AFD - Oseltamivir Resistance in Seasonal Flu

[sharon sanders]

Friday, August 22, 2008

WHO: Oseltamivir Resistance In Seasonal Flu Continues To Spread



# 2250

http://afludiary.blogspot.com/2008_08_01_archive.html




Oseltamivir (Tamiflu) is one of our front line antivirals against the influenza virus, and up until very early this year very few instances of resistance to this drug had been encountered.


On January 25th, 2008 Norwegian authorities notified the WHO (World Health Organization) of a sudden high rate of resistance to Tamiflu among 12 of 16 samples (75%) collected in late 2007.


This resistance is caused by a mutation, known as H274Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 274.


Over the past 6 months, more reports of Oseltamivir resistance have been received by the WHO, and in some regions, the incidence has been as high as 100%.


This (reparagraphed for readability) from the latest WHO surveillance report :

(Hat Tip Ironorehopper for posting this on Flutrackers)

WHO has received several reports from National Influenza Centres in the southern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir.

In South Africa, a total of 139 A(H1N1) viruses have been isolated during the 2008 influenza season to date. Of those, 107 isolates have been tested for oseltamivir resistance by the National Institute of Communicable Diseases (NICD) and 100% were found to be resistant to oseltamivir by genotypic analysis.

Only one of these 107 patients was receiving oseltamivir at the time of sampling, and no unusual clinical features or underlying conditions were found.

From Australia, 10 of 10 A(H1N1) viruses tested, and from Chile, 4 of 32 A(H1N1) viruses tested showed the specific neuraminidase mutation (H274Y) associated with oseltamivir resistance.
​

The WHO maintains a Q&A page on this growing problem here, although it doesn't appear to have been updated since Feb 15th of this year.


A portion of this FAQ, reproduced below, shows that they have few clues as to what is driving this mutation.

Q6. Is there an explanation for the high frequency of oseltamivir resistance?

The frequency of oseltamivir resistance in H1N1 viruses in the current influenza season is unexpected and the reason why a high percentage of these viruses are resistant is currently unknown.

Available information does not indicate selective drug pressure is driving the development of resistance since few of the patients are known to have taken oseltamivir. Influenza viruses are continuously changing and it is possible that a resistant strain has emerged spontaneously or has continued to spread in the community after being selected initially in someone treated with oseltamivir.

Further detailed laboratory characterization of circulating H1N1 viruses and epidemiological information on patients will be needed to help answer this question.
​

With only GSK's Relenza, and potentially older antivirals such as Amantadine (which we essentially stopped using 3 years ago due to growing resistance problems with the H3N2 virus), as alternatives - the expanding incidence of Tamiflu resistance among seasonal H1N1 influenza viruses is worrisome.


Thus far, we've only seen a handful of resistant cases among H5N1 (bird flu) cases, and Tamiflu continues to remain reasonably effective.

Posted by FLA_MEDIC at <a class="timestamp-link" href="http://afludiary.blogspot.com/2008/08/who-oseltamivir-resistance-in-seasonal.html" rel="bookmark" title="permanent link"><abbr class="published" title="2008-08-22T13:25:00-04:00">1:25 PM</abbr>

 

[sharon sanders]

Re: AFD - Oseltamivir Resistance in Seasonal Flu

CIDRAP News: Growing Tamiflu Resistance


# 2257



Robert Roos at CIDRAP (Center For Infectious Disease Research & Policy) news has a good overview of the recent reports of growing oseltamivir (Tamiflu) resistance in H1N1 seasonal influenza samples worldwide.

This is an ongoing story that I've covered here, here, and here.


As usual, CIDRAP provides more background information than most news reports. I've just included a snippet, follow the link to read the entire article.

H1N1 flu viruses growing more resistant to Tamiflu


Robert Roos

News Editor

Aug 25, 2008 (CIDRAP News) ? With influenza season well under way in the southern hemisphere, one of the three kinds of seasonal influenza virus is becoming increasingly resistant to the antiviral drug oseltamivir (Tamiflu), the World Health Organization (WHO) reported last week.

Thirty-one percent (242 of 788) of influenza A/H1N1 isolates from 16 countries that were tested in recent months carried a mutation associated with oseltamivir resistance, the WHO said. In South Africa, all of the 107 isolates tested had this mutation, known as H274Y, the agency reported.

Other countries and areas that tested 10 or more isolates and found resistance included Australia, 100% (10 of 10 isolates); Ghana, 20% (2 of 10) Hong Kong, 17% (97 of 583); and Chile, 13% (4 of 32 isolates).

The findings strengthen a trend that that was first observed last January in Norway and subsequently in many other countries. Overall for the last quarter of 2007 and the first quarter of this year, 16% (1,182 of 7,528) of tested H1N1 isolates carried the resistance mutation, according to WHO figures. Resistance was found in 35 countries, mostly in the northern hemisphere, including in 12% of tested US isolates and 26% of tested Canadian isolates.

"What we're seeing is the evolution of the resistance gene and the distribution of it throughout the world," said Lance Jennings, a clinical virologist with the Canterbury District Health Board in Christchurch, New Zealand, and chair of the Asia-Pacific Advisory Committee on Influenza, as quoted in an Aug 22 Bloomberg News report.

(Continue Reading . . . )
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Posted by FLA_MEDIC at <a class="timestamp-link" href="http://afludiary.blogspot.com/2008/08/cidrap-news-growing-tamiflu-resistance.html" rel="bookmark" title="permanent link"><abbr class="published" title="2008-08-26T09:22:00-04:00">9:22 AM</abbr>