Parasitology Research

, Volume 101, Issue 6, pp 1463–1469

Pathogenesis of anemia in malaria: a concise review

Review

Abstract

Anemia is a common complication in malarial infection, although the consequences are more pronounced with Plasmodium falciparum malaria (Ghosh, Indian J Hematol Blood Tranfus 21(53):128–130, 2003). Anemia in this infection is caused by a variety of pathophysiologic mechanisms, and in areas where malaria infection is endemic, co-morbidities like other parasitic infestations, iron, folate and Vitamin B12 deficiency, deficiency of other nutrients, and anemia, which is aggravated by anti-malarial drugs both through immune and non-immune mechanisms, are important considerations. In different endemic areas, β-thalassemia, α-thalassemia, Hb S, Hb E, G6PD deficiency, or ovalocytosis in different proportions interact with this infection. Finally, aberrant immune response to repeated or chronic falciparum malarial infection may produce tropical splenomegaly syndrome, a proportion of which show clonal proliferation of B lymphocytes. Cooperation between chronic malarial infection and infection with E-B virus infection in producing Burkitt’s lymphoma is well known. In this review, the fascinating and multifaceted pathophysiolgoy of malarial anemia has been discussed.

References

  1. Abdalla SH (1990) Hematopoiesis in human malaria. Blood Cells 16:401–416PubMedGoogle Scholar
  2. Abdalla SH, Wickramasinghe SN (1988) A study of erythroid progenitor cells in the grambian children with falciparum malaria. Clin Lab Haematol 10:33–40PubMedGoogle Scholar
  3. Anyona SB, Schrier SL, Gichuki CW, Waitumbi JN (2006) Pitting of malaria parasites and spherocytes formation. Malaria Journal. Doi 10.1186/1475-2875-5-64 (http://www.malariajournal.com/content/5/1/64)
  4. Arese P, Schwarzwer E (1997) Malarial pigment (haemozoin): a very active “inert” substance. Ann Trop Med Parasitol 91:501–516PubMedCrossRefGoogle Scholar
  5. Ayi K, Turrini F, Piga A, Arese P (2004) Enchanced phagocytosis of ring parasitised mutant erythrocytes: A common mechanism that may explain protection against falciparum malaria in sickle cell trait and beta-thalassemia trait. Blood 104:3364–3371PubMedCrossRefGoogle Scholar
  6. Bates I, Bedu Addo G, Bevan DH (1991) Use of immunoglobin gene rearrangement to show clonal lymphoproliferative is hypereactive malarial splenomegaly. Lancet 337:505–507PubMedCrossRefGoogle Scholar
  7. Casals-Pascual C, Kai O, Cheung JO, Williams S, Lowe B, Nyanoti M, Willimas TN, Maitland K, Molyneux M, Newton CR, Peshu N, Watt SN, Roberts DJ (2006) Suppression of erythropoiesis in malarial anemia is associated with hemozoin in vitro and invivo. Blood 108:2569–2577PubMedCrossRefGoogle Scholar
  8. Chitnis CE (2001) Molecular insights into receptors used by malarial parasites for erythocytes invasion. Curr Opin Hematol 8:85–91PubMedCrossRefGoogle Scholar
  9. Clark IA, Cowden WB (2003) The pathophysiology of falciparum malaria. Pharmacol Ther 99:221–260PubMedCrossRefGoogle Scholar
  10. Clark IA, Rockett KA, Cowden WB (1991) Proposed link between cytokines, nitric acid and human cerebral malaria. Parasitol Today 7:205–207PubMedCrossRefGoogle Scholar
  11. Clark IA, Budd AC, Alleva LM, Cowden WB (2006) Human malarial disease: A consequence of inflammatory cytokine release. Malaria Journal (Biomed Central). Doi 10. 1186/1475-2875-5-85 (http://www.malariajournal.com/content/5/1/85
  12. Conrad ME, Denis LH (1968) Splenic function in experimental malaria. Am J Trop Med Hyg 17:170–172PubMedGoogle Scholar
  13. Facer CA, Bray RS, Brown J (1979) Direct antiglobin reaction in Gambian children with plasmodium malaria. Incidence and class specificity. Clin Exp Immunol 35:119–127PubMedGoogle Scholar
  14. Fink MP (2001) Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin 17:219–237PubMedCrossRefGoogle Scholar
  15. Gamain B, Smith JD, Miller LH, Baruch OI (2001) Modification of CD 36 binding domain of P. falciparum variant antigen are responsible for the inability of chondrointin sulphate A adherent parasites to bond CD 36. Blood 97:3268–3274PubMedCrossRefGoogle Scholar
  16. Ghosh K (2003) Mechanism of anemia in malaria and its management. Indian J Hematol Blood Tranfus 21(53):128–130Google Scholar
  17. Ghosh K, Javeri KN, Mohanty D, Parmar BD, Surati RR, Joshi SH (2001) False positive serological tests in acute malaria. Br J Biodmed Sci 58:20–23Google Scholar
  18. Giribaldi G, Ulliers D, Schwarzer E, Roberts I, Piacibello W, Arese P (2004) Hemozoin and 4 hydroxynonenal-mediated inhibition of erythropoiesis: Possible role in malarial dyserythropoiesis and anemia. Haematologica 89:492–493PubMedGoogle Scholar
  19. Githeko AK, Brandling Bennett AD, Beier M, Mbogo CM, Atieli AK, Owaga ML, Juma F, Collins FH (1993) Confirmation that Plasmodium falciparum has a periodic infectivity to anopheles gambiae. Med Vet Entomol 7:373–376PubMedGoogle Scholar
  20. Harpaz R, Edelman R, Wasserman SS, Levine MM, Davis JR, Sztein MB (1992) Serum cytokine profile in experimental human malaria. Relationship to protection and disease course after challenge. J Clin Invest 90:515–523PubMedGoogle Scholar
  21. Jhaveri KN, Ghosh K, Mohanty D, Parmar BD, Surati RR, Camoens HM, Joshi SH, Iyer YS, Desaii A, Badakere SS (1997) Autoantibodies immunoglobulins, complement and circulating immune complexes in acute malaria. Natl Med J India 54:23–29Google Scholar
  22. Kedar PS, Ghosh K, Colah RB, Mohanty D (2002) Chronic persistent hemolysis in an infant: Can we afford to forget malaria as a cause. Hematol J 3:114–115PubMedCrossRefGoogle Scholar
  23. Kumaratilake LM, Ferrante A, Kumaratikalka JS, Allison C (1994) Extraction of intra erythrocytic malarial parasites by phagotytic cells. Parasitol Today 10:193–196PubMedCrossRefGoogle Scholar
  24. Kurtzhals HA, Rodrigues O, Addae M, Commey JO, Nikrumah FK, Hviid L (1997) Reversible suppression of bone marrow response to erythropoietin in Plasmodium falciparum malaria. Br J Haematol 97:169–174PubMedCrossRefGoogle Scholar
  25. Lee TS, Chau LY (2002) Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8:240–246PubMedCrossRefGoogle Scholar
  26. Looareesuwan S, Ho M, Wattanagoon Y, White NJ, Warrell DA, Bunnaq D, Harinasuta T, Wyler DJ (1987) Dynamic alterations in splenic function during acute falciparum malaria. N Engl J Med 317:678–681CrossRefGoogle Scholar
  27. Luty AJ, Perkins DJ, Lell B, Schmidt-Ott R, Lehman L, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG (2000) Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 68:3909–3915PubMedCrossRefGoogle Scholar
  28. Luzzatto L, Usanga EA, Reddy S (1969) Glucose 6 phosphate dehydrogenase deficient red cells: resistance to infection by malarial parasites. Science 164:839–842PubMedCrossRefGoogle Scholar
  29. Luzzatto L, Nwachuku-Jarrett ES, Reddy S (1970) Increased sickling of parasitized erythrocytes as mechanism of resistance against malaria in the sickle cell trait. Lancet 1:319–322PubMedCrossRefGoogle Scholar
  30. Martiney JA, Sherry B, Metz CN, Espinoza M, Ferrer AS, Calandra T, Broxmeyer HE, Bucala R (2000) Macrophage migration inhibitory factor release by macrophages after ingestion of Plasmodium chaboudi infected erythrocytes: Possible role in the pathogenesis of malarial anemia. Infect Immun 68:2259–2267PubMedCrossRefGoogle Scholar
  31. Mayer DCJ, Kaneko O, Hudson-Taylor DE, Reid ME, Miller LH (2001) Characterization of Plasmodium falciparum erythrocyte binding protein para logous to EBA-175. Proc Natl Acad Sci U S A 98:5222–5227PubMedCrossRefGoogle Scholar
  32. Means RT Jr (2003) The anemia of infection. Bailliere’s Best Pract Res Clin Haematol 13:151–152CrossRefGoogle Scholar
  33. Modiano G, Morpurgo G, Terrenatao L, Novelletto A, DiRienzo A, Colombo B, Purpura M, Marian M, Santachiara-Benerreletti S, Brega A, Dixit KA, Shvestha SL, Lania A, Wanachi Wanawin W, Luzzatto L (1991) Protection against malaria morbidity: near fixation of alpha thalassemia gene in a Nepalese population. Am J Hum Genet 48:390–397PubMedGoogle Scholar
  34. Mohan K, Stevenson MM (1998) Dyserythropoiesis and severe anemia associated with malaria correlate with deficient interleukin- 12 production. Br J Haematol 103:942–949PubMedCrossRefGoogle Scholar
  35. Nussenblatt V, Mukasa G, Metzger A, Garett E, Semba RD (2001) Anaemia and interleukin 10, tumour necrosis factor and erythropoietin levels among children with uncomplicated plasmodium falciparum malaria. Clin Dign Lab Immunol 8:1164–1170CrossRefGoogle Scholar
  36. Newton PN, Chotivanich K, Chierakul W, Ruangveeryuth R, Teerapong P, Silamunt K, Looareesuwan S, White NJ (2001) A comparison of the invivo kinetics of Plasmodium falciparum ring infected erythrocyte surface antigen positive and negative erythrocytes. Blood 98:450–457PubMedCrossRefGoogle Scholar
  37. O’Donnell A, Allen SJ, Mgone CS, Martinson JJ, Clegg JB, Weatherall DJ (1998) Red Cell morphology and malaria anemia in children with south east asian ovalocytosis band 3 in papua new guinea. Bri J Haematol 101:407–412CrossRefGoogle Scholar
  38. Ohno T, Chirasaka A, Sugiyama T, Furnakawa H (1996) Hemophagocytic syndrome induced by Plasmodium falciparum malaria infection. Int J Hematol 64:263–266PubMedCrossRefGoogle Scholar
  39. Oppenheimer SJ (1989) Iron and malaria. Parasitol Today 5:77–82PubMedCrossRefGoogle Scholar
  40. Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhay Kumar V (1999) A low interleukin 10 tumour necrosis factor alpha ratio is associated with malaria anemia in children residing in holoendemic malaria region in western Kenya. J Infect Dis 179:279–282PubMedCrossRefGoogle Scholar
  41. Perkins DJ, Weinberg JB, Kremsner PG (2000) Reduced interleukin- 12 and trans forming growth factor-beta 1 in severe childhood malaria: relationship of cytokine balance with disease severity. J Infect Dis 182:988–992PubMedCrossRefGoogle Scholar
  42. Roberts DJ, Casals-Pascul C, Weatherall DJ (2005) The clinical and pathophysiological features of malarial anemia. Curr Trop Microbiol Immunol 295:137–167CrossRefGoogle Scholar
  43. Sandau KB, Zhou J, Kietzmann T, Brune B (2001) Regulation of hypoxia-inducible factor 1 alpha by the inflammatory mediators nitric oxide and tumor necrosis, factor alpha in contrast to desferroxamine and phenylarsine oxide. J Biol Chem 276:39805–39811PubMedCrossRefGoogle Scholar
  44. Schwarzer E, Ludwig P, Valente E, Arese P (1999) 15(S) hydorxyeicosa tetraenoic acid (15 HETE) a product of arachidomic acid peroxidation, is an active component of hemozoin toxicity to mocytes. Parasitologica 41:199–202Google Scholar
  45. Skorokhod A, Schwarzer E, Gremeo G, Arese P (2007) HNE produced by malaria parasite Plasmodium falciparum generate HNE-protein adducts and decreases erythrocyte deformobility. Redox Rep 12:73–75PubMedCrossRefGoogle Scholar
  46. Snow RW, Craig M, Deichmann U, Marsh K (1999) Estimating mortality morbidity and disability due to malaria among Africa’s non pregnant population. Bull WHO 77:624–640PubMedGoogle Scholar
  47. Srichaikul T, Panikbutr N, Jeumtrakul P (1967) Bone marrow changes in human malaria. Ann Trop Med Parasitol 61:40–51PubMedGoogle Scholar
  48. Stouti JA, Odindo AO, Owuor BO, Mibei EK, Opollo MO, Waitumbi JN (2003) Loss of red blood cell compliment regulatory proteins and susceptibility to severe malarial anemia. J Infect Dis 187:522–525CrossRefGoogle Scholar
  49. Takeman GN, Saul A, Hogarth WL, Collins WE (1999) Anemia of acute malaria infection in non immune patients primarily results from destruction of uninfected erythrocytes. Parasitology 119:127–133CrossRefGoogle Scholar
  50. Turrini F, Giribaldi G, Carta F, Mannu F, Arese P (2003) Mechanism of band-3 oxidation and clustering in the phagocytosis of Plasmodium falciparum-infected erythrocytes. Rodex Report 8:300–303CrossRefGoogle Scholar
  51. Weatherall DJ, Miller LH, Barruch DI, Marsh K, Doumbo OK, Casals-Pasual C, Roberts DJ (2002) Malaria and red cell in “Hematology: ASH education programme book” 35:1–25Google Scholar
  52. Wickramasinghe SN, Abdalla SH (2000) Blood and bone marrow changes in malaria. Bailliere’s Best Pract Res Clin Haematol 13(2):277–299 CrossRefGoogle Scholar
  53. Wickramasinghe SN, Looareesuwan S, Nagachinta B, White NJ (1989) Dyserythropoiesis and ineffective erythropoiesis in Plasmodium vivax malaria. Br J Haemtol 72:91–99Google Scholar
  54. Woodruff AW, Ansdell VE, Pettitt LE (1979) Causes of anemia in malaria. Lancet 1:1055–1059PubMedCrossRefGoogle Scholar
  55. Xie YW, Wolin MS (1996) Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/ reoxygenation. Circulation 94:2580–2586PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Institute of Immunohaematology (ICMR)MumbaiIndia
  2. 2.Department of MedicineKing Edward Memorial Hospital & Seth G.S. Medical CollegeMumbaiIndia

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