Biosafety Advisory: Efficiently Transmissible Engineered Influenza A H5N1 Viruses

February 01, 2012

This biosafety advisory is being provided by the Public Health Agency of Canada (PHAC) in response to recent publications of efficiently transmissible engineered Influenza A H5N1 viruses. The Pathogen Regulation Directorate (PRD) has developed this advisory based on current scientific evidence available on this pathogen and is subject to review and change as more information becomes available. The Risk Group (RG) of efficiently transmissible Influenza A H5N1 viruses is RG4.

1. Background

Influenza A H5N1 is a highly pathogenic avian influenza virus that emerged as a human pathogen in 1997 when it was transmitted from avian populations to humans in Hong Kong(1,2). Since then, various countries around the world have reported human infections, particularly in Southeast Asia, the Middle East, and Africa. From 2003 to 2011, 574 human cases and 337 deaths have been confirmed by the World Health Organization; this correlates to a mortality rate of 59%(3). H5N1 can cause death in healthy individuals with no pre-existing medical conditions.

In November 2011, three independent studies on H5N1 transmission in ferrets were either published online or submitted for publication. These studies have received a significant amount of attention due to their relative success in producing engineered H5N1 viruses capable of efficient transmission in ferrets, including via the air(4-10). Ferrets are considered a good model for studying human influenza viruses(11). The engineered transmissible H5N1 viruses are not currently in circulation, but it is widely agreed that if released, the clinical and economic impact could be devastating.

2. Biosafety Requirements

The following table summarizes the containment requirements for laboratories working with efficiently transmissible engineered Influenza A H5N1 viruses. No containment requirements are stipulated for non-proliferative clinical/diagnostic activities based on the fact that this virus is currently not in circulation. Laboratories should refer to the Laboratory Biosafety Guidelines, 3rd Edition, 2004 for a complete listing of the biosafety requirements.

H5N1 viruses capable of efficient human-to-human transmission, including via aerosols or the airborne route, are considered Risk Group 4 human pathogens and require Containment Level 4 physical containment and operational practices.

Sample Type and Activity Minimum Containment Level Requirements
Non-Proliferative Clinical/ Diagnostic Activities Not in circulation at this time see Section 3
Work Involving Positive Cultures    
In Vivo Work    

3. Additional Risk Considerations

If an efficiently transmissible H5N1 virus was introduced into circulation, a risk assessment would be necessary to determine the regulatory requirements for different types of work, such as non-proliferative clinical/ diagnostic activities.

4. Transportation

Packaging, shipping and transport of specimens containing RG4 pathogens require specific instructions and procedures in accordance with the Transportation of Dangerous Goods Regulations, Transport Canada. For information on how to transport RG4 pathogens please contact the National Microbiological Laboratory (NML) at or, or contact the 24/7 emergency phone line at (204) 999-7996 due to the stringent notification practices involved.

5. Contact Information

Please note that this advisory is based on currently available scientific evidence and is subject to review and change as new information becomes available. Further biosafety information may be obtained from the PHAC Pathogen Regulation Directorate, on our website at: Laboratory Biosafety and Biosecurity or at (613) 957-1779, fax (613) 941-0596 and by email:

6. References

  1. Harada, Y., Ninomiya-Mori, A., Takahashi, Y., Shirakura, M., Kishida, N., Kageyama, T., Tada, Y., Tashiro, M., & Odagiri, T. (2011). Inactivated and adjuvanted whole-virion clade 2.3.4 H5N1 pre-pandemic influenza vaccine possesses broad protective efficacy against infection by heterologous clades of highly pathogenic H5N1 avian influenza virus in mice. Vaccine, doi:10.1016/j.vaccine.2011.08.091
  2. Hui, D. S. (2008). Review of clinical symptoms and spectrum in humans with influenza A/H5N1 infection. Respirology (Carlton, Vic.), 13 Suppl 1, S10-3. doi:10.1111/j.1440-1843.2008.01247.x
  3. World Health Organization. (2011). Cumulative number of confirmed human cases for avian influenza A(H5N1) reported to WHO, 2003-2011World Health Organization.
  4. Chen, L., Blixt, O., Stevens, J., Lipatov, A. S., Davis, C. T., Collins, B. E., Cox, N. J., Paulson, J. C., & Donis, R. O. (2012). In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity. Virology, 422(1), 105-113. doi:10.1016/j.virol.2011.10.006
  5. ProMED. (2011). Avian Influenza (68) : H5N1 Transmissibility to FerretsProMED.
  6. ProMED. (2011). Avian Influenza (70) : Transmissibility in FerretsProMED.
  7. ProMED.Avian Influenza (73) : Ferret Experiment ControversyProMED.
  8. The Canadian Press. (2011). Bird Flu Bioterrorism Fears Prompt Cencorship Bid. U.S. Government Asks Scientific Journals to Redact H5N1 Studies. The Canadian Press.
  9. CIDRAP. (2011). H5N1 Transmission Experiment Stirs Concern. CIDRAP.
  10. Garrett, L. (2011). The Bioterrorist Next Door. Foreign Policy.
  11. Matsuoka et al. The Ferret Model for Influenza. Curr Protoc Microbiol. 2009, May; Chapter 15:Unit 15G.2
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