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Antiviral susceptibility profile of influenza A viruses; keep an eye on immunocompromised patients under prolonged treatment
Author(s)
A. Kossyvakis
A.-F. A. Mentis
K. Tryfinopoulou
V. Pogka
A. Kalliaropoulos
E. Antalis
A. Meijer
S. Tsiodras
P. Karakitsos
A. F. Mentis
Abstract
There was an increase in severe and fatal influenza cases in Greece during the 2011–2015 post-pandemic period. To investigate causality, we determined neuraminidase (NA) inhibitor susceptibility and resistance-conferring NA and hemagglutinin (HA) mutations in circulating influenza type A viruses during the pandemic (2009–2010) and post-pandemic periods in Greece. One hundred thirty-four influenza A(H1N1)pdm09 and 95 influenza A(H3N2) viruses submitted to the National Influenza Reference Laboratory of Southern Greece were tested for susceptibility to oseltamivir and zanamivir. Antiviral resistance was assessed by neuraminidase sequence analysis, as well as the fluorescence-based 50 % inhibitory concentration (IC50) method. Five influenza A(H1N1)pdm09 viruses (2.2 %) showed significantly reduced inhibition by oseltamivir (average IC50 300.60nM vs. 1.19nM) by Gaussian kernel density plot analysis. These viruses were isolated from immunocompromised patients and harbored the H275Y oseltamivir resistance-conferring NA substitution. All A(H1N1)pdm09 viruses were zanamivir-susceptible, and all A(H3N2) viruses were susceptible to both drugs. Oseltamivir-resistant viruses did not form a distinct cluster by phylogenetic analysis. Permissive mutations were detected in immunogenic and non immunogenic NA regions of both oseltamivir- resistant and susceptible viruses in the post-pandemic seasons. Several amino acid substitutions in the HA1 domain of the HA gene of post-pandemic viruses were identified. This study indicated low resistance to NAIs among tested influenza viruses. Antiviral resistance emerged only in immunocompromised patients under long-term oseltamivir treatment. Sequential sample testing in this vulnerable group of patients is recommended to characterise resistance or reinfection and viral evolution.
Part Of
European Journal of Clinical Microbiology & Infectious Diseases
Journal or Serie
European Journal of Clinical Microbiology and Infectious Diseases
Issue
2
Volume
36
Start Page
361
End Page
371
ISSN
09349723
Date Issued
2017-02-01
DOI
10.1007/s10096-016-2809-3
Publisher
Springer Verlag
Subjects
Aged
Antiviral Agents
Drug Resistance
Viral
Female
Genotype
Greece
Hemagglutinin Glycopr...
Influenza Virus
Humans
Immunocompromised Hos...
Influenza A Virus
H1N1 Subtype
H3N2 Subtype
Influenza
Human
Inhibitory Concentrat...
Male
Microbial Sensitivity...
Middle Aged
Mutation
Missense
Neuraminidase
Oseltamivir
Viral Proteins
Zanamivir