resistance, page-2

http://www.recombinomics.com/News/12190901/H274Y_Japan_Fix.html

Commentary

Japan H1N1Tamiflu Resistance Sequences Signal Fixing Start
Recombinomics Commentary 02:19
December 19, 2009

The National Institute of Infectious Diseases in Japan has released 68 full sets of H1N1 sequences from Japan. A few sequences were collected in the spring and early summer, but most are from the late summer and fall and include eight sequences with H274Y. Most of these Tamiflu resistance sequences are among the more recent isolates, signaling the recent spread of Tamilfu resistance. One isolate, A/SHIGA/43/2009, has D225E as well as additional markers found in two isolates from the US, A/Hong Kong/2369/2009 and A/Tennessee/17/2009, which brings the total of H274Y isolates in this well defined sub-clade to three. Recently released sequences from Texas had the same set of markers, but was wild-type at codon 274, suggesting H274Y was circulating as a minor species. Additional sequences from Japan as well as other CDC sequences at GISAID indicate this sub-clade was widespread in both countries and H274Y was silently spreading.

The recently released sequences from Japan and the United States identified addition sub-clades with multiple isolates with H274Y suggesting spread via minor species was common and was likely linked to the recent explosion in H274Y sequences announce by the WHO and CDC. Today the weekly CDC update (week 49) described 15 new H274Y isolates which raised double of such isolates announced in the US in the past 5 weekly reports. Similarly, 13 such isolates have been discovered recently in the Netherlands and recent H274Y cases in the US (Utah) and Netherlands have been fatal. In addition, H274Y and D225N have been detected in the same host in the US (Illinois) and France and both cases were fatal. There have also been three examples of H274Y paired with D225E, but the number of such sequences as minor species is likely to have been much higher.

The recent dramatic rise in Tamiflu sequences is defining the start of the fixing of H275Y in pandemic H1N1, as happened in seasonal flu. This fixing will be facilitated by the drop in cases, which eliminates competing genomes lacking the combination of H274Y and a receptor binding change. The emergence of seasonal H1N1 with H274Y and A193T was facilitated by the emergence of the combination in the southern hemisphere in the summer of 2008, which was followed by fixing in the northern hemisphere in the 2008/2009 season.

The drop in flu activity in the US and Japan will allow for the emergence of H274Y, which could happen in early 2010 when a new peak of activity forms. Thus, these recent changes increase causes for concern.