Volume 71, Issue 2_suppl
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Increasing resistance of malaria to antimalarial drugs is posing a major threat to the global effort to “Roll Back Malaria”. Chloroquine and sulfadoxine-pyrimethamine (SP) are being rendered increasingly ineffective, resulting in increasing morbidity, mortality, and economic and social costs. One strategy advocated for delaying the development of resistance to the remaining armory of effective drugs is the wide-scale deployment of artemisinin-based combination therapy. However, the cost of these combinations are higher than most of the currently used monotherapies and alternative non-artemisinin-based combinations. In addition, uncertainty about the actual impact in real-life settings has made them a controversial choice for first-line treatment. The difficulties in measuring the burden of drug resistance and predicting the impact of strategies aimed at its reduction are outlined, and a mathematical model is introduced that is being designed to address these issues and to clarify policy options.


Article metrics loading...

Loading full text...

Full text loading...



  1. Marsh K, 1998. Malaria disaster in Africa. Lancet 352 : 924.
  2. White NJ, Nosten F, Looareesuwan S, Watkins WM, Marsh K, Snow RW, Kokwaro G, Ouma J, Hien TT, Molyneux ME, Taylor TE, Newbold CI, Ruebush TK, Danis M, Greenwood BM, Anderson RM, Olliaro P, 1999. Averting a malaria disaster. Lancet 353 : 1965–1967.
  3. Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B, 2003. Antifolate anti-malarial resistance in southeast Africa: a population-based analysis. Lancet 361 : 1174–1181.
  4. Takechi M, Matsuo M, Ziba C, MacHeso A, Butao D, Zungu IL, Chakanika I, Bustos MD, 2001. Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine-pyremethamine and other antimalarial drugs in Malawian children. Trop Med Int Health 6 : 429–434.
  5. World Health Organization, 2001. Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation. Geneva: World Health Organization. WHO/CDS/RBM/2001.35.
  6. Fevre EM, Barnish G, 1999. Malaria-treatment policies: when and how should they be changed? Ann Trop Med Parasitol 93 : 549–560.
  7. Goodman CA, Coleman PG, Mills AJ, 1999. Cost-effectiveness of malaria control in sub-Saharan Africa. Lancet 354 : 378–385.
  8. Bloland PB, Ettling M, 1999. Making malaria-treatment policy in the face of drug resistance. Ann Trop Med Parasitol 93 : 5–23.
  9. Rauner MS, 2002. Using simulation for AIDS policy modeling: benefits for HIV/AIDS prevention policy makers in Vienna, Austria. Health Care Manag Sci 5 : 121–134.
  10. Weinstein MC, Toy EL, Sandberg EA, Neumann PJ, Evans JS, Kuntz KM, Graham JD, Hammitt JK, 2001. Modeling for health care and other policy decisions: uses, roles, and validity. Value Health 4 : 348–361.
  11. Baltussen R, Leidl R, Ament A, 1999. Real world designs in economic evaluation. Bridging the gap between clinical research and policy-making. Pharmacoeconomics 16 : 449–458.
  12. Brennan A, Akehurst R, 2000. Modelling in health economic evaluation. What is its place? What is its value? Pharmacoeconomics 17 : 445–459.
  13. Snow RW, Craig M, Deichmann U, Marsh K, 1999. Estimating mortality, morbidity and disability due to malaria among Africa’s non-pregnant population. Bull World Health Organ 77 : 624–640.
  14. Guyatt HL, Snow RW, 2001. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 64 : 36–44.
  15. Steketee RW, Nahlen BL, Parise ME, Menendez C, 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 64 : 28–35.
  16. Holding PA, Snow RW, 2001. Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. Am J Trop Med Hyg 64 : 68–75.
  17. Murphy SC, Breman JG, 2001. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64 : 57–67.
  18. Chima RI, Goodman CA, Mills A, 2003. The economic impact of malaria in Africa: a critical review of the evidence. Health Policy 63 : 17–36.
  19. Sachs J, Malaney P, 2002. The economic and social burden of malaria. Nature 415 : 680–685.
  20. Phillips M, Phillips-Howard PA, 1996. Economic implications of resistance to antimalarial drugs. Pharmacoeconomics 10 : 225–238.
  21. Snow RW, Trape JF, Marsh K, 2001. The past, present and future of childhood malaria mortality in Africa. Trends Parasitol 17 : 593–597.
  22. Trape JF, 2001. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64 : 12–17.
  23. Goodman CA, Coleman PG, Mills A, 2000. Economic Analysis of Malaria Control in Sub-Saharan Africa. Geneva: World Health Organization. Global Forum for Health Research.
  24. Hastings IM, 2001. Modelling parasite drug resistance: lessons for management and control strategies. Trop Med Int Health 6 : 883–890.
  25. Breman JG, 2001. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am J Trop Med Hyg 64 : 1–11.
  26. McCombie SC, 1996. Treatment seeking for malaria: a review of recent research. Soc Sci Med 43 : 933–945.
  27. Hastings IM, 2001. Monitoring antimalarial drug resistance within National Malaria Control Programmes: the EANMAT experience. 2001. Trop Med Int Health 6 : 891–898.
  28. Bloland PB, Kazembe PN, Oloo AJ, Himonga B, Barat LM, Ruebush TK, 1998. Chloroquine in Africa: critical assessment and recommendations for monitoring and evaluating chloroquine therapy efficacy in sub-Saharan Africa. Trop Med Int Health 3 : 543–552.
  29. World Health Organization, 2001. Assessment of Therapeutic Efficacy of Antimalarial Drugs for Uncomplicated Falciparum Malaria. Geneva: World Health Organization. WHO Guideline 2001 Draft.
  30. White NJ, 2002. The assessment of antimalarial drug efficacy. Trends Parasitol 18 : 458–464.
  31. Enserink M, 2000. Malaria researchers wait for industry to join fight. Science 287 : 1956–1958.
  32. Ridley RG, 2002. Introduction. Antimalarial drug resistance: ramifications, explanations and challenges. Microbes Infect 4 : 155–156.
  33. Wellems TE, Plowe CV, 2001. Chloroquine-resistant malaria. J Infect Dis 184 : 770–776.
  34. Peters JM, Chen N, Gatton M, Korsinczky M, Fowler EV, Manzetti S, Saul A, Cheng Q, 2002. Mutations in cytochrome b resulting in atovaquone resistance are associated with loss of fitness in Plasmodium falciparum. Antimicrob Agents Chemother 46 : 2435–2441.
  35. Hastings IM, Watkins WM, White NJ, 2002. The evolution of drug-resistant malaria: the role of drug elimination half-life. Philos Trans R Soc Lond B Biol Sci 357 : 505–519.
  36. White N, 1999. Antimalarial drug resistance and combination chemotherapy. Philos Trans R Soc Lond B Biol Sci 354 : 739–749.
  37. Price RN, Nosten F, Luxemburger C, ter Kuile FO, Paiphun L, Chongsuphajaisiddhi T, White NJ, 1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet 347 : 1654–1658.
  38. Nosten F, Luxemburger C, ter Kuile FO, Woodrow C, Eh JP, Chongsuphajaisiddhi T, White NJ, 1994. Treatment of multi-drug-resistant Plasmodium falciparum malaria with 3-day arte-sunate-mefloquine combination. J Infect Dis 170 : 971–977.
  39. Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White NJ, 2000. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet 356 : 297–302.
  40. Brockman A, Price RN, van Vugt M, Heppner DG, Walsh D, Sookto P, Wimonwattrawatee T, Looareesuwan S, White NJ, Nosten F, 2000. Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. Trans R Soc Trop Med Hyg 94 : 537–544.
  41. Bloland PB, Ettling M, Meek S, 2000. Combination therapy for malaria in Africa: hype or hope? Bull World Health Organ 78 : 1378–1388.
  42. Hien TT, Dolecek C, Mai PP, Dung NT, Truong NT, Thai LH, An DTH, Thanh TT, Stepniewska K, White NJ, Farrar J, 2003. Dihydroartemising-piperaquine against multidrug-resistant Plasmodium falciparum malaria in Vietnam: randomized clinical trial. Lancet 363 : 18–22.
  43. Shwe T, Lwin M, Aung S, 1998. Influence of blister packaging on the efficacy of artesunate + mefloquine over artesunate alone in community-based treatment of non-severe falciparum malaria in Myanmar. Bull World Health Organ 76 : 35–41.
  44. Brugha R, Chandramohan D, Zwi A, 1999. Viewpoint: management of malaria-working with the private sector. Trop Med Int Health 4 : 402–406.
  45. Aron JL, 1982. Malaria epidemiology and detectability. Trans R Soc Trop Med Hyg 76 : 595–601.
  46. Aron JL, 1988. Mathematical modelling of immunity to malaria. Math Biosci 90 : 385–396.
  47. Cross AP, Singer B, 1991. Modelling the development of resistance of Plasmodium falciparum to anti-malarial drugs. Trans R Soc Trop Med Hyg 85 : 349–355.
  48. Curtis CF, Otoo LN, 1986. A simple model of the build-up of resistance to mixtures of anti-malarial drugs. Trans R Soc Trop Med Hyg 80 : 889–892.
  49. Dietz K, Molineaux L, Thomas A, 1974. A malaria model tested in the African savannah. Bull World Health Organ 50 : 347–357.
  50. Fine PEM, 1975. Superinfection—a problem in formulating a problem. Trop Dis Bull 72 : 475–486.
  51. Hastings IM, D’Alessandro U, 2000. Modelling a predictable disaster: the rise and spread of drug-resistant malaria. Parasitol Today 16 : 340–347.
  52. MacDonald G, 1950. The analysis of infection rates in diseases in which superinfection occurs. Trop Dis Bull 47 : 907–914.
  53. Ross R, 1911. The Prevention of Malaria. Second edition. London: Murray.
  54. Buckling A, Read AF, 2001. The effect of partial host immunity on the transmission of malaria parasites. Proc R Soc Lond B Biol Sci 268 : 2325–2330.
  55. Bloland PB, Boriga DA, Ruebush TK, McCormick JB, Roberts JM, Oloo AJ, Hawley W, Lal A, Nahlen B, Campbell CC, 1999. Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. Am J Trop Med Hyg 60 : 641–648.
  56. Djimde AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 : 558–563.
  57. Mayxay M, Chotivanich K, Pukrittayakamee S, Newton P, Looareesuwan S, White NJ, 2001. Contribution of humoral immunity to the therapeutic response in falciparum malaria. Am J Trop Med Hyg 65 : 918–923.
  58. White NJ, 1998. Why is it that antimalarial drug treatments do not always work? Ann Trop Med Parasitol 92 : 449–458.
  59. Baird JK, 1995. Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. Parasitol Today 11 : 105–111.
  60. Taylor-Robinson AW, 2002. A model of development of acquired immunity to malaria in humans living under endemic conditions. Med Hypotheses 58 : 148–156.

Data & Media loading...

  • Received : 28 Aug 2003
  • Accepted : 27 Feb 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