Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: a systematic review and meta-analysis

Abstract

SummaryBackgroundIntermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP.MethodsFollowing PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: “human” AND “dihydroartemisinin-piperaquine” OR “DHA-PPQ”. Studies were eligible if they were randomised controlled trials (RCTs) or prospective cohort studies involving repeat exposures to standard 3-day courses of DP for either seasonal malaria chemoprevention, mass drug administration, or treatment of clinical malaria, conducted at any time and in any geographic location. Random-effects meta-analysis was used to generate pooled incidence rate ratios and relative risks, or risk differences.Findings11 studies were included: two repeat treatment studies (one in children younger than 5 years and one in pregnant women), and nine IPT trials (five in children younger than 5 years, one in schoolchildren, one in adults, two in pregnant women). Comparator interventions included placebo, artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine, SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935 received multiple DP courses (2–18). Monthly IPT-DP was associated with an 84% reduction in the incidence of malaria parasitaemia measured by microscopy compared with placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc intervals were within normal limits, with no significant increase in QTc prolongation with increasing courses of DP.InterpretationMonthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing.FundingBill & Melinda Gates Foundation and NIH.

Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

“…The efficacy of natural products against diseases has been shown in numerous studies, and has led to the use of certain natural products (e.g., artemisinin and curcumin) in current clinical interventions [38,39]. HGK is a flavonoid that is extracted from the flower buds of D. genkwa, a commonly used medicinal herb in Southeast Asian countries; however, knowledge of the bioactivity of HGK remains limited to date.…”

Dihydroartemisinin-piperaquine: if it works for control, can we use it for elimination?

“…3,6,7 In the Lancet Infectious Diseases, Julie Gutman and colleagues analyse the safety, tolerability, and effi cacy of repeated doses of DP, for the treatment and prevention of malaria, with a particular focus on its use as intermittent preventive treatment (IPT). 8 Their meta-analysis, looking at over 4000 patients exposed to repeated courses of DP, substantiates the high effi cacy of this drug in terms of controlling malaria and all-cause hospital admission, and the good tolerability of repeated treatment schemes, with no evidence of arrhythmias secondary to the potential QT prolongation eff ect of cumulative doses of piperaquine after repeated doses. Although numbers are clearly insuffi cient to rule out this rare, life-threatening complication, and the small number of carefully ECG monitored patients calls for caution and further cardio safety studies, this analysis adds up to the growing body of evidence supporting the potential of this drug for IPT strategies.…”

Investigating the Effect of Prompt Treatment on Malaria Prevalence in Children Aged below Five Years in Zambia: A Nested Case-Control Study in a Cross-Sectional Survey

“…Another study recommended a day-three blood slide as a good predictor of treatment success [30]. In the ACTs that are currently used in Zambia, the artemisinin component acts quickly whilst the other components such as Lumifantrine or Piperaquine have a longer acting time with terminal elimination half-life of four to five days and 14 days, respectively [31,32]. So the testing of children for malaria within two weeks after treatment is probably reasonable as clearance of the primary infection would have occurred.…”