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World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Giuseppe

Emeritus
[This document is also posted in Antivirals Resistance thread, at Scientific Library Forum - IOH]

World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere

30 December 2008

[Original PDF Document at LINK. EDITED.]


During the weeks 41–44 (5 October – 1 November), influenza activity remained low.

Sporadic influenza activity was detected in Belarus (A), Belgium (B), Canada (A,B), Chile (H1, B), China (H1), China, Hong Kong Special Administrative Region (H1,H3, B), Denmark (H3), Finland (A), Japan (H1,H3), Kenya (A), Mexico (B), Poland (A), Russian Federation (H1, H3, B), the United Kingdom of Great Britain and Northern Ireland (H1,H3) and the United States of America (A, B).

WHO has received several reports from National Influenza Centres (NIC) in the northern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir for the beginning of 2008/2009 influenza season (week 41-44).

Among A(H1N1) viruses tested, 13 of 14 in the United Kingdom,1 of 1 in Israel, 1 of 1 in Ghana and 1 of 1 in Canada had the specific neuraminidase mutation (H275Y; numbered according to N1 sequence) associated with oseltamivir resistance.

Japan also reported that 13 of 14 A(H1N1) viruses tested were resistant*.

WHO is collecting global data about this phenomenon from multiple laboratories participating in Global Influenza Surveillance Network.

Data from European countries participating in EISS were provided by the EISS and the VirGil project.

This summary table will be updated every four weeks.

Oseltamivir resistance results were based on phenotypic and/or genotypic analyses.

*The National Influenza Centre in Japan reported that 6 of the 14 viruses were obtained from two outbreaks in geographically separated prefectures (3 from a kindergarten in Yamaguchi Prefecture and 3 from a primary school in Miyagi Prefecture).


 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Looks like clade 2C (Hong Kong) has been eliminated.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?
Hitch hiking.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Striking results. Anyone have any ideas as to how these high levels (90%+) of resistance have apparently spread to all areas of the globe so quickly?

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?

This is what I am thinking. The speed at which this has occurred gives thought to the possibilities........:magnify:
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

It seems that H1N1 with H274Y owns some sort of evolutionary advantage against non-H274Y H1N1, perhaps affecting antigenic properties...

Another question: is possible to use the spread pattern of H1N1 as a prototypical scenario of a novel pandemic strain?
No. H274Y has hopped on board the fastest car. Its all about hitch hiking.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

This is what I am thinking. The speed at which this has occurred gives thought to the possibilities........:magnify:
It is hitch hiking that has nothing to do with Tamiflu or H274Y selection.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

we have bottlenecks each year, presumably in SE-Asia. (at least with
H3N2)

Here usually the strains emerge in Summer,Autumn which will be dominant
in US,EU in winter.

Maybe China, maybe Korea, maybe Japan, maybe swine

so, it depends which strain is successful there
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

we have bottlenecks each year, presumably in SE-Asia. (at least with
H3N2)

Here usually the strains emerge in Summer,Autumn which will be dominant
in US,EU in winter.

Maybe China, maybe Korea, maybe Japan, maybe swine

so, it depends which strain is successful there
Wrong. The dominant strain did not come out of Asia.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

<table style="text-align: left; width: 775px; font-family: helvetica,arial,sans-serif; color: rgb(190, 5, 1);" border="0" cellpadding="0" cellspacing="0"><tbody><tr><td style="width: 515px; vertical-align: top;" colspan="5"><big><big>Commentary</big></big>
H1N1 Tamflu Resistance Near 100% In Japan
Recombinomics Commentary 18:19
January 6, 2009

WHO has received several reports from National Influenza Centres (NIC) in the northern hemisphere regarding influenza A(H1N1) virus resistance to oseltamivir for the beginning of 2008/2009 influenza season (week 41-44).

Among A(H1N1) viruses tested, 13 of 14 in the United Kingdom,1 of 1 in Israel, 1 of 1 in Ghana and 1 of 1 in Canada had the specific neuraminidase mutation (H275Y; numbered according to N1 sequence) associated with oseltamivir resistance.

Japan also reported that 13 of 14 A(H1N1) viruses tested were resistant.

The above comments are from the December 30, 2008 WHO report on oseltamivir resistance (H274Y in the northern hemisphere). The number of samples tested is low, because the report covers a very small time period at the beginning of the flu season. Data from the UK has been updated at the UK website to 29/30. The only sensitive isolate was from the very beginning of the season. The same was true in the United States. The one sensitive sample was reported with one resistant sample in the first report. After that, the next 69 isolates had H274Y.

The same sequence of events will probably hold for Japan. As additional samples are collected, the frequency will approach 100%. The figures for Japan are somewhat surprising since last season there was a significant level of clade 2C (Hong Kong), which was oseltamivir sensitive. The same was true for Hawaii in the United States, but this season all reported H1N1 tests have had H274Y in Hawaii, suggesting clade 2B had gain dominance over clade 2C.

The data above for Japan indicates the same dominance had happened there, suggesting the frequency of almost 100% in Europe and North America extends to other northern countries in Asia, like Japan, China, and Russia.

Therefore, it seems likely that clade 2C may have been displaced throughout the northern hemisphere by clade 2B, which is now represented by a dominant sub-clade that has acquired and fixed H274Y.

.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Tamiflu Is Unlikely to Thwart Flu Strain in Europe, Report Says - Bloomberg.com: Japan

Tamiflu Is Unlikely to Thwart Flu Strain in Europe, Report Says

By Jason Gale
Jan. 7 (Bloomberg) --

Tamiflu is unlikely to stop one of the three most-common seasonal flu strains circulating in North America and Europe this winter, with studies showing more than 90 percent resistance to Roche Holding AG's drug.


Since the emergence of a Tamiflu-evading variant of the H1N1 flu virus was reported to the World Health Organization by Norway a year ago, the bug has been found in more than 50 countries. Preliminary data from the U.K., Japan and other northern hemisphere countries last quarter show almost all H1N1 viruses are resistant to the best-selling anti-flu pill, the WHO said in a statement posted on its Web site yesterday.

The discovery is prompting health officials to recommend other medicines, such as GlaxoSmithKline Plc's Relenza, to fight a disease the WHO estimates causes 250,000 to 500,000 deaths annually. All three common flu strains -- H1N1, H3N2 and type B -- are susceptible to Relenza, an inhaled powder. H1N1 is the most-common flu virus circulating in the U.S. this winter, while H3N2 has so far dominated in Europe.

``Since most clinicians are unaware of the flu strain they are trying to treat, it makes sense for them to prescribe, where appropriate, a medication that's effective against the broadest range of viruses,'' said Jennifer McKimm-Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne and a member of an international committee undertaking global surveillance on potential drug resistance.

McKimm-Breschkin was among a group of scientists in Australia that developed Relenza.

Prescribing Advice
In the U.S., doctors prescribing anti-flu treatments should give their patients Relenza or a combination of Tamiflu and an older drug called rimantadine, the Centers for Disease Control and Prevention said in a Dec. 19 statement. Basel, Geneva-based Roche had worldwide Tamiflu sales of $1.74 billion in 2007 and $2.1 billion in 2006.

Of the 73 H1N1 viruses tested in the U.S. since Oct. 1, 99 percent were resistant to Tamiflu, and all were susceptible to Relenza, rimantadine and amantadine, a similar drug, the CDC said in its latest weekly flu report.

Among H1N1 viruses tested last quarter from Ghana, Canada, Israel, Norway, U.K. and Japan, Tamiflu-resistance levels varied from 93 percent to 100 percent. In Argentina, testing of one H1N1 sample found no resistance, according to WHO.

Both Tamiflu and Relenza work by blocking a protein on the surface of influenza particles called neuraminidase which allows the virus to spread from infected cells to other cells in the body. Scientists say some H1N1 viruses have evolved to evade Tamiflu through a single mutation in the neuraminidase that prevents the medicine from clinging to the viral protein, thereby enabling the pathogen to spread. Relenza is unaffected by the change.

To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net
Last Updated: January 6, 2009 22:44 EST
-
<cite cite="http://www.bloomberg.com/apps/news?pid=20601101&sid=alahF2Rlhw2o&refer=japan">Bloomberg.com: Japan</cite>
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

Sequences from H1N1 at elementay school in Sendai, Japan, in October (outbreak closed school) have three RBD changes, G189V, A193T, H196R, which match sequences from Pennsylvania, Texas, and Hawaii this season.
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)



<News> cases were isolated from outbreaks of influenza virus subtype A/H1N1 - Sendai

http://idsc.nih.go.jp/iasr/rapid/pr3481.html

http://blog.goo.ne.jp/publichealth/e/ef660447667fb25f9eab4914b9118a16

2008年10月下旬に仙台市内の小学校1クラスでインフルエンザによる学級閉鎖が報告され、患者の咽頭ぬぐい液を採取し検査した結果、 A/H1N1亜型インフルエンザウイルスを分離したので報告する。​

10 elementary schools in Sendai in 2008 to end a class is closed due to flu reported in the class tests and throat swab samples of the patient, A/H1N1 viruses isolated since reporting flu subtype.

患者発生状況​

Situation caused patient

2008年10月28日に小学校3年生の1クラス(在籍者数40名)の25名がインフルエンザ様症状を呈し、うち14名が欠席したため、学級閉鎖の措置がとられた。​

October 2008 to 28 elementary school students three years of a class (enrollment 40) of 25 influenza-like symptoms, but missed out for 14, was taken in closed classes.

このうち2名が医療機関を受診し、迅速診断キットによりA型インフルエンザであることが確認されたため、調査を実施した。

The doctor and two medical institutions, the A rapid diagnostic kits for avian flu was confirmed that the type of research.

ウイルス検査結果搬入された患者5名(医療機関で迅速キットによりA型インフルエンザ陽性と確認された小学生4名と生徒の母親1名)の咽頭ぬぐい液5検体を、MDCK細胞に接種し、初代および2代継代培養で3検体からウイルスが分離された。

Patient test results were carrying the virus 5 (by medical kit A quick and elementary school students were confirmed to be flu-positive mother of four students and one name) of the five swab samples from the throat, MDCK cells and inoculation, and the first subcultured three generations in an isolated the virus from the samples.

分 離ウイルスについて国立感染症研究所より分与された2008/09シーズン用インフルエンザウイルス同定キットを用いてHI試験を行ったところ、抗A /Brisbane/59/2007(H1N1)血清(ホモ価640)に対しHI価320、抗A/Uruguay/716/2007(H3N2)血清(同 640)、抗B/Brisbane/3/2007血清(同2,560)および抗B/Malaysia /2506/2004血清(同640)に対しては、いずれもHI価<10であった。​

Sharing from the National Institute of Infectious Diseases Virus isolation using the 2008/09 influenza virus identification kits for the season HI test, the anti A/Brisbane/59/2007 (H1N1) Serum (Homo number 640) HI titer against 320 anti A/Uruguay/716/2007 (H3N2) serum (the 640), B/Brisbane/3/2007 anti-serum (in 2560) and anti-B / Malaysia / 2506/2004 serum (the 640) for the HI titer of <10 was.

HA遺伝子(1,014bp)、NA遺伝子(1,044bp)、MP遺伝子(926bp)の相同性解析を行った結果では、分離ウイルス3株の塩基配列は100%一致した。​

HA gene (1014bp), NA gene (1044bp), MP gene (926bp) in the results of homology analysis, three separate sequences of the virus stocks is 100 percent match.

一方、今シーズンのワクチン株であるA/Brisbane/59/2007に対するHA遺伝子、NA遺伝子およびMP遺伝子の相同性はそれぞれ99.2、99.1、99.6%であった。

Meanwhile, the vaccine strain of the season for the HA gene A/Brisbane/59/2007, NA genes and genetic homology of each MP 99.2,99.1,99.6%.

また,HA遺伝子では3カ所のアミノ酸置換(G204V、A208T、H211R)が、NA遺伝子ではオセルタミビルの耐性株の指標となるH275Yのアミノ酸置換が認められたが、M2遺伝子上のアマンタジン耐性株の指標となるS31Nのアミノ酸置換は認められなかった。​

In addition, HA gene is one of three amino acid substitution (G204V, A208T, H211R) are, NA gene is an indicator of the stock H275Y oseltamivir resistance is recognized by amino acid substitution, M2 and the stock index of amantadine-resistant gene S31N amino acid substitution could not be accepted.

NA遺伝子の系統樹解析の結果、今回の分離株はサブクレード2Bに属しており、HA遺伝子やMP遺伝子の系統樹解析でも同じクラスターに分類された(図1、図2、図3)。​

Phylogenetic analysis of the NA gene of the isolates belong to the SABUKUREDO 2B, HA and MP gene clusters that are classified in the same family tree of genetic analysis (Figure 1, Figure 2 and Figure 3).

仙台市内でのインフルエンザウイルスの分離は、これが今シーズン初めてであり、昨シーズンよりも約1カ月早い分離となった。​

Separation of influenza virus in the city of Sendai is the first time this season, than last season was a month early separation.

また、オセルタミビルの耐性株の指標となるH275Yの変異を有するインフルエンザウイルスの分離は仙台市内では初めてであり、今後の分離株についても継続して調査していく必要があると思われる。​

The index of shares and separating the H275Y oseltamivir resistance mutations of the flu virus in the city of Sendai is the first time that we need to continue to investigate the separation of the shares.

仙台市衛生研究所勝見正道 大山 文 関根雅夫 小黒美舎子 熊谷正憲太白区保健福祉センター浅野惠美子 野崎 文 工藤信子 渡辺洋一 永山雄一 吉田菊喜​

Ju Hee Yuuiti Yoshida Nobuko Watanabe Hirokazu Nagayama Emiko Nosaki Asano Aya Kudou Taihaku District Health Center Masanori Kumagai Masao Oguro child beauty Aya Sekine cages Katsumi Masamiti Ooyama Health Laboratory in Sendai

http://idsc.nih.go.jp/iasr/rapid/pr3481.html
 
Re: World Health Organization: Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season, northern hemisphere (1/6/2009)

News> from the 2008/09 season's first cold AH1 separate group of influenza virus subtype - SHIGA


2008年11月、滋賀県において2008/09シーズン初となる小学校での集団かぜ事例から、オセルタミビル耐性のAH1亜型インフルエンザウイルスが分離されたので、その概要を報告する。
November 2008 in Shiga Prefecture in the group of cold cases from the 2008/09 school's first season, it was AH1 oseltamivir-resistant influenza virus subtype are separated, the report summary.

2008年11月13日、滋賀県内の小学校3クラスで集団かぜが発生し、学級閉鎖が実施された。​
2008 November 13, three elementary schools in Shiga Prefecture occurred in the cold group classes, classes were conducted closed.
受診した医療機関において迅速診断キットでA型インフルエンザと診断されたという連絡があり、保健所が調査に入った。​
The rapid diagnostic kit A medical doctor who was in contact with pandemic flu diagnosis, research into the health center.
協力の得られた5名のうがい液が当所に搬入された。​
Cooperation by bringing to five the fluid exchange of gargling.
5名の発病日は11月8~12日、主症状は発熱(38.2~39.8℃)および 上気道症状で、その他頭痛、嘔吐、筋肉痛・関節痛が認められた。​
5, 2007 onset of the November 8-12, the main symptoms are fever (38.2 ~ 39.8 ℃) and upper respiratory symptoms, headache, vomiting, joint pain muscle pain recognition.

当所においてMDCK細胞を用いたインフルエンザウイルスの分離を行ったところ、5名中2名については、MDCK細胞初代培養4日目から細胞変性効果が認められた。​
The premise of the separation of the MDCK cell influenza virus, while two of five people, MDCK cell primary culture were allowed four days from the cytopathic effect.
それらの培養上清はモルモット赤血球(0.6%)を用いた赤血球凝集(HA)試験でHA価64~128を示した。​
These culture supernatant guinea pig red blood cells (0.6%) using hemagglutination (HA) in the HA titer test showed 64-128.
そこで、これらの分離株について、国立感染症研究所から配布された2008/09シーズン用インフルエンザウイルス同定キットを用いて赤血球凝集抑制(HI)試験を行ったところ、抗A/Brisbane/59/2007(H1N1)血清(ホモ価1,280)に対してはHI価320を示したのに対し、抗A/Uruguay/716/2007(H3N2)血清(同1,280) 、抗B/Malaysia/2506/2004血清(同2,560)および 抗B/Brisbane/3/2007血清(同2,560)にはいずれもHI価<10であったことから、分離株をAH1亜型インフルエンザウイルスと同定した。​
Therefore, these isolates were distributed from the National Institute of Infectious Diseases, using the hemagglutination inhibition 2008/09 identification kits for the flu season (HI) test the anti A/Brisbane/59/2007 ( H1N1) Serum (Homo number 1280) for the HI titer of 320 against the anti A/Uruguay/716/2007 (H3N2) Serum (in 1280), B/Malaysia/2506/2004 anti-serum (the 2560) and anti-serum B/Brisbane/3/2007 (in 2560) are both HI titer <10 was, and identified the virus isolate AH1 flu subtype.
また、分離された2株についてNA遺伝子の部分的な遺伝子解析を行ったところ、2株ともオセルタミビル耐性株に特徴的なH275Y耐性マーカーがみられた。​
In addition, the separation of the two NA shares were part of the genetic analysis of genes, that are characteristic of stocks and shares H275Y oseltamivir resistance were resistant marker.
国立感染症研究所ウイルス第三部第一室に確認検査を依頼したところ、耐性株であることが確定された。​
After the inspection request to the third room of the Ministry of National Institute of Infectious Diseases, the virus was confirmed to be resistant stocks.

今回インフルエンザウイルスが分離された2名中1名は11月10日から発病し、11日からタミフルを内服していたが、もう1名は内服していなかった。​
Influenza virus isolated in one of the two people getting sick from November 10 to Sunday, 11 were from the mouth to Tamiflu, the other one did not take.

2008年1~3月に滋賀県内で採取された検体から分離されたAH1亜型インフルエンザウイルス分離株16株については、オセルタミビル耐性株は認められなかった。​
2008 1-3 were isolated from samples taken in Shiga prefecture AH1 to isolate influenza virus subtype 16 shares, the shares oseltamivir resistance was not allowed.
今回、滋賀県で初めて耐性株が分離されたが、2007/08シーズンでは神奈川県や兵庫県などでも耐性株が出現しており、鳥取県においては32.4%が耐性株であったと報告されている(IASR 29: 334-339, 2008 )。​
The separation was the first time in Shiga-resistant stocks, in the 2007/08 season is the emergence of resistance in the stock and Kanagawa and Hyogo, Tottori Prefecture in 32.4% of the shares had been reported and are resistant (IASR 29: 334-339, 2008).

滋賀県感染症発生動向調査におけるインフルエンザ定点当たり患者数によると、2008年第50週(12/8~14)に患者数が1.0以上となり流行が始まった。​
The number of patients in each survey point flu infection occurred, Shiga, 2008, the first 50 weeks (12 / 8 to 14) the number of patients in the epidemic began more than 1.0.
これから本格的なインフルエンザの流行期に入るとみられ、AH1亜型だけでなくAH3亜型およびB型についても耐性株の動向に注目していきたい。​
Believed to enter the flu season in full swing now, AH1 as well as subtype B and subtype AH3 want to look at trends in the shares on-resistance.

滋賀県衛生科学センター松本文美絵 大内好美 南 祐一 田中千香子 吉田とも江 藤田直樹​
Huzita Naoki Yoshida Tomoe Minami Yuuiti Oouti Yoshimi Tanaka Tikako Matsumoto Aya Mie, Shiga Health Science Center

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