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INFLUENZA PANDEMIC (H1N1) 2009 (74): CANADA (ONTARIO) OSELTAMIVIR RESISTANCE
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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: Thu 22 Oct 2009
From: Jonathan Gubbay <jonathan.gubbay@oahpp.ca> [edited]
Ontario Public Health Laboratory (OPHL), Ontario Agency for Health
Protection and Promotion (OAHPP) performs molecular testing for
pandemic (H1N1) 2009 (pH1N1) for the province of Ontario, Canada. In
addition, surveillance for antiviral resistance using the CDC
pyrosequencing assay is done on a selection of samples, with over 300
pH1N1 samples tested at OPHL since the onset of the pandemic(1).
On 9 Aug 2009 influenza A was detected at a referring hospital in a
nasopharyngeal (NP) swab collected from a young adult in his 20s with
an underlying hematological malignancy; the sample was forwarded to
OPHL for subtyping and identified as pH1N1 by real-time reverse
transcriptase PCR (rRT-PCR).
The patient was commenced on oseltamivir on 9 Aug 2009, and received
treatment dose (75 mg twice daily orally) intermittently from 10-20
Aug, 25-26 Aug, 16 Aug-18 Sep, and 25-27 Sep 2009. Influenza A was
detected on repeat NP swabs tested at the local hospital on 17 and 24
Aug, and 1 and 7 Sep 2009.
The 7 Sep 2009 influenza A positive NP swab collected after 24 days
of intermittent therapy was forwarded to OPHL, which was subtyped as
pH1N1 by rRT-PCR. In early October, as part of the Ontario's
surveillance project for antiviral resistance, the sample was tested
by pyrosequencing for oseltamivir resistance, and was found to
contain the H275Y mutation (histidine to tyrosine; H274Y in N2
numbering) conferring oseltamivir resistance. This mutation was
confirmed with Sanger sequencing at OPHL and at Canada's National
Microbiology Laboratory (NML). The original sample collected on 9 Aug
2009 was also tested for oseltamivir resistance with no evidence of
the H275Y mutation. Phenotypic neuraminidase inhibitor resistance
testing is being conducted at NML.
The patient improved clinically and was discharged home one day
following the collection of the NP swab containing the resistant
isolate. Subsequent NP swabs on 9 and 24 Sep 2009 were negative for
influenza A. Unfortunately, he required readmission to the hospital a
few weeks following the discharge due to overwhelming Epstein Barr
virus infection and subsequently died. The NP swab performing during
the 2nd admission (24 Sep 2009) was negative for influenza A by DFA
[direct fluorescent antibody] and PCR.
To our knowledge, this represents Canada's 3rd case of oseltamivir
resistant pH1N1, with Quebec and Alberta documenting one case
each(2,3). As has been previously documented, immunocompromised
patients are at risk of prolonged viral shedding with pH1N1, and
prolonged therapy with oseltamivir predisposes them to develop
infection due to neuraminidase resistant virus during the course of
therapy(4). Resistance should also be considered in patients who
develop pH1N1 infection while on oseltamivir prophylaxis, as has been
recently documented(2,5,6).
Oseltamivir resistance remains very rare, with 35 episodes reported
by the World Health Organization (WHO) as of 16 Oct 2009(6). [The
case in Taiwan reported in the preceding ProMED-mail post entitled
'Influenza pandemic (H1N1) 2009 (73): Taiwan oseltamivir resistance
20091021.3626' will have become the 36th case. - Mod.CP]
Although its prevalence is very low to warrant any change in empiric
antiviral therapy for pH1N1 infection, it is important to continue
with the surveillance for antiviral resistance as it is possible that
resistance to oseltamivir may evolve over time. Resistance testing
also has an important clinical role in patients who are persistently
shedding the virus and not clinically improving despite treatment and
for those who develop pH1N1 infection while receiving oseltamivir prophylaxis.
References
----------
1. World Health Organization: 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>.
2. ProMED-mail. Archive Number 20090722.2597: Oseltamivir resistance.
22 Jul 2009.
3. ProMED-mail. Archive Number 20090917.3260: Influenza pandemic
(H1N1) 2009 (50): oseltamivir resistance. 17 Sep 2009.
4. MMWR: Oseltamivir-Resistant Novel Influenza A (H1N1) Virus
Infection in Two Immunosuppressed Patients - Seattle, Washington,
2009. August 14, 2009 / 58 (Dispatch); 1-4. Available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5832a3.htm>.
5. MMWR: Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Virus
Infection in Two Summer Campers Receiving Prophylaxis - North
Carolina, 2009. September 11, 2009 / 58(35); 969-72. Available at
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5835a1.htm>.
6. WHO Pandemic (H1N1) 2009 - update 70. Weekly update (Virological
surveillance data). Available at
<http://www.who.int/csr/disease/swineflu/laboratory16_10_2009/en/index.html>.
[R Eshaghi1, C Mackie2, AL Winter3, C Lee4, Y Li5, N Bastien5, DE
Low1, and JB Gubbay1
1. Public Health Laboratory, Ontario Agency for Health Protection and
Promotion (OAHPP), Canada
2. Health Protection Division, Hamilton Public Health Services, Ontario, Canada
3. Ontario Ministry of Health and Long-Term Care
4. Medical Microbiology, St Joseph's Healthcare, Hamilton, Ontario, Canada
5. Influenza and Respiratory Viruses Section, National Microbiology
Laboratory, Public Health Agency of Canada]
--
Jonathan Gubbay
Public Health Laboratory, Toronto
Ontario Agency for Health Protection and Promotion (OAHPP)
Toronto, ON M9P 3T1
Canada
<jonathan.gubbay@oahpp.ca>
[As in previous cases of oseltamivir resistance described in
influenza A (H1N1) virus (both seasonal and pandemic 2009 strains) up
to the present, there appears to have been no onward transmission of
oseltamivir-resistant virus to contacts or evidence of spread or
resistant virus in the general community. Likewise the evolution of
oseltamivir resistant virus during the course of treatment has not
been detrimental to final recovery even in the case of this Canadian
patient with a hematological malignancy, who ultimately succumbed to
another viral infection. However, as emphasized by the authors of the
report above, vigilance must be maintained. - Mod.CP]
[see also:
Influenza pandemic (H1N1) 2009 (73): Taiwan oseltamivir resistance
20091021.3626
Influenza pandemic (H1N1) 2009 (50): oseltamivir resistance 20090917.3260
Influenza A(H1N1) virus, oseltamivir resistance (02): N. Hemisphere
20090325.1166
Influenza A(H1N1) virus, oseltamivir resistance: Korea 20090113.0136
2008
----
Influenza A (H1N1) virus, oseltamivir resistance (10): CDC 20081224.4054
Influenza A (H1N1) virus, oseltamivir resistance (09): USA 20081220.4013
Influenza A (H1N1) virus, oseltamivir resistance (08): Europe 20081025.3375
Influenza A (H1N1) virus, oseltamivir resistance (07): Europe 20080906.2783
Influenza A (H1N1) virus, oseltamivir resistance (06): S. Hemisphere
20080825.2648
Influenza virus, oseltamivir resistance (06): Japan 20080228.0812
Influenza A (H1N1) virus, oseltamivir resistance (05): China (HK) 20080203.0438
Influenza A (H1N1) virus, oseltamivir resistance (03): corr. 20080203.0430
Influenza A (H1N1) virus, oseltamivir resistance (04): CA, USA 20080202.0428
Influenza A (H1N1) virus, oseltamivir resistance (03): Europe 20080201.0399
Influenza A (H1N1) virus, oseltamivir resistance (02): Europe 20080129.0371
Influenza A (H1N1) virus, oseltamivir resistance - Norway 20080128.0361
2006
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Avian influenza, human (162): oseltamivir resistance 20061010.2907]
...................................cp/mj/mpp
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