1921
Volume 74, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5–25 kg. A total of 544 patients with uncomplicated malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen ( < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2006.74.991
2006-06-01
2017-11-21
Loading full text...

Full text loading...

/deliver/fulltext/14761645/74/6/0740991.html?itemId=/content/journals/10.4269/ajtmh.2006.74.991&mimeType=html&fmt=ahah

References

  1. Breman JG, Egan A, Keusch GT, 2001. The intolerable burden of malaria: a new look at the numbers. Am J Trop Med Hyg 64 (Suppl): 4i–7i.
  2. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI, 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434 : 214–217.
  3. Greenwood BM, Bojang K, Whitty CJ, Targett GA, 2005. Malaria. Lancet 365 : 1487–1498.
  4. Roll Back Malaria/World Health Organization, 2004. Position of WHO’s Roll Back Malaria Department on malaria treatment policy. Available at: http://www.who.int/malaria/docs/who_apt_position.htm. Accessed 24 November 2005.
  5. White NJ, 2004. Anti-malarial drug resistance. J Clin Invest 113 : 1084–1092.
  6. Muheki C, McIntyre D, Barnes KI, 2004. Artemisinin-based combination therapy reduces expenditure on malaria treatment in KwaZulu Natal, South Africa. Trop Med Int Health 9 : 959–966.
  7. Malenga G, Palmer A, Staedke S, Kazadi W, Mutabingwa T, Ansah E, Barnes KI, Whitty CJ, 2005. Anti-malarial treatment with artemisinin combination therapy in Africa. BMJ 331 : 706–707.
  8. Ashley EA, White NJ, 2005. Artemisinin-based combinations. Curr Opin Infect Dis 18 : 531–536.
  9. Kshirsagar NA, Gogtay NJ, Moorthy NS, Garg MR, Dalvi SS, Chogle AR, Sorabjee JS, Marathe SN, Tilve GH, Bhatt AD, Sane SP, Mull R, Gathmann I, 2000. A randomized, double-blind, parallel-group, comparative safety, and efficacy trial of oral coartemether versus oral chloroquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in India. Am J Trop Med Hyg 62 : 402–408.
  10. Van Vugt M, Wilairatana P, Gemperli B, Gathmann I, Phaipun L, Brockman A, Luxemburger C, White NJ, Nosten F, Looareesuwan S, 1999. Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 60 : 936–942.
  11. Van Vugt M, Looareesuwan S, Wilairatana P, McGready R, Villegas L, Gathmann I, Mull R, Brockman A, White NJ, Nosten F, 2000. Artemether-lumefantrine for the treatment of multi-drug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 94 : 545–548.
  12. Lefevre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I, Mull R, Bakshi R, 2001. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 64 : 247–256.
  13. Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kiguli J, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP, 2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365 : 1467–1473.
  14. Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI, 2005. Efficacy and safety of artemether-lumefantrine (Coartem®) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 99 : 459–467.
  15. Fogg C, Bajunirwe F, Piola P, Biraro S, Checchi F, Kiguli J, Namiiro P, Musabe J, Kyomugisha A, Guthmann JP, 2004. Adherence to a six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Uganda. Am J Trop Med Hyg 71 : 525–530.
  16. Von Seidlein L, Jaffar S, Pinder M, Haywood M, Snounou G, Gemperli B, Gathmann I, Royce C, Greenwood B, 1997. Treatment of African children with uncomplicated falciparum malaria with a new anti-malarial drug, CGP 56697. J Infect Dis 176 : 1113–1116.
  17. Von Seidlein L, Bojang K, Jones P, Jaffar S, Pinder M, Obaro S, Doherty T, Haywood M, Snounou G, Gemperli B, Gathmann I, Royce C, McAdam K, Greenwood B, 1998. A randomized controlled trial of artemether/benflumetol, a new anti-malarial and pyrimethamine/sulfadoxine in the treatment of uncomplicated falciparum malaria in African children. Am J Trop Med Hyg 58 : 638–644.
  18. Hatz C, Abdulla S, Mull R, Schellenberg D, Gathmann I, Kibatala P, Beck HP, Tanner M, Royce C, 1998. Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years. Trop Med Int Health 3 : 498–504.
  19. Van Vugt M, Brockman A, Gemperli B, Luxemburger C, Gathmann I, Royce C, Slight T, Looareesuwan S, White NJ, Nosten F, 1998. Randomized comparison of artemether-benflumetol and artesunate-mefloquine in treatment of multidrug-resistant falciparum malaria. Antimicrob Agents Chemother 42 : 135–139.
  20. Taylor WRJ, White NJ, 2004. Anti-malarial drug toxicity. Drug Saf 27 : 25–61.
  21. Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G, Targett GA, 2005. Reduction of malaria transmission to anopheles mosquitoes with a six-dose regimen of coartemether. PLoS Med 2 : e92.
  22. Brewer TG, Peggins JO, Grate SJ, Petras JM, Levine BS, Weina PJ, Swearengen J, Heiffer MH, Schuster BG, 1994. Neurotoxicity in animals due to arteether and artemether. Trans R Soc Trop Med Hyg 88 (Suppl 1): S33–S36.
  23. Toovey S, Jamieson A, 2004. Audiometric changes associated with the treatment of uncomplicated falciparum malaria with coartemether. Trans R Soc Trop Med Hyg 98 : 261–267.
  24. Hutagalung R, Htoo H, Nwee P, Arunkmomkiri J, Zwang J, Carrara V, Ashley E, Singhasivanon P, White N, Nosten F, 2006. A case control auditory evaluation of patients treated with artemether-lumefantrine. Am J Trop Med Hyg 74 : 211–214.
  25. Von Seidlein L, Jaffar S, Greenwood B, 1997. Prolongation of the QTc interval in African children treated for falciparum malaria. Am J Trop Med Hyg 56 : 494–497.
  26. Bindschedler M, Lefevre G, Ezzet F, Schaeffer N, Meyer I, Thomsen MS, 2000. Cardiac effects of coartemether (artemether/lumefantrine) and mefloquine given alone or in combination to healthy volunteers. Eur J Clin Pharmacol 56 : 375–381.
  27. Van Vugt M, Ezzet F, Nosten F, Gathmann I, Wilairatana P, Looareesuwan S, White NJ, 1999. No evidence of cardiotoxicity during anti-malarial treatment with artemether-lumefantrine. Am J Trop Med Hyg 61 : 964–967.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2006.74.991
Loading
/content/journals/10.4269/ajtmh.2006.74.991
Loading

Data & Media loading...

  • Received : 21 Dec 2005
  • Accepted : 06 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