The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/11582 |
Resumo: | Objective Artemether-lumefantrine (AL), presently the most favoured combination therapy against uncomplicated Plasmodium falciparum malaria in Africa, has recently shown to select for the pfmdr1 86N allele. The objective of this study was to search for the selection of other mutations potentially involved in artemether-lumefantrine tolerance and/or resistance, i.e. pfmdr1 gene amplification, pfmdr1 Y184F, S1034C, N1042D, D1246Y, pfcrt S163R and PfATP6 S769N. Methods The above mentioned SNPs were analysed by PCR-restriction fragment length polymorphism and pfmdr1 gene amplification by real-time PCR based protocols in parasites from 200 children treated with AL for uncomplicated P. falciparum malaria in Zanzibar. Results A statistically significant selection of pfmdr1 184F mostly in combination with 86N was seen in reinfections after treatment. No pfmdr1 gene amplification was found. Conclusion The results suggest that different pfmdr1 alleles are involved in the development of tolerance/resistance to lumefantrine. |
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The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in AfricaSub-Saharan AfricaMefloquine resistanceIncreased sensitivityGeneSelectionMalariaAmplificationHalofantrineAmodiaquineMutationsObjective Artemether-lumefantrine (AL), presently the most favoured combination therapy against uncomplicated Plasmodium falciparum malaria in Africa, has recently shown to select for the pfmdr1 86N allele. The objective of this study was to search for the selection of other mutations potentially involved in artemether-lumefantrine tolerance and/or resistance, i.e. pfmdr1 gene amplification, pfmdr1 Y184F, S1034C, N1042D, D1246Y, pfcrt S163R and PfATP6 S769N. Methods The above mentioned SNPs were analysed by PCR-restriction fragment length polymorphism and pfmdr1 gene amplification by real-time PCR based protocols in parasites from 200 children treated with AL for uncomplicated P. falciparum malaria in Zanzibar. Results A statistically significant selection of pfmdr1 184F mostly in combination with 86N was seen in reinfections after treatment. No pfmdr1 gene amplification was found. Conclusion The results suggest that different pfmdr1 alleles are involved in the development of tolerance/resistance to lumefantrine.Wiley-BlackwellSapientiaSisowath, ChristinFerreira, Pedro E.Bustamante, Leyla Y.Dahlstrom, SabinaMartensson, AndreasBjorkman, AndersKrishna, SanjeevGil, José Pedro2018-12-07T14:53:35Z2007-062007-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/11582eng1360-227610.1111/j.1365-3156.2007.01843.xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:23:25Zoai:sapientia.ualg.pt:10400.1/11582Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:03:04.124123Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
title |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
spellingShingle |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa Sisowath, Christin Sub-Saharan Africa Mefloquine resistance Increased sensitivity Gene Selection Malaria Amplification Halofantrine Amodiaquine Mutations |
title_short |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
title_full |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
title_fullStr |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
title_full_unstemmed |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
title_sort |
The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa |
author |
Sisowath, Christin |
author_facet |
Sisowath, Christin Ferreira, Pedro E. Bustamante, Leyla Y. Dahlstrom, Sabina Martensson, Andreas Bjorkman, Anders Krishna, Sanjeev Gil, José Pedro |
author_role |
author |
author2 |
Ferreira, Pedro E. Bustamante, Leyla Y. Dahlstrom, Sabina Martensson, Andreas Bjorkman, Anders Krishna, Sanjeev Gil, José Pedro |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Sisowath, Christin Ferreira, Pedro E. Bustamante, Leyla Y. Dahlstrom, Sabina Martensson, Andreas Bjorkman, Anders Krishna, Sanjeev Gil, José Pedro |
dc.subject.por.fl_str_mv |
Sub-Saharan Africa Mefloquine resistance Increased sensitivity Gene Selection Malaria Amplification Halofantrine Amodiaquine Mutations |
topic |
Sub-Saharan Africa Mefloquine resistance Increased sensitivity Gene Selection Malaria Amplification Halofantrine Amodiaquine Mutations |
description |
Objective Artemether-lumefantrine (AL), presently the most favoured combination therapy against uncomplicated Plasmodium falciparum malaria in Africa, has recently shown to select for the pfmdr1 86N allele. The objective of this study was to search for the selection of other mutations potentially involved in artemether-lumefantrine tolerance and/or resistance, i.e. pfmdr1 gene amplification, pfmdr1 Y184F, S1034C, N1042D, D1246Y, pfcrt S163R and PfATP6 S769N. Methods The above mentioned SNPs were analysed by PCR-restriction fragment length polymorphism and pfmdr1 gene amplification by real-time PCR based protocols in parasites from 200 children treated with AL for uncomplicated P. falciparum malaria in Zanzibar. Results A statistically significant selection of pfmdr1 184F mostly in combination with 86N was seen in reinfections after treatment. No pfmdr1 gene amplification was found. Conclusion The results suggest that different pfmdr1 alleles are involved in the development of tolerance/resistance to lumefantrine. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-06 2007-06-01T00:00:00Z 2018-12-07T14:53:35Z |
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.uri.fl_str_mv |
http://hdl.handle.net/10400.1/11582 |
url |
http://hdl.handle.net/10400.1/11582 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1360-2276 10.1111/j.1365-3156.2007.01843.x |
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-Blackwell |
publisher.none.fl_str_mv |
Wiley-Blackwell |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133265212211200 |