ArticleInternational journal for parasitology. Drugs and drug resistance2019
Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum.
Article in International journal for parasitology. Drugs and drug resistance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Genomic epidemiology of Plasmodium knowlesi reveals putative genetic drivers of adaptation in Malaysia.PLoS neglected tropical diseases · 2025Article
- Lactam Truncation Yields a Dihydroquinazolinone Scaffold with Potent Antimalarial Activity that Targets PfATP4.ChemMedChem · 2024Article
- Property and Activity Refinement of Dihydroquinazolinone-3-carboxamides as Orally Efficacious Antimalarials that Target PfATP4.Journal of medicinal chemistry · 2024Article
- Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Limited Polymorphism in the Dihydrofolate Reductase (dhfr) and dihydropteroate synthase genes (dhps) of Plasmodium knowlesi isolate from Thailand.Acta tropica · 2023Article
- Effects of the G-quadruplex-binding drugs quarfloxin and CX-5461 on the malaria parasite Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2023Article
- Review
- Quantification of parasite clearance in Plasmodium knowlesi infections.Malaria journal · 2023Article
- Article
- Plasmodium knowlesi: the game changer for malaria eradication.Malaria journal · 2022Review
- Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests forFrontiers in cellular and infection microbiology · 2022Article
- Semi-Synthetic Analogues of Cryptolepine as a Potential Source of Sustainable Drugs for the Treatment of Malaria, Human African Trypanosomiasis, and Cancer.Frontiers in pharmacology · 2022Article
- Article
- Antiplasmodial activity of the natural product compounds alstonine and himbeline.International journal for parasitology. Drugs and drug resistance · 2021Article
- The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957.Scientific reports · 2021Article
- Clinical management of Plasmodium knowlesi malaria.Advances in parasitology · 2021Review
- Boromycin has Rapid-Onset Antibiotic Activity Against Asexual and Sexual Blood Stages ofFrontiers in cellular and infection microbiology · 2021Article
- Novel Endochin-Like Quinolones Exhibit PotentAntimicrobial agents and chemotherapy · 2020Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.
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