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The article presents a placebo-controlled trial which investigated whether rectal artesunate reduced mortality and permanent disability when given before referral to people with malaria. Patients in Bangladesh, Ghana, and Tanzania with malaria who could not be treated orally were randomly assigned to either single artesunate or placebo suppository. They were subsequently referred to clinics for injections. Researchers found that the artesunate suppository substantially reduced the risk of death or permanent disability among patients with severe malaria who could not be treated orally and had delayed access to injections.

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.

Background: Drug prescription practices depend on several factors related to the patient, health worker and health facilities. A better understanding of the factors influencing prescription patterns is essential to develop strategies to mitigate the negative consequences associated with poor practices in both the public and private sectors., Methods: A cross-sectional study was conducted in rural Tanzania among patients attending health facilities, and health workers. Patients, health workers and health facilities-related factors with the potential to influence drug prescription patterns were used to build a model of key predictors. Standard data mining methodology of classification tree analysis was used to define the importance of the different factors on prescription patterns., Results: This analysis included 1,470 patients and 71 health workers practicing in 30 health facilities. Patients were mostly treated in dispensaries. Twenty two variables were used to construct two classification tree models: one for polypharmacy (prescription of ≥3 drugs) on a single clinic visit and one for co-prescription of artemether-lumefantrine (AL) with antibiotics. The most important predictor of polypharmacy was the diagnosis of several illnesses. Polypharmacy was also associated with little or no supervision of the health workers, administration of AL and private facilities. Co-prescription of AL with antibiotics was more frequent in children under five years of age and the other important predictors were transmission season, mode of diagnosis and the location of the health facility., Conclusion: Standard data mining methodology is an easy-to-implement analytical approach that can be useful for decision-making. Polypharmacy is mainly due to the diagnosis of multiple illnesses.