Volume 26-22
15 November 2000

[Table of Contents]

1999-2000 INFLUENZA SEASON: CANADIAN LABORATORY DIAGNOSES AND STRAIN CHARACTERIZATION

Introduction

In collaboration with the World Health Organization (WHO), international collaborating laboratories, provincial laboratories, and other Canadian hospital and university-based laboratories, the National Microbiology Laboratory conducts national surveillance on human influenza viruses. This surveillance monitors influenza activity, detects and describes antigenic changes in the circulating strains of influenza virus in Canada, and estimates, through periodic serosurveys, susceptibility to currently circulating and emerging strains. Canadian influenza surveillance information and actual representative strains are then shared with the WHO's collaborating centres for influenza to contribute to global influenza monitoring.

Influenza Activity

In general, the season in Canada began in late September 1999 and continued into June 2000. In addition, at least one influenza isolate was reported in July and one in August 2000.

Figure 1 indicates the numbers and months of laboratory-confirmed virus isolations, detections, and serodiagnoses reported from laboratories that contribute to the Canadian Virus Reporting (CVR) program, a surveillance program covering all laboratory-diagnosed viral infections. There were 5,771 reports of laboratory-confirmed influenza infections; 5,688 (98.6%) were reported as influenza type A from September through June with the largest number (2,148) occurring in December 1999, and 83 (1.4%) reported as influenza type B viruses that were sporadically isolated throughout the season. By comparison, in the 1998-1999 season, there were 4,500 (84%) reports of influenza A and 865 (14%) reports of influenza B⁽¹⁾, indicating that influenza A viruses remained predominant in the 1999-2000 season and influenza type B virus activity decreased significantly.

Strain Characterization

From 6 October 1999 through 15 August 2000, the National Microbiology Laboratory antigentically characterized 622 influenza viruses received from provincial and hospital laboratories. Table 1 indicates the provincial source and identity of submitted isolates. Of the 579 influenza A viruses tested, 480 (83%) were similar to the vaccine strain A/Sydney/05/97, and 99 (17%) were antigentically more closely related to A/New Caledonia/20/99. A/New Caledonia/20/99 is an antigenic variant which evolved from A/Beijing/262/95-like viruses^(2,3). All 43 of the influenza type B viruses antigentically characterized were similar to the WHO recommended B/Beijing/184/93-like virus represented in the 1999-2000 vaccine by the B/Yamanashi/166/98 virus. Figure 2 shows the change in influenza virus strains by month of submission to National Microbiology Laboratory as the season progressed. A/Sydney/05/97-like(H3N2) viruses accounted for most of the season's influenza A isolates, with the peak occurring in January. Although two influenza A(H1N1) viruses were first isolated in late December of 1999 and later characterized at the United States Centers for Disease Control and Prevention as A/New Caledonia/20/99-like, an increasing number of A/New Caledonia/20/99-like strains were identified in the late season, from February to May 2000, with the peak occurring in March (Figure 2).

Figure 1 Laboratory evidence of human influenza virus infections in Canada, 1999-2000 season

Table 1 Strain characterization completed on influenza isolates in Canada submitted from 6 October 1999 to 15 August 2000

Figure 2 National Microbiology Laboratory antigenic characterization completed on influenza virus isolates in the 1999-2000 season, by month of submission

Drug Susceptibility Tests

Recent increased use of antiviral drugs for the prophylaxis and treatment of infections caused by influenza A virus has made testing of isolates for drug resistance more important than in the past. A rapid assay has been established at the National Microbiology Laboratory to test influenza viruses for resistance to amantadine, an antiviral drug which is currently available in Canada for the prevention and therapy of influenza A infection⁽⁴⁾. The polymerase chain reaction-restriction method was used to analyze 284 isolates collected in Canada during the 1998-1999 season. Sixty of these isolates were obtained from nine influenza outbreaks in nursing homes where amantadine was used for treatment. The other 224 isolates were collected from non-institutional patients (field isolates). The results showed that three (1.3%) of 224 influenza A field isolates received during the 1998-1999 season were found to be amantadine resistant; two of the resistant viruses were isolated from individuals treated with amantadine at the time of specimen collection. There are no data on the drug use in the third case. Of the 60 isolates collected from outbreaks in nursing homes, 15 (25%) were found to have drug-resistant mutations. Analysis of all 18 resistant strains revealed that nine had mutation at amino acid position 26 (Leu to Phe), two at position 27 (Val to Ala), and seven at position 31 (Ser to Asn) of the M2 protein⁽⁵⁾.

Discussion

In Canada, the 1999-2000 influenza season came earlier than the previous season⁽¹⁾. The predominating virus strain were influenza A(H3N2) with sporadic isolations of influenza B throughout the season (Figures 1 and 2). This was the third consecutive season that influenza A/Sydney/05/97-like(H3N2) viruses were the most frequently isoated influenza viruses in Canada. In addition, there was a significant increase in influenza A(H1N1) activity as compared with the previous two seasons^{(1, 4)}. Ninety-nine (17%) of influenza A(H1N1) viruses were isolated and antigenically characterized as A/New Caledonia/20/99-like strains. A/Beijing/262/95-like virus has not been isolated in Canada, although it has been reported in the United States and other countries^{(2, 3)}. In general, the 1999-2000 influenza vaccine strains were well matched to the circulating influenza virus strains^{(2, 3)}.

A rapid test was established to test influenza viruses for resistance to amantadine to obtain information regarding the emergence and spread of resistant influenza viruses. The results of this study indicate that circulation of drug-resistant viruses in field isolates is rare (< 1%), although 25% of amantadine-treated patients with influenza A(H3N2) infection shed resistant virus. The current surveillance for drug resistance will be continued. Such a rapid test could also facilitate reducing the risk of transmission of resistant viruses to patient contact.

Influenza A(H3N2), A(H1N1), and influenza B viruses continued to circulate worldwide. Although A/Sydney/05/97-like(H3N2) viruses have predominated in the United States and Canada for the last three influenza seasons, the majority of influenza A(H3N2) isolates worldwide were antigenically more similar to A/Moscow/10/99 and A/Panama/2007/99 reference strains, two antigenically equivalent viruses. A small proportion of viruses was antigenically distinguishable from A/Moscow/10/99; however, these viruses were heterogenous, and antigenic and genetic analysis did not reveal the emergence of a representative variant⁽³⁾. Influenza A(H1N1) viruses circulated widely in many counties. Most isolates were antigenically similar to A/New Caledonia/20/99. Influenza type B viruses were isolated sporadically and were antigenically similar to B/Beijing184/93 and the widely used vaccine strain B/Yamanashi/166/98. Therefore, WHO recommended the following strains as vaccine components for the 2000-2001 season:

• an A/Moscow/10/99-like(H3N2) virus
• an A/New Caledonia/20/99-like(H1N1) virus
• a B/Beijing/184/93-like virus⁽³⁾

North American manufacturers will use the antigenically equivalent virus strains, A/Panama/2007/99 and B/Yamnashi/166/98 as actual H3N2 and B vaccine components.

Acknowledgements

The collaboration of laboratories in the CVR program and of provincial and hospital laboratories who forwarded early and representative isolates of influenza virus is a vital part of influenza surveillance in Canada. Influenza virus isolates were submitted from the following centres: British Columbia Centre for Disease Control, Virology Services, Vancouver, B.C. Virology and Reference Laboratory, University of British Columbia, Vancouver, B.C. Provincial Laboratory of Public Health for Southern Alberta, Calgary, Alta. Provincial Laboratory of Public Health for Northern Alberta, Edmonton, Alta. Royal University Hospital, Saskatoon, Sask. Saskatchewan Public Health Laboratory, Laboratory and Disease Control Services Branch, Regina, Sask. Cadham Provincial Laboratory, Winnipeg, Man. Regional Public Health Laboratory, Laboratory Services Branch, Virus Laboratory, Toronto, Ont. Regional Public Health Laboratory, Peterborough, Ont. University of Guelph, Guelph, Ont. Regional Public Health Laboratory, Kingston, Ont. Regional Public Health Laboratory, Orillia, Ont. Regional Public Health Laboratory, Ottawa, Ont. Hospital for Sick Children, Toronto, Ont. Regional Public Health Laboratory, Sault Ste. Marie, Ont. Regional Public Health Laboratory, Timmins, Ont. Regional Public Health Laboratory, Thunder Bay, Ont. Laboratoire de santé publique du Québec, Sainte-Anne-de-Bellevue, Que. Centre hospitalier St-Joseph, Trois-Rivères, Que. Hôpital G. L. Dumont, Moncton, N.B. Victoria General Hospital, Halifax, N.S. Newfoundland, Labrador Public Health Laboratory, St. John's, Nfld. Nathalie Bastien, Susan Normand, and Donalda Bowness of the National Microbiology Laboratory conducted influenza strain typing, genetic characterization and amantadine susceptibility testing.

References

1. Li Y. 1998-1999 Influenza season: Canadian laboratory diagnoses and strain characterization. CCDR 1999;25:177-81.

2. CDC. Update: influenza activity - United States and worldwide, 1999-2000 season, and composition of the 1999-2000 influenza vaccine. MMWR 2000;49:375-81.

3. World Health Organization. Recommended composition of influenza virus vaccines for use in the 2000-2001 season. Wkly Epidemiol Rec 2000;75:61-68.

4. Klimov A, Rocha E, Hayden FG et al. Prolonged shedding of amantadine-resistant influenza A viruses by immunodeficient patients: detection by poymerase chain reaction-restriction analysis. J Infect Dis 1995;172:1352-55.

5. Li Y, Normand S, Bastien N et al. Rapid screening and detection of amantadine-resistant influenza viruses from institutional and non-institutional patients. In: Conference program and abstracts of the 4th international conference "Options for the Control of Influenza IV," 23-28 September 2000, Crete, Greece. Abstract P1-102.

Source: Y Li, PhD, Respiratory Viruses Section, National Microbiology Laboratory, Public Health Agency of Canada, Health Canada, Winnipeg, Man.

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