Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria. (17th January 2019)

• Record Type: Journal Article
• Authors: Intharabut, Benjamas; Kingston, Hugh W; Srinamon, Ketsanee; Ashley, Elizabeth A; Imwong, Mallika; Dhorda, Mehul; Woodrow, Charles; Stepniewska, Kasia; Silamut, Kamolrat; Day, Nicholas P J; Dondorp, Arjen M; White, Nicholas J
• Is Part Of: Journal of infectious diseases. Volume 219:Number 9(2019)
• Page Start: 1483
• Page End: 1489
• Publication Date: 2019-01-17
• Subjects: Falciparum malaria -- microscopy -- artemisinin resistance -- parasite clearance -- parasite stage; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy673
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Artemisinin resistance in falciparum malaria is associated with kelch13 propeller mutations, reduced ring stage parasite killing, and, consequently, slow parasite clearance. We assessed how parasite age affects parasite clearance in artemisinin resistance. Methods: Developmental stages of Plasmodium falciparum parasites on blood films performed at hospital admission and their kelch13 genotypes were assessed for 816 patients enrolled in a multinational clinical trial of artemisinin combination therapy. Results: Early changes in parasitemia level (ie, 0–6 hours after admission) were determined mainly by modal stage of asexual parasite development, whereas the subsequent log-linear decline was determined mainly by kelch13 propeller mutations. Older circulating parasites on admission were associated with more-rapid parasite clearance, particularly in kelch13 mutant infections. The geometric mean parasite clearance half-life decreased by 11.6% (95% CI 3.4%–19.1%) in kelch13 wild-type infections and by 30% (95% CI 17.8%–40.4%) in kelch13 mutant infections as the mean age of circulating parasites rose from 3 to 21 hours. Conclusion: Following the start of antimalarial treatment, ongoing parasite sequestration and schizogony both affect initial changes in parasitemia. The greater dependency of parasite clearance half-life on parasite age in artemisinin resistant infections is consistent with ring stage resistance and consequent parasite clearance by sequestration. The stage of parasite development should be incorporated in individual assessments of artemisinin resistance. Abstract : The effect of parasite stage of development on the parasite clearance curve was investigated in areas affected by artemisinin resistance. Parasite stage shapes the early part of the clearance curve and also influences the subsequent log-linear decline.