Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan
Abstract Background In Pakistan, artesunate (AS) in combination with sulfadoxine–pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite r...
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ftdoajarticles:oai:doaj.org/article:04bf58c1e13c45ebba9a33b478ec38c1 2023-05-15T15:16:05+02:00 Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan Adnan Yaqoob Aamer Ali Khattak Muhammad Faisal Nadeem Huma Fatima Gillian Mbambo Amed Ouattara Matthew Adams Nadia Zeeshan Shannon Takala-Harrison 2018-12-01T00:00:00Z https://doi.org/10.1186/s12936-018-2620-y https://doaj.org/article/04bf58c1e13c45ebba9a33b478ec38c1 EN eng BMC http://link.springer.com/article/10.1186/s12936-018-2620-y https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2620-y 1475-2875 https://doaj.org/article/04bf58c1e13c45ebba9a33b478ec38c1 Malaria Journal, Vol 17, Iss 1, Pp 1-9 (2018) Malaria Plasmodium falciparum Drug resistance Pakistan Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-018-2620-y 2022-12-31T12:20:30Z Abstract Background In Pakistan, artesunate (AS) in combination with sulfadoxine–pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite resistance to treatment. Currently, no data are available on molecular markers of artemisinin resistance (K13 mutations) in P. falciparum isolates from Pakistan. In this study, the prevalence of mutations associated with SP and artemisinin resistance was estimated in different regions of Pakistan. Methods A total of 845 blood samples that were positive for malaria parasites by microscopy or rapid diagnostic test were collected from January 2016 to February 2017 from 16 different sites in Pakistan. Of these samples, 300 were positive for P. falciparum by PCR. Polymorphisms in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by pyrosequencing while polymorphisms in the propeller domain of the pfk13 gene were identified by Sanger sequencing. Results The prevalence of the PfDHFR 108N and 59R mutations was 100% and 98.8%, respectively, while the prevalence of PfDHFR 50R and 51I mutations was 8.6%. No mutation was observed at PfDHFR position 164. In PfDHPS, the prevalence of mutations at positions 436, 437, and 613 was 9.9%, 45.2%, and 0.4%, respectively. No mutations were found at PfDHPS positions 540 and 581. The prevalence of double PfDHFR mutants (59R + 108N) ranged from 93.8% to 100%, while the prevalence of parasites having the PfDHFR 59R + 108N mutations in addition to the PfDHPS 437G mutation ranged from 9.5% to 83.3% across different regions of Pakistan. Nine non-synonymous and four synonymous mutations were observed in the PfK13 propeller domain, none of which correspond to mutations validated to contribute to artemisinin resistance. Conclusion The absence of the highly resistant PfDHFR/PfDHPS quintuple mutant parasites and the lack of PfK13 mutations ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 17 1 |
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English |
topic |
Malaria Plasmodium falciparum Drug resistance Pakistan Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Malaria Plasmodium falciparum Drug resistance Pakistan Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Adnan Yaqoob Aamer Ali Khattak Muhammad Faisal Nadeem Huma Fatima Gillian Mbambo Amed Ouattara Matthew Adams Nadia Zeeshan Shannon Takala-Harrison Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
topic_facet |
Malaria Plasmodium falciparum Drug resistance Pakistan Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background In Pakistan, artesunate (AS) in combination with sulfadoxine–pyrimethamine (SP) is the recommended treatment for uncomplicated Plasmodium falciparum malaria. Monitoring molecular markers of anti-malarial drug resistance is crucial for early detection and containment of parasite resistance to treatment. Currently, no data are available on molecular markers of artemisinin resistance (K13 mutations) in P. falciparum isolates from Pakistan. In this study, the prevalence of mutations associated with SP and artemisinin resistance was estimated in different regions of Pakistan. Methods A total of 845 blood samples that were positive for malaria parasites by microscopy or rapid diagnostic test were collected from January 2016 to February 2017 from 16 different sites in Pakistan. Of these samples, 300 were positive for P. falciparum by PCR. Polymorphisms in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by pyrosequencing while polymorphisms in the propeller domain of the pfk13 gene were identified by Sanger sequencing. Results The prevalence of the PfDHFR 108N and 59R mutations was 100% and 98.8%, respectively, while the prevalence of PfDHFR 50R and 51I mutations was 8.6%. No mutation was observed at PfDHFR position 164. In PfDHPS, the prevalence of mutations at positions 436, 437, and 613 was 9.9%, 45.2%, and 0.4%, respectively. No mutations were found at PfDHPS positions 540 and 581. The prevalence of double PfDHFR mutants (59R + 108N) ranged from 93.8% to 100%, while the prevalence of parasites having the PfDHFR 59R + 108N mutations in addition to the PfDHPS 437G mutation ranged from 9.5% to 83.3% across different regions of Pakistan. Nine non-synonymous and four synonymous mutations were observed in the PfK13 propeller domain, none of which correspond to mutations validated to contribute to artemisinin resistance. Conclusion The absence of the highly resistant PfDHFR/PfDHPS quintuple mutant parasites and the lack of PfK13 mutations ... |
format |
Article in Journal/Newspaper |
author |
Adnan Yaqoob Aamer Ali Khattak Muhammad Faisal Nadeem Huma Fatima Gillian Mbambo Amed Ouattara Matthew Adams Nadia Zeeshan Shannon Takala-Harrison |
author_facet |
Adnan Yaqoob Aamer Ali Khattak Muhammad Faisal Nadeem Huma Fatima Gillian Mbambo Amed Ouattara Matthew Adams Nadia Zeeshan Shannon Takala-Harrison |
author_sort |
Adnan Yaqoob |
title |
Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
title_short |
Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
title_full |
Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
title_fullStr |
Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
title_full_unstemmed |
Prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in Plasmodium falciparum from Pakistan |
title_sort |
prevalence of molecular markers of sulfadoxine–pyrimethamine and artemisinin resistance in plasmodium falciparum from pakistan |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-018-2620-y https://doaj.org/article/04bf58c1e13c45ebba9a33b478ec38c1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-9 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-018-2620-y https://doaj.org/toc/1475-2875 doi:10.1186/s12936-018-2620-y 1475-2875 https://doaj.org/article/04bf58c1e13c45ebba9a33b478ec38c1 |
op_doi |
https://doi.org/10.1186/s12936-018-2620-y |
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Malaria Journal |
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17 |
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1 |
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1766346392170659840 |