タミフル耐性インフルエンザの流行/米国

画像 米国のインフルエンザの事実上全ての主要なタイプがタミフル耐性となった。
 昨年は11%であったが、今シーズンは99%となった。変異は薬の乱用によるというよりは自発的なもののようである。昨年欧州で広範囲に及んでいた。
 耐性ウイルスはH1N1型である。CDCはRelenza の使用を推奨しているが、吸入薬であり、7才以下の子どもには推奨されていない。代わりに、タミフルとrimantadineの併用が利用できる。
 H1N1におけるタミフル耐性は、中国、ノルウェー、フランス、ロシアで昨年見られ、N遺伝子上のH274Yの変異により、タミフル使用とは無関係である。他の変異としてH遺伝子上のA193Tがあり、人への感染をおこしやすくしている。
 インフルエンザワクチンは3タイプのインフルエンザの感染を防御するが、A193T変異からの保護はできず、組み合わせの間違いをNiman博士は非難している。
 新タイプは肺炎を起こしやすく、致命的となる可能性がある。米国では年に約36,000人がインフルエンザで死亡している。
---------------------
日本でもタミフル耐性インフルエンザ検出
http://kurie.at.webry.info/200802/article_48.html
タミフル耐性のAソ連型インフルエンザ 欧米で広がる
http://kurie.at.webry.info/200802/article_7.html
---------------------------------------------------------
Major Flu Strain Found Resistant to Leading Drug, Puzzling Scientists
By DONALD G. McNEIL Jr.
Published: January 8, 2009
http://www.nytimes.com/2009/01/09/health/09flu.html

Virtually all the dominant strain of flu in the United States this season is resistant to the leading antiviral drug Tamiflu, and scientists and health officials are trying to figure out why.

The problem is not yet a public health crisis because this has been a below-average flu season so far, and because the Tamiflu-resistant strain, one of three circulating, is still susceptible to other drugs. But infectious disease specialists are worried nonetheless.

Last winter, about 11 percent of the throat swabs from patients with the most common type of flu that were sent to the Centers for Disease Control and Prevention for genetic typing showed a Tamiflu-resistant strain. This season, 99 percent do.

“It’s quite shocking,” said Dr. Kent A. Sepkowitz, director of infection control at Memorial Sloan-Kettering Cancer Center in New York. “We’ve never lost an antimicrobial this fast. It blew me away.”

The single mutation that creates Tamiflu resistance appears to be spontaneous, and not a reaction to overuse of the drug. It may have occurred in Asia, and it was widespread in Europe last year. In response, the disease control agency issued new guidelines two weeks ago. They urged doctors to test suspected flu cases as quickly as possible to see if they are influenza A or influenza B, and if they are A, whether they are H1 or H3 viruses.

The only Tamiflu-resistant strain is an H1N1. Its resistance mutation could fade out, an agency scientist said, or a different flu strain could overtake H1N1 in importance, but right now it causes almost all flu cases in the country, except in a few mountain states, where H3N2 is prevalent.

Complicating the problem, antiviral drugs work only if taken within the first 48 hours of infection. A patient with severe flu could be given the wrong drug and die of pneumonia before test results come in. So the new guidelines suggest that doctors check with their state health departments to see which strains are most common locally and treat for them.

“We’re a fancy hospital, and we can’t even do the A versus B test in a timely fashion,” Dr. Sepkowitz said. “I have no idea what a doctor in an unfancy office without that lab backup can do.”

If a Tamiflu-resistant strain is suspected, the disease control agency suggests using a similar drug, Relenza. But Relenza is harder to take; it is a powder that must be inhaled and can cause lung spasms, and it is not recommended for children under 7.

Relenza, made by GlaxoSmithKline, is known generically as zanamivir. Tamiflu, made by Roche, is known generically as oseltamivir.

Alternatively, patients who have trouble inhaling Relenza can take a mixture of Tamiflu and rimantadine, an older generic drug that the agency stopped recommending two years ago because so many flu strains were resistant to it. By chance, the new Tamiflu-resistant H1N1 strain is not.

“The bottom line is that we should have more antiviral drugs,” said Dr. Arnold S. Monto, a flu expert at the University of Michigan’s School of Public Health. “And we should be looking into multidrug combinations.”

New York City had tested only two flu samples as of Jan. 6, and both were Tamiflu-resistant, said Dr. Annie Fine, an epidemiologist at the city’s health department. Flu cases in the city are only “here and there,” Dr. Fine said, and there have been no outbreaks in nursing homes. Elderly patients and those with the AIDS virus or on cancer therapy are most at risk.

But, she added, because of the resistance problem, the city is speeding its laboratory procedures so it can do both crucial tests in one day.

“And we strongly suggest that people get a flu shot,” Dr. Fine said. “There’s plenty of time and plenty of vaccine.”

Exactly how the Tamiflu-resistant strain emerged is a mystery, several experts said.

Resistance appeared several years ago in Japan, which uses more Tamiflu than any other country, and experts feared it would spread.

But the Japanese strains were found only in patients already treated with Tamiflu, and they were “weak” ― that is, they did not transmit to other people.

“This looks like a spontaneous development of resistance in the most unlikely places ― possibly in Norway, which doesn’t use antivirals at all,” Dr. Monto said.

Dr. Henry L. Niman, a biochemist in Pittsburgh who runs recombinomics.com, a Web site that tracks the genetics of flu cases worldwide, has been warning for months that Tamiflu resistance in H1N1 was spreading.

Dr. Niman argues that it started in China, where Tamiflu use is rare, was seen last year in Norway, France and Russia, then moved to South Africa (where winter is June to September), and back to the Northern Hemisphere in November.

The mutation conferring resistance to Tamiflu, known in the shorthand of genetics as H274Y on the N gene, was actually, Dr. Niman said, “just a passenger, totally unrelated to Tamiflu usage, but hitchhiking on another change.”

The other mutation, he said, known as A193T on the H gene, made the virus better at infecting people.

Furthermore, Dr. Niman blamed mismatched flu vaccines for helping the A193T mutation spread. Flu vaccines typically protect against three flu strains, but none have contained protections against the A193T mutation.

Dr. Joseph S. Bresee, chief of flu prevention at the disease control agency, said he thought Dr. Niman was “probably right” about the resistance having innocently piggy-backed on a mutation on the H gene ― which creates the spike on the outside of the virus that lets it break into human cells. But Dr. Bresee said he doubted that last year’s flu vaccine was to blame, since the H1 strain in it protected “not perfectly, but relatively well” against H1N1 infection.

Dr. Niman said he was worried about two aspects of the new resistance to Tamiflu. Preliminary data out of Norway, he said, suggested that the new strain was more likely to cause pneumonia.

The flu typically kills about 36,000 Americans a year, the C.D.C. estimates, most of them the elderly or the very young, or people with problems like asthma or heart disease; pneumonia is usually the fatal complication.

And while seasonal flu is relatively mild, the Tamiflu resistance could transfer onto the H5N1 bird flu circulating in Asia and Egypt, which has killed millions of birds and about 250 people since 2003. Although H5N1 has not turned into a pandemic strain, as many experts recently feared it would, it still could ― and Tamiflu resistance in that case would be a disaster.

------------------------------------------------------
Common Flu Strain Resistant to Popular Antiviral Drug
But other medications are available that work, CDC officials stress.
By Steven Reinberg
HealthDay Reporter
Jan. 10
http://abcnews.go.com/Health/Healthday/story?id=6607130&page=1

U.S. flu resistant to tamiflu
A common strain of influenza circulating in the United States this winter is resistant to Tamiflu, the most popular drug used to treat it.
(AP Photo)

THURSDAY, Jan. 8 (HealthDay News) -- The most common strain of flu this season is resistant to the popular antiviral drug Tamiflu, but government health officials said Thursday there is no reason to panic.

The fact that the flu season so far has been slow, and that other drugs work well against this particular flu virus, has health officials adopting a watchful attitude for now.

While the cause of the mutation that made the virus resistant to Tamiflu (oseltamivir) isn't known, experts suspect it was caused by the wide use of Tamiflu in other countries to treat upper respiratory infections.

There were reports last year from Europe and other countries that a certain type of flu -- H1N1 -- was resistant to oseltamivir, according to Dr. Joseph Bresee, chief of flu prevention at the U.S. Centers for Disease Control and Prevention.

This year, the CDC was on the lookout for flu resistance to Tamiflu in the United States and, sure enough, it showed up. Moreover, the proportion of the strain that is resistant has gone up from around 10 percent last year to all of the H1N1 strains this year, Bresee said.

Two weeks ago, the CDC issued new guidelines urging doctors to test suspected flu cases to see if they are influenza A or influenza B, and if they are A, whether they are H1 or H3 viruses, Bresee said.

"We didn't want to make a big deal out of this," Bresee said. "We think it's interesting. We think it's worth monitoring closely, but we are still watching. When we see more, then we will get a better sense of what the public health impact of it is. We don't have a good feel of that yet."

The resistant strain is the most common type of flu circulating in the United States right now, but the season is early and the number of cases is low, Bresee said.

As more flu cases are reported, other strains of the virus may become more common, Bresee added.

"What happens frequently is that one type of flu will circulate at one time in the season and be replaced by another type later in the season, so in a week's time, a month's time, we may have mostly H3s or mostly Bs, which oseltamivir works wonderfully for," he explained.

To be most effective, Tamiflu, made by Roche, needs to taken within 48 hours after flu symptoms appear, Bresee said. "Generally, antivirals for influenza are underused in the U.S.," he added.

Most people with flu are not treated, Bresee noted. "Clearly, it's a self-limited disease and you will get over it," he said.

Bresee noted there are alternatives to Tamiflu, including Relenza (zanamivir) made by GlaxoSmithKline. "The viruses that we are seeing that are resistant to Tamiflu are sensitive to zanamivir," he said.

Zanamivir has some limitations, Bresee said. It can't be given to young children and patients with certain lung diseases.

Other treatment options include the antiviral rimantadine (brand name Flumadine).

Bresee added that all the circulating flu stains are prevented by the flu vaccine, and it's not too late to get vaccinated. "Folks who haven't gotten the vaccine so far can still go get it," he said.

Dr. Pascal James Imperato, dean and Distinguished Service Professor of the Graduate Program in Public Health at SUNY Downstate Medical Center in New York City, thinks resistance to Tamiflu developed because of its use in other countries to treat upper respiratory infections.

"The emerging resistance of H1N1 influenza strains to oseltamivir was first noted a few years ago," Imperato said. "At present, based on analyses of H1N1 isolates from 16 countries in 2008, some 31 percent demonstrated resistance to Tamiflu."

Tamiflu resistance has not been documented for the two other common current human influenza strains, H3N2 and influenza B, or for avian influenza (H5N1), Imperato said.

"On the face of it, the emergence of resistance in the presence of limited drug use would seem unusual," Imperato said. "However, in many areas of the world, there is significant Tamiflu use for upper respiratory infections. It is believed that minor mutations in the H1N1 virus can in effect block the action of Tamiflu," he said.

It is important to note that no H1N1 influenza resistance to Relenza has developed, Imperato said. "This is the other drug in the neuraminidase group used to prevent and treat influenza," he said.

Flu usually causes about 36,000 deaths in the United States each year. Most deaths are among the elderly, very young or those with medical conditions such as asthma or heart disease. Pneumonia resulting from flu is usually the fatal complication.

More information

For more on the flu, visit the U.S. Centers for Disease Control and Prevention.

SOURCES: Joseph Bresee, M.D., chief, Epidemiology and Prevention Branch Influenza Division, U.S. Centers for Disease Control and Prevention, Atlanta; Pascal James Imperato, M.D., M.P.H., Dean and Distinguished Service Professor, Graduate Program in Public Health, SUNY Downstate Medical Center, New York City

Copyright 2009 HealthDayNews, Inc. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
----------------------------------------------
インフルエンザ、3割がタミフル効かず
http://www.yomiuri.co.jp/science/news/20090116-OYT1T00807.htm
 国内でこの冬流行しているインフルエンザウイルスの約3割が、治療薬「タミフル」に対する耐性を獲得していると、厚生労働省が16日、発表した。
 国内の医療現場ではタミフルが多く使用されており、厚労省は治療薬を慎重に選ぶよう呼び掛けている。
 耐性ウイルスが確認されたのは、国内で流行している3種類のウイルスのうち36%を占める「Aソ連型」。8日までに国立感染症研究所に届け出があった11都道府県の計35人分中、34人分(97%)で耐性が確認された。
 昨冬の2・6%に比べ極めて高率で、厚労省は残り36府県の検体検査を進めるとともに、研究班を組織して耐性患者の容体や治療法を調査する方針だ。
 厚労省によると、タミフル耐性ウイルスに対しては別のインフルエンザ治療薬「リレンザ」が有効で、Aソ連型以外の「A香港型」「B型」からは耐性ウイルスは見つかっていない。
 Aソ連型の耐性ウイルスは昨冬に全世界で確認され、今冬もすでに米英などで見つかっている。タミフルをほとんど使用しない国でも出現しており、特定の遺伝子が自然変異して耐性を獲得したらしい。
 厚労省は新型インフルエンザ対策にタミフルを2800万人分備蓄しているが、「新型インフルエンザが直ちにタミフル耐性を得るとは考えていない。現段階で備蓄計画に変更はない」と話している。
 耐性ウイルスが見つかった11都道府県は次の通り。▽北海道▽宮城▽千葉▽東京▽静岡▽三重▽滋賀▽大阪▽兵庫▽広島▽山口
(2009年1月17日01時51分 読売新聞)

ブログ気持玉

クリックして気持ちを伝えよう!

ログインしてクリックすれば、自分のブログへのリンクが付きます。

→ログインへ

なるほど(納得、参考になった、ヘー)
驚いた
面白い
ナイス
ガッツ(がんばれ!)
かわいい

気持玉数 : 0

この記事へのコメント

この記事へのトラックバック