Volume 72, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Malaria infection leads to the formation of circulating immune complexes. However, it is unclear whether these complexes play a role in the pathogenesis of complicated malaria. This study aimed at determining if there are differences in the levels of immune complexes between children with severe malaria-associated anemia and cerebral malaria and between each of these two groups and their respective uncomplicated symptomatic malaria or healthy asymptomatic controls. Children with severe malaria-associated anemia and cerebral malaria had significantly higher immune complex levels than their respective controls, but there were no significant differences in the levels between the two severe malaria groups. In addition, there was an inverse relationship between the hemoglobin levels and immune complex levels in the severe anemia controls, suggesting that immune complexes may contribute to erythrocyte destruction in these children. These results suggest that immune complex levels alone cannot account for the differences in the distinct clinical presentation between severe malaria-associated anemia and cerebral malaria.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. World Health Organization, 2002.World Health Report. Geneva: WHO.
  2. Breman JG, Campbell CC, 1988. Combating severe malaria in African children. Bull World Health Organ 66 : 611–620. [Google Scholar]
  3. Clark IA, Cowden WB, 1992. Roles of TNF in malaria and other parasitic infections. Immunol Ser 56 : 365–407. [Google Scholar]
  4. Kwiatkowski D, Hill AV, Sambou I, Twumasi P, Castracane J, Manogue KR, Cerami A, Brewster DR, Greenwood BM, 1990. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336 : 1201–1204. [Google Scholar]
  5. Perlmann P, Perlmann H, Berzins K, Troye-Blomberg M, 1998. Selected problems of malaria blood stage immunity. Tokai J Exp Clin Med 23 : 55–62. [Google Scholar]
  6. Blackman MJ, Holder AA, 1992. Secondary processing of the Plasmodium falciparum merozoite surface protein-1 (MSP1) by a calcium-dependent membrane-bound serine protease: shedding of MSP133 as a noncovalently associated complex with other fragments of the MSP1. Mol Biochem Parasitol 50 : 307–315. [Google Scholar]
  7. Camus D, Hadley TJ, 1985. A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science 230 : 553–556. [Google Scholar]
  8. McGregor IA, Turner MW, Williams K, Hall P, 1968. Soluble antigens in the blood of African patients with severe Plasmodium falciparum malaria. Lancet 1 : 881–884. [Google Scholar]
  9. Mohammed I, 1982. The role of immune complexes in human malaria and some of its complications. J Infect 4 : 97–104. [Google Scholar]
  10. Jarvis JN, Wang W, Moore HT, Zhao L, Xu C, 1997. In vitro induction of proinflammatory cytokine secretion by juvenile rheumatoid arthritis synovial fluid immune complexes. Arthritis Rheum 40 : 2039–2046. [Google Scholar]
  11. Virella G, Munoz JF, Galbraith GM, Gissinger C, Chassereau C, Lopes-Virella MF, 1995. Activation of human monocyte-derived macrophages by immune complexes containing low-density lipoprotein. Clin Immunol Immunopathol 75 : 179–189. [Google Scholar]
  12. Abdalla SH, Kasili FG, Weatherall DJ, 1983. The coombs direct antiglobulin test in Kenyans. Trans R Soc Trop Med Hyg 77 : 99–102. [Google Scholar]
  13. Adam C, Geniteau M, Gougerot-Pocidalo M, Verroust P, Lebras J, Gibert C, Morel-Maroger L, 1981. Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria. Infect Immun 31 : 530–535. [Google Scholar]
  14. Alder JD, Kreier JP, 1989. Immune complexes in serum of rats during infection with Plasmodium berghei. Parasitol Res 76 : 119–126. [Google Scholar]
  15. Boonpucknavig S, Udomsangpetch R, 1983. Immunological aspects in Plasmodium falciparum infection. J Clin Lab Immunol 12 : 37–40. [Google Scholar]
  16. Greenwood BM, Stratton D, Williamson WA, Mohammed I, 1978. A study of the role of immunological factors in the pathogenesis of the anaemia of acute malaria. Trans R Soc Trop Med Hyg 72 : 378–385. [Google Scholar]
  17. Gupta N, Sehgal R, Mahajan RC, Banerjee AK, Ganguly NK, 1988. Role of immune complexes in cerebral malaria. Pathology 20 : 373–376. [Google Scholar]
  18. Houba V, Lambert PH, Voller A, Soyanwo MA, 1976. Clinical and experimental investigation of immune complexes in malaria. Clin Immunol Immunopathol 6 : 1–12. [Google Scholar]
  19. Jhaveri KN, Ghosh K, Mohanty D, Parmar BD, Surati RR, Camoens HM, Joshi SH, Iyer YS, Desai A, Badakere SS, 1997. Autoantibodies, immunoglobulins, complement and circulating immune complexes in acute malaria. Natl Med J India 10 : 5–7. [Google Scholar]
  20. June CH, Contreras CE, Perrin LH, Lambert PH, Miescher PA, 1979. Circulating and tissue-bound immune complex formation in murine malaria. J Immunol 122 : 2154–2161. [Google Scholar]
  21. Kusuhara Y, Maeno Y, Nagase K, Sakai K, Nakazawa S, Kanbara H, Taniguchi K, Nakabayashi T, 2000. Isolation of antigen from the circulating immune complex in mice infected with Plasmodium berghei. Int J Parasitol 30 : 609–615. [Google Scholar]
  22. Tyagi P, Biswas S, 1999. Naturally occurring plasmodia-specific circulating immune complexes in individuals of malaria endemic areas in India. Indian J Malariol 36 : 12–18. [Google Scholar]
  23. Stoute JA, Odindo AO, Owuor BO, Mibei EK, Opollo MO, Waitumbi JN, 2003. Loss of red blood cell complement regulatory proteins and increased levels of circulating immune complexes are associated with severe malarial anemia. J Infect Dis 187 : 522–525. [Google Scholar]
  24. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71 : 441–459. [Google Scholar]
  25. Marsh K, Snow RW, 1999. Malaria transmission and morbidity. Parassitologia 41 : 241–246. [Google Scholar]
  26. el Shoura SM, 1994. Falciparum malaria: IX. Bone marrow changes mimicking malignant histiocytosis. A case report. Parasite 1 : 287. [Google Scholar]
  27. Houba V, 1975. The relation between immunofluorescence patterns of glomerular deposits and subclasses of IgG in patients with nephropathies associated with malaria. Ann N Y Acad Sci 254 : 332–333. [Google Scholar]
  28. Pascual M, Schifferli JA, 1992. The binding of immune complexes by the erythrocyte complement receptor 1 (CR1). Immunopharmacology 24 : 101–106. [Google Scholar]
  29. Waitumbi JN, Opollo MO, Muga RO, Misore AO, Stoute JA, 2000. Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemia. Blood 95 : 1481–1486. [Google Scholar]
  30. Waitumbi JN, Donvito B, Kisserli A, Cohen JH, Stoute JA, 2004. Age-related Changes in Red Blood Cell Complement Regulatory Proteins and the Susceptibility to Severe Malaria. J Infect Dis 190 : 1183–1191. [Google Scholar]
  31. Rowe JA, Moulds JM, Newbold CI, Miller LH, 1997. P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature 388 : 292–295. [Google Scholar]
  32. Rowe JA, Rogerson SJ, Raza A, Moulds JM, Kazatchkine MD, Marsh K, Newbold CI, Atkinson JP, Miller LH, 2000. Mapping of the region of complement receptor (CR) 1 required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates. J Immunol 165 : 6341–6346. [Google Scholar]
  33. Holguin MH, Martin CB, Bernshaw NJ, Parker CJ, 1992. Analysis of the effects of activation of the alternative pathway of complement on erythrocytes with an isolated deficiency of decay accelerating factor. J Immunol 148 : 498–502. [Google Scholar]
  34. Miwa T, Zhou L, Hilliard B, Molina H, Song WC, 2002. Crry, but not CD59 and DAF, is indispensable for murine erythrocyte protection in vivo from spontaneous complement attack. Blood 99 : 3707–3716. [Google Scholar]
  35. Sun X, Funk CD, Deng C, Sahu A, Lambris JD, Song WC, 1999. Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting. Proc Natl Acad Sci U S A 96 : 628–633. [Google Scholar]
  36. Chou YK, Sherwood T, Virella G, 1985. Erythrocyte-bound immune complexes trigger the release of interleukin-1 from human monocytes. Cell Immunol 91 : 308–314. [Google Scholar]
  37. Clark IA, Rockett KA, Burgner D, 2003. Genes, nitric oxide and malaria in African children. Trends Parasitol 19 : 335–337. [Google Scholar]
  38. Kwiatkowski D, 1993. TNF-inducing malaria toxin: a sheep in wolf’s clothing? Ann Trop Med Parasitol 87 : 613–616. [Google Scholar]

Data & Media loading...

  • Received : 09 May 2004
  • Accepted : 07 Jul 2004

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error