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INFLUENZA A (H1N1): OSELTAMIVIR RESISTANCE, ANIMAL RELATED
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A ProMED-mail post
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International Society for Infectious Diseases
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Date: Sun 18 Sep 2011 [accessed]
Source: PLoS ONE Journal, 12 Sep 2011 [abstract, edited]
<http://www.plosone.org/article/info:doi/10.1371/journal.pone.0024742>
Ref: Jarhult JD, Muradrasoli S, Wahlgren J, et al: Environmental
Levels of the Antiviral Oseltamivir Induce Development of Resistance
Mutation H274Y in Influenza A/H1N1 Virus in Mallards. PLoS ONE 2911;
6(9): e24742. doi:10.1371/journal.pone.0024742
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Abstract
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Oseltamivir ('Tamiflu') is the most widely used drug against influenza
infections and is extensively stockpiled worldwide as part of pandemic
preparedness plans. However, resistance is a growing problem and in
2008-2009, seasonal human influenza A/H1N1 virus strains in most parts
of the world carried the mutation H274Y in the neuraminidase gene,
which causes resistance to the drug.
The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is
poorly degraded in sewage treatment plants and surface water and has
been detected in aquatic environments where the natural influenza
reservoir, dabbling ducks, can be exposed to the substance. To assess
if resistance can develop under these circumstances, we infected
mallards with influenza A/H1N1 virus and exposed the birds to 80
nanograms/liter, 1 micrograms/liter and 80 micrograms/liter of OC
through their sole water source. By sequencing the neuraminidase gene
from fecal samples, we found that H274Y occurred at micrograms/liter
of OC and rapidly dominated the viral population at 80
micrograms/liter. IC50 [half maximal inhibitory concentration] for OC
was increased from 2-4 nanomoles in wild-type viruses to 400-700
nanomoles in H274Y mutants as measured by a neuraminidase inhibition
assay. This is consistent with the decrease in sensitivity to OC that
has been noted among human clinical isolates carrying H274Y.
Environmental OC levels have been measured to 58-293 nanograms/liter
during seasonal outbreaks and are expected to reach
microgram/liter-levels during pandemics. Thus, resistance could be
induced in influenza viruses circulating among wild ducks. As
influenza viruses can cross species barriers, oseltamivir resistance
could spread to human-adapted strains with pandemic potential
disabling oseltamivir, a cornerstone in pandemic preparedness
planning.
We propose surveillance in wild birds as a measure to understand the
resistance situation in nature and to monitor it over time. Strategies
to lower environmental levels of OC include improved sewage treatment
and, more importantly, a prudent use of antivirals.
--
Communicated by:
Ken Cokanasiga
<kenc@spc.int>
[This paper has been authored by scientists from the following
scientific establishments:
1. Section of Infectious Diseases, Department of Medical Sciences,
Uppsala University, Uppsala, Sweden,
2. Section of Bacteriology and Food Safety, Department of Biomedical
Sciences and Veterinary Public Health, Swedish University of
Agricultural Sciences, Uppsala, Sweden,
3. Swedish Institute for Infectious Disease Control and Karolinska
Institute, Microbiology and Tumor Biology Center, Stockholm, Sweden,
4. Department of Chemistry, Umea University, Umea, Sweden,
5. Section for Zoonotic Ecology and Epidemiology, School of Natural
Sciences, Linnaeus University, Kalmar, Sweden,
6. Aquatic Biology and Chemistry Group, Kristianstad University,
Kristianstad, Sweden,
7. National Veterinary Institute, Uppsala, Sweden,
8. Section of Pathology, Pharmacology and Toxicology, Department of
Biomedical Sciences and Veterinary Public Health, Swedish University
of Agricultural Sciences, Uppsala, Sweden,
9. Research Institute of Fish Culture and Hydrobiology, Faculty of
Fisheries and Protection of Waters, University of South Bohemia in
Ceske Budejovice, Vodnany, Czech Republic,
10. Section of Clinical Virology, Department of Medical Sciences,
Uppsala University, Uppsala, Sweden
Subscribers are encouraged to read the full text (7 pages), available
at no cost at the source URL above.
The authors mention an alarming scenario of direct transmission if a
high-pathogenic avian influenza virus (such as H5N1) acquires the
H274Y mutation and then adapts to humans. They raise the need for
prudent use of antivirals in medicine and suggest strategies to reduce
environmental levels of OC. They also point at surveillance in wild
bird populations as "an important measure to gain more knowledge of
the resistance situation in nature and to monitor it over time."
Laboratory-backed investigations should be included within ongoing
wildlife surveillance activities; enhancement of additional
surveillance deserves to be considered by international Public and
Animal Health institutions. - Mod.AS]
[see also:
2010
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Influenza seasonal (H1N1) virus: oseltamivir resistance 20100607.1899
Influenza pandemic (H1N1) (25): oseltamivir resistance 20100326.0961
2009
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Influenza pandemic (H1N1) 2009 (110): UK (Wales), Tamiflu resistance
20091120.4000
Influenza pandemic (H1N1) 2009 (77): Taiwan oseltamivir resistance
20091027.3725
Influenza pandemic (H1N1) 2009 (56): antiviral resistance risk
20090925.3363]
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