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This entry refers to the therapeutic interventions evaluated in a randomized, open-label Phase 2 clinical trial (NCT00238719) conducted by the Center for Primary Care and Public Health (Unisante) at the University of Lausanne. The study assessed the safety and efficacy of **Cotrifazid**—a fixed-dose combination of rifampicin, isoniazid, sulfamethoxazole, and trimethoprim—compared to **mefloquine** and the standard treatment of **quinine plus sulfadoxine-pyrimethamine** (SP) for uncomplicated drug-resistant malaria in Papua New Guinea. Cotrifazid targets multiple pathways, including plasmodial RNA synthesis and the folate biosynthesis pathway. However, the trial demonstrated significant parasitological failure by day 14 for both *Plasmodium falciparum* and *Plasmodium vivax*, leading to the conclusion that Cotrifazid, in the tested formulation and regimen, is not an effective alternative for resistant malaria.
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