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JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

Laidback Al

Well-known member
doi:10.1016/j.jiph.2009.04.004
Journal of Infection and Public Health
Volume 2, Issue 2, Pages 74-80 (2009)


Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

Kenneth C. Earharta, Nasr M. Elsayedb, Magdi D. Saada, Larisa V. Gubarevac, Ahmed Nayelb, Varough M. Deydec, Ali Abdelsattarb, Ahmad S. Abdelghanib, Bruce R. Boyntona, Moustafa M. Mansoura, Hala M. Essmatb, Alexander Klimovc, Deidra Shuck-Leea, M.R. Montevillea, Jeffrey A. Tjadena

Received 23 February 2009; received in revised form 30 March 2009; accepted 1 April 2009.

Summary
In December 2006, three human specimens were received that were suspected positive for influenza A(H5N1). The specimens were tested using real time PCR. And the presence of A(H5N1) virus was confirmed in 2 patients (16F and 26M), The NA sequence from A(H5N1) positive specimens collected before and after antiviral therapy revealed a mutation (N294S) (N295S according to N1 numbering), previously associated with resistance to oseltamivir. When tested with NA inhibition assays, the two N294S viruses from Egypt exhibited from 57 to 138-fold reduction in susceptibility to oseltamivir, depending on the assay. To our knowledge, this is the first time oseltamivir resistance has been detected in A(H5N1) infecting a human prior to treatment.

Keywords: Neuraminidase inhibitors, Oseltamivir resistance, Influenza A virus, A(H5N1), Egypt

Abstract at:
http://www.jiph.org/article/PIIS1876034109000318/abstract
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

In December 2006,
That was 3 years ago; I assume they have kept a close watch on it and haven't found any since?

Is N294S in H5N1 the same as H275Y in H1N1?
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

That was 3 years ago; I assume they have kept a close watch on it and haven't found any since?

Is N294S in H5N1 the same as H275Y in H1N1?

Received 23 February 2009; received in revised form 30 March 2009; accepted 1 April 2009

So, do we know if this took 3 years to become a public publication?
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

I doubt that it took 3 years to become a public publication. There were quite a few papers written on panflu within several months.

Apparently they didn't find any more (or at least not in any newsworthy numbers) oseltamivir resistant viruses after those couple. That was before my flubie days, though; maybe someone else remembers more cases?
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

[FONT=Arial, Helvetica, sans-serif][SIZE=+2]Oseltamivir Resistance ? Disabling Our Influenza Defenses

[/SIZE][/FONT]
<table border="0" cellpadding="0" cellspacing="0"><tbody><tr><th align="right" nowrap="nowrap" valign="top">Volume 353:2633-2636</th><td nowrap="nowrap">
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</td><th nowrap="nowrap" valign="top">December 22, 2005</th><td nowrap="nowrap">
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</td><th align="left" nowrap="nowrap" valign="top">Number 25</th></tr></tbody></table>


"There have now been several reports that oseltamivir-resistant<sup> </sup>influenza A (H5N1) viruses with the H274Y mutation have been<sup> </sup>isolated from humans with avian influenza infection who were<sup> </sup>treated with oseltamivir.<sup>4</sup> The cases described by de Jong et<sup> </sup>al. raise the worrisome prospect that even with therapeutic<sup> </sup>doses, oseltamivir resistance may develop during the course<sup> </sup>of illness and may affect clinical outcomes. Nothing is yet<sup> </sup>known about the transmissibility of oseltamivir-resistant influenza<sup> </sup>A (H5N1) viruses in humans, and it will be important to study<sup> </sup>these isolates in animals to determine how the H274Y mutation<sup> </sup>affects virulence, pathogenicity, and transmissibility.<sup> </sup>"

http://www.flutrackers.com/forum/showpost.php?p=56903&postcount=9
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

posted November 20, 2006

"Leading scientists say the UK government is failing to take advantage of scientific developments in the fight to prevent a flu pandemic. A report from the Royal Society and the Academy of Medical Sciences says it is inadequate to stockpile just one anti-viral drug.
It warns the H5N1 virus can develop resistance to Tamiflu, and says the drug Relenza should also be stockpiled.
It also calls for special scientific advisor to help plan for pandemic flu."


http://www.flutrackers.com/forum/showpost.php?p=47852&postcount=1
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

Is N294S in H5N1 the same as H275Y in H1N1?
Not the same mutation. There are a number of sites which confer some level of resistance
 
Re: JIPH. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt

Not the same mutation. There are a number of sites which confer some level of resistance

Do we see much happening at that site?
 
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