Re: Flu and Tamiflu Resistance

[Guest guest]

Thanks for sharing this info, !  Haven’t

seen flu yet, but a colleague thought for sure one fella had it, but test came

back negative.

A. Eads, M.D.

Pinnacle Family Medicine, PLLC

phone fax

P.O.

Box 7275

Woodland

Park, CO 80863

www.PinnacleFamilyMedicine.com

From: [mailto: ] On Behalf Of Locke, MD

Sent: Thursday, January 08, 2009

7:38 PM

Subject:

Flu and Tamiflu Resistance

I've been surprised at the lack of flu so far in our mountain

valley, but did have a patient with fever, chills, myalgias, headache, and

cough this morning.

Flu test showed a faint (+) for flu Type A – faint, but definitely

present.

Anyone else seeing much flu yet?

I'm still anxious about the inevitable Tamiflu resistance – which

is probably already here – see the CDC recommendations below.

The guidelines are definitely changed this year and may affect many of the

treatments we used last year which was different than the year before.

See previous info from December 2008 (end of e-mail), but below is

a google search on the subject and the scary details on increasing resistance.

Guidelines for treatment, too.

Excellent table that describes the various treatment options.

Locke, MD

===============================================

Google on tamiflu resistance…

http://tinyurl.com/6vaal2

http://www.cdc.gov/flu/professionals/antivirals/index.htm

http://www.nytimes.com/2009/01/09/health/09flu.html?ref=health

The single mutation that creates Tamiflu resistance appears to be

spontaneous, and not a reaction to overuse of the drug. It may have occurred in

Asia, and it was widespread in Europe last

year.

Exactly how the Tamiflu-resistant strain emerged is a mystery,

several experts said.

Resistance appeared several years ago in Japan, which

uses more Tamiflu than any other country, and experts feared it would spread.

But the Japanese strains were found only in patients already

treated with Tamiflu, and they were " weak " — that is, they did not

transmit to other people.

" This looks like a spontaneous development of resistance in

the most unlikely places — possibly in Norway, which doesn't use

antivirals at all, " Dr. Monto said.

http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279

CDC Issues Interim

Recommendations for the Use of Influenza Antiviral Medications in the Setting

of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses,

2008-09 Influenza Season

Although influenza activity is low in the United States

to date, preliminary data from a limited number of states indicate that the

prevalence of influenza A (H1N1) virus strains resistant to the antiviral

medication oseltamivir is high. Therefore, CDC is issuing interim

recommendations for antiviral treatment and chemoprophylaxis of influenza during

the 2008-09 influenza season.

When influenza A (H1N1) virus infection or exposure is suspected…

zanamivir (relenza) or a combination of

oseltamivir (Tamiflu) and rimantadine (Flumadine) are more appropriate options

than oseltamivir alone.

Local influenza surveillance data and laboratory testing can help with

physician decision-making regarding the choice of antiviral agents for their

patients. The 2008-09 influenza vaccine is expected to be effective in

preventing or reducing the severity of illness with currently circulating

influenza viruses, including oseltamivir-resistant influenza A (H1N1)

virus strains. Since influenza activity remains low and is expected to increase

in the weeks and months to come, CDC recommends that influenza vaccination efforts

continue

During the 2007-08 influenza season, 10.9% of H1N1 viruses tested

in the U.S.

were resistant to oseltamivir.

Of the 50 H1N1 viruses tested to date from 12 states, 98% were

resistant to oseltamivir, and all were susceptible to zanamivir, amantadine and

rimantadine

Preliminary data indicate that oseltamivir-resistant

influenza A (H1N1) viruses do not cause different or more severe symptoms

compared to oseltamivir sensitive influenza A (H1N1) viruses.

Influenza A (H3N2) and B viruses remain susceptible to oseltamivir.

The proportion of influenza A (H1N1) viruses among all influenza A and B

viruses that will circulate during the 2008-09 season cannot be predicted, and

will likely vary over the course of the season and among communities. Oseltamivir-resistant

influenza A (H1N1) viruses are antigenically similar to the influenza A (H1N1)

virus strain represented in 2008-09 influenza vaccine, and CDC recommends that

influenza vaccination efforts continue as the primary method to prevent influenza.

Interim Recommendations

Persons providing medical care for patients with suspected

influenza or persons who are candidates for chemoprophylaxis against influenza

should consider the following guidance for assessing and treating patients

during the 2008-09 influenza season (see Table below). Guidance Table):

1)

Review local or state influenza virus surveillance data weekly during influenza

season, to determine which types (A or and subtypes of influenza A virus

(H3N2 or H1N1) are currently circulating in the area. For some communities,

surveillance data might not be available or timely enough to provide

information useful to clinicians.

2)

Consider use of influenza tests that can distinguish influenza A from influenza

B.

a. Patients testing positive

for influenza B may be given

either oseltamivir or zanamivir (no preference) if treatment is indicated.

b. At this time, if a patient

tests positive for influenza A,

use of zanamivir should be considered if treatment is indicated. Oseltamivir

should be used alone only if recent local surveillance data indicate that

circulating viruses are likely to be influenza A (H3N2) or influenza B viruses.

Combination treatment with oseltamivir and rimantadine is an acceptable

alternative, and might be necessary for patients that cannot receive zanamivir,

(e.g., patient is <7 years old, has chronic underlying airways disease, or

cannot use the zanamivir inhalation device), or zanamivir is unavailable.

Amantadine can be substituted for rimantadine if rimantadine is unavailable.

c. If a patient tests negative

for influenza, consider treatment options based on local influenza activity and

clinical impression of the likelihood of influenza. Because rapid antigen tests

may have low sensitivity, treatment should still be considered during periods

of high influenza activity for persons with respiratory symptoms consistent

with influenza who test negative and have no alternative diagnosis. Use of

zanamivir should be considered if treatment is indicated. Combination treatment

with oseltamivir and rimantadine (substitute amantadine if rimantadine

unavailable) is an acceptable alternative. Oseltamivir should be used alone

only if recent local surveillance data indicates that circulating viruses are

likely to be influenza A(H3N2) or influenza B viruses.

d. If available, confirmatory

testing with a diagnostic test capable of distinguishing influenza caused by

influenza A (H1N1) virus from influenza caused by influenza A (H3N2) or

influenza B virus can also be used to guide treatment. When treatment is indicated,

influenza A (H3N2) and influenza B virus infections should be treated with

oseltamivir or zanamivir (no preference). Influenza A (H1N1) virus infections

should be treated with zanamivir or combination treatment with oseltamivir and

rimantadine is an acceptable alternative.

3) Persons who are

candidates for chemoprophylaxis (e.g., residents in an assisted living facility

during an influenza outbreak, or persons who are at higher risk for

influenza-related complications and have had recent household or other close

contact with a person with laboratory confirmed influenza) should be provided

with medications most likely to be effective against the influenza virus that

is the cause of the outbreak, if known. Respiratory specimens from ill persons

during institutional outbreaks should be obtained and sent for testing to

determine the type and subtype of influenza A viruses associated with the

outbreak and to guide antiviral therapy decisions.

Persons whose need for chemoprophylaxis is due to potential exposure to a

person with laboratory-confirmed influenza A (H3N2) or influenza B should

receive oseltamivir or zanamivir (no preference).

Zanamivir should be used when persons require chemoprophylaxis due to exposure

to influenza A ( H1N1) virus. Rimantadine can be used if zanamivir use is

contraindicated.

TABLE

Interim recommendations for the selection

of antiviral treatment using laboratory test results and viral surveillance

data, United States, 2008-09 season‡

Rapid antigen or other laboratory test

Predominant virus(es) in community

Preferred medication(s)

Alternative (combination antiviral

treatment)

Not done or negative, but clinical suspicion for

influenza

H1N1 or unknown

Zanamivir

Oseltamivir + Rimantadine*

Not done or negative, but clinical suspicion for

influenza

H3N2 or B

Oseltamivir or Zanamivir

None

Positive A

H1N1 or unknown

Zanamivir

Oseltamivir + Rimantadine*

Positive A

H3N2 or B

Oseltamivir or Zanamivir

None

Positive B

Any

Oseltamivir or Zanamivir

None

Positive A+B**

H1N1 or unknown

Zanamivir

Oseltamivir + Rimantadine*

Positive A+B**

H3N2 or B

Oseltamivir or Zanamivir

None

*Amantadine can be substituted for rimantadine but has increased

risk of adverse events. Human data are lacking to support the benefits of

combination antiviral treatment of influenza; however, these interim

recommendations are intended to assist clinicians treating patients who might

be infected with oseltamivir-resistant influenza A (H1N1) virus.

**Positive A+B indicates a rapid antigen test that cannot

distinguish between influenza and influenza B viruses

‡ Influenza antiviral medications used for treatment are most

beneficial when initiated within the first two days of illness. Clinicians

should consult the package insert of each antiviral medication for specific

dosing information, approved indications and ages, contraindications/warnings/precautions,

and adverse effects.

http://www.cdc.gov/flu/weekly/usmap.htm

Weekly Report: Image

Download

To download the image below, right click

on the map and select the " Save Picture As... " option to save it to

your computer.

http://content.nejm.org/cgi/content/full/353/25/2633

http://content.nejm.org/cgi/content/full/359/10/1074

Volume 359:1074-1076

September 4,

2008

Number 10

Fatal Oseltamivir-Resistant Influenza

Virus Infection

http://content.nejm.org/cgi/content/full/359/24/2579

Volume

359:2579-2585

December 11,

2008

Number 24

Next

Prevention and Treatment of Seasonal

Influenza

W. Glezen, M.D.

=============================

From: Locke [mailto:lockecoloradogmail]

Sent: Saturday, December 06, 2008

2:33 PM

To: kellylockefamilymedicine;

Dewayne Niebur; Kim Scheuer; 'Ann Mass'; Anne Goyette; & Cara

Borchers; 'Dr. Bruce Bowen'; karenlockefamilymedicine; h2ovisioncomcast (DOT) net;

Suzie Zimet

Subject: SuperFlu - Tamiflu

resistance

Should be an interesting winter.

http://news.scotsman.com/scotland/39Superflu39-arrives-in-Scotland.4746980.jp

'Superflu' arrives in Scotland

Published Date: 01 December 2008

By LOUISE HOSIE

TWO cases of a so-called superflu which is resistant to a common

type of anti-viral treatment have been identified in Scotland, it was reported last

night.

The patients have been diagnosed with the strain of the illness

which does not respond to the drug Tamiflu, it was claimed.

Dr Jim McMenamin, consultant epidemiologist for Health Protection Scotland,

said that symptoms caused by the resistant virus were no more severe than those

triggered by normal influenza, but there were fewer treatment options. The

other two common flu drugs have worked against the virus.

" We have not seen the appearance of multiple-drug resistance, we have just

seen this one medicine with this particular virus, " Dr McMenamin said.

" We are continuing to make sure samples are tested to see if there are any

other resistance patterns. "

He added it was essential for people who were vulnerable to the illness to

receive a flu jab from their GP. The resistant strain was first identified in

more than 20 European countries during the last flu season

http://www.recombinomics.com/News/11280802/H274Y_X_Hawaii.html

Commentary

H1N1 Tamiflu Resistance Clade Exchanges in

Hawaii?

Recombinomics

Commentary 19:02

November 28, 2008

Twenty of 21 influenza A (H1N1) viruses tested were resistant to

oseltamivir

The above comment

from this week's CDC report includes information on the 19 isolates tested

since the prior report, and all 19

have H274Y. The level of H274Y in clade 2B (Brisbane/59), was

expected to be at or near 100% based on initial reports from Europe

and Canada,

as well as earlier reports from countries

in the southern hemisphere

where resistance was at or near 100% for the 2008 season.

However, in the United States

the vast majority of H1N1 isolates were from the Pacific region and the highest

levels were in Hawaii, where clade 2B and

clade 2C (Hong Kong) were co-circulating last

season. Last season all clade 2C isolates were amantadine resistant, but

none were oseltamivir resistant (H274Y). Moreover, the level of H274Y in

clade 2B was low.

Therefore, the report that all 19 of the most recent H1N1 were resistant,

raises concerns that H274Y levels were increasing in clade 2C, if there were

significant numbers of clade 2C isolates in the initial reports.

Recently, Hong Kong reported

an increase in H274Y levels, but the 17.% reported for the 3rd quarter was far

below the rate in the US and

Europe which was at or near 100%. The high

levels in the United

State raise concerns that

the high level of H274Y in clade 2B is leading to increases in co-circulating

clade 2C through an exchange of genetic information, either via reaasortment or

recombination

More information on clade 2C representation in the first 21 H1N1 isolates

tested would be useful.

[Guest guest]

I haven't seen any really flu surge yet. Working in an UC in VA that sees between 100-130 patients a day between 4 providers. According to our lab tech that were 2 positive flu tests last weekend, but I'm really suspicious for false positives when a lot of tests are being done. I personally haven't seen a patient who I strongly felt had the flu. Personally, I find strong conjunctival injection along with the typical sxs to be my most specific predictor of a positive flu test and therefore the "real" flu in my practice. The past couple of years the flu has had a late onset, to my thinking, in VA . The Tamiflu rep told me they were seeing sporadic flu in the TIdewater area, alot of military there so it could be possible. What say, ? As far as resistance is concerned; my understanding is that almost all mutations are spontaneous. Genes are not "smart" in the sense that they can predict a coming challenge to the survival of the organism; but once a spontaneous mutation occurs that provides a survival benefit, the individuals with the mutation are more likely to survive and reproduce in the altered environment (i.e. the toxic environment of Tamiflu tainted body fluids) creating a resistant population. Also, if the challenge is removed, the resistant population usually shrinks due to a superior survivability of the "wild" genome which has already evolved to be the most survivable in "normal" environmental circumstances. This may explain why Tamiflu resistant populations are "weak" i.e. the mutation that confers resistance at the same time affects the genes that determine infectiousness and lessens it's ability to be transmitted. StrazThanks for sharing this info, ! Haven’t seen flu yet, but a colleague thought for sure one fella had it, but test came back negative. A. Eads, M.D.Pinnacle Family Medicine, PLLC phone faxP.O. Box 7275Woodland Park, CO 80863www.PinnacleFamilyMedicine.comFrom: [mailto: ] On Behalf Of Locke, MDSent: Thursday, January 08, 2009 7:38 PMSubject: Flu and Tamiflu Resistance I've been surprised at the lack of flu so far in our mountain valley, but did have a patient with fever, chills, myalgias, headache, and cough this morning.Flu test showed a faint (+) for flu Type A – faint, but definitely present. Anyone else seeing much flu yet?I'm still anxious about the inevitable Tamiflu resistance – which is probably already here – see the CDC recommendations below.The guidelines are definitely changed this year and may affect many of the treatments we used last year which was different than the year before. See previous info from December 2008 (end of e-mail), but below is a google search on the subject and the scary details on increasing resistance.Guidelines for treatment, too.Excellent table that describes the various treatment options. Locke, MD=============================================== Google on tamiflu resistance… http://tinyurl.com/6vaal2 http://www.cdc.gov/flu/professionals/antivirals/index.htm http://www.nytimes.com/2009/01/09/health/09flu.html?ref=health The single mutation that creates Tamiflu resistance appears to be spontaneous, and not a reaction to overuse of the drug. It may have occurred in Asia, and it was widespread in Europe last year.Exactly how the Tamiflu-resistant strain emerged is a mystery, several experts said.Resistance appeared several years ago in Japan, which uses more Tamiflu than any other country, and experts feared it would spread.But the Japanese strains were found only in patients already treated with Tamiflu, and they were "weak" — that is, they did not transmit to other people."This looks like a spontaneous development of resistance in the most unlikely places — possibly in Norway, which doesn't use antivirals at all," Dr. Monto said. http://www2a.cdc.gov/HAN/ArchiveSys/ViewMsgV.asp?AlertNum=00279 CDC Issues Interim Recommendations for the Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses, 2008-09 Influenza SeasonAlthough influenza activity is low in the United States to date, preliminary data from a limited number of states indicate that the prevalence of influenza A (H1N1) virus strains resistant to the antiviral medication oseltamivir is high. Therefore, CDC is issuing interim recommendations for antiviral treatment and chemoprophylaxis of influenza during the 2008-09 influenza season. When influenza A (H1N1) virus infection or exposure is suspected…zanamivir (relenza) or a combination of oseltamivir (Tamiflu) and rimantadine (Flumadine) are more appropriate options than oseltamivir alone. Local influenza surveillance data and laboratory testing can help with physician decision-making regarding the choice of antiviral agents for their patients. The 2008-09 influenza vaccine is expected to be effective in preventing or reducing the severity of illness with currently circulating influenza viruses, including oseltamivir-resistant influenza A (H1N1) virus strains. Since influenza activity remains low and is expected to increase in the weeks and months to come, CDC recommends that influenza vaccination efforts continueDuring the 2007-08 influenza season, 10.9% of H1N1 viruses tested in theU.S. were resistant to oseltamivir. Of the 50 H1N1 viruses tested to date from 12 states, 98% were resistant to oseltamivir, and all were susceptible to zanamivir, amantadine and rimantadine Preliminary data indicate that oseltamivir-resistant influenza A (H1N1) viruses do not cause different or more severe symptoms compared to oseltamivir sensitive influenza A (H1N1) viruses. Influenza A (H3N2) and B viruses remain susceptible to oseltamivir. The proportion of influenza A (H1N1) viruses among all influenza A and B viruses that will circulate during the 2008-09 season cannot be predicted, and will likely vary over the course of the season and among communities. Oseltamivir-resistant influenza A (H1N1) viruses are antigenically similar to the influenza A (H1N1) virus strain represented in 2008-09 influenza vaccine, and CDC recommends that influenza vaccination efforts continue as the primary method to prevent influenza. Interim Recommendations Persons providing medical care for patients with suspected influenza or persons who are candidates for chemoprophylaxis against influenza should consider the following guidance for assessing and treating patients during the 2008-09 influenza season (see Table below). Guidance Table):1) Review local or state influenza virus surveillance data weekly during influenza season, to determine which types (A or and subtypes of influenza A virus (H3N2 or H1N1) are currently circulating in the area. For some communities, surveillance data might not be available or timely enough to provide information useful to clinicians.2) Consider use of influenza tests that can distinguish influenza A from influenza B.a. Patients testing positive for influenza B may be given either oseltamivir or zanamivir (no preference) if treatment is indicated.b. At this time, if a patient tests positive for influenza A, use of zanamivir should be considered if treatment is indicated. Oseltamivir should be used alone only if recent local surveillance data indicate that circulating viruses are likely to be influenza A (H3N2) or influenza B viruses. Combination treatment with oseltamivir and rimantadine is an acceptable alternative, and might be necessary for patients that cannot receive zanamivir, (e.g., patient is <7 years old, has chronic underlying airways disease, or cannot use the zanamivir inhalation device), or zanamivir is unavailable. Amantadine can be substituted for rimantadine if rimantadine is unavailable.c. If a patient tests negative for influenza, consider treatment options based on local influenza activity and clinical impression of the likelihood of influenza. Because rapid antigen tests may have low sensitivity, treatment should still be considered during periods of high influenza activity for persons with respiratory symptoms consistent with influenza who test negative and have no alternative diagnosis. Use of zanamivir should be considered if treatment is indicated. Combination treatment with oseltamivir and rimantadine (substitute amantadine if rimantadine unavailable) is an acceptable alternative. Oseltamivir should be used alone only if recent local surveillance data indicates that circulating viruses are likely to be influenza A(H3N2) or influenza B viruses.d. If available, confirmatory testing with a diagnostic test capable of distinguishing influenza caused by influenza A (H1N1) virus from influenza caused by influenza A (H3N2) or influenza B virus can also be used to guide treatment. When treatment is indicated, influenza A (H3N2) and influenza B virus infections should be treated with oseltamivir or zanamivir (no preference). Influenza A (H1N1) virus infections should be treated with zanamivir or combination treatment with oseltamivir and rimantadine is an acceptable alternative. 3) Persons who are candidates for chemoprophylaxis (e.g., residents in an assisted living facility during an influenza outbreak, or persons who are at higher risk for influenza-related complications and have had recent household or other close contact with a person with laboratory confirmed influenza) should be provided with medications most likely to be effective against the influenza virus that is the cause of the outbreak, if known. Respiratory specimens from ill persons during institutional outbreaks should be obtained and sent for testing to determine the type and subtype of influenza A viruses associated with the outbreak and to guide antiviral therapy decisions. Persons whose need for chemoprophylaxis is due to potential exposure to a person with laboratory-confirmed influenza A (H3N2) or influenza B should receive oseltamivir or zanamivir (no preference). Zanamivir should be used when persons require chemoprophylaxis due to exposure to influenza A ( H1N1) virus. Rimantadine can be used if zanamivir use is contraindicated. TABLEInterim recommendations for the selection of antiviral treatment using laboratory test results and viral surveillance data, United States, 2008-09 season‡Rapid antigen or other laboratory testPredominant virus(es) in communityPreferred medication(s)Alternative (combination antiviral treatment)Not done or negative, but clinical suspicion for influenzaH1N1 or unknownZanamivirOseltamivir + Rimantadine*Not done or negative, but clinical suspicion for influenzaH3N2 or BOseltamivir or ZanamivirNonePositive AH1N1 or unknownZanamivirOseltamivir + Rimantadine*Positive AH3N2 or BOseltamivir or ZanamivirNonePositive BAnyOseltamivir or ZanamivirNonePositive A+B**H1N1 or unknownZanamivirOseltamivir + Rimantadine*Positive A+B**H3N2 or BOseltamivir or ZanamivirNone*Amantadine can be substituted for rimantadine but has increased risk of adverse events. Human data are lacking to support the benefits of combination antiviral treatment of influenza; however, these interim recommendations are intended to assist clinicians treating patients who might be infected with oseltamivir-resistant influenza A (H1N1) virus.**Positive A+B indicates a rapid antigen test that cannot distinguish between influenza and influenza B viruses‡ Influenza antiviral medications used for treatment are most beneficial when initiated within the first two days of illness. Clinicians should consult the package insert of each antiviral medication for specific dosing information, approved indications and ages, contraindications/warnings/precautions, and adverse effects.http://www.cdc.gov/flu/weekly/usmap.htmWeekly Report: Image DownloadTo download the image below, right click on the map and select the "Save Picture As..." option to save it to your computer.<image002.jpg> http://content.nejm.org/cgi/content/full/353/25/2633 <image005.jpg> http://content.nejm.org/cgi/content/full/359/10/1074 Volume 359:1074-1076<image006.gif>September 4, 2008<image006.gif>Number 10 Fatal Oseltamivir-Resistant Influenza Virus Infection http://content.nejm.org/cgi/content/full/359/24/2579 Volume 359:2579-2585<image006.gif>December 11, 2008<image006.gif>Number 24Next<image007.gif>Prevention and Treatment of Seasonal InfluenzaW. Glezen, M.D. ============================= From: Locke [mailto:lockecoloradogmail] Sent: Saturday, December 06, 2008 2:33 PMTo: kellylockefamilymedicine; Dewayne Niebur; Kim Scheuer; 'Ann Mass'; Anne Goyette; & Cara Borchers; 'Dr. Bruce Bowen'; karenlockefamilymedicine; h2ovisioncomcast (DOT) net; Suzie ZimetSubject: SuperFlu - Tamiflu resistance Should be an interesting winter. http://news.scotsman.com/scotland/39Superflu39-arrives-in-Scotland.4746980.jp'Superflu' arrives in Scotland Published Date: 01 December 2008By LOUISE HOSIETWO cases of a so-called superflu which is resistant to a common type of anti-viral treatment have been identified in Scotland, it was reported last night.The patients have been diagnosed with the strain of the illness which does not respond to the drug Tamiflu, it was claimed.Dr Jim McMenamin, consultant epidemiologist for Health Protection Scotland, said that symptoms caused by the resistant virus were no more severe than those triggered by normal influenza, but there were fewer treatment options. The other two common flu drugs have worked against the virus."We have not seen the appearance of multiple-drug resistance, we have just seen this one medicine with this particular virus," Dr McMenamin said."We are continuing to make sure samples are tested to see if there are any other resistance patterns."He added it was essential for people who were vulnerable to the illness to receive a flu jab from their GP. The resistant strain was first identified in more than 20 European countries during the last flu season http://www.recombinomics.com/News/11280802/H274Y_X_Hawaii.html CommentaryH1N1 Tamiflu Resistance Clade Exchanges in Hawaii?Recombinomics Commentary 19:02November 28, 2008Twenty of 21 influenza A (H1N1) viruses tested were resistant to oseltamivirThe above comment from this week's CDC report includes information on the 19 isolates tested since the prior report, and all 19 have H274Y. The level of H274Y in clade 2B (Brisbane/59), was expected to be at or near 100% based on initial reports from Europe and Canada, as well as earlier reports from countries in the southern hemisphere where resistance was at or near 100% for the 2008 season.However, in the United States the vast majority of H1N1 isolates were from the Pacific region and the highest levels were in Hawaii, where clade 2B and clade 2C (Hong Kong) were co-circulating last season. Last season all clade 2C isolates were amantadine resistant, but none were oseltamivir resistant (H274Y). Moreover, the level of H274Y in clade 2B was low.Therefore, the report that all 19 of the most recent H1N1 were resistant, raises concerns that H274Y levels were increasing in clade 2C, if there were significant numbers of clade 2C isolates in the initial reports.Recently, Hong Kong reported an increase in H274Y levels, but the 17.% reported for the 3rd quarter was far below the rate in the US and Europewhich was at or near 100%. The high levels in the United State raise concerns that the high level of H274Y in clade 2B is leading to increases in co-circulating clade 2C through an exchange of genetic information, either via reaasortment or recombinationMore information on clade 2C representation in the first 21 H1N1 isolates tested would be useful.