Flu Found Resistant to Main Antiviral Drug

[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

[From Italian Ministry of Health weekly update. LINK. IOH.]

(...)
Figure1. Phylogenetic tree for HA1 portion of hemagglutinin of H1N1 viruses isolated during 2008/2009 season in Italy, with particular attention to Parma's isolates.

With respect to trivalent influenza vaccine reference strain, it is noteworthy the homology between Italian H1N1 isolates and the vaccine strain A/Brisbane/59/07(H1N1).

However, Italian A/(H1N1) isolates show several amino-acid changes in HA (A189T, G185A, S141N), respect to vaccine strain.

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Figure 1. Phylogenetic tree of HA1 domain of HA, recent Italian A/(H1N1) virus isolates. (Elaborated by ISS through Kimura 2 method for the genetic distance calculation and Neighbor-Joining algorithm for phylogenetic tree building.)

(...)
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The changes are S145N, G189A, and A193T using H3 numbering. These correspond to WA8 and WI17 in the US. HI19 and the recently released sequence from the Philippines has G189A and A193T, which are also widespread in Asia, including Japan.

[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

Commentary at

http://www.recombinomics.com/News/02180901/H274Y_Vaccine_X.html

[AlaskaDenise]

Re: Flu Found Resistant to Main Antiviral Drug

Commentary at

http://www.recombinomics.com/News/02...Vaccine_X.html

Commentary

Emergence of Vaccine and Tamiflu Resistant H1N1
Recombinomics Commentary 23:15
February 18, 2009


Italian A/(H1N1) isolates show several amino-acid changes in HA (A189T, G185A, S141N), respect to vaccine strain.

The above comments from Italy's weekly influenza report , indicate that the vaccine and Tamiflu resistant H1N1 isolates (A/Parma/23/2009, A/Parma/24/2009, A/Parma/25/2009, A/Parma/26/2009) match recently released US sequences, A/Wisconsin17/2008 and A/Washington/8/2008. The HA sequence for both isolates have the same three changes (A193T, G189A, S145N using H3 numbering). Moreover, the two changes flanking the receptor binding domain, G189A and A193T are in A/Hawaii/19/2008, and A/Mbagathi/7586/2008, as well as the recently released A/Philippines/1159/2008. Moreover, phylogenetic analysis of the NA sequences predict these changes will also be in Japan isolates, Miyagi/35/08, Yamaguchi/26/08, Yamaguchi/27/08, Yamaguchi/28/08. Both Japan and South Korea have had explosions of H1N1 Tamiflu resistant cases, suggesting that the vaccine resistant H1N1 is widespread.

The A193T is in all public H1N1 Tamiflu resistant sequences in the United States and is now also in all public isolates in Spain, and the vast majority if not all isolates in Japan. Although A193T was also linked to the fixing of Adamantane resistance in H1N1 clade 2C as well as Tamiflu resistance in H1N1 clade 2B, it is not in the current vaccine for the northern hemisphere in 2008/2009, and is not vaccine for the southern hemisphere in 2009, nor the northern hemisphere in 2009/2010.
The absence of these important changes in seasonal flu vaccine targets remain a cause for concern.

In Italy, three of the first five H1N1 isolates were from patients who had taken this season's vaccine, suggesting the H1N1 was not only Tamiflu resistant, but also vaccine resistant. Similarly, a report from Taiwan cited vaccine resistance levels at 70% for H1N1, and Japan also reported lower titers for H1N1 isolates when compared to the Bisbane/59 isolate used to represent H1N1 in the current vaccine.

Similarly, both South Korea and Japan reported explosions of cases linked to H1N1 and recently released sequences in the United States have the same three acquisitions reported in Spain. Moreover, recent weekly reports from the CDC do not show a reduction in the levels of H1N1. The vast majority of influenza in the US is influenza A, and the vast majority of influenza A is H1N1, with Tamifu resistance levels approaching 100% (the few sensitive isolates appear to be clade 2C).
Thus, the current approach of using vaccines to chase viral evolution continues to be a cause for concern. The fixing of H274Y in H1N1 seasonal flu raises serious concerns about the potential use of Tamiflu in an H5N1 bird flu pandemic.

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[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

H1N1 phylogenetic tree with 2009 isolates from Tokyo (I think it is same to assume that red isolates have H274Y

http://idsc.tokyo-eiken.go.jp/flu/2008-09/0809keitouAH1.pdf

[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

ANTIVIRAL RESISTANCE DETECTED IN INFLUENZA VIRUSES FROM EUROPEAN COUNTRIES DURING THE SEASON 2008/2009 [ECDC, 2/18/2009]

[Original texts at European Centre of Diseases Prevention and Control website page. LINK. EDITED.]



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[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

H274Y in Japan at 99.5% (420/422 H1N1 tested)

http://idsc.nih.go.jp/iasr/graph/tamiful1.gif

[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

Daiichi Sankyo to launch flu preventive drug-Nikkei | Reuters

Daiichi Sankyo to launch flu preventive drug-Nikkei

Sun Feb 22, 2009 10:51am IST
TOKYO, Feb 22 (Reuters) -

Japan's Daiichi Sankyo Co plans to launch as early as 2011 a new influenza preventive drug that could be effective against a strain unresponsive to widely used Tamiflu of Roche, the Nikkei business daily said.


Japan's third-largest drugmaker plans to seek regulatory approval for the drug by March 2011, the Nikkei said on Sunday.

It said animal testing has suggested the new drug under development is effective against a strain that has tolerance against Tamiflu, made by Swiss pharmaceutical company Roche.

A Daiichi Sankyo spokesman told Reuters the company is developing a new influenza treatment drug and it may seek regulatory approval in Japan by the end of calendar 2009, but declined to comment on Nikkei's report of the preventive drug.

(Reporting by Kiyoshi Takenaka; Editing by Anshuman Daga)
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<cite cite="http://in.reuters.com/article/asiaCompanyAndMarkets/idINT28150220090222">Daiichi Sankyo to launch flu preventive drug-Nikkei | Reuters</cite>

[gsgs]

Re: Flu Found Resistant to Main Antiviral Drug

CS-8958 , "Super Relenza"

http://www.flutrackers.com/forum/showthread.php?t=92115

[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

ECDC. Antiviral resistance detected in influenza viruses from EU member countries during 2008/2009 season (as per Feb. 25, 2009)

[Original table is available at this LINK. EDITED.]


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[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

Killer flu H1N1 resistant to Tamiflu and flu jab vital

By Sue Dunlevy
The Daily Telegraph
March 05, 2009 12:00am
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Killer influenza strain resistant to drugs ... The only protection is a vaccination which Praveen Haider received from nurse Clare MacDuwell yesterday. Picture: Gary Ramage.


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<!-- // article intro ************************************** -->ONE of the killer influenza strains heading to Australia this winter is almost totally resistant to the only anti-viral tablet that can treat it - Tamiflu.
<!-- // END article intro ************************************** --><!-- // article corpus ************************************** -->This means having a vaccination may be the only way for many to beat the flu this year.
Just 10 years after the breakthrough flu drug hit the market the virus has fought back.
A study in this week's Journal of the American Medical Association found 98.5 per cent of the H1N1 influenza virus circulating in the US is now resistant to the antiviral drug Tamiflu.
The H1N1 form of influenza accounted for one in five flu infections in the United States between September 2008 and February 2009.
And four patients with this drug resistant flu died in the United States another two patients with the drug resistant flu died in the Netherlands.
Australia's expert Influenza Vaccine Committee has asked that the H1N1 strain be included in the 2009 flu vaccination available to people here.
The drug company which manufactures Tamiflu, Roche, says there is no evidence that the Tamiflu resistant virus results in more severe illness or that it is more easily transmitted.
Related Coverage
And it says the drug is still fully active against other types of influenza.
In the last 30 years influenza H3N2 has been the main strain circulating in Australia, the company says.
The World Health Organisation estimates around 500,000 people die every year from flu related health complications.
Before the 2007-08 season the level of resistance to Tamiflu among circulating flu viruses in the United States was less than 1 per cent.
By March last year 16 per cent of H1N1 influenza viruses tested had become resistant to Tamiflu, now 98.5 per cent of this strain of the flu is resistant.
The H1N1 virus is still susceptible to the flu medication Relenza but this inhaled product is not suitable for children, those with asthma or breathing problems or those with milk allergies.
The doctors who carried out the American study say it is unclear how H1N1 viruses had changed and become able to circulate between humans so successfully.
The mutation of this virus is of great concern because it has implications for a possible outbreak of the even more deadly birdflu some strains of which are also showing resistance to tamiflu.
The Australian Government has millions of doses of taxpayer funded Tamiflu stockpiled to use in the fight against a birdflu outbreak.
Tamiflu, taken in pill form, is the most commonly used flu treatment drug.
It has to be taken within 48 hours of the first onset of flu symptoms and studies show it speeds recovery from the flu by 30 per cent or 1.3 days.
It is suitable for adults and children aged over a year and requires a doctors prescription but is not subsidised by our drug subsidy scheme.
It won't work to fight off colds or other viruses.
Relenza is the only other flu medication available.
It too has to be taken within 48 hours of symptoms appearing and has to be inhaled so it can be delivered direct to the lungs.More than 500 Australians a week are having flu vaccinations in time for the onset of winter.
"We were early for vaccines this year, because last year's northern hemisphere vaccine was the same as the southern hemisphere - so we got a bit of a flying start," said Dr Tony Gherardin, from the Travel Doctor Group, specialising in vaccinations.
Dr Gherardin said vaccines were diverted from overseas to Australia to provide an early start to protecting against the flu season.
"There's increasing recognition that flu vaccines are safe, therefore increasing recommendation for a much wider group of people to be vaccinated including young children," he said.
Vaccines cost $25.50 each with people aged over nine needing a single shot while children aged between six months to nine needing two shots
"It's best that you crank up the immunity across the community before winter hits," Dr Gherardin said.
Parents are encouraged to vaccinate their children however doctors say people who are allergic to eggs should avoid the vaccine.
The numbers of vaccinations is expected to rise across Australia from next month.

http://www.news.com.au/entertainment/story/0,28383,25138931-5007185,00.html

[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

ECDC. Monitoring of Influenza antiviral resistance in EU during 2008-09 season (3/4/2009)

[Original page at this LINK. EDITED.]


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[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

ECDC. Monitoring of Influenza antiviral resistance in EU during 2008-09 season (March 11, 2009)

Monitoring of Influenza antiviral resistance in EU during 2008-09 season

[Original text is available at this LINK. EDITED.]

Monitoring of antiviral resistance in EU for the season 2008-09 is currently ongoing. The coordinators of The Community Network of Reference Laboratories for Human Influenza in Europe (CNRL), routinely collect, analyze and disseminate information on antiviral resistance from Influenza viruses isolated from 25 European (European Union, EEA/EFTA) countries.

The analysis of resistance against Neuraminidase Inhibitors and Adamantanes is done by measuring IC50 values and/or by genotyping of viruses for detection of known drug resistance mutations.

Summary information on antiviral resistance in EU will be published weekly in the EISS bulletin (LINK) (also featured in the weekly ECDC influenza News)



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[Giuseppe]

Re: Flu Found Resistant to Main Antiviral Drug

From EISS weekly bulletin (March 13, 2009. Post #412 Seasonal Influenza thread, http://www.flutrackers.com/forum/sho...&postcount=412)

- Russian Federation. As a result of 21 strains of influenza A(H3) virus testing it was shown that all isolates from St. Petersburg and Kaliningrad were drift variants of the reference virus A/Brisbane/10/07 and reacted with antiserum to these strains up to 1/4 - 1/16 of homologous titer. All 19 isolates of influenza B virus belonged to the Victoria lineage. Four of ten influenza A(H1) viruses and 22 of 28 influenza A(H3) viruses isolated in Russia appeared to be resistant to rimantadine.
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[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

CDC Update

http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4416B1-1.pdf

[HenryN]

Re: Flu Found Resistant to Main Antiviral Drug

New comments

http://precedings.nature.com/documents/2832/version/1