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August 12th, 2009, 01:44 PM
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China, Singapore report Tamiflu-resistant H1N1 viruses
China, Singapore report Tamiflu-resistant H1N1 viruses
Updated Wed. Aug. 12 2009 1:19 PM ET
The Canadian Press
The World Health Organization says China and Singapore have joined the list of countries that have reported Tamiflu-resistant swine flu viruses.
Charles Penn, a scientist with the Geneva-based agency, says the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses but he won't say where they were found.
The WHO has received formal notification of seven cases of Tamiflu resistance among people with the pandemic flu -- three from Japan and one each from Canada, Denmark, Hong Kong and Singapore.
Chinese authorities haven't yet filed a formal report including information about its case but alerted the WHO of the initial laboratory finding through the Global Influenza Surveillance Network.
Penn says to date there is no evidence that Tamiflu-resistant viruses are spreading.
He says all the reported cases to date have been isolated, with no connections among them and no sign that the infected people passed resistant viruses to their contacts.
http://www.ctv.ca/servlet/ArticleNew...812?hub=Health
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August 12th, 2009, 01:46 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
China, Singapore report Tamiflu-resistant H1N1 viruses
Updated Wed. Aug. 12 2009 1:19 PM ET
The Canadian Press
The World Health Organization says China and Singapore have joined the list of countries that have reported Tamiflu-resistant swine flu viruses.
Charles Penn, a scientist with the Geneva-based agency, says the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses but he won't say where they were found.
http://www.ctv.ca/servlet/ArticleNew...812?hub=Health
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Plot is definitely thickening.
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August 12th, 2009, 01:49 PM
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Resident
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
Plot is definitely thickening.
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Do you want to bet that the "no-tell" location is Texas?
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August 12th, 2009, 01:53 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by Mamabird
Do you want to bet that the "no-tell" location is Texas?
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No, Texas is definitely at the top of my list (along with Thailand, which has been confirmed).
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August 12th, 2009, 03:24 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
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August 12th, 2009, 06:03 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Singapore, China find Tamiflu-resistant H1N1 viruses: WHO
By Helen Branswell (CP) – 27 minutes ago
More cases of Tamiflu resistant swine flu viruses have come to light, the World Health Organization said Wednesday.
China and Singapore have found Tamiflu-resistant pandemic viruses, Charles Penn, a scientist with the Geneva-based agency, said in an interview with The Canadian Press.
He revealed that the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses. He would not say where they were found or how many there were in total.
"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said.
The WHO has received formal notification of seven cases where people suffering from pandemic flu were found to be infected with viruses resistant to Tamiflu, one of only two flu drugs that work against these H1N1 viruses. Since the time of their emergence earlier this year, the pandemic viruses have been resistant to two older flu drugs, amantadine and rimantadine.
Japan has reported finding three cases of resistance. Canada, Denmark, Hong Kong and Singapore have each found one.
Chinese authorities haven't yet filed a formal report including information about their case but WHO was alerted to the initial laboratory finding through the Global Influenza Surveillance Network, Penn said. The case occurred Hunan province.
Formal notification involves reporting on details of the case, including whether the patient was taking Tamiflu for treatment of flu or prophylaxis (prevention).
The WHO also wants to know whether the virus has been checked to see if all the genes are those of the pandemic virus or whether the pandemic virus might have swapped genes with the seasonal H1N1 virus.
That would be an unwelcome turn of events: virtually all the human H1N1 viruses circulating over the past year or so have been resistant to Tamiflu. It's an attribute public health authorities would not like to see the pandemic virus acquire.
Penn said to date there is no evidence of that kind of gene swapping - called reassortment. Nor is there any sign that the resistant pandemic H1 viruses are spreading from person to person, he said.
"Basically what it looks like is they are all individual isolated cases. No onward transmission and no suggestion or implication of them having originated, if you like, from a common source," he said.
It has always been expected that some degree of resistance to the drug would arise. Studies done years ago by the drug's maker, Roche, found that in rare cases people taking the drug either for treatment or prevention develop resistance.
"It's been there all the time as an event which can happen with a low frequency. And therefore what we're seeing now is no more or less than we would have expected from those early data," Penn said.
It was long thought Tamiflu-resistant flu viruses would not spread and so didn't pose much of a threat. But in the winter of 2008, the explosive development of resistance in seasonal H1N1 viruses showed the conventional wisdom was unfounded.
Laboratories around the world are on the lookout for changes in the pandemic viruses that might suggest a similar problem of resistance is emerging in them. But so far, no evidence has been found, Penn said.
http://www.google.com/hostednews/can..._dOPlbPaGheujw
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August 12th, 2009, 06:23 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
Singapore, China find Tamiflu-resistant H1N1 viruses: WHO
By Helen Branswell (CP) – 27 minutes ago
The WHO also wants to know whether the virus has been checked to see if all the genes are those of the pandemic virus or whether the pandemic virus might have swapped genes with the seasonal H1N1 virus.
That would be an unwelcome turn of events: virtually all the human H1N1 viruses circulating over the past year or so have been resistant to Tamiflu. It's an attribute public health authorities would not like to see the pandemic virus acquire.
http://www.google.com/hostednews/can..._dOPlbPaGheujw |
WHO is in need of a reality check. The key changes that led to H274Y dominance were on HA and NA (and human HA and NA would be like the isolates in Saskatchen, which acquired H274Y but were not likely to lead to a pandemic). The FULL sequences from the Hong Kong isolate, which was NOT linked to Tamiflu, and the two most recent sequences which were likely not linked to Tamiflu (Singapore and Hunan) have been published. They have NO human genes and NO human genes have been reported in ANY pandemic sequences.
Thus, even AFTER the data has been published, they are STILL looking for reassortment (WELL beyond hopes and dreams).
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August 12th, 2009, 06:35 PM
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Editor, Senior Moderator
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
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Commentary
Additional Spread of Tamiflu Resistant Pandemic H1N1
Recombinomics Commentary 20:07
August 12, 2009
Charles Penn, a scientist with the Geneva-based agency, says the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses but he won't say where they were found.
The above comments describe additional cases of Tamiflu resistance (H274Y) but provide no detail on the circumstances or locations. Who has acknowledged the resistance that was evident in the sequences released from Singapore and Hunan, China, as well as the examples previously described in Denmark, Canada, Hong Kong, and Japan (3 times). However, the number and location of additional cases and circumstances remains unclear.
Media reports have described H274Y in Thailand, but it remains unclear how many cases were found. In addition, there were reports of resistance along the Texas / Mexican border, but those reports were denied. However, the denial only addressed the cited locations. There was no statement that the rumored cases were false. The media report was quite detailed about the cases (at least two), which raised concerns that the resistance was widespread, because multiple cases were reported in the same general area.
To date there are no reports of resistance developing during treatment. Several cases were discovered in patients receive prophylactic Tamiflu, but the development of symptoms on the fifth day or prophylactic treatment suggested the H274Y discovered was already present as a minor component and the preventive treatment led to the discovery of the H274Y.
All reported cases have H274Y, which matches the change in seasonal H1N1 and each pandemic sequence represents a different genetic background, raising concerns that the H274Y is spreading via recombination in mild cases which are not tested and in cases were the virus is a mixture dominated by wild type. Consequently, new isolates are being discovered, although reports are clearly being delayed.
The Singapore sequence, deposited at GISAID last week was from the third patient confirmed in Singapore, an American (28F) who became ill in flight from Honolulu to Singapore. Her cases was mild and she was discharged on May 31, three days after confirmation. Similarly, the sequence from Hunan was also released last week, from a patient (63F) which was confirmed June 13. These long delays, and the WHO refusal to give detail on the additional cases, increase concerns that the H274Y is widespread and it presence is either not being detected, or not being reported.
Details on the number and locations of the other isolates, as well as the circumstance surrounding the detection, would be useful. The patient from Hong Kong was not linked to Tamiflu, and circumstances surrounding cases in Singapore, China, and Thailand suggest that the H274Y was discovered during routine surveillance and therefore collected in the absence of or prior to oseltamivir treatment, raising additional concerns of spread of evolutionarily fit pandemic H1N1 with H274Y.
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__________________
"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
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August 13th, 2009, 01:38 AM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
Singapore, China find Tamiflu-resistant H1N1 viruses: WHO
By Helen Branswell (CP) – 27 minutes ago
Chinese authorities haven't yet filed a formal report including information about their case but WHO was alerted to the initial laboratory finding through the Global Influenza Surveillance Network, Penn said. The case occurred Hunan province.
http://www.google.com/hostednews/can..._dOPlbPaGheujw |
If the above network is GISAID, then I think something is confused. The CDC published their Singapore sequence, A/Singapore57/2009, at GISAID, and that sequnece is not at Genbank (but Singapore is said to have notified WHO). China desposited the Hunan sequence at Genbank, A/Hunan/WSL3/2009. but it hasn't been uploaded to GISAID yet. The collection date for Singapore (May 30) and Hunan (June 13) suggest both were sequenced during routine surveillance, and the Singapore patient (28F) was described in detail at the MOH website (American working in Singapore and returning on May 26 on flight from Honoloulu with Tokyo stopover).
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August 13th, 2009, 02:02 AM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Only the HA, NA, and MP sequences for A/Singapore/57/2009 are at GISAID amd the travel log for the intersting, but silent HA polymorphism is below
gb|CY044080.1| Influenza A virus (A/New York/3715/2009(H1N1))... 28.3 1.2
gb|CY044072.1| Influenza A virus (A/New York/3702/2009(H1N1))... 28.3 1.2
gb|CY042320.1| Influenza A virus (A/swine/Illinois/Sg-00445/2... 28.3 1.2
gb|CY042316.1| Influenza A virus (A/swine/Illinois/Sg-00444/2... 28.3 1.2
gb|CY042312.1| Influenza A virus (A/swine/Illinois/Sg-00443/2... 28.3 1.2
gb|GQ414768.1| Influenza A virus (A/Sao Paulo/43812/2009(H1N1... 28.3 1.2
gb|GQ377095.1| Influenza A virus (A/California/24/2009(H1N1))... 28.3 1.2
gb|GQ359765.1| Influenza A virus (A/Stockholm/31/2009(H1N1)) ... 28.3 1.2
gb|GQ292961.1| Influenza A virus (A/Mexico City/22/2009(H1N1)... 28.3 1.2
gb|GQ229365.1| Influenza A virus (A/swine/Hong Kong/NS623/200... 28.3 1.2
gb|GQ229357.1| Influenza A virus (A/swine/Hong Kong/9656/2001... 28.3 1.2
gb|GQ229348.1| Influenza A virus (A/swine/Hong Kong/NS857/200... 28.3 1.2
gb|GQ229333.1| Influenza A virus (A/swine/Hong Kong/1562/2005... 28.3 1.2
gb|GQ229293.1| Influenza A virus (A/swine/Hong Kong/NS1659/20... 28.3 1.2
gb|GQ229269.1| Influenza A virus (A/swine/Hong Kong/915/2004(... 28.3 1.2
gb|GQ229261.1| Influenza A virus (A/swine/Hong Kong/NS837/200... 28.3 1.2
gb|GQ232085.1| Influenza A virus (A/Guangdong/02/2009(H1N1)) ... 28.3 1.2
gb|GQ223435.1| Influenza A virus (A/Guangdong/05/2009(H1N1)) ... 28.3 1.2
gb|GQ161163.1| Influenza A virus (A/swine/Granstedt/IDT3475/2... 28.3 1.2
gb|GQ161145.1| Influenza A virus (A/swine/Kitzen/IDT6142/2007... 28.3 1.2
gb|GQ161143.1| Influenza A virus (A/swine/Groitzsch/IDT6016-2... 28.3 1.2
gb|GQ161141.1| Influenza A virus (A/swine/Groitzsch/IDT6016-1... 28.3 1.2
gb|GQ161104.1| Influenza A virus (A/swine/Bakum/1832/2000(H1N... 28.3 1.2
gb|CY040604.1| Influenza A virus (A/swine/North Carolina/9675... 28.3 1.2
gb|CY040603.1| Influenza A virus (A/swine/North Carolina/4871... 28.3 1.2
gb|CY040602.1| Influenza A virus (A/swine/North Carolina/4775... 28.3 1.2
gb|CY040601.1| Influenza A virus (A/swine/North Carolina/4509... 28.3 1.2
gb|CY040600.1| Influenza A virus (A/swine/North Carolina/4488... 28.3 1.2
gb|CY040599.1| Influenza A virus (A/swine/North Carolina/4427... 28.3 1.2
gb|CY040598.1| Influenza A virus (A/swine/North Carolina/3668... 28.3 1.2
gb|CY040597.1| Influenza A virus (A/swine/North Carolina/2969... 28.3 1.2
gb|CY040596.1| Influenza A virus (A/swine/North Carolina/2676... 28.3 1.2
gb|CY040595.1| Influenza A virus (A/swine/North Carolina/9856... 28.3 1.2
gb|CY040594.1| Influenza A virus (A/swine/North Carolina/4511... 28.3 1.2
gb|CY040593.1| Influenza A virus (A/swine/North Carolina/4488... 28.3 1.2
gb|CY040592.1| Influenza A virus (A/swine/North Carolina/4452... 28.3 1.2
gb|CY040591.1| Influenza A virus (A/swine/North Carolina/4350... 28.3 1.2
gb|CY040590.1| Influenza A virus (A/swine/North Carolina/4162... 28.3 1.2
gb|CY040589.1| Influenza A virus (A/swine/North Carolina/3789... 28.3 1.2
gb|CY040588.1| Influenza A virus (A/swine/North Carolina/3527... 28.3 1.2
gb|CY040587.1| Influenza A virus (A/swine/North Carolina/2948... 28.3 1.2
gb|CY040586.1| Influenza A virus (A/swine/North Carolina/1286... 28.3 1.2
gb|CY040578.1| Influenza A virus (A/swine/North Carolina/4257... 28.3 1.2
gb|CY040576.1| Influenza A virus (A/swine/North Carolina/3876... 28.3 1.2
gb|CY040573.1| Influenza A virus (A/swine/North Carolina/2629... 28.3 1.2
gb|CY040571.1| Influenza A virus (A/swine/North Carolina/1286... 28.3 1.2
gb|CY040569.1| Influenza A virus (A/swine/North Carolina/3456... 28.3 1.2
gb|CY040567.1| Influenza A virus (A/swine/North Carolina/901/... 28.3 1.2
gb|CY040565.1| Influenza A virus (A/swine/North Carolina/4613... 28.3 1.2
gb|CY040563.1| Influenza A virus (A/swine/North Carolina/4390... 28.3 1.2
gb|CY040561.1| Influenza A virus (A/swine/North Carolina/2812... 28.3 1.2
gb|CY040559.1| Influenza A virus (A/swine/North Carolina/9647... 28.3 1.2
gb|CY040557.1| Influenza A virus (A/swine/North Carolina/4743... 28.3 1.2
gb|CY040555.1| Influenza A virus (A/swine/North Carolina/4685... 28.3 1.2
gb|CY040553.1| Influenza A virus (A/swine/North Carolina/4620... 28.3 1.2
gb|CY040551.1| Influenza A virus (A/swine/North Carolina/4401... 28.3 1.2
gb|CY040549.1| Influenza A virus (A/swine/North Carolina/4395... 28.3 1.2
gb|CY040547.1| Influenza A virus (A/swine/North Carolina/4311... 28.3 1.2
gb|CY040545.1| Influenza A virus (A/swine/North Carolina/7571... 28.3 1.2
gb|CY040543.1| Influenza A virus (A/swine/North Carolina/7386... 28.3 1.2
gb|CY040541.1| Influenza A virus (A/swine/Texas/36440-2/2005(... 28.3 1.2
gb|CY039991.1| Influenza A Virus (A/New Jersey/8/1976(H1N1)) ... 28.3 1.2
gb|GQ132144.1| Influenza A virus (A/Canada-ON/RV1529/2009(H1N... 28.3 1.2
gb|CY039925.1| Influenza A Virus (A/swine/Indiana/1726/1988(H... 28.3 1.2
gb|CY039917.1| Influenza A Virus (A/swine/Wisconsin/1915/1988... 28.3 1.2
gb|CY039909.1| Influenza A Virus (A/Maryland/12/1991(H1N1)) s... 28.3 1.2
gb|FJ986621.1| Influenza A virus (A/Ohio/02/2007(H1N1)) segme... 28.3 1.2
gb|FJ986620.1| Influenza A virus (A/Ohio/01/2007(H1N1)) segme... 28.3 1.2
gb|FJ986619.1| Influenza A virus (A/Wisconsin/87/2005(H1N1)) ... 28.3 1.2
gb|AY377936.2| Influenza A virus (A/swine/Pingtung/92-2/2003(... 28.3 1.2
gb|EU604689.1| Influenza A virus (A/swine/OH/511445/2007(H1N1... 28.3 1.2
gb|CY036863.1| Influenza A virus (A/swine/Tennessee/107/1977(... 28.3 1.2
gb|CY036799.1| Influenza A virus (A/swine/Wisconsin/30954/197... 28.3 1.2
dbj|AB434416.1| Influenza A virus (A/swine/Saitama/1996(H1N2)... 28.3 1.2
dbj|AB434408.1| Influenza A virus (A/swine/Ehime/1/1980(H1N2)... 28.3 1.2
dbj|AB434400.1| Influenza A virus (A/swine/Niigata/1/1977(H1N... 28.3 1.2
dbj|AB434392.1| Influenza A virus (A/swine/Hokkaido/2/1981(H1... 28.3 1.2
gb|FJ357104.1| Influenza A virus (A/turkey/NC/17026/1988(H1N1... 28.3 1.2
gb|CY035070.1| Influenza A virus (A/swine/Memphis/1/1990(H1N1... 28.3 1.2
gb|CY035030.1| Influenza A virus (A/X-53A(Puerto Rico/8/1934-... 28.3 1.2
gb|EU798784.1| Influenza A virus (A/swine/Korea/Asan04/2006(H... 28.3 1.2
gb|EU798783.1| Influenza A virus (A/swine/Korea/JL04/2005(H1N... 28.3 1.2
gb|EU798781.1| Influenza A virus (A/swine/Korea/JL01/2005(H1N... 28.3 1.2
gb|EU798780.1| Influenza A virus (A/swine/Korea/Hongsong2/200... 28.3 1.2
gb|EU798779.1| Influenza A virus (A/swine/Korea/CAS08/2005(H1... 28.3 1.2
gb|EU743159.1| Influenza A virus (A/turkey/IA/21089-3/1992(H1... 28.3 1.2
gb|EU743175.1| Influenza A virus (A/chicken/NY/21665-73/1998(... 28.3 1.2
gb|CY032929.1| Influenza A virus (A/swine/Tennessee/109/1977(... 28.3 1.2
dbj|AB434384.1| Influenza A virus (A/swine/Kyoto/3/1979(H1N1)... 28.3 1.2
gb|EU735786.1| Influenza A virus (A/turkey/NC/19762/1988(H1N1... 28.3 1.2
gb|EU735794.1| Influenza A virus (A/chicken/PA/35154/1991(H1N... 28.3 1.2
gb|EU742636.1| Influenza A virus (A/turkey/KS/4880/1980(H1N1)... 28.3 1.2
gb|EU409960.1| Influenza A virus (A/swine/Ohio/C62006/06(H1N1... 28.3 1.2
gb|EU409948.1| Influenza A virus (A/swine/Ohio/24366/07(H1N1)... 28.3 1.2
gb|CY030735.1| Influenza A virus (A/swine/Tennessee/9/1978(H1... 28.3 1.2
gb|CY028780.1| Influenza A virus (A/swine/California/T9001707... 28.3 1.2
gb|CY028788.1| Influenza A virus (A/swine/Iowa/1/1986(H1N1)) ... 28.3 1.2
gb|CY028435.1| Influenza A virus (A/swine/Tennessee/7/1978(H1... 28.3 1.2
gb|CY028427.1| Influenza A virus (A/swine/Tennessee/4/1978(H1... 28.3 1.2
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August 14th, 2009, 04:20 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
More Tamiflu resistance to swine flu in Asia
August 14, 11:59 AM  Miami Health Care ExaminerDeborah Shlian
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More Tamiflu resistance in Asia
Tamiflu resistance to A/H1N1 swine flu has been formally reported by the World Health Organization (WHO) in Hunan, China and Singapore adding to the three cases in Japan, two in Hong Kong (the second just reported today) and one each in Denmark and Canada. There have also been media reports of some resistance in Thailand, but it is unclear how many cases were found and if they were even confirmed. Resistance first reported along the Texas / Mexican border was later denied.
The Japanese, Danish, Canadian and second Hong Kong patients all had been taking Tamiflu as a preventive measure after exposure to the disease and still developed symptoms of flu around the fifth day of their prophylactic treatment, suggesting development of resistant strains after taking the drug.
The f irst Hong Kong case involved a 16 year old American teen flying from San Francisco who had not taken Tamiflu before she became ill. The patient seen in Singapore was a 28 year old American woman flying from Hawaii. Although the details are not clear, it is possible that she too already had contracted a circulating resistant strain of the virus prior to treatment.
Lack of details from WHO has fostered concerns that Tamiflu resistance may be more widespread than officially reported. Speaking to the Canadian Press, Dr. Charles Penn, a scientist with WHO said that "reported cases to date have been isolated, with no connections among them and no sign that the infected people passed resistant viruses to their contacts."
Tamiflu and Relenza are currently the only two antiviral drugs available to treat swine flu. Since its emergence in April, the now pandemic A/H1N1 swine flu virus has been resistant to two older antivirals, amantadine and rimantadine.
Dr. Penn stated that laboratories around the world are monitoring the virus, looking for changes in the strain that might suggest a similar problem of resistance.
For more information: CDC
Florida Department of Health
Other Examiner.com swine flu updates
http://www.examiner.com/x-9303-Miami...ne-flu-in-Asia
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August 14th, 2009, 04:23 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Singapore Confirms First Tamiflu-Resistant A/H1N1 Case
Singapore's Ministry of Health on Friday confirmed that the country has found its first Tamiflu- resistant A/H1N1 case.
A Health Ministry spokesperson said that the isolated case involved a patient who fell sick towards the end of May and was admitted to hospital for isolation and treatment.
The patient was infected by a Tamiflu-susceptible strain of the virus and treated with Tamiflu. The resistant strain emerged during treatment and was detected through laboratory testing but by then the patient had already improved clinically.
"Patients can recover from their illness even if they are infected with a Tamiflu-resistant influenza strain because the immune system plays an important part in clearing the body of the virus," the spokesperson said.
The spokesperson did not reveal the age and gender of the patient.
"So far, we have not detected any other cases of antiviral resistance. We will continue to conduct surveillance for antiviral resistance," the spokesperson said.
Singapore reported its first confirmed case of flu A/H1N1 on May 27. The country's first A/H1N1 related death case was reported on July 18. The country has reported 11 A/H1N1 related death cases so far.
http://english.cri.cn/6966/2009/08/14/1961s509031.htm
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August 14th, 2009, 04:35 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
A Health Ministry spokesperson said that the isolated case involved a patient who fell sick towards the end of May and was admitted to hospital for isolation and treatment.
The patient was infected by a Tamiflu-susceptible strain of the virus and treated with Tamiflu. The resistant strain emerged during treatment and was detected through laboratory testing but by then the patient had already improved clinically.
http://english.cri.cn/6966/2009/08/14/1961s509031.htm |
The above description matches the 28F who was the source of A/Singapore/57/2009. She was an American working in Singapore who became ill on a flight from Honolulu to Singapore, with a stopover in Toyko. She was not detected by fever scanners in Singaore when she arrive May 26. Since she still had symptoms on May 27, she went in for testing and was confirmed May 28. She was briefly hospitalized, by here infection was mild and she was dischanrged on May 31. The sequence with H274Y was reported to collected on May 30. Thefore the H274Y was present after two or three days of treatment (although the Singapore MOH website does not mention Tamiflu treatment). The emergence of H274Y after only 2-3 days of treatment again indcates the H274Y was present PRIOR to teh start of treatment (de novo creation of H274Y at teh start of treament would not yield detectable H274Y in 2-3 days, in a case that was discharged the following day).
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August 14th, 2009, 04:38 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
WHO: More Tamiflu resistance discovered
August 14, 2009 — 10:51am ET | By Tracy Staton
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More cases of H1N1 resistant to Roche's Tamiflu antiviral have cropped up. According to the World Health Organization, China and Singapore have each found Tamiflu-resistant viruses. And Charles Penn, a WHO scientist, told the Canadian Press that WHO has been formally alerted to a small number of other resistant pandemic viruses.
"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said, declining to specify where the H1N1 resistance was found or how many resistant viruses it has found overall. The Canadian Press reports that Japan has found three cases of resistance, with Canada, Denmark, Hong Kong and Singapore each discovering one.
The big question: Whether the resistant virus found in China has been checked to see if the pandemic H1N1 virus might have swapped genes with seasonal H1N1. As you know, last year Tamiflu was declared all but useless for the dominant strain of seasonal flu; if the pandemic flu did pick up those resistance genes, it would render government stockpiles of the drug much less effective to treat severe cases or slow spread of the virus. And it might steer new business to GlaxoSmithKline's Relenza drug.
So far, there's no evidence of that sort of gene reassortment. And there's no evidence that the resistant cases are spreading from person to person.
http://www.fiercepharma.com/story/wh...red/2009-08-14
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August 14th, 2009, 04:45 PM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
WHO: More Tamiflu resistance discovered
August 14, 2009 — 10:51am ET | By Tracy Staton
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The big question: Whether the resistant virus found in China has been checked to see if the pandemic H1N1 virus might have swapped genes with seasonal H1N1. As you know, last year Tamiflu was declared all but useless for the dominant strain of seasonal flu; if the pandemic flu did pick up those resistance genes, it would render government stockpiles of the drug much less effective to treat severe cases or slow spread of the virus.
http://www.fiercepharma.com/story/wh...red/2009-08-14 |
Although the above is a reasonal interpretation of the Canadian Press story, it is utter nonsense. The sequence from China (Hunan) was public long before the Canadian Press and story above were written.
The full sequence of the Hunan isolate is public. It has no new seasonal flu genes. All eight gene segments are closley related to the swine pandemic sequences including NA:
http://www.ncbi.nlm.nih.gov/nuccore/GQ463202
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August 16th, 2009, 10:32 AM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
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August 16th, 2009, 11:32 AM
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Editor, Senior Moderator
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
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Commentary
WHO Failure to See Spread of Tamiflu Resistant Pandemic H1N1
Recombinomics Commentary 15:19
August 16, 2009
China and Singapore have found Tamiflu-resistant pandemic viruses, Charles Penn, a scientist with the Geneva-based agency, said in an interview with The Canadian Press.
He revealed that the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses. He would not say where they were found or how many there were in total.
"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said.
The above comments were issued in response to queries about osletamivir resistance in Singapore and Hunan, China, as indicated by sequences made public at GISAID and Genbank. Those two instances were acknowledged, but the rationale behind the withholding of additional cases remains unclear. At the time Thailand had already acknowledged at least one case, and additional reports from Hong Kong and an MMWR Dispatch describing two immuno-compromised patients in Washington State were made public on Friday. Cases in Texas along the border with Mexico are still being denied, although the initial report included detail on two of the cases, suggesting the denials were largely based on semantics.
The cases in Texas would change the inferred scale, because the cases were at opposite ends of the border and had much in common with the initial H1N1 described in southern California. Those cases were unlinked to each other or swine, yet the sequences were virtually identical, indicating the virus was widespread. The same conclusion could be made from the cases in Texas, which may be related to the withholding of the information associated with these cases.
However, the detail that has come out in the past few days has left little doubt that the WHO's "scale of what we are seeing" is false. The failure to see the true scale of the H274Y spread is due to the limited testing, which is largely focused on samples collected prior to Tamiflu treatment, which can be "seen" in results from patients on prophylactic Tamiflu treatment or in samples collected a few days after the start of Tamiflu treatment in symptomatic patients.
The Hong Kong case described Friday was another patient who became symptomatic while on prophylactic Tamiflu. Earlier detail on patients in Denmark and Japan indicated they became symptomatic on day 5 of prophylactic treatment. Since the incubation period of influenza is in the range of 2-4 days, the slightly longer time period indicated the H274Y was already present when Tamiflu treatment began, but because it was a minor component, disease onset was delayed by 1-2 days. The recent patient in Hong Kong developed symptoms on day 6.
However, the confirmatory data on silent spread of H274Y came from Singapore, where additional data on first confirmed case was disclosed. The sequence was from a May 30 sample from a 28F, but the detailed reports at the MOH indicated the patient (American working in Singapore who arrived late on May 26 after becoming symptomatic during flight, but passed fever scans, but was hospitalized on May 27 and confirmed on May 28). The recent comments indicated the patient was initially Tamiflu sensitive (May 28 test), and resistance was discovered after patient improved (she was discharged May 31). Thus, the resistance in the May 30 sample was present only a few days after the start of treatment and the sequences (on HA, NA. MP) had no evidence of a mixture, indicating the resistant sequence quickly replaced the wild type sequence, signaling silently spread of H274Y.
Thus, the WHO failure to see the resistance was linked to limited and delayed testing of samples collected a few days after the start of treatment, and the standard testing / sequencing failed to detect the H274Y transmitting as a minor population. The HA Singapore sequence has a polymorphism that was found in isolates in the US, Sweden, China, and Argentina, raising concerns that the H274Y was creating additional problems in Tamiflu treated patients as seen in the two immune-compromised patients in Washington State as well as rising fatalitiesbeing reported worldwide.
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August 17th, 2009, 09:02 AM
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
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August 18th, 2009, 08:00 PM
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Editor, Senior Moderator
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Re: China, Singapore report Tamiflu-resistant H1N1 viruses
Quote:
Originally Posted by niman
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Commentary
WHO Withholding Tamiflu Resistant Pandemic H1N1 Locations
Recombinomics Commentary 13:55
August 17, 2009
He revealed that the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses. He would not say where they were found or how many there were in total.
"It's a small number. It certainly doesn't change the scale of what we're seeing," Penn said.
The above comments by WHO are curious. WHO is funded by member nations and has a mandate to protect citizens of member nations. The withholding of important information such as the number and location of Tamiflu resistant pandemic H1N1 virus is not consistent with that mission. Tamiflu is widely used and recommended by WHO, so the withholding of information on resistance leads to inappropriate use of the antiviral, and places patient care and health care systems at risk.
This type of risk was easily seen in the two immuno-suppressed patients detailed in the recent MMWR dispatch. WHO has maintained that resistance is rare and due to spontaneous mutations selected in Tamiflu treated patients. However, recent data, including that from the patients in Washington state suggested that the limited number of reports is related to limited and delayed testing, which is compounded by the withholding of information on identified isolated.
The MMWR describe patients who were H1N1 infected in June. The patients were treated with Tamiflu and detectable resistance developed quickly. However, treatment was increased and resistance was not confirmed until August, after one patient developed a Tamiflu resistant recurrence and the other patient continues to be hospitalized in spite of treatment with Tamiflu, Relenza, and ribavirin. The ability of Tamiflu resistant pandemic H1N1 to persistence in such aggressively treated patients increases concerns that the recent worldwide rise in patient deaths and hospitalizations is linked in part to such resistance.
When WHO stated it was withholding the information on resistance, there had already been 8 examples in patients which were supported by sequence data. Another example (in Thailand) had already been described in media reports and shortly after the proclamation by WHO, Hong Kong reported another cases of resistance in a patient being treated prophylatically and the two patients in Washington State were detailed. Moreover, additional information on the American patient in Singapore provided compelling data that H274Y was silently circulating because the vast majority by WHO and consultants involved samples collected prior to Tamiflu treatment, which were failing to detect the H274Y present as a mixture in the H1N1 samples being sequenced.
The WHO should be encouraging countries to promptly report resistance and expand testing to patients who have been briefly treated with Tamiflu. A true accounting of H274Y in pandemic H1N1 is long overdue.
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
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