BACKGROUND For malaria elimination efforts it is important to better understand parasite transmission to mosquitoes and develop models for early-clinical evaluation of transmission-blocking interventions. METHODS In a randomized open-label trial, 24 participants were infected by bites from Plasmodium falciparum 3D7-infected mosquitoes (MB, n=12) or by induced blood stage malaria with the same parasite line (IBSM, n=12). Following subcurative piperaquine treatment, asexual parasite and gametocytes kinetics were assessed and mosquito feeding experiments were performed. RESULTS Study procedures were well tolerated. Median peak gametocyte density was 1304 gametocytes/mL (interquartile range (IQR) 308-1607) following IBSM compared to 14 gametocytes/mL (IQR 10-64) following MB (P < 0.001), despite similar peak asexual parasite densities (P = 0.478). Peak gametocyte density correlated with preceding pfap2-g transcripts, indicative of gametocyte commitment (ρ = 0.62; P = 0.002). Direct feeding assays resulted in mosquito infections from 9/12 participants following IBSM versus 0/12 following MB (P < 0.001). CONCLUSIONS We observed a striking effect of inoculation method on gametocyte production, suggesting higher gametocyte commitment following IBSM. Our direct comparison of MB and IBSM establishes the CHMI-transmission model using intravenous administration of Pf-infected erythrocytes as a model for early-clinical evaluation of interventions that aim to interrupt malaria transmission.

中文翻译：

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一项随机临床试验，比较恶性疟原虫配子细胞血症和血液阶段或蚊虫叮咬诱导的受控疟疾感染后的感染性。

背景 对于消除疟疾的努力，重要的是更好地了解寄生虫对蚊子的传播，并开发模型以对传播阻断干预措施进行早期临床评估。方法 在一项随机开放标签试验中，24 名参与者被恶性疟原虫 3D7 感染的蚊子叮咬（MB，n=12）或由同一寄生虫系诱导的血液期疟疾（IBSM，n=12）感染。在亚治愈性哌喹治疗后，评估了无性寄生虫和配子体动力学，并进行了蚊子喂养实验。结果 研究程序的耐受性良好。尽管无性寄生虫的峰值密度相似（P = 0.478）。峰值配子体密度与先前的 pfap2-g 转录本相关，表明配子体承诺（ρ = 0.62；P = 0.002）。直接喂养试验导致 IBSM 后 9/12 的参与者感染蚊子，而 MB 后为 0/12（P < 0.001）。结论 我们观察到接种方法对配子体产生的显着影响，表明 IBSM 后配子体承诺更高。我们对 MB 和 IBSM 的直接比较建立了 CHMI 传播模型，使用静脉注射 Pf 感染的红细胞作为早期临床评估旨在阻断疟疾传播的干预措施的模型。直接喂养试验导致 IBSM 后 9/12 的参与者感染蚊子，而 MB 后为 0/12（P < 0.001）。结论 我们观察到接种方法对配子体产生的显着影响，表明 IBSM 后配子体承诺更高。我们对 MB 和 IBSM 的直接比较建立了 CHMI 传播模型，使用静脉注射 Pf 感染的红细胞作为早期临床评估旨在阻断疟疾传播的干预措施的模型。直接喂养试验导致 IBSM 后 9/12 的参与者感染蚊子，而 MB 后为 0/12（P < 0.001）。结论 我们观察到接种方法对配子体产生的显着影响，表明 IBSM 后配子体承诺更高。我们对 MB 和 IBSM 的直接比较建立了 CHMI 传播模型，使用静脉注射 Pf 感染的红细胞作为早期临床评估旨在阻断疟疾传播的干预措施的模型。