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CDC Issues H1N1 Alert In United States
Recombinomics Commentary 14:10
January 18, 2011

consideration of antiviral treatment for any previously healthy, non high-risk symptomatic outpatient with confirmed or suspected influenza, based upon clinical judgment, if treatment can be initiated within 48 hours of illness onset.

The above comment is included in the recent CDC health alert on influenza antiviral treatment and diagnostic tests.  This January 14, 2011 alert follows a significant outbreak of H1N1 in the UK and reports of increased H1N1 activity in the northern hemisphere. 

Initial reports from the UK indicated most fatal cases were young adults without underlying conditions.  Subsequent reports have focused on patients with underlying conditions, but the high frequency of fatal cases without underlying conditions raised concern. 

A similar death cluster was reported in Lehigh, Pennsylvania and recently released sequences by the CDC demonstrated the presence of S186P in the identical HA sequences from the two Pennsylvania cases, which were closely related to UK sequences. 

Moreover, one of the sequences, A/India/5103/2010, without changes at positions 156-159 was declared a low reactor, and this sequence had S186P and S188T.  These two changes are widespread in the UK, with 22/41 cases having S188T and another 14/41 cases having S186P.  In addition to the case in India, a sequence from Japan, A/KANAGAWA/74/2010, also had both changes, and the most recent sequence from Japan, A/NIIGATA/1581/2010 also had S188T.

Other combinations were seen in the UK and Bhutan.  In the UK there were sequences with S188T combined with D190G (A/England/4640543/2010) and S186P combined with D190Y (A/England/4500186/2010). Similarly, A/Bhutan/72/2010 had S186P combined with A189T.  These combinations are similar to the immunological escape of seasonal H1N1 associated with the fixing of H275Y in 2008/2009 which involved A193T combined with at least one change at positions 187, 189, or 196.

These genetic changes indicate the current vaccine, direct against A/California/7/2009 will have less than optimal efficacy as sequences with the above receptor binding domain changes emerge and dominate.  As noted, 36/41 recent sequences from the UK had S188T or S186P, and these changes are rapidly spreading throughout the northern hemisphere.

The CDC alert does not mention these changes, but includes antiviral recommendations, which includes use in previously health young adults.

The current H1N1 vaccine target, A/California/2009, has remained unchanged since it was selected in the spring of 2009.  It is currently recommended for the 2010/2011 season in the northern hemisphere, and is the target for the 2011 season in the southern hemisphere.

Recommendations for the 2011/2012 northern hemishere flu season will be made next month.  A target change is long overdue.

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