Retention of erythrocytes in the spleen: A double-edged process in human malaria

Current Opinion in Hematology

Volumn 16, Issue 3, 2009, Pages 157-164

  Buffet, Pierre A ^a,b   Safeukui, Innocent ^b   Milon, Geneviève ^c   Mercereau Puijalon, Odile ^b   David, Peter H ^b  

^a PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^b CNRS   (France)

^c INSTITUT PASTEUR   (France)

Author keywords

Cerebral malaria; Plasmodium falciparum; Severe malarial anaemia; Spleen; Splenomegaly

Indexed keywords

ANEMIA; BRAIN MALARIA; CHILD; CLINICAL FEATURE; DISEASE ASSOCIATION; DISEASE TRANSMISSION; ERYTHROCYTE; ERYTHROPOIESIS; HUMAN; MALARIA FALCIPARUM; NONHUMAN; PARASITEMIA; PATHOGENESIS; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; REVIEW; SPLEEN SIZE; SPLENECTOMY; SPLENOMEGALY;

ANEMIA; CHILD; CHRONIC DISEASE; ERYTHROCYTES; HUMANS; MALARIA, CEREBRAL; MALARIA, FALCIPARUM; SPLEEN; SPLENOMEGALY;

EID: 67749120495     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e32832a1d4b     Document Type: Review

References (83)

1. Boone KE, Watters DA. The incidence of malaria after splenectomy in Papua New Guinea. BMJ 1995; 311:1273.
2. Bach O, Baier M, Pullwitt A, et al. Falciparum malaria after splenectomy: a prospective controlled study of 33 previously splenectomized Malawian adults. Trans R Soc Trop Med Hyg 2005; 99:861-867.
3. Davidson RN, Wall RA. Prevention and management of infections in patients without a spleen. Clin Microbiol Infect 2001; 7:657-660.
4. Zingman BS, Viner BL. Splenic complications in malaria: case report and review. Clin Infect Dis 1993; 16:223-232.
5. Hackett LW. Spleen measurement in malaria. J Nat Mal Soc 1944; 3:121-133.
6. Urban BC, Hien TT, Day NP, et al. Fatal Plasmodium falciparum malaria causes specific patterns of splenic architectural disorganization. Infect Immun 2005; 73:1986-1994.
7. Lubitz JM. Pathology of the ruptured spleen in acute vivax malaria. Blood 1949; 4:1168-1176.
8. Imbert P, Rapp C, Buffet PA. Pathological rupture of the spleen in malaria: analysis of 55 cases (1958-2008). Travel Med Infect Dis 2009 [Epub ahead of print]. doi: 10.1016/j.tmaid.2009.01.002. This exhaustive analysis of published cases of pathological spleen rupture in malaria provides a state-of-the-art review on the management of this rare complication and shows interesting similarities between P. falciparum and P. vivaxinduced spleen rupture.
9. Urban BC, Ferguson DJ, Pain A, et al. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells [see comments]. Nature 1999; 400:73-77.
10. Chen LT, Weiss L. Electron microscopy of the red pulp of human spleen. Am J Anat 1972; 134:425-457.
11. Newton PN, Chotivanich K, Chierakul W, et al. A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigenpositive and -negative erythrocytes. Blood 2001; 98:450-457.
12. Looareesuwan S, Ho M, Wattanagoon Y, et al. Dynamic alteration in splenic function during acute falciparum malaria. N Engl J Med 1987; 317:675-679.
13. White NJ, Chapman D, Watt G. The effects of multiplication and synchronicity on the vascular distribution of parasites in falciparum malaria. Trans R Soc Trop Med Hyg 1992; 86:590-597.
14. Howard RJ, Gilladoga AD. Molecular studies related to the pathogenesis of cerebral malaria. Blood 1989; 74:2603-2618.
15. Su X-Z, Heatwole VM, Wertheimer SP, et al. The large diverse family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 1995; 82:89-100.
16. Scherf A, Hernandez Rivas R, Buffet P, et al. Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J 1998; 17:5418-5426.
17. Udomsangpetch R, Pipitaporn B, Silamut K, et al. Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci U S A 2002; 99:11825-11829.
18. Pouvelle B, Buffet PA, Lepolard C, et al. Cytoadhesion of Plasmodium falciparum ring-stage-infected erythrocytes. Nat Med 2000; 6:1264-1268.
19. Silamut K, Phu NH, Whitty C, et al. A quantitative analysis of the microvascular sequestration of malaria parasites in the human brain. Am J Pathol 1999; 155:395-410.
20. Miller LH, Good MF, Milon G. Malaria pathogenesis. Science 1994; 264:1878-1883.
21. Borst P, Bitter W, McCulloch R, et al. Antigenic variation in malaria. Cell 1995; 82:1-4.
22. Chen LT, Weiss L. The role of the sinus wall in the passage of erythrocytes through the spleen. Blood 1973; 41:529-537.
23. Groom AC, Schmidt EE, MacDonald IC. Microcirculatory pathways and blood flow in spleen: new insights from washout kinetics, corrosion casts, and quantitative intravital videomicroscopy. Scanning Microsc 1991; 5:159-173; discussion 73-74.
24. Cranston HA, Boylan CW, Carroll GL, et al. Plasmodium falciparum maturation abolishes physiologic red cell deformability. Science 1984; 223:400-403.
25. Mills JP, Diez-Silva M, Quinn DJ, et al. Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum. Proc Natl Acad Sci U S A 2007; 104:9213-9217.
26. Safeukui I, Correas JM, Brousse V, et al. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood 2008; 112:2520-2528. These authors explored the interactions between P. falciparum-infected erythrocytes and the human spleen. Contrast ultrasonography and ex-vivo perfusion show that a proportion of rings are retained in the slow, open circulation of the red pulp in which erythrocytes physiologically undergo a stringent deformability challenge. Laser-based analysis confirms the increased stiffness of rings, consistent with a mechanical clearance process.
27. Li J, Dao M, Lim CT, Suresh S. Spectrin-level modeling of the cytoskeleton and optical tweezers stretching of the erythrocyte. Biophys J 2005; 88:3707-3719.
28. Dondorp AM, Chotivanich KT, Fucharoen S, et al. Red cell deformability, splenic function and anaemia in thalassaemia. Br J Haematol 1999; 105:505-508.
29. Dondorp AM, Angus BJ, Chotivanich K, et al. Red blood cell deformability as a predictor of anemia in severe falciparum malaria. Am J Trop Med Hyg 1999; 60:733-737.
30. Dondorp AM, Angus BJ, Hardeman MR, et al. Prognostic significance of reduced red blood cell deformability in severe falciparum malaria. Am J Trop Med Hyg 1997; 57:507-511.
31. Giha HA, Elghazali G, A-Elgadir TM, et al. Severe malaria in an unstable setting: clinical and laboratory correlates of cerebral malaria and severe malarial anemia and a paradigm for a simplified severity scoring. Eur J Clin Microbiol Infect Dis 2008 [Epub ahead of print]. doi: 10.1007/s10096-008- 0665-5. These authors provide a very precise description of clinical and laboratory features in children with severe malaria, including data not frequently captured in large field studies: spleen prevalence, spleen size and duration of fever. Because this study is in an unstable setting, most children had very few previous malaria episodes.
32. Marsh K. Clinical features of malaria. In: Wahlgren M, Perlmann P, editors. Malaria: molecular and clinical aspects. Amsterdam: Harwood Academic Publishers; 1999. pp. 87-117.
33. Schellenberg D, Menendez C, Kahigwa E, et al. African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death. Am J Trop Med Hyg 1999; 61:431-438.
34. Giha HA, Elghazali G, A-Elgadir TM, et al. Clinical pattern of severe Plasmodium falciparum malaria in Sudan in an area characterized by seasonal and unstable malaria transmission. Trans R Soc Trop Med Hyg 2005; 99:243-251.
35. Price RN, Simpson JA, Nosten F, et al. Factors contributing to anemia after uncomplicated falciparum malaria. Am J Trop Med Hyg 2001; 65:614-622.
36. Buffet PA, Milon G, Brousse V, et al. Ex vivo perfusion of human spleens maintains clearing and processing functions. Blood 2006; 107:3745-3752.
37. Simpson JA, Aarons L, Collins WE, et al. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 2002; 124 (Pt 3):247-263.
38. Walther M, Tongren JE, Andrews L, et al. Upregulation of TGF-beta, FOXP3, and CD4(+)CD25(+) regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 2005; 23:287-296.
39. Calis JC, Phiri KS, Faragher EB, et al. Severe anemia in Malawian children. N Engl J Med 2008; 358:888-899. This case-control study in preschool African children with severe anaemia analyses an impressive number of clinical features (including splenomegaly) as well as potential infectious, genetic and environmental risk factors. The authors provide a structural equation model for severe anaemia, iron deficiency and malaria. This is a reference framework for future pathophysiological approaches in that field.
40. Dondorp AM, Desakorn V, Pongtavornpinyo W, et al. Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med 2005; 2:e204.
41. Pongponratn E, Riganti M, Harinasuta T, Bunnag D. Electron microscopy of the human brain in cerebral malaria. Southeast Asian J Trop Med Public Health 1985; 16:219-227.
42. Kai OK, Roberts DJ. The pathophysiology of malarial anaemia: where have all the red cells gone? BMC Med 2008; 6:24. These authors set up a clear perspective on how age-dependent expression of the complement control proteins may influence the outcome of malaria infection, with a special focus on severe anaemia. They also propose that innate resistance to one syndrome of malaria may be at the expense of susceptibility to another syndrome, and mention the potential role of EPO in this process.
43. Casals-Pascual C, Idro R, Gicheru N, et al. High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria. Proc Natl Acad Sci U S A 2008; 105:2634-2639. These authors report a strong association between high concentrations of plasma EPO and reduced risk of neurological sequelae in African children with cerebral malaria, even after careful adjustment for potential confounding factors. They also show an independent influence of age on EPO-related protection. These results bear important pathophysiological consequences and support adjunctive therapeutic applications in cerebral malaria.
44. Abdalla SH. Hematopoiesis in human malaria. Blood Cells 1990; 16:401-416; discussion 417-419.
45. Kurtzhals JA, Addae MM, Akanmori BD, et al. Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg 1999; 93:623-627.
46. Helleberg M, Goka BQ, Akanmori BD, et al. Bone marrow suppression and severe anaemia associated with persistent Plasmodium falciparum infection in African children with microscopically undetectable parasitaemia. Malar J 2005; 4:56.
47. Weatherall DJ, Abdalla S. The anaemia of Plasmodium falciparum malaria. Br Med Bull 1982; 38:147-151.
48. Vafa M, Israelsson E, Maiga B, et al. Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. Acta Trop 2009; 109:12-16. The latest article of an impressive series on the expression of P. falciparum infection in sympatric groups in Burkina Faso. This study challenges the commonly accepted idea that anti-P. falciparum antibody levels are strongly associated with parasite prevalence and splenomegaly, raising the hypothesis that either fine antibody specifities or an innate mechanism may be the determinant factor of parasite control in Fulanis.
49. Modiano D, Petrarca V, Sirima BS, et al. Plasmodium falciparum malaria in sympatric ethnic groups of Burkina Faso, west Africa. Parassitologia 1995; 37:255-259.
50. Modiano D, Petrarca V, Sirima BS, et al. Different response to Plasmodium falciparum malaria in west African sympatric ethnic groups. Proc Natl Acad Sci U S A 1996; 93:13206-13211.
51. Modiano D, Chiucchiuini A, Petrarca V, et al. Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina Faso. Am J Trop Med Hyg 1998; 58:220-224.
52. Torcia MG, Santarlasci V, Cosmi L, et al. Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria. Proc Natl Acad Sci U S A 2008; 105:646-651. This in-depth analysis of peripheral patterns of cellular response in selected patients from two sympatric groups shows that gene expression reflecting T regulatory activity is decreased, and serum levels of transforming growth factor β are also decreased in Fulanis. In this group, proliferative response to malaria antigens is not affected by the depletion of CD25 regulatory cells, suggesting that the lower activity of Treg cells is central in the resistance of Fulani to P. falciparum infection.
53. Brandao MM, Fontes A, Barjas-Castro ML, et al. Optical tweezers for measuring red blood cell elasticity: application to the study of drug response in sickle cell disease. Eur J Haematol 2003; 70:207-211.
54. Williams TN, Mwangi TW, Wambua S, et al. Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases. J Infect Dis 2005; 192:178-186.
55. May J, Evans JA, Timmann C, et al. Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA 2007; 297:2220-2226.
56. Crompton PD, Traore B, Kayentao K, et al. Sickle cell trait is associated with a delayed onset of malaria: implications for time-to-event analysis in clinical studies of malaria. J Infect Dis 2008; 198:1265-1275. This cleverly designed study shows that sickle cell trait-dependent protection against malaria results in a more than 1-month delay to the first malaria episode in a seasonal setting. These data strongly support the inclusion of Hb typing in the design of future studies and may help clarify the mechanisms of the protective effect of the sickle cell trait.
57. Weatherall DJ. Genetic variation and susceptibility to infection: the red cell and malaria. Br J Haematol 2008; 141:276-286.
58. Cholera R, Brittain NJ, Gillrie MR, et al. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A 2008; 105:991-996. This in-vitro study with fresh clinical isolates in Mali shows that infected AS genotype RBCs bind less to endothelial cells than control parasitized AA genotype RBCs. Reduced binding correlates with the altered display of P. falciparum iRBC (erythrocyte) membrane protein 1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the RBC surface.
59. De Franceschi L, Sada S, Andreoli A, et al. Sickle cell disease and hyperreactive malarial splenomegaly (HMS) in young immigrants from Africa. Blood 2005; 106:4415-4417.
60. Charmot G, Rigaud JL, Andre L, Fouchet M. Considerations on the etiology of tropical splenomegaly. Bull Soc Pathol Exot Filiales 1963; 56:133-137.
61. Crane GG, Pryor DS. Malaria and the tropical splenomegaly syndrome in New Guinea. Trans R Soc Trop Med Hyg 1971; 65:315-324.
62. Facer CA, Crane GG. Hyperreactive malarious splenomegaly. Lancet 1991; 338:115-116.
63. Bedu-Addo G, Bates I. Causes of massive tropical splenomegaly in Ghana. Lancet 2002; 360:449-454.
64. Puente S, Rubio JM, Subirats M, et al. The use of PCR in the diagnosis of hyper-reactive malarial splenomegaly (HMS). Ann Trop Med Parasitol 2000; 94:559-563.
65. Mothe B, Lopez-Contreras J, Torres OH, et al. A case of hyper-reactive malarial splenomegaly. The role of rapid antigen-detecting and PCR-based tests. Infection 2008; 36:167-169.
66. Torres JR, Villegas L, Perez H, et al. Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive malarious splenomegaly and acute haemolysis. Ann Trop Med Parasitol 2003; 97:125-130.
67. Allam MM, Alkadarou TA, Ahmed BG, et al. Hyper-reactive malarial splenomegaly (HMS) in malaria endemic area in Eastern Sudan. Acta Trop 2008; 105:196-199.
68. De Iaco G, Saleri N, Perandin F, et al. Hyper-reactive malarial splenomegaly in a patient with human immunodeficiency virus. Am J Trop Med Hyg 2008; 78:239-240.
69. Bisoffi Z, Eseme F, Lodesani C, et al. Early hyper-reactive malaria splenomegaly: a definite clinical entity that should be recognized and treated. Proc Med Health Tropics Congress 2005; 1:29.
70. Bates I, Bedu-Addo G. Chronic malaria and splenic lymphoma: clues to understanding lymphoma evolution. Leukemia 1997; 11:2162-2167.
71. Bates I, Bedu-Addo G, Bevan DH, Rutherford TR. Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly. Lancet 1991; 337:505-507.
72. Bates I, Bedu-Addo G, Rutherford T, Bevan DH. Splenic lymphoma with villous lymphocytes in tropical West Africa. Lancet 1992; 340:575-577.
73. Suarez F, Lortholary O, Hermine O, Lecuit M. Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood 2006; 107:3034-3044.
74. van der Heyde HC, Nolan J, Combes V, et al. A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 2006; 22:503-508.
75. Yeo TW, Lampah DA, Gitawati R, et al. Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci U S A 2008; 105:17097-17102. This study shows that the angiogenetic factor angiopoietin-2 - the plasma levels of which are associated with increased venous lactate, parasite biomass and mortality - is a very accurate marker of malaria-induced acute organ failures (coma, acute renal failure and hyperbilirubinemia). These observations markedly advance the understanding of endothelial activation and impaired perfusion in malaria and may lead to significant progress in the adjunctive therapy of severe malaria.
76. Beare NA, Harding SP, Taylor TE, et al. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 2009; 199:263-271. With these dynamic observations, using fluorescein retinal angiography, these authors add an important contribution to their seminal description of malaria retinopathy. Perfusion abnormalities directly observed in the central nervous system microvasculature of patients affected by cerebral malaria are highly suggestive of sequestration. Although late leakage is noticed in a proportion of patients, observed patterns point to hypoxia and ischaemia as pivotal factors in the pathogenesis of cerebral malaria.
77. Montgomery J, Mphande FA, Berriman M, et al. Differential var gene expression in the organs of patients dying of falciparum malaria. Mol Microbiol 2007; 65:959-967.
78. Bull PC, Lowe BS, Kaleli N, et al. Plasmodium falciparum infections are associated with agglutinating antibodies to parasite-infected erythrocyte surface antigens among healthy Kenyan children. J Infect Dis 2002; 185:1688-1691.
79. Reyburn H, Mbatia R, Drakeley C, et al. Association of transmission intensity and age with clinical manifestations and case fatality of severe Plasmodium falciparum malaria. JAMA 2005; 293:1461-1470.
80. Odhiambo CO, Otieno W, Adhiambo C, et al. Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: implications for the development of severe anemia. BMC Med 2008; 6:23.
81. Ayi K, Turrini F, Piga A, Arese P. Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood 2004; 104:3364-3371.
82. Price RN, Tjitra E, Guerra CA, et al. Vivax malaria: neglected and not benign. Am J Trop Med Hyg 2007; 77 (6 Suppl):79-87.
83. Suwanarusk R, Cooke BM, Dondorp AM, et al. The deformability of red blood cells parasitized by Plasmodium falciparum and P. vivax. J Infect Dis 2004; 189:190-194.