title: Emergence of oseltamivir resistance: control and management of influenza before, during and after the pandemic.
abstract: Neuraminidase inhibitors (NAIs), such as oseltamivir and zanamivir, are the medicines of choice against influenza A or B. Oseltamivir resistance can be conferred by a single point missense mutation from histidine to tyrosine at position 275 (H275Y) of the neuraminidase gene. Oseltamivir resistance in seasonal influenza A/H1N1 strains rose markedly during the 2007-2008 season. Furthermore, oseltamivir resistant (OsR) strains of pandemic influenza A/H1N1 2009 (influenza A(H1N1)pdm09) have been increasingly isolated, although the majority remain sensitive. These OsR strains retain virulence, replicative fitness and transmissibility from person to person, with outbreaks reported. Treatment options in those at risk of severe or complicated disease are limited to zanamivir which is only licenced in those over the age of 5 years; of further concern, strains demonstrating low level resistance to both oseltamivir and zanamivir have been reported. Strategies to reduce emergence of resistant strains, such as higher dose oseltamivir regimens, need further examination.
authors.affiliation: National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Locked Bag 4001, Westmead, NSW 2145, Australia.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Dixit
authors.forename: Gulam
authors.initials: G
authors.lastname: Khandaker
authors.forename: Scott
authors.initials: S
authors.lastname: Ilgoutz
authors.forename: Harunor
authors.initials: H
authors.lastname: Rashid
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
mesh_terms: D000328:Adult; D019072:Antibiotic Prophylaxis; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014943:Global Health; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control / Q000821:virology; D020125:Mutation, Missense; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics; D053139:Oseltamivir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058873:Pandemics / Q000517:prevention & control; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D053243:Zanamivir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir