Rebelo Maria, Pawliw Rebecca, Gower Jeremy, Webb Lachlan, Mitchell Hayley, Pava Zuleima, Watts Rebecca E, Davenport Miles P, McCarthy James S, Khoury David S
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Kirby Institute, University of New South Wales (Sydney), Sydney, New South Wales, Australia.
J Infect Dis. 2021 Jun 15;223(12):2154-2163. doi: 10.1093/infdis/jiaa678.
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.
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.
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.
These results demonstrate that in vivo drug activity of artesunate is faster than is indicated by the parasite clearance half-life.
青蒿素衍生物是主要的抗疟药物类别，因其起效迅速且能快速清除循环中的寄生虫。寄生虫清除半衰期衡量治疗后寄生虫从血液中损失的速率，目前用于评估新型药物的抗疟活性及监测耐药性。然而，近期多项研究对使用寄生虫清除来衡量药物活性提出质疑，认为许多循环中的寄生虫可能已无活力。
在一项疟疾志愿者感染研究中，对10名感染恶性疟原虫的受试者给予单剂量青蒿琥酯（2毫克/千克）。通过定量聚合酶链反应（qPCR）评估循环中的寄生虫浓度。通过对从受试者采集的寄生虫体外生长进行数学建模，估算青蒿琥酯给药后寄生虫的活力。
我们发现，在对青蒿素敏感的感染中，给药后8小时内，有活力的寄生虫降至基线的<0.1%，而通过定量聚合酶链反应测得的循环寄生虫总数保持不变。在相同时间段内的青蒿素耐药感染中，有活力的寄生虫降至基线的51.4%（平均标准误差，4.6%）。
这些结果表明，青蒿琥酯的体内药物活性比寄生虫清除半衰期所显示的要快。
