Publication: Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria
Issued Date
2019-01-01
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15376613
00221899
00221899
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2-s2.0-85064991127
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Infectious Diseases. Vol.219, No.9 (2019), 1483-1489
Suggested Citation
Benjamas Intharabut, Hugh W. Kingston, Ketsanee Srinamon, Elizabeth A. Ashley, Mallika Imwong, Mehul Dhorda, Charles Woodrow, Kasia Stepniewska, Kamolrat Silamut, Nicholas P.J. Day, Arjen M. Dondorp, Nicholas J. White Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria. Journal of Infectious Diseases. Vol.219, No.9 (2019), 1483-1489. doi:10.1093/infdis/jiy673 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/52349
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Title
Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria
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Abstract
© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. 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.