, and there was an equal number of males and females. The estimated incubation period was 2 to 5 days.

Seven cases were hospitalized; the index case (A) died before hospitalization. Four cases had underlying disease, including two with diabetes. All patients presented with a temperature of > 38° C as well as both cough and shortness of breath. Symptoms of an upper respiratory tract infection were not prominent in these cases. At presentation, all eight patients had an infiltrate on chest radiograph and lymphopenia. As well, one out of seven had thrombocytopenia (< 150,000/µL), five out of six had elevated creatinine kinase levels and three out of six had elevated levels of alanine aminotransferase/aspartate aminotransferase.

Upon recognition of SARS, airborne precautions were implemented immediately. Five of the hospitalized patients required mechanical ventilation. Therapy included broad-spectrum antibiotics appropriate for the management of severe, community-acquired pneumonia, as well as oseltamivir and intravenous ribavirin. Some patients also received intravenous steroids. The overall case fatality ratio was 37.5% (3/8).

Laboratory Results

Testing of initial specimens from SARS cases received at the National Microbiology Laboratory was initiated upon receipt. For bacterial isolation, samples were cultured on sheep blood agar, chocolate agar, buffered charcoal yeast extract agar enriched with cysteine, mycoplasma agar and broth, were incubated at 37°C under aerobic conditions, and were inspected daily for 5 days. All cultures were negative. All materials were applied to slides for direct microscopic examination using the Gram stain,and no significant bacterial agents were observed. DNA was extracted from all clinical specimens. PCR (polymerase chain reaction) tests for targets specific to atypical pneumonia agents Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydophila (Chlamydia) pneumoniae and C. psittaci as well as for Chlamydophila at the genus level were found to be negative. No product was obtained using universal primers targeting the 16S rRNA gene sequence. For completeness, real time PCR testing targeting two of the bacterial agents of bioterrorism (Yersinia pestis and Bacillus anthracis) was done, and all specimens were found to be negative. Available sera were tested using microimmunofluorescence and found to be negative for C. pneumoniae, C. psittaci and C. trachomatis.

For virologic examinations, RNA and DNA extractions were performed on nasopharyngeal swab, bronchoalveolar lavage and sputum specimens as well as serum and whole blood samples using commercial kits (Quiagen, Tryzol). Reverse transcriptase-PCR was performed using primers specific for the following RNA viruses: influenza A and B, respiratory syncytial virus, parainfluenza virus subtypes 1-4, human metapneumovirus, filoviruses (Ebola and Marburg viruses), arenaviruses, measles virus, mumps virus, hantaviruses, and Crimean Congo hemorrhagic fever virus. PCR was also performed using primers specific for the following DNA viruses: adenoviruses, parvoviruses, circoviruses, herpesviruses and orthopoxviruses. Electron microscopy was performed on bronchoalveolar lavage specimens and nasopharyngeal swabs. Specimens were inoculated into embryonated hen eggs, into the brains of suckling mice and onto cell culture (Vero cells and MDCK cells).

Within 24 hours of receipt, the serologic and molecular tests for known viral agents were largely complete. All results were negative. Virus isolation attempts have not been completed but are negative to date. Subsequently, a number of strategies for identification of unknown agents were undertaken. These included immune electron microscopy on nasopharyngeal swabs and bronchoalveolar lavage specimens using convalescent sera from the British Columbia case, RT-PCR for conserved portions of the polymerase gene of RNA viruses, and genus-specific degenerative primers for paramyxoviruses and bunyaviruses and nested PCR approaches.

All results are negative to date with the exception of testing for human metapneumovirus, which could be amplified using a nested PCR approach from six patients. For confirmation, the amplicons were sequenced and found to be unique, excluding cross-contamination in the laboratory.

Public Health Actions

When the WHO issued a global alert for cases of atypical pneumonia on 12 March, 2003, Health Canada immediately notified all provinces and territories. As a result, Ontario and BC rapidly reported the initial cases of SARS. In collaboration with provinces and territories, national case definitions were developed and enhanced surveillance for SARS cases was instituted.

Health Canada is monitoring the international situation closely and has issued updated travel advisories, which are available at the Travel Medicine Program Web site <http://www.phac-aspc.gc.ca/tmp-pmv/index.html>. Officials at international airports were contacted immediately to activate protocols to track potentially infected passengers. From 18 March, Health Canada began distributing Health Alert Notices to international passengers arriving in or returning directly to Canada from affected areas in Asia (City of Hanoi, Viet Nam), Singapore, and China (Guangdong Province and Hong Kong SAR), which advised passengers to see a physician if they began to have symptoms related to SARS. Passenger manifests for the cases' return flights to Canada are under review, and passengers seated in the same row, the two rows ahead and the two rows behind the cases are being assessed by provincial/territorial public health authorities. To date, none of the passengers contacted has developed symptoms of SARS.

Summary

As of 23 March, 2003, 11 cases of SARS have been reported in Canada. Three patients had travelled to China, including Hong Kong SAR. The remaining eight had a history of close contact with cases. There have been three deaths. To date, evidence for human metapneumovirus has been found in six cases; further studies are ongoing to determine whether this virus is the causative agent of the SARS or whether other, so far undetected, pathogens are responsible. Public health measures are being implemented at the local, provincial, and national levels to identify new cases and prevent secondary transmission of SARS.

For additional information on SARS, please contact Health Canada's information line at: 1-800-454-8302, or visit the Health Canada Web site .

Acknowledgments

This report is based on data provided by B Henry, MD and staff, Toronto Public Health, Toronto; Ontario Ministry of Health and Long-Term Care, Toronto; A McGeer, MD, and S Poutanen, MD, Mount Sinai Hospital, University of Toronto, Toronto; DE Low, MD, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto; S Finkelstein, MD, Scarborough Grace Hospital, Toronto; I Salit, MD, University Health Network, University of Toronto, Toronto; A Simor, MD, Sunnybrook and Women's College Hospital, University of Toronto, Toronto; DM Skowronski, MD, M Krajden, MD, L MacDougall, L Srour, MD, M Naus, MD, M Petric, MD, B Gamage, R Brunham, MD, BC Centre for Disease Control, Vancouver; P Kendall, MD, Office of the Provincial Health Officer, British Columbia; W Bowie, MD, E Bryce, MD, K Craig, MD, P Doyle, MD, J Ronco, MD, and F Ryan, MD, University of British Columbia and Vancouver Hospital and Health Sciences Center, Vancouver; S Wilson, M Varia, S Sarwal, MD, Field Epidemiology Training Program, Centre for Surveillance Coordination, Health Canada, Ottawa; and Centre for Emergency Preparedness and Response, Health Canada, Ottawa.

Reference

1. Hong Kong Department of Health, News Bulletin. URL: <http://www.info.gov.hk/dh/new/bulletin/03-03-19e2.htm>
accessed 19 March 2003.

Source: Immunization and Respiratory Infections Division, Centre for Infectious Disease Prevention and Control, Health Canada, Ottawa, Canada, and National Microbiology Laboratory, Health Canada, Winnipeg, Canada. 

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