Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola

Detalhes bibliográficos
Autor(a) principal: Kiaco, Kinanga
Data de Publicação: 2015
Outros Autores: Teixeira, Joana, Machado, Marta, Do Rosário, Virgílio, Lopes, Dinora
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.1186/s12936-015-1018-3
Resumo: Background: Drug resistance in Plasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem®). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99 %. Methods: 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR-RFLP and sequencing for pfk13-propeller genotype. Results: The cure rate was 91.3 %. The obtained results showed that from 103 patients, 12.6 % (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4 % (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14 % of these samples showed increased pfmdr1 copy number; 100 % (n = 21) had wild-type allele of k13 gene in all the studied positions. Discussion: These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.
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spelling Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, AngolaAngolaArtemether-lumefantrinepfatp6pfK13pfmdr1Plasmodium falciparumPolymorphismsTherapeutic efficacyParasitologyInfectious DiseasesSDG 3 - Good Health and Well-beingBackground: Drug resistance in Plasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem®). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99 %. Methods: 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR-RFLP and sequencing for pfk13-propeller genotype. Results: The cure rate was 91.3 %. The obtained results showed that from 103 patients, 12.6 % (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4 % (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14 % of these samples showed increased pfmdr1 copy number; 100 % (n = 21) had wild-type allele of k13 gene in all the studied positions. Discussion: These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.Instituto de Higiene e Medicina Tropical (IHMT)Centro de Malária e outras Doenças Tropicais (CMDT)RUNKiaco, KinangaTeixeira, JoanaMachado, MartaDo Rosário, VirgílioLopes, Dinora2018-05-11T22:02:44Z2015-12-162015-12-16T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttps://doi.org/10.1186/s12936-015-1018-3engPURE: 1724004http://www.scopus.com/inward/record.url?scp=84950150572&partnerID=8YFLogxKhttps://doi.org/10.1186/s12936-015-1018-3info: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:RCAAP2024-05-22T17:32:35Zoai:run.unl.pt:10362/36586Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T17:32:35Repositório 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 Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
title Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
spellingShingle Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
Kiaco, Kinanga
Angola
Artemether-lumefantrine
pfatp6
pfK13
pfmdr1
Plasmodium falciparum
Polymorphisms
Therapeutic efficacy
Parasitology
Infectious Diseases
SDG 3 - Good Health and Well-being
title_short Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
title_full Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
title_fullStr Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
title_full_unstemmed Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
title_sort Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola
author Kiaco, Kinanga
author_facet Kiaco, Kinanga
Teixeira, Joana
Machado, Marta
Do Rosário, Virgílio
Lopes, Dinora
author_role author
author2 Teixeira, Joana
Machado, Marta
Do Rosário, Virgílio
Lopes, Dinora
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Higiene e Medicina Tropical (IHMT)
Centro de Malária e outras Doenças Tropicais (CMDT)
RUN
dc.contributor.author.fl_str_mv Kiaco, Kinanga
Teixeira, Joana
Machado, Marta
Do Rosário, Virgílio
Lopes, Dinora
dc.subject.por.fl_str_mv Angola
Artemether-lumefantrine
pfatp6
pfK13
pfmdr1
Plasmodium falciparum
Polymorphisms
Therapeutic efficacy
Parasitology
Infectious Diseases
SDG 3 - Good Health and Well-being
topic Angola
Artemether-lumefantrine
pfatp6
pfK13
pfmdr1
Plasmodium falciparum
Polymorphisms
Therapeutic efficacy
Parasitology
Infectious Diseases
SDG 3 - Good Health and Well-being
description Background: Drug resistance in Plasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem®). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99 %. Methods: 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR-RFLP and sequencing for pfk13-propeller genotype. Results: The cure rate was 91.3 %. The obtained results showed that from 103 patients, 12.6 % (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4 % (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14 % of these samples showed increased pfmdr1 copy number; 100 % (n = 21) had wild-type allele of k13 gene in all the studied positions. Discussion: These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.
publishDate 2015
dc.date.none.fl_str_mv 2015-12-16
2015-12-16T00:00:00Z
2018-05-11T22:02:44Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv https://doi.org/10.1186/s12936-015-1018-3
url https://doi.org/10.1186/s12936-015-1018-3
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PURE: 1724004
http://www.scopus.com/inward/record.url?scp=84950150572&partnerID=8YFLogxK
https://doi.org/10.1186/s12936-015-1018-3
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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
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