Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons

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 i...

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Main Authors: Thiago das Chagas Sousa, Jessica Santa Cruz Carvalho Martins, Milene Dias Miranda, Cristiana Couto Garcia, Paola Cristina Resende, Cliomar A. Santos, Maria do Carmo Debur, Rodrigo Ribeiro Rodrigues, Andrea Cony Cavalcanti, Tatiana Schäffer Gregianini, Felipe Campos de Melo Iani, Felicidade Mota Pereira, Sandra Bianchini Fernandes, Jessylene de Almeida Ferreira, Katia Correa de Oliveira Santos, Fernando Motta, David Brown, Walquiria Aparecida Ferreira de Almeida, Marilda Mendonça Siqueira, Aline da Rocha Matos
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Public Health
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpubh.2022.944277/full
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author Thiago das Chagas Sousa
Jessica Santa Cruz Carvalho Martins
Milene Dias Miranda
Cristiana Couto Garcia
Paola Cristina Resende
Cliomar A. Santos
Maria do Carmo Debur
Rodrigo Ribeiro Rodrigues
Rodrigo Ribeiro Rodrigues
Andrea Cony Cavalcanti
Tatiana Schäffer Gregianini
Felipe Campos de Melo Iani
Felicidade Mota Pereira
Sandra Bianchini Fernandes
Jessylene de Almeida Ferreira
Katia Correa de Oliveira Santos
Fernando Motta
David Brown
Walquiria Aparecida Ferreira de Almeida
Marilda Mendonça Siqueira
Aline da Rocha Matos
author_facet Thiago das Chagas Sousa
Jessica Santa Cruz Carvalho Martins
Milene Dias Miranda
Cristiana Couto Garcia
Paola Cristina Resende
Cliomar A. Santos
Maria do Carmo Debur
Rodrigo Ribeiro Rodrigues
Rodrigo Ribeiro Rodrigues
Andrea Cony Cavalcanti
Tatiana Schäffer Gregianini
Felipe Campos de Melo Iani
Felicidade Mota Pereira
Sandra Bianchini Fernandes
Jessylene de Almeida Ferreira
Katia Correa de Oliveira Santos
Fernando Motta
David Brown
Walquiria Aparecida Ferreira de Almeida
Marilda Mendonça Siqueira
Aline da Rocha Matos
author_sort Thiago das Chagas Sousa
collection DOAJ
description 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.
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spelling doaj.art-c5d7be96979748cb906cc0e43c3f17c42022-12-22T03:16:17ZengFrontiers Media S.A.Frontiers in Public Health2296-25652022-09-011010.3389/fpubh.2022.944277944277Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasonsThiago das Chagas Sousa0Jessica Santa Cruz Carvalho Martins1Milene Dias Miranda2Cristiana Couto Garcia3Paola Cristina Resende4Cliomar A. Santos5Maria do Carmo Debur6Rodrigo Ribeiro Rodrigues7Rodrigo Ribeiro Rodrigues8Andrea Cony Cavalcanti9Tatiana Schäffer Gregianini10Felipe Campos de Melo Iani11Felicidade Mota Pereira12Sandra Bianchini Fernandes13Jessylene de Almeida Ferreira14Katia Correa de Oliveira Santos15Fernando Motta16David Brown17Walquiria Aparecida Ferreira de Almeida18Marilda Mendonça Siqueira19Aline da Rocha Matos20Laboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratório Central de Saúde Publica de Sergipe (LACEN-SE), Aracaju, Sergipe, BrazilLaboratório Central do Estado do Paraná (LACEN-PR), Curitiba, Paraná, BrazilLaboratório de Saúde Pública do Estado do Espírito Santo, Secretaria de Saúde do Estado do Espírito Santo (LACEN-ES), Vitória, Espirito Santo, BrazilNúcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, Espirito Santo, BrazilLaboratório Central de Saúde Pública do Rio de Janeiro (LACEN-RJ), Rio de Janeiro, BrazilLaboratório Central de Saúde Pública da Secretaria de Saúde do estado do Rio Grande do Sul, (LACEN-RS)/CEVS/SES-RS, Porto Alegre, Rio Grande do Sul, BrazilLaboratório Central de Saúde Pública de Minas Gerais (LACEN-MG), Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, BrazilLaboratório Central da Saúde Pública do estado da Bahia (LACEN-BA), Salvador, Bahia, Brazil0Laboratório Central de Santa Catarina (LACEN-SC), Florianópolis, Santa Catarina, Brazil1Instituto Evandro Chagas, Belém, Pará, Brazil2Laboratório Central de Saúde Pública do Estado de São Paulo (LACEN-SP), Instituto Adolfo Lutz, São Paulo, São Paulo, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, Brazil3Departamento de Imunização e Doenças Transmissíveis (DEIDT)/Secretaria de Vigilância em Saúde (SVS)/Ministério da Saúde (MS), Brasília, Distrito Federal, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilLaboratory of Respiratory Viruses and Measles, Oswaldo Cruz Institute, FIOCRUZ Fundation, Rio de Janeiro, BrazilThe 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.https://www.frontiersin.org/articles/10.3389/fpubh.2022.944277/fullinfluenza A virusresistanceneuraminidase (NA) inhibitorsoseltamivirbaloxavir marboxiladamantane
spellingShingle Thiago das Chagas Sousa
Jessica Santa Cruz Carvalho Martins
Milene Dias Miranda
Cristiana Couto Garcia
Paola Cristina Resende
Cliomar A. Santos
Maria do Carmo Debur
Rodrigo Ribeiro Rodrigues
Rodrigo Ribeiro Rodrigues
Andrea Cony Cavalcanti
Tatiana Schäffer Gregianini
Felipe Campos de Melo Iani
Felicidade Mota Pereira
Sandra Bianchini Fernandes
Jessylene de Almeida Ferreira
Katia Correa de Oliveira Santos
Fernando Motta
David Brown
Walquiria Aparecida Ferreira de Almeida
Marilda Mendonça Siqueira
Aline da Rocha Matos
Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
Frontiers in Public Health
influenza A virus
resistance
neuraminidase (NA) inhibitors
oseltamivir
baloxavir marboxil
adamantane
title Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
title_full Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
title_fullStr Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
title_full_unstemmed Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
title_short Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
title_sort low prevalence of influenza a strains with resistance markers in brazil during 2017 2019 seasons
topic influenza A virus
resistance
neuraminidase (NA) inhibitors
oseltamivir
baloxavir marboxil
adamantane
url https://www.frontiersin.org/articles/10.3389/fpubh.2022.944277/full
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