AUTHOR=Sousa Thiago das Chagas , Martins Jessica Santa Cruz Carvalho , Miranda Milene Dias , Garcia Cristiana Couto , Resende Paola Cristina , Santos Cliomar A. , Debur Maria do Carmo , Rodrigues Rodrigo Ribeiro , Cavalcanti Andrea Cony , Gregianini Tatiana Schäffer , Iani Felipe Campos de Melo , Pereira Felicidade Mota , Fernandes Sandra Bianchini , Ferreira Jessylene de Almeida , Santos Katia Correa de Oliveira , Motta Fernando , Brown David , Almeida Walquiria Aparecida Ferreira de , Siqueira Marilda Mendonça , Matos Aline da Rocha TITLE=Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons JOURNAL=Frontiers in Public Health VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.944277 DOI=10.3389/fpubh.2022.944277 ISSN=2296-2565 ABSTRACT=

The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V (n = 6) and NA:N329K (n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis.