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

Details

• Alternative Title:
  Lancet Infect Dis
• Personal Author:
  Gutman, Julie ; Kovacs, Stephanie ; Dorsey, Grant ; Stergachis, Andy ; ter Kuile, Feiko O
• Description:
  Background ; Intermittent 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. ; Methods ; Following 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. ; Findings ; 11 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. ; Interpretation ; Monthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing. ; Funding ; Bill & Melinda Gates Foundation and NIH.
• Subjects:
  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Drug Therapy, Combination
  • Humans
  • Malaria
  • Pyrimethamine
  • Quinolines
  • Randomized Controlled Trials as Topic
  • Sulfadoxine
• Source:
  Lancet Infect Dis. 2017; 17(2):184-193.
• Pubmed ID:
  27865890
• Pubmed Central ID:
  PMC5266794
• Document Type:
  Journal Article
• Funding:
  TL1 TR000422/TR/NCATS NIH HHS/United States
• Volume:
  17
• Issue:
  2
• Download URL:
  https://stacks.cdc.gov/view/cdc/44047/cdc_44047_DS1.pdf
• File Type:
  [PDF - 629.15 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:a7ff1be4c4dca090bb174ba2566c46819dd44a6abe5a95d5a3d99c3a2208316d