Antimalarial efficacy of piperaquine‐based antimalarial combination therapies: facts and uncertainties
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.
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