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

Tanilu Grande, Andrea Bernasconi, Annette Erhart, Dioni Gamboa, Martin Casapia, Christopher Delgado, Kathy Torres, Caterina Fanello, Alejandro Llanos-Cuentas, Umberto D'Alessandro, Tanilu Grande, Andrea Bernasconi, Annette Erhart, Dioni Gamboa, Martin Casapia, Christopher Delgado, Kathy Torres, Caterina Fanello, Alejandro Llanos-Cuentas, Umberto D'Alessandro

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Trial profile.
Figure 1. Trial profile.
Figure 2. Proportions of patients with gametocytemia…
Figure 2. Proportions of patients with gametocytemia during the follow up.

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