Maiga Mohamed, Wicha Sebastian G, Diallo Fatoumata, Traoré Issa, Samaké Abdoul Karim, Sogore Fanta, Diakité Ousmaila, Dao François, Diallo Djeneba, Traoré Aliou, Djimde Abdoulaye A, Spangenberg Thomas, Demarta-Gatsi Claudia, Dembele Laurent
Faculty of Pharmacy, Malaria Research and Training Centre (MRTC), Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), Bamako, Mali.
Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0186324. doi: 10.1128/aac.01863-24. Epub 2025 Jun 17.
Evaluating the efficacy of antimalarial drugs is crucial in the fight against malaria, as the parasiticidal effectiveness of these drugs often predicts their clinical success. Parasite Reduction Ratio (PRR) assay is the current method of choice for assessing antimalarial's ability to halt parasite recovery after treatment; however, it is time-consuming and resource-intensive, making it less ideal for low-resource or clinical settings. Recent advancements in parasite viability assessment, such as use of the MitoTracker (MT) which probes stain active mitochondria in live cells, provide a faster way to distinguish live from dead parasites using the flow cytometry, providing, thus, timely insights to inform treatment outcomes in clinical trials. In this study, the accuracy of direct viability assessment (DVA) of the parasite using MT staining was compared with the previously established PRR assay to evaluate the efficacy of four reference antimalarial drugs (dihydroartemisinin, chloroquine, atovaquone, and pyrimethamine) using 3D7 strain. Additionally, a mathematical model was developed to estimate key parameters, such as maximum killing rate and lag phase. The model yielded comparable values for these compounds across both assays reinforcing the reliability of the DVA assay for rapidly assessing antimalarial drug efficacy. In conclusion, the DVA relies on specialized equipment and technical expertise. However, it can emerge as an alternative to the PRR, offering a faster and more clinically suited approach for studies.
评估抗疟药物的疗效在抗击疟疾的斗争中至关重要，因为这些药物的杀寄生虫效力往往预示着其临床治疗的成功。寄生虫减少率（PRR）测定法是目前评估抗疟药物在治疗后阻止寄生虫恢复能力的首选方法；然而，该方法耗时且资源密集，对于资源匮乏或临床环境而言不太理想。寄生虫活力评估方面的最新进展，例如使用MitoTracker（MT）来探测活细胞中的活性线粒体，提供了一种通过流式细胞术更快地区分活寄生虫和死寄生虫的方法，从而为临床试验中的治疗结果提供及时的见解。在本研究中，使用MT染色对寄生虫进行直接活力评估（DVA）的准确性与先前建立的PRR测定法进行了比较，以评估四种参考抗疟药物（双氢青蒿素、氯喹、阿托伐醌和乙胺嘧啶）对3D7菌株的疗效。此外，还开发了一个数学模型来估计关键参数，如最大杀灭率和滞后期。该模型在两种测定法中得出的这些化合物的值具有可比性，这加强了DVA测定法在快速评估抗疟药物疗效方面的可靠性。总之，DVA依赖于专业设备和技术专长。然而，它可以成为PRR的替代方法，为研究提供一种更快且更适合临床的方法。
