Volume 81, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The treatment efficacy and effects of artesunate-mefloquine (AMQ) and mefloquine (MQ) on malaria-associated anemia (MAA) were evaluated in 342 children ≤ 10 years of age with uncomplicated malaria randomized to receive either drug/drug combination. All children recovered clinically. Fever clearance times were similar. Parasite clearance was significantly faster with AMQ (mean ± SD = 1.4 ± 0.6 days, 95% confidence interval [CI] = 1.3–1.5, < 0.0001), but polymerase chain reaction–corrected cure rates were similar (97% versus 94%). Gametocyte carriage rates and the drug-attributable fall in hematocrit were significantly lower with AMQ (mean ± SD = 4.8 ± 3.8%, 95% CI = 3.6–6.0, = 0.03), but the rates of resolution of MAA were similar. Both regimens were well tolerated. AMQ clears parasitemia and reduces gametocyte carriage more rapidly and causes lesser fall in hematocrit than MQ, but both regimens are effective treatment of uncomplicated malaria in Nigerian children.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. World Health Organization, 2001. The Use of Antimalarial Drugs. Report of a WHO Technical Consultation. Geneva: World Health Organization.
  2. World Health Organization, 2001. Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation. Geneva: World Health Organization.
  3. Trape J-F, Pison G, Preziosi M-P, Enel C, Du Lou AD, Delaunay V, Samb B, Lagarde E, Molez J-F, Simondon F, 1998. Impact of chloroquine resistance on malaria mortality. Life Sci 321: 689–697. [Google Scholar]
  4. Trape JF, 2001. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64 (Suppl 1–2): 12–17. [Google Scholar]
  5. White N, 1999. Antimalarial drug resistance and combination chemotherapy. Phil Trans R Soc Lond Series B 354: 739–749. [Google Scholar]
  6. Hien TT, White NJ, 1993. Qinghaosu. Lancet 341: 603–608. [Google Scholar]
  7. Price RN, Nosten F, Luxemburger C, ter Kuile FO, Paiphun L, Chongsuphajasiddhi T, White NJ, 1996. Effects of artemisinin derivatives on malaria transmissibility. Lancet 347: 1654–1658. [Google Scholar]
  8. Price R, van Vugt M, Nosten F, Luxemburger C, Brockman A, Phaipun L, Chongsuphajaisiddhi T, White NJ, 1998. Artesunate versus artemether for the treatment of recrudescent multi-drug resistant falciparum malaria. Am J Trop Med Hyg 59: 883–888. [Google Scholar]
  9. 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 P-B, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WRJ, 2002. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial. Lancet 359: 1365–1372. [Google Scholar]
  10. Sowunmi A, Fehintola FA, Adedeji AA, Gbotosho GO, Tambo E, Fateye BA, Happi TC, Oduola AMJ, 2005. Open randomized studyofartesunate-amodiaquinevs.chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children. Trop Med Inter Hlth 10: 1161–1170. [Google Scholar]
  11. Mokuolu OA, Okoro EO, Ayetoro SO, Adewara AA, 2007. Effect of artemisinin-based treatment policy on consumption pattern of antimalarials. Am J Trop Med Hyg 76: 7–11. [Google Scholar]
  12. Oduola AMJ, Milhous WK, Salako LA, Walker O, Desjardins RE, 1987. Reduced in vitro susceptibility to mefloquine in West African isolates of Plasmodium falciparum from Nigeria. Lancet ii: 1304–1305. [Google Scholar]
  13. Oduola AMJ, Sowunmi A, Milhous WK, Kyle DE, Martin RK, Walker O, Salako LA, 1992. Innate resistance to new antima-larial drugs in Plasmodium falciparum from Nigeria. Trans R Soc Trop Med Hyg 86: 123–126. [Google Scholar]
  14. Sowunmi A, Oduola AMJ, Salako LA, Ogundahunsi OAT, Laoye OJ, Walker O, 1992. The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro. Trans R Soc Trop Med Hyg 86: 368–371. [Google Scholar]
  15. Bukirwa H, Orton L, 2005. Artesunate plus mefloquine versus mefloquine for treating uncomplicated malaria. Cochrane Database Syst Rev 4: CD004531. [Google Scholar]
  16. Salako LA, Ajayi FO, Sowunmi A, Walker O, 1990. Malaria in Nigeria: a revisit. Ann Trop Med Parasitol 84: 435–445. [Google Scholar]
  17. Sowunmi A, Salako LA, Walker O, Ogundahunsi OAT, 1990. Clinical efficacy of mefloquine in children suffereing from chloro-quine-resistant Plasmodium falciparum malaria in Nigeria. Trans R Soc Trop Med Hyg 84: 761–764. [Google Scholar]
  18. Lilijveld J, Kortmann H, 1970. The eosin colour test of Dill and Glazko: a simple field test to detect chloroquine in urine. Bull Wld Health Org 42: 477–479. [Google Scholar]
  19. World Health Organization, 1986. Chemotherapy of Malaria. Second Edition. Geneva: World Health Organization.
  20. World Health Organization, 2000. Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 (Suppl 1): 1–90. [Google Scholar]
  21. Happi TC, Thomas SM, Gbotosho GO, Falade CO, Akinboye DO, Gerena L, Hudson T, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AMJ, 2003. Point mutations in the pfcrt and pfmdr-1 genes of Plasmodium falciparum and clinical response to chlo-roquine, among malaria patients from Nigeria. Ann Trop Med Parasitol 97: 439–451. [Google Scholar]
  22. Happi CT, Gbotosho GO, Sowunmi A, Falade CO, Akinboye DO, Gerena L, Kyle DE, Milhous W, Wirth DF, Oduola AMJ, 2004. Molecular analysis of Plasmodium falciparum recrudescent malaria infections in children treated with chloroquine in Nigeria. Am J Trop Med Hyg 70: 20–26. [Google Scholar]
  23. Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AMJ, 2005. Polymorphism in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop 95: 183–193. [Google Scholar]
  24. Happi CT, Gbotosho GO, Folarin OA, Bolaji OM, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AMJ, 2006. Association between mutations in Plasmodium falciparum chloroquine resistance transporter and P. falciparum multidrug resistance 1 genes and in vivo amodiaquine resistance in P. falciparum malaria-infected children in Nigeria. Am J Trop Med Hyg 75: 155–161. [Google Scholar]
  25. World Health Organization, 1973. Chemotherapy of Malaria and Resistance to Antimalarials . Geneva: World Health Organization.
  26. World Health Organization, 2003. Assessment and Monitoring of Antimalarial Drug Efficacy for the Treatment of Uncomplicated Falciparum Malaria. Geneva: World Health Organization.
  27. Anonymous, 1994. Epi Info Version 6. A Word Processing Data Base and Statistics Program for Public Health on IBM-compatible Microcomputers. Atlanta, GA: Centers for Disease Control and Prevention.
  28. Anonymous, 1999. SPSS for Windows Release 10.01 (Standard Version). Chicago, IL: SPSS.
  29. Wernsdorfer H, Landgraf B, Wiedermann G, Kollatriscg H, 1994. Inverse correlation of sensitivity in vivo of Plasmodium falci-parum to chloroquine and mefloquine in Ghana. Trans R Soc Trop Med Hyg 88: 443–444. [Google Scholar]
  30. Sowunmi A, Fateye BA, Adedeji AA, Fehintola FA, Gbotosho GO, Happi TC, Tambo E, Oduola AMJ, 2005. Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance. Trans R Soc Trop Med Hyg 99: 535–544. [Google Scholar]
  31. Fryauff DJ, Owusu-Agyei S, Utz G, Baird JK, Koram KA, Nkrumah F, Hoffman SL, 2006. Mefloquine treatment for uncomplicated falciparum malaria in young children 6–24 months of age in Northern Ghana. Am J Trop Med Hyg 76: 224–231. [Google Scholar]
  32. Smithus F, Kyaw MK, Phe O, Aye KZ, Htet L, Barends M, Lindegardh N, Singtoroj T, Asley E, Lwin S, Stepniewska K, White NJ, 2006. Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomized comparison. Lancet 367: 2075–2085. [Google Scholar]
  33. Piyaphanee W, Krudsood S, Tangpukdee N, Thanachartwet W, Silachamroon U, Phophak N, Duangdee C, Haoharn O, Faithong S, Wilairatana P, Leowattana W, Looaresuwan S, 2006. Emergence and clearance of gametocytes in uncomplicated Plasmodium falciparum malaria. Am J Trop Med Hyg 74: 432–435. [Google Scholar]
  34. Tangpukdee N, Krudsood S, Srivilairit S, Phophak N, Chonsawat P, Yanpanich W, Kano S, Wilairatana P, 2008. Gametocyte clearance in uncomplicated and severe Plasmodium falciparum malaria after artesunate-mefloquine treatment in Thailand. Korean J Parasitol 46: 65–70. [Google Scholar]
  35. Bousema JT, Schneider P, Gougna LC, Drakeley CJ, Tostmann A, Houben R, Githure JI, Ord R, Sutherland CJ, Omar SA, Sauerwein RW, 2006. Moderate effect of artemisinin-based combination therapy on transmission of Plasmodium falci-parum. J Infect Dis 193: 1151–1159. [Google Scholar]
  36. Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looaresuwan S, White NJ, 2000. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand. Lancet 356: 297–302. [Google Scholar]
  37. van Vugt M, Brockman A, Gemperll B, Luxemburger C, Gathmann I, Royce C, Slight T, Looaresuwan S, White NJ, Nosten F, 1998. Randomized comparison of artemether-benflumetol and arte-sunate-mefloquine in the treatment of multidrug-resistant fal-ciparum malaria. Antimicrob Agents Chemother 42: 135–139. [Google Scholar]
  38. Marquino W, Hulca M, Galampa C, Falconi E, Cabezas C, Naupay R, Ruebush TK II, 2003. Efficacy of mefloquine and a meflo-quine-artesunate combination therapy for the treatment of uncomplicated Plasmodiun falciparum malaria in the Amazon Basin of Peru. Am J Trop Med Hyg 68: 608–612. [Google Scholar]
  39. Krudsood S, Looaresuwan S, Silachamroon U, Chalermrut K, Pittron D, Cambon N, Mueller EA, 2002. Artesunate-mefloquine given simultaneously for three days via pre-packed blister is equally effective and tolerated as a standard sequential treatment of uncomplicated acute Plasmodium falciparum malaria: randomizes double-blind study in Thailand. Am J Trop Med Hyg 67: 465–472. [Google Scholar]
  40. Hutagalung R, Paiphun L, Ashley EA, McGready R, Brockman A, Thwai KL, Singhasivanon P, Jelinek T, White NJ, Nosten FH, 2005. A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand. Malar J 4: 46., doi: 10.11186/1475-2875-4.46. [Google Scholar]
  41. Agomo PU, Meremikwu MM, Watila IM, Omalu IJ, Odey FA, Oguche S, Ezeiru VI, Aina OO, 2008. Efficacy, safety and tolerability of artesunate-mefloquine in the treatment of uncomplicated Plasmodium falciparum malaria in four geographic zones of Nigeria. Malaria J 7: 172. [Google Scholar]
  42. Wongsrichanalai C, Meshnick SR, 2008. Declining artesunate-mefloquine efficacy against falciparum malaria on the Cam-bodia-Thailand border. Emerg Infect Dis 14: 716–719. [Google Scholar]
  43. Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, Brockman A, Anderson T, McGready R, Phaiphun L, Proux S, van Vugt M, Hutagalung R, Lwin KM, Phyo AP, Preechapornkul P, Imwong M, Pukrittayakamee S, Singhasivanon P, White NJ, Nosten F, 2009. Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS One 4: e4551. [Google Scholar]
  44. Dondorp AM, Nosten F, Poravuth Yi, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NPJ, Lindegardh K, Socheat D, White NJ, 2009. Artemisinin resistance in Plasmodium falci-parum. New Eng J Med 361: 455–467. [Google Scholar]
  45. Barrett P, Emmins P, Clarke P, Bradley D, 1996. Comparison of adverse events associated with the use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: postal and telephone survey of travelers. BMJ 313: 525–528. [Google Scholar]
  46. Phillips M, Kass R, 1996. User acceptability patterns of meflo-quine and doxycycline malaria chemoprophylaxis. J Travel Med 3: 10–15. [Google Scholar]
  47. Huzley D, 1996. Malaria chemoprophylaxis in German tourists: a prospective study on compliance and adverse reactions. J Travel Med 3: 148–155. [Google Scholar]
  48. Schwartz E, Potasman I, Rotenberg I, Almog S, Sadetzski S, 2001. Serious adverse events of mefloquine in relation to blood level and gender. Am J Trop Med Hyg 65: 189–192. [Google Scholar]
  49. Rendi-Wagner P, Noedl H, Wernsdorfer WH, Wiedermann G, Mikolasek A, Kollatrisch H, 2002. Unexpected frequency, duration and spectrum of adverse events after therapeutic dose of mefloqine in healthy adults. Acta Trop 81: 167–173. [Google Scholar]
  50. van Remsdijk MM, Sturkenboom MCJM, Ditters JM, Tulen JHM, Lighthelm RJ, Overbosch D, Stricker BH, 2004. Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine. Br J Clin Pharmacol 57: 506–512. [Google Scholar]
  51. Mattison D, Zajicek A, 2006. Gaps in knowledge in treating pregnant women. Gend Med 3: 169–182. [Google Scholar]
  52. Sowunmi A, Salako LA, Oduola AMJ, Walker O, Akindele JA, Ogundahunsi OAT, 1993. Neuropsychiatric side effects of mefloquine in Africans. Trans R Soc Trop Med Hyg 87: 462–463. [Google Scholar]
  53. Chotivanich K, Udomsangpetch R, Dondorp A, Williams T, Angus B, Simpson JA, Pukrittayakamee S, Looaresuwan S, Newbold CI, White NJ, 2000. The mechanism of parasite clearance after antimalarial treatment of Plasmodium falciparum malaria. J Infect Dis 182: 629–633. [Google Scholar]
  54. Sowunmi A, Balogun ST, Gbotosho GO, Happi CT, 2009. Effects of amoqiauine, artesunate, and artesunate-amodiaquine on Plasmodium falciparum malaria-associated anaemia in children. Acta Trop 109: 55–60. [Google Scholar]
  55. Obonyo CO, Taylor W, Ekvall H, Kaneko A, ter Kuile F, Olliaro P, Bjorkman A, Oloo AJ, 2007. Effects of artesunate plus sulfa-doxine-pyrimethamine on haematological recovery and anaemia in Kenyan children with uncomplicated Plasmodium falciparum malaria. Ann Trop Med Parasitol 101: 281–295. [Google Scholar]

Data & Media loading...

  • Received : 13 Jul 2009
  • Accepted : 27 Aug 2009

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