Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/4697 |
Resumo: | 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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Sousa, Thiago das ChagasMartins, Jessica Santa Cruz CarvalhoMiranda, Milene DiasGarcia, Cristiana CoutoResende, Paola CristinaSantos, Cliomar Alves dosDebur, Maria do CarmoRodrigues, Rodrigo RibeiroCavalcanti, Andrea ConyGregianini, Tatiana SchafferIani, Felipe Campos de MeloFernandes, Sandra BianchiniFerreira, Jessylene de AlmeidaSantos, Katia Correa de OliveiraMotta, FernandoBrown, DavidAlmeida, Walquiria Aparecida Ferreira deSiqueira, Marilda MendonçaMatos, Aline da RochaPereira, Felicidade Mota2022-10-27T18:05:11Z2022-10-27T18:05:11Z2022SOUSA, Thiago das Chagas et al. Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons. Frontiers in Public Health, v. 10, n. 944277, p. 1-9, 2022. DOI: https://doi.org/10.3389/fpubh.2022.944277. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516282/pdf/fpubh-10-944277.pdf.2296-2565https://patua.iec.gov.br/handle/iec/4697The 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.This project was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Programa Estratégico de Apoio à Pesquisa em Saúde (PAPES), Fundação Oswaldo Cruz, CNPq, and Coordenação Geral de Laboratórios de Saúde Pública (CGLAB) from the Brazilian Ministry of Health.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública de Sergipe. Aracaju, SE, Brazil.Laboratório Central de Saúde Pública de Sergipe. Aracaju, SE, Brazil.Laboratório Central do Estado do Paraná. Curitiba, PR, Brazil.Laboratório Central do Estado do Paraná. Curitiba, PR, Brazil.Secretaria de Saúde do Estado do Espírito Santo. Laboratório de Saúde Pública do Estado do Espírito Santo. Vitória, ES, Brazil / Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brazil.Secretaria de Saúde do Estado do Espírito Santo. Laboratório de Saúde Pública do Estado do Espírito Santo. Vitória, ES, Brazil / Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brazil.Laboratório Central de Saúde Pública do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública do Rio de Janeiro. Rio de Janeiro, RJ, Brazil.Secretaria de Saúde do estado do Rio Grande do Sul. Laboratório Central de Saúde Pública. Porto Alegre, RS, Brazil.Secretaria de Saúde do estado do Rio Grande do Sul. Laboratório Central de Saúde Pública. Porto Alegre, RS, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública de Minas Gerais. Belo Horizonte, MG, Brazil.Fundação Ezequiel Dias. Laboratório Central de Saúde Pública de Minas Gerais. Belo Horizonte, MG, Brazil.Laboratório Central da Saúde Pública do estado da Bahia. Salvador, BA, Brazil.Laboratório Central da Saúde Pública do estado da Bahia. Salvador, BA, Brazil.Laboratório Central de Santa Catarina. Florianópolis, SC, Brazil.Laboratório Central de Santa Catarina. Florianópolis, SC, Brazil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Ananindeua, PA. Brasil.Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos. Instituto Evandro Chagas. Ananindeua, PA. Brasil.Instituto Adolfo Lutz. Laboratório Central de Saúde Pública do Estado de São Paulo. São Paulo, SP, Brazil.Instituto Adolfo Lutz. Laboratório Central de Saúde Pública do Estado de São Paulo. São Paulo, SP, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Brasília, DF, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Brasília, DF, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. Rio de Janeiro, RJ, Brazil.Fiocruz Fundation. Oswaldo Cruz Institute. Laboratory of Respiratory Viruses and Measles. 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dc.title.pt_BR.fl_str_mv |
Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons |
title |
Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons |
spellingShingle |
Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons Sousa, Thiago das Chagas Vírus da Influenza A / patogenicidade Neuraminidase / farmacologia Baloxavir / farmacologia Farmacorresistência Viral |
title_short |
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_sort |
Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons |
author |
Sousa, Thiago das Chagas |
author_facet |
Sousa, Thiago das Chagas Martins, Jessica Santa Cruz Carvalho Miranda, Milene Dias Garcia, Cristiana Couto Resende, Paola Cristina Santos, Cliomar Alves dos Debur, Maria do Carmo Rodrigues, Rodrigo Ribeiro Cavalcanti, Andrea Cony Gregianini, Tatiana Schaffer Iani, Felipe Campos de Melo 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 Pereira, Felicidade Mota |
author_role |
author |
author2 |
Martins, Jessica Santa Cruz Carvalho Miranda, Milene Dias Garcia, Cristiana Couto Resende, Paola Cristina Santos, Cliomar Alves dos Debur, Maria do Carmo Rodrigues, Rodrigo Ribeiro Cavalcanti, Andrea Cony Gregianini, Tatiana Schaffer Iani, Felipe Campos de Melo 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 Pereira, Felicidade Mota |
author2_role |
author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Sousa, Thiago das Chagas Martins, Jessica Santa Cruz Carvalho Miranda, Milene Dias Garcia, Cristiana Couto Resende, Paola Cristina Santos, Cliomar Alves dos Debur, Maria do Carmo Rodrigues, Rodrigo Ribeiro Cavalcanti, Andrea Cony Gregianini, Tatiana Schaffer Iani, Felipe Campos de Melo 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 Pereira, Felicidade Mota |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Vírus da Influenza A / patogenicidade Neuraminidase / farmacologia Baloxavir / farmacologia Farmacorresistência Viral |
topic |
Vírus da Influenza A / patogenicidade Neuraminidase / farmacologia Baloxavir / farmacologia Farmacorresistência Viral |
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. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-10-27T18:05:11Z |
dc.date.available.fl_str_mv |
2022-10-27T18:05:11Z |
dc.date.issued.fl_str_mv |
2022 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SOUSA, Thiago das Chagas et al. Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons. Frontiers in Public Health, v. 10, n. 944277, p. 1-9, 2022. DOI: https://doi.org/10.3389/fpubh.2022.944277. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516282/pdf/fpubh-10-944277.pdf. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/4697 |
dc.identifier.issn.-.fl_str_mv |
2296-2565 |
identifier_str_mv |
SOUSA, Thiago das Chagas et al. Low prevalence of influenza A strains with resistance markers in Brazil during 2017–2019 seasons. Frontiers in Public Health, v. 10, n. 944277, p. 1-9, 2022. DOI: https://doi.org/10.3389/fpubh.2022.944277. Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9516282/pdf/fpubh-10-944277.pdf. 2296-2565 |
url |
https://patua.iec.gov.br/handle/iec/4697 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
instname_str |
Instituto Evandro Chagas (IEC) |
instacron_str |
IEC |
institution |
IEC |
reponame_str |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
collection |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
bitstream.url.fl_str_mv |
https://patua.iec.gov.br/bitstreams/716e9a74-9e51-4502-b0d1-ff7a11818abe/download https://patua.iec.gov.br/bitstreams/70a1596a-188a-428e-89c6-375bbb94799f/download https://patua.iec.gov.br/bitstreams/dcf19f76-e819-42c1-b63a-9d777239ec3f/download https://patua.iec.gov.br/bitstreams/ec0137af-bbeb-4e09-824f-a3c257904e78/download https://patua.iec.gov.br/bitstreams/59fc0b86-4491-4209-ac3f-f58d658f2f98/download |
bitstream.checksum.fl_str_mv |
ed5579239f75d6b66ae7a29bf044fdf3 11832eea31b16df8613079d742d61793 8cf8b8624f84ddb8452ce7aab60c0ed3 884c9c841f3b93ab089d891ad1f6aee6 884c9c841f3b93ab089d891ad1f6aee6 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC) |
repository.mail.fl_str_mv |
clariceneta@iec.gov.br || Biblioteca@iec.gov.br |
_version_ |
1809190058340646912 |