Safety and efficacy of dihydroartemisinin/piperaquine (Artekin®) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children

Abstract

In Rwanda, amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) is the current first-line treatment for malaria, introduced in 2001 as an interim strategy before the future deployment of an artemisinin-based combination treatment (ACT). Dihydroartemisinin/piperaquine (DHA-PQP) is a new co-formulated and well tolerated ACT increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria. We tested the efficacy, safety and tolerability of DHA-PQP in children with uncomplicated P. falciparum malaria. A randomised, open trial was carried out in 2003-2004. Seven hundred and sixty-two children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to one of the following treatments: amodiaquine+artesunate; AQ+SP; or DHA-PQP. Patients were followed-up until Day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Children treated with DHA-PQP or AQ+AS had a significantly higher cure rate compared with those treated with amodiaquine+sulfadoxine/pyrimethamine (95.2% and 92.0% vs. 84.7%, respectively). Parasite clearance was significantly faster in children treated with DHA-PQP and AQ+AS compared with those treated with amodiaquine+sulfadoxine/pyrimethamine. The frequency of adverse events was significantly lower in patients treated with DHA-PQP than in those treated with combinations containing amodiaquine. A 3-day treatment with DHA-PQP proved to be efficacious with a good safety and tolerability profile and could be a good candidate for the next first-line treatment.

Efficacy of Artesunate Plus Amodiaquine for Treatment of Uncomplicated Clinical Falciparum Malaria in Severely Malnourished Children Aged 6–59 Months, Democratic Republic of Congo

“…Lastly, the most common adverse events observed were anorexia, vomiting, nausea and diarrhoea. These events observed are consistent with those in Rwanda using AS+AQ [31]. Given that drug retention explained by the pathophysiological changes occurring in malnutrition which could result in adverse events which may be masked by a constellation of signs malnutrition, in our study, the drug tolerance was globally good among children including those with SAM despite their weakness.…”

Efficacy and safety of dihydroartemisinin-piperaquine

“…The P. falciparum recrudescences and new infections all occurred between days 28 and 35 in one Vietnamese study, whereas in the Thai studies the majority of patients' recrudescences appeared between days 43 and 63 with a median (range) time to recrudescence of 56 (28-63) days (Ashley et al, 2004(Ashley et al, , 2005Hien et al, 2004). The lowest efficacy of DHA-PIP reported was 88.6% (80.3-93.7) at 28 days, observed in Rukara, one of the Rwandan sites (Karema et al, 2006). This is a site of high seasonal transmission and thus difficulty in genotype assessment (i.e., reinfections may have been called recrudescence).…”

“…Current formulations contain only DHA 40 mg and PIP 320 mg per tablet. DHA-PIP has been evaluated in large clinical trials in Southeast Asia, China and Rwanda (Ashley et al, 2004(Ashley et al, , 2005Denis et al, 2002;Giao et al, 2004;Hien et al, 2004;Hung et al, 2004;Karema et al, 2006;Karunajeewa et al, 2004;Mayxay et al, 2006;Smithuis et al, 2006;Tangpukdee et al, 2005;Wilairatana et al, 2002;Ying et al, 2003). Further studies in Africa, Asia Oceania and South America have been conducted but not yet reported.…”

Spatial modelling of malaria risk factors in Ruhuha sector in the east of Rwanda

“…In Rwanda, studies about malaria mainly addressed malaria control policies and programmes. Thus, the focus was on the contribution of anti-malarial drugs, mosquito nets and residual sprays (Karema et al, 2006;NISR, 2012;President's Malaria Initiative, 2013), the prevalence of malaria in pregnant HIV positive women (Ivan et al, 2012) and the resistance of Plasmodium falciparum to antimalarial drugs (Karema et al, 2012). Most all the studies done in Rwanda have established a comprehensive malaria framework (causing factors, transmission and control measures), but they did not take into consideration geospatial factors that might affect malaria infection.…”