A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru

PLoS One. 2007 Oct 31;2(10):e1101. doi: 10.1371/journal.pone.0001101.

Abstract

Background: Multi-drug resistant falciparum malaria is an important health problem in the Peruvian Amazon region. We carried out a randomised open label clinical trial comparing mefloquine-artesunate, the current first line treatment in this region, with dihydroartemisinin-piperaquine.

Methods and findings: Between July 2003 and July 2005, 522 patients with P. falciparum uncomplicated malaria were recruited, randomized (260 with mefloquine-artesunate and 262 with dihydroartemisinin-piperaquine), treated and followed up for 63 days. PCR-adjusted adequate clinical and parasitological response, estimated by Kaplan Meier survival and Per Protocol analysis, was extremely high for both drugs (99.6% for mefloquine-artesunate and 98.4% and for dihydroartemisinin-piperaquine) (RR: 0.99, 95%CI [0.97-1.01], Fisher Exact p = 0.21). All recrudescences were late parasitological failures. Overall, gametocytes were cleared faster in the mefloquine-artesunate group (28 vs 35 days) and new gametocytes tended to appear more frequently in patients treated with dihydroartemisinin-piperaquine (day 7: 8 (3.6%) vs 2 (0.9%), RR: 3.84, 95%CI [0.82-17.87]). Adverse events such as anxiety and insomnia were significantly more frequent in the mefloquine-artesunate group, both in adults and children.

Conclusion: Dihydroartemisinin-piperaquine is as effective as mefloquine-artesunate in treating uncomplicated P. falciparum malaria but it is better tolerated and more affordable than mefloquine-artesunate (US$1.0 versus US$18.65 on the local market). Therefore, it should be considered as a potential candidate for the first line treatment of P. falciparum malaria in Peru.

Trial registration: ClinicalTrials.gov NCT00373607.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / pharmacology*
  • Artemisinins / administration & dosage*
  • Artesunate
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Malaria, Falciparum / drug therapy*
  • Male
  • Mefloquine / administration & dosage
  • Middle Aged
  • Peru
  • Quinolines / administration & dosage*
  • Sesquiterpenes / administration & dosage*

Substances

  • Antimalarials
  • Artemisinins
  • Quinolines
  • Sesquiterpenes
  • Artesunate
  • dihydroartemisinin
  • piperaquine
  • Mefloquine

Associated data

  • ClinicalTrials.gov/NCT00373607