GOUVERNEMENT knowing the risk keep it for first group clients " their employees "
All of this was predicted by analyses of the molecular structure of oseltamivir, zanaivir and neuraminidase. But those predictions were also based on snapshots of structures. New work by Landon et al. and Russell reveals the N1 version is more flexible than thought and that once bound the shape can change from a form similar to N2 behavior to a more open form in N1. Thus the tidy story may not be so tidy after all, or at least our explanations need some modification. The claim of increased resistance to oseltamivir in H1N1 is based on the appearance of H274Y, not yet on the demonstration that H274Y is of clinical importance in the treatment of influenza. Is there evidence that would mitigate its importance? Not much, but there is some. There is a body of work to show that the viruses that carry H274Y are not as fit as the ones that don't. Unfortunately some of this published work comes from the maker, Roche, so there will be well founded suspicion (this is a burden Roche scientists must bear as a result of the behavior of their employer and the whole industry of which it is a part). What that work seems to show (subject to the qualifications just stated) is that H1N1 carrying H274Y replicates a thousand times less well than the unmutated version and that its ability to cause disease in the ferret model (thought to mimic human infection) is also significantly compromised (see Ives et al.). There are little clinical data shedding light on the efficacy of Tamiflu in H274Y carrying H5N1 viruses, although the mutation has been found there in some patients. A paper by de Jong et al. in 2005 described two fatal cases of H5N1 in Vietnamese patients where H274Y viruses replicated to produce moderate to high viral loads even during timely Tamiflu treatment.
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