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

[Giuseppe]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

(...)


ECDC Threat Assessment

First isolation of a secondary oseltamivir - resistant A(H1N1)v strain in Denmark, 29 June, 2009

SOURCE: Internal request following a EWRS message from Denmark health authorities
PUBLIC HEALTH ISSUE: Isolation of a mutant A(H1N1)v virus containing a genetic marker of resistance to oseltamivir.
CONSULTED EXPERTS: Internal experts

EVENT BACKGROUND INFORMATION:

Event reported by Danish EWRS Focal point on 29 July 2009 :

In the context of tracing contacts of a cluster of 3 imported cases in Denmark, a female contact who initially tested negative on PCR, was given prophylaxis with oseltamivir (75 mg per day). Five days later, despite reportedly having complied with treatment, she developed flu-like symptoms and was tested positive for A(H1N1)v. Sequencing of the virus showed a single mutation H275Y (H274Y in N2 nomenclature) in the neuraminidase gene. The presence of the resistance marker and the phenotypic (in vitro) resistance was confirmed by a WHO collaborating Centre. The virus is not a re-assortant and is presumed to remain susceptible to zanamivir (another neuraminidase inhibitor). All other virus isolated as part of this cluster investigation, including the presumed source patient, did not show the mutation.


ECDC THREAT ASSESSMENT FOR THE EU

The A(H1N1)v virus related to the ongoing pandemic has always be found sensitive to oseltamivir and zanamivir and resistant to adamantanes (M2 blockers). This is the first observation of a genetic marker of resistance to oseltamivir in a A(H1N1)v virus.

The mutation consists of the substitution of histidine to tyrosine at amino acid position 275 in the neuraminidase segment gene (position 274 in N2 nomenclature). This mutation has been described in the past, associated with secondary resistance to oseltamivir acquired during treatment. This was documented some years back in children in Japan where the drug was used more commonly than in Europe(1). The mutation was detected in up to 16% of oseltamivir-treated children in Japan, perhaps associated with under-dosing(2). Studies have shown that the virus containing this mutation is unfit in terms of transmissibility(3) and possibly also in terms of pathogenicity(4) as demonstrated in animal studies. Therefore, such mutation is of limited public health concern since it has not resulted in the past in a virus that demonstrated sustained person-to-person transmission.

According to the available epidemiological and virological data, this reported event in Denmark is almost certainly secondary resistance acquired during post-exposure prophylaxis. This is supported by the time sequence and the absence of similar genotypic markers in viruses isolated in the other cases of the cluster.

There is no evidence in this case that the isolated resistant virus has transmitted to other persons, meaning that the risk of spread of a resistant virus is nearly zero. It is however likely that such mutation will be observed again in the future. This observation does highlight the increased likelihood of such event arising from widespread use of anti-virals especially in prophylaxis.

Secondary resistance, arising due to treatment, must not be confused with more complex mutations including the H274Y substitution resulting from primary resistance. Such primary resistance was first observed in seasonal A(H1N1) influenza virus in the 2007-2008. It spread worldwide generally displacing other seasonal A(H1N1) viruses (98% resistance in EU in 2008-2009)(5). Following that phenomenon some EU countries have diversified their anti-virals stockpiles adding zanamivir to oseltamivir.

There is always a theoretical risk of re-assortment of A(H1N1)v with primary resistant seasonal viruses notably the seasonal influenza virus A(H1N1) containing the H274Y mutation.


CONCLUSIONS AND RECOMMENDATIONS

The emergence of secondary resistance while on antiviral treatment is a well recognised phenomenon in influenza viruses. As in the past, there is no evidence the mutation has led to a virus capable of transmitting from person to person. Therefore, though resistant viruses are always a concern, the emergence of A(H1N1)v resistant to oseltamivir does not represent a public health threat. It can be expected to happen again.

Surveillance of genetic resistance for detecting early primary resistance is of particular importance for the future course of the pandemic

CONTACT: support@ecdc.europa.eu


References

(1) Whitley RJ, Hayden FG, Reisinger K, Young N, Dutkowski R, Ipe D, et al. Oral oseltamivir treatment of influenza in children. Ped Infect Dis J 2001; 20(2):127-33.
(2) Ward P, Small I, Smith J, Suter P, Dutkowski R. Oseltamivir (Tamiflu(R)) and its potential for use in the event of an influenza pandemic. J Antimicrob Chemother 2005; 55(suppl_1): i5-21.
(3) Compromised transmission: Herlocher ML, Truscon R, Elias S; et al. Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis. 2004;190(9):1627-30
(4) Attenuated pathogenicity: Ives JA, Carr JA, Mendel DB; et al. The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res. 2002; 55(2): 307-17
(5) Meijer A, Lackenby A, Hungnes O, Lina B, van der Werf S, Schweiger B, et al. Oseltamivir-resistant influenza A (H1N1) virus, Europe, 2007?08 season. Emerg Infect Dis. 2009; 15(4):552-60

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http://www.ecdc.europa.eu/en/files/pdf/Health_topics/Situation_Report_090630_1700hrs.pdf

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[HenryN]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Meanwhile, lab workers in Denmark are reporting the first known case of swine flu that is resistant to Tamiflu, the main anti-viral drug that governments have been stockpiling in case this strain of H1N1 turns nasty this summer. The single case of drug resistance is worth noting but not yet cause for alarm, according to the CDC. NPR's Richard Knox sent this background note to explain why:
"It's not good. But experts say it doesn't necessarily mean all or even most swine flu viruses will soon become resistant to the mainstay antiviral.
The Danish patient reportedly has recovered from the flu. And as far as anyone knows, he or she did not pass the resistant virus on to anyone else.
Experts have been worried swine flu might become Tamiflu-resistant because many of the ordinary seasonal flu viruses that circulated in North America this past season were unfazed by the drug. One of these unfazed seasonal strains is also from the H1N1 family.
Roche, which makes Tamiflu, says the Danish patient's virus had only one genetic mutation, called H-274-Y. That mutation has long been known to arise in the viruses infecting a small percentage of people on Tamiflu, in response to treatment. But here's the difference: The Tamiflu-resistant seasonal flu virus has a half-dozen mutations, including H-274-Y. Scientists don't know if the swine flu virus can or will acquire this suite of resistance mutations.
Actually, it's pretty surprising that the pandemic virus hasn't acquired the H-274-Y mutation more often, given the thousands of people treated with Tamiflu lately.
"It's certainly likely that we will see this in the United States," says Dr. Carolyn Bridges of the Centers for Disease Control. But so far the CDC has tested almost 200 swine flu viruses for Tamiflu resistance and hasn't found any.
One reason, Bridges says, is that the new H1N1 virus has an "N1" gene that's very different from the corresponding gene of the seasonal H1N1. That's significant, because Tamiflu works by blocking neuraminidase --- that's what the "N" stands for. So maybe the pandemic virus's N-gene isn't as susceptible to the Tamiflu resistance mutation as the analogous gene in its very distant cousin, the seasonal H1N1 virus.
But the Danish case shows that it can happen.

http://www.npr.org/blogs/health/2009/06/morning_rounds_updates_on_swin.html?ft=1&f=103537970

[HenryN]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Roche Sees First Case of Tamiflu-Resistant Swine Flu (Update1)


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By Christian Wienberg and Marthe Fourcade
June 29 (Bloomberg) -- Roche Holding AG said a swine flu patient treated with its Tamiflu drug in Denmark showed resistance to the antiviral medicine for the first time.
The patient was given a low dose of Tamiflu preventively after coming in contact with someone infected with the H1N1 pandemic virus, said David Reddy, who heads Roche?s influenza task force. The person developed flu symptoms and was found to have a virus mutation that evaded the drug, Reddy said on a conference call today.
The patient has recovered and doctors have found no other people carrying the resistant strain, Denmark?s National Board of Health said today in a statement on its Web site. Tamiflu studies show that 0.4 percent of adults and 4 percent of children with seasonal influenza develop resistance, according to Reddy.
?We know from seasonal flu that a proportion of patients can develop resistance,? Reddy said. ?We fully expect that this also can occur during treatment with a new flu strain.?
The new virus, which has killed more than 300 people worldwide, ?remains sensitive to the drug,? Reddy said. ?What this does underscore is the continued need for resistance monitoring.?
Gauging Resistance
The virus hasn?t acquired new characteristics that make it resistant to Tamiflu, according to Reddy. Instead, in this one patient, when faced with a low dose of the medicine it found a way to evade it, he said. That?s known as drug-induced resistance, he said.
Roche, based in Basel, Switzerland, is studying flu sufferers in several countries to gauge drug resistance.
Swine flu hasn?t previously shown resistance to Roche?s Tamiflu or GlaxoSmithKline Plc?s Relenza, antiviral medicines that reduce the severity of the disease when administered in the first few days. The World Health Organization reported today that there have been 70,893 cases of the virus globally, including 44 people in Denmark.
?This one case of a resistant virus doesn?t change our recommendations to use Tamiflu and the treatment remains part of Denmark?s preparedness measures,? the National Board of Health said in the statement.
To contact the reporter on this story: Christian Wienberg in Copenhagen at cwienberg@bloomberg.net; Marthe Fourcade in Paris at mfourcade@bloomberg.net
Last Updated: June 29, 2009 11:52 EDT

http://www.bloomberg.com/apps/news?pid=20601085&sid=an3udfKwF4Do

[theforeigner]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

My translation of the black highlighted part of the newsreport:

The person was originally not ill at all. The person was in precaution treatment with Tamiflu, because the person had been in close contact with a person who was infected with Swine Flu abroad (OR the person had been abroad and been in close contact with a H1N1 infected person, can´t be sure which it is). After 5 days treatment with Tamiflu, the person suddenly got sick with H1N1, but it didn´t seem like the treatment had any effect. It turned out via tests her in Denmark and in UK, that the person had developed resistance twards Tamiflu, explains Nils Strandberg ( President & CEO of -Statens Serum Institut )
Insted the person was treated with Relenza. - We can be glad that the person today is well and have not infected others said Nils Strandberg.

The Journalist ask Nils Strandberg:
But isen´t it a worrying perspectives that Tamiflu now no longer can be concidered a safe tratment against Swine Flu?

-Yes it is worrying if Tamiflu does not work on the most vulnerable groups. But there are still things that work if a vulnerable patient get infected with H1n1. There is another treatment Relenza.

http://ekstrabladet.dk/kup/sundhed/article1188161.ece

Dansker er resistent overfor Tamiflu



En dansker er som den første i verden blevet resistent overfor medicin mod svineinfluenza H1N1. Dystre perspektiver for risiko-patienter

16:40 - 29. jun. 2009 | Frederik Bjerre Andersen, Gitte Hejberg


Statens Serum Institut har fundet den første person i verden, der er resistent overfor medicinen oseltamivir, der sælges under navnet Tamiflu og blandt andet har vist sig virksom mod svineinfluenzaen H1N1.

Det er det første tilfælde af resistens overfor medicinen på verdensplan. Det er forventeligt, at influenzavirus kan mutere spontant. Resistensen har ikke ændret H1N1-virus’ evne til at smitte eller fremkalde sygdom, meddeler instuttet.

- Både bakterier og vira kan mutere og blive resistente. Og det er altså det, der er sket her, bekræfter administrerende direktør på Statens Serums Institut Nils Strandberg.

- Vedkommende var til at begynde med slet ikke syg. Den pågældende var i forebyggende behandling med Tamiflu, fordi vedkommende havde været i tæt kontakt med en svineinfluenza-ramt i udlandet. Da der var gået fem dage med Tamiflu, blev personen så pludselig syg med H1N1, men det så ikke ud til, at medicinen virkede. Det viste sig så via prøver her og i England, at personen var blevet resistens, fortæller Nils Strandberg.

Uheldigt for alvorligt syge
I stedet blev patienten behandlet med medicinen Relenza.

- Vi kan glæde os over, at personen i dag er helt rask og ikke har smittet andre, siger Nils Standberg.

- Men der er vel dystre perspektiver i, at Tamiflu nu ikke længere kan betragtes som et sikkert middel mod svineinfluenza?

- Ja, det er bekymrende, hvis Tamiflu ikke virker på de mest udsatte grupper. Men der er stadig noget at gøre, hvis en svagelig patient bliver smittet med H1N1. Der er jo et andet stof, som man kan bruge.
Skruer ned for forebyggende brug
Ifølge Nils Strandberg vil fundet af den resistente dansker betyde, at lægerne fremover vil blive mere tilbageholdende med at bruge Tamiflu forebyggende - med mindre der altså ligefrem er tale om meget syge og skrøbelige patienter.

- Hvorfor er det netop en dansker, der bliver den første resistente influenza-patient?

- Det beror nok mest på et tilfælde. Vi har et godt system, hvor vi er gode til at overvåge situationen.

Episoden slår fast, at influenza-virus kan mutere, og at Tamiflu på ingen måde kan betragtes som mirakelmedicin. Tamiflu kan i forvejen ikke kurere influenza, men medicinen kan nedsætte symptomerne og forkorte forløbet.

Epidemi til efteråret
Selv om sommeren, udendørslivet og de lukkede skoler er ensbetydende med mindre influenzasmitte i Danmark, vil danskernes rejseaktivitet sommeren over betyde, at der bliver slæbt mere smitte til landet.

- Vi skal formodentlig frem til det sene efterår eller vinter, før vi kan risikere en H1N1-epidemi herhjemme. Men det behøver ikke at give problemer, da det stadig er en ret mild influenzatype, siger Nils Standberg.

[Gert van der Hoek]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

UPDATE 1-Roche finds 1st case of H1N1 resistance to Tamiflu

Mon Jun 29, 2009
.
(Adds details)

ZURICH, June 29 (Reuters) - A patient with H1N1 influenza in Denmark showed resistance to Roche Holding AG's (ROG.VX) Tamiflu, the main antiviral flu drug, a company executive said on Monday.

"While receiving the drug, the patient appeared to develop resistance to it," David Reddy, Roche's pandemic taskforce leader, told reporters on a conference call on the Danish case. "This is the first report we have of it in H1N1."

The World Health Organisation has raised its pandemic flu alert on the H1N1 flu virus to phase 6 on a six-point scale, indicating the first influenza pandemic since 1968 is under way.

Common seasonal flu can resist Tamiflu and Reddy said a case of resistance in H1N1 was not unexpected, adding Roche has been working on strategies to counter such a development.

http://www.reuters.com/article/marketsNews/idUSLT21784420090629

[Gert van der Hoek]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Official press release, credits theforeigner for the link.

caution google translated, please correct if translation is wrong.

29. June 2009 -

Resistance of pandemic influenza A H1N1v detected in Denmark

The first case of resistance to oseltamivir (Tamiflu ?) in the pandemic influenza A H1N1v found in Denmark. This is the first identified cases worldwide.

It is well known and expected that influenza virus can mutate spontaneously. Resistance has not changed the virus' ability to infect or cause disease, the assessment is that they are a relatively mild flu.

The person is now healthy, and there is no further evidence of infection with resistant virus. The infection was in preventative treatment with oseltamivir (Tamiflu ?) because of close contact with a case that was infected abroad.

Yet he had flu symptoms. A test showed that the person was infected with influenza A H1N1v. Further studies at Statens Serum Institut has now shown that the virus has mutated. It is resistant to the antiviral agent oseltamivir (Tamiflu ?), while zanamivir (Relenza ?) can continue to be used for treatment.

World Health Organization Calls on the basis of the Danish case for increased attention to the possibility of development of resistance in the pandemic influenza A H1N1v.

A similar development of resistance to oseltamivir (Tamiflu ?) is also seen in the winter influenza A H1N1, which has circulated the past two winter seasons.

Each fund in Denmark is mentioned not unexpected. It does not constitute a risk to public health and does not need to change the recommendations for the use of oseltamivir (Tamiflu ?).

In Denmark the situation continues to follow closely in the monitoring of disease incidence and investigation of all isolated influenza A H1N1v.

http://www.ssi.dk/sw174.asp?PAGE=1&ArtNo=3651423

[Gert van der Hoek]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Articles say no spreading of this resistant strain was found.

Articles also say the man was treated with Tamiflu first, but kept displaying symptoms, than he was treated with Relenza. And was cured.

[Gert van der Hoek]

Re: Denmark - Dane with novel H1N1 found resistant to Tamiflu

Dane resistant to pandemic medicine

/ Ritzau /

Last updated on Monday 29th June 2009, 15:30

The first case in the world of resistance to influenza drug Tamiflu in people with influenza H1N1 has been found in Denmark. The person is now healthy, and there is no further evidence of infection with resistant virus, according to Statens Serum Institut.

The infection had been in close contact with another infected person, and was therefore prevented treatment with Tamiflu. Yet the person had flu symptoms and are instead treated with another type of flu drugs, Relenza. World Health Organization Calls for the Danish case for more attention to the possibility of development of resistance in the virus.

It is not unusual for a flu virus mutating spontaneously and in a press release calls the Statens Serum Institut is "well known and expected." They also emphasized that it does not pose a threat to public health. /

http://www.horsens-folkeblad.dk/?rartikel=K2JN-7TGHD8201175

[Gert van der Hoek]

Tamiflu resistance in pandemic influenza - historical compilation of news

caution - google translated

The first case in the world of resistance to influenza drug Tamiflu in people with influenza H1N1 has been found in Denmark.


Dane resistant to Tamiflu

29. June 2009

The first case in the world of resistance to influenza drug Tamiflu in people with influenza H1N1 has been found in Denmark.

The person is now healthy, and there is no further evidence of infection with resistant virus, according to Statens Serum Institut.

http://www.dr.dk/Nyheder/Indland/2009/06/29/151411.htm?rss=true

[kiwibird]

Tamiflu resistance in pandemic influenza - historical compilation of news

http://lite.alertnet.org/thenews/newsdesk/SIN462788.htm

Australia, NZ, Taiwan, Singapore order Relenza-GSK
29 Jun 2009 07:57:29 GMT
Source: Reuters
SINGAPORE, June 29 (Reuters) - The governments of Australia, New Zealand, Taiwan and Singapore have bought GlaxoSmithKline's <GSK.L> Relenza flu treatment since the H1N1 outbreak began in April, a top GSK official said on Monday.

GSK Asia Pacific director Christophe Weber told Reuters the firm had advised governments to keep the inhaled Relenza drug at 30-50 percent of their overall flu drug stockpiles, which mainly comprise the Tamiflu capsule made by competitor Roche <ROG.VX>.

"There have been some publications showing that there is some level of resistance developed for Tamiflu," Weber said on the sidelines of a GSK media seminar in Singapore.

"In case there will be more resistance to Tamiflu, and Relenza will be a good alternative," he said.

Weber declined to say amount or value of orders by the four countries, saying he would rather those governments disclosed their orders themselves.

Glaxo's partner Biota Holdings <BTA.AX>, which originally developed the medicine and earns a 10 percent royalty on Australian sales, said in May that Canberra had bought an additional 1.6 million courses at A$43 million ($33.7 million).

On completion of the supply contract, the Australian National Medical Stockpile will hold 3.4 million courses of Relenza, or 33 percent of the country's total stockpile of antiviral flu drugs.

The World Health Organisation (WHO) declared the first 21st century flu pandemic this month and advised governments to prepare for a long battle against the new H1N1 flu virus.

As of June 26, it had killed 306 worldwide with the number of confirmed cases of H1N1 at least 67,072.

The flu has spread widely after emerging in April in Mexico and the United States. The WHO warned the pandemic could last a year or two. (Reporting by Nopporn Wong-Anan; Editing by Alex Richardson)

AlertNet news is provided by

[dr kockosh]

Re: NZ Swine flu tally 258

Swine flu mutation, drug resistance feared



The Press


Last updated 05:00 22/06/2009
Share

Swine flu may become resistant to Tamiflu if it mingles with one of this season's influenza strains, experts warn.
World-renowned Canterbury virologist Dr Lance Jennings said one of the two strains of seasonal influenza circulating this year was resistant to Tamiflu.
It was possible this resistant strain would mutate with the influenza A (H1N1) virus and affect Tamiflu's ability to medicate swine flu, Jennings said.
"Viruses do mutate ... The only thing we can do is be prepared."
If swine flu became resistant to Tamiflu, New Zealand had stocks of another drug, Relenza, that could combat influenza, he said. Relenza was developed before Tamiflu and its chemical makeup made it tougher for viruses to develop resistance.

"If A (H1N1) became resistant to Tamiflu, that would be bad. But the worst-case scenarios are Avian flu mutating, so it can spread between humans, or the swine flu developing into a more deadly form," Jennings said.
Environmental Science and Research virologist Sue Huang, head of the World Health Organisation national influenza centre in Upper Hutt, also voiced concerns.
"Viruses are notoriously unpredictable and strains change constantly ... if there was mixing of the novel virus with other A/H1N1 strains circulating, such as in a person infected with both strains, the novel virus could take on resistant characteristics," she said.

Seriously ill swine flu patients flocked to Canterbury's new influenza centre over the weekend. More than 142 people had visited the Christchurch assessment centre since it opened on Friday. All were "reasonably or seriously" unwell, with symptoms such as high fever, rasping coughs and breathing problems, centre managers said.
Yesterday, the Ministry of Health said a rise in cases of serious illness was inevitable. The number of confirmed cases nationwide is 258 an increase of 42 since Friday. More than 200 of those cases had been reported in the past week, mainly in the three major cities.

Last night Canterbury had 67 confirmed cases. However, there was only one other case in the Nelson-Marlborough region in the South Island.
Canterbury Primary Pandemic Group co-ordinator Phil Schroeder said the screening centre was seeing only those with more serious flu symptoms.
Concerned Cantabrians had been calling the free information and triage line, meaning only those who needed to see a doctor came to the centre, he said.
A 30-year-old woman remained in a critical condition in Wellington Hospital last night with swine flu, and underlying medical problems.

Ministry of Health director of public health Dr Mark Jacobs said while most cases had been mild to moderate, over the coming weeks and months there would be a big increase in the number and severity of cases
People who did not have serious symptoms should stay at home and leave health services for those who needed them most.
If you think you have swine flu, ring 0800 373



As i have said before the NZ govt has only stockpiled tamiflu and recently aquired 125,000 courses of relenza - which won't go far - at this point in time relenza is available thru private sector at Lee and Hart pharmacy in warkworth nth of auckland. they will post it to you - you will need a presciption from your Dr - to get this - you will need to be showing symptoms or be planning an overseas trip. Worthwhile taking with you incase the much expected tamiflu resistant mutation is aquired - hospitals all full and you are basically on your own.

[Sally Furniss]

Re: Australia defends swine flu cruise ship Pacific Dawn handling

Fears home may breed superbug

Kathleen Donaghey
May 30th, 2009
<!-- p> THE house of an Oxenford family which contracted both swine flu and influenza A on the Pacific Dawn cruise ship could be the perfect breeding ground for a superbug. </p -->

THE house of an Oxenford family which contracted both swine flu and influenza A on the Pacific Dawn cruise ship could be the perfect breeding ground for a superbug.

Nick and Kiralea Campbell are recovering from swine flu in quarantine at home while their children have contracted influenza A.

Scientists have warned if the two viruses mix it could lead to an aggressive new superbug or, at the very least, one that is resistant to Tamiflu.

Swine flu and the seasonal flu have been confirmed on the Pacific Dawn cruise.

Gold Coast influenza expert Professor Mark von Itzstein yesterday described the situation as 'a dangerous environment'.

Prof von Itzstein said the house would be a 'melting pot' that could lead to a virus rapidly morphing.

He said people in this situation should be kept in hospital as a matter of priority.

"If you start co-infecting each other with a different virus, that's the mixing pot," said Prof von Itzstein. "Personally I think if there is, in the same family, two influenza viruses ... they should be placed as a higher risk family.

"These people should be quarantined in a hospital somewhere," he said.

Prof von Itzstein said the two viruses could either 're-assort' to create a superbug, or, if the influenza A strain was resistant to Tamiflu, make a superbug also resistant to the anti-viral drug.

Prof von Itzstein said all governments should be considering the scenario.

However, if the family was properly quarantined and did not come into contact with any other people, then he said the risks were 'negligible'.

Fears of a new superbug in Australia have been mounting as the winter season approaches and more people start taking Tamiflu.

The drug is solely produced by the pharmaceutical company Roche which in recent years had predicted falls in sales. Tamiflu has already been proven useless against several human flu strains, except swine flu, while the drug Relenza, created by Prof von Itzstein works against all flus.

Australia has more Tamiflu stockpiled than Relenza.

Mrs Campbell said no one at Queensland Health warned the family of the risks of having the different illness mixing at home.

"They haven't mentioned that it could change into something more," said Mrs Campbell.

"I don't think they know what to expect to be honest. They were unprepared and unsure of the outcome to be honest."

Queensland Health was unable to comment last night.

Bond University Professor Chris Del Mar said there was potential in Australia for swine flu developing resistance to Tamiflu.

Prof Del Mar will fly to Geneva in June as Australia's only scientific representative at an upcoming World Health Organisation convention on swine flu.

For two days a team of experts will develop a set of guidelines to tackle the spread.

Prof Del Mar said he was concerned Australia and other countries were being 'too liberal' in the use of Tamiflu.

Some health authorities interstate and overseas have been handing out the drug to school children who may have been exposed but weren't sick.

"It might be a very good thing if we're all sick and dying. I'm not sure if we should be using it on people at the same school as someone infected," he said.

Meanwhile, Australia's National Health and Research Council yesterday announced $7 million for groups wanting to undertake research into swine flu.

Prof von Itzstein, who heads Griffith University's Institute for Glycomics, said his team would apply so they could study the flu's susceptibility to antiviral medications and its capacity to change.

http://www.goldcoast.com.au/article/2009/05/30/83801_gold-coast-news.html

[Blueforest]

Tamiflu resistance in pandemic influenza - historical compilation of news

Swine flu: Can science save us from the second wave?
06 May 2009 by Debora MacKenzie

**snipped**

The problem with antivirals

If the prospect of swine flu in its current form isn't worrisome, a drug-resistant strain emerging and going pandemic should be.

Although the influenza A H1N1 strain now racing around the world is sensitive to two major flu antivirals, oseltamivir (Tamiflu) and zanamivir (Relenza), they put pressure on the virus to develop resistance. "The problem is you use, you lose," says Scott Layne, an epidemiologist at the University of California, Los Angeles.

A big wake-up call came in the 2007-08 flu season when several strains of H1N1 evolved resistance to Tamiflu. Arnold Monto, an influenza specialist at the University of Michigan, Ann Arbor, says that tests had wrongly suggested that oseltamivir-resistant viruses would be crippled and unlikely to spread widely in humans.

Now most human H1N1 strains are oseltamivir-resistant, and researchers worry that swine flu could follow suit, either by mutation or through swapping genes. "Commingling is a chilling thought," Layne says. Prudent use of drugs is no guarantee against resistance, Monto says. Resistant strains of human H1N1 developed in countries that skimp on oseltamivir.

As with HIV, a drug cocktail is one option, as mutations conferring simultaneous resistance to multiple drugs are less likely. A mix of zanamivir and oseltamivir might not be effective, though, Layne cautions. The former works only in the lungs and the latter all over the body, so some flu virus would escape this double treatment.

http://www.newscientist.com/article/mg20227073.500-swine-flu-can-science-save-us-from-the-second-wave.html

[Possibilities]

CDC Telebriefing May 11, 2009, 1 p.m. ET

http://www.cdc.gov/media/transcripts/2009/t090511.htm

CDC Telebriefing on Investigation of Human Cases of H1N1 Flu
May 11, 2009, 1 p.m. ET

Audio recording (MPEG)


Dave Daigle: This is Dave Daigle from CDC Media Relations. Dr. Anne Schuchat from respiratory diseases will update us on the novel H1N1 outbreak.


***Snipped***


Operator: The next is from Fred Mogul, WNYC. Your line is open.

Fred Mogul: Yes, hello, Dr. Schuchat. It's a perennial in general question, but concern in a way, perhaps highlighted by the recent outbreak of H1N1 which is to say doctors prescribing, you know, antibiotics much of the year and in this case, antivirals and big rushes reported on pharmacies for Tamiflu. The CDC has been issuing guidelines and for many, many years has been trying to discourage this kind of behavior among physicians. I just wonder what you can say about past and current campaigns on that front.

Anne Schuchat: You know, appropriate use of antibiotics and antiviral drugs is important. We want the medicines that we have to work when we need them and overuse or abuse of these medicines can contribute to resistance developing in some of the microbes. With the antiviral drugs that have been developed for influenza, the focus right now is on use and treatment and our guidance for this interim time, the H1N1 interim guidance focuses on treatment in persons who are presenting with severe illness or people with underlying medical conditions who might be at risk for a worst time for influenza, so, yes, we do think these are wonderful drugs to use appropriately, but the inappropriate use can contribute to resistance and to them not working when we really need them to.


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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

[AlaskaDenise]

Re: Canada: Farm worker with H1N1 may have infected pigs on Alberta farm

Commentary

http://www.recombinomics.com/News/05..._H1N1_H2S.html

Commentary

Swine H1N1 Transmision From Human to Swine

Recombinomics Commentary 07:10
June 3, 2009

The pigs in Alberta were thought to be infected by a farm worker who returned from Mexico on April 12 and began working on the farm two days later. Officials noticed the pigs had flu-like symptoms April 24, Evans said.

Approximately 10 percent of the 2,200 pigs on the farm have been infected, Evans said.

The above comments describe the transmission of the H1N1 swine flu from an infected farm worker to swine in Alberta, Canada. This efficient transmission from human to swine suggests that much of the speculation in the past week is overly optimistic.

The virus is swine, WHO newspeak notwithstanding, and contains six swine gene segments as well as a human PB1 and an avian PB2 that have been in swine for more than a decade. Therefore, although swine to swine transmission is not unexpected, the transmission from human to swine is striking. The H1N1 is called swine H1N1 for scientific reason. It is not a “nickname” as some media accounts mis-report, but a descriptive name that defines its normal host. The species differences in sequence are easily determined, and species jumps are rare, but can be deadly. Usually the virus replicates most effectively in its host species.

The jump to humans is cause for concern. The last time as swine flu jumped to human and was efficiently spread in the new host was in 1918.

The fact that the virus can jump from human to swine as well as swine to humans suggests this virus is not going to fade away. It has already moved into the southern hemisphere. Suspect cases have been reported in Brazil, Australia, and New Zealand, where the seasonal flu season is just beginning.

Co-circulation of human and swine H1N1 provide significant opportunities for adaptation to the human host via recombination. Two polymorphisms are already fixed in seasonal flu, H274Y for Tamiflu resistance, and E627K in PB2 which allows the virus to more efficiently replicate at lower temperatures.

These changes can lead to adaptation in humans, as well antiviral resistance. Therefore, the evolution of the H1N1 over the summer will be closely monitored. The current H1N1 has already acquired tandem human H1N1 polymorphism in HA, which may have led to the species jump from swine to human.

Thus, the efficient transmission from swine to human and vice versa, raises concerns that further adaptation to humans can lead to a fall pandemic similar to 1918. The species jump indicates the virus can adapt to a new host, and additional acquisitions over the summer continue to be a cause for concern.

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