tetano
Editor, Senior Moderator
J Infect Dis. (2012) doi: 10.1093/infdis/jis337
Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia
A.C. Hurt1,*,
K. Hardie2,
N. J. Wilson3,
Y.M. Deng1,
M. Osbourn2,
S.K. Leang1,
R.T.C. Lee4,
P. Iannello1,
N. Gehrig3,
R. Shaw1,
P. Wark5,
N. Caldwell1,
R. C. Givney3,
L. Xue1,
S. Maurer-Stroh4,6,7,
D.E. Dwyer8,
B. Wang8,
D.W. Smith9,10,
A. Levy9,
R. Booy11,12,13,
R. Dixit11,
T. Merritt2,
A. Kelso1,
C. Dalton2,
D. Durrheim2 and
I.G. Barr1
+ Author Affiliations
1WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia
2Hunter New England Population Health, Newcastle, New South Wales, Australia
3Hunter Area Pathology Service, A Division of Pathology North, Newcastle, New South Wales, Australia
4Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore
5Centre for Asthma and Respiratory Disease, University of Newcastle, New South Wales, Australia
6School of Biological Sciences, Nanyang Technological University (NTU), Singapore
7National Public Health Laboratory (NPHL), Ministry of Health, Singapore
8Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, Westmead Hospital and University of Sydney, New South Wales, Australia
9PathWest Laboratory Medicine, Nedlands, Western Australia, Australia
10School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia
11National Centre for Immunisation Research and Surveillance of Vaccine Preventable Disease, Kids Research Institute, The Children's Hospital at Westmead, New South Wales, Australia
12Sydney Institute for Emerging infections and Biosecurity (SEIB), The University of Sydney, New South Wales, Australia
13Academic Unit of Child Health, Queen Mary University of London, London, United Kingdom
↵*Corresponding Author: Aeron Hurt (PhD), WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St, North Melbourne, Victoria 3051, Australia. phone: +613 9342 3914, email: aeron.hurt@influenzacentre.org
Abstract
Background Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community-transmission has not previously been reported.
Methods Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses.
Results Twenty nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only one patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including one strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K and N386S in these viruses may offset the destabilizing effect of the H275Y substitution.
Conclusions This cluster represents the first widespread community-transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
http://jid.oxfordjournals.org/content/early/2012/05/04/infdis.jis337.short?rss=1
Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia
A.C. Hurt1,*,
K. Hardie2,
N. J. Wilson3,
Y.M. Deng1,
M. Osbourn2,
S.K. Leang1,
R.T.C. Lee4,
P. Iannello1,
N. Gehrig3,
R. Shaw1,
P. Wark5,
N. Caldwell1,
R. C. Givney3,
L. Xue1,
S. Maurer-Stroh4,6,7,
D.E. Dwyer8,
B. Wang8,
D.W. Smith9,10,
A. Levy9,
R. Booy11,12,13,
R. Dixit11,
T. Merritt2,
A. Kelso1,
C. Dalton2,
D. Durrheim2 and
I.G. Barr1
+ Author Affiliations
1WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia
2Hunter New England Population Health, Newcastle, New South Wales, Australia
3Hunter Area Pathology Service, A Division of Pathology North, Newcastle, New South Wales, Australia
4Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore
5Centre for Asthma and Respiratory Disease, University of Newcastle, New South Wales, Australia
6School of Biological Sciences, Nanyang Technological University (NTU), Singapore
7National Public Health Laboratory (NPHL), Ministry of Health, Singapore
8Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR, Westmead Hospital and University of Sydney, New South Wales, Australia
9PathWest Laboratory Medicine, Nedlands, Western Australia, Australia
10School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Western Australia, Australia
11National Centre for Immunisation Research and Surveillance of Vaccine Preventable Disease, Kids Research Institute, The Children's Hospital at Westmead, New South Wales, Australia
12Sydney Institute for Emerging infections and Biosecurity (SEIB), The University of Sydney, New South Wales, Australia
13Academic Unit of Child Health, Queen Mary University of London, London, United Kingdom
↵*Corresponding Author: Aeron Hurt (PhD), WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St, North Melbourne, Victoria 3051, Australia. phone: +613 9342 3914, email: aeron.hurt@influenzacentre.org
Abstract
Background Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community-transmission has not previously been reported.
Methods Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses.
Results Twenty nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only one patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including one strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K and N386S in these viruses may offset the destabilizing effect of the H275Y substitution.
Conclusions This cluster represents the first widespread community-transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
http://jid.oxfordjournals.org/content/early/2012/05/04/infdis.jis337.short?rss=1