Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon
Autor(a) principal: | |
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Data de Publicação: | 1991 |
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/2583 |
Resumo: | Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium fakiparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prey alence ofthis mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. fakiparum strains from a wide section ofthe Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrime thamine resistance, four samples contained only the wild-type Ser-l08 codon AOC, and none contained the Thr-l08 codon ACC found in cycloguanil-resistant pyrimethamine sensitive strains. These findings indicate that a very high incidence of the Asn-l08 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are con sistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine. |
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Peterson, David SDi Santi, Silvia MPóvoa, Marinete MarinsCalvosa, Vanja Suely PachianoRosário, Virgílio E. doWellem, Thomas E2017-06-06T13:12:18Z2017-06-06T13:12:18Z1991PETERSON, David S. et al. Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon. American Journal of Tropical Medicine and Hygiene, v. 45, n. 4, p. 492-497, 1991.0002-9637https://patua.iec.gov.br/handle/iec/2583Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium fakiparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prey alence ofthis mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. fakiparum strains from a wide section ofthe Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrime thamine resistance, four samples contained only the wild-type Ser-l08 codon AOC, and none contained the Thr-l08 codon ACC found in cycloguanil-resistant pyrimethamine sensitive strains. These findings indicate that a very high incidence of the Asn-l08 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are con sistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine.United States-Brazil Science and Technology mi tiative (Project 832 13 18) / The UNDP-World Bank WHO Special Program for Research and Training in Tropical Diseases (Project 870284) / The Fundação Nacional de Saúde. Instituto Evandro ChagasNational Institutes of Health. National Institute of Allergy and Infrctious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USAGoverno do Estado de São Paulo. Superintendência de Controle de Endemias. São Paulo, SP, Brazil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brasil.Ministério da Saúde. Fundação Nacional de Saúde. Instituto Evandro Chagas. Belém, PA, Brazil.Instituto de Higiene e Medicina Tropical. Lisboa, Portugal.Instituto de Higiene e Medicina Tropical. Lisboa, Portugal.engAmerican Society of Tropical Medicine and HygienePrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazoninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMaláriaPlasmodium falciparumAntimaláricosPirimetamina / uso terapêuticoinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdfPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdfapplication/pdf759197https://patua.iec.gov.br/bitstreams/28321113-4ac9-47d1-a993-544ee85a4ff7/download193301ef84b5fa262efe08fd697127e3MD51TEXTPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdf.txtPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdf.txtExtracted texttext/plain20040https://patua.iec.gov.br/bitstreams/7860da90-dd77-46ca-bda2-7950b78af8ce/download50d93bb9278d2d0d925de1718c5e195fMD55THUMBNAILPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdf.jpgPrevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon.pdf.jpgGenerated Thumbnailimage/jpeg5999https://patua.iec.gov.br/bitstreams/de00148e-f2c1-4be0-93f9-3b9b8e2a9d54/downloadffd8b13bb7f4e9a6685dce36d934931bMD56LICENSElicense.txtlicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
title |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
spellingShingle |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon Peterson, David S Malária Plasmodium falciparum Antimaláricos Pirimetamina / uso terapêutico |
title_short |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
title_full |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
title_fullStr |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
title_full_unstemmed |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
title_sort |
Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon |
author |
Peterson, David S |
author_facet |
Peterson, David S Di Santi, Silvia M Póvoa, Marinete Marins Calvosa, Vanja Suely Pachiano Rosário, Virgílio E. do Wellem, Thomas E |
author_role |
author |
author2 |
Di Santi, Silvia M Póvoa, Marinete Marins Calvosa, Vanja Suely Pachiano Rosário, Virgílio E. do Wellem, Thomas E |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Peterson, David S Di Santi, Silvia M Póvoa, Marinete Marins Calvosa, Vanja Suely Pachiano Rosário, Virgílio E. do Wellem, Thomas E |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Malária Plasmodium falciparum Antimaláricos Pirimetamina / uso terapêutico |
topic |
Malária Plasmodium falciparum Antimaláricos Pirimetamina / uso terapêutico |
description |
Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium fakiparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prey alence ofthis mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. fakiparum strains from a wide section ofthe Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrime thamine resistance, four samples contained only the wild-type Ser-l08 codon AOC, and none contained the Thr-l08 codon ACC found in cycloguanil-resistant pyrimethamine sensitive strains. These findings indicate that a very high incidence of the Asn-l08 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are con sistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine. |
publishDate |
1991 |
dc.date.issued.fl_str_mv |
1991 |
dc.date.accessioned.fl_str_mv |
2017-06-06T13:12:18Z |
dc.date.available.fl_str_mv |
2017-06-06T13:12:18Z |
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 |
PETERSON, David S. et al. Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon. American Journal of Tropical Medicine and Hygiene, v. 45, n. 4, p. 492-497, 1991. |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/2583 |
dc.identifier.issn.-.fl_str_mv |
0002-9637 |
identifier_str_mv |
PETERSON, David S. et al. Prevalence of the dihydrofolate reductase ASN- 108 mutation as the basis for pyrimethamine-resistant falciparum malaria in the brazilian amazon. American Journal of Tropical Medicine and Hygiene, v. 45, n. 4, p. 492-497, 1991. 0002-9637 |
url |
https://patua.iec.gov.br/handle/iec/2583 |
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 |
American Society of Tropical Medicine and Hygiene |
publisher.none.fl_str_mv |
American Society of Tropical Medicine and Hygiene |
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reponame:Repositório Digital do Instituto Evandro Chagas (Patuá) instname:Instituto Evandro Chagas (IEC) instacron:IEC |
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Instituto Evandro Chagas (IEC) |
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IEC |
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IEC |
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Repositório Digital do Instituto Evandro Chagas (Patuá) |
collection |
Repositório Digital do Instituto Evandro Chagas (Patuá) |
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