Update on Influenza Vaccination for the 2005-2006 Season

Canada Communicable Disease Report

Canada Communicable Disease Report
Volume 32 • ACS-2 1 March 2006

An Advisory Committee Statement (ACS)

Advisory Committee On Immunization (NACI) *†

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The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to immunization. The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of the Public Health Agency of Canada’s Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.


Since the publication of the Statement on Influenza Vaccination for the 2005-2006 season on 15 June, 20051, the National Advisory Committee on Immunization has received information regarding the high rate of adamantane resistance among circulating influenza A (H3N2) viruses. This update will provide an interim recommendation on the use of antiviral agents for the remainder of the 2005-2006 influenza season. Since NACI does not provide recommendations on treatment, this recommendation is limited to chemoprophylaxis.

For more detailed information regarding the use of antivirals and the epidemiology of influenza in Canada, readers are referred to the 6th edition of the Canadian Immunization Guide 2, the June 2005 NACI Statement on Influenza Vaccination for the 2005-2006 Season(1), and the most recent FluWatch reports3.

National and international surveillance for antiviral resistance

Two antiviral drugs are approved for the prophylaxis of influenza in Canada: amantadine, an adamantane (or M2 ion channel inhibitor), and oseltamivir (Tamiflu®), a neuraminidase inhibitor. The adamantanes are active only against influenza A viruses, whereas neuraminidase inhibitors are active against both influenza A and B viruses.

Resistance of influenza A viruses to adamantanes can occur spontaneously or emerge rapidly during treatment4. A single point mutation in the codons for amino acids at positions 26, 27, 30, 31, or 34 of the M2 protein confers cross-resistance to both amantadine and rimantadine. Drug-resistant genotypes correlate with phenotypic resistance as determined by biological assays5. Adamantane-resistant viruses can be transmitted from one person to another and retain their pathogenicity. Adamantanes will have no effect in preventing an infection caused by a resistant virus6.

The National Microbiology Laboratory (NML) of the Public Health Agency of Canada has completed genetic sequencing for 57 influenza A (H3N2) isolates submitted by four provinces from 23 September, 2005, to 19 January, 2006, the results of which show that 51 isolates (89%) contain an amino acid change at position 31 of the M2 protein from serine to asparagines (a S31N substitution), which confers resistance to amantadine. The only influenza A (H1N1) strain sequenced at the NML during the current season is sensitive to amantadine.

The United States has seen similar results: 91% of influenza A (H3N2) viruses that have been screened for antiviral resistance at the Centers for Disease Control and Prevention (CDC) have demonstrated resistance to the adamantane antiviral drugs. Among the three influenza A (H1N1) strains tested by the CDC, none contained any mutations associated with resistance. All U.S. influenza viruses screened for antiviral resistance at CDC have been susceptible to the neuraminidase inhibitors (oseltamivir)7.

A recent study of the worldwide prevalence of adamantane-resistant influenza A viruses showed a significant increase in adamantane resistance among field isolates since the 2002-2003 season (from under 2% prior to 2002 to13.3% during 2002- 2003). Although amantadine has been used for chemoprophylaxis against influenza A in long-term care facilities in Canada for many years, the prevalence of resistance has been low. The frequency of adamantane resistance among influenza A isolates tested by the NML from 1998-1999 to the 2002-2003 season has been very low (1.3% for the 1998-1999 season, 0.4% for the 1999-2000 season, 0% for the 2000-2001 season, and 0.7% for the 2001-2002 season). However, in the 2003-2004 season, 30% of Canadian influenza A (H3N2) isolates demonstrated amantadine resistance. Neuraminidase inhibitor resistance remains rare worldwide 5.


Annual seasonal vaccination remains the primary strategy for preventing influenza and the most effective means to reduce its impact.

The 2005-2006 NACI influenza statement recommends the prophylactic use of either amantadine or oseltamivir against influenza1. However, on the basis of the high rates of resistance to amantadine detected among influenza A (H3N2) viruses tested during this season, NACI is recommending that amantadine should not be used for the prophylaxis of influenza in Canada for the remainder of the 2005-2006 season, and that oseltamivir should be used if an antiviral medication is indicated for influenza chemoprophylaxis.

Testing of influenza isolates at the NML for the 2005-2006 season will continue, and recommendations will be updated according to the results.


  1. National Advisory Committee on Immunization (NACI). Statement on influenza vaccination for the 2005-2006 season. CCDR 2005;31(ACS-6):1-30. URL: <http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/05vol31/asc-dcc-6/index-eng.php>.

  2. Health Canada. Influenza vaccine. In: Canadian immunization guide, 6th ed. Ottawa: Health Canada, 2002;120-7. Cat No H49-8/2002E. URL: <http://www.phac-aspc.gc.ca/publicat/cig-gci/index-eng.php>.

  3. FluWatch reports. URL: <http://www.phac-aspc.gc.ca/fluwatch/index-eng.php>.

  4. Belshe RB, Smith MH, Hall CB et al. Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J Virol 1988;62:1508-12.

  5. Bright RA, Medina MJ, Xu X et al. Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: A cause for concern. Lancet 2005;366:1175-81.

  6. Hayden FG, Belshe RB, Clover RD et al. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 1989;321(25):1696-1702.

  7. CDC Health Alert. CDC recommends against the use of amantadine and rimantadine for the treatment or prophylaxis of influenza in the United States during the 2005-06 influenza season. URL: <http://www.cdc.gov/flu/han011406.htm >. Accessed 18 January, 2006.

* Members: Dr. M. Naus (Chair), Dr. T. Tam (Executive Secretary), Dr. S. Dobson, Dr. B. Duval, Dr. J. Embree, Ms. A. Hanrahan, Dr. J. Langley, Dr. A. McGeer, Dr. K. Laupland, Dr. M.N. Primeau, Dr. B. Tan, Dr. B.Warshawsky, Dr. S. McNeil.

Liaison Representatives: S. Callery (CHICA), Dr. J. Carsley (CPHA), Dr. J.C. Smith (CDC), Dr. D. Money (SOGC), A. Honish (CNCI), Dr. B. Larke (CCMOH), Dr. B. Law (ACCA), Dr. M. Salvadori (AMMI Canada), Dr. S. Rechner (CFPC), Dr. J. Salzman (CATMAT), Dr. L. Samson (CPS), Dr. D. Scheifele (CAIRE).

Ex-Officio Representatives: Dr. S. Deeks (CIDPC), Dr. H. Rode (BGTD), Dr. M. Lem (FNIHB), Dr. M. Tepper (DND).

This statement was prepared by Dr. Salwa Bishay (CIDPC), Dr. Theresa Tam (CIDPC) and Dr. Joanne Langley. It was approved by NACI and by the Public Health Agency of Canada (PHAC).

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