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. 2011 Mar;84(3):390-6.
doi: 10.4269/ajtmh.2011.10-0256.

Low anticoagulant heparin disrupts Plasmodium falciparum rosettes in fresh clinical isolates

Anna M Leitgeb  1 , Karin Blomqvist, Fidelis Cho-Ngwa, Moses Samje, Peter Nde, Vincent Titanji, Mats Wahlgren
Affiliations

Low anticoagulant heparin disrupts Plasmodium falciparum rosettes in fresh clinical isolates

Anna M Leitgeb et al. Am J Trop Med Hyg. 2011 Mar.

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.

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Figures

Figure 1.
Figure 1.
Rosetting rates before and after the addition of LAHs in the 47 isolates. The mean rosetting rate ± SEM is shown. Rosetting rate before addition of LAH (black bars), DFX232 (dark grey bars), or Sevuparin (light gray bars). *Not done. (A) DFX232 and Sevuparin at concentrations of 100 μg/mL. (B) DFX232 and Sevuparin at concentrations of 1,000 μg/mL.
Figure 2.
Figure 2.
Relative rosetting rate after the addition of LAH compared with control. The mean relative rosetting rate (the proportion of remaining rosettes after treatment compared with the control-treated erythrocytes) ± SEM is shown. Significant rosette disruption ≥ 15% is indicated by the horizontal line. Dark grey bars = DFX232; light grey bars = Sevuparin. *Not done. (A) DFX232 and Sevuparin at concentrations of 100 μg/mL. Significant disruption was shown in 42 of 47 samples with DFX232 and 39 of 47 samples with Sevuparin. (B) DFX232 and Sevuparin at concentrations of 1,000 μg/mL. Significant disruption was shown in 34 of 47 samples with DFX232 and 36 of 47 samples with Sevuparin.
Figure 3.
Figure 3.
(A) Overall rosette disruption effect of the two different LAHs. The mean relative rosetting rate (the proportion of remaining rosettes after treatment compared with the control-treated erythrocytes) ± SEM is shown. There was a significant disruption effect for DFX232 and Sevuparin at both concentrations compared with the mock-treated samples. There was no statistically significant difference between the two LAH preparations. ***P < 0.001. (B and C) Rosette disruption effect in isolates from mild and complicate malaria cases. The mean relative rosetting rate (the proportion of remaining rosettes after treatment compared with the control-treated erythrocytes) ± SEM is shown. Dark grey bars = mild malaria; light grey bars = complicated malaria. The mean relative rosetting rate is shown. (B) DFX232 and Sevuparin at concentrations of 100 μg/mL. (C) DFX232 and Sevuparin at concentrations of 1,000 μg/mL.
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References

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