Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.
Curr Opin Infect Dis. 2019 Oct;32(5):413-418. doi: 10.1097/QCO.0000000000000584.
Malaria threatens the lives of over 200 million individuals with the disease each year. Plasmodium falciparum is the predominant cause of severe malaria which may be lethal and result in neurocognitive sequelae despite appropriate treatment. We review recent advances regarding the pathophysiology of severe malaria and treatment recommendations for severe disease in the United States.
Infected red blood cell (iRBC) sequestration in microvascular beds is a critical factor in the development of severe malaria syndromes. Interactions between iRBC variant adhesive peptides and the endothelial protein C receptor (EPCR) result in perturbations of coagulation and cytopreservation pathways. Alterations in the protein C/EPCR axis are implicated in cerebral malaria, respiratory distress, and anemia. Brain MRIs reveal the posterior reversible encephalopathy syndrome in cerebral malaria patients. Transcriptomic analysis reveals commonalities in disease pathogenesis in children and adults despite differences in clinical presentation. US guidelines for severe malaria treatment currently recommend intravenous artesunate including in pregnant women and children.
Despite advances in our understanding of malarial pathogenesis much remains unknown. Antimalarial agents eradicate parasites but no treatments are available to prevent or ameliorate severe malaria or prevent disease sequelae. Further study is needed to develop effective adjunctive therapies.
目的综述：疟疾每年威胁着超过 2 亿人的生命。恶性疟原虫是导致严重疟疾的主要原因，尽管给予了适当的治疗，严重疟疾仍可能致命，并导致神经认知后遗症。我们综述了有关严重疟疾病理生理学的最新进展，以及美国严重疾病的治疗建议。
最近的发现：感染的红细胞（iRBC）在微血管床中的扣押是严重疟疾综合征发展的一个关键因素。iRBC 变异黏附肽与内皮蛋白 C 受体（EPCR）之间的相互作用导致凝血和细胞保存途径的紊乱。蛋白 C/EPCR 轴的改变与脑型疟疾、呼吸窘迫和贫血有关。脑 MRI 显示脑型疟疾患者存在后部可逆性脑病综合征。转录组分析显示，尽管临床表现不同，但儿童和成人的疾病发病机制存在共同之处。美国严重疟疾治疗指南目前建议静脉注射青蒿琥酯，包括孕妇和儿童。
总结：尽管我们对疟疾发病机制的理解有了进展，但仍有许多未知之处。抗疟药物可消灭寄生虫，但目前尚无预防或改善严重疟疾或预防疾病后遗症的治疗方法。需要进一步研究以开发有效的辅助治疗方法。
