The efficacy and tolerability of artemisinin-piperaquine (Artequick®) versus artesunate-amodiaquine (Coarsucam™) for the treatment of uncomplicated Plasmodium falciparum malaria in south-central Vietnam

Nguyen Xuan Thanh,Huynh Hong Quang,Trieu Nguyen Trung,Nguyen Chinh Phong,Bui Dai,G Dennis Shanks,Michael D Edstein,Marina Chavchich

doi:10.1186/1475-2875-11-217

Abstract

BackgroundIn Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria. However, limited efficacy and tolerability data are available on alternative forms of ACT in Vietnam in case there is a reduction in the susceptibility of dihydroartemisinin-piperaquine. A study was conducted to compare the efficacy and tolerability of two fixed-dose formulations of ACT, artemisinin–piperaquine (Artequick®, ARPQ) and artesunate-amodiaquine (Coarsucam™, ASAQ) for the treatment of P. falciparum malaria in south-central Vietnam.MethodsA randomized, open-label trial was conducted comparing the efficacy of a two-day regimen of ARPQ (~2.8 mg/kg artemisinin plus ~17.1 mg/kg of piperaquine per day) and a three-day regimen of ASAQ (~4.7 mg/kg of artesunate plus ~12.6 mg/kg of amodiaquine per day) for the treatment of children and adults with uncomplicated falciparum malaria. Primary efficacy endpoint was day 42, PCR-corrected, parasitological cure rate. Secondary endpoints were parasite and fever clearance times and tolerability.ResultsOf 128 patients enrolled, 63 were administered ARPQ and 65 ASAQ. Of the patients who completed the 42 days follow-up period or had a recurrence of malaria, 55 were on ARPQ (30 children, 25 adults) and 59 were on ASAQ (31 children, 28 adults). Recrudescent parasitaemia was PCR-confirmed for one patient in each treatment group, with cure rates at day 42 of 98% (95% CI: 88–100) for both forms of ACT. The median parasite clearance time was significantly slower in the ARPQ group compared with the ASAQ group (48 h vs. 36 h, P<0.001) and fever clearance times were shorter in the ASAQ group (12 h vs. 24 h, P = 0.07). The two forms of ACT were well tolerated with no serious adverse events.ConclusionBoth forms of ACT were highly efficacious in the treatment of uncomplicated P. falciparum malaria. Although the two-day course of ARPQ was equally as effective as the three-day course of ASAQ, parasite and fever clearance times were shorter with ASAQ. Further studies are warranted in different regions of Vietnam to determine the nationwide efficacy of ASAQ.Trial registrationAustralian New Zealand Clinical Trials Registry Number, ACTRN12609000816257

Highlights

In Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria
Reduced PCR-adjusted 42-day cure rates of about 80% have been reported in western and southern Cambodia following treatment with artesunate plus mefloquine [12,13]. These findings of emerging ACT-resistant P. falciparum malaria are of immense concern, as the Cambodia-Thailand border region has been the epicentre of anti-malarial drug resistance [14], which historically has spread westward from South Asia to Africa [5]
The study was conducted between May 2008 and December 2009, with 128 patients enrolled consisting of 63 patients on ARPQ and 65 patients on ASAQ (Figure 1)

Summary

Introduction

In Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine is currently used for first-line treatment of uncomplicated Plasmodium falciparum malaria. For first-line treatment of uncomplicated Plasmodium falciparum malaria worldwide, WHO recommends artemisinin-based combination therapy (ACT), such as artemether-lumefantrine, artesunateamodiaquine, artesunate-mefloquine, artesunate-sulphadoxine-pyrimethamine and dihydroartemisinin-piperaquine [2] Most of these formulations of ACT are available as fixed-dosed co-formulations, facilitating improved adherence, convenience and prevention against misuse [3]. Reduced PCR-adjusted 42-day cure rates of about 80% have been reported in western and southern Cambodia following treatment with artesunate plus mefloquine [12,13] These findings of emerging ACT-resistant P. falciparum malaria are of immense concern, as the Cambodia-Thailand border region has been the epicentre of anti-malarial drug resistance [14], which historically has spread westward from South Asia to Africa [5]

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Results

Discussion

Conclusion