Oseltamivir-resistant influenza viruses circulating during the first year of the influenza A(H1N1)2009 pandemic in the Asia-Pacific region, March 2009 to March 2010

Abstract

During the first year of the influenza A(H1N1)2009 pandemic, unprecedented amounts of the neuraminidase inhibitors, predominantly oseltamivir, were used in economically developed countries for the treatment and prophylaxis of patients prior to the availability of a pandemic vaccine. Due to concerns about the development of resistance, over 1,400 influenza A(H1N1)2009 viruses isolated from the Asia-Pacific region during the first year of the pandemic (March 2009 to March 2010) were analysed by phenotypic and genotypic assays to determine their susceptibility to the neuraminidase inhibitors. Amongst viruses submitted to the World Health Organization Collaborating Centre for Reference and Research in Melbourne, Australia, oseltamivir resistance was detected in 1.3% of influenza A(H1N1)2009 strains from Australia and 3.1% of strains from Singapore, but none was detected in specimens received from other countries in Oceania or south-east Asia, or in east Asia. The overall frequency of oseltamivir resistance in the Asia-Pacific region was 16 of 1,488 (1.1%). No zanamivir-resistant viruses were detected. Of the 16 oseltamivir-resistant isolates detected, nine were from immunocompromised individuals undergoing oseltamivir treatment and three were from immunocompetent individuals undergoing oseltamivir treatment. Importantly, four oseltamivir-resistant strains were from immunocompetent individuals who had not been treated with oseltamivir, demonstrating limited low-level community transmission of oseltamivir-resistant strains. Even with increased use of oseltamivir during the pandemic, the frequency of resistance has been low, with little evidence of community-wide spread of the resistant strains. Nevertheless, prudent use of the neuraminidase inhibitors remains necessary, as does continued monitoring for drug-resistant influenza viruses.

A Randomized Study of Standard versus Double dose Oseltamivir for Treating Influenza in the Community

“…Higher doses of oseltamivir may more rapidly reduce viral load, averting the selection of resistant strains, but evidence of this is lacking. Double dose (DD) regimens of oseltamivir have been used in both immunocompromised and artificially ventilated patients [6,24,25]. This study aimed to investigate whether this would be an effective strategy to reduce oseltamivir resistance, particularly amongst children (≤15 years), recruited from both the children's hospital and a general practice.…”

“…Since NAIs were introduced in 1999 and until 2007, ≤1% of viruses tested had mutations conferring oseltamivir resistance [1,2]. Oseltamivir-resistant (OsR) influenza A/H1N1 was first detected in Europe during the northern hemisphere winter of 2007-2008 and spread globally, such that by the 2008-2009 northern hemisphere winter, most strains of seasonal influenza A/H1N1 were OsR [3][4][5][6]. No difference in clinical severity was noted between the OsR and oseltamivir-sensitive (OsS) viruses [7].…”

“…In preparation for an influenza pandemic many nations stockpiled oseltamivir, preferring it to zanamivir for its oral administration, systemic bioavailability and licensure for use from ≥1 year of age, as opposed to ≥5 years with zanamivir. Filled oseltamivir prescriptions in Australia increased from approximately 25,000 in 2008 to more than 350,000 in 2009, a process that may potentially promote the emergence of OsR viruses [6].…”

In Vitro and In Vivo Antiviral Studies of New Heteroannulated 1,2,3-Triazole Glycosides Targeting the Neuraminidase of Influenza A Viruses

“…This highlights the urgent need to develop new anti-influenza drugs, particularly with the emergence of variants in the amino acid composition of different proteins of influenza virus causing multidrug resistance in humans. The co-crystallized ligand zanamivir (Relenza) has been used because it shows less resistance and has fewer side effects than adamantane groups [6,32]. All H3N2 viruses show adamantine resistance but are still sensitive to neuraminidase inhibitors; seasonal H1N1 virus resistance to oseltamivir was nearly 100% during 2009-2010 [8].…”

Infrared Thermal Imaging of Patients With Acute Upper Respiratory Tract Infection: Mixed Methods Analysis

“…Because the antigen on the surface of this subtype of human virus can readily directly undergo immune mutation, new immune subtypes are generated, and there is no possibility of direct crossover between different novel subtypes for immunization. Therefore, the disease can not only occur repeatedly within one year in the same person but can also cause widespread epidemics in a few years [5,6].…”