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Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology
Thesis (Ph.D (Biochemistry))--University of Pretoria, 2024.
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University of Pretoria
2025
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| _version_ | 1867613595767930880 |
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| access_status_str | Open Access |
| author2 | Birkholtz, Lyn-Marie |
| author_browse | Birkholtz, Lyn-Marie |
| author_facet | Birkholtz, Lyn-Marie |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (Ph.D (Biochemistry))--University of Pretoria, 2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/100690 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:39.160Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/100690 Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology Birkholtz, Lyn-Marie u14006325@tuks.co.za Van der Watt, Mariëtte Greyling, Nicola UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Clinical isolates Genetic diversity Gametocytes Malaria Thesis (Ph.D (Biochemistry))--University of Pretoria, 2024. Malaria elimination requires interventions able to target both the asexual blood stage (ABS) parasites and transmissible gametocyte stages of Plasmodium falciparum. Lead antimalarial candidates are evaluated against clinical isolates to address key concerns regarding efficacy and to confirm that the current, circulating parasites from endemic regions lack resistance against these candidates. While this has largely been performed on ABS parasites, limited data are available on the transmission-blocking efficacy of compounds with multistage activity. Here, we evaluated the efficacy of lead antimalarial candidates against both ABS parasites and late-stage gametocytes side-by-side, against clinical P. falciparum isolates from southern Africa. We additionally correlated drug efficacy to the genetic diversity of the clinical isolates as determined with a panel of well-characterized, genome-spanning microsatellite markers. Our data indicate varying sensitivities of the isolates to key antimalarial candidates, both for ABS parasites and gametocyte stages. While ABS parasites were efficiently killed, irrespective of genetic complexity, antimalarial candidates lost some gametocytocidal efficacy when the gametocytes originated from genetically complex, multiple-clone infections. This suggests a fitness benefit to multiclone isolates to sustain transmission and reduce drug susceptibility. In conclusion, this is the first study to investigate the efficacy of antimalarial candidates on both ABS parasites and gametocytes from P. falciparum clinical isolates where the influence of parasite genetic complexity is highlighted, ultimately aiding the malaria elimination agenda. National Research Foundation (NRF) Biochemistry, Genetics and Microbiology (BGM) Ph.D (Biochemistry) Unrestricted Natural and Agricultural Sciences SDG-03: Good health and well-being 2025-02-11T10:52:06Z 2025-02-11T10:52:06Z 2024-10 Thesis Greyling N, van der Watt M, Gwarinda H, van Heerden A, Greenhouse B, Leroy D, Niemand J, Birkholtz L-M. Genetic complexity alters drug susceptibility of asexual and gametocyte stages of Plasmodium falciparum to antimalarial candidates. Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0129123. doi: 10.1128/aac.01291-23. Epub 2024 Jan 23. PMID: 38259087; PMCID: PMC10916389. 10.1128/aac.01291-23 A2025 http://hdl.handle.net/2263/100690 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Clinical isolates Genetic diversity Gametocytes Malaria Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title | Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title_full | Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title_fullStr | Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title_full_unstemmed | Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title_short | Genetically diverse Plasmodium falciparum Southern Africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| title_sort | genetically diverse plasmodium falciparum southern africa isolates provides insights into antimalarial drug sensitivity and gametocyte biology |
| topic | UCTD Sustainable Development Goals (SDGs) Plasmodium falciparum Clinical isolates Genetic diversity Gametocytes Malaria |
| url | http://hdl.handle.net/2263/100690 |