Quinine dihydrochloride 125mg/5ml oral solution

BackgroundThe artemisinin derivatives are the preferred antimalaria drugs for treating severe Plasmodium falciparum malaria. However, their clinical effectiveness compared to each other is unknown. Our objective, therefore, was to evaluate the efficacy and safety of the artemisinin derivatives and quinine for treating severe P. falciparum malaria in children and adults using a network meta-analysis.Methods and findingsReview protocol was registered with PROSPERO, CRD42020218190. We updated the search strategies of three Cochrane systematic reviews which included published and unpublished randomised control trials (RCTs) that have compared specific artemisinin derivatives to quinine in treating severe malaria. Search included CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and trial registries up to February 2021. We screened studies, extracted data, assessed risk of bias, and quality of evidence in duplicate. Separate network meta-analyses in the frequentist framework, using a random effects model, with quinine as reference, were conducted for adults and children, and rankings were produced using p-scores to assess mortality, parasite clearance, coma recovery, fever clearance, neurological sequela and adverse events. Searches identified 818 citations, 33 RCTs were eligible. We pooled 7795 children and 3182 adults. The networks involved artesunate, artemether, rectal artemisinin, arteether and quinine. Compared to quinine, artesunate reduced mortality in children (risk ratio (RR), 0.76; 95%CI [0.65 to 0.89], moderate quality), adults (RR, 0.55; 95%CI [0.40 to 0.75], moderate quality) and in cerebral malaria (RR, 0.72; 95%CI [0.55 to 0.94], moderate quality). Compared to rectal artemisinin and intramuscular arteether, the efficacy and safety of parenteral artesunate, and intramuscular artemether in treating severe malaria are not clear. Rankings showed that none of the artemisinin drugs were consistently superior in all the outcomes assessed. Indirect evidence produced were of very low ratings due to suspected publication bias and imprecision.ConclusionsArtesunate reduces mortality compared to quinine for both adults and children in Asia and Africa including cerebral malaria. The artemisinin derivatives remain the best treatment for severe malaria but their comparative clinical effectiveness is yet to be fully explored.

Abstract licence: CC BY

BackgroundTreatment for severe malaria must be prompt with effective parenteral antimalarial drugs for at least 24 h to achieve fast parasite clearance, and when the patient can tolerate oral therapy, treatment should be completed with effective artemisinin based combination therapy (ACT) for complete parasite clearance and to prevent recrudescence. We evaluated piperaquine concentration and malaria treatment outcomes among Ugandan children treated for severe malaria with intravenous artesunate (AS) or quinine (QN) plus dihydroartemisinin-piperaquine (DP), in Tororo District Hospital in Eastern Uganda.MethodsCapillary blood piperaquine concentration data were obtained from a randomized clinical trial whose objective was to evaluate parasite clearance, 42-day parasitological treatment outcomes and safety, following treatment of severe malaria with intravenous AS or QN, plus artemether-lumefantrine or DP among children in Tororo District Hospital, in Eastern Uganda.ResultsPiperaquine concentration data from 150 participants who received DP were analyzed. Participants with unadjusted treatment failure had lower median day 7 capillary piperaquine concentration than those with treatment success (34.7 (IQR) (17.9-49.1) vs 66.7 (IQR) (41.8-81.9), p  57 ng/mL).ConclusionConsidering the low day 7 concentrations of piperaquine reported in the patients studied here, we suggest to adopt the recently recommended higher dose of DP in young children or a prolonged 5-day dosing in children living in malaria endemic areas who have suffered an initial episode of severe malaria in order to achieve adequate drug exposures for effective post-treatment prophylactic effects.Trial registrationThe study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011.

Abstract licence: CC BY