Anti-viral resistance in 2009 A/H1N1 flu - historical compilation of news

[Snowy Owl]

Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

US swine flu patients on immunosuppressant drugs develop Tamiflu resistance​

http://www.google.com/hostednews/canadianpress/article/ALeqM5gIJ9xcW9U9jwX40p8MsxNzEVCjkg

Thanks to Crofsblog

a CP story by Helen Branswell: US swine flu patients on immunosuppressant drugs develop Tamiflu resistance. Excerpt:

Two cases of Tamiflu-resistant swine flu have been found in the United States, in leukemia patients who were highly immunosuppressed, the U.S. Centers for Disease Control reported Friday.

The cases, both from Seattle, are not linked. And there is no evidence either person transmitted drug-resistant pandemic viruses to either the health-care workers looking after them or their personal contacts.

But the findings underscore the reality that people who are highly immunocompromised and who contract the novel H1N1 virus could generate and spread drug resistant variants of the pandemic virus.

"That's a legitimate public health concern," said Dr. Frederick Hayden, an antiviral expert at the University of Virginia.

These are the first cases of Tamiflu-resistant swine flu found in the United States, though not the first to arise there. Last month it was reported that an California teenager quarantined with swine flu immediately after arriving in Hong Kong was found to be infected with a Tamiflu-resistant strain. She contracted the flu before leaving San Francisco, where she lives.

These new cases highlight the catch-22 of treating pandemic influenza in people who are severely immunosuppressed. These patients should be given flu drugs because their immune status leaves them highly vulnerable to severe illness.

But giving them the drugs raises at least the theoretical risk that they will develop and spread antiviral resistant strains of the novel H1N1 flu.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in WA

Re: Two Tamiflu-resistant swine flu cases reported in WA

To my knowledge none of the other instances of Tamiflu resistance have been in people with immune system problems, but it seems very likely that segment of the population has received a fair amount of Tamiflu. Really, what is the likelihood that two people in the same county developed it spontaneously?

As the frequency of detection / reporting increases, the likelihood that these acquistions are due to random mutations becomes increasingly remote. The best data for the silent spread actually is the Singapore patient, which was said to be sensitive in the initial test, which was on May 28. The resistance was on a May 30 sample, too soon for "spontaneous" generation.
H274Y is clearly spreading silently, and detection rates will increase (which will be very clear very soon, unless the data is withheld, as was announced by WHO earlier this week).

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in WA

Re: Two Tamiflu-resistant swine flu cases reported in WA

it can acquire NA (and others...) and not HA.

any such reassortment is dangerous since it could change virulence.
e.g. it could acquire PB1 with a functional PB1-F2

reassortment means prolonged evolution. Once it goes loose
the virus may get other ideas how to change

It "could" do a lot of things. However, swine H1N1 that acquires human N almost always also acquires human H. In Sasketchewan, 2 or 3 farm workers were infected with a triple reassortant that was Tamiflu resistance because the virus had acquired the N1 from Bisbane/59, which had H274Y. However, it also acquired H1 from Brisbane/59, so the resulting virus had a human H1N1 serotype, but a pandemic strain is defined by a new serotype. Brisbane/59 H1N1 is not new (and most humans have immunity by virtue of earlier H1N1 seasonal flu infections and earlier vaccination with Brisbane/59 H1N1).

 

[Mamabird]

Re: Two Tamiflu-resistant swine flu cases reported in WA

Re: Two Tamiflu-resistant swine flu cases reported in WA

Wrong. The acquiring a Brisbane/59 H and N would produce a strain similar to seasonal H1N1 (population would already have antibodies). Its hopes and dreams on steroid.
It has already happened in Saskatchewan with another triple reassortant.

I take it by this very surprising response that it is your view that the existing Swine Flu cannot reassort with Seasonal Flu to acquire only the NA segment making it Tamiflu resistant.

Otherwise, none of this makes any sense, or you have just misinterpreted the question posed.

Many of us in our responses agree with you on your recombination theory of Tamiflu resistance acquisition, but a reader would not necessarily get that impression by the way you respond to our posts on this forum. You simply say "no" or "wrong" to anything anyone else posts.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in WA

Re: Two Tamiflu-resistant swine flu cases reported in WA

I take it by this very surprising response that it is your view that the existing Swine Flu cannot reassort with Seasonal Flu to acquire only the NA segment making it Tamiflu resistant.

Otherwise, none of this makes any sense, or you have just misinterpreted the question posed.

Many of us in our responses agree with you on your recombination theory of Tamiflu resistance acquisition, but a reader would not necessarily get that impression by the way you respond to our posts on this forum. You simply say "no" or "wrong" to anything anyone else posts.

There is quite a bit of data on swine H1N1 acquiring H and N human genes. I don't know of any instance where one was acquired without the other, Swine H3N2 is now fairly widespread and both the H3 and N2 are human. In the earlier series on Canadian swine in 2003/2004, most isolates had human PB1 with seven other swine genes. Two had human H and N (I believe they were both H1N2), and one had all 8 gene segments (thus none had a human H with a swine N or a human N and a swine H). Same is true for the recent "novel" isolate in Sasketchewan. It was a triple reassortant (it wasn't clear if it was H3N2 or H1N1 prior to the acquisition of human H1 and N1) and acquired Bribane/59 H1 AND N1 (and the N1 had H274Y).
I didn't say that picking up N1 without H1 was likely and I know of any such example (human N1 with swine H1 or swine H3).
If you know of such and example, post it. I asked GS for an example and he posted ZERO.
I didn't say human N1 with swine H1 made sense. WHO and CDC did, as did media reports, but they are fixated on reassortment and as seen by the nonsense about a concern that acquisition of N1 from brisbane/59, they have no current examples (without also acquiring a human H1), and I doubt that they have any prior examples.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

I admit to being confused even after Niman explained.

By the little summary I posted, I thought it was clear that the resistance developed "in" both people and was not the result of seasonal combining with panflu (or silent spreading). Considering that a certain percent of people will normally develop a resistance to Tamiflu, I just imagined this was much better than if it had combined.

It wasn't at all clear that the resistance developed "in" the patient. It just expanded in the patients (like Singapore, were the resistance was present 2-3 days after the start of treatment - too soon for de novo H274Y).

 

[Snowy Owl]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Please confer to

US swine flu patients on immunosuppressant drugs develop Tamiflu resistance

Snowy

 

[Mamabird]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Snowy,
About all I got from that blog was this:

The more we talk about this, the less clear the issue becomes to me. People talk about this like it's a reality but here he calls the risk theoretical. It can't be both.

There is a ton of evidence from Japan that shows when you take Tamiflu, the target virus soon learns how to wire around the meds and become resistant. This is especially true for children (who normally have immature immune systems) that have been given the drug. Even Roche, the manufacturer of the drug admits to this and even provides a percentage of how often it occurs.

The "new" theory is that the resistance has just been silently hiding in the background all along, and therefore was not previously detectable.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Are we just making this up as we go along?

Please provide some scientific basis to go along with this novel theory to go along with our continuing spreading and ever more resistant novel virus.

To distinguish between a de novo mutation instead the selection of a minor population requires some tight collection dates. In Singapore the patient developed symptoms on May 26, was hospitalized on May 27, and was tamiflu sensitive on May 28. Treatment began on May 27 or 28 and collection on May 30 was resistant. The 2-3 period is too short for detection of de novo resistance. The patient was infected with a mixture and the H274Y was obvious (no wild type detected) a few days after the start of Tamiflu treatment.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

There is a ton of evidence from Japan that shows when you take Tamiflu, the target virus soon learns how to wire around the meds and become resistant. This is especially true for children (who normally have immature immune systems) that have been given the drug. Even Roche, the manufacturer of the drug admits to this and even provides a percentage of how often it occurs.

The "new" theory is that the resistance has just been silently hiding in the background all along, and therefore was not previously detectable.

There is a big difference between earlier data in Japan and the H274Y seen in seasonal or pandemic H1N1. In Japan, sub-optimal levels produced resistance in H3N2 as well as H1N1 and at multiple positions (and only in patients being treated).
In the past several years there have been NO reports of Tamiflu resistance in H3N2. In addition, all resistance in H1N1 has been H274Y.

This pattern alone suggest that the H274Y isn't due to selection of random errors because only one "error" is selected. Moreover, in seasonal flu, almost all cases of resistance were in patients not taking Tamiflu (and have no such selection).

In pandemic H1N1, the detection has been too quick for de novo. In asymptomatic patients, incubation times are normallly 2-4 days. Patients have been developing symptoms in 5 days. The slightly longer time period indicates a lower than normal level of virus, because the virus with H274Y is a minor population (at 1-10% of the infectious virus). As a result, it takes a day or two longer to produce symptoms. For Singapore, the patient already had symptoms prior to treatment, but the detected virus switched from sensitive to resistant in a couple of days, which is too short for detection of a virus that starts from a recent copy error.

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Two cases of swine flu resilient to the drug Tamiflu were diagnosed over the weekend, the U.S. Centers for Disease Control and Prevention said yesterday. Tamiflu and Relenza were the only two medications that had thusfar proven effective in treating the virus (also known as H1N1), which already proved resilient to other seasonal flu remedies.

Tamiflu had been particularly popular, as it is ingested orally. Relenza, which is inhaled, is therefore not recommended for patients with respiratory conditions. Both drugs work by disabling an enzyme the virus needs in order to grow. Many governments in the world, including Israel's, have stockpiled Tamiflu in large quantities since the swine-flu pandemic began. <TABLE border=0 cellSpacing=0 cellPadding=0 align=right><TBODY><TR><TD rowSpan=2>

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Reports of Tamiflu-resistant strains of swine flu began in late June. In patients with weakened immune systems the virus might stay active for longer periods, acquiring resistance to Tamiflu and potentially spreading to others.
http://www.haaretz.com/hasen/spages/1107725.html
At the end of June, a representative of the Swiss pharmaceutical company Roche, which manufactures Tamiflu, said a Danish patient infected with a strain of the virus was not responding to the medicine. Earlier studies on Tamiflu indicated that 0.4 percent of adults and 4 percent of children afflicted with normal seasonal flu were likely not to respond to the drug.

Ten more such patients were identified in the world since June, with three in Japan, one in Singapore, one in China, one in Denmark, one in Canada, and two in the United States. However, no patient-to-patient transmission of the Tamiflu-resistant strain has yet been documented.

The two U.S. cases reported over the weekend were documented in Seattle. The swine flu patients were said to be suffering from leukemia and a depleted immune system. One patient is a young man who received a marrow transplant in May, and was said to be recovering at home; the other is a woman in her forties, who is still hospitalized. The two were said to have not been in contact, nor has it been documented that they have infected family members or medical staff with the Tamiflu-resistant strain.

The World Health Organization said it was following the reports, but no changes were yet made to its guidelines on treating the virus.

No Tamiflu-resistant strains have been recorded in Israel, where five more labs for testing for the disease are soon to be allocated by the health ministry. "The spread of a drug-resistant strain is usually slow, and by the time it spreads significantly vaccines against the disease will, in all likelihood, be developed. However, Tamiflu is one of the only medicines that can slow or weaken the disease, so it's crucial that swine flu react to it," said Dr. Amnon Kiro, chief of influenza research at the Israeli Pediatric Association research network.

At the moment, checks for swine flu are only carried out at the Health Ministry laboratory in Tel Hashomer, and in a laboratory at Hadassah University Hospital, Ein Kerem in Jerusalem. The checks are only meant to identify the virus, rather than test its response to Tamiflu.

Thirteen Israelis are presently in intensive care due to swine flu, and seven fatalities have so far been reported.
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[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Local swine flu patients resistant to Tamiflu

<!----><!-- cc -->By JENNIFER FARRINGTON
MyNorthwest.com staff


Two patients being treated for H1N1 virus (swine flu) have been found to be resistant to the antiviral Tamiflu used to treat the infection, according to Seattle and King County Public Health.
The two patients, a male teenager and a female in her 40s, are believed to have no connection with one another. Both patients have been identified as having compromised immune systems, raising their risk of developing an infection and antiviral resistance. One patient has recovered while the other has ongoing symptoms and is currently being treated with zanamivir, another antiviral medication.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health Seattle & King County in a news release. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available." The health department says the general public's risk is very low and there is no evidence that health care workers in contact with the patients became infected. However, local and state officials are working with the Center for Disease Control and are taking precautionary measures to monitor for other antiviral drug resistant influenza cases.

http://www.mynw.com/?nid=189&sid=200937

 

[AlaskaDenise]

Re: China, Singapore report Tamiflu-resistant H1N1 viruses

Re: China, Singapore report Tamiflu-resistant H1N1 viruses

Commentary

http://www.recombinomics.com/News/08160901/H274Y_WHO_See_NOT.html

Commentary

WHO Failure to See Spread of Tamiflu Resistant Pandemic H1N1

Recombinomics Commentary 15:19
August 16, 2009

China and Singapore have found Tamiflu-resistant pandemic viruses, Charles Penn, a scientist with the Geneva-based agency, said in an interview with The Canadian Press.

He revealed that the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses. He would not say where they were found or how many there were in total.

"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said.

The above comments were issued in response to queries about osletamivir resistance in Singapore and Hunan, China, as indicated by sequences made public at GISAID and Genbank. Those two instances were acknowledged, but the rationale behind the withholding of additional cases remains unclear. At the time Thailand had already acknowledged at least one case, and additional reports from Hong Kong and an MMWR Dispatch describing two immuno-compromised patients in Washington State were made public on Friday. Cases in Texas along the border with Mexico are still being denied, although the initial report included detail on two of the cases, suggesting the denials were largely based on semantics.

The cases in Texas would change the inferred scale, because the cases were at opposite ends of the border and had much in common with the initial H1N1 described in southern California. Those cases were unlinked to each other or swine, yet the sequences were virtually identical, indicating the virus was widespread. The same conclusion could be made from the cases in Texas, which may be related to the withholding of the information associated with these cases.

However, the detail that has come out in the past few days has left little doubt that the WHO's "scale of what we are seeing" is false. The failure to see the true scale of the H274Y spread is due to the limited testing, which is largely focused on samples collected prior to Tamiflu treatment, which can be "seen" in results from patients on prophylactic Tamiflu treatment or in samples collected a few days after the start of Tamiflu treatment in symptomatic patients.

The Hong Kong case described Friday was another patient who became symptomatic while on prophylactic Tamiflu. Earlier detail on patients in Denmark and Japan indicated they became symptomatic on day 5 of prophylactic treatment. Since the incubation period of influenza is in the range of 2-4 days, the slightly longer time period indicated the H274Y was already present when Tamiflu treatment began, but because it was a minor component, disease onset was delayed by 1-2 days. The recent patient in Hong Kong developed symptoms on day 6.

However, the confirmatory data on silent spread of H274Y came from Singapore, where additional data on first confirmed case was disclosed. The sequence was from a May 30 sample from a 28F, but the detailed reports at the MOH indicated the patient (American working in Singapore who arrived late on May 26 after becoming symptomatic during flight, but passed fever scans, but was hospitalized on May 27 and confirmed on May 28). The recent comments indicated the patient was initially Tamiflu sensitive (May 28 test), and resistance was discovered after patient improved (she was discharged May 31). Thus, the resistance in the May 30 sample was present only a few days after the start of treatment and the sequences (on HA, NA. MP) had no evidence of a mixture, indicating the resistant sequence quickly replaced the wild type sequence, signaling silently spread of H274Y.

Thus, the WHO failure to see the resistance was linked to limited and delayed testing of samples collected a few days after the start of treatment, and the standard testing / sequencing failed to detect the H274Y transmitting as a minor population. The HA Singapore sequence has a polymorphism that was found in isolates in the US, Sweden, China, and Argentina, raising concerns that the H274Y was creating additional problems in Tamiflu treated patients as seen in the two immune-compromised patients in Washington State as well as rising fatalities being reported worldwide.

.

 

[GennieF]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Drug-resistant swine flu cases discovered in patients in Seattle

By SANDI DOUGHTON
The Seattle Times
Published: Saturday, Aug. 15, 2009 - 7:03 pm
Last Modified: Sunday, Aug. 16, 2009 - 5:08 am

SEATTLE -- The country's first cases of drug-resistant swine flu were discovered in two leukemia patients in Seattle, the U.S. Centers for Disease Control and Prevention reported Friday.

Both patients, who had weakened immune systems from chemotherapy and stem-cell transplants, developed flu strains resistant to the anti-viral drug oseltamivir, sold as Tamiflu.

There was no connection between the cases and no threat to the public, said Dr. Jeff Duchin, chief of communicable-disease control for Public HealthSeattle & King County. None of the patients' family members, or the health workers who cared for them, contracted the disease.

The Seattle cases bring to 11 the worldwide total of people diagnosed with Tamiflu-resistant infections of the H1N1 virus.

"These are rare, isolated types of phenomena," Duchin said. "It's not something we expect is going to lead to widespread drug resistance in the community."

But the cases underscore the need for judicious use of anti-viral drugs to ensure resistant strains do not become more common, he said.

Last month, CDC officials warned summer camps to stop the practice of handing out Tamiflu to healthy children in an effort to ward off infection.

"Anti-viral drugs should be used to treat an infection after it's occurred - once the cat is out of the bag," Duchin said. "The more promiscuous use ... the more chances we have to develop resistant viruses."

Patients with weakened immune systems are most vulnerable because their bodies are not able to join forces with the drugs to fight off the virus. That means the virus persists longer in the presence of the anti-viral drugs, which is a recipe for the evolution of drug-resistant bugs.

One of the patients is a teenage boy who received a stem-cell transplant in May. He contracted the flu virus later that month and has since recovered.

The second patient, a woman in her 40s who relapsed after an earlier stem-cell transplant, remains hospitalized.

Genetic analysis showed that over several weeks of Tamiflu treatment, the flu bugs in their bodies mutated and were no longer sensitive to the drug.

The account of the cases, published in CDC's Morbidity and Mortality Weekly Report, identifies the hospitals as Seattle Children's and the University of Washington Medical Center.

Local and state health officials are working with the CDC to boost monitoring for drug-resistant flu viruses.

http://www.sacbee.com/847/story/2112883.html

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Drug-resistant swine flu cases discovered in patients in Seattle

Genetic analysis showed that over several weeks of Tamiflu treatment, the flu bugs in their bodies mutated and were no longer sensitive to the drug.

http://www.sacbee.com/847/story/2112883.html

The above statement is quite misleading (as was the MMWR dispatch). Although both patients initially tested as tamiflu sensitive, and one patient was still senstive on day 4 (June 4) after the start of treatment (June 1), there is no data supporting development of resistance "over several weeks". The first patient developed resistance between days 4 and day 11 (June 11 collection had H274Y) of treatment (clearly NOT over SEVERAL weeks) and the second patient developed resistance between day 1 (June 26) and day 18 day (July 14 sample had H274Y). i.e. resistance may have been detected on day 1 of treatment if such a sample was collected and TESTED. The detection on day 18 was of the FIRST REPORTED result on a sample collected after the start of treatment (the report was SILENT on samples collected earlier in July and did not indicate that such samples were sent to the CDC for testing).

 

[HenryN]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

The above statement is quite misleading (as was the MMWR dispatch). Although both patients initially tested as tamiflu sensitive, and one patient was still senstive on day 4 (June 4) after the start of treatment (June 1), there is no data supporting development of resistance "over several weeks". The first patient developed resistance between days 4 and day 11 (June 11 collection had H274Y) of treatment (clearly NOT over SEVERAL weeks) and the second patient developed resistance between day 1 (June 26) and day 18 day (July 14 sample had H274Y). i.e. resistance may have been detected on day 1 of treatment if such a sample was collected and TESTED. The detection on day 18 was of the FIRST REPORTED result on a sample collected after the start of treatment (the report was SILENT on samples collected earlier in July and did not indicate that such samples were sent to the CDC for testing).

The specifics on the second case indicate her initial treatment was between June 26-July 1 and the initial testing was on samples collected June 21 (prior to treatment and no H274Y) and July 28 (day 27 after the 5 day treatment course and having H274Y). However, additional samples were sent and although samples were collected on July 3, 6 and 14 it is not clear what was sent, other than July 14, which had H274Y. Thus, it is not clear that the July 3 and 6 samples were sent, if they were tested, or if tested, whether they did or did not have H274Y.

 

[HenryN]

Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

GP diary: beware Tamiflu panic

Updated on 14 August 2009
By Channel 4 News

Dr Peter Stott, writing for Channel 4 News from his surgery in Surrey, explains why irresponsible Tamiflu use could boost the spread of swine flu.


I was chatting about swine flu to one of my patients today and we got on to the subject of Tamiflu.
"I've already got some," she said. "I rang the flu advice line and pretended to have symptoms. They gave me a number to get some from the chemist.
"I wanted to take some with me on holiday just in case."
I told her that I thought this was the height of irresponsibility and that I was surprised that one of my apparently sensible patients should have behaved in this way.
Tamiflu works by stopping the virus multiplying in the body and it does this in a very clever way.
Viruses are effectively parasites which use mechanisms inside human or animal cells to replicate.
The new viruses buds off from the surface of the infected cell and is released to infect others.
This process requires a chemical called neuraminidase and Tamiflu blocks the action of this chemical.
So the virus cannot escape and stays inside the first cell. Tamiflu has to be taken early in the infection before too many cells have been affected.
After this time, the host's natural immune mechanisms like interferon will kick in and give protection.
In clinical trials Tamiflu reduces the duration of symptoms by approximately one day - a benefit that many consider may not be worth the cost and effort for patients who have only a mild illness.
The flu virus however is very clever and very quickly develops ways to become resistant to antivirals.
It is rather like trying to find your way to your favourite restaurant in a city centre. Even if they close one road, there are always other routes. It may take a little time to find it, but you will do eventually.
Similarly, there are lots of types of neuraminidases - lots of ways for the virus to get out of the cell and eventually the flu virus will mutate and be able to produce one.
We categorise neuraminidases as N1, N2, N3 etc but there are also sub-types. Swine flu is one of the H1N1viruses which are usually the nasty ones.
Tamiflu has been used for several winters now, given to patients with normal H1N1 winter strains and we are already beginning to see signs of resistance.
In the fourth quarter of 2008, the World Health Organisation reported that of that winter?s circulating influenza A (H1N1) flu virus, 95 per cent were resistant. We have only seen one resistant case of swine flu this year, in Denmark.
Happily this has not spread, but the fear of scientists is that swine flu will combine with one of these resistant strains, a change which would render Tamiflu ineffective.
So back to my patient. Why was I so upset?
First using Tamiflu for mild cases in fit people is probably not necessary. Second, widespread use will lead to increased resistance because the virus will get used to Tamiflu and it may be ineffective when we might really need it ? if the virus mutates to become more pathogenic.
Last, it's costing a lot of money for only minimal benefit. We have stockpiled 33m doses of Tamiflu which at normal pharmacy prices is worth over half a billion pounds - money that could be better spent on lots of other things.
There is a direct corollary between antivirals and antibiotics. Everyone understands that antibiotics have to be used responsibly. Otherwise resistance will develop and they will become ineffective. This will inevitably happen for antivirals too.
The government and the Department of Health have made antivirals very easily available through this flu epidemic, much more easily available than antibiotics have ever been.
You can get them immediately, on the phone, online and without a doctor's prescription. Be assured they will be there if you need them.
It is everyone's duty to use these medicines responsibly in the correct people, in the correct circumstance and for the correct illness.
Not to do so will only encourage viral resistance and could as a result, put the whole population at increased risk.

Dr Peter Stott is a GP at the Tadworth Medical Centre in Surrey.
<!--googleoff: index-->http://www.channel4.com/news/articles/science_technology/gp+diary+beware+tamiflu+panic/3308757

 

[Giuseppe]

Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

Changing seasons herald a new phase in the H1N1 pandemic (The Lancet Infectious Diseases, excerpt, edited)

The Lancet Infectious Diseases, Volume 9, Issue 9, Page 529, September 2009

doi:10.1016/S1473-3099(09)70214-2


Changing seasons herald a new phase in the H1N1 pandemic

Priya Shetty


As the northern hemisphere gears up for a new influenza season, the looming question is whether or not there will be a vaccine available by autumn. The issue has taken on a new urgency with the realisation that the spread of the pandemic means that attempts at containment are pointless and that there have been cases of drug resistance to oseltamivir (tamiflu), one of the key anti-H1N1 drugs. Europe is pushing hard to develop a vaccine, and the European Medicines Agency (EMEA) has said it will fas ...

(...)
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<cite cite="http://www.thelancet.com/journals/laninf/article/PIIS1473309909702142/fulltext?rss=yes">Changing seasons herald a new phase in the H1N1 pandemic : The Lancet Infectious Diseases</cite>

 

[AlaskaDenise]

Re: China, Singapore report Tamiflu-resistant H1N1 viruses

Re: China, Singapore report Tamiflu-resistant H1N1 viruses

Commentary

http://www.recombinomics.com/News/08170902/H274Y_WHO_Locations.html

Commentary

WHO Withholding Tamiflu Resistant Pandemic H1N1 Locations

Recombinomics Commentary 13:55
August 17, 2009

He revealed that the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses. He would not say where they were found or how many there were in total.

"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said.

The above comments by WHO are curious. WHO is funded by member nations and has a mandate to protect citizens of member nations. The withholding of important information such as the number and location of Tamiflu resistant pandemic H1N1 virus is not consistent with that mission. Tamiflu is widely used and recommended by WHO, so the withholding of information on resistance leads to inappropriate use of the antiviral, and places patient care and health care systems at risk.

This type of risk was easily seen in the two immuno-suppressed patients detailed in the recent MMWR dispatch. WHO has maintained that resistance is rare and due to spontaneous mutations selected in Tamiflu treated patients. However, recent data, including that from the patients in Washington state suggested that the limited number of reports is related to limited and delayed testing, which is compounded by the withholding of information on identified isolated.

The MMWR describe patients who were H1N1 infected in June. The patients were treated with Tamiflu and detectable resistance developed quickly. However, treatment was increased and resistance was not confirmed until August, after one patient developed a Tamiflu resistant recurrence and the other patient continues to be hospitalized in spite of treatment with Tamiflu, Relenza, and ribavirin. The ability of Tamiflu resistant pandemic H1N1 to persistence in such aggressively treated patients increases concerns that the recent worldwide rise in patient deaths and hospitalizations is linked in part to such resistance.

When WHO stated it was withholding the information on resistance, there had already been 8 examples in patients which were supported by sequence data. Another example (in Thailand) had already been described in media reports and shortly after the proclamation by WHO, Hong Kong reported another cases of resistance in a patient being treated prophylatically and the two patients in Washington State were detailed. Moreover, additional information on the American patient in Singapore provided compelling data that H274Y was silently circulating because the vast majority by WHO and consultants involved samples collected prior to Tamiflu treatment, which were failing to detect the H274Y present as a mixture in the H1N1 samples being sequenced.

The WHO should be encouraging countries to promptly report resistance and expand testing to patients who have been briefly treated with Tamiflu. A true accounting of H274Y in pandemic H1N1 is long overdue.

.

 

[AlaskaDenise]

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Re: Two Tamiflu-resistant swine flu cases reported in Washington

Commentary

http://www.recombinomics.com/News/08170901/H274Y_Fit_US.html

Commentary

Fit Tamiflu Resistant Pandemic H1N1 in the United States

Recombinomics Commentary 11:20
August 17, 2009

Genetic analysis showed that over several weeks of Tamiflu treatment, the flu bugs in their bodies mutated and were no longer sensitive to the drug.

The above comment on the recent MMWR dispatch warning of prolong shedding of oseltamivir resistant pandemic H1N1 in immunosuppressed patients is in error. The two patients from Washington state were the first confirmed cases of H274Y in swine H1N1 in the United States, but the presentation of the resistance data helped create the above misconception that the H1N1 muted within the patients over a period of several weeks. MMWR dispatches are used to quickly alert physicians to significant medical concerns and the inclusion of August 11 data in the August 14 publication signals the rapid publication of such data as well as the urgency of such reports. However, the description of the resistance could easily be misinterpreted and lead to the false conclusions stated in the above media report.

Recent data on the detection of H274Y in pandemic H1N1 has supported the silent spread of the polymorphism which is usually detected in patients treated with osletamivir. Since the H274Y is present as a mixture, sequence analysis of untreated patients produces a "Tamiflu sensitive" genotype, with H274. Indeed, the only reported case of H274Y in a patient who was not treated with Tamiflu was a San Francisco resident who was identified in Hong Kong through routine surveillance. However, multiple examples of H274Y in patients who have been briefly treated with Tamiflu support a relatively high level of H274Y prior to treatment. Published sequences are a consensus and represent the dominant nucleotide at a given position, so samples with H274Y in 10-20% of the virions will not be represented in the published sequence. When levels approach 50% the consensus sequence will show a mixed signal at the position, but sequences published to date have either had wild type or H274Y at position 274. This is due in part by the ability of the Tamiflu, in combination with and the host's immune system, to rapidly clear the wild type sequences (and most patients can clear the H1N1 without antiviral treatment)..

This type of data was most clearly presented in the recently released sequence from an American traveling from Honolulu to Singapore. The patient developed symptoms during the flight, but successfully passed through the thermal scanner. However, her condition did not improve and she was hospitalized the next day, May 27. The H1N1 was confirmed on May 28 and the sequence indicated the virus was Tamiflu sensitive. The infection was mild and the patient was discharge on May 31. However, a sample was collected on May 30, and the associated sequence had H274Y, signaling the rapid appearance of the resistance, and the rapid clearing of the wild type sequence (the sequence had no mixed signals).

This rapid appearance of H274Y was also seen in multiple patients on prophylactic Tamiflu. These were asymptomatic contacts of confirmed cases infected with Tamiflu sensitive H1N1. However patients in Denmark and Japan developed symptoms after 5 days of treatment and a patient from Hong Kong developed symptoms on day 6. Since the incubation period of influenza is 2-4 days, the slightly longer than normal incubation period indicated the H274Y was silently spreading as a minor component, which was subsequently detected after brief Tamiflu treatment.

In the two patients in Washington, the clearance of wild type was likely delayed somewhat by their immuno-compromised state. The first patient responded to Tamiflu treatment, but then had an H1N1 recurrence which had H274Y. Testing of samples collected earlier showed that prior to treatment the virus was sensitive, as was the sample from treatment day 4. However, H274Y was identified on day 11 after the start of treatment, indicating the H274Y reached a detectable level between days 4-11 post initiation of treatment, and the H1N1 was evolutionarily fit and produced a recurrence in the patient.

Data from the second patient produced similar results, but that H1N1 with H274Y has produced a persistent infection which has not been cleared by aggressive Tamiflu treatment or treatment with inhaled and intravenous Relenza, as well as ribavirin. The patient remains hospitalized with H274Y positive H1N1, again demonstrating the virus is evolutionarily fit. Data on earlier collections indicated that the H1N1 was sensitive prior to treatment and H274Y was detected on day 18 after the start of treatment. However results on earlier collections on day 3 and 6 of treatment were not disclosed, so the H274Y reached detectable at some time between day 1-18 post treatment. Testing of samples collected on days 3 and 6 could help resolve the initial date of detectable H274Y.

However, the above data clearly show that H1N1 is evolutionarily fit and can cause significant medical problems linked to prolonged shedding, as well as the condition of infected patients. These data increase concerns that H1N1 with H274Y could be linked to the increased number of fatal and hospitalized patients, who are frequently treated with Tamiflu.

Testing of samples collected after the start of Tamiflu treatment would be useful because, as seen in recently released data, virus which is Tamiflu sensitive prior to treatment can be quickly replaced by Tamiflu resistant H1N1, leading to significant complications.

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