Volume 75, Issue 2_suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


We present a dynamic model of the highly pathogenic first wave of asexual parasitemia in non-immune persons. The model was successfully fitted to malaria therapy data. This required four case-specific parameters: the basic two-day multiplication factor, the time of onset of adaptive immunity, and the effective dose 50 densities for the innate and adaptive immune responses, respectively. All four parameters show large case-dependent variation that is mainly attributable to host factors. According to the model, the maximum value of the first wave is controlled mainly by the innate immune response. We used the model to explore the expected effects of vaccines targeting the parasite’s asexual blood stages on the basis of what we consider to be the biologically most plausible assumptions concerning the parameter modifications induced by vaccination. According to our simulations, the benefit of antiparasitic vaccination is strongly host dependent and vaccine efficacy at low immunogenicity is much larger against severe disease than against fever. This has implications for the early testing of the protective efficacy of a vaccine in humans.


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  1. Richie TL, Saul A, 2002. Progress and challenges for malaria vaccines. Nature 415 : 694–701.
  2. Moorthy VS, Good MF, Hill AVS, 2004. Malaria vaccine developments. Lancet 363 : 150–156.
  3. Ballou WR, Arevalo-Herrera M, Carucci D, Richie TL, Corradin G, Diggs C, Druilhe P, Giersing BK, Saul A, Heppner DG, Kester KE, Lanar DE, Lyon JL, Hill AVS, Pan W, Cohen JD, 2004. Update on the clinical development of candidate malaria vaccines. Am J Trop Med Hyg 71 (Suppl 2): 239–247.
  4. Collins WE, Jeffery GM. 1999. A retrospective examination of the patterns of recrudescence in patients infected with Plasmodium falciparum. Am J Trop Med Hyg 61 (Suppl): 44–48.
  5. Molineaux L, Diebner HH, Eichner M, Collins WE, Jeffery GM, Dietz K, 2001. Plasmodium falciparum parasitemia described by a new mathematical model. Parasitology 122 : 379–391.
  6. Collins WE, Jeffery GM. 1999. A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum: development of parasitologic and clinical immunity during primary infection. Am J Trop Med Hyg 61 (Suppl): 4–19.
  7. Earle WC, Perez M, 1932. Enumeration of parasites in the blood of malarial patients. J Lab Clin Med 17 : 1124–1130.
  8. Stevenson MM, Riley EM, 2004. Innate immunity to malaria. Nat Rev Immunol 4 : 169–180.
  9. Jeffery GM, Young MD, Burgess RW, Eyles DE, 1959. Early activity in sporozoite–induced Plasmodium falciparum infections. Ann Trop Med Parasitol 53 : 51–58.
  10. Besset DH, 2001. Object-Oriented Implementation of Numerical Methods. San Francisco: Morgan Kaufmann.
  11. Powell MJD, 1964. An efficient method for finding the minimum of a function of several variables without calculating derivatives. Comput J 7 : 155–162.
  12. Weijer C, 1999. Another Tuskegee? Am J Trop Med Hyg 61 (Suppl): 1–3.
  13. Molineaux L, Dietz K, 1999. Review of intra-host models of malaria. Parassitologia 41 : 221–231.
  14. McKenzie FE, Bossert WH, 2005. An integrated model of Plasmodium falciparum dynamic. J Theor Biol 232 : 411–426.
  15. Saul A, 1994. Testing the Vaccine. Good MF, Saul A, eds. Molecular Immunological Considerations in Malaria Vaccine Development. Boca Raton, FL: CRC Press, 245–259.
  16. Simpson JA, Aarons L, Collins WE, Jeffery GM, White JN, 2002. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124 : 247–263.
  17. Haydon DT, Matthews L, Timms R, Colegrave N, 2003. Top-down or bottom-up regulation of intra-host blood-stage malaria: do malaria parasites most resemble the dynamics of prey or predator? Proc R Soc Lond B Biol Sci 270 : 289–298.
  18. Paget-McNicol S, Gatton M, Hastings I, Saul A, 2002. The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling. Parasitology 124 : 225–235.
  19. Greenwood B, Marsh K, Snow R, 1991. Why do some African children develop severe malaria? Parasitol Today 7 : 277–281.
  20. Marsh K, 1992. Malaria - a neglected disease? Parasitology 04 : S53–S69.
  21. White NJ, Ho M, 1992. Pathophysiology of malaria. Adv Parasitol 31 : 84–175.
  22. Miller LH, Dror IB, Marsh K, Doumbo OK, 2002. The pathogenic basis of malaria. Nature 415 : 673–679.
  23. Artavanis-Tsakonas K, Tongren JE, Riley EM, 2003. The war between the malaria parasite and the immune system: immunity, immunoregulation and immunopathology. Clin Exp Immunol 133 : 145–152.
  24. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, Mandomando I, Spiessens B, Guinovart C, Espasa M, Bassat Q, Aide P, Ofori-Anyinam O, Navia MM, Corachan S, Ceuppens M, Dubois MC, Demoitié MA, Dubovsky F, Menéndez C, Tornieporth N, Ballou WR, Thompson R, Cohen J, 2004. Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364 : 1411–1420.
  25. Alonso PL, Lindsay SW, Armstrong JRM, Conteh M, Hill AG, David PH, Fegan G, De Francisco A, Hall AJ, Shenton FC, Cham K, Greenwood BM, 1991. The effect of insecticide-treated bed nets on mortality of Gambian children. Lancet 37 : 1499–1502.
  26. Molineaux L, Träuble M, Collins WE, Jeffery GM, Dietz K, 2002. Malaria therapy reinoculation data suggest individual variation of an innate immune response and independent acquisition of antiparasitic and antitoxic immunities. Trans R Soc Trop Med Hyg 96 : 1–5.
  27. Kremsner PG, Winkler S, Brandts S, Wilding E, Jenne L, Graninger W, Prada J, Bienzle U, Juillard P, Grau GE, 1995. Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production. Am J Trop Med Hyg 53 : 532–538.
  28. Mordmüller BG, Metzger WG, Juillard P, Brinkman BMN, Verweij CL, Grau GE, Kremsner PG, 1997. Tumor necrosis factor in Plasmodium falciparum malaria: high plasma level is associated with fever, but high production capacity is associated with rapid fever clearance. Eur Cytokine Netw 8 : 29–35.
  29. Perkins DJ, Kremsner PG, Schmid D, Misukonis MA, Kelly MA, Weinberg JB, 1999. Blood mononuclear cell nitric oxide production and plasma cytokine levels in healthy Gabonese children with prior mild or severe malaria. Infect Immun 67 : 4977–4981.
  30. Luty JF, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Migot-Nabias F, Deloron P, Nussenzweig RS, Kremsner PG, 1999. Interferon-γ responses are associated with resistance to reinfection with Plasmodium falciparum in young African children. J Infect Dis 179 : 980–988.
  31. Landau I, Chabaud A, 1994. Plasmodium species infecting Thamnomys rutilans: a zoological study. Adv Parasitol 33 : 49–90.

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  • Received : 18 Sep 2005
  • Accepted : 08 May 2006

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