QIMR Berghofer Medical Research Institute.
The University of Queensland.
J Infect Dis. 2020 Mar 2;221(6):948-955. doi: 10.1093/infdis/jiz102.
Plasmodium malariae is considered a minor malaria parasite, although its global disease burden is underappreciated. The aim of this study was to develop an induced blood-stage malaria (IBSM) model of P. malariae to study parasite biology, diagnostic assays, and treatment.
This clinical trial involved 2 healthy subjects who were intravenously inoculated with cryopreserved P. malariae-infected erythrocytes. Subjects were treated with artemether-lumefantrine after development of clinical symptoms. Prior to antimalarial therapy, mosquito-feeding assays were performed to investigate transmission, and blood samples were collected for rapid diagnostic testing and parasite transcription profiling. Serial blood samples were collected for biomarker analysis.
Both subjects experienced symptoms and signs typical of early malaria. Parasitemia was detected 7 days after inoculation, and parasite concentrations increased until antimalarial treatment was initiated 25 and 21 days after inoculation for subjects 1 and 2 respectively (peak parasitemia levels, 174 182 and 50 291 parasites/mL, respectively). The parasite clearance half-life following artemether-lumefantrine treatment was 6.7 hours. Mosquito transmission was observed for 1 subject, while in vivo parasite transcription and biomarkers were successfully profiled.
An IBSM model of P. malariae has been successfully developed and may be used to study the biology of, diagnostic testing for, and treatment of this neglected malaria species.
ACTRN12617000048381.
疟原虫疟疾病原被认为是一种次要的疟原虫，尽管其全球疾病负担被低估。本研究旨在建立一种诱导的血期疟原虫（IBSM）模型来研究寄生虫生物学、诊断检测和治疗。
本临床试验涉及 2 名健康受试者，他们通过静脉内接种冷冻保存的疟原虫感染红细胞。在出现临床症状后，受试者接受青蒿琥酯-咯萘啶治疗。在抗疟治疗之前，进行了蚊子喂养试验以研究传播情况，并采集血液样本进行快速诊断检测和寄生虫转录谱分析。收集连续的血液样本进行生物标志物分析。
两名受试者均出现早期疟疾的症状和体征。接种后 7 天检测到寄生虫血症，寄生虫浓度增加，直到接种后 25 天和 21 天对受试者 1 和 2 分别开始抗疟治疗（峰值寄生虫血症水平分别为 174182 和 50291 个/毫升）。青蒿琥酯-咯萘啶治疗后寄生虫清除半衰期为 6.7 小时。1 名受试者观察到蚊子传播，而体内寄生虫转录和生物标志物也成功进行了分析。
成功建立了疟原虫 IBSM 模型，可用于研究这种被忽视的疟原虫物种的生物学、诊断检测和治疗。
ACTRN12617000048381。
