Leitgeb Anna M, Blomqvist Karin, Cho-Ngwa Fidelis, Samje Moses, Nde Peter, Titanji Vincent, Wahlgren Mats
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
Am J Trop Med Hyg. 2011 Mar;84(3):390-6. doi: 10.4269/ajtmh.2011.10-0256.
The binding of Plasmodium falciparum parasitized erythrocytes to uninfected erythrocytes (rosetting) is associated with severe malaria. The glycosaminoglycan heparan sulfate is an important receptor for rosetting. The related glycosaminoglycan heparin was previously used in treatment of severe malaria, although abandoned because of the occurrence of severe bleedings. Instead, low anticoagulant heparin (LAH) has been suggested for treatment. LAH has successfully been evaluated in safety studies and found to disrupt rosettes and cytoadherence in vitro and in vivo in animal models, but the effect of LAH on fresh parasite isolates has not been studied. Herein, we report that two different LAHs (DFX232 and Sevuparin) disrupt rosettes in the majority of fresh isolates from Cameroonian children with malaria. The rosette disruption effect was more pronounced in isolates from complicated cases than from mild cases. The data support LAH as adjunct therapy in severe malaria.
恶性疟原虫寄生的红细胞与未感染红细胞的结合(形成花结)与严重疟疾相关。糖胺聚糖硫酸乙酰肝素是花结形成的重要受体。相关的糖胺聚糖肝素曾被用于治疗严重疟疾,尽管因发生严重出血而被弃用。取而代之的是,有人建议使用低抗凝肝素(LAH)进行治疗。LAH已在安全性研究中成功得到评估,并发现其在动物模型的体外和体内均能破坏花结和细胞黏附,但LAH对新鲜寄生虫分离株的作用尚未得到研究。在此,我们报告两种不同的LAH(DFX232和舍普帕肝素)能破坏来自喀麦隆疟疾患儿的大多数新鲜分离株中的花结。花结破坏效应在复杂病例的分离株中比在轻症病例中更为明显。这些数据支持LAH作为严重疟疾的辅助治疗方法。