Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa.
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.
Hurt
Aeron C
AC
WHO Collaborating Centre for Reference and Research on Influenza, Victoria, Australia. aeron.hurt@influenzacentre.org
Ernest
Joanne
J
Deng
Yi-Mo
YM
Iannello
Pina
P
Besselaar
Terry G
TG
Birch
Chris
C
Buchy
Philippe
P
Chittaganpitch
Malinee
M
Chiu
Shu-Chun
SC
Dwyer
Dominic
D
Guigon
Aurélie
A
Harrower
Bruce
B
Kei
Ip Peng
IP
Kok
Tuckweng
T
Lin
Cui
C
McPhie
Ken
K
Mohd
Apandi
A
Olveda
Remigio
R
Panayotou
Tony
T
Rawlinson
William
W
Scott
Lesley
L
Smith
David
D
D'Souza
Holly
H
Komadina
Naomi
N
Shaw
Robert
R
Kelso
Anne
A
Barr
Ian G
IG
D000146:Acids, Carbocyclic; D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D001210:Asia, Southeastern; D016000:Cluster Analysis; D003517:Cyclopentanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology*; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism; D044349:Oceania; D053139:Oseltamivir / Q000494:pharmacology*; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013019:South Africa; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D053243:Zanamivir / Q000494:pharmacology
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D012367:RNA, Viral; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir