Malaria Parasite Clearance: What Are We Really Measuring?. Issue 5 (May 2020)

• Record Type: Journal Article
• Authors: Khoury, David S.; Zaloumis, Sophie G.; Grigg, Matthew J.; Haque, Ashraful; Davenport, Miles P.
• Is Part Of: Trends in parasitology. Volume 36:Issue 5(2020)
• Page Start: 413
• Page End: 426
• Publication Date: 2020-05
• Subjects: malaria -- drug development -- drug efficacy -- parasite clearance -- viability; Parasitology -- Periodicals; Parasitology -- Periodicals; Biology -- Periodicals; Parasitology; Biology; Parasitologie -- Périodiques; Online resources; 571.999
• DOI: 10.1016/j.pt.2020.02.005
• Languages: English
• ISSNs: 1471-4922

Abstract

Abstract : Antimalarial drugs are vital for treating malaria and controlling transmission. Measuring drug efficacy in the field requires large clinical trials and thus we have identified proxy measures of drug efficacy such as the parasite clearance curve. This is often assumed to measure the rate of drug activity against parasites and is used to predict optimal treatment regimens required to completely clear a blood-stage infection. We discuss evidence that the clearance curve is not measuring the rate of drug killing. This has major implications for how we assess optimal treatment regimens, as well as how we prioritise new drugs in the drug development pipeline. Highlights: The parasite clearance half-life is used to assess the efficacy of antimalarial drugs. It is usually assumed that a parasite will be rapidly removed by the host after it is killed by a drug. This shapes our interpretation of the parasite clearance half-life. The parasite clearance curve is not always measuring how quickly a drug kills parasites, because parasites that are killed may remain in circulation for some time. Experimental approaches can be used to determine whether circulating parasites are viable or nonviable after treatment. These approaches allow us to assess how quickly parasites are killed. Approaches that distinguish between viable and nonviable parasites would assist in better assessing the efficacy of antimalarials in vivo .