World Health Organization, 2008. World Malaria Report. Geneva, Switzerland: World Health Organization.
Udomsangpetch R, WĆ„hlin 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: 1835ā1840.
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: 812ā819.
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: 385ā401.
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: 503ā510.
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: 5849ā5856.
Roberts DJ, Pain A, Kai O, Kortok M, Marsh K, 2000. Autoagglutination of malaria-infected red blood cells and malaria severity. Lancet 355: 1427ā1428.
Rowe A, Obeiro J, Newbold CI, Marsh K, 1995. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun 63: 2323ā2326.
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: 1457ā1460.
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: 3909ā3914.
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: 458ā460.
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: 77ā87.
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: 15ā23.
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: 101ā110.
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: 89ā100.
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: 2405ā2411.
Vogt AM, Winter G, Wahlgren M, Spillmann D, 2004. Heparan sulphate identified on human erythrocytes: a Plasmodium falciparum receptor. Biochem J 381: 593ā597.
Carlson J, Wahlgren M, 1992. Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions. J Exp Med 176: 1311ā1317.
Rowe A, Berendt AR, Marsh K, Newbold CI, 1994. Plasmodium falciparum: a family of sulphated glycoconjugates disrupts erythrocyte rosettes. Exp Parasitol 79: 506ā516.
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: 211ā219.
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: 3594ā3599.
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: 133ā143.
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.
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: 595ā602.
Jaroonvesama N, 1972. Intravascular coagulation in falciparum malaria. Lancet 1: 221ā223.
Munir M, Tjandra H, Rampengan TH, Mustadjab I, Wulur FH, 1980. Heparin in the treatment of cerebral malaria. Paediatr Indones 20: 47ā50.
Rampengan TH, 1991. Cerebral malaria in children. Comparative study between heparin, dexamethasone and placebo. Paediatr Indones 31: 59ā66.
Sheehy TW, Reba RC, 1967. Complications of falciparum malaria and their treatment. Ann Intern Med 66: 807ā809.
Smitskamp H, Wolthuis FH, 1971. New concepts in treatment of malignant tertian malaria with cerebral involvement. BMJ 1: 714ā716.
World Health Organization, 1986. Severe and complicated malaria. World Health Organization Malaria Action Programme. Trans R Soc Trop Med Hyg 80 (Suppl): 3ā50.
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: 3198ā3202.
Petitou M, Lormeau JC, Choay J, 1988. Interaction of heparin and antithrombin III. The role of O-sulfate groups. Eur J Biochem 176: 637ā640.
Fransson LA, 1978. Periodate oxidation of D-glucuronic acid residues in heparan sulfate and heparin. Carbohydr Res 62: 235ā244.
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: 1453ā1458.
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: 7736ā7746.
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: 74ā83.
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: 10689ā10694.
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: 748ā755.
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: 284ā289.
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: 643ā649.
Moll K, Ljungstrƶm I, Perlmann H, Scherf A, Wahlgren M, 2008. Methods in Malaria Research. MR4/ATCC, Manassas, Virginia. Paris, France: BioMalPar.
Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193: 673ā675.
European Pharmacopoeia, 2003. Heparins Low-Molecular-Mass, Monograph 0828. Strasbourg, France: European Directorate for the Quality of Medicines and Health Care.
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: 1321ā1326.
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: 539ā541.
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: 686ā687.
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: 333ā340.
Past two years | Past Year | Past 30 Days | |
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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.
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.
World Health Organization, 2008. World Malaria Report. Geneva, Switzerland: World Health Organization.
Udomsangpetch R, WĆ„hlin 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: 1835ā1840.
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: 812ā819.
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: 385ā401.
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: 503ā510.
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: 5849ā5856.
Roberts DJ, Pain A, Kai O, Kortok M, Marsh K, 2000. Autoagglutination of malaria-infected red blood cells and malaria severity. Lancet 355: 1427ā1428.
Rowe A, Obeiro J, Newbold CI, Marsh K, 1995. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun 63: 2323ā2326.
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: 1457ā1460.
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: 3909ā3914.
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: 458ā460.
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: 77ā87.
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: 15ā23.
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: 101ā110.
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: 89ā100.
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: 2405ā2411.
Vogt AM, Winter G, Wahlgren M, Spillmann D, 2004. Heparan sulphate identified on human erythrocytes: a Plasmodium falciparum receptor. Biochem J 381: 593ā597.
Carlson J, Wahlgren M, 1992. Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin-like interactions. J Exp Med 176: 1311ā1317.
Rowe A, Berendt AR, Marsh K, Newbold CI, 1994. Plasmodium falciparum: a family of sulphated glycoconjugates disrupts erythrocyte rosettes. Exp Parasitol 79: 506ā516.
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: 211ā219.
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: 3594ā3599.
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: 133ā143.
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.
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: 595ā602.
Jaroonvesama N, 1972. Intravascular coagulation in falciparum malaria. Lancet 1: 221ā223.
Munir M, Tjandra H, Rampengan TH, Mustadjab I, Wulur FH, 1980. Heparin in the treatment of cerebral malaria. Paediatr Indones 20: 47ā50.
Rampengan TH, 1991. Cerebral malaria in children. Comparative study between heparin, dexamethasone and placebo. Paediatr Indones 31: 59ā66.
Sheehy TW, Reba RC, 1967. Complications of falciparum malaria and their treatment. Ann Intern Med 66: 807ā809.
Smitskamp H, Wolthuis FH, 1971. New concepts in treatment of malignant tertian malaria with cerebral involvement. BMJ 1: 714ā716.
World Health Organization, 1986. Severe and complicated malaria. World Health Organization Malaria Action Programme. Trans R Soc Trop Med Hyg 80 (Suppl): 3ā50.
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: 3198ā3202.
Petitou M, Lormeau JC, Choay J, 1988. Interaction of heparin and antithrombin III. The role of O-sulfate groups. Eur J Biochem 176: 637ā640.
Fransson LA, 1978. Periodate oxidation of D-glucuronic acid residues in heparan sulfate and heparin. Carbohydr Res 62: 235ā244.
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: 1453ā1458.
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: 7736ā7746.
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: 74ā83.
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: 10689ā10694.
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: 748ā755.
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: 284ā289.
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: 643ā649.
Moll K, Ljungstrƶm I, Perlmann H, Scherf A, Wahlgren M, 2008. Methods in Malaria Research. MR4/ATCC, Manassas, Virginia. Paris, France: BioMalPar.
Trager W, Jensen JB, 1976. Human malaria parasites in continuous culture. Science 193: 673ā675.
European Pharmacopoeia, 2003. Heparins Low-Molecular-Mass, Monograph 0828. Strasbourg, France: European Directorate for the Quality of Medicines and Health Care.
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: 1321ā1326.
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: 539ā541.
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: 686ā687.
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: 333ā340.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 35 | 35 | 14 |
Full Text Views | 413 | 109 | 1 |
PDF Downloads | 124 | 38 | 1 |