title: Antimalarial efficacy of piperaquine-based antimalarial combination therapies: facts and uncertainties.
abstract: Piperaquine is a bisquinoline antimalarial drug extensively used as monotherapy in China in the 1980s and subsequently included as one of the components of the artemisinin-based combination therapies (ACTs) in the 1990s. Among them, dihydroartemisinin-piperaquine (DHA-PQP) represents a new and extremely promising fixed combination. Several clinical trials have repeatedly shown that DHA-PQP is a safe and highly efficacious therapy against uncomplicated Plasmodium falciparum and the asexual stages of Plasmodium vivax malaria. Studies conducted with this drug have reported cure rates consistently above 95%, with the only exception being a study carried out in Papua New Guinea which reported a high rate of treatment failures. Although it has been hypothesized that such treatment failures could be related to cross-resistance mechanisms between piperaquine and other quinolines or to a reduced susceptibility of parasites to artemisinin derivatives, a critical review of the studies published so far seems to exclude both of these possibilities. Overall, there is now sufficient evidence on the safety and efficacy of the DHA-PQP therapy. Accordingly, the use of this ACT for the treatment of P. falciparum malaria has been recently approved in the EU via a centralized procedure by the European Medicines Agency. Moreover, it is now recommended globally by the World Health Organization as an option for the first-line treatment of uncomplicated malaria.
authors.affiliation: R&D Area, Sigma-tau Industrie Farmaceutiche Riunite S.p.A., Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gargano
authors.forename: Fabio
authors.initials: F
authors.lastname: Cenci
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
mesh_terms: D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016780:Malaria, Vivax / Q000188:drug therapy*; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines