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

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Gutman, Julie, Kovacs, Stephanie, Dorsey, Grant, Stergachis, Andy and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2017) 'Safety, tolerability and efficacy of repeated doses of dihydroartemisinin-piperaquine for the prevention and treatment of malaria: A systematic review and meta-analysis'. Lancet Infectious Diseases, Vol 17, Issue 2, pp. 184-193.

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Abstract

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 determine the efficacy and safety of repeated treatment with DP.

Methods
Following PRISMA guidelines, we searched multiple databases on September 1, 2016 with the terms: “human” AND “dihydroartemisinin-piperaquine” OR “DHA-PPQ.”. Prospective studies of IPT-DP or repeat DP courses for case-management were eligible. Random effects models were used.

Findings
Eleven studies were included: two repeat treatment studies (one in children <5y and one in pregnant women), and nine IPT trials (five in children <5y; 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 trimethoprim-sulfamethoxazole. Of 14,628 participants, 3,935 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 to placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily trimethoprim-sulfamethoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women), 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 Source
Bill & Melinda Gates Foundation and NIH

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
WA Public Health > Health Problems of Special Population Groups > WA 310 Maternal welfare
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WS Pediatrics > By Age Groups > WS 460 Adolescence (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1016/S1473-3099(16)30378-4
Depositing User: Tracy Seddon
Date Deposited: 26 Oct 2016 14:06
Last Modified: 06 Feb 2018 13:13
URI: https://archive.lstmed.ac.uk/id/eprint/6231

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