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H1N1 Tamiflu Resistance in the United States in 2007

Recombinomics Commentary 03:11
January 29, 2008

The European Centres for Disease Control said that while Tamiflu could still provide benefits, 13 per cent of samples of the H1N1 seasonal flu virus affecting Europe tested last November and December – most in Norway – contained a mutation associated with high levels of resistance.

The above comments describe the appearance of the oseltamivir resistance marker, H274Y, in recent H1N1 isolates in Europe. 

However, a search of public sequences identifies H274Y suddenly appearing in 2007 H1N1 isolates from the United States (see list below.  The number of complete human influenza sequences has grown steadily, largely because of the NIAID influenza sequencing project.  At the Los Alamos sequence database, there are 1030 N1 sequences from H1N1 human isolates.  340 are from 2007 and all of the sequences below are from 2007.  Thus, although the percentage of samples was low, all were from 2007 and all were Solomon Island-like.

These Solomon-Island lake sequences trace back to Asia, where Tamiflu blankets are frequently applied in the treatment of H5N1.  The N1 in H5N1 has donor sequences for human N1 in the region adjacent to the acquisition which generates H274Y, which is the precise change found in the most common form of oseltamivir resistance in H5N1 patients, primarily in Vietnam.

In 2005 a milder version of H5N1 emerged in northern Vietnam.  However, initial data supporting widespread mild infections of H5N1 were denied, even after initial results were independently confirmed. 

Testing continued until negatives were achieved.  The possibility of widespread H5N1 in people in Vietnam was largely discounted and use of Tamiflu in contacts of suspect patients was common.

Now Tamiflu chickens may be coming home to roost.

ISDN282211  A/Hawaii/21/2007  H1N1  
ISDN282224  A/Hawaii/28/2007  H1N1  
ISDN282222  A/Hawaii/28/2007  H1N1  
CY027037      A/Kansas/UR06-0104/2007  H1N1  
ISDN282240  A/Minnesota/23/2007  H1N1  
ISDN263890  A/Texas/31/2007  H1N1 

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