1921
Volume 68, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

In the Amazon Basin of Peru, more than 50% of patients with uncomplicated malaria fail to respond to treatment with chloroquine or sulfadoxine-pyrimethamine. To assist the National Malaria Control Program in identifying an alternative first-line therapy for this region, we conducted a trial of the safety and efficacy of mefloquine (MQ) compared with mefloquine-artesunate (MQ-AS) combination therapy. Patients with uncomplicated infections between the ages of 5 and 50 years were randomly assigned to be treated with either MQ (15 mg/kg in a single oral dose) or MQ (15 mg/kg) plus AS (4 mg/kg/day for three days). A total of 98 patients were enrolled and followed for 28 days. None of the 47 patients who received MQ alone or the 51 patients who received MQ-AS combination therapy had recurrences of parasitemia during the 28-day follow-up period. Asexual parasite densities decreased significantly more rapidly and the proportion of patients with gametocytes was significantly lower on days 3–21 in the MQ-AS group than in patients treated with MQ alone. All patients tolerated the medication well. Based on the results of this study and with the objective of slowing the development of resistance, the Peruvian Ministry of Health has decided to revise its malaria treatment policy and recommend combination therapy with MQ-AS as the new first-line treatment of uncomplicated malaria in the Amazon region.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2003.68.608
2003-05-01
2017-11-23
Loading full text...

Full text loading...

/deliver/fulltext/14761645/68/5/0680608.html?itemId=/content/journals/10.4269/ajtmh.2003.68.608&mimeType=html&fmt=ahah

References

  1. World Health Organization, 1998. The Use of Artemisinin and its Derivatives as Anti-Malarial Drugs: Report of a Joint CTD/DMP/TDR Informal Consultation. Geneva: World Health Organization. WHO Document WHO/MAL/98.1086.
  2. White NJ, 1998. Preventing antimalarial drug resistance through combinations. Drug Resist Updates 1 : 3–9.
  3. 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.
  4. Pan American Health Organization, 1998. Evaluation of the Therapeutic Efficacy of Drugs for the Treatment of Uncomplicated Plasmodium falciparum Malaria in the Americas. Washington, DC: Pan American Health Organization. OPS/HCP/ HCT/113/98.<bok>
  5. Bruce-Chwatt LJ, Black RH, Canfield CJ, Clyde DF, Peters W, 1986. Chemotherapy of Malaria. World Health Organization Monograph Series No 27, Geneva: World Health Organization.
  6. Ministerio da Saúde, 2001. Fundação Nacional de Saúde, Manual de Terapêutica de Malária. Brasilia: Brazil.
  7. de Souza JM, 1983. A phase II clinical trial of mefloquine in Brazilian male subjects. Bull World Health Organ 61 : 815–820.
  8. Cardoso BS, Dourado HV, Pinheiro MCN, Crescente JAB, Amoras WW, Baena J, Saraty S, 1996. Estudo da eficácia e tolerância do artesunato oral isolado e em associação com mefloquina no tratamento da malária falciparum não complicada em área endêmica do Pará. Res Soc Bras Med Trop 29 : 251–257.
  9. Cerutti C, Durlacher RR, de Alencar FEC, Segurado AAC, Pang LW, 1999. In vivo efficacy of mefloquine for the treatment of falciparum malaria in Brazil. J Infect Dis 180 : 2077–2080.
  10. Price RN, Nosten F, Luxemburger C, Kham Am, Brockman A, Chongsuphajaisiddhi T, White NJ, 1995. Artesunate versus artemether in combination with mefloquine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 89 : 523–527.
  11. 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.
  12. Simpson JA, Watkins ER, Price RN, Aarons L, Kyle DE, White NJ, 2000. Mefloquine pharmacokinetic-pharmacodynamic models: implications for dosing and resistance. Antimicrob Agents Chemother 44 : 3414–3424.
  13. Weidekamm E, Rüsing G, Caplain H, Sörgel F, Crevoisier C, 1998. Lack of bioequivalence of a generic mefloquine tablet with the standard product. Eur J Clin Pharmacol 54 : 615–619.
  14. Na-Bangchang K, Karbwang J, Palacios PAC, Ubalee R, Saengtersilapachai S, Wernsdorfer WH, 2000. Pharmacokinetics and bioequivalence evaluation of three commercial tablet formulations of mefloquine when given in combination with dihydroartemisinin in patients with acute uncomplicated falciparum malaria. Eur J Clin Pharmacol 55 : 743–748.
  15. ter Kuile FO, Nosten F, Luxemburger C, Kyle D, Teja-Isavatharm P, Phaipun L, Price R, Chongsuphajaisiddhi T, White NJ, 1995. Mefloquine treatment of acute falciparum malaria: a prospective study of non-serious adverse effects in 3,673 patients. Bull World Health Organ 73 : 631–642.
  16. Luxemburger C, Price RN, Nosten F, ter Kuile FO, Chongsuphajaisiddhi T, White NJ, 1996. Mefloquine in infants and young children. Ann Trop Paediatr 16 : 281–286.
  17. Ministerio de Salud, 1999. Programa de Control de Malaria y Otras Enfermedades Metaxénicas, Política Nacional de Medicamentos para el Control de la Malaria en el Perú. Lima, Peru.
  18. Nosten F, Luxemburger C, ter Kuile FO, Woodrow C, Pa Eh J, Chongsuphajaisiddhi T, White NJ, 1994. Treatment of multi-drug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis 170 : 971–977.
  19. Price RN, Nosten F, Luxemburger C, van Vugt M, Phaipun L, Chongsuphajaisiddhi T, White NJ, 1997. Artesunate/ mefloquine treatment of multi-drug resistant falciparum malaria. Trans R Soc Trop Med Hyg 91 : 574–577.
  20. Watkins WM, Mosobo M, 1993. Treatment of Plasmodium falciparum malaria with PSD: selective pressure for resistance is a function of long elimination half life. Trans R Soc Trop Med Hyg 87 : 75–78.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2003.68.608
Loading
/content/journals/10.4269/ajtmh.2003.68.608
Loading

Data & Media loading...

  • Received : 05 Mar 2002
  • Accepted : 12 Dec 2002

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