Surveillance for Oseltamivir-Resistant Influenza A(H1N1)pdm09 Virus Infections During 2015–2016, United States

Abstract

Background. Since A(H1N1)pdm09 emerged, the prevalence of oseltamivir-resistant A(H1N1)pdm09 viruses in the United States has been <2%. All oseltamivir-resistant viruses contain an H275Y substitution in the neuraminidase (NA). During 2013- 14, 57% of oseltamivir-resistant viruses were unrelated to prior oseltamivir use and 11 of 60 (18%) contained additional NA substitutions (termed "permissive”) at V2411, N369K, and N386K that are thought to prevent a H275Y-induced reduction in virus fitness. We describe findings from US surveillance for oseltamivir-resistant A(H1N1) pdm09 viruses during 2015-16. Methods. The Centers for Disease Control and Prevention requested state public health laboratories to submit up to 8 virus isolates (2 of each subtype/lineage) every 2 weeks for NA inhibition assay testing and 5 additional A(H1N1)pdm09 clinical specimens for pyrosequencing for H275Y. NA sequencing was performed on resistant viruses. A standard case form was collected from all persons infected with oseltamivirresistant A(H1N1)pdm09. Results. From 1 October 2015 to 5 May 2016, 1832 A(H1N1)pdm09 clinical specimens and virus isolates were tested. Overall, 14 (0.8%) oseltamivir-resistant A(H1N1) pdm09 were detected from 8 states; all contained H275Y. Full-length NA sequences were completed for 4 cases; all 4 contained the 3 permissive NA substitutions (V241I, N369K, and N386K). None of the 14 A(H1N1)pdm09 viruses were resistant to zanamivir. The 14 patients had a median age of 48 years (range 9 months-85 years); 5 (36%) reported no exposure to oseltamivir prior to specimen collection, 8 were taking oseltamivir at the time of specimen collection, and oseltamivir receipt was unknown for 1. Eight (57%) of the 14 patients with resistant virus infection were hospitalized, 7 had an immunosuppressive condition, and 5 died. Conclusion. During the 2015-16 influenza season, oseltamivir-resistant A(H1N1) pdm09 infections were rare but this virus continued to circulate at low levels in the community and was in some cases unrelated to drug use. Permissive NA substitutions were identified in all viruses for which full length NA sequences were available. Ongoing surveillance for trends in oseltamivir-resistant H1N1pdm09 is critical to inform clinical care and public health policies.