Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum
Abstract Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast As...
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-021-03987-6 |
| _version_ | 1818401504328941568 |
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| author | Afolabi Owoloye Michael Olufemi Emmanuel T. Idowu Kolapo M. Oyebola |
| author_facet | Afolabi Owoloye Michael Olufemi Emmanuel T. Idowu Kolapo M. Oyebola |
| author_sort | Afolabi Owoloye |
| collection | DOAJ |
| description | Abstract Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance. Methods Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved. Results Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation. Conclusions This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent. Graphical Abstract |
| first_indexed | 2024-12-14T07:53:31Z |
| format | Article |
| id | doaj.art-118424902a0b4d6d95dcc1d5bc867d44 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-14T07:53:31Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-118424902a0b4d6d95dcc1d5bc867d442022-12-21T23:10:36ZengBMCMalaria Journal1475-28752021-12-0120111210.1186/s12936-021-03987-6Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparumAfolabi Owoloye0Michael Olufemi1Emmanuel T. Idowu2Kolapo M. Oyebola3Genomic Research in Biomedicine Laboratory, Biochemistry and Nutrition Department, Nigerian Institute of Medical ResearchGenomic Research in Biomedicine Laboratory, Biochemistry and Nutrition Department, Nigerian Institute of Medical ResearchParasitology and Bioinformatics Unit, Department of Zoology, Faculty of Science, University of LagosGenomic Research in Biomedicine Laboratory, Biochemistry and Nutrition Department, Nigerian Institute of Medical ResearchAbstract Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance. Methods Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved. Results Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation. Conclusions This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent. Graphical Abstracthttps://doi.org/10.1186/s12936-021-03987-6Artemisinin-based combination therapyPartial resistancePlasmodium falciparumKelch-13Pfcoroninpfatpase6 |
| spellingShingle | Afolabi Owoloye Michael Olufemi Emmanuel T. Idowu Kolapo M. Oyebola Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum Malaria Journal Artemisinin-based combination therapy Partial resistance Plasmodium falciparum Kelch-13 Pfcoronin pfatpase6 |
| title | Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum |
| title_full | Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum |
| title_fullStr | Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum |
| title_full_unstemmed | Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum |
| title_short | Prevalence of potential mediators of artemisinin resistance in African isolates of Plasmodium falciparum |
| title_sort | prevalence of potential mediators of artemisinin resistance in african isolates of plasmodium falciparum |
| topic | Artemisinin-based combination therapy Partial resistance Plasmodium falciparum Kelch-13 Pfcoronin pfatpase6 |
| url | https://doi.org/10.1186/s12936-021-03987-6 |
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