title: Community- and hospital-acquired infections with oseltamivir- and peramivir-resistant influenza A(H1N1)pdm09 viruses during the 2015-2016 season in Japan.
abstract: We report five cases of community- and hospital-acquired infections with oseltamivir- and peramivir-resistant A(H1N1)pdm09 viruses possessing the neuraminidase (NA) H275Y mutation during January-February 2016 in Japan. One case was hospitalized and was receiving oseltamivir for prophylaxis. The remaining four cases were not taking antiviral drugs at the time of sampling. These cases were geographically distant and epidemiologically unrelated. The five viruses showed ~300-fold rise in IC50values against oseltamivir and peramivir, defined as highly reduced inhibition according to the WHO definition. Overall, the prevalence of the H275Y A(H1N1)pdm09 viruses was 1.8 % (5/282). The resistant viruses possessed the V241I, N369 K, and N386 K substitutions in the NA that have been previously reported among A(H1N1)pdm09 to alter transmission fitness. Analysis of Michaelis constant (Km) revealed that two of the isolates had reduced NA affinity to MUNANA, while the other three isolates displayed a slightly decreased affinity compared to the sensitive viruses. Further studies are needed to monitor the community spread of resistant viruses and to assess their transmissibility.
authors.affiliation: Division of International Health, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hibino
authors.affiliation: Division of International Health, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Masaki Respiratory Medicine Clinic, Nagasaki, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Masaki
authors.affiliation: Infection Disease Control Section, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Yoiko-no-Syounika Sato Clinic, Niigata, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Sato
authors.affiliation: Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takemae
authors.affiliation: Division of Transboundary Animal Disease, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.|Center for Infectious Disease Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hassan
authors.initials: H
authors.lastname: Zaraket
authors.affiliation: Division of International Health, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan. jasmine@med.niigata-u.ac.jp.
authors.forename: Reiko
authors.identifier: http://orcid.org/0000-0002-1554-8226
authors.initials: R
authors.lastname: Saito
mesh_terms: D000146:Acids, Carbocyclic; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections; D003428:Cross Infection; D003517:Cyclopentanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D005814:Genes, Viral; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics*; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053139:Oseltamivir / Q000494:pharmacology; D010802:Phylogeny; D012621:Seasons; D055815:Young Adult
chemical_list: D000146:Acids, Carbocyclic; D003517:Cyclopentanes; D006146:Guanidines; D053139:Oseltamivir; C414210:peramivir
keywords: Antiviral drug susceptibility; Community transmission; Enzymatic property; Influenza virus A(H1N1)pdm09; Neuraminidase; Oseltamivir resistant