Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria

BACKGROUND Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

【背景】脑型疟疾是恶性疟原虫（Plasmodium falciparum）感染引发的致死性并发症，亟需更优化的治疗策略。既往针对小鼠实验性脑型疟疾（murine experimental cerebral malaria, ECM）的研究显示，相较于单独使用蒿甲醚（artemether），蒿甲醚联合腹腔输注全血可改善血管完整性并提升小鼠存活率。但此前尚未有研究评估经静脉途径输注全血或血浆对ECM的干预效果。
【目的】评估经静脉输注全血与静脉输注血浆分别对接受蒿甲醚治疗的ECM小鼠的血液学参数、血管完整性及存活率的影响。
【方法】晚期ECM小鼠接受单独蒿甲醚治疗，或蒿甲醚联合经颈静脉输注的全血、血浆。本研究的结局指标包括：红细胞比容与血小板计数；血浆血管生成素1（angiopoietin 1）、血管生成素2（angiopoietin 2）及触珠蛋白（haptoglobin）水平；血脑屏障（blood-brain barrier）通透性；以及小鼠存活率。
【结果】仅接受蒿甲醚治疗的小鼠存活率为54%，蒿甲醚联合静脉输注全血组的存活率提升至90%；静脉输注血浆组的存活率则降至18%。静脉输注可快速且显著改善红细胞比容、血小板计数、血管生成素水平及血脑屏障完整性。
【主要结论】对于接受蒿甲醚治疗的ECM小鼠，静脉输注全血可改善其预后，而静脉输注血浆则会恶化预后。与既往经腹腔途径输注的研究相比，经静脉途径给药的治疗效果更为显著。