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Alarming Increase In H1N1 Low Reactors In Japan
Recombinomics Commentary 23:55
July 1, 2011

Today NIID released 37 HA sequences from 2011 (at GISAID), which were associated with frequent Tamifu resistance (H274Y) in most associated NA sequences, as well as one NA sequence with S246N, signaling additional clonal expansion

However, the HA sequences had an alarming number of changes at positions 156-159, with 6,1,9,2 changes respectively.  The prior data on 33 HA sequences from Japan had postion 156-159 chnages of 1,3,5,1, respectively. Changes at these positions are linked to low reactors which have titers reduced four fold or more when tested against the current H1N1 vaccine target, A/California/07/2009.  These numbers are likely to represent an underestimate because the isolates involved growth on mammalian MDCK cells, which are rich in gal 2,6 gal.  Isolation with eggs, which are rich in 2,3 gal receptors would have selected addition examples of changes at this position.  These changes are biologically and clinically relevant because they are associated with vaccine escape as well as preferential growth in human lung, which is rich in gal 2,3 receptors.

The changes are increasing in prevalence, but these alarming changes are being discounted with claims that the changes are artifacts of culture since detection is more difficult in direct sequencing of clinical samples since the changes are frequently present as mixtures with wild type.

The discounting of these changes has significant consequences.  In the United States Pneumonia and Influenza (P&I) deaths were at record levels in 2011 and were similar to rates recorded in 2008.  However, in 2008 the vaccine mismatches with all three vaccine target were eventually acknowledged and all three targets were updated for the following season.  In contrast, in 2011 claims were made that all three targets were “matches” due in part to extensive manipulation of laboratory test results, including claims that negative data invalidated positive data.  Consequently, all three vaccine targets remained unchanged for the 2011/2012 season.

In addition to the elevated P&I death rate, the frequency of Tamiflu resistance has also increased and significant clonal expansion has been seen in the United States and Japan for H274Y.  The reported numbers are underestimates because WHO collaborating centers have agreed to not report Tamiflu resistance when H274Y levels are less than 50% of the sample signal. In addition, clonal expansion of Tamiflu and Relenza resistance (S246N) has been reported in Singapore and Australia, including 30% of H1N1 isolates from Darwin.

These increases in low reactors as well as Tamiflu resistance highlight the folly of lab manipulations to generate under-estimates for “scientific” public reports published by government and international agencies, and these policies and publications remain hazardous to the world’s health.

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