23 August 2008

WHO reports that 107/= 107 (100%) of influenza A (H1N1) human viruses this flu season are resis= tant to oseltamivir (Tamiflu) (Note: This is not avian H5N1)

The World Health Organization (WHO) reported on their influenza website 20 August 2008 a three page document listing the results = of Influenza A (H1N1) virus resistance to oseltamivir (Tamiflu) in 2008 for nations in the southern hemisp= here as well as the northern hemisphere. Of note, in the southern hemisphereR= 17;s current flu season 107/107 H1H1 human influenza isolates that have been tes= ted from South Africa and 10/10 H1N1 human flu isolates from Australia have been found to be resistant to oseltamivir by genotypic analysis.

The explanation is uncertain, especially given the fact = that only one of the 107 patients in South Africa was reported to be receiving oseltamivir. In Chil= e, 4/32 H1N1 isolates (13%) were resistant to oseltamivir, specifically the H2= 74Y resistance mutation. No increase in virulence of the H1N1 influenza illness= was noted.

In Hong Kong, a secon= d peak of influenza typically occurs in July-August each year, albeit smaller than= the usual peak in the winter months (December-March) of the northern hemisphere. From the second q= uarter of 2008 until 20 August, a total of 583 influenza A (H1N1) virus isolates f= rom patients in Hong Kong have been tested and 97 (17%) have been found to be resistant to oseltamivir.

During the past winter flu season in the northern hemisphere,, from the last quarter of 2007 until 31 March 2008, WHO’s update on 20 August showed Influenza A (H1N1) resistance to oseltamivir rat= es to be: e.g., Norway 178/265 (= 67%); France 231/496 (47%); Russian Federation 58/128 (45%), Ukraine 23/67 (34%); Switzerland 10/53 (19%); USA 126/1026 (12%); Hong Kong 79/666 (12%); UK 37/= 346 (11%); Spain 2/106 (2%).

As discussed in several “Washington Newsletters= 221; on this website earlier this year (January 30, Feb 1, Feb 8, Feb 19, Feb 28, 2008)), the surprising and unexplained sharp increase in Influenza A (H1N1) resistance to oseltamivir was reported by the European CDC and WHO at the s= tart of 2008 ). =

Of particular concern is the fact that such oseltamivir resistant human influenza A viruses are being transmitted person-to-person. Previous observations were that some, but not all, oseltamvir-resistant influenza viruses had an impaired biological “fitness” such that their ability to spread from person to pers= on was impaired.

Given that influenza A (H1N1) viruses can become resista= nt to oseltamivir AND be transmitted person-to-person-to person, how likely is= it that avian influenza A (H5N1) will acquire the ability to become resistant = to oseltamivir AND be transmissible from person-to-person-to person?

Rare instances of such H5N1 avian influenza viruses resistant to oseltamivir have already been reported in the scientific literature (e.g., from Vietnam). Fortunately, neither these H5N1 vi= ruses nor any others have acquired the ability to be spread in a sustained manner from person-to-person-to person.

This 20 August report from the WHO should be grounds to develop faster additional novel anti-influenza medications that could be used for prevention and treatment, both of current human influenza viruses and potential pandemic human threats such as avian influenza viruses H5N1, H7N7, H7N3, H7N2, H9N2 and other flu viruses of avian origin not yet recognized to infect humans.

Lastly, ongoing international work to identify the mecha= nism of acquiring oseltamivir resistance by human Influenza = A (H1N1) viruses should be strongly supported in order to make appropriate interventions as soon as possible.

Daniel R. Lucey, MD, MPH

EROne Institutes, Washington Hospital Center

Adjunct Professor of Microbiology and Immunology

Geo= rgetown University Medical<= /st1:PlaceName> Center=

Was= hington, D.C.

Website for this newsletter: www.BePast.org

e-mail:DRL23@Georgetown.edu

=