Pradines B. Dose responses of proveblue methylene blue in an experimental murine cerebral malaria model. Antimicrob Agents Chemother 2013;57:4080e1

Proveblue, which is amethylene blue preparation that complieswith the European Pharmacopoeia and contains limited or-ganic impurities and heavy metals of recognized toxicity, has pre-viously been demonstrated to possess in vitro antimalarial activity (1). Proveblue exhibited noticeable synergistic effects in combina-tion with mefloquine and quinine and high synergistic effects in combination with dihydroartemisinin, the active metabolite of artemisinin derivatives (2). Treatment with 10 mg/kg of body weight of Proveblue for 5 days significantly reduced or prevented cerebral malaria (CM) in mice (3, 4). However, this dose was too high to show synergistic effects in combination with dihydroarte-misinin or atorvastatin in malaria cerebral prevention. The objective of the present work was to evaluate the in vivo efficacy of Proveblue at several doses in a murine model of exper-imental CM and determine doses for future in vivo combination evaluation