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The assessment in real-life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine-artesunate (PA) in real-life conditions in Burkina Faso's health system. This was a single-arm, open-label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM). At inclusion (day-0), PA was administered orally once a day for 3 days. Patients spontaneous reported any clinical adverse events (AEs) occurring within 28 days following the treatment. Additionally, the study focused on AEs of special interest (AESI), namely clinical signs related to hepatotoxicity and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A nested subset of patients with blood sample collection at day-0 and day-7 were monitored to investigate the effect of PA on biochemistry parameters. From September 2017 to October 2018, 2786 patients were treated with PA. About 97.8% (2720/2786) of patients did not report any AE. The most commonly reported events were respiratory, thoracic, and mediastinal disorders (8.3 per 1000), infections and infestations (7.9 per 1000), and gastrointestinal disorders (7.2 per 1000). No clinical or biological hepatotoxicity event related to PA was reported during the follow-up. Changes in biochemistry parameters remained within laboratory reference ranges. The study showed that PA is a well-tolerated drug and should be considered as a good option by malaria control programs in countries where existing first-line antimalarial drugs are continuously threatened by the emergence of drug resistance., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration. Laboratory analyses included haematology and clinical chemistry. The main objective of the ECG assessment in this study was to evaluate the effect of administration of DHA/PPQ on QTc intervals and the association of QTc intervals with changes in blood biochemistry, full and differential blood count over time after the DHA/PPQ administration. A total of 1315 patients gave consent and were enrolled of which 1147 (87%) had complete information for analyses. Of the enrolled patients 488 (42%), 323 (28%), 213 (19%) and 123 (11%) were from Ghana, Burkina Faso, Tanzania and Mozambique, respectively. Median (lower-upper quartile) age was 8 (5-14) years and a quarter of the patients were children under five years of age (n = 287). Changes in blood biochemistry, full and differential blood count were temporal which remained within clinical thresholds and did not require any intervention. The mean QTcF values were significantly higher than on day 1 when measured on day 3 before and after administration of the treatment as well as on day 7, four days after completion of treatment (12, 22 and 4 higher, p < 0.001). In all age groups the values of QT, QTcF and QTcB were highest on day 3 after drug intake. The mean extreme QTcF prolongation from baseline was lowest on day 3 before drug intake (33 ms, SD = 19) and highest on day 3 after the last dose (60 ms, SD = 31). There were 79 (7%) events of extreme mean QTcF prolongation which were not clinically significant. Nearly a half of them (n = 37) were grade 3 and mainly among males (33/37). Patients in Burkina Faso, Mozambique and Tanzania had significantly lower mean QTcF than patients in Ghana by an average of 3, 4 and 11 ms, respectively. We found no evidence that Eurartesim® administered in therapeutic doses in patients with uncomplicated malaria and no predisposing cardiac conditions in Africa was associated with adverse clinically significant QTc prolongation., Competing Interests: The authors have declared that no competing interests exist.

Background: Dihydroartemisinin-piperaquine (DHA-PQ) is one of five WHO recommended artemisinin combination therapy (ACT) for the treatment of uncomplicated malaria. However, little was known on its post-registration safety and effectiveness in sub-Saharan Africa. DHA-PQ provides a long post-treatment prophylactic effect against re-infection; however, new infections have been reported within a few weeks of treatment, especially in children. This paper reports the clinical outcomes following administration of DHQ-PQ in real-life conditions in public health facilities in Burkina Faso, Ghana, Mozambique, and Tanzania for the treatment of confirmed uncomplicated malaria., Methods: An observational, non-comparative, longitudinal study was conducted on 10,591 patients with confirmed uncomplicated malaria visiting public health facilities within seven health and demographic surveillance system sites in four African countries (Ghana, Tanzania, Burkina Faso, Mozambique) between September 2013 and April 2014. Patients were treated with DHA-PQ based on body weight and followed up for 28 days to assess the clinical outcome. A nested cohort of 1002 was intensely followed up. Clinical outcome was assessed using the proportion of patients who reported signs and symptoms of malaria after completing 3 days of treatment., Results: A total of 11,097 patients were screened with 11,017 enrolled, 94 were lost to follow-up, 332 withdrew and 10,591 (96.1%) patients aged 6 months-85 years met protocol requirements for analysis. Females were 52.8 and 48.5% were <5 years of age. Malaria was diagnosed by microscopy and rapid diagnostic test in 69.8% and 29.9%, respectively. At day 28, the unadjusted risk of recurrent symptomatic parasitaemia was 0.5% (51/10,591). Most of the recurrent symptomatic malaria patients (76%) were children <5 years. The mean haemoglobin level decreased from 10.6 g/dl on day 1 to 10.2 g/dl on day 7. There was no significant renal impairment in the nested cohort during the first 7 days of follow-up with minimal non-clinically significant changes noted in the liver enzymes., Conclusion: DHA-PQ was effective and well tolerated in the treatment of uncomplicated malaria and provides an excellent alternative first-line ACT in sub-Saharan Africa.