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

[Giuseppe]

Re: 1,000 Members!!!

Vaccine. 2009 Oct 23;27(45):6317-23.

Structural basis for oseltamivir resistance of influenza viruses.

Collins PJ, Haire LF, Lin YP, Liu J, Russell RJ, Walker PA, Martin SR, Daniels RS, Gregory V, Skehel JJ, Gamblin SJ, Hay AJ. - MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

Oseltamivir, one of the two anti-neuraminidase drugs, is currently the most widely used drug against influenza. Resistance to the drug has occurred infrequently among different viruses in response to drug treatment, including A H5N1 viruses, but most notably has emerged among recently circulating A H1N1 viruses and has spread throughout the population in the absence of drug use. Crystal structures of enzyme-drug complexes, together with enzymatic properties, of mutants of H5N1 neuraminidase have provided explanations for high level oseltamivir resistance due to the common H275Y mutation, with retention of zanamivir susceptibility, and intermediate level resistance due to the N295S mutation. Complementation of enhanced NA activity due to a D344N mutation by the H275Y mutation suggests an explanation for the recent emergence and predominance of oseltamivir-resistant influenza A H1N1 viruses.

PMID: 19840667 [PubMed - in process]

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[sharon sanders]

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Tamiflu resistance in the prefecture's check

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2009年10月29日

October 29, 2009
<!-- ここから記事本文エリア --><table class="npic" width="1"><!-- Start of photo --><!--★★写真ここから★★--><!--★★写真ここまで★★--><!-- End of photo --></table><!-- google_ad_section_start(name=s1) --><!--★★本文ここから★★-->

横浜市は２８日、新型インフルエンザに感染した横浜市都筑区の男児（６）から、タミフルに耐性を示すウイル スが見つかったと発表した。

March 28, Yokohama, Tsuzuki-ku, Yokohama boy infected with pandemic influenza (6) and announced that the resistant virus was found in the full Tami.

男児はすでに回復している。

The boy has already recovered.

タミフルが効きにくくなる耐性ウイルスが確認されたのは、県内では初めて。

Resistant virus was confirmed the effectiveness of Tamiflu has become difficult, the first time in the prefecture.

全国で１２例目という。

That of 12 cases nationwide.

市健康安全課によると、男児は９月２３日、タミフルを処方された。

According to City Health and Safety Division, the boy on September 23, Tamiflu was prescribed.

症状の改善が見られないため２８日に別の医師を受診したところ、軽度の肺炎の疑いがあり入院し た。

Because no improvement of symptoms of 28 just another day of visits to doctors, were hospitalized with suspected pneumonia are mild.

２９日、遺伝子検査により新型インフルエンザ感染が確認されたという。

29, a new influenza infection was confirmed by genetic testing.

市衛生研究所の遺伝子解析で今月１６日、タミフル耐性の結果が出たため、国立感染症研究所が調査し、確認し た。

Genome Institute of Health in the city this month 16, showed a resistance to Tamiflu, the Infectious Diseases Institute survey confirmed.

市は「子どもは長い時間ウイルスが体内にあるので、一般的には体内でウイルスが変異したと考えられる」とし ている。

The city is "a virus in the body so the children a long time, is generally considered a mutant virus in the body" and that.

http://mytown.asahi.com/kanagawa/news.php?k_id=15000000910290003

[Treyfish]

Re: 1,000 Members!!!

.
<!-- end: .tools -->
<!-- end: .hd --><CITE class=vcard>By Amanda Gardner
HealthDay Reporter by Amanda Gardner
healthday Reporter </CITE>– <ABBR class=recenttimedate title=2009-10-29T11:02:53-0700>20 mins ago</ABBR>
<!-- end .byline -->THURSDAY, Oct. 29 (HealthDay News) -- U.S. researchers say they've spotted the first case of a Tamiflu-resistant H1N1 flu virus passing between two people -- raising the specter that more widespread resistance will render the antiviral drug less useful in combating the pandemic.

A second study found that children are still shedding H1N1 virus nearly two weeks after symptoms first appeared, although the lead author of that study emphasized that this is not synonymous with the virus being infectious for that long.

The H1N1 virus is spreading rapidly, although it has not changed from the typically mild illness observed last spring and summer, experts said at a press conference held Thursday at the Infectious Diseases Society of America's annual meeting in Philadelphia.

"We have the same [H1N1] disease from the spring and summer but just a lot more of it right now," said Rear Admiral Dr. Stephen Redd, director of the Influenza Coordination Unit at the U.S. Centers for Disease Control and Prevention.

"An increasing proportion of people are visiting doctors with influenza-like illness, the disease is widespread and we are seeing more deaths in children in particular, and we would expect that to continue as the number of cases increases," he said.

Antiviral drugs have been dispatched from the U.S. government stockpile to treat children, Redd added.

So far, almost all strains of H1N1 have responded to both oseltamivir (Tamiflu) and another antiviral, zanamivir (Relenza), while displaying resistance to amantadine, a drug in a different class. As a result, Tamiflu and Relenza have been used widely for both the prevention and treatment of H1N1.

However, in June and July of 2009, 65 campers and staff at a summer camp in North Carolina became ill with H1N1 and were treated with Tamiflu, while 600 other campers and staff took the antiviral to prevent the illness.

Two females who shared a cabin developed symptoms after starting on Tamiflu and were later found to have a virus with two viral mutations that rendered them resistant to the drug. The mutated virus was not found in other people tested.

What's troubling is that one of the females appears to have transmitted the mutated virus to her cabin mate. "It is likely that this resistant virus was passed from one camper to the other based on the timing between the illnesses and 2 genetic mutations found in the virus in both campers," explained Dr. Natalie Janine Dailey, lead author of the study and an epidemic intelligence service officer with the North Carolina Division of Public Health Communicable Disease Branch. "A small number of cases of oseltamivir-resistant have been seen in the U.S. so far, but these were the first cases reported in otherwise healthy individuals and the first which appeared to have spread from one person to another."

"This suggests that using oseltamivir to prevent influenza in healthy people may increase the risk of resistance," she said. "If resistance became widespread, oseltamivir would no longer be effective."

With this in mind, Dailey believes that the H1N1 vaccine, instead of antivirals, should be used for prevention as it becomes available, although treatment with antivirals should begin immediately in people who are hospitalized or who are at high risk, such as pregnant women, children under the age of 2 and people with underlying health conditions.

A second team of researchers looked at 26 elementary-school students in Pennsylvania and their household contacts who had tested positive for H1N1 to assess virus "shedding patterns."

"We found the median duration of shedding to be six days, with a minimum of one day and a maximum of 13 days," said study author Dr. Achuyt Bhattarai, an epidemic intelligence service officer with the CDC.

The same numbers were found in children over the age of 9, representing a longer time frame that is typically seen in adults. Bhattarai said, "this is consistent with earlier studies of seasonal flu."

This and future data should help officials decide when children should be allowed to return to school.

The teleconference also addressed the current delays and shortages in available H1N1 vaccine.

"We're all disappointed and frustrated by the current situation with the vaccine supply but we need to recognize we're not alone. The situation is true globally," said Dr. Bruce Gellin, director of the U.S. Department of Health and Human Services' National Vaccine Program.
The situation points up problems in the current vaccine production system, which relies on eggs as incubators of the virus.
"There's certainly lots of room for improvement in these systems," Gellin said. "Some of the early issues are resolving, particularly real difficulties with yield and variability among manufacturers. Some yields were half what was expected, some were less than half. That was a large part of the issue. We're encouraged that many of these things are being optimized and it's the same with the seasonal vaccine every year. We continue to do tune-ups which are going to translate to more doses over the coming weeks and hopefully then, the lines will get shorter."http://news.yahoo.com/s/hsn/20091029...ontopersoninus

[Giuseppe]

Re: 1,000 Members!!!

Oseltamivir-resistant pandemic (H1N1) 2009 influenza virus, October 2009 (Weekly Epidemiological Record, edited)

[Original Full PDF Document: LINK. EDITED.]

Weekly epidemiological record - 30 october 2009, 84th year - No. 44, 2009, 84, 453?468 - http://www.who.int/wer

Oseltamivir-resistant pandemic (H1N1) 2009 influenza virus, October 2009


The earliest isolates of pandemic (H1N1) 2009 influenza virus were shown to be sensitive to the influenza virus neuraminidase inhibitors oseltamivir and zanamivir but resistant to the M2 inhibitors amantadine and rimantadine.1 WHO and other organizations have developed guidelines for the use of antiviral drugs in the clinical management of pandemic (H1N1) 2009 influenza virus infections on the basis of these data.2,3

Since the initial characterization of pandemic (H1N1) 2009 influenza virus in March 2009, laboratories worldwide have been monitoring its susceptibility to neuraminidase inhibitors. The purpose of this article is to summarize current knowledge on oseltamivir-resistant pandemic (H1N1) 2009 influenza viruses and to highlight actions and recommendations that can minimize the emergence and transmission of resistant viruses. The information contained in this report is derived from published case reports, notifications to WHO under the International Health Regulations (2005), and analyses by WHO?s collaborating centres and other laboratories. This information is subject to change as case investigations and epidemiological investigations are completed.


Description of cases of oseltamivir resistance

WHO received the first report of an oseltamivir-resistant pandemic (H1N1) 2009 virus in July 2009. As of 22 October 2009, a total of 39 cases had been described, 7 of which are still under investigation.

In general, cases of oseltamivir resistance have been geographically dispersed, sporadic and not linked to one another. Extensive susceptibility testing of clinical samples and virus isolates suggests that such viruses are not circulating at a community level (Table 1).

The 32 isolates for which information is available share several features:

• all have a mutation in the neuraminidase gene resulting in an amino acid change from histidine to tyrosine at amino acid 275 (referred to as H275Y). Where enzyme-inhibition assays have been undertaken, the viruses have been shown to be resistant to oseltamivir, but they remain sensitive to zanamivir;
• none of these viruses has arisen as a result of reassortment between the pandemic (H1N1) 2009 influenza virus and any other influenza virus, including the seasonal H1N1 strain;
• there has been no evidence of transmission of these viruses beyond the immediate setting in which they were discovered;
• except for cases arising in severely immunosuppressed patients and 2 children who developed pneumonia (discussed below), all the patients with oseltamivir-resistant virus infection had typical influenza-like illness and all have recovered without complication.

Of these 32 reported cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus, 16 were associated with the treatment of influenza, including in 7 immunosuppressed patients; 13 with chemoprophylaxis (usually following known exposure to another infected person); and 3 had no history of oseltamivir treatment or prophylaxis.


Immunosuppressed patients

Seven cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus were associated with treatment of immunosuppressed patients. Of these, 4 were in the United States, 2 in the United Kingdom and 1 in Australia. Reports of 2 of the cases from the United States have been published in detail.4 Although both cases were from the same city, the patients were treated in different hospitals and were not epidemiologically linked. Both patients received extended or repeated courses of treatment with oseltamivir; despite this, both continued to shed virus. Virus in samples taken early in the course of the influenza infection was sensitive to oseltamivir, indicating that the resistant viruses emerged during the course of treatment.

The emergence of drug-resistant influenza viruses in severely immunosuppressed or immunocompromised patients undergoing antiviral treatment is not unexpected and has been well documented.5 Virus replication can persist in such patients for prolonged periods of time despite antiviral treatment, creating an environment in which drug-resistant viruses can readily be selected. This phenomenon has been observed for all antiviral drugs for influenza, including zanamivir, to which resistant isolates have not arisen under other clinical circumstances.6


Chemoprophylaxis

Most of the 13 cases associated with prophylaxis have been isolated events with no epidemiological linkages. Two linked cases have been reported in detail.7 Two girls, staying in the same cabin at a summer camp in North Carolina (USA), developed influenzalike illness 3 days apart. The viruses had the H275Y mutation as well as another mutation in the neuraminidase gene (I223V). There are insufficient data to determine whether the resistant virus in these cases arose independently in the 2 individuals, was transmitted from a common source or passed from one girl to the other.

Of the 11 remaining cases associated with oseltamivir prophylaxis, 5 were isolated in Japan, 2 from the United States and 1 each from Canada, China and the Special Administrative Region (SAR) of Hong Kong, and Denmark. The association of oseltamivir- resistant influenza viruses with chemoprophylaxis has not been documented previously and, although these cases are few in number, this is a concern. In 2 clinical studies of oseltamivir?s effectiveness in preventing influenza among household contacts, no oseltamivir-resistant variants were detected.8,9

The number of cases of influenza infection occurring during prophylaxis in these studies was 338 and 11.9

There are 2 possible mechanisms for emergence and detection of resistance during prophylaxis. First, a resistant virus may be transmitted from a prior contact, especially if that contact was being treated with oseltamivir. This phenomenon has been well documented for the M2 inhibitor rimantadine, where the emergence of a drug-resistant virus in treated index cases and its subsequent onward transmission contributed to the failure of prophylaxis in contacts.10 However, such a scenario does not account for all 13 cases associated with post-exposure prophylaxis. In 1 case, the prior contact had been treated with zanamivir, not oseltamivir, while in some of the other cases there is no recorded use of oseltamivir in the presumed prior contacts. In contrast to the situation described for rimantadine,10 treating index cases with oseltamivir did not result in the emergence or transmission of oseltamivir-resistant virus during household studies.9

The second possible mechanism is for the mutated virus to originate during low-level replication in the individual taking oseltamivir prophylaxis (either prior to, or during use of, the antiviral). The lower frequency of administration of oseltamivir for prophylaxis (once per day versus twice daily for treatment) may be a contributing factor, as has been suggested previously.5

In all cases where samples have been available from the prior contact case (n=6), they have been shown to comprise oseltamivir-sensitive virus, indicating that the resistant virus has likely arisen within the case cluster.

In all of these prophylaxis-associated cases, the illness was typical influenza that resolved without complication.

Some patients received no further treatment, while others started a new treatment course of oseltamivir.

Two were treated with zanamivir.


Treatment

Of the 32 cases, 9 emerged during oseltamivir treatment in immunocompetent patients, 3 of whom were in Japan, 3 in Viet Nam11 and 1 each in Canada and Singapore. The point of contact in Taipei also reported 1 case. Where data are available, (n=6) the virus present in samples taken before the start of treatment was sensitive to oseltamivir.

In 2 cases, the oseltamivir-resistant viruses were discovered as a result of repeated sampling due to prolonged illness. One patient was being treated for bacterial pneumonia, which responded to antibiotics, and the second had viral pneumonia, which resolved following a second course of oseltamivir.


No association with antiviral use

Three cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus were detected in patients who had not taken oseltamivir for treatment or prophylaxis. One case was reported from Japan and 2 from Hong Kong SAR, although there is no epidemiological link between them. The first was in a traveller returning from San Francisco (USA).12 The source of infection in this case remains unknown. The second was from 1 of 3 contacts of a patient being treated with oseltamivir. Viruses from the other 2 contacts who developed influenza-like illness before and after the index case remained sensitive to oseltamivir.


Implications

Detection and investigation of cases

The risk of resistance is considered higher in patients who have prolonged illness (particularly those with severely compromised or suppressed immune systems) and who have received antiviral treatment for an extended duration and still test positive for the virus. The risk of resistance is also considered higher in people who receive oseltamivir for post-exposure prophylaxis following exposure to another person with influenza and who then develop illness despite taking oseltamivir. In both of these clinical situations (prolonged influenza illness and chemoprophylaxis failure), health-care staff should have a high level of suspicion that oseltamivir resistance has developed. A laboratory investigation should be undertaken to determine whether resistant virus is present. Clinical specimens or virus isolates for virological investigation should be sent to a specialized laboratory capable of performing antiviral susceptibility testing, such as one of the WHO collaborating centres for influenza13 or a national influenza centre.14

Samples that should be considered for testing include those from patients who have had >5 days of antiviral treatment and still have unresolved or complicated illness, and patients who present with influenza-like illness despite taking antiviral chemoprophylaxis.

When a drug-resistant virus is detected, WHO recommends that an epidemiological investigation be undertaken to determine the source of infection and whether onward transmission of the resistant virus has occurred.

This investigation should include contact tracing and virological investigation. In addition, community surveillance for oseltamivir-resistant pandemic (H1N1) 2009 influenza virus strains should be enhanced.

The detection of oseltamivir-resistant viruses to date has been strongly biased by the sampling strategies used for pandemic surveillance. The overwhelming majority of samples are taken on initial clinical presentation; relatively few examples of post-treatment specimens have been collected. More data need to be collected on a case-by-case basis and through prospective studies to better assess the risk of oseltamivir-resistant virus developing during treatment of both severe, prolonged illness and uncomplicated illness in the community.


Clinical case management

In general, WHO does not recommend using antiviral drugs for prophylaxis against pandemic (H1N1) 2009 influenza. For people who have been exposed to an infected person and who are at a higher risk of developing severe or complicated illness, an alternative option is to closely monitor them for symptoms and promptly administer antiviral treatment if symptoms develop. This option has 2 potential benefits. First, it reduces the risk that a suboptimal dose may be used in patients already infected at the time chemoprophylaxis starts (as may have been the case for at least 1 of the patients described here).5 Second, it ensures that treatment is administered only when needed.

WHO does not recommend using a particular antiviral in cases in whom the virus is known to be or is highly likely to be resistant to it.2 For this reason, zanamivir is the treatment of choice for patients who become ill while on oseltamivir prophylaxis, and it should also be considered for patients who develop prolonged viral illness despite treatment with oseltamivir. Since all of the oseltamivir-resistant pandemic (H1N1) 2009 influenza viruses characterized to date remain sensitive to zanamivir, it remains a therapeutic alternative for all patients with serious illness caused by oseltamivir-resistant pandemic (H1N1) 2009 influenza virus.

So far, there is no evidence of sustained transmission of these oseltamivir-resistant pandemic (H1N1) 2009 viruses; there is, however, strong suspicion that very limited transmission occured among close contacts in some of these cases. Where drug-resistant virus is suspected, appropriate infection-control measures should be reinforced to prevent spread.15


Conclusions

Growing international experience in the treatment of pandemic (H1N1) 2009 influenza virus infections underscores the importance of early treatment with the antiviral drugs oseltamivir or zanamivir. The experience of clinicians (including those who have treated severe cases of pandemic influenza) and national authorities suggests that prompt administration of these drugs following the onset of symptoms reduces the risk of complications and may also improve the clinical outcome in patients with severe disease.

This underscores the need to protect the effectiveness of these drugs by minimizing the occurrence and impact of drug resistance. WHO expects that these medicines will, and should continue to, be used in accordance with their respective guidelines,10 but urges clinicians and public health authorities to be alert to the emergence of oseltamivir-resistant viruses that might have an impact on patient care and public health.

The relatively small number of sporadic cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus recorded so far merits close monitoring but does not constitute a public health threat at this time. There is no evidence that such viruses are circulating at a community level, nor have they been associated with altered or unexpected severity of disease. There is, however, a need to monitor vigilantly for changes in transmissibility or pathogenicity, which may not be evident on a case-by-case basis. For this reason, WHO urges all clinicians, laboratories and agencies to promptly notify WHO of all cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus and to provide the relevant clinical and epidemiological data.


Acknowledgements

WHO thanks the collaborating centres for influenza and other national influenza centres for providing information on oseltamivir-resistant viruses.


[Table 1 Geographical distribution of oseltamivir-resistant pandemic (H1N1) 2009 influenza viruses, 22 October 2009]

[Isolates ? WHO Region - Number of oseltamivir-resistant isolates reported - Number of isolates or clinical specimens tested for antiviral susceptibility (a)]

• African 0 -71
• Eastern Mediterranean 0 - 45
• European 4 - 2313
• Americas 16 - 6160
• South-East Asia 0 - 20
• Western Pacific 19 - 3900

(a) Data compiled from information provided by WHO collaborating centres for reference and research on influenza, national influenza centres, and from published reports from national health agencies.


Reference:

1. Drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. Morbidity and Mortality Weekly Report, 2009, 58:433?435 (LINK, accessed October 2009).
2. WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza and other influenza viruses. Geneva, World Health Organization, 2009 (LINK, accessed October 2009).
3. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for the 2009?2010 season. Atlanta, GA, 2009 (LINK, accessed October 2009).
4. Oseltamivir-resistant novel influenza A(H1N1) virus infection in two immunosuppressed patients. Morbidity and Mortality Weekly Report, 2009, 58:893?896 (LINK, accessed October 2009).
5. Hayden FG. Antiviral resistance in influenza viruses: clinical and epidemiological aspects. In: Mayers DL, ed. Antimicrobial drug resistance. New York, Humana Press, 2009:1011?1034.
6. Gubareva LV et al. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. Journal of Infectious Diseases, 1998, 178:1257?1262.
7. Oseltamivir-resistant 2009 pandemic influenza (H1N1) virus infection in two summer campers receiving prophylaxis ? North Carolina, 2009. Morbidity and Mortality Weekly Report, 2009, 58:969?972 (LINK, accessed October 2009).
8. Welliver R et al. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. Journal of the American Medical Association, 2001, 285:748?754.
9. Hayden, FG et al. Management of influenza in households: a prospective randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. Journal of Infectious Diseases, 2004, 189:440?449.
10. Hayden FG et al. Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. New England Journal of Medicine, 1989, 321:1696?1702.
11. Van Doorn R. Influenza pandemic (H1N1) 2009 (68): Viet Nam, virus clearance. Pro-Med mail (Archive number 20091011.3519 11 October 2009 (available from LINK, accessed October 2009).
12. Leung TWC et al. Detection of an oseltamivir-resistant pandemic influenza A/H1N1 virus in Hong Kong. Journal of Clinical Virology, 2009, 46:298?299.
13. For more information, see LINK
14. For more information, see LINK
15. For more information, see LINK

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[Giuseppe]

Re: 1,000 Members!!!

Biochem Biophys Res Commun. 2009 Oct 20. [Epub ahead of print]

Amantadine- and oseltamivir-resistant variants of influenza A viruses in Thailand.

Bai GR, Chittaganpitch M, Kanai Y, Li YG, Auwanit W, Ikuta K, Sawanpanyalert P. - Section of Viral Infections, Thailand-Japan Research Collaboration Center on Emerging and Re-emerging Infections (RCC-ERI), Nonthaburi 11000, Thailand; Department of Virology, Research Institute for Microbial Diseases, Osaka University, Yamada-oka 3-1, Suita, Osaka 565-0871, Japan.


Amantadine and oseltamivir are used to treat influenza A virus infections; however, resistance to these drugs has been widely reported throughout the world. In this study, the frequency and genetic characteristics of the drug-resistant influenza A viruses that circulated in Thailand from 2006 to 2008 were investigated. The nucleotide sequences of the NA and M2 genes were elucidated in order to identify mutations that confer oseltamivir- and amantadine-resistant phenotypes, respectively. A total of 66 influenza A viruses including 44 H1N1 and 22 H3N2 subtypes isolated in Bangkok and 13 provinces of Thailand from 2006 to 2008 were analyzed. Our results demonstrated that seven out of 32 (22%) of the H1N1 viruses isolated in 2006 in Thailand carried the amino acid S31N substitution, which confers amantadine-resistance, although no isolates in 2007 or 2008 possessed the mutation. In the cases of oseltamivir-resistance, four of 10 (40%) of the H1N1 viruses isolated in 2008 were predicted to be resistant to the drug, although none of the 34 viruses isolated in 2006 or 2007 were predicted to be resistant. Surprisingly, all 9 H3N2 viruses isolated in 2008 appeared to be resistant to the amantadine and none were resistant in 2006 or 2007. Phylogenetic analysis based on the HA, M, and NA genes demonstrated that the amantadine-resistant H1N1 isolates had been produced by genetic reassortment. All of the amantadine-resistant H3N2 viruses were clustered in one of these three genes and possessed double mutations of S193F and D225N in the HA gene.

PMID: 19850010 [PubMed - as supplied by publisher]
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[Gert van der Hoek]

Re: 1,000 Members!!!

machinetranslated, edited

Swine flu patient resistant to Tamiflu

GRONINGEN - In the University Hospital Groningen a swine flu patient was found to be resistant to the virus inhibitor Tamiflu. This is the first case in the Netherlands. Worldwide, only 32 cases of Tamiflu resistance were found.

The patient was hosptitalised last week in the UMCG. Despite treatment with Tamiflu the swine flu did not disappear, after research the resistance
could be confirmed.

The UMCG with National Institute of Mental Health and Public Health and Environment (RIVM) research to anyone in contact with the patient.
This to avoid spread f the resistant variant .

Tuesday, 03/11/2009

http://www.oogtv.nl/ontwikkelen/php/home.php?subaction=showfull&id=13715

[Francoise Ramona]

Re: 1,000 Members!!!

Grippe H1N1 : premier cas de r?sistance au Tamiflu aux Pays-Bas
(AFP) ?
LA HAYE ? Un premier cas de r?sistance au Tamiflu, principal antiviral utilis? contre la grippe H1N1, a ?t? constat? aux Pays-Bas, a annonc? mercredi l'Institut n?erlandais pour la sant? et l'environnement (RIVM).
"Un patient pr?sentant de graves sympt?mes de la grippe a ?t? infect? par un virus H1N1 r?sistant ? l'oseltamivir", commercialis? sous le nom de Tamiflu, a pr?cis? le RIVM dans un communiqu?.
"C'est la premi?re fois aux Pays-Bas qu'un virus H1N1 r?siste ? l'oseltamivir", a-t-il ajout?.
Le virus r?sistant de la grippe "se transmet moins rapidement", a expliqu? ? l'AFP une porte-parole du RIVM, Jessica Grootenboer. "Il n'y a absolument aucune raison de paniquer", a-t-elle insist?.
L'Organisation mondiale de la sant? (OMS) a recens? ? ce jour 39 cas de r?sistance dans le monde, selon le RIVM.
Dix personnes sont mortes des suites d'une infection au virus H1N1 aux Pays-Bas, qui sont confront?s ? une "petite ?pid?mie", d'apr?s le RIVM. Un millier de personnes meurent chaque ann?e de la grippe saisonni?re dans le pays.
La grippe pand?mique H1N1 a fait "au moins 5.700 morts" depuis l'apparition de la maladie en mars-avril, selon un bilan de l'OMS rendu public le 30 octobre

[Gert van der Hoek]

Re: Netherlands: First case of swine flu resistance to Tamiflu

google translated

Tamiflu-resistant flu virus did not spread

GRONINGEN - The Tamiflu resistant swine flu virus did not spread , says Jan Wilschut virologist at the University Medical Center Groningen.

Wednesday it was announced that the variant was detected in one patient in the UMCG. The man is in isolation in the intensive care unit of the hospital. He is in stable condition. The man suffers from an immune disorder, so the virus could easily mutate and multiply. By Tamiflu treatment the resistant strain of the virus prevailed. Wilschut expects that the new variant is milder.

The resistance has nothing to do with the vaccination against the Mexican flu. Wilschut press people at heart when they take the vaccine within the target designated by the government fall.

http://www.rtvnoord.nl/nieuws/indexwm.asp?actie=totaalbericht&pid=86328

[sharon sanders]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

"...China news agency, Hong Kong, November 6 (Reporter Xiao Ping) - Found in pigs in Hong Kong on the 5th for the first time just because "people pass pig" infected with a stream, and also confirmed the fifth case occurred in Hong Kong A flow of drug-resistant cases of influenza A H1N1 influenza re-emergence of concern changes, indicating a flow of the epidemic in Hong Kong can not be ignored..."

http://www.chinanews.com.cn/ga/news/2009/11-06/1952030.shtml

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

according to latest WER from WHO -

"....cases associated with oseltamivir prophylaxis, 5 were isolated in Japan, 2 from the United States and 1 each from Canada, China and the Special Administrative Region (SAR) of Hong Kong..."

http://www.flutrackers.com/forum/showthread.php?p=311967

[sharon sanders]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

hat tip Makoto -

<table border="0" cellpadding="10" cellspacing="0" width="100%"><tbody><tr><td class="j25" bgcolor="#ffffff">Tami Shiga full immunity from the 6-year-old girl

国内１３例目

13 cases of domestic </td></tr><tr valign="top"><td class="j14">

滋賀県は５日、新型インフルエンザを発症した県内の女児（６）から採取したウイルスに、治療薬タミフルへの 耐性を示す遺伝子変異が確認されたと発表した。

Shiga Prefecture, the prefecture girls who develop pandemic influenza (6) taken from the virus, and its mutation was found to be resistant to Tamiflu treatment.

厚生労働省によると、タミフル耐性ウイルスの確認は国内１３例目。

According to the Ministry of Health, confirmed in 13 of 13 domestic cases of Tamiflu-resistant virus.

県は「タミフル服用後に体内でウイルスが変異した」とみている。

County, "the mutant virus in the body after taking Tamiflu," the official said.

県によると、女児は１０月１４日に入院しタミフルを処方したが、１９日に再び高熱となり、治療薬をリレンザ に切り替えた。

According to the county on Oct. 14 girls were admitted to prescribe Tamiflu, 19 and again on Wednesday with high fever, switched to the drug Relenza.

既に回復し、周囲への感染拡大は確認されていない。

The recovery has already spread to the environment has not been confirmed.

（共同通信）

(Kyodo News)

http://translate.google.com/translate?langpair=auto|en&u=http://translate.google.co.jp/translate?prev=hp&hl=ja&js=y&u=http://www.kyoto-np.co.jp/article.php?mid=P2009110500236%26genre=C4%26area=S00&sl=ja&tl=fr&history_state0=&swap=1

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[Tonka]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

http://health.usnews.com/articles/health/healthday/2009/11/11/tamiflu-resistant-swine-flu-found-in-canadian.html

Tamiflu-Resistant Swine Flu Found in Canadian Father
Latest case underscores need to use the antiviral properly, experts say
Posted November 11, 2009
By Steven Reinberg
HealthDay Reporter

WEDNESDAY, Nov. 11 (HealthDay News) -- Researchers report that a father in a Canadian family developed a strain of the H1N1 swine flu that was resistant to the antiviral Tamiflu, after being given the drug to prevent the disease.

To date, the World Health Organization has reported some 45 cases of H1N1 swine flu that were resistant to Tamiflu, which is why the U.S. Centers for Disease Control and Prevention and others caution against using Tamiflu to prevent the disease in people who are symptomless.

"We have a person who was taking post-exposure prophylaxis with Tamiflu, probably at the time he was already incubating the virus, but before symptoms developed," said lead researcher Dr. Guy Boivin, of the Centre Hospitalier Universitaire de Quebec, in Quebec.

According to the report, when the father's 13-year-old asthmatic son was hospitalized with H1N1 swine flu, other family members were given a reduced dose of Tamiflu to prevent them from getting the disease. These included the 59-year-old father, who suffered from chronic obstructive pulmonary disease (COPD), his 50-year-old wife and two teenage daughters.

Within a day the father developed flu symptoms, but he did not see a doctor for eight days. A test of his virus showed that it was resistant to Tamiflu. None of the other family members developed flu. The father recovered from the flu, according to the report in the Nov. 11 online edition of the New England Journal of Medicine.

The mutated strain of H1N1 swine flu remained susceptible to another antiviral, Relenza, Boivin added.

The family's experience was a good setting for resistance to emerge, Boivin said. When someone has the H1N1 swine flu, Tamiflu is given twice a day for five days. But when the drug is used to prevent the disease, it is given only once a day for 10 days, he explained.

Since the father was most likely already infected with swine flu, the dose of Tamiflu he received was ineffective at stopping the virus and low enough to allow the virus to develop resistance to the drug, Boivin said.

"In that context, Tamiflu is a risk factor for the emergence of resistance," he explained.

Boivin said that one-third of the known cases of H1N1 virus resistant to Tamiflu have been among people already exposed to the pandemic flu. "Another third emerged in imuno-compromised [weakened immune system] patients who received prolonged therapy with Tamiflu," he said.

The mutation of the H1N1 virus that caused its resistance to Tamiflu was the same one that was found in seasonal flu resistant to the drug. Last year, one strain of the seasonal flu was resistant to Tamiflu, Boivin said.

"You should be careful when you use post-exposure prophylaxis," Boivin said. In most cases, Tamiflu should be reserved for early treatment of flu when symptoms develop, he said.

Dr. Marc Siegel, an internist and associate professor of medicine at New York University Langone Medical Center in New York City, said that "Tamiflu prophylaxis given to the wrong people can increase your risk of a resistant strain developing -- and that's the last thing we need."

Siegel thinks, however, that Tamiflu used correctly can help prevent people from getting the flu, especially when the vaccine is in short supply.

"In the absence of available vaccine, one of the ways you can cut down on the spread of H1N1, to people you feel are at risk, is with the proper use of Tamiflu prophylaxis," he said.

Another expert, Dr. Pascal James Imperato, dean and Distinguished Service Professor of the School of Public Health at SUNY Downstate Medical Center in Brooklyn, N.Y., said that "based on our current knowledge, it appears that resistance of influenza viruses to the anti-influenza drug Tamiflu occurs in a setting of drug overuse."

This reported case from Canada underscores the need to limit the use of Tamiflu in people who aren't displaying flu symptoms, Imperato said.

"It also points out the need for increasing the dose of the drug to therapeutic levels in anyone who develops symptoms of influenza while on lower post-exposure prophylactic doses," he said

[estacion]

Tamiflu resistance in A/H1N1 flu - historical compilation of news

Mueren por gripe A dos ni?as de cuatro y 13 a?os en Catalu?a
Las menores no ten?an patolog?as previas que pudieran haber agravado la enfermedad, por lo que se trata de los dos primeros casos en Espa?a de pacientes sanos que pierdan la vida a causa del virus H1N1

COLPISA - 14/11/2009 17:36

La peque?a de cuatro a?os resid?a en el Prat de Llobregat y falleci? el jueves de forma repentina, igual que la otra menor, de 13 a?os, que viv?a en Barcelona. El Departamento catal?n de la Salud confirm? que ninguna de las dos ni?as padec?a "aparentemente problemas respiratorios, ni tampoco ten?an malformaciones cardiovasculares, ni siquiera obesidad", como casi todos los fallecidos por gripe A hasta la fecha.

Salud se?al? este s?bado que los m?dicos de los dos centros sanitarios donde perdieron la vida las ni?as investigan las causas de la muerte y sobre todo por qu? ninguna de las dos hab?a respondido a los antivirales que se les suministraron durante toda la semana.

Ante la gravedad del asunto, Salud y el departamento de Educaci?n han puesto en marcha de forma urgente los protocolos de informaci?n y seguimiento entre los padres de los alumnos de los centros donde estudiaban las menores fallecidas. Los centros escolares, no obstante, se han mantenido en el anonimato para no generar m?s alarma.

A estos dos casos se une el fallecimiento, tambi?n el jueves, de la primera menor en Catalu?a, en este caso una ni?a de 12 a?os de Castelldefels. Los profesores y m?dicos de los tres centros donde estaban escolarizadas las ni?as se esfuerzan desde el jueves en tranquilizar a los padres, seg?n inform? este s?bado el diario 'Avui'.

La incidencia de la gripe A en Catalu?a se ha disparado con la llegada del fr?o, la pasada semana. Al margen de las v?ctimas mortales, el n?mero de afectados se ha duplicado. Por ello, la consejera de Salud, Marina Geli, insiste constantemente en que "no hay que confiarse, ya que detecto una cierta relajaci?n entre la poblaci?n". Las muertes sin factores de riesgo previos ten?an que llegar, seg?n aseguraban tambi?n con cierta asiduidad los expertos. Y lo han hecho entre los ni?os no porque sean m?s vulnerables, sino porque la gripe est? masivamente extendida en esta franja de edad.

En Catalu?a han muerto por gripe A 14 personas, todas ellas con problemas y patolog?as previas y la mayor?a de edad avanzada, salvo las tres ?ltimas ni?as.

La campa?a de vacunaci?n comienza el lunes. Todo el personal sanitario ha sido convocado para que se vacunen no s?lo para su propia protecci?n, sino para evitar contagios a sus pacientes. Tambi?n estar? disponible para quien tenga dolencias cr?nicas y para mujeres embarazadas. Salud no ha incluido a los menores entre los grupos de riesgo a quienes recomienda vacunarse.

Fuente: Diari de Tarragona

http://www.diaridetarragona.com/panorama/036432/mueren/gripe/ninas/cuatro/13/anos/barcelona

Die from influenza A two children of four and 13 years in Catalonia
The minors had previous pathologies that could have aggravated the disease, so this is the first two cases of healthy patients in Spain who lose their lives because of the H1N1 virus

COLPISA - 14/11/2009 17:36

The small four-year resident in El Prat de Llobregat and died suddenly on Thursday, as the other minor, aged 13, who lived in Barcelona. The Catalan Health Department has confirmed that none of the two girls suffered from "apparent respiratory problems, nor had cardiovascular malformations, even obesity," as almost all deaths from influenza to date.

Health said Saturday that doctors in the two health centers where girls lost their lives researching the causes of death and especially why none of them had responded to antivirals that were provided throughout the week.

Given the seriousness of the case, Health and Education Department have launched an urgent information protocols and monitoring among parents of students in schools where the children studied who died. Schools, however, have remained anonymous to generate no more alarm.

These two cases are compounded by the death, also on Thursday, the first child in Catalonia, in this case a girl of 12 years of Castelldefels. The professors and doctors from the three schools where girls were struggling in school since Thursday to reassure parents, according to the newspaper reported Saturday 'Avui'.

The incidence of influenza A in Catalonia has been triggered by the arrival of the cold last week. Besides the fatalities, the number of affected children has doubled. Therefore, the Minister of Health, Marina Geli, constantly insists that "there must be trusted, and I detect a certain relaxation in the population. The deaths without previous risk factors had to come as well with some regularity claimed experts. They have done among children not because they are most vulnerable, but because flu is massively extended at this age.

In Catalonia has died of bird 14 people, all with problems and previous pathologies and most elderly, except the last three girls.

The vaccination campaign starts Monday. All healthcare staff have been subpoenaed to vaccinate not only for their own protection, but to avoid infecting their patients. It will also be available for anyone with chronic conditions and for pregnant women. Health has not included children between the risk groups who get immunized.

Source: Diari de Tarragona

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[Gert van der Hoek]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

Drug-resistant swine flu found

Published Date: 16 November 2009

SCOTLAND could be facing a drug-resistant strain of swine flu after two patients failed to respond to treatment.

One patient in the Lothians and another believed to be from Fife failed to respond to Tamiflu, one of the only treatments for the H1N1 virus.

Doctors around the world have seen a handful of cases where the virus has mutated to develop resistance to the drug.

NHS Lothian confirmed it has seen one patient with Tamiflu-resistant swine flu.

A spokesman for the Scottish Government said: "We are aware of Tamiflu resistance in two Scottish H1N1 patients.

"We have asked Health Protection Scotland to monitor the situation closely."

http://news.scotsman.com/health/Drugresistant-swine-flu-found.5826882.jp

[mixin]

Re: Tamiflu resistance in A/H1N1 flu - historical compilation of news

Update 74 Nov. 13, 2009

The WHO: To date, 52 oseltamivir resistant pandemic H1N1 influenza viruses have been detected and characterized worldwide. All of these viruses show the same H275Y mutation. All these viruses remain sensitive to zanamivir. Worldwide, more than 10,000 clinical specimens (samples and isolates) of the pandemic H1N1 virus have been tested and found to be sensitive to oseltamivir.

http://www.who.int/csr/disease/swineflu/laboratory13_11_2009/en/index.html