hat tip Miso -
Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa
Aeron C. Hurt<sup>a</sup><sup>, </sup><sup>b</sup><sup>, </sup><sup></sup><sup>, </sup><sup></sup>, Joanne Ernest<sup>a</sup>, Yi-Mo Deng<sup>a</sup>, Pina Iannello<sup>a</sup>, Terry G. Besselaar<sup>c</sup>, Chris Birch<sup>d</sup>, Philippe Buchy<sup>e</sup>, Malinee Chittaganpitch<sup>f</sup>, Shu-Chun Chiu<sup>g</sup>, Dominic Dwyer<sup>h</sup>, Aur?lie Guigon<sup>i</sup>, Bruce Harrower<sup>j</sup>, Ip Peng Kei<sup>k</sup>, Tuckweng Kok<sup>l</sup>, Cui Lin<sup>m</sup>, Ken McPhie<sup>h</sup>, Apandi Mohd<sup>n</sup>, Remigio Olveda<sup>o</sup>, Tony Panayotou<sup>p</sup>, William Rawlinson<sup>q</sup>, Lesley Scott<sup>r</sup>, David Smith<sup>s</sup>, Holly D'Souza<sup>t</sup>, Naomi Komadina<sup>a</sup>, Robert Shaw<sup>a</sup>, Anne Kelso<sup>a</sup> and Ian G. Barr<sup>a</sup><sup>, </sup><sup>b</sup>
<!-- authorsNoEnt --> <sup>a</sup>WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia
<sup>b</sup>Monash University, Churchill, Victoria, Australia
<sup>c</sup>National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, South Africa
<sup>d</sup>Victorian Infectious Diseases Reference Laboratory, Victoria, Australia
<sup>e</sup>Institut Pasteur, Phnom Penh, Cambodia
<sup>f</sup>National Institute of Health, Nonthaburi, Thailand
<sup>g</sup>Center for Research and Diagnostics, Centers for Disease Control, Taiwan
<sup>h</sup>Centre for Infectious Diseases and Microbiology, ICPMR, Westmead Hospital, NSW, Australia
<sup>i</sup>Pasteur Institute, New Caledonia
<sup>j</sup>Queensland Health Forensic and Scientific Services, QLD, Australia
<sup>k</sup>Public Health Laboratory, Health Bureau, Macao
<sup>l</sup>Institute of Medical and Veterinary Science, South Australia, Australia
<sup>m</sup>National Public Health Laboratory, Ministry of Health, Singapore
<sup>n</sup>Institute Penyelidikan Perubatan, Kuala Lumpur, Malaysia
<sup>o</sup>Research Institute of Tropical Medicine, Manila, Philippines
<sup>p</sup>Southern Health, Victoria, Australia
<sup>q</sup>Prince of Wales Hospital, NSW, Australia
<sup>r</sup>Centre for Disease Control, Darwin, Australia
<sup>s</sup>PathWest Laboratories, Perth, WA, Australia
<sup>t</sup>Auckland Hospital, Auckland, New Zealand
<!-- authorsNoEnt -->
<!-- articleText -->
Received 13 January 2009;
<!-- articleText -->revised 2 March 2009;
<!-- articleText -->accepted 4 March 2009.
<!-- articleText -->Available online 24 March 2009.
<!-- articleText -->
<!-- articleText --> Abstract
The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.
<!-- articleText --> Keywords: Influenza A; Oseltamivir; Tamiflu; Resistance; Neuraminidase inhibitors; H274Y; Antivirals
Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa
Aeron C. Hurt<sup>a</sup><sup>, </sup><sup>b</sup><sup>, </sup><sup></sup><sup>, </sup><sup></sup>, Joanne Ernest<sup>a</sup>, Yi-Mo Deng<sup>a</sup>, Pina Iannello<sup>a</sup>, Terry G. Besselaar<sup>c</sup>, Chris Birch<sup>d</sup>, Philippe Buchy<sup>e</sup>, Malinee Chittaganpitch<sup>f</sup>, Shu-Chun Chiu<sup>g</sup>, Dominic Dwyer<sup>h</sup>, Aur?lie Guigon<sup>i</sup>, Bruce Harrower<sup>j</sup>, Ip Peng Kei<sup>k</sup>, Tuckweng Kok<sup>l</sup>, Cui Lin<sup>m</sup>, Ken McPhie<sup>h</sup>, Apandi Mohd<sup>n</sup>, Remigio Olveda<sup>o</sup>, Tony Panayotou<sup>p</sup>, William Rawlinson<sup>q</sup>, Lesley Scott<sup>r</sup>, David Smith<sup>s</sup>, Holly D'Souza<sup>t</sup>, Naomi Komadina<sup>a</sup>, Robert Shaw<sup>a</sup>, Anne Kelso<sup>a</sup> and Ian G. Barr<sup>a</sup><sup>, </sup><sup>b</sup>
<!-- authorsNoEnt --> <sup>a</sup>WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia
<sup>b</sup>Monash University, Churchill, Victoria, Australia
<sup>c</sup>National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, South Africa
<sup>d</sup>Victorian Infectious Diseases Reference Laboratory, Victoria, Australia
<sup>e</sup>Institut Pasteur, Phnom Penh, Cambodia
<sup>f</sup>National Institute of Health, Nonthaburi, Thailand
<sup>g</sup>Center for Research and Diagnostics, Centers for Disease Control, Taiwan
<sup>h</sup>Centre for Infectious Diseases and Microbiology, ICPMR, Westmead Hospital, NSW, Australia
<sup>i</sup>Pasteur Institute, New Caledonia
<sup>j</sup>Queensland Health Forensic and Scientific Services, QLD, Australia
<sup>k</sup>Public Health Laboratory, Health Bureau, Macao
<sup>l</sup>Institute of Medical and Veterinary Science, South Australia, Australia
<sup>m</sup>National Public Health Laboratory, Ministry of Health, Singapore
<sup>n</sup>Institute Penyelidikan Perubatan, Kuala Lumpur, Malaysia
<sup>o</sup>Research Institute of Tropical Medicine, Manila, Philippines
<sup>p</sup>Southern Health, Victoria, Australia
<sup>q</sup>Prince of Wales Hospital, NSW, Australia
<sup>r</sup>Centre for Disease Control, Darwin, Australia
<sup>s</sup>PathWest Laboratories, Perth, WA, Australia
<sup>t</sup>Auckland Hospital, Auckland, New Zealand
<!-- authorsNoEnt -->
<!-- articleText -->
Received 13 January 2009;
<!-- articleText -->revised 2 March 2009;
<!-- articleText -->accepted 4 March 2009.
<!-- articleText -->Available online 24 March 2009.
<!-- articleText -->
<!-- articleText --> Abstract
The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.
<!-- articleText --> Keywords: Influenza A; Oseltamivir; Tamiflu; Resistance; Neuraminidase inhibitors; H274Y; Antivirals
Comment