Low Anticoagulant Heparin Disrupts Plasmodium falciparum Rosettes in Fresh Clinical Isolates

Anna M. Leitgeb Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Karin Blomqvist Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Fidelis Cho-Ngwa Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Moses Samje Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Peter Nde Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Vincent Titanji Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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Mats Wahlgren Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden; Dilafor AB, Solna, Sweden; Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon

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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.

Author Notes

*Address correspondence to Mats Wahlgren, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, PO Box 280, SE-171 77 Stockholm, Sweden. E-mail: mats.wahlgren@ki.se
†These authors contributed equally.

Authors' addresses: Anna M. Leitgeb, Dilafor AB, Solna, Sweden, E-mail: anna.leitgeb@dilafor.com. Karin Blomqvist and Mats Wahlgren, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet (MTC), Stockholm, Sweden, E-mails: karin.blomqvist@ki.se and mats.wahlgren@ki.se. Fidelis Cho-Ngwa, Moses Samje, Peter Nde, and Vincent Titanji, University of Buea, Biotechnology Unit, Faculty of Science, Buea, Cameroon, E-mails: chongwa_ub@yahoo.co.uk, msamje@yahoo.com, ndepf@yahoo.com, and vpk.titanji@yahoo.com.

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