Volume 69, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Experimental systems that model some of the complex interactions between parasite and host can be extremely valuable in identifying and developing new prophylactics and therapeutics against human diseases. Because primates have similar immune systems to humans, we have characterized a baboon model for understanding host response to . Ten intact olive baboons () of either sex were experimentally infected with H strain erythrocytic parasites. The infection in these baboons was either acute or chronic. Animals with acute infection developed multiple system organ dysfunction and cerebral involvement. In chronically infected animals, only the spleen was moderately enlarged. The parasitemia profile in baboons and rhesus monkeys was comparable. However, some clinical symptoms of the baboons and -infected humans were similar. These studies demonstrate for the first time that is a suitable host for for studying clinical symptoms and pathology.


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  1. Bontrop RE, 2001. Non-human primates: essential partners in biomedical research. Immunol Rev 183 : 5–9. [Google Scholar]
  2. Kennedy RC, Shearer MH, Hildebrand W, 1997. Nonhuman primate models to evaluate vaccine safety and immunogenicity. Vaccine 15 : 903–908. [Google Scholar]
  3. 1988. Role of non-human primates in malaria vaccine development: memorandum from a WHO meeting. Bull World Health Organ 66 : 719–728. [Google Scholar]
  4. King FA, Yarbrough CJ, Anderson DC, Gordon TP, Gould KG, 1988. Primates. Science 240 : 1475–1482. [Google Scholar]
  5. Stowers AW, Miller LH, 2001. Are trials in New World monkeys on the critical path for blood-stage malaria vaccine development? Trends Parasitol 17 : 415–419. [Google Scholar]
  6. Butcher GA, 1996. Models for malaria: nature knows best. Parasitol Today 12 : 378–382. [Google Scholar]
  7. Wengelnik K, Vidal V, Ancelin ML, Cathiard AM, Morgat JL, Kocken CH, Calas M, Herrera S, Thomas AW, Vial HJ, 2002. A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science 295 : 1311–1314. [Google Scholar]
  8. Garnham PCC, 1966. Malaria Parasites and Other Haemosporidia. Oxford: Blackwell Scientific Publications.
  9. Cox FEG, 1988. Malaria: Principles and Practice of Malariology. Edinburgh: Churchill Livingstone 1988, 1503–1543.
  10. Escalante AA, Freeland DE, Collins WE, Lal AA, 1998. The evolution of primate malaria parasites based on the gene encoding cytochrome b from the linear mitochondrial genome. Proc Natl Acad Sci USA 95 : 8124–8129. [Google Scholar]
  11. Escalante AA, Ayala FJ, 1994. Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences. Proc Natl Acad Sci U S A 91 : 11373–11377. [Google Scholar]
  12. Coatney GR, Collins WE, Warren M, Contacos PG, 1971. The Primate Malarias. Bethesda, MD: U.S. Department of Health, Education and Welfare, National Institutes of Health.
  13. Deans JA, Thomas AW, Alderson T, Cohen S, 1984. Biosynthesis of a putative protective Plasmodium knowlesi merozoite antigen. Mol Biochem Parasitol 11 : 189–204. [Google Scholar]
  14. Kocken CH, Dubbeld MA, Van Der Wel A, Pronk JT, Waters AP, Langermans JA, Thomas AW, 1999. High-level expression of Plasmodium vivax apical membrane antigen 1 (AMA-1) in Pichia pastoris: strong immunogenicity in Macaca mulatta immunized with P. vivax AMA-1 and adjuvant SBAS2. Infect Immun 67 : 43–49. [Google Scholar]
  15. Deans JA, Knight AM, Jean WC, Waters AP, Cohen S, Mitchell GH, 1988. Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen. Parasite Immunol 10 : 535–552. [Google Scholar]
  16. Rogers WO, Baird JK, Kumar A, Tine JA, Weiss W, Aguiar JC, Gowda K, Gwadz R, Kumar S, Gold M, Hoffman SL, 2001. Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques. Infect Immun 69 : 5565–5572. [Google Scholar]
  17. Gwadz RW, Koontz LC, 1984. Plasmodium knowlesi: persistence of transmission blocking immunity in monkeys immunized with gamete antigens. Infect Immun 44 : 137–140. [Google Scholar]
  18. Collins WE, Contacos PG, Chin W, 1978. Infection of the squirrel monkey Saimiri sciureus, with Plasmodium knowlesi. Trans R Soc Trop Med Hyg 72 : 662–663. [Google Scholar]
  19. Dutta GP, Singh PP, Banyal HS, 1978. Macaca assamensis as a new host for experimental Plasmodium knowlesi infection. Indian J Med Res 68 : 923–926. [Google Scholar]
  20. Dutta GP, Singh PP, Saibaba P, 1981. Presbytis entellus as a new host for experimental Plasmodium knowlesi infection. Indian J Med Res 73 (Suppl) : 63–66. [Google Scholar]
  21. Dutta GP, Banyal HS, Kamboj KK, 1982. Bonnet monkey (Macaca radiata) as a suitable host for chronic non-fatal Plasmodium knowlesi infection. Indian J Med Res 76 : 134–140. [Google Scholar]
  22. Langhorne J, Cohen S, 1979. Plasmodium knowlesi in the marmoset (Callithrix jacchus). Parasitology 78 : 67–76. [Google Scholar]
  23. Chin W, Contacos PG, Coatney GR, Kimball HR, 1965. A naturally acquired quotidian-type malaria in man transferable to monkey. Science 149 : 865. [Google Scholar]
  24. Escalante AA, Barrio E, Ayala FJ, 1995. Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene. Mol Biol Evol 12 : 616–626. [Google Scholar]
  25. van der Wel AM, Tomas AM, Kocken CH, Malhotra P, Janse CJ, Waters AP, Thomas AW, 1997. Transfection of the primate malaria parasite Plasmodium knowlesi using entirely heterologous constructs. J Exp Med 185 : 1499–1503. [Google Scholar]
  26. Kocken CH, Ozwara H, van Der Wel A, Beetsma AL, Mwenda JM, Thomas AW, 2002. Plasmodium knowlesi provides a rapid in vitro and in vivo transfection system that enables double-crossover gene knockout studies. Infect Immun 70 : 655–660. [Google Scholar]
  27. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B, 2002. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419 : 498–511. [Google Scholar]
  28. Barnwell JW, Howard RJ, Coon HG, Miller LH, 1983. Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria. Infect Immun 40 : 985–994. [Google Scholar]
  29. Pongponratn E, Riganti M, Punpoowong B, Aikawa M, 1991. Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study. Am J Trop Med Hyg 44 : 168–175. [Google Scholar]
  30. Hearn J, Rayment N, Landon DN, Katz DR, de Souza JB, 2000. Immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature. Infect Immun 68 : 5364–5376. [Google Scholar]
  31. Aikawa M, 1988. Human cerebral malaria. Am J Trop Med Hyg 39 : 3–10. [Google Scholar]
  32. Aikawa M, Iseki M, Barnwell JW, Taylor D, Oo MM, Howard RJ, 1990. The pathology of human cerebral malaria. Am J Trop Med Hyg 43 : 30–37. [Google Scholar]
  33. World Health Organization, Division of Control of Tropical Diseases, 1990. Severe and complicated malaria. Trans R Soc Trop Med Hyg 84 (Suppl 2) : 1–65. [Google Scholar]
  34. Aikawa M, Brown AE, Smith CD, Tegoshi T, Howard RJ, Hasler TH, Ito Y, Collins WE, Webster HK, 1992. Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral malaria. Mem Inst Oswaldo Cruz 87 (Suppl 3) : 443–447. [Google Scholar]
  35. Kawai S, Aikawa M, Kano S, Suzuki M, 1993. A primate model for severe human malaria with cerebral involvement: Plasmodium coatneyi-infected Macaca fuscata. Am J Trop Med Hyg 48 : 630–636. [Google Scholar]
  36. Mahdi AA, Ahmad S, 1991. Pathogenesis of cerebral malaria. Indian J Exp Biol 29 : 267–271. [Google Scholar]
  37. Ibiwoye MO, Howard CV, Sibbons P, Hasan M, van Velzen D, 1993. Cerebral malaria in the rhesus monkey (Macaca mulatta): observations on host pathology. J Comp Pathol 108 : 303–310. [Google Scholar]
  38. Barnwell JW, Howard RJ, Miller LH, 1982. Altered expression of Plasmodium knowlesi variant antigen on the erythrocyte membrane in splenectomized rhesus monkeys. J Immunol 128 : 224–226. [Google Scholar]
  39. Miller LH, Fremount HN, Luse SA, 1971. Deep vascular schizogony of Plasmodium knowlesi in Macaca mulatta. Distribution in organs and ultrastructure of parasitized red cells. Am J Trop Med Hyg 20 : 816–824. [Google Scholar]
  40. al-Khedery B, Barnwell JW, Galinski MR, 1999. Antigenic variation in malaria: a 3′ genomic alteration associated with the expression of a P. knowlesi variant antigen. Mol Cell 3 : 131–141. [Google Scholar]
  41. Abildgaard C, Harrison J, DeNardo S, Spangler W, Gribble D, 1975. Simian Plasmodium knowlesi malaria: studies of coagulation and pathology. Am J Trop Med Hyg 24 : 764–768. [Google Scholar]
  42. Tatke M, Malik GB, 1990. Pulmonary pathology in severe malaria infection in health and protein deprivation. J Trop Med Hyg 93 : 377–382. [Google Scholar]
  43. Spangler WL, Gribble D, Abildgaard C, Harrison J, 1978. Plasmodium knowlesi malaria in the rhesus monkey. Vet Pathol 15 : 83–91. [Google Scholar]
  44. Rosen S, Hano JE, Barry KG, 1968. Malarial nephropathy in the rhesus monkey. Arch Pathol 85 : 36–44. [Google Scholar]
  45. Schmidt LH, Fradkin R, Harrison J, Rossan RN, 1977. Differences in the virulence of Plasmodium knowlesi for Macaca irus (fascicularis) of Philippine and Malayan origins. Am J Trop Med Hyg 26 : 612–622. [Google Scholar]
  46. Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M, 1999. The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis 180 : 1288–1297. [Google Scholar]
  47. Hill AV, 1998. The immunogenetics of human infectious diseases. Annu Rev Immunol 16 : 593–617. [Google Scholar]
  48. Tubbs H, 1980. Endotoxin in human and murine malaria. Trans R Soc Trop Med Hyg 74 : 121–123. [Google Scholar]
  49. Jakobsen PH, Baek L, Jepsen S, 1988. Demonstration of soluble Plasmodium falciparum antigens reactive with Limulus amoebocyte lysate and polymyxin B. Parasite Immunol 10 : 593–606. [Google Scholar]

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  • Received : 22 Aug 2002
  • Accepted : 02 Jun 2003

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