title: Low anticoagulant heparin disrupts Plasmodium falciparum rosettes in fresh clinical isolates.
abstract: 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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden. anna.leitgeb@dilafor.com
authors.forename: Anna M
authors.initials: AM
authors.lastname: Leitgeb
authors.forename: Karin
authors.initials: K
authors.lastname: Blomqvist
authors.forename: Fidelis
authors.initials: F
authors.lastname: Cho-Ngwa
authors.forename: Moses
authors.initials: M
authors.lastname: Samje
authors.forename: Peter
authors.initials: P
authors.lastname: Nde
authors.forename: Vincent
authors.initials: V
authors.lastname: Titanji
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
mesh_terms: D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D002163:Cameroon / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000469:parasitology*; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000276:immunology; D012397:Rosette Formation
chemical_list: D000962:Antimalarials; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin