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: Anna M Leitgeb, Karin Blomqvist, Fidelis Cho-Ngwa, Moses Samje, Peter Nde, Vincent Titanji, Mats Wahlgren
• Journal: The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 84 Issue 3 Pg. 390-6 (Mar 2011) ISSN: 1476-1645 [Electronic] United States
• PMID: 21363975 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Heparin, Low-Molecular-Weight
• Heparin

Topics

• Adolescent
• Animals
• Antimalarials (chemistry, pharmacology)
• Cameroon (epidemiology)
• Child
• Child, Preschool
• Erythrocytes (parasitology)
• Heparin (analogs & derivatives, pharmacology)
• Heparin, Low-Molecular-Weight (pharmacology)
• Humans
• Infant
• Malaria, Falciparum (blood, epidemiology, parasitology)
• Plasmodium falciparum (drug effects, immunology)
• Rosette Formation