Skip to main content
Top
Published in: BMC Medicine 1/2008

Open Access 01-12-2008 | Commentary

The pathophysiology of malarial anaemia: where have all the red cells gone?

Authors: Oscar K Kai, David J Roberts

Published in: BMC Medicine | Issue 1/2008

Login to get access

Abstract

Malarial anaemia is an enormous public health problem in endemic areas and occurs predominantly in children in the first 3 years of life. Anaemia is due to both a great increase in clearance of uninfected cells and a failure of an adequate bone marrow response. Odhiambo, Stoute and colleagues show how the age distribution of malarial anaemia and the haemolysis of red blood cells may be linked by an age-dependent increase in the capacity of red blood cells to inactivate complement components absorbed or deposited directly on to the surface of the red blood cell. In this commentary, we discuss what has been established about the role of complement deposition on the surface of red blood cells in the pathology of malarial anaemia, how genetic polymorphisms of the complement control proteins influence the outcome of malaria infection and how the findings of Odhiambo, Stoute and colleagues and others shed light on the puzzling age distribution of different syndromes of severe malaria.
Literature
1.
go back to reference Odhiambo CO, Otieno W, Adhiambo C, Odera MM, Stoute JA: Increased deposition of C3b on red cells with low CR1and CD55 in a malaria endemic region of western Kenya: Implications for the development of severe anemia. BMC Medicine. 2008, 6: 23-10.1186/1741-7015-6-23.CrossRefPubMedPubMedCentral Odhiambo CO, Otieno W, Adhiambo C, Odera MM, Stoute JA: Increased deposition of C3b on red cells with low CR1and CD55 in a malaria endemic region of western Kenya: Implications for the development of severe anemia. BMC Medicine. 2008, 6: 23-10.1186/1741-7015-6-23.CrossRefPubMedPubMedCentral
2.
go back to reference Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI: The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005, 434: 214-217. 10.1038/nature03342.CrossRefPubMedPubMedCentral Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI: The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005, 434: 214-217. 10.1038/nature03342.CrossRefPubMedPubMedCentral
3.
go back to reference Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, Newbold C, Gupta S, Marsh K: Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa [see comments]. Lancet. 1997, 349: 1650-1654. 10.1016/S0140-6736(97)02038-2.CrossRefPubMed Snow RW, Omumbo JA, Lowe B, Molyneux CS, Obiero JO, Palmer A, Weber MW, Pinder M, Nahlen B, Obonyo C, Newbold C, Gupta S, Marsh K: Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa [see comments]. Lancet. 1997, 349: 1650-1654. 10.1016/S0140-6736(97)02038-2.CrossRefPubMed
4.
go back to reference Lamikanra AA, Brown D, Potocnik A, Casals-Pascual C, Langhorne J, Roberts DJ: Malarial anemia: of mice and men. Blood. 2007, 110: 18-28. 10.1182/blood-2006-09-018069.CrossRefPubMed Lamikanra AA, Brown D, Potocnik A, Casals-Pascual C, Langhorne J, Roberts DJ: Malarial anemia: of mice and men. Blood. 2007, 110: 18-28. 10.1182/blood-2006-09-018069.CrossRefPubMed
5.
go back to reference Jakeman GN, Saul A, Hogarth WL, Collins WE: Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes. Parasitology. 1999, 119: 127-133. 10.1017/S0031182099004564.CrossRefPubMed Jakeman GN, Saul A, Hogarth WL, Collins WE: Anaemia of acute malaria infections in non-immune patients primarily results from destruction of uninfected erythrocytes. Parasitology. 1999, 119: 127-133. 10.1017/S0031182099004564.CrossRefPubMed
6.
go back to reference Brown AE, Webster HK, Teja-Isavadharm P, Keeratithakul D: Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma. Clin Exp immunol. 1990, 82: 97-101.CrossRefPubMedPubMedCentral Brown AE, Webster HK, Teja-Isavadharm P, Keeratithakul D: Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma. Clin Exp immunol. 1990, 82: 97-101.CrossRefPubMedPubMedCentral
7.
go back to reference Mohan K, Dubey ML, Ganguly NK, Mahajan RC: Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane damage and red cell loss during malaria. Exp Parasitol. 1995, 80: 54-63. 10.1006/expr.1995.1007.CrossRefPubMed Mohan K, Dubey ML, Ganguly NK, Mahajan RC: Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane damage and red cell loss during malaria. Exp Parasitol. 1995, 80: 54-63. 10.1006/expr.1995.1007.CrossRefPubMed
8.
go back to reference Ladhani S, Lowe B, Cole AO, Kowuondo K, Newton CR: Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. Br J Haematol. 2002, 119: 839-847. 10.1046/j.1365-2141.2002.03904.x.CrossRefPubMed Ladhani S, Lowe B, Cole AO, Kowuondo K, Newton CR: Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. Br J Haematol. 2002, 119: 839-847. 10.1046/j.1365-2141.2002.03904.x.CrossRefPubMed
9.
go back to reference Jenkins NE, Chakravorty SJ, Urban BC, Kai OK, Marsh K, Craig AG: The effect of Plasmodium falciparum infection on expression of monocyte surface molecules. Trans R Soc Trop Med Hyg. 2006, 100: 1007-1012. 10.1016/j.trstmh.2006.01.005.CrossRefPubMed Jenkins NE, Chakravorty SJ, Urban BC, Kai OK, Marsh K, Craig AG: The effect of Plasmodium falciparum infection on expression of monocyte surface molecules. Trans R Soc Trop Med Hyg. 2006, 100: 1007-1012. 10.1016/j.trstmh.2006.01.005.CrossRefPubMed
10.
go back to reference Dondorp AM, Angus BJ, Hardeman MR, Chotivanich KT, Silamut K, Ruangveerayuth R, Kager PA, White NJ, Vreeken J: Prognostic significance of reduced red blood cell deformability in severe falciparum malaria. Am J Trop Med Hyg. 1997, 57: 507-511.PubMed Dondorp AM, Angus BJ, Hardeman MR, Chotivanich KT, Silamut K, Ruangveerayuth R, Kager PA, White NJ, Vreeken J: Prognostic significance of reduced red blood cell deformability in severe falciparum malaria. Am J Trop Med Hyg. 1997, 57: 507-511.PubMed
11.
go back to reference Dondorp AM, Nyanoti M, Kager PA, Mithwani S, Vreeken J, Marsh K: The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion. Trans R Soc Trop Med Hyg. 2002, 96: 282-286. 10.1016/S0035-9203(02)90100-8.CrossRefPubMed Dondorp AM, Nyanoti M, Kager PA, Mithwani S, Vreeken J, Marsh K: The role of reduced red cell deformability in the pathogenesis of severe falciparum malaria and its restoration by blood transfusion. Trans R Soc Trop Med Hyg. 2002, 96: 282-286. 10.1016/S0035-9203(02)90100-8.CrossRefPubMed
12.
go back to reference Facer CA, Bray RS, Brown J: Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. I. Incidence and class specificity. Clin Exp Immunol. 1979, 35: 119-127.PubMedPubMedCentral Facer CA, Bray RS, Brown J: Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. I. Incidence and class specificity. Clin Exp Immunol. 1979, 35: 119-127.PubMedPubMedCentral
13.
go back to reference Facer CA: Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of erythrocyte-bound IgG. Clin Exp Immunol. 1980, 39: 279-288.PubMedPubMedCentral Facer CA: Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of erythrocyte-bound IgG. Clin Exp Immunol. 1980, 39: 279-288.PubMedPubMedCentral
14.
go back to reference Layez C, Nogueira P, Combes V, Costa FT, Juhan-Vague I, da Silva LH, Gysin J: Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage. Blood. 2005, 106: 3632-3638. 10.1182/blood-2005-04-1574.CrossRefPubMed Layez C, Nogueira P, Combes V, Costa FT, Juhan-Vague I, da Silva LH, Gysin J: Plasmodium falciparum rhoptry protein RSP2 triggers destruction of the erythroid lineage. Blood. 2005, 106: 3632-3638. 10.1182/blood-2005-04-1574.CrossRefPubMed
15.
go back to reference Waitumbi JN, Opollo MO, Muga RO, Misore AO, Stoute JA: Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemia. Blood. 2000, 95: 1481-1486.PubMed Waitumbi JN, Opollo MO, Muga RO, Misore AO, Stoute JA: Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemia. Blood. 2000, 95: 1481-1486.PubMed
16.
17.
go back to reference Stoute JA, Odindo AO, Owuor BO, Mibei EK, Opollo MO, Waitumbi JN: Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis. 2003, 187 (3): 522-525. 10.1086/367712.CrossRefPubMed Stoute JA, Odindo AO, Owuor BO, Mibei EK, Opollo MO, Waitumbi JN: Loss of red blood cell-complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis. 2003, 187 (3): 522-525. 10.1086/367712.CrossRefPubMed
18.
go back to reference Waitumbi JN, Donvito B, Kisserli A, Cohen JH, Stoute JA: Age-related changes in red blood cell complement regulatory proteins and susceptibility to severe malaria. J Infect Dis. 2004, 190: 1183-1191. 10.1086/423140.CrossRefPubMed Waitumbi JN, Donvito B, Kisserli A, Cohen JH, Stoute JA: Age-related changes in red blood cell complement regulatory proteins and susceptibility to severe malaria. J Infect Dis. 2004, 190: 1183-1191. 10.1086/423140.CrossRefPubMed
19.
go back to reference Xiang L, Rundles JR, Hamilton DR, Wilson JG: Quantitative alleles of CR1: coding sequence analysis and comparison of haplotypes in two ethnic groups. J Immunol. 1999, 163: 4939-4945.PubMed Xiang L, Rundles JR, Hamilton DR, Wilson JG: Quantitative alleles of CR1: coding sequence analysis and comparison of haplotypes in two ethnic groups. J Immunol. 1999, 163: 4939-4945.PubMed
20.
go back to reference Cockburn IA, Mackinnon MJ, O'Donnell A, Allen SJ, Moulds JM, Baisor M, Bockarie M, Reeder JC, Rowe JA: A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc Natl Acad Sci USA. 2004, 101: 272-277. 10.1073/pnas.0305306101.CrossRefPubMed Cockburn IA, Mackinnon MJ, O'Donnell A, Allen SJ, Moulds JM, Baisor M, Bockarie M, Reeder JC, Rowe JA: A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria. Proc Natl Acad Sci USA. 2004, 101: 272-277. 10.1073/pnas.0305306101.CrossRefPubMed
21.
go back to reference Rowe JA, Moulds JM, Newbold CI, Miller LH: P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature. 1997, 388: 292-295. 10.1038/40269.CrossRefPubMed Rowe JA, Moulds JM, Newbold CI, Miller LH: P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature. 1997, 388: 292-295. 10.1038/40269.CrossRefPubMed
22.
go back to reference Udomsangpetch R, Wahlin B, Carlson J, Berzins K, Torii M, Aikawa M, Perlman P, Wahlgren M: Plasmodium falciparum-infected erythrocytes form spontaneous erythrocyte rosettes. J Exp Med. 1989, 169: 1835-1840. 10.1084/jem.169.5.1835.CrossRefPubMed Udomsangpetch R, Wahlin B, Carlson J, Berzins K, Torii M, Aikawa M, Perlman P, Wahlgren M: Plasmodium falciparum-infected erythrocytes form spontaneous erythrocyte rosettes. J Exp Med. 1989, 169: 1835-1840. 10.1084/jem.169.5.1835.CrossRefPubMed
23.
go back to reference O'Donnell A, Premawardhena A, Arambepola M, Allen SJ, Peto TE, Fisher CA, Rees DC, Olivieri NF, Weatherall DJ: Age-related changes in adaptation to severe anemia in childhood in developing countries. Proc Natl Acad Sci USA. 2007, 104: 9440-9444. 10.1073/pnas.0703424104.CrossRefPubMedPubMedCentral O'Donnell A, Premawardhena A, Arambepola M, Allen SJ, Peto TE, Fisher CA, Rees DC, Olivieri NF, Weatherall DJ: Age-related changes in adaptation to severe anemia in childhood in developing countries. Proc Natl Acad Sci USA. 2007, 104: 9440-9444. 10.1073/pnas.0703424104.CrossRefPubMedPubMedCentral
24.
go back to reference Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B, Nyanoti M, Williams TN, Maitland K, Molyneux M, Newton CR, Peshu N, Watt SM, Roberts DJ: Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood. 2006, 108: 2569-2577. 10.1182/blood-2006-05-018697.CrossRefPubMed Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B, Nyanoti M, Williams TN, Maitland K, Molyneux M, Newton CR, Peshu N, Watt SM, Roberts DJ: Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and in vivo. Blood. 2006, 108: 2569-2577. 10.1182/blood-2006-05-018697.CrossRefPubMed
25.
go back to reference Casals-Pascual C, Idro R, Gicheru N, Gwer S, Kitsao B, Gitau E, Mwakesi R, Roberts DJ, Newton CR: High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria. Proc Natl Acad Sci USA. 2008, 105: 2634-2639. 10.1073/pnas.0709715105.CrossRefPubMedPubMedCentral Casals-Pascual C, Idro R, Gicheru N, Gwer S, Kitsao B, Gitau E, Mwakesi R, Roberts DJ, Newton CR: High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria. Proc Natl Acad Sci USA. 2008, 105: 2634-2639. 10.1073/pnas.0709715105.CrossRefPubMedPubMedCentral
Metadata
Title
The pathophysiology of malarial anaemia: where have all the red cells gone?
Authors
Oscar K Kai
David J Roberts
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2008
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-6-24

Other articles of this Issue 1/2008

BMC Medicine 1/2008 Go to the issue