SURVEILLANCE OF ANTIVIRAL RESISTANT INFLUENZA FROM 2006-2008 BY A NETWORK OF U.S. STATE PUBLIC HEALTH LABORATORIES

Background: Surveillance of circulating influenza A(H3N2) viruses in New York State and Wisconsin State during the 2005-2006 influenza season showed predominant resistance to adamantane antiviral agents, while influenza A(H1N1) viruses remained sensitive to adamantanes.  During the 2007-2008 influenza season there has been an increased level of resistance among circulating influenza A(H1N1) viruses to the neuraminidase inhibitor oseltamivir (Tamiflu).  We have developed a state public health laboratory network of participant states that regularly screen for influenza antiviral resistance. 

Methods: We screened influenza primary specimens and tissue culture isolates collected in our respective states during the 2006-2007 and 2007-2008 influenza seasons for adamantane and neuraminidase inhibitor antiviral resistance mutations.  Pyrosequencing and/or dideoxy sequencing methods were employed for the matrix and neuraminidase genes.  Surveillance results from participants were compared to CDC surveillance results. 

Results: Collectively for the 2006-2007 influenza season, network participants detected adamantane resistance rates of 82.7% and 0% for influenza A(H3N2) and A(H1N1) viruses, respectively. All resistant influenza A(H3N2) viruses contained the S31N mutation in the matrix gene.  No neuraminidase inhibitor resistance (determined only in New York during this season) was detected to either oseltamivir or zanamivir in influenza A or B, as compared to CDC rates of 0.7% to oseltamivir for influenza A(H1N1) and 0% for influenza A(H3N2) and B viruses.  Collectively for the 2007-2008 influenza season (as of mid February 2008), network participants detected adamantane resistance rates of 100% and 1.7% for influenza A(H3N2) and A(H1N1) viruses respectively, compared to CDC detected rates of 98.6% and 7.2%.  Oseltamivir resistance rates were 12.1% for influenza A(H1N1), and 0% for influenza A(H3N2) and B viruses, compared to CDC detected rates of 8.7% for influenza A(H1N1) and 0% for influenza A(H3N2) and B viruses.  All oseltamivir resistant influenza A(H1N1) viruses contained the neuraminidase mutation H274Y (which does not confer resistance to zanamivir) but retained susceptibility to adamantanes. 

Conclusion: These results indicate that resistance to adamantane and oseltamivir antivirals among circulating influenza viruses in participant states is increasing at a comparable rate to that seen nationally.  Implications of these results include the possibility of the development of sub-type specific rapid influenza tests to guide therapeutic decisions.  In order to correctly monitor future test kit accuracy and changing antiviral resistance rates, the state public health laboratory surveillance network for antiviral susceptibility resistance should be expanded to include other states.  Such a network could provide antiviral test results in support of CDC testing efforts, especially in outbreak situations in which patients are not responding to antiviral treatment or during a pandemic.