Drug-Resistant Flu Strain Turns Up In Denmark but Doesn’t Last Long - page 2

June 30, 2009 Global Update Drug-Resistant Flu Strain Turns Up In Denmark but Doesn’t Last Long By DONALD G. McNEIL Jr. The first case of swine flu resistant to the antiviral drug Tamiflu has been found in Denmark,... Read More

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    Tamiflu resistant H1N1 from Hong Kong more worrying than earlier findings


    Quote from www.google.com

    TORONTO — All cases of Tamiflu resistance are not created equal. So while the first three instances of swine flu infection with Tamiflu-resistant viruses were reported in the past week, it was Number 3, not Number 1 that put influenza experts on edge.
    Public health authorities in Hong Kong announced Friday they have found a case of Tamiflu resistance in a woman who hadn't taken the drug. That means she was infected with swine flu viruses that were already resistant to Tamiflu, the main weapon in most countries' and companies' pandemic drug arsenals.

    The two earlier cases, reported from Denmark and Japan, involved people who had been taking the medication. While always unwelcome, that type of resistance is known to occur with seasonal strains and may be less of a threat to the long-term viability of this key flu drug.

    "It was not at all surprising to see resistance in patients on treatment but seeing it in someone who was not treated, it certainly is more concerning," says Dr. Malik Peiris, a flu expert at the University of Hong Kong.

    There is a risk inherent in using the drug to prevent illness. If people who are already infected but aren't yet experiencing symptoms are put on prophylaxis, there won't be enough drug in their systems to kill all the viruses they house. Those that survive develop resistance to the drug.

    And that, it appears, may be what happened in the resistance cases in Denmark and Japan. In both instances the women involved had been given Tamiflu prophylaxis after a contact developed swine flu.

    But the Hong Kong case was different. A 16-year old girl travelling from San Francisco was stopped in Hong Kong's airport in mid-June after setting off a fever detection device.

    She was taken to hospital where she tested positive for swine flu. She had not been taking antivirals and declined to be treated with the drug. She was kept in isolation until she recovered.

    It was previously thought flu viruses that developed resistance to the drug would be crippled in the process and would not transmit to others. But that belief was shattered in 2008 when it was discovered Tamiflu-resistant versions of the seasonal H1N1 viruses were spreading rapidly around the globe. They have since all but wiped out Tamiflu-susceptible seasonal H1N1 viruses.
    "This is a patient that hasn't been treated, who has gone from San Francisco to Hong Kong. What that means is that she has caught a resistant virus in San Francisco," says McKimm-Breschkin, virology project leader at the Commonwealth Science and Research Organization - known as CSIRO - in Melbourne. (McKimm-Breschkin does not receive royalties for sales of Relenza.)
    "So that means this virus has been transmitted from somebody who's presumably been treated. Which means it's been fit enough to transmit. And that is of a lot more concern than just resistance in a treated patient."
    Experts have worried the seasonal H1N1 viruses might reassort or swap genes with the swine H1N1. If swine flu picked up with neuraminidase gene - the N in a flu virus' name - from the seasonal H1N1, it would acquire the resistance its seasonal cousin has developed.

    Authorities in Hong Kong have not yet told the WHO whether that is what has happened in this case.
    But whether the Hong Kong resistance case is due to reassortment, or from the fact that some swine flu viruses have developed resistance on their own, the situation demands careful monitoring, Fukuda and others say.

    "The really big question for any finding of antiviral drug resistance with these viruses is whether it's an isolated event or whether it's a tip of a larger phenomenon," he explains.
    "The bottom line, as is so often the bottom line with influenza, is that the real answer to the current situation is monitoring as closely as possible - which in this instance is really being done since an extraordinary number of viruses are being collected and looked at."

    - Follow Canadian Press Medical Writer Helen Branswell's flu updates on Twitter at CP-Branswell

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    Quote from www.flutrackers.com

    originally posted by gjs47
    what is the difference in effect between h274y and the 627 that was being discussed previously?

    h274y is on na and causes tamiflu not to work. e627k is on the polymerase b2 (pb2) that allows the virus to copy its genes faster at a lower temperature (like mammals) so it spreads more easily and growths to a higher level in humans.

    both are in h1n1 seasonal flu and will be in pandemic h1n1 because of recombination.

    Quote from www.flutrackers.com

    originally posted by shiloh
    "this is a patient that hasn't been treated, who has gone from san francisco to hong kong. what that means is that she has caught a resistant virus in san francisco," says mckimm-breschkin, virology project leader at the commonwealth science and research organization.

    "so that means this virus has been transmitted from somebody who's presumably been treated. which means it's been fit enough to transmit. and that is of a lot more concern than just resistance in a treated patient."
    at least now they are admitting the obvious.

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    Public kept in dark as institute compiles thesis on mutated virus


    Don't believe that scientists would engage in unethical behavior? This has been going on all along with regards to information on H5N1, bird flu. One would think that in the middle of a pandemic, this type of behavior would cease, but no, it has not. Actually, two weeks is nothing. There is a plethora of sequence information on the much more virulent bird flu virus that has NEVER been released, and that virus is still a threat.

    I am so very tired of the fear of panic excuse. What anxiety? What arrogance that only experts would understand the implications of Tamiflu resistance. If the public did not get what only experts could understand, why would anyone feel anxiety?

    Quote from www.asahi.com

    -A prefectural research institute withheld from the public for two weeks its discovery of a mutated swine flu virus, but it swiftly submitted a thesis on the finding to a U.S. medical journal.

    The Osaka Prefectural Institute of Public Health only made the announcement of the Tamiflu-resistant virus last Thursday, two weeks after confirming it on June 18. In fact, the health ministry had to instruct the institute to make the announcement.

    It was the first confirmation of the mutated virus in the world. But even the Osaka prefectural government's health and medical treatment department failed to announce the detection immediately after it received a report from the institute on June 22.

    The mutated virus is resistant to Tamiflu, an anti-flu drug widely used in Japan to treat patients infected with new swine flu.

    "If researchers are working for public health, they should know as common sense that (withholding the discovery) is wrong," said Shigeru Omi, a professor of public health at Jichi Medical University and chairman of a government advisory council on new influenza.

    A teacher in her 40s in Osaka Prefecture who had been in close contact with an infected person started receiving Tamiflu on May 18 as a preventive measure.

    She had a slight fever on May 24 and was confirmed infected with the new swine flu virus on May 29.

    The Osaka institute conducted a genetic examination of her virus samples and confirmed on June 18 that the virus had genetically mutated and was resistant to Tamiflu.

    The World Health Organization, which demands immediate public disclosure of drug-resistant viruses, said June 29 that the world's first Tamiflu-resistant virus had been confirmed in Denmark.

    Meanwhile, the Osaka institute, still keeping the public in the dark, compiled and submitted a thesis on the mutated virus to U.S. medical journal Emerging Infectious Diseases on June 24. As of Saturday, it was not known when the thesis will be published.

    The Ministry of Health, Labor and Welfare and the National Institute of Infectious Diseases were only informed of the Tamiflu-resistant virus on Wednesday, prompting the ministry to call for an immediate announcement.

    Kazuo Takahashi, vice director of the institute, denied the researchers were seeking fame from the discovery.

    "We refrained from announcing the detection to the public, thinking that an announcement at an uncertain stage would only add to public anxiety," he said. "But we thought experts would be able to understand the discovery."

    At the news conference Thursday, institute officials said the researchers did not announce the mutated virus for two weeks because they were conducting cell experiments to confirm the virus was resistant to Tamiflu.

    Professor Omi said this explanation is not convincing.

    On June 24, the thesis submitted to the Emerging Infectious Diseases had already reported confirmation that the genetically mutated virus showed resistance to Tamiflu.

    "We can hardly respond to such critical questions about which side we are working for--experts or the public," said Tatsuya Oshita, a senior official at the prefectural health department. "As a (local) government, we should have announced the detection immediately."

    The ministry reported the discovery of the mutated virus to the WHO on Friday.(IHT/Asahi: July 6,2009)
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    Hong Kong Tamiflu Resistant Pandemic Sequence Released


    Finally! A Tamiflu resistant swine flu sequence has been released on the case from Hong Kong. As expected, H274Y is present.

    Quote from /www.recombinomics.com

    The NA sequence from the Hong Kong teenager with oseltamivir Tamiflu resistance, A/Hong Kong/2369/2009, has been released. The sequence is clearly that of pandemic H1N1 and exactly matches (other than H274Y) the sequence of an earlier isolate A/New Jersey/1/2009. Similarly, the HA sequence is also swine and has two recently acquired polymorphisms, one of which is also in New Jersey/1/2009. Thus this sequence is in circulation and as was seen in the isolates in Denmark and Japan, the H274Y is appended onto a swine H1N1 background.

    These results mimic that seen in seasonal flu, where H274Y was appended onto multiple seasonal flu background. The polymorphisms jumped from one background to the next, via genetic hitchhiking and recombination. Thus like seasonal flu, the pandemic H1N1 has no evidence of reassortment. The H274Y is on an evolutionarily fit H1N1 that will allow the H274Y to move about through the pandemic H1N1 gene pool. This movement will be facilitated by widespread Tamiflu usage, which will select minor populations as happened in Denmark and Japan, where H274Y was identified in patients receiving a maintenance dose of Tamiflu.

    However, in Hong Kong, like the many examples of H274Y in H1N1 seasonal flu, the resistance is in patients not receiving Tamiflu. However, the lessons of H274Y in seasonal flu were not learned. Recent comments have described H274Y acquisitions through random mutation and reassortment. However, there has been no examples of recent seasonal H1N1 flu genes in the pandemic H1N1 sequences, and the H274Y in patients receiving Tamiflu likely represent selection of a minor population with H274Y that is silently spread. The release of the sequences from Denmark and Japan would be useful.
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    Swine flu testing to grow after resistant US case


    They are not talking about testing people. They are going to to test viral samples, probably a certain percentage in various localities, looking for more Tamiflu resistant strains of flu. Ah, but will they reveal what they find? We are still waiting on the sequences from Japan and Denmark, btw.

    Quote from www.google.com

    U.S. health officials are stepping up testing of swine flu cases for Tamiflu resistance.

    The action comes after an American teen was diagnosed with a resistant strain. The San Francisco teenager was diagnosed with swine flu last month after arriving in Hong Kong, and has since recovered.

    Officials on Tuesday confirmed the 16-year-old lived in San Francisco and likely was infected in the United States.
    She's just the third person in the world known to have a strain resistant to Tamiflu, the main weapon against swine flu.
    (hat tip flutrackers/shiloh)
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    Hello, Houston, oops, I meant Geneva. I think we have a problem here...

    Quote from english.vietnamnet.vn

    Dr. Nguyen Van Kinh, director of the National Institute for Infectious and Tropical Diseases, said that only four of 19 A/H1N1 cases in the north were still being treated at the hospital. However, two of them, who returned from Australia, showed some signs of Tamiflu resistance. They were treated by Tamiflu for seven days but test results were positive for H1N1 though clinical symptoms disappeared after three days of treatment.

    The institute sent samples to the National Institute for Epidemiology for testing again to seek the reason.
    (hat tip Avian Flu Diary)

    Sounds exactly like what happened in India which strangely has never been mentioned again. If you are positive, you can most likely still shed virus to other people.


    While his wife recovered and tested negative for A (H1N1) after about 10 days, the husband continued to test positive even after the treatment was completed.

    Though he showed no symptoms, his tests kept coming back positive
    Dr. Elango said.

    “This is a case to be studied, definitely. The virus should not remain in his blood after the treatment. It is possible that it is a mutation of the virus. I have instructed the officials at the NIV to sequence the strain [from the samples] as soon as possible. Once we have that, we can have the alternative drugs to treat the patient,” Dr. Katoch explained.

    He said the patient at the CDH could be treated on recommended doses of the drug ‘Relenza’ available in India.
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    So they are monitoring for Tamiflu resistance particularly in northern California where the Hong Kong case came from originally. They are saying "it does not appear to be widespread." This sounds like they have found other cases in the area, but not many maybe, and they are not testing most of the population of possible carriers in northern Cal.

    Remember the Hong Kong case was a traveler. Obviously, she was not sick enough to go to a doctor, and maybe never felt sick at all. She would not take the Tamiflu that was offered. Point being, resistant carriers could be among the population of people that are still working and are out and about in the community shedding virus because they don't feel sick enough to stay home.

    We may be on borrowed time for the use of Tamiflu for swine flu. Instead of arguing about it or ignoring it, perhaps they should be talking to drug companies and clinicians about using drug cocktails or some other possible antivirals if they exist.

    Quote from www.nytimes.com

    Health officials said that they were aware of fears that a Tamiflu-resistant strain of the virus is already spreading silently in the United States, but that they had not seen evidence that it is a threat.

    The worry stems from a single case found in a teenage girl who flew to Hong Kong from San Francisco on June 12. According to Hong Kong media reports, she was found to have a fever during a routine airport screening and was hospitalized as a precaution and tested.

    She was never dangerously ill, was not treated with Tamiflu and recovered. But the sequence of her virus, released by Hong Kong authorities last week, showed that it had a mutation, known as H274Y on the neuraminidase gene, making it resistant to Tamiflu, a neuraminidase inhibitor.

    The fact that she had a resistant strain without being treated suggests that she caught an already resistant virus from someone else, presumably in Northern California, said Henry L. Niman, who runs a Web site tracking flu mutations (recombinomics.com). Because sequencing in the United States is done on only the tiny fraction of flu cases serious enough to be hospitalized, Tamiflu-resistant virus could be circulating without being detected.

    Dr. Frieden said the disease control centers had begun intensifying its monitoring in Northern California, “and it does not appear to be widespread.”

    Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease, said there was little reason to worry unless it becomes the dominant strain.

    “But certainly you want to keep your eye on it,” he added.

    Different strains of virus “compete” with each other each year, and the drug-resistant strains do not always win. But a Tamiflu-resistant strain of seasonal H1N1 flu utterly crushed its rivals during the last American flu season, rising to 99 percent of sequenced samples.
  8. 0

    Information on the Japanese case is now available so that just leaves the Denmark sequence, the Indian case and the Vietnamese case whose sequences have not been released. Again, we see that H274Y, the piece of genetic material that causes Tamiflu resistance is present.

    This does not mean that Tamiflu is useless in treating severe cases of swine flu. It just means that we only have an unknown amount of time before most swine flu cases will become resistant. That could be next year or sooner. Nobody knows, and CDC/WHO are certainly very concerned about this despite what they are saying.

    The following commentary may be a little over your head but I think that you can get the jist of it. Dr. Niman is comparing what happened with seasonal H1N1 developing resistance to what is occurring with swine flu. He is also pointing out that the latest novel H1N1 that was found in those Canadian workers on the pig farm also was Tamiflu resistant. In other words, this resistance is appearing in many places at once, and it is not a good sign.

    So the question is, what's the plan? Clinicians need to know, and someone has to be working on this. Relenza is the only other effective drug left if we lose Tamiflu, but it must be inhaled, making it less useful.

    Quote from www.recombinomics.com

    The NA sequence of the first pandemic isolate in Sapporo, Japan (A/Sopporo/1/2009) was released at Genbank today. Since Hokkaido's first report case was June 15, the isolate is relatively recent. It exactly matches the first isolate from New Jersey, A/New Jersey/1/2009, which was from a patient (22F) in Bergen county (see map) and collected in April. Both of these isolates match the California traveler who was tested at Hong Kong airport on June 11 and was found to be infected with oseltamivir resistant H1N1 (A/Hong Kong/2369/2009) based on H274Y, which was the only difference between the Hong Kong sequence and those form Bergen, New Jersey and Sopporo. The same sequence in these three locations indicates the evolutionarily fit H1N1 is widespread and has been circulating for months, but the number of pubic sequences remains low.

    The Hong Kong, ex-San Francisco case was mild. The patient recovered without taking any antivirals, raising concerns that the resistance is circulating worldwide. The same genetic change, H274Y, has also been reported in patients receiving prophylactic levels of Tamiflu in Denmark and Osaka, Japan. The Osaka sequence, other than H274Y, matches multiple isolates from Japan, and is distinct from the Hong Kong/San Francisco/Sapporo/Bergen sub-clade. The sequence from Denmark has not been made public.

    However, other countries are reporting suspect Tamiflu resistance in patients who have been treated for at least a month and are symptom free, but shed detectable H1N1. These reports raise concerns that H274Y is more widespread than the 3 confirmed cases and one presumed case in San Francisco.

    The finding of H274Y in all confirmed cases raises concerns that the pattern in pandemic H1N1 will follow the pattern seen for seasonal flu, where H274Y increased to almost 100% in the Brisbane/59 strain of seasonal flu. The spread of H274Y in the Brisbane strain was facilitated by the acquisition of key polymorphisms from the Hong Kong (clade 2C) strain of H1N1. However, H274Y had also been reported in clade 1 and clade 2c isolates from patients who were not receiving Tamiflu, and in countries where Tamiflu suage was low. The H274Y jumped from one sub-clade to another via genetic hitchhiking and recombination explaned the pattern of acquisitions.'

    The spread of H274Y in pandemic flu may be accelerated by widespread Tamiflu usage, levels approaching 100% in H1N1 seasonal flu, and the novel H1N1 reported in Canadian farm workers infected with an H3N2 triple reassortant that has acquired Brisbane/59 H1 and N1, with H274Y.

    Thus, the detection of H274Y in pandemic H1N1 from patients who were and were not taking Tamiflu, as well as Brisbane N1 in H1N1 seasonal flu and H1N1 novel flu raises concerns that the levels of H274Y will markedly increase in the near term.
  9. 1
    Preparing for Fall


    Quote from www.boston.com

    The government is also considering buying even more antiviral drugs, including more of GlaxoSmithKline's inhaled drug Relenza and pediatric doses of Roche AG's Tamiflu, officials told a swine flu "summit" at the National Institutes of Health.

    "We have a little bit more than a month ... to get our acts together," Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention said at the meeting.

    The federal government has 52 million treatment courses of Tamiflu and Relenza in its strategic national stockpile. Tamiflu, or oseltamivir, is made by Roche under license from Gilead Sciences while Relenza, or zanamivir, is made by Glaxo under license from Australia's Biota Inc.

    Dr. Robin Robinson of HHS said the department is also considering buying another tranche of drugs, including zanamivir and pediatric doses of Tamiflu.

    A third drug, Biocryst Inc's peramivir, is nearing final trials before approval, Robinson said. "That would be used for severely ill individuals in hospitals," he said.

    Having three different drugs would help address the issue of resistance. Some cases of the new H1N1 swine flu have been resistant to Tamiflu and that drug is now generally ineffective against the seasonal version of H1N1, a distant cousin of the pandemic strain.
    (Thank you to Avian Flu Diary for the link)
    Last edit by indigo girl on Jul 10, '09
    lamazeteacher likes this.
  10. 1
    Single-Dose Intravenous Peramivir Effective for Seasonal Acute Influenza


    Here is our only alternative to Tamiflu given po, and inhaled Relenza. This drug is given intravenously or injected. It is yet another neuraminidase inhibitor like Tamiflu and Relenza. All these drugs seem to attack the virus in the same fashion.

    Quote from ww.medscape.com

    October 30, 2008 (Washington, DC) — Peramivir, a novel neuraminidase inhibitor, was effective for the treatment of seasonal acute influenza after a single-dose intravenous infusion, according to results from a double-blind placebo-controlled phase 2 Japanese study.

    This late-breaking abstract was presented here at the 48th Annual ICAAC/IDSA 46th Annual Meeting, a joint meeting of the American Society for Microbiology and the Infectious Diseases Society of America.

    Emphasizing the real-world benefits of this agent, lead author Shigeru Kohno, MD, PhD, dean of the Nagasaki University School of Medicine, in Japan, said: "If you ask patients to take a medicine for 4 or 5 days or more, they may forget. One shot is perfect."

    Ann Falsey, MD, associate professor of medicine at the University of Rochester, in New York, and a researcher in the epidemiology and immunology of influenza, who was not involved in this study, highlighted another important benefit of a nonoral medication. "I think what this offers in addition to the usual antibiotic is an alternative to patients for whom oral therapy is a problem.

    "It is also important to think ahead to pandemic flu," Dr. Falsey said. "Those patients might be extremely sick, and their digestive tracts may not be working. They may be in intensive care. So I think it's important to have an armamentarium of drugs available in intravenous form. It looks like this drug was similar to Tamiflu [oseltamivir phosphate] in its effectiveness."

    The study was funded by BioCryst Pharmaceuticals, codeveloper of peramivir. Dr. Kohno is a consultant for Shionogi & Co, Ltd, which is in partnership with BioCryst. Dr. Falsey has disclosed no relevant financial relationships.

    48th Annual ICAAC/IDSA 46th Annual Meeting: A Joint Meeting of the American Society for Microbiology and the Infectious Diseases Society of America: Abstract V-4154a. Presented October 28, 2008.
    I remember hearing about this drug back when we had several kids hospitalized from seasonal flu in Alabama. The company that makes Peramivir was located in Alabama also, and had just received a govt grant for research for a pandemic flu drug. Who knew
    we would really need it?

    post #21 - http://allnurses.com/general-nursing...ml#post2005438
    lamazeteacher likes this.

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