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


Most mathematical models for acquired immunity to consider effects of immunity on duration of infection and infectiousness, but do not consider the most evident effect of immunity, which is to reduce parasite densities. Few attempts have been made to fit such models to field data. We propose a stochastic simulation model to predict the distributions of parasite densities in endemic areas, in which acquired immunity acts by reducing parasite densities. We have fitted this model to age-specific prevalence and geometric mean densities from settings in Ghana, Nigeria, and Tanzania. The model appears to reproduce reasonably well the parasitologic patterns seen in malariologic surveys in endemic areas and is appropriate for predicting the impact of interventions such as vaccination in the context of continual exposure to .


Article metrics loading...

Loading full text...

Full text loading...



  1. Molineaux L, Muir DA, Spencer HC, Wernsdorfer WH, 1988 The epidemiology of malaria and its measurement. Wernsdorfer WH, Mc Gregor I, eds. Malaria, Principles and Practice of Malariology. Edinburgh: Churchill Livingstone, 999–1089.
  2. Alonso PL, Sacarlal J, Aponte J, 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, Demoitie MA, Dubovsky F, Menendez 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.
  3. Molineaux L, Diebner HH, Eichner M, Collins WE, Jeffery GM, Dietz K, 2001. Plasmodium falciparum parasitaemia described by a new mathematical model. Parasitology 122 : 379–391.
  4. 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.
  5. Dietz K, Molineaux L, Thomas A, 1974. A malaria model tested in the African savannah. Bull World Health Organ 50 : 347–357.
  6. Aron JL, 1988. Mathematical-modeling of immunity to malaria. Math Biosci 90 : 385–396.
  7. Struchiner CJ, Halloran ME, Spielman A, 1989. Modeling malaria vaccines. I: New uses for old ideas. Math Biosci 94 : 87–113.
  8. Elderkin RH, Berkowitz DP, Farris FA, Gunn CF, Hickernell FJ, Kass SN, Mansfield FI, Taranto RG, 1977. On the steady state of an age-dependent model for malaria. Lakschmikantham V, ed. Nonlinear Systems and Applications. New York: Academic Press, 491–512.
  9. Molineaux L, Gramiccia G, 1980. The Garki Project. Geneva: World Health Organization.
  10. Macdonald G, 1957. The Epidemiology and Control of Malaria. London: Oxford, United Kingdom: Oxford University Press.
  11. Sama W, Killeen G, Smith T, 2004. Estimating the duration of Plasmodium falciparum infection from trials of indoor residual spraying. Am J Trop Med Hyg 70 : 625–634.
  12. Gupta S, Day KP, 1994. A theoretical framework for the immunoepidemiology of Plasmodium falciparum malaria. Parasite Immunol 16 : 361–370.
  13. Smith T, Beck H-P, Kitua A, Mwankusye S, Felger I, Fraser-Hurt N, Irion A, Alonso PL, Teuscher T, Tanner M, 1999. Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity. Trans R Soc Trop Med Hyg 93 (Suppl 1): 15–20.
  14. Smith T, Vounatsou P, 2003. Estimation of infection and recovery rates for highly polymorphic parasites when detectability is imperfect, using hidden Markov models. Stat Med 22 : 1709–1724.
  15. Collins WE, Jeffery GM, 1999. A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity. Am J Trop Med Hyg 61 : 36–43.
  16. Smith T, Maire N, Dietz K, Killeen GF, Vounatsou P, Molineaux L, Tanner M, 2006. Relationships between the entomologic inoculation rate and the force of infection for Plasmodium falciparum malaria. Am J Trop Med Hyg 75 (Suppl 2) 11–18.
  17. Kitua A, Smith T, Alonso PL, Masanja H, Urassa H, Menendez C, Kimario J, Tanner M, 1996. Plasmodium falciparum malaria in the first year of life in an area of intense and perennial transmission. Trop Med Int Health 1 : 475–484.
  18. Vounatsou P, Smith T, Kitua A, Alonso PL, Tanner M, 2000. Apparent tolerance of Plasmodium falciparum in infants in a highly endemic area. Parasitology 120 : 1–9.
  19. Shute GT, 1988. The microscopic diagnosis of malaria. Wernsdorfer WH, Mc Gregor I, eds. Malaria, Principles and Practice of Malariology. Edinburgh: Churchill Livingstone, 781–784.
  20. Earle WC, Perez M, 1932. Enumeration of parasites in the blood of malarial patients. J Lab Clin Med 17 : 1124–1132.
  21. Glynn JR, Bradley DJ, 1995. Inoculum size, incubation period and severity of malaria. Analysis of data from malaria therapy records. Parasitology 110 : 7–19.
  22. Ross A, Smith T, 2006. The effect of malaria transmission intensity on neonatal mortality in endemic areas. Am J Trop Med Hyg 75 (Suppl 2): 74–81.
  23. Charlwood JD, Smith T, Lyimo E, Kitua A, Masanja H, Booth M, Alonso PL, Tanner M, 1998. Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines. Am J Trop Med Hyg 59 : 243–251.
  24. Smith T, Charlwood JD, Kihonda J, Mwankusye S, Billingsley P, Meuwissen J, Lyimo E, Takken W, Teuscher T, Tanner M, 1993. Absence of seasonal variation in malaria parasitaemia in an area of intense seasonal transmission. Acta Trop 54 : 55–72.
  25. Beier JC, Oster CN, Onyango FK, Bales JD, Sherwood JA, Perkins PV, Chumo DK, Koech DV, Whitmire RE, Roberts CR, 1994. Plasmodium falciparum incidence relative to entomologic inoculation rates at a site proposed for testing malaria vaccines in western Kenya. Am J Trop Med Hyg 50 : 529–536.
  26. Kirkpatrick S, Gelatt CD Jr, Vecchi MP, 1983. Optimization by simulated annealing. Science 220 : 671–680.
  27. Press WH, Flannery BP, Teukolsky SA, Vetterling WT, 1988. Numerical Recipes in C: the Art of Scientific Computing. Cambridge, United Kingdom: Cambridge University Press.
  28. Beier JC, Killeen G, Githure JI, 1999. Short report: entomologic inoculation rates and Plasmodium falciparum malaria prevalence in Africa. Am J Trop Med Hyg 61 : 109–113.
  29. Babiker H, Ranford-Cartwright L, Currie D, Charlwood JD, Billingsley P, Teuscher T, Walliker D, 1994. Random mating in a natural population of the malaria parasite Plasmodium falciparum. Parasitology 109 : 413–421.
  30. Paul RE, Packer MJ, Walmsley M, Lagog M, Ranford-Cartwright L, Paru R, Day KP, 1995. Mating patterns in malaria parasite populations of Papua New Guinea. Science 269 : 1709–1711.
  31. Owusu-Agyei S, Smith T, Beck H-P, Amenga-Etego L, Felger I, 2002. Molecular epidemiology of Plasmodium falciparum infections among asymptomatic inhabitants of a holoendemic malarious area in northern Ghana. Trop Med Int Health 7 : 421–428.
  32. Smith T, Killeen G, Maire N, Ross A, Molineaux L, Tediosi F, Hutton G, Utzinger J, Dietz K, Tanner M, 2006. Mathematical modeling of the impact of malaria vaccines on the clinical epidemiology and natural history of Plasmodium falciparum malaria. Am J Trop Med Hyg 75 (Suppl 2): 1–10.
  33. Kinyanjui SM, Bull P, Newbold C, Marsh K, 2003. Kinetics of antibody responses to Plasmodium falciparum-infected erythrocyte variant surface antigens. J Infect Dis 187 : 667–674.
  34. Deloron P, Chougnet C, 1992. Is immunity to malaria really short-lived? Parasitol Today 8 : 375–378.
  35. Anderson RM, May RM, 1991. Infectious Diseases of Humans: Dynamics and Control. Oxford, United Kingdom: Oxford University Press.
  36. Woolhouse ME, 1998. Patterns in parasite epidemiology: the peak shift. Parasitol Today 14 : 428–434.
  37. Greenwood BM, Groenendaal F, Bradley AK, Greenwood AM, Shenton F, Tulloch S, Hayes R, 1987. Ethnic differences in the prevalence of splenomegaly and malaria in The Gambia. Ann Trop Med Parasitol 81 : 345–354.
  38. Modiano D, Petrarca V, Sirima BS, Nebie I, Diallo D, Esposito F, Coluzzi M, 1996. Different response to Plasmodium falciparum malaria in west African sympatric ethnic groups. Proc Natl Acad Sci U S A 93 : 13206–13211.
  39. World Health Organization, 1993. A Global Strategy for Malaria Control. Geneva, World Health Organization.
  40. Binka F, Kubaje A, Adjuik M, Williams LA, Lengeler C, Maude G, Armah GE, Kajihara B, Adiamah JH, Smith PG, 1996. Impact of permethrin impregnated bednets on child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial. Trop Med Int Health 1 : 147–154.
  41. Binka F, Nazzar A, Phillips JF, 1995. The Navrongo Community Health and Family Planning Project. Stud Fam Plann 26 : 121–139.
  42. Recker M, Nee S, Bull P, Kinyanjui S, Marsh K, Newbold C, Gupta S, 2004. Transient cross-reactive immune responses can orchestrate antigenic variation in malaria. Nature 429 : 555–558.
  43. United Nations, 2002. Demographic Yearbook 2000. New York: United Nations.
  44. INDEPTH Network, 2002. Population, Health and Survival at INDEPTH Sites. Ottawa, Ontario, Canada: International Development Research Centre.
  45. Alonso PL, Smith T, Schellenberg JR, Masanja H, Mwankusye S, Urassa H, Bastos de Azevedo I, Chongela J, Kobero S, Menendez C, 1994. Randomised trial of efficacy of SPf66 vaccine against Plasmodium falciparum malaria in children in southern Tanzania. Lancet 344 : 1175–1181.

Data & Media loading...

  • Received : 18 Sep 2005
  • Accepted : 07 Feb 2006

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