Oseltamivir resistant influenza A viruses in Thailand during 2009-2011

Abstract

Abstract
Influenza A (H1N1) pdm09 viruses have been spread in Thailand since June 2009 and have become one of the circulating strains ever since. This study aims to provide the prevalence data of influenza A [pandemic influenza and seasonal influenza (H1/H3)] viruses, including the oseltamivir-resistant strains in Thailand during the first 3-year of pandemic (2009 - 2011) using both genotypic and phenotypic assays. The 7,264 nasopharyngeal wash samples were collected from patients presented with influenza-like illness during June 2009 - December 2011. Influenza A (H1N1) pdm09 viruses was detected in 692 (9.5%) of suspected cases. Seasonal influenza H3 and H1 viruses were detected in 322 (4.4%) and 1 (0.01%) cases, respectively. Among 692 positive Influenza A (H1N1) pdm09 virus samples, 6 (0.86%) viruses contained oseltamivir drug resistant mutation codon (H275Y) in NA gene, which was not found in seasonal influenza H3 and H1 viruses. All 5 oseltamivir-resistant Influenza A (H1N1) pdm09 virus-infected cases were immunocompromised patients; 3 of which were oseltamivir treatment-related and were fatal cases. Mutation at D239G in HA gene was revealed in virus isolated from one dead case, which possibly was related to severe clinical outcome. The phenotypic assay showed that the IC 50 value of the influenza A viruses isolated in 2009 was lower than that of the viruses isolated in 2010. The mean IC 50 of the oseltamivir-resistant Influenza A (H1N1) pdm09 virus strain was 69.18±18.25 nM. Whole genome sequence analysis of 6 oseltamivir-resistant isolates showed mutation codons at HA-E391K, PA-V14I, PA-K716Q and PB1-K736E, which was in agreement with the new viral variants reported in Singapore. Only mutations of HA-E391K, HA-S200T and NS1-I123V were commonly found in the oseltamivirresistant influenza A (H1N1) pdm2009 viruses isolated in 2010, which were absent in the resistant-strain isolated in 2009.