Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6

Detalhes bibliográficos
Autor(a) principal: Ferreira, Isabel D
Data de Publicação: 2008
Outros Autores: Martinelli, Axel, Rodrigues, Louise A, Carmo, Ediclei Lima do, Rosário, Virgílio E do, Póvoa, Marinete Marins, Cravo, Pedro
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/1062
Resumo: Objective To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and ⁄ or altered copy numbers in the putative resistance-associated pfcrt, pfmdr1 and pfATPase6 genes. methods In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and ⁄ or PCR-RFLP. We used real-time quantitative PCR to assess gene copy numbers. results ATN and ATH geometric mean IC50s were 0.85 nm, 95% CI (0.55–1.15) and 3.0 nm, 95% CI (1.5–4.5), respectively. There was extremely limited diversity of pfcrt and pfmdr1 genotypes and three SNPs were identified in the pfATPase6 gene: one T to A synonymous mutation at nucleotide 2694 and two non-synonymous (both G to A) mutations at nucleotides 110 and 1916, causing predicted aminoacid shifts of arginine to lysine and of glycine to aspartate, respectively. The previously reported S769N mutation was not detected in any of the isolates inspected. In addition, no gene amplifications were detected in a subset of eight isolates. conclusion Artemisinin derivatives display satisfactory in vitro activity locally and the pfATPase6 gene is distinct from that reported in French Guiana, suggesting that those haplotypes have not been introduced regionally.
id IEC-2_d00a38bec8e345e0c11aa4063976edb1
oai_identifier_str oai:patua.iec.gov.br:iec/1062
network_acronym_str IEC-2
network_name_str Repositório Digital do Instituto Evandro Chagas (Patuá)
repository_id_str
spelling Ferreira, Isabel DMartinelli, AxelRodrigues, Louise ACarmo, Ediclei Lima doRosário, Virgílio E doPóvoa, Marinete MarinsCravo, Pedro2016-01-26T11:43:21Z2016-01-26T11:43:21Z2008FERREIRA, Isabel D. et al. Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Tropical Medicine and International Health, v. 13, n. 1, p. 199-207, Feb. 20081360-2276https://patua.iec.gov.br/handle/iec/106210.1111/j.1365-3156.2007.01991.xObjective To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and ⁄ or altered copy numbers in the putative resistance-associated pfcrt, pfmdr1 and pfATPase6 genes. methods In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and ⁄ or PCR-RFLP. We used real-time quantitative PCR to assess gene copy numbers. results ATN and ATH geometric mean IC50s were 0.85 nm, 95% CI (0.55–1.15) and 3.0 nm, 95% CI (1.5–4.5), respectively. There was extremely limited diversity of pfcrt and pfmdr1 genotypes and three SNPs were identified in the pfATPase6 gene: one T to A synonymous mutation at nucleotide 2694 and two non-synonymous (both G to A) mutations at nucleotides 110 and 1916, causing predicted aminoacid shifts of arginine to lysine and of glycine to aspartate, respectively. The previously reported S769N mutation was not detected in any of the isolates inspected. In addition, no gene amplifications were detected in a subset of eight isolates. conclusion Artemisinin derivatives display satisfactory in vitro activity locally and the pfATPase6 gene is distinct from that reported in French Guiana, suggesting that those haplotypes have not been introduced regionally.Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais. UEI Biologia Molecular. UEI Malária. Lisbon, Portugal.Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais. UEI Biologia Molecular. UEI Malária. Lisbon, Portugal.Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais. UEI Biologia Molecular. UEI Malária. Lisbon, Portugal.Ministério da Saúde. Secretaria de Vigilância em Saúde . Instituto Evandro Chagas. Belém, PA, Brasil.Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais. UEI Biologia Molecular. UEI Malária. Lisbon, Portugal.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Instituto de Higiene e Medicina Tropical. Centro de Malária e Outras Doenças Tropicais. UEI Biologia Molecular. UEI Malária. Lisbon, Portugal.application/pdfengWileyPlasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleArtemisininas / administração & dosagemArtemisininas / análisePlasmodium falciparum / efeitos de drogasMalária / prevenção & controleBiomarcadoresinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALPlasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6 .pdfapplication/pdf293948https://patua.iec.gov.br/bitstreams/bdb90e9e-d0d6-4a24-b7be-dbac6bf7a435/downloada510f436594b20157ff43abb89de2aa3MD51TEXTfile_1.pdf.txtfile_1.pdf.txtExtracted texttext/plain41196https://patua.iec.gov.br/bitstreams/56a8507b-ddd3-4b1b-9a97-876c5d9436db/download197dabb041acb61ecc0487823b3cd261MD52Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6 .pdf.txtPlasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6 .pdf.txtExtracted texttext/plain42154https://patua.iec.gov.br/bitstreams/afe5fcb5-e71b-4cdb-86be-d9dedd4a06f1/download1ebf8ae51911d972b92355c808fbc854MD56THUMBNAILPlasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6 .pdf.jpgPlasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6 .pdf.jpgGenerated Thumbnailimage/jpeg5604https://patua.iec.gov.br/bitstreams/f7ffafbb-3e94-4051-907e-dc98fcee5026/download3690356e85423c36262938770ac88ce9MD57LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/eee96045-a33e-45ab-841f-4641dac75894/download11832eea31b16df8613079d742d61793MD55iec/10622022-10-20 22:06:50.518oai:patua.iec.gov.br:iec/1062https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T22:06:50Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
title Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
spellingShingle Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
Ferreira, Isabel D
Artemisininas / administração & dosagem
Artemisininas / análise
Plasmodium falciparum / efeitos de drogas
Malária / prevenção & controle
Biomarcadores
title_short Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
title_full Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
title_fullStr Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
title_full_unstemmed Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
title_sort Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6
author Ferreira, Isabel D
author_facet Ferreira, Isabel D
Martinelli, Axel
Rodrigues, Louise A
Carmo, Ediclei Lima do
Rosário, Virgílio E do
Póvoa, Marinete Marins
Cravo, Pedro
author_role author
author2 Martinelli, Axel
Rodrigues, Louise A
Carmo, Ediclei Lima do
Rosário, Virgílio E do
Póvoa, Marinete Marins
Cravo, Pedro
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ferreira, Isabel D
Martinelli, Axel
Rodrigues, Louise A
Carmo, Ediclei Lima do
Rosário, Virgílio E do
Póvoa, Marinete Marins
Cravo, Pedro
dc.subject.decsPrimary.pt_BR.fl_str_mv Artemisininas / administração & dosagem
Artemisininas / análise
Plasmodium falciparum / efeitos de drogas
Malária / prevenção & controle
Biomarcadores
topic Artemisininas / administração & dosagem
Artemisininas / análise
Plasmodium falciparum / efeitos de drogas
Malária / prevenção & controle
Biomarcadores
description Objective To evaluate the in vitro efficacy of artesunate (ATN) and artemether (ATH) against Plasmodium falciparum isolates from the Brazilian Amazon state of Pará and to search for mutations and ⁄ or altered copy numbers in the putative resistance-associated pfcrt, pfmdr1 and pfATPase6 genes. methods In vitro efficacy of ATN and ATH was successfully measured in 56 freshly collected P. falciparum isolates, using a conventional WHO microtest with minor modifications. Single nucleotide polymorphisms (SNPs) in the same isolates were inspected using DNA sequencing and ⁄ or PCR-RFLP. We used real-time quantitative PCR to assess gene copy numbers. results ATN and ATH geometric mean IC50s were 0.85 nm, 95% CI (0.55–1.15) and 3.0 nm, 95% CI (1.5–4.5), respectively. There was extremely limited diversity of pfcrt and pfmdr1 genotypes and three SNPs were identified in the pfATPase6 gene: one T to A synonymous mutation at nucleotide 2694 and two non-synonymous (both G to A) mutations at nucleotides 110 and 1916, causing predicted aminoacid shifts of arginine to lysine and of glycine to aspartate, respectively. The previously reported S769N mutation was not detected in any of the isolates inspected. In addition, no gene amplifications were detected in a subset of eight isolates. conclusion Artemisinin derivatives display satisfactory in vitro activity locally and the pfATPase6 gene is distinct from that reported in French Guiana, suggesting that those haplotypes have not been introduced regionally.
publishDate 2008
dc.date.issued.fl_str_mv 2008
dc.date.accessioned.fl_str_mv 2016-01-26T11:43:21Z
dc.date.available.fl_str_mv 2016-01-26T11:43:21Z
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 FERREIRA, Isabel D. et al. Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Tropical Medicine and International Health, v. 13, n. 1, p. 199-207, Feb. 2008
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/1062
dc.identifier.issn.-.fl_str_mv 1360-2276
dc.identifier.doi.-.fl_str_mv 10.1111/j.1365-3156.2007.01991.x
identifier_str_mv FERREIRA, Isabel D. et al. Plasmodium falciparum from Pará state (Brazil) shows satisfactory in vitro response to artemisinin derivatives and absence of the S769N mutation in the SERCA-type PfATPase6. Tropical Medicine and International Health, v. 13, n. 1, p. 199-207, Feb. 2008
1360-2276
10.1111/j.1365-3156.2007.01991.x
url https://patua.iec.gov.br/handle/iec/1062
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.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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/bdb90e9e-d0d6-4a24-b7be-dbac6bf7a435/download
https://patua.iec.gov.br/bitstreams/56a8507b-ddd3-4b1b-9a97-876c5d9436db/download
https://patua.iec.gov.br/bitstreams/afe5fcb5-e71b-4cdb-86be-d9dedd4a06f1/download
https://patua.iec.gov.br/bitstreams/f7ffafbb-3e94-4051-907e-dc98fcee5026/download
https://patua.iec.gov.br/bitstreams/eee96045-a33e-45ab-841f-4641dac75894/download
bitstream.checksum.fl_str_mv a510f436594b20157ff43abb89de2aa3
197dabb041acb61ecc0487823b3cd261
1ebf8ae51911d972b92355c808fbc854
3690356e85423c36262938770ac88ce9
11832eea31b16df8613079d742d61793
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_ 1809190045326770176