Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy
Abstract Background Artemisinin-based combination therapy (ACT) is the mainstay of global efforts for treatment of Plasmodium falciparum malaria, but decline in its efficacy is the most important obstacle towards malaria control and elimination. Therefore, the present molecular analysis provides inf...
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ftdoajarticles:oai:doaj.org/article:a1b44d414d9b44a69c73003f6944cef5 2023-05-15T15:17:13+02:00 Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy Zakeri Sedigheh Hemati Samaneh Pirahmadi Sakineh Afsharpad Mandana Raeisi Ahmad Djadid Navid D 2012-11-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-373 https://doaj.org/article/a1b44d414d9b44a69c73003f6944cef5 EN eng BMC http://www.malariajournal.com/content/11/1/373 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-373 1475-2875 https://doaj.org/article/a1b44d414d9b44a69c73003f6944cef5 Malaria Journal, Vol 11, Iss 1, p 373 (2012) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-373 2022-12-31T04:58:41Z Abstract Background Artemisinin-based combination therapy (ACT) is the mainstay of global efforts for treatment of Plasmodium falciparum malaria, but decline in its efficacy is the most important obstacle towards malaria control and elimination. Therefore, the present molecular analysis provides information on putative mutations associated with artemisinin resistance in P . falciparum clinical population unexposed and exposed to artesunate 4 years after adoption of ACT as the first-line anti-malarial therapy in Iran. Methods In this study, blood samples (n = 226) were collected from uncomplicated P . falciparum -infected patients from different health centers of Chabahar district in Sistan and Baluchistan province in the south-eastern part of Iran, during 2003 to 2010. All collected isolates were analysed for putative candidate mutations (TTA) L263E (GAA), (GAA) E431K (AAA), (GCA) A623E (GAA) and (AGT) S769N (AAT) of pfatpase6 gene using nested PCR/RFLP, followed by sequencing. Furthermore, the gene copy number was assessed by real-time quantitative PCR (RT-qPCR) in the presence of SYBR green. Results Neither the pfatpase6 L263E nor the A623E mutation was detected among all examined isolates. The E431K mutation was found in 23% of the analysed samples unexposed to ACT; however, it was detected in 17.8% (34/191) of P . falciparum isolates exposed to artesunate after 2007. High frequency of this single nucleotide polymorphisms (SNP) (overall 18.6%) among both examined groups ( X 2 test, P >0.05) indicated that this SNP should be considered as an unrelated mutation to artemisinin resistance. In contrast, S769N mutation was not detected in unexposed isolates; however, it was found in 2.6% (5/191), four years after introduction of ACT in this malaria setting. Also, detected SNPs were not significantly frequent in both unexposed and exposed examined isolates ( X 2 test, P > 0.05). Investigation in the copy number of pfatpase6 gene revealed a similar number of copy (n = 1) as in an isolate sensitive to ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Zakeri Sedigheh Hemati Samaneh Pirahmadi Sakineh Afsharpad Mandana Raeisi Ahmad Djadid Navid D Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Artemisinin-based combination therapy (ACT) is the mainstay of global efforts for treatment of Plasmodium falciparum malaria, but decline in its efficacy is the most important obstacle towards malaria control and elimination. Therefore, the present molecular analysis provides information on putative mutations associated with artemisinin resistance in P . falciparum clinical population unexposed and exposed to artesunate 4 years after adoption of ACT as the first-line anti-malarial therapy in Iran. Methods In this study, blood samples (n = 226) were collected from uncomplicated P . falciparum -infected patients from different health centers of Chabahar district in Sistan and Baluchistan province in the south-eastern part of Iran, during 2003 to 2010. All collected isolates were analysed for putative candidate mutations (TTA) L263E (GAA), (GAA) E431K (AAA), (GCA) A623E (GAA) and (AGT) S769N (AAT) of pfatpase6 gene using nested PCR/RFLP, followed by sequencing. Furthermore, the gene copy number was assessed by real-time quantitative PCR (RT-qPCR) in the presence of SYBR green. Results Neither the pfatpase6 L263E nor the A623E mutation was detected among all examined isolates. The E431K mutation was found in 23% of the analysed samples unexposed to ACT; however, it was detected in 17.8% (34/191) of P . falciparum isolates exposed to artesunate after 2007. High frequency of this single nucleotide polymorphisms (SNP) (overall 18.6%) among both examined groups ( X 2 test, P >0.05) indicated that this SNP should be considered as an unrelated mutation to artemisinin resistance. In contrast, S769N mutation was not detected in unexposed isolates; however, it was found in 2.6% (5/191), four years after introduction of ACT in this malaria setting. Also, detected SNPs were not significantly frequent in both unexposed and exposed examined isolates ( X 2 test, P > 0.05). Investigation in the copy number of pfatpase6 gene revealed a similar number of copy (n = 1) as in an isolate sensitive to ... |
format |
Article in Journal/Newspaper |
author |
Zakeri Sedigheh Hemati Samaneh Pirahmadi Sakineh Afsharpad Mandana Raeisi Ahmad Djadid Navid D |
author_facet |
Zakeri Sedigheh Hemati Samaneh Pirahmadi Sakineh Afsharpad Mandana Raeisi Ahmad Djadid Navid D |
author_sort |
Zakeri Sedigheh |
title |
Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
title_short |
Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
title_full |
Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
title_fullStr |
Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
title_full_unstemmed |
Molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed Plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
title_sort |
molecular assessment of atpase6 mutations associated with artemisinin resistance among unexposed and exposed plasmodium falciparum clinical isolates to artemisinin-based combination therapy |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-373 https://doaj.org/article/a1b44d414d9b44a69c73003f6944cef5 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 373 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/373 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-373 1475-2875 https://doaj.org/article/a1b44d414d9b44a69c73003f6944cef5 |
op_doi |
https://doi.org/10.1186/1475-2875-11-373 |
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Malaria Journal |
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11 |
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