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

BACKGROUND: In 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. METHODS: A 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. RESULTS: Of 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. CONCLUSION: Both 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 REGISTRATION: Australian New Zealand Clinical Trials Registry Number, ACTRN12609000816257.

Open label randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam.

OBJECTIVE: Artesunate-amodiaquine (AAQ) is efficacious for the treatment of uncomplicated Plasmodium falciparum malaria in Africa, but little is known about its efficacy in Southeast Asia. We compared the efficacy of dihydroartemisinin-piperaquine (DHP) and AAQ against falciparum malaria in central Vietnam. METHODS: Open, randomized clinical trial of 116 patients (36 children aged 6-14 years, 80 adults aged 15-60 years) were randomly allocated a 3-day course of either DHP (approximately 2.3 mg/kg dihydroartemisinin plus approximately 18.5 mg/kg of piperaquine per day) or AAQ (approximately 4.4 mg/kg of artesunate plus approximately 10.6 mg/kg of amodiaquine per day). The follow-up period was 42 days. RESULTS: The two drug combinations were well tolerated by all age groups with no obvious drug associated adverse events. Of the patients who completed 42 days of follow-up, 49 were on DHP (15 children, 34 adults) and 49 were on AAQ (14 children, 35 adults). The 42 day cure rates adjusted for reinfection identified by PCR genotyping for the two groups were similar [100% (49/49) and 98% (48/49) for DHP and AAQ, respectively]. With fewer reinfections, DHP appears to possess greater post-treatment prophylactic activity than AAQ. CONCLUSION: AAQ, an inexpensive artemisinin-based combination, could be an additional option to DHP for the treatment of multidrug-resistant falciparum malaria in Vietnam.

A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria.

OBJECTIVE: The study aimed to evaluate and compare the efficacy and safety of dihydroartemisinin-piperaquine phosphate (Artekin) and artemisinin-piperaquine (Artequick) in the treatment of uncomplicated falciparum malaria. METHODS: A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups: 52 cases in the Artequick group, and 51 cases in the Artekin group. The patients in the Artequick group were administered with Artequick, twice in 24 h, whereas the patients in the Artekin group were given Artekin 4 times in 2 days. The mean parasite clearance time, mean fever clearance time, 28-day cure rate and parasite recrudescence rates of the two groups were then compared. RESULTS: The mean parasite clearance time and the mean fever clearance time were 43.2+/-13.9 h and 24.7+/-9.9 h, in the Artequick group, and 36.5+/-17.1 h and 22.7+/-11.2 h, in the Artekin group. In both groups the 28-day cure rate was 100%, and the parasite recrudescence rate was 0. CONCLUSION: Both medicines had high cure rates, low recrudescence rates, and no serious adverse reactions. The administration of Artequick, however, was more convenient and lower incidence of gastrointestinal side effects than that of Artekin, so as to increase the efficacy in the malaria population.

In Vivo Efficacy and Tolerability of Artesunate-Azithromycin for the Treatment of Falciparum Malaria in Vietnam.

Safe and effective antimalarial drugs are required for the treatment of pregnant women. We report a 3-day regimen of artesunate (4 mg/kg/day)-azithromycin (25 mg/kg/day) (ASAZ) to be efficacious (polymerase chain reaction-corrected cure rate of 96.7%) and well tolerated in the treatment of Plasmodium falciparum malaria in children (N = 11) and adults (N = 19), in Vietnam in 2010. In comparison, the cure rate for artesunate (4 mg/kg on day 0, 2 mg/kg on days 1-6) was 90.0% in children (N = 7) and adults (N = 23). Because azithromycin is considered safe in pregnancy, our findings provide further evidence that ASAZ should be evaluated for the treatment of pregnant women with malaria.

Forest malaria in central Vietnam.

Studies were conducted in a village in central Vietnam to explain the existence of a forest malaria cycle of transmission external to the village. The findings suggested no malaria transmission in the village because of the absence of a suitable vector, but suggested evidence for transmission in villagers when attending garden plots in the forested hills surrounding the village. A sizeable population residing near these garden plots, the presence of Anopheles dirus (a highly efficient vector), and a degree of malaria immunity within the inhabitants created suitable conditions to sustain malaria transmission outside the village.