Volume 69, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


In a randomized controlled trial, chloroquine monotherapy was compared with the combination of artesunate and chloroquine for treating uncomplicated malaria in 536 Gambian children. Chloroquine-treated children exhibited a 28-day clinical failure rate of 15% (95% confidence interval [CI] = 9.2–22%) compared with 11% (7.8–15%) among children receiving the combination ( = 0.08, by Wilcoxon test). Seventy-three percent of chloroquine-treated children exhibited parasitemia during follow-up compared with 49% of children receiving the combination (relative risk = 1.5, 95% CI = 1.3–1.7; χ = 21.18, < 0.001). A significant reduction in clinical and parasitologic treatment failure in the combination group occurred in the first two weeks following treatment, but this was eroded over weeks three and four of follow-up. The impact of combination therapy on the transmission of chloroquine-resistant parasites is discussed. Chloroquine plus artesunate is not sufficiently efficacious to justify its introduction as a replacement for chloroquine monotherapy in The Gambia.


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  1. Menon A, Otoo LN, Herbage EA, Greenwood BM, 1990. A national survey of the prevalence of chloroquine resistant Plasmodium falciparum malaria in The Gambia. Trans R Soc Trop Med Hyg 84 : 638–640. [Google Scholar]
  2. von Seidlein L, Duraisingh,MT, Drakeley CJ, Bailey R, Greenwood BM, Pinder M,1997. Polymorphism of the Pfmdr1 gene and chloroquine resistance in Plasmodium falciparum in The Gambia. Trans R Soc Trop Med Hyg 91 : 450–453. [Google Scholar]
  3. Muller O, Boele van Hensbroek M, Jaffar S, Drakeley C, Okorie C, Joof D, Pinder M, Greenwood B, 1996. A randomised trial of chloroquine, amodiaquine and pyrimethamine-sulphadoxine in Gambian children with uncomplicated malaria. Trop Med Int Health 1 : 124–132. [Google Scholar]
  4. Sutherland CJ, Alloueche A, Curtis J, Drakeley CJ, Ord R, Duraisingh M, Greenwood BM, Pinder M, Warhurst DC, Targett GA, 2002. Gambian children successfully treated with chloroquine can harbor and transmit Plasmodium falciparum gametocytes carrying resistance genes. Am J Trop Med Hyg 67 : 578–585. [Google Scholar]
  5. Trape JF, Pison G, Preziosi MP, Enel C, Desgrees du Lou A, Delaunay V, Samb B, Lagarde E, Molez JF, Simondon F, 1998. Impact of chloroquine resistance on malaria mortality. C R Acad Sci III 321 : 689–697. [Google Scholar]
  6. Ronn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 : 179–181. [Google Scholar]
  7. Nwanyanwu OC, Ziba C, MacHeso A, Kazembe P, 2000. Efficacy of sulphadoxine-pyrimethamine for acute uncomplicated malaria due to Plasmodium falciparum in Malawian children under five years old. Trop Med Int Health 5 : 355–358. [Google Scholar]
  8. von Seidlein L, Milligan P, Pinder M, Bojang K, Anyalebechi C, Gosling R, Coleman R, Ude JI, Sadiq A, Duraisingh M, Warhurst D, Alloueche A, Targett G, McAdam K, Greenwood B, Walraven G, Olliaro P, Doherty T, 2000. Efficacy of artesunate plus pyrimethamine-sulphadoxine for uncomplicated malaria in Gambian children: a double-blind, randomised, controlled trial. Lancet. 355 : 352–357. [Google Scholar]
  9. Targett G, Drakeley C, Jawara M, von Seidlein L, Coleman R, Deen J, Pinder M. Doherty T, Sutherland C, Walraven G, Milligan P, 2001. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae. J Infect Dis 183 : 1254–1259. [Google Scholar]
  10. Greenwood BM, Armstrong JRM, 1991. Comparison of two simple methods for determining malaria parasite density. Trans R Soc Trop Med Hyg 85 : 186–188. [Google Scholar]
  11. Collet D, 1994. Modelling Survival Data in Medical Research. London: Chapman and Hall.
  12. WHO, 1999. A Practical Handbook for Antimalarial Drug Therapeutic Efficacy Testing for the District Health Worker. WHO Regional Office for Africa. Geneva: World Health Organization.
  13. von Seidlein L, Jawara M, Coleman R, Doherty T, Walraven G, Targett G, 2001. Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria. Trop Med Int Health 6 : 92–98. [Google Scholar]
  14. White NJ, 1994. Clinical pharmacokinetics and pharmacodynamics of artemisinin and derivatives. Trans R Soc Trop Med Hyg 88 (Suppl 1): S41–S43. [Google Scholar]
  15. Hoshen MB, Na-Bangchang K, Stein WD, Ginsburg H, 2000. Mathematical modelling of the chemotherapy of Plasmodium falciparum malaria with artesunate: postulation of ‘dormancy’, a partial cytostatic effect of its drug, and its implication for treatment regimens. Parasitology 121 : 237–246. [Google Scholar]
  16. Sutherland CJ, Alloueche A, McRobert L, Ord R, Leggat J, Snounou G, Pinder M, Targett GAT, 2002. Genetic complexity of Plasmodium falciparum gametocytes isolated from the peripheral blood of treated Gambian children. Am J Trop Med Hyg 66 : 700–705. [Google Scholar]
  17. Dollery C, ed., 1999. Therapeutic Drugs. Second edition. London: Churchill Livingstone.
  18. Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR, 2002. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet 359 : 1365–1372. [Google Scholar]
  19. Dorsey G, Njama D, Kamya M, Cattamanchi A, Kyabayinze D, Staedke S, Gasasira A, Rosenthal P, 2002. Sulphadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomized trial. Lancet 360 : 2031–2038. [Google Scholar]
  20. Price R, Nosten F, Luxemburger C, Kuile FOT, Paiphun L, Chongsuphajaisiddhi T, White NJ, 1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet 347 : 1654–1658. [Google Scholar]
  21. Fivelman QL, Walden JC, Smith PJ, Folb PI, Barnes KI, 1999. The effect of artesunate combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 93 : 429–432. [Google Scholar]
  22. Warhurst DC, Duraisingh MT, 2001. Rational use of drugs against Plasmodium falciparum. Trans R Soc Trop Med Hyg 95 : 345–346. [Google Scholar]

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  • Received : 25 Jan 2003
  • Accepted : 02 Apr 2003

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