Clinical characteristics of platelet-mediated killing circulating parasite of major human malaria

Microscopy was used to characterize platelet-Plasmodium-infected erythrocyte interactions in patients infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale or Plasmodium malariae, and to investigate the relationship between platelet-associated parasite killing and parasite clearance. Data from 244 malaria patients admitted to the Fourth People’s Hospital of Nanning between 1 January 2011 and 30 September 2022, and 45 healthy controls, were collected prospectively and assessed retrospectively. Characteristics of platelet–erythrocyte interactions were visualized by microscopy, and blood cell count and clinical profiles of these participants were obtained from the electronic medical records. ANOVA, contingency tables and Cox proportional hazards regression models were used to do statistical analysis on the subgroups. Platelet enlargement and minor pseudopodia development were observed. Platelets were found directly attaching to parasitized erythrocytes by all Plasmodium species studied, especially mature stages, and lysis of parasitized erythrocytes was connected to platelet-mediated cytolysis. Platelet counts were correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone in clearing Plasmodium in patients with thrombocytopenia. Platelet-parasitized erythrocytes cell-to-cell contacts initiated platelet-associated parasite killing and helped to limit Plasmodium infection in cases of human malaria. The weakening platelet-associated parasite killing effects could be counteracted by artemisinin combination therapy in patients with thrombocytopenia. Platelets directly attaching to parasitized erythrocytes. Platelets correlated inversely with parasitaemia and duration of parasite clearance. Artemisinin combination therapy was more effective than artemisinin alone. Weakening killing effects may counteract by artemisinin combination therapy.

本研究采用显微镜技术对感染恶性疟原虫(Plasmodium falciparum)、间日疟原虫(Plasmodium vivax)、卵形疟原虫(Plasmodium ovale)或三日疟原虫(Plasmodium malariae)的患者体内血小板与疟原虫感染红细胞的相互作用进行表征，并探讨血小板介导的寄生虫杀伤作用与寄生虫清除之间的关联。本研究前瞻性收集2011年1月1日至2022年9月30日期间入住南宁市第四人民医院的244例疟疾患者及45名健康对照者的相关数据，并进行回顾性评估。通过显微镜可视化血小板-红细胞相互作用的特征，受试者的血细胞计数与临床资料均从电子病历中提取。采用方差分析(ANOVA)、列联表及Cox比例风险回归模型对各亚组开展统计学分析。本研究观测到血小板体积增大及伪足轻度形成；本次研究涉及的所有疟原虫虫种均可介导血小板直接黏附于受感染红细胞，尤以疟原虫成熟阶段更为显著，且受感染红细胞的裂解与血小板介导的细胞裂解密切相关。血小板计数与寄生虫血症水平及寄生虫清除时长呈负相关。对于血小板减少症患者，青蒿素联合疗法在清除疟原虫方面的效果优于单用青蒿素疗法。在人类疟疾病例中，血小板与受疟原虫感染的红细胞之间的细胞间接触可触发血小板介导的寄生虫杀伤作用，从而有助于限制疟原虫感染；对于血小板减少症患者，青蒿素联合疗法可抵消血小板介导的寄生虫杀伤作用的减弱效应。血小板直接黏附于受感染红细胞，血小板计数与寄生虫血症水平及寄生虫清除时长呈负相关，青蒿素联合疗法的抗疟效果优于单用青蒿素疗法，寄生虫杀伤作用的减弱可被青蒿素联合疗法抵消。