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

Re: Japan Reports Tamiflu-Resistant H1N1 Influenza Case

Re: Japan Reports Tamiflu-Resistant H1N1 Influenza Case




Oseltamivir in Osaka Press Release (Products: Tamiflu) for the avian flu virus was detected indicating the mutant gene from Osaka ○ resistance, indicating that the H275Y Tamiflu-resistant isolates with a mutated avian flu virus genes were reported on the Summary, as attached, to provide information.

○ The virus, now, WHO, National Institute of Infectious Diseases in collaboration center, is scheduled to be implemented and drug susceptibility testing.

In Japan, about 500 nationwide surveillance by the virus are carried out in cooperation with the medical institution where the future for the new influenza virus, and not knowing what is expected from the drug-resistant gene mutation .

○ In addition, gene mutations that are resistant to Tamiflu, the severity of the virus (pathogenic) is a direct influence is not.

Oseltamivir in Osaka (product name: Tamiflu) Description of a new flu virus was detected in a mutant gene be resistant.

○ Description of patients from patients living in Osaka, with the avian flu virus resistant to Tamiflu indicates the gene mutation.

If this is to begin on May 15, May 17, concentrated contacts of patients confirmed that the avian flu patients.

○ 5 prophylactic administration of the drug from the Monday 18 days (10 days) were made,

May 24 with a fever on May 28 to contact the Counseling Center, fever, and on May 29 in the diagnosis of avian flu.

Sunday May 29 from 5-day Zanamivir (Product name: Relenza) treated by recovery.

The samples were collected from patients in the Osaka Prefectural Institute of Public Health,

After separation of the virus culture, the gene sequence was confirmed, June 18,

Be resistant to Tamiflu H275Y mutant gene was confirmed.

○ In addition, the May 15 analysis has been similar for patients who develop the virus strain, indicating the mutant gene was confirmed Tamiflu resistant.

○ then spread to the surrounding, including the Family is not approved.

○ neuraminidase was carried out by the Osaka Prefectural Institute of Public Health (NA) part of the gene (250bp) and the analysis of mutations in the gene (point mutation)(A/H1N1; mutation) which arises, seasonal influenza (A/H1N1;Soviet-type) which is caused by hybridization of the year.


○ 6 Monday 30 of the European Center for Disease Control (ECDC) said, in Denmark, as the avian flu patients contact the rich history of travel abroad, who had prophylactic administration of Tamiflu, the drug administration 5 The tests for flu-like symptoms after day, is found to be infected with avian flu.

Then I check the status of drug-resistant, and has been recognized that drug-resistant mutation.

○ For this case, ECDC will never be shown to isolate the virus-resistant gene mutations full TAMI patients are given Tamiflu, a phenomenon that is observed in the seasonal flu, Tamiflu will be resistant For influenza virus, has not been confirmed to be infected by the surrounding public health risk and are not considered.

※ In addition, ECDC's report, in Japan, found that children infected with seasonal flu are being treated by a full TAMI, the 16

The virus was separated from the TAMI shows the percent of full immunity, the infection is introduced, studies that were low.
 
Re: Japan Reports Tamiflu-Resistant H1N1 Influenza Case

Re: Japan Reports Tamiflu-Resistant H1N1 Influenza Case

<TABLE class=lan18 border=0 cellSpacing=0 cellPadding=0 width="97%" align=center><TBODY><TR><TD class=hei22 height=25 vAlign=bottom>Japan reports first case of Tamiflu-resistant H1N1 flu
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TOKYO, July 3 (Xinhua) -- Japanese has detected the first genetic mutation of the new H1N1 strain of influenza A that develops resistance to the anti-flu drug Tamiflu, the health ministry said late Thursday.

The Tamiflu-resistant virus was detected in a woman in her 40s infected with the new influenza in Osaka Prefecture, it said.
The ministry added she is already recovering after being administered Relenza, another anti-flu drug.
The female patient had been administered Tamiflu since May 18 as a preventive measure after she was found to have had close contact with another confirmed infected patient the previous day. She was confirmed infected with A/H1N1 influenza on May 28. An analysis of a virus taken from her detected the genetic mutation that does not respond to Tamiflu on June 18. The first case of HINI that showed resistance to Tamiflu was reported in Denmark at the end of last month.

http://news.xinhuanet.com/english/2009-07/03/content_11644518.htm

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Re: HONG KONG, PRC SAR: RESPONSE AND TRACKING (by Govt Agencies) [857 cases, 0 deaths, 3 in hospital, as 07/02/09]

Re: HONG KONG, PRC SAR: RESPONSE AND TRACKING (by Govt Agencies) [857 cases, 0 deaths, 3 in hospital, as 07/02/09]

Hong Kong: Detection of human swine influenza virus resistant to Tamiflu (7/3/09)

A spokesman for the Department of Health (DH) said the department's Public Health Laboratory Services Branch (PHLSB) today (July 3) detected a strain of human swine influenza (HSI) virus which was resistant to oseltamivir (Tamiflu).


The virus was identified during PHLSB's routine sensitivity test of HSI virus to oseltamivir and zanamivir, the spokesman said.

"This is the first time Tamiflu resistance in HSI virus found in Hong Kong," he said, adding that similar cases were also reported in Denmark and possibly Japan.

"Tests showed that this strain is sensitive to zanamivir (Relenza)," he said.


The virus was isolated from the specimen taken from a 16-year-old girl coming from San Francisco. She was intercepted by Port Health Office at the Hong Kong International Airport on June 11 upon arrival. The girl was then admitted to Queen Mary Hospital for isolation. She was tested positive to HSI but opted not to take tamiflu. She had mild symptoms and was eventually discharged upon recovery on June 18.

The spokesman noted that PHLSB conducted routine sensitivity tests on specimens taken from confirmed HSI patients.

"This is the only Tamiflu-resistant strain so far among some 200 HSI samples tested in Hong Kong. Further tests are underway," he said.

Hong Kong has maintained an antiviral stockpile of both Tamiflu and Relenza.

The case will be reported to the World Health Organization (WHO), the spokesman said. He reiterated that Hong Kong had an intensive influenza surveillance system on antiviral resistant influenza viruses.

"We will closely liaise with WHO and overseas health authorities and monitor the global development of antiviral resistant HSI virus," he said.
-

View Original Article
 
First Tamiflu-resistant swine flu case found in teenager (Hong Kong ex San Francisco)

First Tamiflu-resistant swine flu case found in teenager (Hong Kong ex San Francisco)

<TABLE class=bodyCopy border=0 cellSpacing=1 cellPadding=1 width=500 align=center><TBODY><TR><TD>First Tamiflu-resistant swine flu case found in teenager
(10 mins ago)
A 16-year-old girl was found to be infected with a mutation of the swine flu virus that is resistant to the antiviral Tamiflu soon after arriving from San Francisco, the Department of Health said today.

It is the first such case in Hong Kong. Similar cases have been reported in Denmark and Japan.

The teenager was intercepted at the airport on June 11 and admitted to Queen Mary Hospital.

She opted not to be put on a course of Tamiflu before testing positive for the swine flu strain, which is known to be resistant to the antiviral.

She had mild symptoms and was discharged on June 18.

The case will be reported to the World Health Organization.

Danish health authorities have used Relenza, an alternative anti-flu medication, to successfully treat a female patient with the same strain.

The Japanese said a patient was found to be resistant to Tamiflu after being put on the drug since she was being diagnosed with the H1N1 virus around two weeks ago, Kyodo news agency reported yesterday.

The Osaka prefecture patient was recovering after having been given Relenza.

A spokeswoman for Swiss pharmaceuticals giant Roche, which makes Tamiflu, said the company had been informed of the case and described as ''normal'' such resistance to the drug.

''It is absolutely normal,'' she said, adding that ''0.4 percent of adults develop resistance'' to Tamiflu.

She said such cases do not indicate Tamiflu has become less effective against swine flu.

http://www.thestandard.com.hk/breaking_news_detail.asp?id=15461</TD></TR></TBODY></TABLE>
 
Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Tamiflu-Resistant Swine Flu Virus Found in Hong Kong (Update2)


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By Nipa Piboontanasawat and Jason Gale
July 3 (Bloomberg) -- Tamiflu-resistant swine flu was found in a teenager who hadn?t taken Roche Holding AG?s best-selling antiviral medicine, Hong Kong?s health department said.
The city?s Public Health Laboratory Services Branch identified the drug-evading variant during routine surveillance of flu specimens, the department said in a statement today.
This marks the first known case of Tamiflu resistance in a swine flu patient not treated with the drug, which has been stockpiled by governments worldwide to fight pandemic influenza. The specimen was collected from a 16-year-old girl who flew from San Francisco and was intercepted by officials at Hong Kong International Airport on June 11, according to the statement.
?Picking it up in a patient who was not treated is a cause for concern,? Malik Peiris, professor of microbiology at Hong Kong University, said in an interview. ?One case doesn?t change the world, but if we are seeing more and more cases in patients who are not treated, then I think it would be more serious.?
The patient, who was admitted to Queen Mary Hospital for isolation, tested positive for the new H1N1 flu strain and opted not to take Tamiflu, Hong Kong?s health department said. She had mild symptoms and was discharged upon recovery on June 18.
Denmark, Japan
Basel, Switzerland-based Roche said on June 29 that a swine flu patient treated with Tamiflu in Denmark showed resistance to the drug for the first time. Japan?s health ministry reported a case of resistance yesterday in a woman from Osaka who had taken a 10-day course.
Studies have shown that Tamiflu-resistant bugs develop in 0.4 percent to 4 percent of adults and children treated for seasonal influenza, Claudia Schmitt, a spokeswoman at Roche, said by phone from Basel today.
It?s likely the few reported cases of drug-resistant swine flu emerged independently, Hong Kong University?s Peiris said.
?The key point is whether the strains will become dominant and then we will have a problem,? he said. ?At this moment, I don?t think there is cause for alarm. There is certainly cause for heightened surveillance.?
The new H1N1 pandemic virus and a seasonal H1N1 variant are more likely to develop resistance to Tamiflu than other common flu strains, Peiris said. About 95 percent of the H1N1 seasonal flu viruses circulating around the world evade the Roche pill, according to a March 21 World Health Organizationreport.
Glaxo?s Relenza
No widespread resistance to GlaxoSmithKline Plc?s flu drug Relenza has been reported in seasonal flu, and there have been no reports of resistance in swine flu.
?Constant, random mutation is the survival mechanism of the microbial world,? WHO Director-General Margaret Chan said in an address to a meeting on the flu pandemic in Cancun, Mexico, yesterday. ?Like all influenza viruses, H1N1 has the advantage of surprise on its side.?
Tamiflu and Relenza, an inhaled powder, reduce the severity and the duration of flu symptoms by 24 to 30 hours if treatment is started within the first two days of illness, according to the companies.
Both drugs work by blocking a protein on the surface of influenza particles called neuraminidase, which allows the virus to spread from infected cells to other cells in the body.
Scientists say mutant H1N1 viruses have evolved to evade Tamiflu through a single mutation in the neuraminidase that prevents the medicine from clinging to the viral protein, enabling the pathogen to spread.
The case in Hong Kong indicates that the mutant virus is capable of being transmitted among people, said Jennifer McKimm- Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne.
?It?s very disturbing that, fresh into the human population, this one appears now to be able to retain fitness despite having the mutation and to be able to spread,? she said in a telephone interview today.
To contact the reporters on this story: Nipa Piboontanasawat in Hong Kong at npiboontanas@bloomberg.net; To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net.
Last Updated: July 3, 2009 07:46 EDT

http://www.bloomberg.com/apps/news?pid=20601202&sid=a9GPdD61pf30
 
Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu (7/3/09)

Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu (7/3/09)

Commentary

Surveillance Flaws Drive Silent Spread of Tamiflu Resistant H1N1

Recombinomics Commentary 15:18
July 3, 2009


The virus was isolated from the specimen taken from a 16-year-old girl coming from San Francisco. She was intercepted by Port Health Office at the Hong Kong International Airport on June 11 upon arrival. The girl was then admitted to Queen Mary Hospital for isolation. She was tested positive to HSI but opted not to take tamiflu. She had mild symptoms and was eventually discharged upon recovery on June 18.


The above comments from a Hong Kong DOH press release on Tamiflu resistance in pandemic H1N1 highlight severe limitations in worldwide surveillance. Although this case was identified by routine surveillance of H1N1 positive patients in Hong Kong, it is an effort largely focused on travelers. Like countries outside of the Americas, most efforts have focused on travelers and largely ignored local community spread. The recent explosion in cases in the UK has led to a focus on the community spread there, but many other counties in Europe are reporting low numbers of confirmed pandemic H1N1 because of limited testing in the community.

In the US, efforts are focused on the community, but severe cases are targetted. Most states have stopped reporting and testing mild cases, so real monitoring of this group is minimal. However, the case in Hong Kong originated in San Francisco and was mild. The United States has not reported any Tamiflu resistance. The CDC has tested over 200 isolates and failed to identify H274Y.


This may be due in part to virus mixtures. In Denmark and Japan the H274Y was discovered in patients undergoing Tamiflu prophylactic treatment. The Tamiflu treatment would reduce wild type H1N1 and allow a minor population with H274Y to expand and be detected. Therefore, it is likely that the H274Y is spreading silently and under the radar of the sequencing efforts, which are focused on the dominant (consensus) sequence.


The acquisition of H274Y by pandemic H1N1 was not unexpected. H274Y has a history of jumping from one sub-clade to another, as well as jumping to multiple different backgrounds within a subclade via recombination and genetic hitchhiking. This has produced resistance that is limited to H1N1 and H274Y within H1N1. The co-circulation of human H1N1 seasonal flu with swine H1N1 in humans, has created a favorable environment for the jump of H274Y from seasonal flu to pandemic flu. Moreover, the widespread use of Tamiflu in patients infected with pandemic H1N1 will drive the rate of spread in pandemic H1N1.


Although countries have been placing sequences on deposit in a timely manner, there are still major deficiencies in the surveillance program, as described above. Moreover, the recent reports of Tamiflu resistance in isolates in Denmark, Japan, and Hong Kong have not lead to the release of these sequences.


An increase in surveillance and release of full sequences is still necessary. The pandemic H1N1 is now rapidly spreading in the southern hemisphere, which is just beginning its flu season. Sequences from fatal and mild cases are required to determine important changes in pandemic H1N1 associated with increased virulence as well as increased spread.


A serious comprehensive surveillance program is long overdue.


.
 
Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Commentary

Lesson Not Learned in H1N1 Tamiflu Resistant Spread

Recombinomics Commentary 18:26
July 3, 2009

"Picking it up in a patient who was not treated is a cause for concern," Malik Peiris, professor of microbiology at Hong Kong University, said in an interview. "One case doesn't change the world, but if we are seeing more and more cases in patients who are not treated, then I think it would be more serious."

The patient, who was admitted to Queen Mary Hospital for isolation, tested positive for the new H1N1 flu strain and opted not to take Tamiflu, Hong Kong's health department said. She had mild symptoms and was discharged upon recovery on June 18.

"The key point is whether the strains will become dominant and then we will have a problem," he said. "At this moment, I don't think there is cause for alarm. There is certainly cause for heightened surveillance."

"Constant, random mutation is the survival mechanism of the microbial world," WHO Director-General Margaret Chan said in an address to a meeting on the flu pandemic in Cancun, Mexico, yesterday. "Like all influenza viruses, H1N1 has the advantage of surprise on its side."

Studies have shown that Tamiflu-resistant bugs develop in 0.4 percent to 4 percent of adults and children treated for seasonal influenza, Claudia Schmitt, a spokeswoman at Roche, said by phone from Basel today.

The above comments on the emergence of H274Y and associated oseltamivir (Tamiflu) resistance clearly show that lessons were not learned from the spread of H274Y in seasonal flu (limited to H1N1). The spread of H274Y in seasonal flu destroyed the old paradigm of influenza evolution by selection of "random mutations", but as seen above, WHO is still citing that mechanism to try to explain the emergence of H274Y in pandemic H1N1 in Denmark, Japan, Hong Kong, and San Francisco.

Roche is still citing old data on the emergence of resistance in Japan years ago, when children were treated with sub-optical doses. That data provided a classical example of resistance, which was linked to the sub-optimal dosing, as well as mutations in H1N1 and H3N2 at multiple locations within each sero-type. However, those changes were only viable in the presence of Tamiflu, which killed off the competing wild type strains.

In 2005 when resistance developed in treated patients or contacts infected with H5N1 the same assurances on lack of fitness and failure to spread were offered. The first example was a patient on a prophylactic dose because her brother was a confirmed case. She developed an infection, but responded to a therapeutic dose, even though H5N1 with H274Y as well as N296S was identified in sub-clones from the patient.

Although the spread of resistant H5N1 in patients was not reported, the appearance of H274Y in H1N1 in wild birds later that year was cause for concern. The wild birds in Russia were not given oseltamivir, yet H5N1 was isolated from dead birds indicating H5N1 with H274Y was evolutionarily fit, leading to transmission between birds and fatal infections.

Concerns of H274Y were increased the following year when it was reported in seasonal flu in China. The clade 2C (Hong Kong strain) with H274Y was found in patients who were not taking Tamiflu, again showing that evolutionarily fit could transmit to humans who were not taking Tamiflu.

The following season (2006/2007), H274Y jumped to another H1N1 sub-clade (clade 1 - New Caledonia strain) in the United States and United Kingdom. The multiple sub-clades within clade 1 signaled multiple introductions into patients not taking Tamiflu.

The following season (2007/2008), H274Y jumped again. Initial cases in the United States were in Hawaii were clade 2B (Brisbane strain), but did not spread. However, the H274Y jumped onto another clade 2B sub-clade which did spread in the United States and Europe. This sub-clade was initially reported in Norway in early 2008, but had been silently spreading throughout the fall.

In the summer of 2008 the H274Y in combination with HA A193T emerged, which then led to the fixing of H274Y at levels approaching 100% of H1N1. The A193T, as well as several additional polymorphisms had been co-circulating on clade 2C. The acquisition of these polymorphisms, including three consecutive polymorphisms in NA signaled recombination, because the NA polymorphisms were not only consecutive, but included a synonymous change, which offered no obvious selection pressure.

Thus, the data was inconsistent with a "random mutation" mechanism. The key changes were co-circulating on a related sub-clade, and were appended onto a clade 2B backbone. The H274Y jumped from background to background in patients who were not taking Tamiflu. This spread of H274Y via recombination and genetic hitchhiking did not require de novo mutations. The key polymorphisms were already circulating in clade 2C, and had earlier been found in other H1N1 or H1N2 isolates.

The mechanism of evolution raised serious concerns when swine H1N1 acquire efficient transmission in humans. This transmission offered the opportunity of genetic exchanges between human seasonal H1N1 and swine H1N1 which was now also in humans. Dual infections would allow for H274Y jumping form seasonal flu to pandemic flu in patients infected with both viruses.

Thus, the detection of H274Y in Denmark this week was not a surprised. However, since the patient had been on a prophylactic dose of oseltamivir, the random mutation paradigm was used to explain the data and offer assurances that the resistance wouldn't spread. However, the appearance of H274Y in the treated patient raised concerns that H274Y was lurking in a minor sub-population that was missing in sequencing of untreated patients, and was detected only in treated patients.

The data from Denmark was repeated in Japan this week, when another patient being treated with a prophylactic dose of oseltamivir also gave rise to the detection of H274Y. However, the appearance of H274Y in the absence of other resistance changes raised concerns that H274Y had already been acquired via recombination and was silently spreading in association with wild type H1N1.

The concerns were increased by the announcement in Hong Kong at a traveler from San Francisco, who was not taking Tamiflu was harboring a resisitant sequence, which was almost certainly H274Y. The presence of resistance in a patient not taking Tamiflu indicated the pandemic H1N1 with H274Y was evolutionarily fit and not only was in Hong Kong, but was also in San Francisco, the origin of the traveler.

However, H274Y has not been reported in the United States, raising serious surveillance concerns. Most efforts are directed to hospitalized serious cases, and state across the country announced that they were no longer testing mild cases. However, the Hong Kong, ex-San Francisco case was mild, which may explain the lack of detection.

However, of greater concern is the ability of H274Y to jump from one background to another in the absence of oseltamivir selection.

However, statements above indicate the lesson from seasonal flu was not learned, and the old discredited random mutation explain is once again offered, along with assurances that the H274Y will not spread (even after it has been found or implied on three continents).

Increased surveillance will demonstrate not only that H274Y can spread, but that it has already spread, under the radar of the current surveillance system. Moreover, the reliance of the old "random mutation" paradigm will lead to more "surprises" but those who adhere to an paradigm which is inconsistent with the sequence data.

An increase in surveillance and sequencing will allow for more accurate products of future acquisitions, which are due to recombination and not due to de novo mutations, as repeated again and again by those who ignore the data, or quote those who ignore the data.

.
 
Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Here;s data for Hawaii at Genbank. One NA sequence that was just deposited from a collection in April

LOCUS GQ338360 1410 bp cRNA linear VRL 01-JUL-2009
DEFINITION Influenza A virus (A/Hawaii/09/2009(H1N1)) segment 6 neuraminidase
(NA) gene, complete cds.
ACCESSION GQ338360
VERSION GQ338360.1 GI:243031419
DBLINK Project:37813
KEYWORDS .
SOURCE Influenza A virus (A/Hawaii/09/2009(H1N1))
ORGANISM Influenza A virus (A/Hawaii/09/2009(H1N1))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (bases 1 to 1410)
AUTHORS Garten,R.
TITLE Direct Submission
JOURNAL Submitted (01-JUL-2009) Centers for Disease Control and Prevention,
NCIRD/Influenza Division/VSDB, Centers for Disease Control and
Prevention, Atlanta, 1600 Clifton Road, N.E., Atlanta, GA 30333,
USA
COMMENT Swine influenza A (H1N1) virus isolated during human swine flu
outbreak of 2009. For more information, see http://www.cdc.gov/.

Some of the information does not have GenBank feature identifiers
and is being provided in the comment section.

##EpifluData-START##
Isolate A/Hawaii/09/2009
Subtype H1N1
Segment_name NA
Host_gender F
Host_age 37
Passage_history C1
Antigen_character A/California/07/2009-LIKE (H1N1)V
Adamantane_resistance resistant
Zanamivir_resistance sensitive
Oseltamivir_resistance sensitive
Country USA
State/Province Hawaii state
Collection_day 30
Collection_month 4
Collection_year 2009
Isolate_note Comment: Human case of 2009 H1N1 swine
influenza.
EPI_accession EPI184367
Lineage swl
##EpifluData-END##
FEATURES Location/Qualifiers
source 1..1410
/organism="Influenza A virus (A/Hawaii/09/2009(H1N1))"
/mol_type="viral cRNA"
/strain="A/Hawaii/09/2009"
/serotype="H1N1"
/host="Homo sapiens; gender F; age 37"
/db_xref="taxon:656491"
/segment="6"
/country="USA: Hawaii state"
/collection_date="30-Apr-2009"
gene 1..1410
/gene="NA"
CDS 1..1410
/gene="NA"
/codon_start=1
/product="neuraminidase"
/protein_id="ACS94509.1"
/db_xref="GI:243031420"
/translation="MNPNQKIITIGSVCMTIGMANLILQIGNIISIWISHSIQLGNQN
QIETCNQSVITYENNTWVNQTYVNISNTNFAAGQSVVSVKLAGNSSLCPVGGWAIYSK
DNSVRIGSKGDVFVIREPFISCSPLECRTFFLTQGALLNDKHSNGTIKDRSPYRTLMS
CPIGEVPSPYNSRFESVAWSASACHDGINWLTIGISGPDNGAVAVLKYNGIITDTIKS
WRNNILRTQESECACVNGSCFTVMTDGPSNGQASYKIFRIEKGKIVKSVEMNAPNYHY
EECSCYPDSSEITCVCRDNWHGSNRPWVSFNQNLEYQIGYICSGIFGDNPRPNDKTGS
CGPVSSNGANGVKGFSFKYGNGVWIGRTKSISSRNGFEMIWDPNGWTGTDNNFSIKQD
IVGINEWSGYSGSFVQHPELTGLDCIRPCFWVELIRGRPKENTIWTSGSSISFCGVNS
DTVGWSWPDGAELPFTIDK"
ORIGIN
1 atgaatccaa accaaaagat aataaccatt ggttcggtct gtatgacaat tggaatggct
61 aacttaatat tacaaattgg aaacataatc tcaatatgga ttagccactc aattcaactt
121 gggaatcaaa atcagattga aacatgcaat caaagcgtca ttacttatga aaacaacact
181 tgggtaaatc agacatatgt taacatcagc aacaccaact ttgctgctgg acagtcagtg
241 gtttccgtga aattagcggg caattcctct ctctgccctg ttggtggatg ggctatatac
301 agtaaagaca acagtgtaag aatcggttcc aagggggatg tgtttgtcat aagggaacca
361 ttcatatcat gctccccctt ggaatgcaga accttcttct tgactcaagg ggccttgcta
421 aatgacaaac attccaatgg aaccattaaa gacaggagcc catatcgaac cctaatgagc
481 tgtcctattg gtgaagttcc ctctccatac aactcaagat ttgagtcagt cgcttggtca
541 gcaagtgctt gtcatgatgg catcaattgg ctaacaattg gaatttctgg cccagacaat
601 ggggcagtgg ctgtgttaaa gtacaacggc ataataacag acactatcaa gagttggaga
661 aacaatatat tgagaacaca agagtctgaa tgtgcatgtg taaatggttc ttgctttact
721 gtaatgaccg atggaccaag taatggacag gcctcataca agatcttcag aatagaaaag
781 ggaaagatag tcaaatcagt cgaaatgaat gcccctaatt atcactatga ggaatgctcc
841 tgttatcctg attctagtga aatcacatgt gtgtgcaggg ataactggca tggctcgaat
901 cgaccgtggg tgtctttcaa ccagaatctg gaatatcaga taggatacat atgcagtggg
961 attttcggag acaatccacg ccctaatgat aagacaggca gttgtggtcc agtatcgtct
1021 aatggagcaa atggagtaaa aggattttca ttcaaatacg gcaatggtgt ttggataggg
1081 agaactaaaa gcattagttc aagaaacggt tttgagatga tttgggatcc gaacggatgg
1141 actgggacag acaataactt ctcaataaag caagatatcg taggaataaa tgagtggtca
1201 ggatatagcg ggagttttgt tcagcatcca gaactaacag ggctggattg tataagacct
1261 tgcttctggg ttgaactaat cagagggcga cccaaagaga acacaatctg gactagcggg
1321 agcagcatat ccttttgtgg tgtaaacagt gacactgtgg gttggtcttg gccagacggt
1381 gctgagttgc catttaccat tgacaagtaa

</PRE></P>
 
Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

Re: Hong Kong: Detection of human swine influenza virus resistant to Tamiflu in person from USA

<TABLE dir=ltr border=1 cellSpacing=0 cellPadding=7 width=831><TBODY><TR><TD height=0 vAlign=top width="13%">
98​

</TD><TD height=0 vAlign=top width="13%">F/36
</TD><TD height=0 vAlign=top width="13%">Asymptomatic
</TD><TD height=0 vAlign=top width="13%">Returned from San Francisco with mother and
</TD><TD height=0 vAlign=top width="13%">Imported
</TD><TD height=0 vAlign=top width="13%">Singapore Airlines(flight no SQ1) Arrived on June 11
</TD><TD height=0 vAlign=top width="13%">Daughter (confirmed patient), mother, two sisters , a brother
</TD><TD height=0 vAlign=top width="13%">Ping Tin Estate

</TD></TR></TBODY></TABLE>
The above data indicates the patient with Tamiflu resistant H1N1 was ASYMPTOMATIC!
 
Re: India - H1N1 Tamiflu resistance suspected

Re: India - H1N1 Tamiflu resistance suspected

USA link


Possible case of ?resistant? A (H1N1) virus

Ramya Kannan

Positive tests, even after treatment, suggest a mutation

Blood sample to be sent to National Institute of Virology

CHENNAI: The Indian Council of Medical Research will investigate what seems to be a case of ?resistant? A (H1N1) virus in Chennai, its Director-General V. M. Katoch said. This is the first such case reported in the country.

The State health authorities have been asked to send a blood sample of the infected person to the National Institute of Virology (NIV), Pune.

The patient, a man who had flown in from the U.S. in the third week of June, had tested positive along with his wife.

They were quarantined at the Communicable Diseases Hospital (CDH) here and started on a course of Tamiflu. ?This was through the Directly Observed Treatment Short-course method, which means we know he took every tablet and did not miss out on even a single dose. Missing on doses can lead to resistance, but that is not the case with this patient,? Director of Public Health S. Elango said.

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

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

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

He said the patient at the CDH could be treated on recommended doses of the drug ?Relenza? available in India.

When told that the patient was anxious to go home, Dr. Katoch categorically said that he could not be discharged as long as he continued to test positive, even if he was not symptomatic.

?He is certainly a carrier and can spread the virus to members of his family, and thereby take it into the community. That should not be allowed to happen. Indigenous transmission of the virus from this person will lead to a huge public health problem,? Dr. Katoch said.

The issue would be sorted out as soon as the sequence was drawn up. ?That way we will also be ready for any future occurrences.?

http://www.thehindu.com/2009/07/04/stories/2009070456041300.htm
 
Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

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Saturday, July 4, 2009
Osaka fails to report swine flu mutation

Kyodo News
An Osaka health official found a genetic mutation of swine flu
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that is resistant to Tamiflu on June 18 — nearly two weeks before the "first" finding was reported in Denmark
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— but failed to disclose it, the health ministry said Thursday.
The mutation, found in a woman in her 40s in Toyonaka who caught the H1N1 influenza A virus in May, is the first reported case of Tamiflu-resistant swine flu
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in Japan.
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<!-- MooterMedia Javascript Ad Snippet end here -->The World Health Organization
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declared the new flu a pandemic on June 11.
The case "is considered to pose no public health threat, given no infections have been confirmed around her," an official of the Health, Labor and Welfare Ministry said.
Nationwide, swine flu cases have topped 1,500, surfacing in 44 prefectures, but none has been fatal, the ministry said.
At an unscheduled press conference called around midnight Wednesday, Tetsuro Noda, chief of health issues related to infectious diseases at the Osaka Prefectural Institute of Public Health, was inundated with questions about why he failed to promptly report the discovery.
"The virus was dead in the patient and we judged it unnecessary to report it swiftly," Noda said. "In terms of public health, I didn't think it was a serious case and I feel sorry for the delay in the disclosure."
Osaka Prefecture said the woman carrying the Tamiflu-resistant strain recovered after being treated with Relenza, another antiviral drug.
The prefecture confirmed the genetic mutation on June 18 but did not report it to the health ministry until Wednesday, even though no other cases of Tamiflu-resistance had been reported worldwide. It was told to tell the public the next day.

http://search.japantimes.co.jp/cgi-bin/nn20090704a4.html
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Re: India - Has H1N1 virus mutated? Man on Tamiflu tests +ve

Re: India - Has H1N1 virus mutated? Man on Tamiflu tests +ve

Man on Tamiflu tests negative for H1N1, discharged from hospital

5 Jul 2009,

CHENNAI: Officials at the state health department heaved a sigh of relief on Saturday when they received a message from the National Institute of
Communicable Diseases, New Delhi, stating that a 29-year-old man who had remained positive for H1N1 virus despite being on Tamiflu treatment has tested negative.

He was discharged from the Communicable Diseases Hospital (CDS) here on Saturday.

Earlier, directorate of public health staff had expressed concerns when the man was discharged on Friday by CDH despite having remained positive for H1N1. He was brought back to the quarantine ward on Saturday and even his family members were instructed to start a course of anti-viral therapy to prevent infection.

Doctors were awaiting orders from the NICD on the further course of treatment for the patient - either another course of Tamiflu or another drug, Relenza.

"We are relieved that he is not a carrier anymore. He has been discharged. However, we have asked laboratories to investigate and let us know if there has been any mutation of the virus. We can't help the suspicion; it took him two courses of Tamiflu, against the normal one course, to recover," said director of public health Dr S Elango.

The man and his wife had arrived in Chennai airport on July 18. They were kept in quarantine at CDH after they showed symptoms of H1N1. Two days later, they were put on a course of Tamiflu treatment after laboratories confirmed they had tested positive for the viral infection.

They were given two 75 mg Tamiflu tablets, one in the morning and the other at night.

While the woman tested negative a week later, the man continued to be positive. He was then started on a second course of Tamiflu.


"We want to know why it took him so long to recover. It could be because of a mutation of the virus," Dr Elango said. The National Institute of Virology in Pune will now investigate why it took the patient almost a fortnight for recovery.

http://timesofindia.indiatimes.com/...charged-from-hospital/articleshow/4738884.cms
 
Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

Source: http://www.google.com/hostednews/canadianpress/article/ALeqM5jb6J6PJB7Burz1l0V3UoN6Q7mYOA

Tamiflu resistant H1N1 from Hong Kong more worrying than earlier findings

By Helen Branswell ? 13 minutes ago

TORONTO ? All cases of Tamiflu resistance are not created equal. So while the first three instances of swine flu infection with Tamiflu-resistant viruses were reported in the past week, it was Number 3, not Number 1 that put influenza experts on edge.

Public health authorities in Hong Kong announced Friday they have found a case of Tamiflu resistance in a woman who hadn't taken the drug. That means she was infected with swine flu viruses that were already resistant to Tamiflu, the main weapon in most countries' and companies' pandemic drug arsenals.

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

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

There is currently no evidence Tamiflu-resistant viruses are spreading widely. Still, some experts see the Hong Kong case as a warning Tamiflu's role in this pandemic may not be as long-lived as pandemic planners would like.

"I think it's too early to judge," says Dr. Frederick Hayden, an expert on influenza antivirals who teaches at the University of Virginia. "But I think that possibility has existed from the beginning."

"And it's something that needs to be certainly considered in making determinations about things like antiviral stockpiling, management of patients with more serious illness in hospital and how the available drugs will be used."

Some experts say this early sign of resistance should prompt a rethink of how often and in which circumstances Tamiflu is used to battle the novel H1N1 virus.

"It ... probably highlights the importance of not using these antiviral drugs indiscriminately, given that the disease is relatively mild," says Peiris, whose hospital monitored the woman who was found to be carrying the resistant virus.

"In people who don't have underlying risk factors, it probably should not be treated with Tamiflu, basically."

Others suggest countries should limit how often they use the drug to prevent infection, a regimen known as prophylaxis. In prophylaxis, people who've been exposed to the virus are given one pill a day for 10 days, compared to the treatment regime of two pills a day for five days.

Some countries, including Canada, have been reserving prophylaxis for people at high risk from this flu, such as pregnant women.

But others have taken a different approach, using Tamiflu to try to curb spread of the virus. For instance, Britain has made the drug widely available to contacts of confirmed cases, though it announced this past week it was changing that policy.

The World Health Organization is drafting guidance for countries on the use of antivirals. While the WHO advises rather than instructs, it has been stressing that saving these drugs for treatment makes the most sense, says Dr. Keiji Fukuda, the agency's top flu expert.

"In general we have been pushing the advice that using these drugs for treatment is definitely the priority use of them," says Fukuda, the acting assistant director general for health security and environment.

"And I think this is not just from a theoretical resistance perspective, but also from the fact that if you have limited amounts of antiviral drugs, then you need to make some choices about how you use them."

From their first sighting, the new H1N1 viruses have been resistant to two older flu drugs, amantadine and rimantadine. That left the only two other influenza drugs, oseltamivir (Tamiflu) and zanamivir (Relenza), as the sole options for treatment and prophylaxis.

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

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

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

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

Dr. Jennifer McKimm-Breschkin, an influenza expert from Australia and a member of the team that developed Relenza, says this case shows resistant swine flu viruses can spread.

It was previously thought flu viruses that developed resistance to the drug would be crippled in the process and would not transmit to others. But that belief was shattered in 2008 when it was discovered Tamiflu-resistant versions of the seasonal H1N1 viruses were spreading rapidly around the globe. They have since all but wiped out Tamiflu-susceptible seasonal H1N1 viruses.

"This is a patient that hasn't been treated, who has gone from San Francisco to Hong Kong. What that means is that she has caught a resistant virus in San Francisco," says McKimm-Breschkin, virology project leader at the Commonwealth Science and Research Organization - known as CSIRO - in Melbourne. (McKimm-Breschkin does not receive royalties for sales of Relenza.)

"So that means this virus has been transmitted from somebody who's presumably been treated. Which means it's been fit enough to transmit. And that is of a lot more concern than just resistance in a treated patient."

Experts have worried the seasonal H1N1 viruses might reassort or swap genes with the swine H1N1. If swine flu picked up with neuraminidase gene - the N in a flu virus' name - from the seasonal H1N1, it would acquire the resistance its seasonal cousin has developed.

Authorities in Hong Kong have not yet told the WHO whether that is what has happened in this case.

But whether the Hong Kong resistance case is due to reassortment, or from the fact that some swine flu viruses have developed resistance on their own, the situation demands careful monitoring, Fukuda and others say.

"The really big question for any finding of antiviral drug resistance with these viruses is whether it's an isolated event or whether it's a tip of a larger phenomenon," he explains.

"The bottom line, as is so often the bottom line with influenza, is that the real answer to the current situation is monitoring as closely as possible - which in this instance is really being done since an extraordinary number of viruses are being collected and looked at."


The Canadian Press
 
Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

announcement+ (AP) - OSAKA, July 5 (Kyodo)—The Osaka prefectural government sent a research paper to a U.S. medical journal on the first case in Japan of a genetic mutation of the new strain of influenza A virus resistant to Tamiflu about a week before making the finding public, local officials said Saturday.
"It's not that we intentionally placed priority on the manuscript and delayed the announcement," said Tatsuya Oshita, an official of the prefectural government's health and medical care department. "As it turned out, we dealt with the matter in a way that could be criticized and we are sorry."

The Tamiflu-resistant H1N1 flu virus was found in a woman in her 40s in Osaka Prefecture on June 18 -- two weeks before the announcement -- through virus sample analysis at the Osaka Prefectural Institute of Public Health, according to the officials.
Subsequently, a staff member of the institute submitted a manuscript on the analysis result to the U.S. journal on June 24, but it had not been used in the magazine as of Sunday, the officials said.
The prefectural government reported the case to the Health, Labor and Welfare Ministry on Wednesday and held a press conference the next day to make it public based on advice from the ministry, they said.
The local government had said its report to the ministry was delayed as it took time to study the methods for examining abnormalities in viruses themselves in order to substantiate the finding.
The woman had been given Tamiflu since May 18 as a preventive measure after she was found to have had close contact with another confirmed infected patient the previous day, according to the ministry and other sources.
She developed a slight fever on May 24, was confirmed infected with the new influenza May 28 and had recovered after being treated with Relenza, another antiflu drug, they said.

http://www.breitbart.com/article.php?id=D9981UD00&show_article=1
 
Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

It is worth noting that NO pandemic H1N1 sequences with H274Y are public, even though Denmark and Japan media reports specifically stated that the Tamiflu (oseltamivir) resistance was due to H274Y (aka H275Y), and the Hong Kong statement also stongly implied that the resisatnce was due to H274Y (if it wasn't H274Y or if it was due to reassortment with a human NA, they would have said so).

Thus, NA sequences from Denmark, Japan, and Hong Kong (with H274Y) are NOT available at Genbank or GISAID.
 
Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

Re: Osaka sent paper on Tamiflu-resistant virus to journal before announcement

Public kept in dark as institute compiles thesis on mutated virus

THE ASAHI SHIMBUN

2009/7/6
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OSAKA--A prefectural research institute withheld from the public for two weeks its discovery of a mutated swine flu virus, but it swiftly submitted a thesis on the finding to a U.S. medical journal.
The Osaka Prefectural Institute of Public Health only made the announcement of the Tamiflu-resistant virus last Thursday, two weeks after confirming it on June 18. In fact, the health ministry had to instruct the institute to make the announcement.
It was the first confirmation of the mutated virus in the world. But even the Osaka prefectural government's health and medical treatment department failed to announce the detection immediately after it received a report from the institute on June 22.
The mutated virus is resistant to Tamiflu, an anti-flu drug widely used in Japan to treat patients infected with new swine flu.
"If researchers are working for public health, they should know as common sense that (withholding the discovery) is wrong," said Shigeru Omi, a professor of public health at Jichi Medical University and chairman of a government advisory council on new influenza.
A teacher in her 40s in Osaka Prefecture who had been in close contact with an infected person started receiving Tamiflu on May 18 as a preventive measure.
She had a slight fever on May 24 and was confirmed infected with the new swine flu virus on May 29.
The Osaka institute conducted a genetic examination of her virus samples and confirmed on June 18 that the virus had genetically mutated and was resistant to Tamiflu.
The World Health Organization, which demands immediate public disclosure of drug-resistant viruses, said June 29 that the world's first Tamiflu-resistant virus had been confirmed in Denmark.
Meanwhile, the Osaka institute, still keeping the public in the dark, compiled and submitted a thesis on the mutated virus to U.S. medical journal Emerging Infectious Diseases on June 24. As of Saturday, it was not known when the thesis will be published.
The Ministry of Health, Labor and Welfare and the National Institute of Infectious Diseases were only informed of the Tamiflu-resistant virus on Wednesday, prompting the ministry to call for an immediate announcement.
Kazuo Takahashi, vice director of the institute, denied the researchers were seeking fame from the discovery.
"We refrained from announcing the detection to the public, thinking that an announcement at an uncertain stage would only add to public anxiety," he said. "But we thought experts would be able to understand the discovery."
At the news conference Thursday, institute officials said the researchers did not announce the mutated virus for two weeks because they were conducting cell experiments to confirm the virus was resistant to Tamiflu.
Professor Omi said this explanation is not convincing.
On June 24, the thesis submitted to the Emerging Infectious Diseases had already reported confirmation that the genetically mutated virus showed resistance to Tamiflu.
"We can hardly respond to such critical questions about which side we are working for--experts or the public," said Tatsuya Oshita, a senior official at the prefectural health department. "As a (local) government, we should have announced the detection immediately."
The ministry reported the discovery of the mutated virus to the WHO on Friday.(IHT/Asahi: July 6,2009)

http://www.asahi.com/english/Herald-asahi/TKY200907060104.html
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

I know that this isn't a discussion board, so I'd like to ask Dr. Niman if he will start a thread over there to explain this to the laymen like me. It seems very important, but I don't understand anything except that the H1N1 has developed a resistance to Tamiflu? Thanks.
Briefly, H274Y in H1N1 seasonal flu could not be explained by the two pillars of influenza genetics, drift by random mutation introduced by copy errors, and shifts by reassortment.

The H274Y jumped from genetic background to genetic background, eliminating reassortment, but "random errors" made no sense because there was no involvement of Tamiflu, and Tamiflu causes other resisatnce changes in H1N1 and H3N2, but all resistance was linked H274Y in H1N1. Moreover, the emergence of H274Y in the Brisbane strain (clade 2B) was linked to additional acquistions, and the key acquistions were in clade 2C (Hong Kong strain) which was co-circulating.

The acquistions in seasonal flu were detailed here

http://precedings.nature.com/documents/2832/version/1

and were due to genetic hitchhiking and recombination - and the gateway from H274Y in H5N1 and H274Y in H1N1 was the Indiana seasonal flu sequence, which was the same gateway used to move H274Y from seasonal H1N1 to pandemic (swine) H1N1.
 
Tamiflu resistance in pandemic influenza - historical compilation of news

Tamiflu resistance in pandemic influenza - historical compilation of news

http://www.reuters.com/article/healthNews/idUSTRE5664ML20090707

WHO sees little Tamiflu-resistant H1N1 flu spread
Tue Jul 7, 2009 12:59pm EDT

* WHO says Tamiflu-resistant cases sporadic, not spreading

* Not changing recommendations about H1N1 patient treatment

By Laura MacInnis and Stephanie Nebehay

GENEVA (Reuters) - Tamiflu-resistant H1N1 flu does not appear to be spreading in a sustained or worrisome way, a World Health Organization official said on Tuesday.

"At this point we are not recommending any clinical changes to the approach in treating patients," WHO Acting Assistant Director-General Keiji Fukuda said, responding to the discovery of drug-resistant H1N1 viruses in three people.

"Right now these examples of oseltamivir resistance remain sporadic cases. We do not see any evidence of widespread movement of oseltamivir resistant viruses," he told a briefing, using the generic name for Tamiflu, an anti-viral tablet made by Roche and Gilead Sciences.

The three people whose H1N1 virus samples did not respond to Tamiflu -- in Denmark, Japan and Hong Kong -- have recovered completely from their infection, Fukuda said. He described the Tamiflu-resistant viruses as mutations and not a reassortment or combination with other influenza strains.

So far all discovered Tamiflu-resistant viruses have been sensitive to treatment with the other anti-viral recommended by the WHO, the inhaled drug Relenza made by GlaxoSmithKline under license from Biota, according to Fukuda.

Relenza is known generically as zanamivir.

The WHO, a Geneva-based United Nations agency, raised its global flu alert to the highest level on June 11, declaring the first influenza pandemic since 1968 was underway.

While the H1N1 virus has caused mild flu symptoms in most people, 440 people have died from it and health experts are keeping close watch in case it changes into a more serious form and stops being treatable with existing drugs.

WHO Director-General Margaret Chan has said that patients with mild symptoms may not need any medicines to recover, and that hospital visits are not necessary unless those infected with flu have certain warning signs.

These include long-lasting high fever in adults and a lack of alertness in children. Pregnant women and people with health problems including diabetes have also been identified as vulnerable to more severe effects from the new flu strain.

Last month, Chan also said that the H1N1 virus was stable and there were no signs yet it had mixed with other influenza viruses such as the deadly H5N1 bird flu strain.

Signs of mutations in the H1N1 virus are also critically important to vaccine makers who are trying to develop formulas to match the strain that is now spreading around the world, most commonly known as swine flu.

Leading flu vaccine makers include Sanofi-Aventis, Novartis, Baxter, GlaxoSmithKline and Solvay.

(Editing by Janet Lawrence)

? Thomson Reuters 2009 All rights reserved
 
Re: WHO sees little Tamiflu-resistant H1N1 flu spread

Re: WHO sees little Tamiflu-resistant H1N1 flu spread

Source: http://www.nbc15.com/health/headlines/50165487.html

H1N1 Flu Testing to Grow After Resistant US Case
Posted Tuesday, July 7, 2009 --- 5:45 p.m.

By MIKE STOBBE
AP Medical Writer

ATLANTA (AP) -- U.S. health officials are stepping up testing of H1N1 flu cases for Tamiflu resistance.

The action comes after an American teen was diagnosed with a resistant strain. The San Francisco teenager was diagnosed with H1N1 flu last month after arriving in Hong Kong, and has since recovered.

Officials on Tuesday confirmed the 16-year-old lived in San Francisco and likely was infected in the United States.

She's just the third person in the world known to have a strain resistant to Tamiflu, the main weapon against H1N1 flu.

Copyright 2009 by The Associated Press. All Rights Reserved.
 
Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Re: Tamiflu Resistant Pandemic H1N1 Sequence Released (Hong Kong)

Commentary

Tamiflu Resistant Pandemic H1N1 Surveillance Failures in US

Recombinomics Commentary 14:41
July 11, 2009

The recent report of osletamivir resistant pandemic H1N1 in Hong Kong in a traveler (16F) from San Francisco, A/Hong Kong 2369/2009 raised concerns because the traveler had not take osletamivir and her case was mild. She recovered without any antiviral treatment, but the presence of H274Y raised concerns that resistant virus was silently circulating because most mild cases in the United States were no longer tested or reported.

The publication of the sequence increased concerns, because the NA sequence, except for H274Y, exactly matched the sequence from the first case in New Jersey, A/New Jersey/1/2009, a Bergen county women (22F) infected in April. Since the Hong Kong case was in June, the identity between the two sequences indicated that the virus had spread across the United States undetected between April and June, and was only detected when it was exported to Hong Kong, through routine osletamivir resistant testing of pandemic isolates.

The sequence in Hong Kong matched a sequence from Japan, A/Sapporo/1/2009, which was published in Genbank a few days later. Like New Jersey, the Japan sequence did not have H274Y, but it also was detected in a traveler (20M) from the United States (Hawaii), increasing concerns that this sequence was transmitting in the United States undetected.

The next day, two more sequences were released. One was a partial NA sequence from Catalonia, Spain (A/Catalonia/387/2009), which also exactly matched the sequence from New Jersey and Japan, while the other was from Vastra Gotalands , Sweden (A/Stockholm/37/2009), which also matched the above sequences, but had one additional change. The isolate from Sweden was also from a traveler (2M) from the United States. Both isolates were also from patients infected in June, so the Tamiflu flu resistant sequence, or precursor, was detected in Hong Kong, China, Sapporo, Japan, Catalonia, Spain, and Vastra Gotalands, Sweden in the month of June, and at least three of the four isolates were from patients traveling from the United States. However, the only match in isolates from the United States was in a New Jersey patient infected in April.

The export of infections from a country not reporting corresponding infections signals a poor surveillance system. Although the number of sequences from the United States is the highest in the world, the failure to identify the oseltamivir resistant precursor sequences matching those found worldwide in travelers from United States is cause for concern.

After the resistant isolate was announced, assurances were given, citing on the lack of detection of resistance in the United States. This failure however may be due an emphasis on severe cases and lack of testing of mild cases. Moreover, even if precursor sequences are detected, a low abundance version would not be identified in a consensus sequence.

In any event, the failure to identify the precursor since April, when the sequence is detected worldwide in June travelers from the United States, raises serious concerns about surveillance programs which focus efforts on severe cases and largely ignore milder cases.

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