Re: Two Tamiflu-resistant swine flu cases reported in Washington
Yes. Singapore was sensitive on May 28 and resistant on May 30.
-
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Two Tamiflu-resistant swine flu cases reported in Washington
- Thread starter HenryN
- Start date
Re: Two Tamiflu-resistant swine flu cases reported in Washington
There is a ton of evidence from Japan that shows when you take Tamiflu, the target virus soon learns how to wire around the meds and become resistant. This is especially true for children (who normally have immature immune systems) that have been given the drug. Even Roche, the manufacturer of the drug admits to this and even provides a percentage of how often it occurs.
The "new" theory is that the resistance has just been silently hiding in the background all along, and therefore was not previously detectable.
There is a ton of evidence from Japan that shows when you take Tamiflu, the target virus soon learns how to wire around the meds and become resistant. This is especially true for children (who normally have immature immune systems) that have been given the drug. Even Roche, the manufacturer of the drug admits to this and even provides a percentage of how often it occurs.
The "new" theory is that the resistance has just been silently hiding in the background all along, and therefore was not previously detectable.
Re: Two Tamiflu-resistant swine flu cases reported in Washington
To distinguish between a de novo mutation instead the selection of a minor population requires some tight collection dates. In Singapore the patient developed symptoms on May 26, was hospitalized on May 27, and was tamiflu sensitive on May 28. Treatment began on May 27 or 28 and collection on May 30 was resistant. The 2-3 period is too short for detection of de novo resistance. The patient was infected with a mixture and the H274Y was obvious (no wild type detected) a few days after the start of Tamiflu treatment.
sharon sanders
Editor-in-Chief & President
Re: Two Tamiflu-resistant swine flu cases reported in Washington
I will make one comment. Everyone is aware of the "issue" that we have with Niman and the name of his mapping project.
Also, I have forbid him from using the words "Please" and "Nonsense" to attack other posters.
However, if I see any "Niman baiting" I will impose sanctions on those posters.
Do not mistake a disagreement with Niman for a license to provoke him into displaying "bad behavior".
We are a charity. We are interested in the pursuit of the truth - where ever it takes us.
Thanks everyone for a great discussion!
:yinyang:
I will make one comment. Everyone is aware of the "issue" that we have with Niman and the name of his mapping project.
Also, I have forbid him from using the words "Please" and "Nonsense" to attack other posters.
However, if I see any "Niman baiting" I will impose sanctions on those posters.
Do not mistake a disagreement with Niman for a license to provoke him into displaying "bad behavior".
We are a charity. We are interested in the pursuit of the truth - where ever it takes us.
Thanks everyone for a great discussion!
:yinyang:
Re: Two Tamiflu-resistant swine flu cases reported in Washington
What do you mean "a mixture"? Are you saying she had 2 different viral strains at once?
Re: Two Tamiflu-resistant swine flu cases reported in Washington
If people can't control their rudness, then that's their problem. Nobody is baiting Niman by asking him to explain what he's talking about and to back his theories.
If people can't control their rudness, then that's their problem. Nobody is baiting Niman by asking him to explain what he's talking about and to back his theories.
gsgs
Registered User
Re: Two Tamiflu-resistant swine flu cases reported in Washington
yes, I think he means different viruses, a mixture.
You rarely get infected by a single virus and mutants evolving
during infection is normal.
But usually you still get the same virus on different samples
of the same person or 1-2 differences occasionally
yes, I think he means different viruses, a mixture.
You rarely get infected by a single virus and mutants evolving
during infection is normal.
But usually you still get the same virus on different samples
of the same person or 1-2 differences occasionally
sharon sanders
Editor-in-Chief & President
Re: Two Tamiflu-resistant swine flu cases reported in Washington
I agree. Jus' sayin'....
I agree. Jus' sayin'....
Re: Two Tamiflu-resistant swine flu cases reported in Washington
The testing doesn't detect a few viruses. 2-3 days is too short to get enough virus to detect in a clinical sample like a throat swab (in fact sequencing won't even generate a consensus sequence when the minor species is below 10-20% - you almost need a 50/50 ratio to get mixed signals).
AlaskaDenise
In Memoriam
Re: Two Tamiflu-resistant swine flu cases reported in Washington
Why is there a problem detecting de novo in a short time period?
.
Why is there a problem detecting de novo in a short time period?
.
Re: Two Tamiflu-resistant swine flu cases reported in Washington
In the past several years there have been NO reports of Tamiflu resistance in H3N2. In addition, all resistance in H1N1 has been H274Y.
This pattern alone suggest that the H274Y isn't due to selection of random errors because only one "error" is selected. Moreover, in seasonal flu, almost all cases of resistance were in patients not taking Tamiflu (and have no such selection).
In pandemic H1N1, the detection has been too quick for de novo. In asymptomatic patients, incubation times are normallly 2-4 days. Patients have been developing symptoms in 5 days. The slightly longer time period indicates a lower than normal level of virus, because the virus with H274Y is a minor population (at 1-10% of the infectious virus). As a result, it takes a day or two longer to produce symptoms. For Singapore, the patient already had symptoms prior to treatment, but the detected virus switched from sensitive to resistant in a couple of days, which is too short for detection of a virus that starts from a recent copy error.
There is a big difference between earlier data in Japan and the H274Y seen in seasonal or pandemic H1N1. In Japan, sub-optimal levels produced resistance in H3N2 as well as H1N1 and at multiple positions (and only in patients being treated).
In the past several years there have been NO reports of Tamiflu resistance in H3N2. In addition, all resistance in H1N1 has been H274Y.
This pattern alone suggest that the H274Y isn't due to selection of random errors because only one "error" is selected. Moreover, in seasonal flu, almost all cases of resistance were in patients not taking Tamiflu (and have no such selection).
In pandemic H1N1, the detection has been too quick for de novo. In asymptomatic patients, incubation times are normallly 2-4 days. Patients have been developing symptoms in 5 days. The slightly longer time period indicates a lower than normal level of virus, because the virus with H274Y is a minor population (at 1-10% of the infectious virus). As a result, it takes a day or two longer to produce symptoms. For Singapore, the patient already had symptoms prior to treatment, but the detected virus switched from sensitive to resistant in a couple of days, which is too short for detection of a virus that starts from a recent copy error.
Re: Two Tamiflu-resistant swine flu cases reported in Washington
It takes time for a virus to go from a copy error to a detectable level. De novo starts with a few virions. 1-10% of an infectious dose is in the millions or billions of virions
Re: Two Tamiflu-resistant swine flu cases reported in Washington
INFLUENZA PANDEMIC (H1N1) 2009 (31): DRUG RESISTANCE
****************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Fri 14 Aug 2009
Source: MMWR Dispatch, 14 Aug 2009 / 58 (Dispatch); 1-4
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0814a1.htm?s_cid=mm58d0814a1_e>
Oseltamivir-resistant influenza pandemic (H1N1) 2009 virus infection in 2
immunosuppressed patients
--------------------------------------------------------------------
Influenza (H1N1) 2009 virus infection continues to cause illness and death
among persons worldwide. Immunosuppressed patients with influenza virus
infection can shed virus for prolonged periods, increasing the chances for
development of drug resistance (1-3). On 6 Aug 2009, the Centers for
Disease Control and Prevention (CDC) detected evidence of resistance to the
antiviral medication oseltamivir in 2 severely immunosuppressed patients
with novel influenza A (H1N1) virus [that is, Influenza pandemic (H1N1)
2009 virus] infection in Seattle, Washington. The 2 patients were treated
in 2 different hospitals, and their cases were not epidemiologically
linked. Both were being treated with oseltamivir for novel influenza A
(H1N1) virus infection and had prolonged viral shedding. In both patients,
the virus was documented as initially susceptible to oseltamivir, and
resistance developed subsequently during treatment with the drug. Testing
of viral RNA from both patients by pyrosequencing detected a mutation that
results in a histidine-to-tyrosine substitution at position 275 (H275Y) in
the neuraminidase, known to be associated with oseltamivir resistance
(4,5). The results were confirmed by pyrosequencing, sequencing of the
neuraminidase gene, and neuraminidase inhibition testing of virus isolates
on 11 Aug 2009. One patient's symptoms resolved after treatment with
oseltamivir, and the other patient was receiving treatment with zanamivir
and ribavirin as of 13 Aug 2009. An investigation of health care personnel
(HCP) contacts and other close contacts revealed no evidence of virus
transmission. This report summarizes the case histories and resulting
investigations and highlights the importance of 1) close monitoring for
antiviral drug resistance among immunosuppressed patients receiving
treatment for novel influenza A (H1N1) virus infection and 2) the
implications for infection control.
Case reports
------------
Case 1. A teenaged male was diagnosed with leukemia in November 2008 and
subsequently received outpatient immunosuppressive chemotherapy. On 29 Apr
2009, he was hospitalized for a hematopoietic stem cell transplant, which
he received on 7 May 2009. He received immunosuppressive treatment prior to
his transplantation and remained hospitalized in a single-patient room
after the transplantation. On 31 May 2009, he developed fever, mild cough,
and rhinorrhea, was placed on droplet and contact precautions, and HCP
began using respirators (fit-tested N95 or higher-level protection) for his
care. A nasal wash specimen collected on 31 May 2009 tested positive for
novel influenza A (H1N1) virus by real-time reverse
transcription-polymerase chain reaction (rRT-PCR) at the University of
Washington Virology Laboratory. On 1 Jun 2009, the patient was enrolled in
an influenza antiviral treatment study and he began a 10-day course of
oseltamivir. However, on 4 Jun 2009, novel influenza A (H1N1) virus was
detected again by rRT-PCR and viral culture in nasal wash specimens, and
oseltamivir treatment was extended to a 20-day course, to 20 Jun 2009. The
patient improved and was discharged to a nearby apartment on 7 Jun 2009.
Virus again was detected in nasal wash specimens on 11 Jun 2009. On 7 Jul
2009, a nasal wash specimen collected for routine follow-up on an
outpatient basis was positive for novel influenza A (H1N1) virus by
rRT-PCR; oseltamivir therapy was resumed on 8 Jul 2009.
The patient remained well until 14 Jul 2009, when he was hospitalized with
fever and treated for coagulase-negative staphylococcal infection of an
indwelling central venous catheter. A nasal wash specimen collected on 14
Jul 2009 tested positive for novel influenza A (H1N1) virus by rRT-PCR, and
his oseltamivir was increased to a high dose, 150 mg orally, twice a day.
Increased rhinorrhea and mild cough were noted on 16 Jul 2009. The patient
was discharged on oseltamivir on 18 Jul 2009.
Because of prolonged shedding of novel influenza A (H1N1) virus and
suspected oseltamivir resistance, nasal wash specimens previously collected
from the patient were sent to CDC for antiviral resistance testing and
arrived on 5 Aug 2009. On 6 Aug 2009, pyrosequencing at CDC of viral RNA
from a specimen collected on 4 Jun 2009 revealed susceptibility to
oseltamivir. However, pyrosequencing of a follow-up specimen collected on
30 Jul 2009 indicated oseltamivir resistance, based on detection of the
H275Y mutation (4,5). Treatment of the patient with oseltamivir was stopped
on 6 Aug 09, when CDC pyrosequencing results from the specimens became
available. Because the patient was asymptomatic, no further treatment was
indicated.
On 10 Aug 2009, CDC received previously collected virus isolates from the
patient for pyrosequencing on 11 Aug 2009, which confirmed the previous
results. A novel influenza A (H1N1) virus isolate from a specimen collected
on 31 May 2009 was identified as susceptible to oseltamivir by
pyrosequencing at CDC, but viruses isolated from specimens collected on 11
Jun 2009 and 14 Jul 2009 had the H275Y mutation, indicating oseltamivir
resistance.
Seattle-King County health department investigators interviewed hospital
infection-control staff and the patient's family members and visitors.
Surveillance for influenza-like illness (ILI) among staff members is
standard policy at the hospital where the patient was treated. No cases of
ILI were reported among approximately 100 HCP contacts of the patient.
Active surveillance, involving personal interviews of HCP contacts during
the 2 weeks before diagnosis of oseltamivir resistance did not identify any
HCP with ILI.
After each hospital discharge, the patient lived under voluntary home
isolation according to standard protocol for patients in the
post-hematopoietic stem cell transplant (HSCT) period; he did not attend
any school. When traveling in public, the patient reported wearing a
surgical mask per protocol for immunosuppressed HCST recipients and
avoiding close contact with other persons and crowds. None of the 12 family
member contacts or other persons who had visited the patient while he was
in isolation reported symptoms of ILI.
Case 2: A female patient in her 40s who had a hematopoietic stem cell
transplant for leukemia had a recurrence of leukemia in December 2008. She
underwent 2 cycles of immunosuppressive chemotherapy during March--April
2009. On 21 Jun 2009, she was admitted to the hospital for further
chemotherapy; she also had developed a fever and symptoms of an upper
respiratory infection. She was placed in a single-patient room with droplet
and contact precautions, and a nasal wash specimen was obtained for direct
fluorescent antibody staining (DFA) and viral culture. The DFA result was
indeterminate because of an inadequate cellular specimen; however, on 26
Jun 2009, the University of Washington Virology Laboratory reported
isolation of influenza A virus from the specimen. Antiviral treatment with
high-dose oseltamivir (150 mg orally, twice a day) and rimantadine (100 mg
orally, twice a day) was administered during 26 Jun 26--1 Jul 2009. On 3
Jul 2009, the viral isolate was identified as novel influenza A (H1N1), and
high-dose oseltamivir and rimantadine were restarted. The patient's
respiratory status worsened, and she required supplemental oxygen for
hypoxia. Novel influenza A (H1N1) virus was isolated from additional nasal
wash specimens collected on 6 Jul 2009 and 14 Jul 2009, and from
bronchoalveolar lavage specimens obtained on 16 and 28 Jul 2009. Because of
prolonged viral shedding, specimens were sent to CDC on 4 Aug 2009 for
antiviral susceptibility testing. Treatment with inhaled zanamivir was
attempted, but was poorly tolerated, and oseltamivir was continued.
On 6 Aug 2009, CDC determined that pyrosequencing of viral RNA from the 1st
clinical specimen collected on 21 Jun 2009 did not detect the H275Y
mutation. However, the mutation was detected by pyrosequencing of viral RNA
from a nasal wash specimen collected on 28 Jul 2009. Treatment of the
patient with oseltamivir was discontinued when results became available.
Treatment with inhaled zanamivir after identification of oseltamivir
resistance again was attempted but poorly tolerated. On 7 Aug 2009,
intravenous zanamivir, acquired through an emergency investigational new
drug application for compassionate use, and aerosolized ribavirin therapy
were initiated. As of 13 Aug 2009, the patient remained symptomatic and
hospitalized on intravenous zanamivir and had been switched to oral
ribavirin because of intolerance of aerosolized ribavirin. The patient's
hospital course was complicated by prolonged neutropenia and protracted
bone marrow recovery, neutropenic fever, coagulase-negative Staphylococcus
bacteremia, and _Pneumocystis jirovecii_ pneumonia. On 10 Aug 2009, CDC
received other previously collected virus isolates from this patient for
testing, and pyrosequencing of a virus isolated from a specimen collected
on 14 Jul 2009 had the H275Y mutation, confirming oseltamivir resistance.
The patient was hospitalized in a single-patient room upon admission on 21
Jun 2009. She was initially placed on droplet and contact precautions.
Immediately after confirmation of novel influenza A (H1N1) virus infection,
use of N95 repirators by HCP also was implemented. Active surveillance for
respiratory illness among staff members is routine at the hospital where
the patient was treated, and no cases of ILI or other acute respiratory
illness were reported among the approximately 200 HCP contacts who cared
for the patient. No breaches of personal protective equipment
recommendations (including use of fit-tested N-95 respirators) were
reported among HCP contacts caring for this patient.
Testing of clinical specimens for oseltamivir resistance
--------------------------------------------------------
CDC has tested virus isolates or clinical specimens collected from 37
additional Washington residents with confirmed novel influenza A (H1N1)
virus infection during 26 Apr-30 Jul 2009. None of these viruses had
evidence of the H275Y mutation. As of 11 Aug 2009, of the 670 novel
influenza A (H1N1) viruses collected since April 2009 in the United States
and tested at CDC, 318 had been tested for oseltamivir and zanamivir
resistance by neuraminidase inhibition assay, and 352 clinical specimens
had been screened for oseltamivir resistance for the H275Y mutation by
pyrosequencing. No other oseltamivir-resistant viruses had been identified.
Oseltamivir-resistant viruses isolated from both patients described in this
report were determined to be susceptible to zanamivir by neuraminidase
inhibition assay at CDC. Sequence analysis of the neuraminidase gene of
these oseltamivir-resistant viruses showed that oseltamivir resistance was
not the result of gene reassortment with seasonal influenza A (H1N1) virus.
[byline: J Englund, MD, D Zerr, MD, J Heath, Seattle Children's Hospital,
Univ of Washington, and Fred Hutchinson Cancer Research Center; S Pergam,
MD, J Kuypers, PhD, J Yager, MD, M Boeckh, MD, D Mattson, N Whittington, E
Whimbey, MD, Univ of Washington Medical Center and Fred Hutchinson Cancer
Research Center; J Duchin, MD, Public Health --- Seattle and King County,
Washington. T Uyeki, MD, V Deyde, PhD, M Okomo-Adhiambo, PhD, T Sheu, A
Trujillo, A Klimov, PhD, ScD, L Gubareva, MD, PhD, Influenza Div, National
Center for Immunization and Respiratory Diseases; M Kay, DVM, EIS Officer,
CDC.]
MMWR editorial note:
--------------------
This report describes oseltamivir-resistant novel influenza A (H1N1) virus
infection in 2 severely immunosuppressed patients who were treated with
oseltamivir for acute illness symptoms of laboratory-confirmed influenza.
Initially, both patients were infected with oseltamivir-susceptible
viruses; oseltamivir resistance developed later during antiviral treatment.
The 2 patients were not epidemiologically linked and were treated at
different hospitals. No evidence was found that HCP or other patient
contacts developed ILI caused by oseltamivir-resistant novel influenza A
(H1N1) virus infection.
Immunosuppressed patients are at increased risk for complications of
influenza and are recommended for annual influenza vaccination, although
the immune response to vaccination can be decreased in some persons (6,7).
In otherwise healthy adults with seasonal influenza virus infection, viral
shedding generally resolves within 7 days, compared with immunosuppressed
patients, who can experience prolonged viral shedding for weeks to months.
Antiviral resistance can develop during treatment of influenza in these
patients, and prolonged viral shedding (1,2) of up to 18 months has been
reported, including shedding of oseltamivir-resistant seasonal influenza A
virus for more than 1 year (3). Clinicians caring for immunosuppressed
patients with novel influenza A (H1N1) virus infection should be aware of
the potential for development of antiviral drug resistance during therapy
and prolonged viral shedding. Recommendations for prevention and control of
seasonal influenza among hematopoietic stem cell transplant recipients,
their family members, and HCP have been published (8). Strict adherence to
recommended personal protective equipment and infection-control measures is
advised until an immunosuppressed patient with influenza virus infection
has serial respiratory specimens that remain negative when tested by both
rRT-PCR and viral culture. Interim infection-control guidance for novel
influenza A (H1N1) is available on the CDC website, available at
<http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm>.
Only sporadic cases of oseltamivir resistance associated with the H275Y
mutation in the neuraminidase have been detected in immunocompetent persons
exposed to oseltamivir (9). As of 11 Aug 2009, no evidence had been found
of ongoing transmission of oseltamivir-resistant novel influenza A (H1N1)
virus in the United States or elsewhere in the world. The public health
risk of virus transmission from these 2 immunosuppressed cases with
oseltamivir-resistant novel influenza A (H1N1) virus infection appears to
be low. Currently, enhanced surveillance for oseltamivir resistance among
novel influenza A (H1N1) virus strains isolated from outpatients and
hospitalized patients is being conducted in Washington in collaboration
with CDC. The 2 cases in immunosuppressed patients described in this report
and sporadic cases of oseltamivir resistance in persons with oseltamivir
exposure, highlight the need for ongoing global virologic surveillance and
monitoring of antiviral resistance (10).
All circulating novel influenza A (H1N1) virus strains worldwide remain
susceptible to oseltamivir and zanamivir but resistant to amantadine and
rimantadine. CDC continues to recommend oseltamivir or zanamivir for
treatment of all hospitalized patients with suspected or confirmed novel
influenza A (H1N1) virus infection and for outpatients at increased risk
for influenza-related complications (for example, young children, pregnant
women, and persons with certain chronic medical conditions) with suspected
or confirmed novel influenza A (H1N1) virus infection. Novel influenza A
(H1N1) virus strains with the H275Y mutation are susceptible to zanamivir.
Therefore, in immunosuppressed patients with oseltamivir-resistant novel A
(H1N1) virus infection, zanamivir should be considered the antiviral
treatment of choice; however, zanamivir is not recommended for persons with
underlying airway disease. Additional interim guidance on the use of
antiviral medications for the treatment and prevention of novel influenza A
(H1N1) virus infection is available on the CDC website, available at
<http://www.cdc.gov/h1n1flu/recommendations.htm>.
References:
-----------
1. Klimov AI, Rocha E, Hayden FG, Shult PA, Roumillat LF, Cox NJ. Prolonged
shedding of amantadine-resistant influenzae A viruses by immunodeficient
patients: detection by polymerase chain reaction-restriction analysis. J
Infect Dis 1995; 172: 1352-5.
2. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG. Recovery of
drug-resistant influenza virus from immunocompromised patients: a case
series. J Infect Dis 2006; 193: 760-4.
3. Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of
multidrug-resistant influenza A virus in an immunocompromised patient. N
Engl J Med 2003; 27; 348: 867-8.
4. Deyde VM, Gubareva LV. Influenza genome analysis using pyrosequencing
method: current applications for a moving target. Expert Rev Mol Diagn
2009; 9: 493-509.
5. WHO. CDC pyrosequencing assay to detect H275Y mutation in the
neuraminidase of novel A (H1N1) viruses. Available at
<http://www.who.int/csr/resources/publications/swineflu/NA_DetailedPyrosequencing_20090513.pdf>.
6. CDC. Prevention and control of seasonal influenza with vaccines:
recommendations of the Advisory Committee on Immunization Practices (ACIP),
2009. MMWR 2009; 58(No. RR-8).
7. Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a
review of infection frequency, morbidity, mortality, and vaccine responses.
Lancet Infect Dis 2009; 9: 493-504.
8. CDC. Guidelines for preventing opportunistic infections among
hematopoietic stem cell transplant recipients: recommendations of CDC, the
Infectious Disease Society of America, and the American Society of Blood
and Marrow Transplantation. MMWR 2000; (No. RR-10).
9. WHO. Pandemic (H1N1) 2009. Update 60. Laboratory-confirmed cases of
pandemic (H1N1) 2009 as officially reported to WHO by states parties to the
IHR (2005) as 31 Jul 2009. Available at
<http://www.who.int/csr/don/2009_08_04/en/index.html>.
10. Sheu TG, Deyde VM, Okomo-Adhiambo M, et al. Surveillance for
neuraminidase inhibitor resistance among human influenza A and B viruses
circulating worldwide in 2004--2008. Antimicrob Agents Chemother 2008; 52:
3284-92.
--
communicated by:
ProMED-mail
<promed@promedmail.org>
[It is perhaps not unexpected that uncontained replication of influenza
pandemic (H1N1) 2009 virus in immunosuppressed individuals treated with
high doses of oseltamivir would favour the appearance of resistant virus.
It is reassuring that in the cases described above resistance was conferred
by the H275Y mutation in the NA gene and that the resistant viruses remain
sensitive to inhibition by the alternate neuraminidase inhibitor zanamivir.
Oseltamivir resistance is not uniquely associated with immunosuppression.
There have been previous reports, the most recent concerning a single
patient in a care home in Hong Kong: see
<http://www.news.gov.hk/en/category/healthandcommunity/090814/txt/090814en05006.htm>.
- Mod.CP]
[see also:
Influenza pandemic (H1N1) 2009 (30): assumptions 20090813.287
Influenza pandemic (H1N1) 2009 (29): child treatment 20090811.2869
Influenza pandemic (H1N1) 2009 (28): child treatment 20090811.2859
Influenza pandemic (H1N1) 2009 (27): Viet Nam, patient data update
20090809.2819
Influenza pandemic (H1N1) 2009 (26): update 20090807.2801
Influenza pandemic (H1N1) 2009 (25): Australia, UK, updates 20090806.2784
Influenza pandemic (H1N1) 2009 (24): global update 20090805.2766
Influenza pandemic (H1N1) 2009 (23): (China, Taiwan), co-circ. H3N2
20090802.2713
Influenza pandemic (H1N1) 2009 (22): Australia (NSW), swine 20090801.2698
Influenza pandemic (H1N1) 2009 (21): vaccine priorities 20090730.2669
Influenza pandemic (H1N1) 2009 (20): Peru, 33 percent asymptomatic
20090730.2668
Influenza pandemic (H1N1) 2009 (10): vaccine 20090720.2577
Influenza pandemic (H1N1) 2009 (08): pandemic origins 20090718.2559
Influenza pandemic (H1N1) 2009 (06): case reporting 20090717.2553
Influenza pandemic (H1N1) 2009 (05): vaccine 20090716.2540
Influenza pandemic (H1N1) 2009 (04): pandemic origins 20090715.2527
Influenza pandemic (H1N1) 2009 (03): vaccine 20090713.2505
Influenza pandemic (H1N1) 2009 (02): obesity risk factor 20090711.2482
Influenza pandemic (H1N1) 2009 - Viet Nam: patient data 20090708.2450]
..................cp/ejp/sh
INFLUENZA PANDEMIC (H1N1) 2009 (31): DRUG RESISTANCE
****************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Fri 14 Aug 2009
Source: MMWR Dispatch, 14 Aug 2009 / 58 (Dispatch); 1-4
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0814a1.htm?s_cid=mm58d0814a1_e>
Oseltamivir-resistant influenza pandemic (H1N1) 2009 virus infection in 2
immunosuppressed patients
--------------------------------------------------------------------
Influenza (H1N1) 2009 virus infection continues to cause illness and death
among persons worldwide. Immunosuppressed patients with influenza virus
infection can shed virus for prolonged periods, increasing the chances for
development of drug resistance (1-3). On 6 Aug 2009, the Centers for
Disease Control and Prevention (CDC) detected evidence of resistance to the
antiviral medication oseltamivir in 2 severely immunosuppressed patients
with novel influenza A (H1N1) virus [that is, Influenza pandemic (H1N1)
2009 virus] infection in Seattle, Washington. The 2 patients were treated
in 2 different hospitals, and their cases were not epidemiologically
linked. Both were being treated with oseltamivir for novel influenza A
(H1N1) virus infection and had prolonged viral shedding. In both patients,
the virus was documented as initially susceptible to oseltamivir, and
resistance developed subsequently during treatment with the drug. Testing
of viral RNA from both patients by pyrosequencing detected a mutation that
results in a histidine-to-tyrosine substitution at position 275 (H275Y) in
the neuraminidase, known to be associated with oseltamivir resistance
(4,5). The results were confirmed by pyrosequencing, sequencing of the
neuraminidase gene, and neuraminidase inhibition testing of virus isolates
on 11 Aug 2009. One patient's symptoms resolved after treatment with
oseltamivir, and the other patient was receiving treatment with zanamivir
and ribavirin as of 13 Aug 2009. An investigation of health care personnel
(HCP) contacts and other close contacts revealed no evidence of virus
transmission. This report summarizes the case histories and resulting
investigations and highlights the importance of 1) close monitoring for
antiviral drug resistance among immunosuppressed patients receiving
treatment for novel influenza A (H1N1) virus infection and 2) the
implications for infection control.
Case reports
------------
Case 1. A teenaged male was diagnosed with leukemia in November 2008 and
subsequently received outpatient immunosuppressive chemotherapy. On 29 Apr
2009, he was hospitalized for a hematopoietic stem cell transplant, which
he received on 7 May 2009. He received immunosuppressive treatment prior to
his transplantation and remained hospitalized in a single-patient room
after the transplantation. On 31 May 2009, he developed fever, mild cough,
and rhinorrhea, was placed on droplet and contact precautions, and HCP
began using respirators (fit-tested N95 or higher-level protection) for his
care. A nasal wash specimen collected on 31 May 2009 tested positive for
novel influenza A (H1N1) virus by real-time reverse
transcription-polymerase chain reaction (rRT-PCR) at the University of
Washington Virology Laboratory. On 1 Jun 2009, the patient was enrolled in
an influenza antiviral treatment study and he began a 10-day course of
oseltamivir. However, on 4 Jun 2009, novel influenza A (H1N1) virus was
detected again by rRT-PCR and viral culture in nasal wash specimens, and
oseltamivir treatment was extended to a 20-day course, to 20 Jun 2009. The
patient improved and was discharged to a nearby apartment on 7 Jun 2009.
Virus again was detected in nasal wash specimens on 11 Jun 2009. On 7 Jul
2009, a nasal wash specimen collected for routine follow-up on an
outpatient basis was positive for novel influenza A (H1N1) virus by
rRT-PCR; oseltamivir therapy was resumed on 8 Jul 2009.
The patient remained well until 14 Jul 2009, when he was hospitalized with
fever and treated for coagulase-negative staphylococcal infection of an
indwelling central venous catheter. A nasal wash specimen collected on 14
Jul 2009 tested positive for novel influenza A (H1N1) virus by rRT-PCR, and
his oseltamivir was increased to a high dose, 150 mg orally, twice a day.
Increased rhinorrhea and mild cough were noted on 16 Jul 2009. The patient
was discharged on oseltamivir on 18 Jul 2009.
Because of prolonged shedding of novel influenza A (H1N1) virus and
suspected oseltamivir resistance, nasal wash specimens previously collected
from the patient were sent to CDC for antiviral resistance testing and
arrived on 5 Aug 2009. On 6 Aug 2009, pyrosequencing at CDC of viral RNA
from a specimen collected on 4 Jun 2009 revealed susceptibility to
oseltamivir. However, pyrosequencing of a follow-up specimen collected on
30 Jul 2009 indicated oseltamivir resistance, based on detection of the
H275Y mutation (4,5). Treatment of the patient with oseltamivir was stopped
on 6 Aug 09, when CDC pyrosequencing results from the specimens became
available. Because the patient was asymptomatic, no further treatment was
indicated.
On 10 Aug 2009, CDC received previously collected virus isolates from the
patient for pyrosequencing on 11 Aug 2009, which confirmed the previous
results. A novel influenza A (H1N1) virus isolate from a specimen collected
on 31 May 2009 was identified as susceptible to oseltamivir by
pyrosequencing at CDC, but viruses isolated from specimens collected on 11
Jun 2009 and 14 Jul 2009 had the H275Y mutation, indicating oseltamivir
resistance.
Seattle-King County health department investigators interviewed hospital
infection-control staff and the patient's family members and visitors.
Surveillance for influenza-like illness (ILI) among staff members is
standard policy at the hospital where the patient was treated. No cases of
ILI were reported among approximately 100 HCP contacts of the patient.
Active surveillance, involving personal interviews of HCP contacts during
the 2 weeks before diagnosis of oseltamivir resistance did not identify any
HCP with ILI.
After each hospital discharge, the patient lived under voluntary home
isolation according to standard protocol for patients in the
post-hematopoietic stem cell transplant (HSCT) period; he did not attend
any school. When traveling in public, the patient reported wearing a
surgical mask per protocol for immunosuppressed HCST recipients and
avoiding close contact with other persons and crowds. None of the 12 family
member contacts or other persons who had visited the patient while he was
in isolation reported symptoms of ILI.
Case 2: A female patient in her 40s who had a hematopoietic stem cell
transplant for leukemia had a recurrence of leukemia in December 2008. She
underwent 2 cycles of immunosuppressive chemotherapy during March--April
2009. On 21 Jun 2009, she was admitted to the hospital for further
chemotherapy; she also had developed a fever and symptoms of an upper
respiratory infection. She was placed in a single-patient room with droplet
and contact precautions, and a nasal wash specimen was obtained for direct
fluorescent antibody staining (DFA) and viral culture. The DFA result was
indeterminate because of an inadequate cellular specimen; however, on 26
Jun 2009, the University of Washington Virology Laboratory reported
isolation of influenza A virus from the specimen. Antiviral treatment with
high-dose oseltamivir (150 mg orally, twice a day) and rimantadine (100 mg
orally, twice a day) was administered during 26 Jun 26--1 Jul 2009. On 3
Jul 2009, the viral isolate was identified as novel influenza A (H1N1), and
high-dose oseltamivir and rimantadine were restarted. The patient's
respiratory status worsened, and she required supplemental oxygen for
hypoxia. Novel influenza A (H1N1) virus was isolated from additional nasal
wash specimens collected on 6 Jul 2009 and 14 Jul 2009, and from
bronchoalveolar lavage specimens obtained on 16 and 28 Jul 2009. Because of
prolonged viral shedding, specimens were sent to CDC on 4 Aug 2009 for
antiviral susceptibility testing. Treatment with inhaled zanamivir was
attempted, but was poorly tolerated, and oseltamivir was continued.
On 6 Aug 2009, CDC determined that pyrosequencing of viral RNA from the 1st
clinical specimen collected on 21 Jun 2009 did not detect the H275Y
mutation. However, the mutation was detected by pyrosequencing of viral RNA
from a nasal wash specimen collected on 28 Jul 2009. Treatment of the
patient with oseltamivir was discontinued when results became available.
Treatment with inhaled zanamivir after identification of oseltamivir
resistance again was attempted but poorly tolerated. On 7 Aug 2009,
intravenous zanamivir, acquired through an emergency investigational new
drug application for compassionate use, and aerosolized ribavirin therapy
were initiated. As of 13 Aug 2009, the patient remained symptomatic and
hospitalized on intravenous zanamivir and had been switched to oral
ribavirin because of intolerance of aerosolized ribavirin. The patient's
hospital course was complicated by prolonged neutropenia and protracted
bone marrow recovery, neutropenic fever, coagulase-negative Staphylococcus
bacteremia, and _Pneumocystis jirovecii_ pneumonia. On 10 Aug 2009, CDC
received other previously collected virus isolates from this patient for
testing, and pyrosequencing of a virus isolated from a specimen collected
on 14 Jul 2009 had the H275Y mutation, confirming oseltamivir resistance.
The patient was hospitalized in a single-patient room upon admission on 21
Jun 2009. She was initially placed on droplet and contact precautions.
Immediately after confirmation of novel influenza A (H1N1) virus infection,
use of N95 repirators by HCP also was implemented. Active surveillance for
respiratory illness among staff members is routine at the hospital where
the patient was treated, and no cases of ILI or other acute respiratory
illness were reported among the approximately 200 HCP contacts who cared
for the patient. No breaches of personal protective equipment
recommendations (including use of fit-tested N-95 respirators) were
reported among HCP contacts caring for this patient.
Testing of clinical specimens for oseltamivir resistance
--------------------------------------------------------
CDC has tested virus isolates or clinical specimens collected from 37
additional Washington residents with confirmed novel influenza A (H1N1)
virus infection during 26 Apr-30 Jul 2009. None of these viruses had
evidence of the H275Y mutation. As of 11 Aug 2009, of the 670 novel
influenza A (H1N1) viruses collected since April 2009 in the United States
and tested at CDC, 318 had been tested for oseltamivir and zanamivir
resistance by neuraminidase inhibition assay, and 352 clinical specimens
had been screened for oseltamivir resistance for the H275Y mutation by
pyrosequencing. No other oseltamivir-resistant viruses had been identified.
Oseltamivir-resistant viruses isolated from both patients described in this
report were determined to be susceptible to zanamivir by neuraminidase
inhibition assay at CDC. Sequence analysis of the neuraminidase gene of
these oseltamivir-resistant viruses showed that oseltamivir resistance was
not the result of gene reassortment with seasonal influenza A (H1N1) virus.
[byline: J Englund, MD, D Zerr, MD, J Heath, Seattle Children's Hospital,
Univ of Washington, and Fred Hutchinson Cancer Research Center; S Pergam,
MD, J Kuypers, PhD, J Yager, MD, M Boeckh, MD, D Mattson, N Whittington, E
Whimbey, MD, Univ of Washington Medical Center and Fred Hutchinson Cancer
Research Center; J Duchin, MD, Public Health --- Seattle and King County,
Washington. T Uyeki, MD, V Deyde, PhD, M Okomo-Adhiambo, PhD, T Sheu, A
Trujillo, A Klimov, PhD, ScD, L Gubareva, MD, PhD, Influenza Div, National
Center for Immunization and Respiratory Diseases; M Kay, DVM, EIS Officer,
CDC.]
MMWR editorial note:
--------------------
This report describes oseltamivir-resistant novel influenza A (H1N1) virus
infection in 2 severely immunosuppressed patients who were treated with
oseltamivir for acute illness symptoms of laboratory-confirmed influenza.
Initially, both patients were infected with oseltamivir-susceptible
viruses; oseltamivir resistance developed later during antiviral treatment.
The 2 patients were not epidemiologically linked and were treated at
different hospitals. No evidence was found that HCP or other patient
contacts developed ILI caused by oseltamivir-resistant novel influenza A
(H1N1) virus infection.
Immunosuppressed patients are at increased risk for complications of
influenza and are recommended for annual influenza vaccination, although
the immune response to vaccination can be decreased in some persons (6,7).
In otherwise healthy adults with seasonal influenza virus infection, viral
shedding generally resolves within 7 days, compared with immunosuppressed
patients, who can experience prolonged viral shedding for weeks to months.
Antiviral resistance can develop during treatment of influenza in these
patients, and prolonged viral shedding (1,2) of up to 18 months has been
reported, including shedding of oseltamivir-resistant seasonal influenza A
virus for more than 1 year (3). Clinicians caring for immunosuppressed
patients with novel influenza A (H1N1) virus infection should be aware of
the potential for development of antiviral drug resistance during therapy
and prolonged viral shedding. Recommendations for prevention and control of
seasonal influenza among hematopoietic stem cell transplant recipients,
their family members, and HCP have been published (8). Strict adherence to
recommended personal protective equipment and infection-control measures is
advised until an immunosuppressed patient with influenza virus infection
has serial respiratory specimens that remain negative when tested by both
rRT-PCR and viral culture. Interim infection-control guidance for novel
influenza A (H1N1) is available on the CDC website, available at
<http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm>.
Only sporadic cases of oseltamivir resistance associated with the H275Y
mutation in the neuraminidase have been detected in immunocompetent persons
exposed to oseltamivir (9). As of 11 Aug 2009, no evidence had been found
of ongoing transmission of oseltamivir-resistant novel influenza A (H1N1)
virus in the United States or elsewhere in the world. The public health
risk of virus transmission from these 2 immunosuppressed cases with
oseltamivir-resistant novel influenza A (H1N1) virus infection appears to
be low. Currently, enhanced surveillance for oseltamivir resistance among
novel influenza A (H1N1) virus strains isolated from outpatients and
hospitalized patients is being conducted in Washington in collaboration
with CDC. The 2 cases in immunosuppressed patients described in this report
and sporadic cases of oseltamivir resistance in persons with oseltamivir
exposure, highlight the need for ongoing global virologic surveillance and
monitoring of antiviral resistance (10).
All circulating novel influenza A (H1N1) virus strains worldwide remain
susceptible to oseltamivir and zanamivir but resistant to amantadine and
rimantadine. CDC continues to recommend oseltamivir or zanamivir for
treatment of all hospitalized patients with suspected or confirmed novel
influenza A (H1N1) virus infection and for outpatients at increased risk
for influenza-related complications (for example, young children, pregnant
women, and persons with certain chronic medical conditions) with suspected
or confirmed novel influenza A (H1N1) virus infection. Novel influenza A
(H1N1) virus strains with the H275Y mutation are susceptible to zanamivir.
Therefore, in immunosuppressed patients with oseltamivir-resistant novel A
(H1N1) virus infection, zanamivir should be considered the antiviral
treatment of choice; however, zanamivir is not recommended for persons with
underlying airway disease. Additional interim guidance on the use of
antiviral medications for the treatment and prevention of novel influenza A
(H1N1) virus infection is available on the CDC website, available at
<http://www.cdc.gov/h1n1flu/recommendations.htm>.
References:
-----------
1. Klimov AI, Rocha E, Hayden FG, Shult PA, Roumillat LF, Cox NJ. Prolonged
shedding of amantadine-resistant influenzae A viruses by immunodeficient
patients: detection by polymerase chain reaction-restriction analysis. J
Infect Dis 1995; 172: 1352-5.
2. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG. Recovery of
drug-resistant influenza virus from immunocompromised patients: a case
series. J Infect Dis 2006; 193: 760-4.
3. Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of
multidrug-resistant influenza A virus in an immunocompromised patient. N
Engl J Med 2003; 27; 348: 867-8.
4. Deyde VM, Gubareva LV. Influenza genome analysis using pyrosequencing
method: current applications for a moving target. Expert Rev Mol Diagn
2009; 9: 493-509.
5. WHO. CDC pyrosequencing assay to detect H275Y mutation in the
neuraminidase of novel A (H1N1) viruses. Available at
<http://www.who.int/csr/resources/publications/swineflu/NA_DetailedPyrosequencing_20090513.pdf>.
6. CDC. Prevention and control of seasonal influenza with vaccines:
recommendations of the Advisory Committee on Immunization Practices (ACIP),
2009. MMWR 2009; 58(No. RR-8).
7. Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a
review of infection frequency, morbidity, mortality, and vaccine responses.
Lancet Infect Dis 2009; 9: 493-504.
8. CDC. Guidelines for preventing opportunistic infections among
hematopoietic stem cell transplant recipients: recommendations of CDC, the
Infectious Disease Society of America, and the American Society of Blood
and Marrow Transplantation. MMWR 2000; (No. RR-10).
9. WHO. Pandemic (H1N1) 2009. Update 60. Laboratory-confirmed cases of
pandemic (H1N1) 2009 as officially reported to WHO by states parties to the
IHR (2005) as 31 Jul 2009. Available at
<http://www.who.int/csr/don/2009_08_04/en/index.html>.
10. Sheu TG, Deyde VM, Okomo-Adhiambo M, et al. Surveillance for
neuraminidase inhibitor resistance among human influenza A and B viruses
circulating worldwide in 2004--2008. Antimicrob Agents Chemother 2008; 52:
3284-92.
--
communicated by:
ProMED-mail
<promed@promedmail.org>
[It is perhaps not unexpected that uncontained replication of influenza
pandemic (H1N1) 2009 virus in immunosuppressed individuals treated with
high doses of oseltamivir would favour the appearance of resistant virus.
It is reassuring that in the cases described above resistance was conferred
by the H275Y mutation in the NA gene and that the resistant viruses remain
sensitive to inhibition by the alternate neuraminidase inhibitor zanamivir.
Oseltamivir resistance is not uniquely associated with immunosuppression.
There have been previous reports, the most recent concerning a single
patient in a care home in Hong Kong: see
<http://www.news.gov.hk/en/category/healthandcommunity/090814/txt/090814en05006.htm>.
- Mod.CP]
[see also:
Influenza pandemic (H1N1) 2009 (30): assumptions 20090813.287
Influenza pandemic (H1N1) 2009 (29): child treatment 20090811.2869
Influenza pandemic (H1N1) 2009 (28): child treatment 20090811.2859
Influenza pandemic (H1N1) 2009 (27): Viet Nam, patient data update
20090809.2819
Influenza pandemic (H1N1) 2009 (26): update 20090807.2801
Influenza pandemic (H1N1) 2009 (25): Australia, UK, updates 20090806.2784
Influenza pandemic (H1N1) 2009 (24): global update 20090805.2766
Influenza pandemic (H1N1) 2009 (23): (China, Taiwan), co-circ. H3N2
20090802.2713
Influenza pandemic (H1N1) 2009 (22): Australia (NSW), swine 20090801.2698
Influenza pandemic (H1N1) 2009 (21): vaccine priorities 20090730.2669
Influenza pandemic (H1N1) 2009 (20): Peru, 33 percent asymptomatic
20090730.2668
Influenza pandemic (H1N1) 2009 (10): vaccine 20090720.2577
Influenza pandemic (H1N1) 2009 (08): pandemic origins 20090718.2559
Influenza pandemic (H1N1) 2009 (06): case reporting 20090717.2553
Influenza pandemic (H1N1) 2009 (05): vaccine 20090716.2540
Influenza pandemic (H1N1) 2009 (04): pandemic origins 20090715.2527
Influenza pandemic (H1N1) 2009 (03): vaccine 20090713.2505
Influenza pandemic (H1N1) 2009 (02): obesity risk factor 20090711.2482
Influenza pandemic (H1N1) 2009 - Viet Nam: patient data 20090708.2450]
..................cp/ejp/sh
Re: Two Tamiflu-resistant swine flu cases reported in Washington
Two cases of swine flu resilient to the drug Tamiflu were diagnosed over the weekend, the U.S. Centers for Disease Control and Prevention said yesterday. Tamiflu and Relenza were the only two medications that had thusfar proven effective in treating the virus (also known as H1N1), which already proved resilient to other seasonal flu remedies.
Tamiflu had been particularly popular, as it is ingested orally. Relenza, which is inhaled, is therefore not recommended for patients with respiratory conditions. Both drugs work by disabling an enzyme the virus needs in order to grow. Many governments in the world, including Israel's, have stockpiled Tamiflu in large quantities since the swine-flu pandemic began. <TABLE border=0 cellSpacing=0 cellPadding=0 align=right><TBODY><TR><TD rowSpan=2>
</TD><TD class=t9></TD></TR><TR><TD align=right></TD></TR></TBODY></TABLE>
Reports of Tamiflu-resistant strains of swine flu began in late June. In patients with weakened immune systems the virus might stay active for longer periods, acquiring resistance to Tamiflu and potentially spreading to others.
http://www.haaretz.com/hasen/spages/1107725.html
At the end of June, a representative of the Swiss pharmaceutical company Roche, which manufactures Tamiflu, said a Danish patient infected with a strain of the virus was not responding to the medicine. Earlier studies on Tamiflu indicated that 0.4 percent of adults and 4 percent of children afflicted with normal seasonal flu were likely not to respond to the drug.
Ten more such patients were identified in the world since June, with three in Japan, one in Singapore, one in China, one in Denmark, one in Canada, and two in the United States. However, no patient-to-patient transmission of the Tamiflu-resistant strain has yet been documented.
The two U.S. cases reported over the weekend were documented in Seattle. The swine flu patients were said to be suffering from leukemia and a depleted immune system. One patient is a young man who received a marrow transplant in May, and was said to be recovering at home; the other is a woman in her forties, who is still hospitalized. The two were said to have not been in contact, nor has it been documented that they have infected family members or medical staff with the Tamiflu-resistant strain.
The World Health Organization said it was following the reports, but no changes were yet made to its guidelines on treating the virus.
No Tamiflu-resistant strains have been recorded in Israel, where five more labs for testing for the disease are soon to be allocated by the health ministry. "The spread of a drug-resistant strain is usually slow, and by the time it spreads significantly vaccines against the disease will, in all likelihood, be developed. However, Tamiflu is one of the only medicines that can slow or weaken the disease, so it's crucial that swine flu react to it," said Dr. Amnon Kiro, chief of influenza research at the Israeli Pediatric Association research network.
At the moment, checks for swine flu are only carried out at the Health Ministry laboratory in Tel Hashomer, and in a laboratory at Hadassah University Hospital, Ein Kerem in Jerusalem. The checks are only meant to identify the virus, rather than test its response to Tamiflu.
Thirteen Israelis are presently in intensive care due to swine flu, and seven fatalities have so far been reported.
</TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
Two cases of swine flu resilient to the drug Tamiflu were diagnosed over the weekend, the U.S. Centers for Disease Control and Prevention said yesterday. Tamiflu and Relenza were the only two medications that had thusfar proven effective in treating the virus (also known as H1N1), which already proved resilient to other seasonal flu remedies.
Tamiflu had been particularly popular, as it is ingested orally. Relenza, which is inhaled, is therefore not recommended for patients with respiratory conditions. Both drugs work by disabling an enzyme the virus needs in order to grow. Many governments in the world, including Israel's, have stockpiled Tamiflu in large quantities since the swine-flu pandemic began. <TABLE border=0 cellSpacing=0 cellPadding=0 align=right><TBODY><TR><TD rowSpan=2>
Reports of Tamiflu-resistant strains of swine flu began in late June. In patients with weakened immune systems the virus might stay active for longer periods, acquiring resistance to Tamiflu and potentially spreading to others.
http://www.haaretz.com/hasen/spages/1107725.html
At the end of June, a representative of the Swiss pharmaceutical company Roche, which manufactures Tamiflu, said a Danish patient infected with a strain of the virus was not responding to the medicine. Earlier studies on Tamiflu indicated that 0.4 percent of adults and 4 percent of children afflicted with normal seasonal flu were likely not to respond to the drug.
Ten more such patients were identified in the world since June, with three in Japan, one in Singapore, one in China, one in Denmark, one in Canada, and two in the United States. However, no patient-to-patient transmission of the Tamiflu-resistant strain has yet been documented.
The two U.S. cases reported over the weekend were documented in Seattle. The swine flu patients were said to be suffering from leukemia and a depleted immune system. One patient is a young man who received a marrow transplant in May, and was said to be recovering at home; the other is a woman in her forties, who is still hospitalized. The two were said to have not been in contact, nor has it been documented that they have infected family members or medical staff with the Tamiflu-resistant strain.
The World Health Organization said it was following the reports, but no changes were yet made to its guidelines on treating the virus.
No Tamiflu-resistant strains have been recorded in Israel, where five more labs for testing for the disease are soon to be allocated by the health ministry. "The spread of a drug-resistant strain is usually slow, and by the time it spreads significantly vaccines against the disease will, in all likelihood, be developed. However, Tamiflu is one of the only medicines that can slow or weaken the disease, so it's crucial that swine flu react to it," said Dr. Amnon Kiro, chief of influenza research at the Israeli Pediatric Association research network.
At the moment, checks for swine flu are only carried out at the Health Ministry laboratory in Tel Hashomer, and in a laboratory at Hadassah University Hospital, Ein Kerem in Jerusalem. The checks are only meant to identify the virus, rather than test its response to Tamiflu.
Thirteen Israelis are presently in intensive care due to swine flu, and seven fatalities have so far been reported.
</TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
Last edited by a moderator:
AlaskaDenise
In Memoriam
Re: Two Tamiflu-resistant swine flu cases reported in Washington
From the above ProMed report:
Will the viral load being shed during these prolonged shedding time be enough that these people can be considered "superspreaders"?
I assume at some point during the shedding period these people become asymtomatic. During their asymtomatic period, will they stay on antivirals to stop the viral shedding, or is there another way to halt the shedding?
.
Will the viral load being shed during these prolonged shedding time be enough that these people can be considered "superspreaders"?
I assume at some point during the shedding period these people become asymtomatic. During their asymtomatic period, will they stay on antivirals to stop the viral shedding, or is there another way to halt the shedding?
.
Re: Two Tamiflu-resistant swine flu cases reported in Washington
Local swine flu patients resistant to Tamiflu
<!----><!-- cc -->By JENNIFER FARRINGTON
MyNorthwest.com staff
Two patients being treated for H1N1 virus (swine flu) have been found to be resistant to the antiviral Tamiflu used to treat the infection, according to Seattle and King County Public Health.
The two patients, a male teenager and a female in her 40s, are believed to have no connection with one another. Both patients have been identified as having compromised immune systems, raising their risk of developing an infection and antiviral resistance. One patient has recovered while the other has ongoing symptoms and is currently being treated with zanamivir, another antiviral medication.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health Seattle & King County in a news release. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available." The health department says the general public's risk is very low and there is no evidence that health care workers in contact with the patients became infected. However, local and state officials are working with the Center for Disease Control and are taking precautionary measures to monitor for other antiviral drug resistant influenza cases.
http://www.mynw.com/?nid=189&sid=200937
Local swine flu patients resistant to Tamiflu
<!----><!-- cc -->By JENNIFER FARRINGTON
MyNorthwest.com staff
Two patients being treated for H1N1 virus (swine flu) have been found to be resistant to the antiviral Tamiflu used to treat the infection, according to Seattle and King County Public Health.
The two patients, a male teenager and a female in her 40s, are believed to have no connection with one another. Both patients have been identified as having compromised immune systems, raising their risk of developing an infection and antiviral resistance. One patient has recovered while the other has ongoing symptoms and is currently being treated with zanamivir, another antiviral medication.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health Seattle & King County in a news release. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available." The health department says the general public's risk is very low and there is no evidence that health care workers in contact with the patients became infected. However, local and state officials are working with the Center for Disease Control and are taking precautionary measures to monitor for other antiviral drug resistant influenza cases.
http://www.mynw.com/?nid=189&sid=200937
wotan
Well-known member
Re: Two Tamiflu-resistant swine flu cases reported in Washington
Is anyone else noticing the wording:
Its as if they are saying the patients don't respond to treatment, as opposed to the virus. I don't recall seeing that way of reporting in cases of bacterial resistance to antibiotics.
Is anyone else noticing the wording:
Its as if they are saying the patients don't respond to treatment, as opposed to the virus. I don't recall seeing that way of reporting in cases of bacterial resistance to antibiotics.
Re: Two Tamiflu-resistant swine flu cases reported in Washington
Drug-resistant swine flu cases discovered in patients in Seattle
By SANDI DOUGHTON
The Seattle Times
Published: Saturday, Aug. 15, 2009 - 7:03 pm
Last Modified: Sunday, Aug. 16, 2009 - 5:08 am
SEATTLE -- The country's first cases of drug-resistant swine flu were discovered in two leukemia patients in Seattle, the U.S. Centers for Disease Control and Prevention reported Friday.
Both patients, who had weakened immune systems from chemotherapy and stem-cell transplants, developed flu strains resistant to the anti-viral drug oseltamivir, sold as Tamiflu.
There was no connection between the cases and no threat to the public, said Dr. Jeff Duchin, chief of communicable-disease control for Public HealthSeattle & King County. None of the patients' family members, or the health workers who cared for them, contracted the disease.
The Seattle cases bring to 11 the worldwide total of people diagnosed with Tamiflu-resistant infections of the H1N1 virus.
"These are rare, isolated types of phenomena," Duchin said. "It's not something we expect is going to lead to widespread drug resistance in the community."
But the cases underscore the need for judicious use of anti-viral drugs to ensure resistant strains do not become more common, he said.
Last month, CDC officials warned summer camps to stop the practice of handing out Tamiflu to healthy children in an effort to ward off infection.
"Anti-viral drugs should be used to treat an infection after it's occurred - once the cat is out of the bag," Duchin said. "The more promiscuous use ... the more chances we have to develop resistant viruses."
Patients with weakened immune systems are most vulnerable because their bodies are not able to join forces with the drugs to fight off the virus. That means the virus persists longer in the presence of the anti-viral drugs, which is a recipe for the evolution of drug-resistant bugs.
One of the patients is a teenage boy who received a stem-cell transplant in May. He contracted the flu virus later that month and has since recovered.
The second patient, a woman in her 40s who relapsed after an earlier stem-cell transplant, remains hospitalized.
Genetic analysis showed that over several weeks of Tamiflu treatment, the flu bugs in their bodies mutated and were no longer sensitive to the drug.
The account of the cases, published in CDC's Morbidity and Mortality Weekly Report, identifies the hospitals as Seattle Children's and the University of Washington Medical Center.
Local and state health officials are working with the CDC to boost monitoring for drug-resistant flu viruses.
http://www.sacbee.com/847/story/2112883.html
Drug-resistant swine flu cases discovered in patients in Seattle
By SANDI DOUGHTON
The Seattle Times
Published: Saturday, Aug. 15, 2009 - 7:03 pm
Last Modified: Sunday, Aug. 16, 2009 - 5:08 am
SEATTLE -- The country's first cases of drug-resistant swine flu were discovered in two leukemia patients in Seattle, the U.S. Centers for Disease Control and Prevention reported Friday.
Both patients, who had weakened immune systems from chemotherapy and stem-cell transplants, developed flu strains resistant to the anti-viral drug oseltamivir, sold as Tamiflu.
There was no connection between the cases and no threat to the public, said Dr. Jeff Duchin, chief of communicable-disease control for Public HealthSeattle & King County. None of the patients' family members, or the health workers who cared for them, contracted the disease.
The Seattle cases bring to 11 the worldwide total of people diagnosed with Tamiflu-resistant infections of the H1N1 virus.
"These are rare, isolated types of phenomena," Duchin said. "It's not something we expect is going to lead to widespread drug resistance in the community."
But the cases underscore the need for judicious use of anti-viral drugs to ensure resistant strains do not become more common, he said.
Last month, CDC officials warned summer camps to stop the practice of handing out Tamiflu to healthy children in an effort to ward off infection.
"Anti-viral drugs should be used to treat an infection after it's occurred - once the cat is out of the bag," Duchin said. "The more promiscuous use ... the more chances we have to develop resistant viruses."
Patients with weakened immune systems are most vulnerable because their bodies are not able to join forces with the drugs to fight off the virus. That means the virus persists longer in the presence of the anti-viral drugs, which is a recipe for the evolution of drug-resistant bugs.
One of the patients is a teenage boy who received a stem-cell transplant in May. He contracted the flu virus later that month and has since recovered.
The second patient, a woman in her 40s who relapsed after an earlier stem-cell transplant, remains hospitalized.
Genetic analysis showed that over several weeks of Tamiflu treatment, the flu bugs in their bodies mutated and were no longer sensitive to the drug.
The account of the cases, published in CDC's Morbidity and Mortality Weekly Report, identifies the hospitals as Seattle Children's and the University of Washington Medical Center.
Local and state health officials are working with the CDC to boost monitoring for drug-resistant flu viruses.
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