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Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08.

Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O - Emerging Infect. Dis. (2009)

Bottom Line: Clinical data were obtained for 265 patients.Resistance was not associated with prior use of antiviral drugs.Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure.

View Article: PubMed Central - PubMed

Affiliation: Norwegian Institute of Public Health, Oslo, Norway.

ABSTRACT
In Norway in January 2008, unprecedented levels of oseltamivir resistance were found in 12 of 16 influenza viruses A (H1N1) tested. To investigate the epidemiologic and clinical characteristics of these viruses, we used sequence analysis to test all available subtype H1N1 viruses from the 2007-08 season for resistance. Questionnaires from physicians provided information on predisposing diseases, oseltamivir use, symptoms, and complications. Clinical data were obtained for 265 patients. In total, 183 (67.3%) of 272 viruses were oseltamivir resistant. Resistance was not associated with prior use of antiviral drugs. Symptoms and hospitalization rates did not differ for patients infected with a resistant or a susceptible virus. Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure. The ability of these viruses to sustain their fitness and spread among persons should be considered when shaping future strategies for treating and preventing seasonal and pandemic influenza.

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Related in: MedlinePlus

Phylogenetic reconstruction of the H1 genes of influenza viruses A (H1N1) in Norway, 2007–08 season. The analysis was performed on an alignment spanning positions 84–1054 of viral RNA segment 4. Pairwise distances were calculated by using the Kimura 2-parameter model with a transition:transversion ratio of 2.0; the phylogenetic tree was constructed by the neighbor-joining method, as implemented in the programs DNADIST and NEIGHBOR in the PHYLIP package (14 15,). Published sequences were obtained from the Influenza Sequence Database, Los Alamos National Laboratory (16). Boldface indicates viruses from the 2007–08 influenza season in Norway; red indicates oseltamivir-resistant viruses; blue, susceptible viruses. New sequences presented in this analysis have been deposited in GenBank (accession nos. CY036664–CY036694).
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Figure 1: Phylogenetic reconstruction of the H1 genes of influenza viruses A (H1N1) in Norway, 2007–08 season. The analysis was performed on an alignment spanning positions 84–1054 of viral RNA segment 4. Pairwise distances were calculated by using the Kimura 2-parameter model with a transition:transversion ratio of 2.0; the phylogenetic tree was constructed by the neighbor-joining method, as implemented in the programs DNADIST and NEIGHBOR in the PHYLIP package (14 15,). Published sequences were obtained from the Influenza Sequence Database, Los Alamos National Laboratory (16). Boldface indicates viruses from the 2007–08 influenza season in Norway; red indicates oseltamivir-resistant viruses; blue, susceptible viruses. New sequences presented in this analysis have been deposited in GenBank (accession nos. CY036664–CY036694).

Mentions: A total of 196 viral isolates were available (133 carried the resistance mutation); of these, 113 (79 with the resistant genotype) were reference tested by the VIRGIL laboratory. Phenotypic and genotypic reference analysis results agreed completely with the in-country genotypic testing results; all mutant viruses showed large reductions in susceptibility to oseltamivir when compared with non-H274Y viruses (IC50 260–2,161 nM, mean 673 nM, for the 274Y mutant and 0.4–5.6 nM, mean 2.6 nM, for the nonmutant viruses). No evidence of mixed genotype or phenotype was observed. In phylogenetic analysis of the H1 gene, all viruses tested grouped together in subclade 2B (Figure 1). In the phylogenetic tree, the resistant viruses from Norway all formed a single branch that was distinct, but closely related, to the susceptible viruses from Norway.


Oseltamivir-resistant influenza viruses A (H1N1), Norway, 2007-08.

Hauge SH, Dudman S, Borgen K, Lackenby A, Hungnes O - Emerging Infect. Dis. (2009)

Phylogenetic reconstruction of the H1 genes of influenza viruses A (H1N1) in Norway, 2007–08 season. The analysis was performed on an alignment spanning positions 84–1054 of viral RNA segment 4. Pairwise distances were calculated by using the Kimura 2-parameter model with a transition:transversion ratio of 2.0; the phylogenetic tree was constructed by the neighbor-joining method, as implemented in the programs DNADIST and NEIGHBOR in the PHYLIP package (14 15,). Published sequences were obtained from the Influenza Sequence Database, Los Alamos National Laboratory (16). Boldface indicates viruses from the 2007–08 influenza season in Norway; red indicates oseltamivir-resistant viruses; blue, susceptible viruses. New sequences presented in this analysis have been deposited in GenBank (accession nos. CY036664–CY036694).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2657637&req=5

Figure 1: Phylogenetic reconstruction of the H1 genes of influenza viruses A (H1N1) in Norway, 2007–08 season. The analysis was performed on an alignment spanning positions 84–1054 of viral RNA segment 4. Pairwise distances were calculated by using the Kimura 2-parameter model with a transition:transversion ratio of 2.0; the phylogenetic tree was constructed by the neighbor-joining method, as implemented in the programs DNADIST and NEIGHBOR in the PHYLIP package (14 15,). Published sequences were obtained from the Influenza Sequence Database, Los Alamos National Laboratory (16). Boldface indicates viruses from the 2007–08 influenza season in Norway; red indicates oseltamivir-resistant viruses; blue, susceptible viruses. New sequences presented in this analysis have been deposited in GenBank (accession nos. CY036664–CY036694).
Mentions: A total of 196 viral isolates were available (133 carried the resistance mutation); of these, 113 (79 with the resistant genotype) were reference tested by the VIRGIL laboratory. Phenotypic and genotypic reference analysis results agreed completely with the in-country genotypic testing results; all mutant viruses showed large reductions in susceptibility to oseltamivir when compared with non-H274Y viruses (IC50 260–2,161 nM, mean 673 nM, for the 274Y mutant and 0.4–5.6 nM, mean 2.6 nM, for the nonmutant viruses). No evidence of mixed genotype or phenotype was observed. In phylogenetic analysis of the H1 gene, all viruses tested grouped together in subclade 2B (Figure 1). In the phylogenetic tree, the resistant viruses from Norway all formed a single branch that was distinct, but closely related, to the susceptible viruses from Norway.

Bottom Line: Clinical data were obtained for 265 patients.Resistance was not associated with prior use of antiviral drugs.Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure.

View Article: PubMed Central - PubMed

Affiliation: Norwegian Institute of Public Health, Oslo, Norway.

ABSTRACT
In Norway in January 2008, unprecedented levels of oseltamivir resistance were found in 12 of 16 influenza viruses A (H1N1) tested. To investigate the epidemiologic and clinical characteristics of these viruses, we used sequence analysis to test all available subtype H1N1 viruses from the 2007-08 season for resistance. Questionnaires from physicians provided information on predisposing diseases, oseltamivir use, symptoms, and complications. Clinical data were obtained for 265 patients. In total, 183 (67.3%) of 272 viruses were oseltamivir resistant. Resistance was not associated with prior use of antiviral drugs. Symptoms and hospitalization rates did not differ for patients infected with a resistant or a susceptible virus. Oseltamivir-resistant influenza viruses A (H1N1) did not show diminished capability to spread in the absence of selective pressure. The ability of these viruses to sustain their fitness and spread among persons should be considered when shaping future strategies for treating and preventing seasonal and pandemic influenza.

Show MeSH
Related in: MedlinePlus