1921
Volume 84, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The binding of 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 and 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 ) 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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References

  1. World Health Organization, 2008. World Malaria Report. Geneva, Switzerland: World Health Organization. [Google Scholar]
  2. Udomsangpetch R, Wåhlin B, Carlson J, Berzins K, Torii M, Aikawa M, Perlmann P, Wahlgren M, , 1989. Plasmodium falciparum-infected erythrocytes form spontaneous erythrocyte rosettes. J Exp Med 169: 18351840.[Crossref] [Google Scholar]
  3. Kaul DK, Roth EF, Jr Nagel RL, Howard RJ, Handunnetti SM, , 1991. Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions. Blood 78: 812819. [Google Scholar]
  4. MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA, , 1985. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119: 385401. [Google Scholar]
  5. Treutiger CJ, Hedlund I, Helmby H, Carlson J, Jepson A, Twumasi P, Kwiatkowski D, Greenwood BM, Wahlgren M, , 1992. Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria. Am J Trop Med Hyg 46: 503510. [Google Scholar]
  6. Heddini A, Pettersson F, Kai O, Shafi J, Obiero J, Chen Q, Barragan A, Wahlgren M, Marsh K, , 2001. Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infect Immun 69: 58495856.[Crossref] [Google Scholar]
  7. Roberts DJ, Pain A, Kai O, Kortok M, Marsh K, , 2000. Autoagglutination of malaria-infected red blood cells and malaria severity. Lancet 355: 14271428.[Crossref] [Google Scholar]
  8. Rowe A, Obeiro J, Newbold CI, Marsh K, , 1995. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun 63: 23232326. [Google Scholar]
  9. Carlson J, Helmby H, Hill AV, Brewster D, Greenwood BM, Wahlgren M, , 1990. Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet 336: 14571460.[Crossref] [Google Scholar]
  10. Carlson J, Nash GB, Gabutti V, al-Yaman F, Wahlgren M, , 1994. Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation. Blood 84: 39093914. [Google Scholar]
  11. Rowe JA, Obiero J, Marsh K, Raza A, , 2002. Short report: positive correlation between rosetting and parasitemia in Plasmodium falciparum clinical isolates. Am J Trop Med Hyg 66: 458460. [Google Scholar]
  12. Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ, , 1995. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82: 7787.[Crossref] [Google Scholar]
  13. Chen Q, Barragan A, Fernandez V, Sundstrom A, Schlichtherle M, Sahlen A, Carlson J, Datta S, Wahlgren M, , 1998. Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum . J Exp Med 187: 1523.[Crossref] [Google Scholar]
  14. Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH, , 1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82: 101110.[Crossref] [Google Scholar]
  15. Su XZ, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE, , 1995. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82: 89100.[Crossref] [Google Scholar]
  16. Vogt AM, Barragan A, Chen Q, Kironde F, Spillmann D, Wahlgren M, , 2003. Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1. Blood 101: 24052411.[Crossref] [Google Scholar]
  17. Vogt AM, Winter G, Wahlgren M, Spillmann D, , 2004. Heparan sulphate identified on human erythrocytes: a Plasmodium falciparum receptor. Biochem J 381: 593597.[Crossref] [Google Scholar]
  18. Carlson J, Wahlgren M, , 1992. Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions. J Exp Med 176: 13111317.[Crossref] [Google Scholar]
  19. Rowe A, Berendt AR, Marsh K, Newbold CI, , 1994. Plasmodium falciparum: a family of sulphated glycoconjugates disrupts erythrocyte rosettes. Exp Parasitol 79: 506516.[Crossref] [Google Scholar]
  20. Moll K, Pettersson F, Vogt AM, Jonsson C, Rasti N, Ahuja S, Spangberg M, Mercereau-Puijalon O, Arnot DE, Wahlgren M, Chen Q, , 2007. Generation of cross-protective antibodies against Plasmodium falciparum sequestration by immunization with an erythrocyte membrane protein 1-duffy binding-like 1 alpha domain. Infect Immun 75: 211219.[Crossref] [Google Scholar]
  21. Barragan A, Fernandez V, Chen Q, von Euler A, Wahlgren M, Spillmann D, , 2000. The duffy-binding-like domain 1 of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a heparan sulfate ligand that requires 12 mers for binding. Blood 95: 35943599. [Google Scholar]
  22. Barragan A, Spillmann D, Kremsner PG, Wahlgren M, Carlson J, , 1999. Plasmodium falciparum: molecular background to strain-specific rosette disruption by glycosaminoglycans and sulfated glycoconjugates. Exp Parasitol 91: 133143.[Crossref] [Google Scholar]
  23. Vogt AM, Pettersson F, Moll K, Jonsson C, Normark J, Ribacke U, Egwang TG, Ekre HP, Spillmann D, Chen Q, Wahlgren M, , 2006. Release of sequestered malaria parasites upon injection of a glycosaminoglycan. PLoS Pathog 2: e100.[Crossref] [Google Scholar]
  24. Carlson J, Ekre HP, Helmby H, Gysin J, Greenwood BM, Wahlgren M, , 1992. Disruption of Plasmodium falciparum erythrocyte rosettes by standard heparin and heparin devoid of anticoagulant activity. Am J Trop Med Hyg 46: 595602. [Google Scholar]
  25. Jaroonvesama N, , 1972. Intravascular coagulation in falciparum malaria. Lancet 1: 221223.[Crossref] [Google Scholar]
  26. Munir M, Tjandra H, Rampengan TH, Mustadjab I, Wulur FH, , 1980. Heparin in the treatment of cerebral malaria. Paediatr Indones 20: 4750. [Google Scholar]
  27. Rampengan TH, , 1991. Cerebral malaria in children. Comparative study between heparin, dexamethasone and placebo. Paediatr Indones 31: 5966. [Google Scholar]
  28. Sheehy TW, Reba RC, , 1967. Complications of falciparum malaria and their treatment. Ann Intern Med 66: 807809.[Crossref] [Google Scholar]
  29. Smitskamp H, Wolthuis FH, , 1971. New concepts in treatment of malignant tertian malaria with cerebral involvement. BMJ 1: 714716.[Crossref] [Google Scholar]
  30. World Health Organization, 1986. Severe and complicated malaria. World Health Organization Malaria Action Programme. Trans R Soc Trop Med Hyg 80 (Suppl): 350. [Google Scholar]
  31. Lindahl U, Backstrom G, Hook M, Thunberg L, Fransson LA, Linker A, , 1979. Structure of the antithrombin-binding site in heparin. Proc Natl Acad Sci USA 76: 31983202.[Crossref] [Google Scholar]
  32. Petitou M, Lormeau JC, Choay J, , 1988. Interaction of heparin and antithrombin III. The role of O-sulfate groups. Eur J Biochem 176: 637640.[Crossref] [Google Scholar]
  33. Fransson LA, , 1978. Periodate oxidation of D-glucuronic acid residues in heparan sulfate and heparin. Carbohydr Res 62: 235244.[Crossref] [Google Scholar]
  34. Skidmore MA, Dumax-Vorzet AF, Guimond SE, Rudd TR, Edwards EA, Turnbull JE, Craig AG, Yates EA, , 2008. Disruption of rosetting in Plasmodium falciparum malaria with chemically modified heparin and low molecular weight derivatives possessing reduced anticoagulant and other serine protease inhibition activities. J Med Chem 51: 14531458.[Crossref] [Google Scholar]
  35. Pettersson F, Vogt AM, Jonsson C, Mok BW, Shamaei-Tousi A, Bergstrom S, Chen Q, Wahlgren M, , 2005. Whole-body imaging of sequestration of Plasmodium falciparum in the rat. Infect Immun 73: 77367746.[Crossref] [Google Scholar]
  36. Blomqvist K, Normark J, Nilsson D, Ribacke U, Orikiriza J, Trillkott P, Byarugaba J, Egwang TG, Kironde F, Andersson B, Wahlgren M, , 2010. var gene transcription dynamics in Plasmodium falciparum patient isolates. Mol Biochem Parasitol 170: 7483.[Crossref] [Google Scholar]
  37. Peters J, Fowler E, Gatton M, Chen N, Saul A, Cheng Q, , 2002. High diversity and rapid changeover of expressed var genes during the acute phase of Plasmodium falciparum infections in human volunteers. Proc Natl Acad Sci USA 99: 1068910694.[Crossref] [Google Scholar]
  38. Peters JM, Fowler EV, Krause DR, Cheng Q, Gatton ML, , 2007. Differential changes in Plasmodium falciparum var transcription during adaptation to culture. J Infect Dis 195: 748755.[Crossref] [Google Scholar]
  39. Kimbi HK, Tetteh KK, Polley SD, Conway DJ, , 2004. Cross-sectional study of specific antibodies to a polymorphic Plasmodium falciparum antigen and of parasite antigen genotypes in school children on the slope of Mount Cameroon. Trans R Soc Trop Med Hyg 98: 284289.[Crossref] [Google Scholar]
  40. Wanji S, Tanke T, Atanga SN, Ajonina C, Nicholas T, Fontenille D, , 2003. Anopheles species of the mount Cameroon region: biting habits, feeding behaviour and entomological inoculation rates. Trop Med Int Health 8: 643649.[Crossref] [Google Scholar]
  41. Moll K, Ljungström I, Perlmann H, Scherf A, Wahlgren M, , 2008. Methods in Malaria Research. MR4/ATCC, Manassas, Virginia. Paris, France: BioMalPar. [Google Scholar]
  42. Trager W, Jensen JB, , 1976. Human malaria parasites in continuous culture. Science 193: 673675.[Crossref] [Google Scholar]
  43. European Pharmacopoeia, 2003. Heparins Low-Molecular-Mass, Monograph 0828. Strasbourg, France: European Directorate for the Quality of Medicines and Health Care. [Google Scholar]
  44. Kyriacou HM, Steen KE, Raza A, Arman M, Warimwe G, Bull PC, Havlik I, Rowe JA, , 2007. In vitro inhibition of Plasmodium falciparum rosette formation by Curdlan sulfate. Antimicrob Agents Chemother 51: 13211326.[Crossref] [Google Scholar]
  45. Billa RF, Biwole MS, Juimo AG, Bejanga BI, Blackett K, , 1991. Gall stone disease in African patients with sickle cell anaemia: a preliminary report from Yaounde, Cameroon. Gut 32: 539541.[Crossref] [Google Scholar]
  46. Havlik I, Rovelli S, Kaneko Y, , 1994. The effect of curdlan sulphate on in vitro growth of Plasmodium falciparum . Trans R Soc Trop Med Hyg 88: 686687.[Crossref] [Google Scholar]
  47. Havlik I, Looareesuwan S, Vannaphan S, Wilairatana P, Krudsood S, Thuma PE, Kozbor D, Watanabe N, Kaneko Y, , 2005. Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 99: 333340.[Crossref] [Google Scholar]
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  • Received : 04 May 2010
  • Accepted : 10 Dec 2010

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