1921
Volume 76, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Mefloquine (MQ) single dose 20 mg/kg treatment of falciparum malaria was evaluated in 186 children of 6–24 months of age in northern Ghana. There were 15 RII/RIII-type parasitologic failures, all with Day 2 MQ blood levels significantly lower than children whose parasitemias cleared before Day 7 and remained clear through 28 days. Predictors of RII/RIII parasitologic response were vomiting after MQ dosing, Day 2 MQ levels < 500 ng/mL, and undetectable Day 2 levels of the carboxymefloquine metabolite. There were 50 cases of delayed RI parasitologic failure, but 71% of these cases had undetectable Day 28 blood levels of MQ and drug levels in the remaining 29% ranged below the 620 ng/mL level that suppresses MQ sensitive strains of Drug levels among infants that tolerated MQ well were not associated with age, weight, hemoglobin, parasitemia, and pre-existing symptoms of vomiting or diarrhea. An observed recurrent parasitemia of 34,400 trophozoites/μL against a MQ blood concentration of 550 ng/mL was taken as indication of tolerance to suppressive levels of the drug at this location.

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2007-02-01
2017-09-24
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References

  1. World Health Organization, 2001. Drug Resistance in Malaria. Geneva, Switzerland: World Health Organization.
  2. Wongsrichanalai C, Prajakwong S, Meshnick SR, Shanks GD, Thimasarn K, 2004. Mefloquine—its 20 years in the Thai Malaria Control Program. SE Asian J Trop Med Publ Hlth 35 : 300–308.
  3. Nosten F, ter Kuile F, Chongsphajaisiddhi T, Luxemburger C, Webster HK, Edstein M, Phaipun L, Thew KL, White NJ, 1991. Mefloquine-resistant falciparum malaria on the Thai-Burmese border. Lancet 337 : 1140–1143.
  4. Oduola AMJ, Milhous WK, Salako LA, Walker O, Desjardins RE, 1987. Reduced in-vitro susceptibility to mefloquine in West African isolates of Plasmodium falciparum. Lancet ii : 1304–1305.
  5. Brasseur P, Kouamouo J, Moyou-Somo R, Druilhe P, 1992. Multi-drug resistant falciparum malaria in Cameroon in 1987–1988. II. Mefloquine resistance confirmed in vivo and in vitro and its correlation with quinine resistance. Am J Trop Med Hyg 46 : 8–14.
  6. Mockenhaupt FP, 1995. Mefloquine resistance in Plasmodium falciparum. Parasitol Today 11 : 248–253.
  7. Lobel HO, Varma JK, Mianai M, Green M, Todd GD, Grady K, Barber AM, 1998. Monitoring for mefloquine-resistant Plasmodium falciparum in Africa: implications for travelers’ health. Am J Trop Med Hyg 59 : 129–132.
  8. Hale BR, Owusu-agyei S, Fryauff DJ, Koram KA, Adjuik M, Oduro AR, Prescott WR, Baird JK, Nkrumah FR, Franke ED, Binka FN, Richie TL, Horton J, Hoffman SL, 2003. A randomized, double-blind, placebo-controlled dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clin Infect Dis 36 : 541–549.
  9. Baird JK, Owusu-Agyei S, Utz GC, Koram KA, Barcus MJ, Jones TR, Fryauff DJ, Binka FN, Hoffman SL, Nkrumah FN, 2002. Seasonal malaria attack rates in infants and young children in northern Ghana. Am J Trop Med Hyg 66 : 280–286.
  10. Slutsker LM, Khoromana CO, Payne D, Allen CR, Wirima JJ, Heymann DL, Patchen L, Steketee RW, 1990. Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: In vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. Bull WHO 68 : 53–59.
  11. ter Kuile FO, Luxemburger C, Nosten F, Thwai KL, Chongsuphajaisiddhi T, White NJ, 1995. Predictors of mefloquine treatment failure: a prospective study of 1590 patients with uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 89 : 660–664.
  12. Boudreau EF, Fleckenstein L, Pang LW, Childs GE, Schroeder AC, Ratnaratorn B, Phintuyothin P, 1990. Mefloquine kinetics in cured and recrudescent patients with acute falciparum malaria and in healthy volunteers. Clin Pharmacol Ther 48 : 399–409.
  13. Karbwang J, White NJ, 1990. Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet 19 : 264–279.
  14. Dubos F, Delattre P, Demar M, Carme B, Gendrel D, 2004. Safety of mefloquine in infants with acute falciparum malaria. Ped Inf Dis J 23 : 679–681.
  15. Looareesuwan S, White NJ, Warrell DA, Forgo I, Dubach UG, Ranalder UB, Schwartz DE, 1987. Studies on mefloquine bio-availability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers. Br J Clin Pharmacol 24 : 37–42.
  16. Fontanet AL, Johnston BD, Walker AM, Bergqvist Y, Hellgren U, Rooney W, 1994. Falciparum malaria in eastern Thailand: A randomized trial of the efficacy of a single dose of mefloquine. Bull WHO 72 : 73–78.
  17. Singhasivanon V, Chongsuphajaisiddhi T, Sabcharoen A, Attanath P, Webster HK, Wernsdorfer WH, Sheth UK, Djaja Lika I, 1992. Pharmacokinetics of mefloquine in children aged 6 to 24 months. Eur J Drug Metab Pharmacokinet 17 : 275–279.
  18. Hatin I, Trape J-F, Legros F, Bauchet J, Le Bras J, 1992. Susceptibility of Plasmodium falciparum strains to mefloquine in an urban area in Senegal. Bull WHO 70 : 363–367.
  19. MacArthur JR, Stennies GM, Macheso A, Kolczak MS, Green MD, Ali D, Barat LM, Kazembe PN, Ruebush TK II, 1998. Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998. Am J Trop Med Hyg 64 : 679–684.
  20. Appawu M, Owusu-Agyei S, Dadzie S, Asoala V, Anto F, Koram K, Rogers W, Nkrumah FK, Hoffman SL, Fryauff DJ, 2004. Malaria transmission dynamics at a site in northeastern Ghana proposed for testing malaria vaccine. Trop Med Int Hlth 9 : 164–170.
  21. Bergqvist Y, Kabbani JA, Krysén B, Palme IB, Rombo L, 1993. High-performance liquid chromatographic method for the simultaneous determination of mefloquine and its carboxylic metabolite in 100-ul capillary blood samples dried on paper. J Chromatog 615 : 297–302.
  22. Lobel HO, Miani M, Eng T, Bernard KW, Hightower AW, Campbell CC, 1993. Long-term malaria prophylaxis with weekly mefloquine. Lancet 341 : 848–851.
  23. Hogerzeil HV, Hogewoning AA, Van Doorn JW, Wernsdorfer WH, Van der Kaay HJ, 1985. In vitro assessment of sensitivity of Plasmodium falciparum to chloroquine and mefloquine in Ghana. Trans R Soc Trop Med Hyg 79 : 808–811.
  24. Sowunmi A, Oduola AM, 1995. Open comparison of mefloquine, mefloquine/sulfadoxine/ pyrimethamine and chloroquine in acute uncomplicated falciparum malaria in children. Trans R Soc Trop Med Hyg 89 : 303–305.
  25. Okoyeh JN, Lege-Oguntoye L, Ugbode RO, Ogunrinde GO, 1997. Responses of multidrug-resistant Plasmodium falciparum parasites to mefloquine in Nigerian childfren. Trop Med Int Hlth 2 : 319–324.
  26. White NJ, 1988. Drug treatment and prevention of malaria. Eur J Clin Pharmacol 34 : 1–14.
  27. Karbwang J, Na-Bangchang K, 1994. Clinical application of mefloquine pharmacokinetics in the treatment of P. falciparum malaria. Fundam Clin Pharmacol 8 : 491–502.
  28. Nosten F, ter Kuile F, Chongsuphajaisiddhi T, Na Bangchang K, Karbwang J, White NJ, 1991. Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria. Br J Clin Pharmacol 31 : 556–559.
  29. Todd GD, Hopperus Buma APCC, Green MD, Jaspers CAJJ, Lobel HO, 1997. Comparison of whole blood and serum levels of mefloquine and its carboxylic acid metabolite. Am J Trop Med Hyg 57 : 399–402.
  30. Na-Bangchang K, Davis TME, Looareesuwan S, White NJ, Bunnag D, Karbwang J, 1994. Mefloquine pharmacokinetics in pregnant women with acute falciparum malaria. Trans R Soc Trop Med Hyg 88 : 321–323.
  31. Franssen G, Rouveix B, Lebras J, Bauchet J, Verdier F, Michon C, Bricaire F, 1989. Divided-dose kinetics of mefloquine in man. Br J Clin Pharmac 28 : 179–184.
  32. Wallace MR, Sharp TW, Smoak B, Iriye C, Rozmajzl P, Thornton SA, Batchelor R, Magill AJ, Lobel HO, Longer CF, Burans JP, 1996. Malaria among United States troops in Somalia. Am J Med 100 : 49–56.
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  • Received : 26 Jul 2005
  • Accepted : 06 Jul 2006

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