Oseltamivir resistance among influenza viruses in northern Viet Nam, 2009–2012.

Abstract

Background. Antiviral resistance has been reported in seasonal influenza A viruses and avian influenza A/H5N1 viruses in Vietnam, raising concerns about the efficacy of treatment.

Methods. We analyzed isolates from influenza-positive samples collected from influenza-like illness patients at sentinel clinics of NISS in northern Vietnam and isolates from patients with confirmed A/H5N1 infections during 2009-2012. Pyrosequencing was used to detect mutations: H275Y (for A/H1N1 and A/H5N1), E119V(for A/H3N2) and I117V(for A/H5N1). The neuraminidase inhibition (NAI) assay was used to determine the IC₅₀ values for all influenza A and B isolates.

Results. All 19 seasonal A/H1N1 samples collected in 2009 contained the H275Y neuraminidase substitution, and the IC₅₀ values observed from six isolates (6/19) were 1000-fold higher than baseline. A total of 215 samples and 27 A/H1N1pdm09 isolates were tested; we determined H275Y on three (0.7%) samples and referred   with IC₅₀ values ranging from 118.59 to 127.91 nM (i.e. >200-fold higher than baseline). Other subtypes A/H3N2 (100 samples) and A/H5N1 ( seven isolats)  were determined to be sensitive to oseltamivir by both pyrosequencing and NAI assays.. Influenza B (67 isolates) was determined to be sensitive to oseltamivir as IC₅₀ values were within the susceptibility range.

Discussion.

Mutations associated with oseltamivir-resistance were identified in seasonal influenza A/H1N1 and A/H1N1pdm09 viruses from northern Vietnam. Seasonal influenza vaccines and human H5N1 vaccines are not currently available, thus, underscoring the need for effective treatment. To control the efficacy of oseltamivir for treatment, active surveillance for oseltamivir resistance among influenza viruses circulating in Vietnam should be expanded.