Emergence of oseltamivir resistance: control and management of influenza before, during and after the pandemic

Rashmi Dixit; Gulam Khandaker; Scott Ilgoutz; Harunor Rashid; Robert Booy

doi:10.2174/18715265112129990006

Emergence of oseltamivir resistance: control and management of influenza before, during and after the pandemic

Infect Disord Drug Targets. 2013 Feb;13(1):34-45. doi: 10.2174/18715265112129990006.

Authors

Rashmi Dixit¹, Gulam Khandaker, Scott Ilgoutz, Harunor Rashid, Robert Booy

Affiliation

¹ 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.

PMID: 23675925
DOI: 10.2174/18715265112129990006

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adult
Antibiotic Prophylaxis
Antiviral Agents / administration & dosage
Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use*
Child
Dose-Response Relationship, Drug
Drug Resistance, Viral*
Enzyme Inhibitors / administration & dosage
Enzyme Inhibitors / pharmacology
Enzyme Inhibitors / therapeutic use
Global Health*
Humans
Influenza A Virus, H1N1 Subtype / drug effects*
Influenza A Virus, H1N1 Subtype / enzymology
Influenza A Virus, H1N1 Subtype / growth & development
Influenza A Virus, H1N1 Subtype / isolation & purification
Influenza, Human / drug therapy*
Influenza, Human / epidemiology
Influenza, Human / prevention & control
Influenza, Human / virology
Mutation, Missense
Neuraminidase / antagonists & inhibitors
Neuraminidase / genetics
Oseltamivir / administration & dosage
Oseltamivir / pharmacology
Oseltamivir / therapeutic use*
Pandemics* / prevention & control
Viral Proteins / antagonists & inhibitors
Viral Proteins / genetics
Zanamivir / administration & dosage
Zanamivir / pharmacology
Zanamivir / therapeutic use

Substances

Antiviral Agents
Enzyme Inhibitors
Viral Proteins
Oseltamivir
NA protein, influenza A virus
Neuraminidase
Zanamivir