Saturday, July 19, 2008

Increased Tamiflu Resistance In Seasonal Influenza

 

# 2157

 

 

Roughly 6 months ago an increased number of H1N1 influenza samples with resistance to Tamiflu began showing up in Norway.  These viruses carried a specific neuraminidase mutation called  H274Y that results in a decreased sensitivity to oseltamivir (Tamiflu).

 

Prior to this time, very few instances of tamiflu resistance among seasonal flu samples had been detected.  In the 2006-2007 flu season, laboratories found no resistant strains in Europe or Japan, and in less than 1% of samples from the United States.

 

 

This year, we've seen a sudden surge of Tamiflu resistance, and this has many scientists worried.   Thus far, we are talking about the H1N1 seasonal flu virus.   Widespread resistance has not shown up in the H5N1 avian flu virus, nor is it being seen in the H3N2 seasonal flu.

 

 

It was just three years ago that Amantadine resistance suddenly exploded, and in 2005 the CDC recommended that it no longer be prescribed for influenza.  

 

That pretty much left Tamiflu and Relenza as our only alternatives.

 

The WHO (World Health Organization) is now actively analyzing virus samples from all over the world, looking to see how many have this H274Y mutation, and attempting to figure out why it is happening.

 

Last month we learned that roughly 25% of European samples tested this spring showed this mutation.    Yesterday, a new report was released showing that 100% of South African samples tested now carry this mutation.

 

Here is the analysis from this month's WHO report (reparagraphed for readability).

 

 

 

Influenza A(H1N1) virus resistance to oseltamivir - 2008 influenza season, southern hemisphere

 

18 July 2008


During weeks 26–27 (15 -28 June), the level of overall influenza activity in the world increased reflecting the situation in southern hemisphere. However, influenza A(H1N1)virus circulation remains generally low in all countries reporting influenza activity at this time (see Seasonal influenza activity in the world, 2008)


 

WHO has received several reports from National Influenza Centres in the southern hemisphere regarding influenza A(H1N1)virus resistance to oseltamivir.

 

In South Africa, a total of 90 A(H1N1) viruses have been isolated during the 2008 influenza season to date, and all of the 23 influenza A(H1N1) viruses tested by the WHO collaborating Centres in London and Melbourne were found to have resistance to oseltamivir by neuraminidase enzyme-inhibition assay.

 

None of these patients were receiving oseltamivir at the time of sampling, and no unusual clinical feature or underlying conditions have been found.

 

To date, preliminary test results show that the viruses carry the specific neuraminidase mutation (H274Y) that confers oseltamivir resistance in N1, while no sign of adamantane resistance by genetic analysis have been found. From Chile, three of the 24 A(H1N1) viruses tested showed the specific neuraminidase mutation (H274Y).

 

 

 

Oseltamivir resistance, at least among the H1N1 viruses, seems to be spreading rapidly.   The numbers from South Africa, showing 23 out of 23 samples tested with the mutation are particularly surprising.

 

And the lack of Amantadine resistance in these samples, something that was running as high as 90% three years ago, is also a bit of a surprise.

 

None of this means that Tamiflu has become useless against a pandemic virus, but it is worrisome that the same mutation now being seen in the H1N1 virus is identical to the mutation seen in a handful of H5N1 cases that turned out to be resistant to Tamiflu.