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Emergence and spread of oseltamivir-resistant A(H1N1) influenza viruses in Oceania, South East Asia and South Africa.

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.
AuthorsAeron C Hurt, Joanne Ernest, Yi-Mo Deng, Pina Iannello, Terry G Besselaar, Chris Birch, Philippe Buchy, Malinee Chittaganpitch, Shu-Chun Chiu, Dominic Dwyer, Aurélie Guigon, Bruce Harrower, Ip Peng Kei, Tuckweng Kok, Cui Lin, Ken McPhie, Apandi Mohd, Remigio Olveda, Tony Panayotou, William Rawlinson, Lesley Scott, David Smith, Holly D'Souza, Naomi Komadina, Robert Shaw, Anne Kelso, Ian G Barr
JournalAntiviral research (Antiviral Res) Vol. 83 Issue 1 Pg. 90-3 (Jul 2009) ISSN: 1872-9096 [Electronic] Netherlands
PMID19501261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acids, Carbocyclic
  • Antiviral Agents
  • Cyclopentanes
  • Guanidines
  • RNA, Viral
  • Viral Proteins
  • Oseltamivir
  • NA protein, influenza A virus
  • Neuraminidase
  • Zanamivir
  • peramivir
Topics
  • Acids, Carbocyclic
  • Amino Acid Substitution (genetics)
  • Antiviral Agents (pharmacology)
  • Asia, Southeastern
  • Cluster Analysis
  • Cyclopentanes (pharmacology)
  • Drug Resistance, Viral
  • Guanidines (pharmacology)
  • Humans
  • Influenza A Virus, H1N1 Subtype (drug effects, isolation & purification)
  • Influenza, Human (virology)
  • Microbial Sensitivity Tests
  • Mutation, Missense
  • Neuraminidase (genetics, metabolism)
  • Oceania
  • Oseltamivir (pharmacology)
  • Phylogeny
  • RNA, Viral (genetics)
  • Sequence Analysis, DNA
  • Sequence Homology
  • South Africa
  • Viral Proteins (genetics, metabolism)
  • Zanamivir (pharmacology)

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