31 January 2008

Increasi= ng Numbers of European Nations (9) Report High Level (H274Y) Oseltamivir (Tamiflu)-Resistant Human influenza A H1N1 (not H5N1 avian flu)<= /span>

On January 31, 20= 08 the journal “European Surveillance” posted online a rapid communication paper and accompanying editorial

describing= oseltamivir (Tamiflu)-resistant seasonal H1N1 human influenza viruses in 9 European nations.&n= bsp; Earlier this week such flu viruses were reported from isolates in fo= ur European nations. Of note, no= ne of these influenza viruses are the avian flu virus H5N1. Today’s report = by Nicoll and colleagues can be found at:

www.eu= rosurveillance.org/edition/v13n05/080131_2.asp.

This report updat= es that of January 27^th and now includes a total of 437 influenza A (H1N= 1) virus isolates from 18 European nations. Of these, 50 (14%) show oseltamivir resistance by H274Y genotypic testing, or IC50 phenotypic resistance testing (see Table 1 of this paper by Nicoll et al.). One or more oseltamivir-resistance influenza H1N1 viruses were found in 9 of the 18 nations: Norway (26/37 vir= us isolates =3D70%), France (15/87=3D17%), UK (8/162=3D6%), Germany (3/42=3D7%= ), Finland (2/7), Portugal (2/6), Denmark (1/10), Sweden (1/13), and Netherlands (1/16= ).

These viruses with the H274Y mutation were reported to have IC50 values increased from ~ 1nM to over 400nM. As in the smaller initial report earlier this week, all these viruses remain sensitive to the three other anti-influenza drugs: zanamivir, rimantidine, and amantidine.

The majority of t= hese oseltamivir-resistant viruses have been isolated from adults, although the = ages of the patients range from 1 month to 61 years. Of note, none of these pati= ents are known to have taken oseltamivir for therapy or prophylaxis, or to have = been in contact with anyone taking oseltamivir. Thus, the authors conclude that = this is “the first clear evidence that influenza A (H1N1) virus with the H= 274Y mutation can readily transmit between individuals”.

The accompanying editorial by Nicoll et al. emphasizes that these oseltamivir-resistant H1N1 influenza viruses are well-matched with the current influenza vaccine. The editorial by Lackenby et al., can be found at www.eu= rosurveillance.org/edition/v13n05/080131_2.asp

The January 31st New York Times (page A8, by Larence K. Altman) reports that in the USA the oseltamivir-resistant influenza A (H1N1 H274Y) strain has been found in 9/1= 35 (6.7%) isolates of H1N1 viruses tested so far this flu season. The article also reported that the= World Health Organization (WHO) on Tuesday (January 29^th) held a two-h= our teleconference with experts from multiple nations, according to a phone interview with Dr. Frederick Hayden, an influenza expert at WHO.

Further informati= on from Europe, North America, and around the world will be forthcoming in the days and weeks ahead as influenza isolates are tested for oseltamivir-resistance. More are likely to be found. Fortunately, none of these v= iruses are the H5N1 avian influenza strain that has generated much concern as a possible pandemic precursor virus.

At the same time,= the fact that this is the “first clear evidence” that significant p= erson-to-person spread of oseltamivir-resistant (H274Y) seasonal human influenza A (H1N1) v= irus is occurring is worrisome. Previously, it was thought that the acquisition = of this oseltamivir resistance typically conferred “less biologically fi= t” flu viruses that were not readily transmitted from person-to-person in a sustained manner. =

Only the future w= ill tell whether this phenomenon turns out to be an example of “past-as-prologue” in terms of other influenza viruses such as H3N2, H9N2, H7N7, H7N3, H7N2, H5N1 following the same pattern as oseltamivir-resistant H1N1 H274Y person-to-person transmission.

Daniel R. Lucey, = MD, MPH

Director, Center = for Biologic Counterterrorism and Emerging Diseases

EROne Institutes, Department of Emergency Medicine

Washington Hospit= al Center-Medstar Health

Adjunct Professor= of Microbiology and Immunology

Georgetown Univer= sity Medical Center

Washington, DC

Website for this posting: www.BePast.org

e-mail:DRL23@Geor= getown.edu