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

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.

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).

Figure 2

Oseltamivir-resistant (n = 183) and oseltamivir-susceptible (n = 89) influenza viruses A (H1N1) in the 2007–08 influenza season in Norway, by week of sampling.

Figure 3

Comparison of virus shedding, measured as relative viral RNA content, in respiratory specimens taken from patients infected with oseltamivir-susceptible and oseltamivir-resistant influenza viruses A (H1N1), respectively, during the 2007–08 influenza season in Norway. Viral RNA content is expressed as the reverse-transcription–PCR cycle number (Ct) during which the fluorescence threshold was exceeded.

Figure 4

Proportion of oseltamivir-resistant influenza viruses A (H1N1) in the 2007–08 influenza season in Norway, by county of sampling. The total number of samples analyzed for each county is given inside each county.