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Denmark - Dane with novel H1N1 found resistant to Tamiflu

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

from post #131:



Is the N1 gene of novel H1N1 very different from seasonal?

Do the the words "isn't as susceptible to the antiviral resistance mutation" mean they believe it is less likely to reassort because it is so different?

If I remember correctly, the NA is swinish, so is there antiviral resistance in influenza commonly circulating in pigs?

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All 8 gene segments in swine are quite a bit different than human. Even the PB1, which is human, is close to H3N2 PB1 from 5-15 years ago.
 
Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

So are you in agreement with Carolyn Bridges's statement that the N1 gene is different from the seasonal version, therefore " the pandemic virus isn't as susceptible to the antiviral resistance mutation" ?

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Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

So are you in agreement with Carolyn Bridges's statement that the N1 gene is different from the seasonal version, therefore " the pandemic virus isn't as susceptible to the antiviral resistance mutation" ?

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No. There has already been one report from a VERY limited dataset. Now that H274Y in swine H1N1 has been reported, I expect more sequences and more examples. Although sequences are deposited promptly, surveillance, even for pandemic H1N1, still has some VERY serious issues (the grand total for Denmark remains at ONE, which is one more than many countries).
 
Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

If H274Y takes hold and takes out both tamiflu and peramivir it does seem that for all practical purposes we would be left with inhaled Relenza (and its inherent problems of being able to be inhaled deep enough in young children and in people with lung problems)... 2 other drugs in the pipeline A-315675 (a possible oral alternative to tamiflu) and long acting zanamivir dimers also both look like they have their problems in development .. A-315675 though may be worth some clinical trials as it appears to have some effectiveness against H274Y although it appears difficult to sort out its in vitro and in vivo effectiveness (in mice)...


http://www.sciencedirect.com/scienc...serid=10&md5=30c45280c3e0da047dde530560201c11

""These results confirm the potent inhibitory effect of A-315675 against oseltamivir-resistant influenza viruses of the N1 and N2 subtypes and support the clinical development of its bioavailable prodrug A-322278.""


http://aac.asm.org/cgi/content/full/53/2/791

"""Finally, we confirmed that the A/H1N1 H274Y mutant virus is as virulent as the WT virus, at least in this mouse model and in the A/WSN/33 background (2), which correlates with its natural occurrence and high transmissibility in humans during the 2007 to 2008 influenza season. Of note, A-322278 appears to be somewhat less effective in protecting mice challenged with the NA H274Y mutant virus than those infected with the WT virus. As we have previously reported similar 50% lethal dose values for the two viruses in mice (i.e., 103 PFU) (2), it is possible that such differences in activity could be attributable to low-level cross-resistance between the two drugs that is not measurable in in vitro assays. Clinical trials of A-322278 are warranted in the context of an eventual pandemic and in consideration of the limited alternatives to oseltamivir. """
Resisatnce discover in Hong Kong in patient from San Francisco who was NOT taking Tamiflu. It is fit.
 
Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Please. Drug resistance is a phenotype. This is high school definition time.

Phenotype = the observable characteristics and traits of an organism. In this case, we observe drug resistance.

Genotype = the genetic makeup of an organism. H274Y is one of several genotypes that can confer the phenotype of drug resistance.

Until and unless the sequences from the Danish patient are published, we do not know the genotype of the flu strain she had, but we do know that the phenotype was a drug resistant one. There are no grounds for the assertion that the resistance is due to H274Y. However, if the patient she caught it from had a non-resistant strain, then that would constitute very good evidence that the resistance is due to a de novo mutation in this individual patient, and not indicative of wider circulation of a resistant strain.
H274Y has now been confirmed in Denmark and Japan, and the resistance in Hong Kong (from San Franciso) is in patient NOT taking Tamiflu, so it is almost CERTAINLY H274Y and is spreading silently in the United States due to poor surveillance (at best).
 
Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Google translation

- He had to start with no ill. That was in the preventive treatment with Tamiflu, because he had been in close contact with a swine influenza hit abroad. Since there had been five days of Tamiflu, the person suddenly ill with H1N1, but it not appear that the medicine worked.
Symptoms five days after the start of prophylatic treatment matches the most recent case in Japan.
 
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