We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Parasite Viability as a Superior Measure of Antimalarial Drug Activity in Humans.
- Authors
Rebelo, Maria; Pawliw, Rebecca; Gower, Jeremy; Webb, Lachlan; Mitchell, Hayley; Pava, Zuleima; Watts, Rebecca E; Davenport, Miles P; McCarthy, James S; Khoury, David S
- Abstract
<bold>Background: </bold>Artemisinin derivatives are the leading class of antimalarial drugs due to their rapid onset of action and rapid clearance of circulating parasites. The parasite clearance half-life measures the rate of loss of parasites from blood after treatment, and this is currently used to assess antimalarial activity of novel agents and to monitor resistance. However, a number of recent studies have challenged the use of parasite clearance to measure drug activity, arguing that many circulating parasites may be nonviable.<bold>Methods: </bold>Plasmodium falciparum-infected subjects (n = 10) in a malaria volunteer infection study were administered a single dose of artesunate (2 mg/kg). Circulating parasite concentration was assessed by means of quantitative polymerase chain reaction (qPCR). Parasite viability after artesunate administration was estimated by mathematical modeling of the ex vivo growth of parasites collected from subjects.<bold>Results: </bold>We showed that in artemisinin-sensitive infection, viable parasites declined to <0.1% of baseline within 8 hours after artesunate administration, while the total number of circulating parasites measured with quantitative polymerase chain reaction remained unchanged. In artemisinin-resistant infections over the same interval, viable parasites declined to 51.4% (standard error of the mean, 4.6%) of baseline.<bold>Conclusions: </bold>These results demonstrate that in vivo drug activity of artesunate is faster than is indicated by the parasite clearance half-life.
- Subjects
ARTEMISININ derivatives; BLOOD parasites; POLYMERASE chain reaction; PARASITES; TRYPANOSOMA cruzi; PLASMODIUM falciparum; DRUG therapy for malaria; PROTOZOA; RESEARCH; MATHEMATICAL models; RESEARCH methodology; DRUG resistance; EVALUATION research; COMPARATIVE studies; THEORY; ANTIMALARIALS
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 12, p2154
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa678