Influenza antiviral resistance testing in new york and wisconsin, 2006 to 2008: methodology and surveillance data
Jennifer M Laplante1, Steven A Marshall, Matthew Shudt
1New York State Department of Health, Wadsworth Center, Albany, New York 12201-0509, USA.
Abstract:
The need for effective influenza antiviral susceptibility surveillance methods has increased due to the emergence of near-universal adamantane resistance in influenza A/H3N2 viruses during the 2005-2006 season and the appearance of oseltamivir resistance in the influenza A/H1N1 virus subtype during the 2007-2008 season. The two classes of influenza antivirals, the neuraminidase inhibitors (NAIs) and the adamantanes, are well characterized, as are many mutations that can confer resistance to these drugs. Adamantane resistance is imparted mainly by a S31N mutation in the matrix gene, while NAI resistance can result from a number of mutations in the neuraminidase gene. During the 2007-2008 season, a neuraminidase mutation (H274Y) conferring resistance to the NAI oseltamivir emerged worldwide in the A/H1N1 virus subtype. Surveillance methodology and data from New York (NY) and Wisconsin (WI) for the 2006-2007 and 2007-2008 influenza seasons are presented. We used an existing pyrosequencing method (R. A. Bright et al., Lancet 366:1175-1181, 2005) and a modified version of this method for detection of adamantane resistance mutations. For NAI resistance mutation detection, we used a mutation-specific pyrosequencing technique and developed a neuraminidase gene dideoxy sequencing method. Adamantane resistance in the A/H3N2 virus samples was 100% for 2007-2008, similar to the 99.8% resistance nationwide as reported by the CDC. Adamantane resistance was found in only 1.2% of NY and WI A/H1N1 virus samples, compared to that found in 10.8% of samples tested nationwide as reported by the CDC. Influenza A/H1N1 virus H274Y mutants were found in 11.1% of NY samples for 2007-2008, a level comparable to the 10.9% nationwide level reported by the CDC; in contrast, mutants were found in 17.4% of WI samples. These results indicate the need for regional influenza antiviral surveillance.
Insights
Antiviral resistance surveillance is crucial due to emerging drug-resistant influenza strains. Regional monitoring in New York and Wisconsin revealed varying resistance levels, highlighting the need for localized influenza antiviral surveillance.
Area of Science:
- Virology and infectious diseases
- Antimicrobial resistance surveillance
- Public health epidemiology
Background:
- Increased need for influenza antiviral susceptibility surveillance methods due to widespread adamantane resistance in influenza A/H3N2 and oseltamivir resistance in influenza A/H1N1.
- Adamantane resistance is primarily linked to the S31N mutation, while neuraminidase inhibitor (NAI) resistance involves various neuraminidase gene mutations.
- The H274Y mutation conferring oseltamivir resistance emerged globally in influenza A/H1N1 during the 2007-2008 season.
Purpose of the Study:
- To present surveillance methodology and data for influenza antiviral resistance from New York and Wisconsin during the 2006-2007 and 2007-2008 seasons.
- To detect adamantane and neuraminidase inhibitor resistance mutations in circulating influenza viruses.
- To assess the need for regional influenza antiviral surveillance based on observed resistance patterns.
Main Methods:
- Utilized an established pyrosequencing method and a modified version for detecting adamantane resistance mutations.
- Employed mutation-specific pyrosequencing and developed a neuraminidase gene dideoxy sequencing method for NAI resistance mutation detection.
- Analyzed surveillance data from New York and Wisconsin for the 2006-2007 and 2007-2008 influenza seasons.
Main Results:
- Adamantane resistance in influenza A/H3N2 was 100% in 2007-2008, consistent with national data.
- Adamantane resistance in influenza A/H1N1 was low (1.2%) in NY and WI samples compared to national levels (10.8%).
- The H274Y oseltamivir resistance mutation in influenza A/H1N1 was detected in 11.1% of NY samples and 17.4% of WI samples, comparable to national figures.
Conclusions:
- Regional variations in influenza antiviral resistance patterns necessitate localized surveillance efforts.
- The study confirms the emergence and spread of oseltamivir resistance in influenza A/H1N1.
- Effective surveillance methods are critical for monitoring antiviral resistance and guiding public health interventions.
