Mechanisms of Quinoline Resistance

Abstract

For decades, the 4-aminoquinoline chloroquine (CQ) was the mainstay for the prevention and treatment of malaria because of its low cost, safety, and efficacy. However, CQ-resistant Plasmodium falciparum has now been reported from almost every malaria endemic country, and this drug can no longer be considered appropriate for the treatment of malaria in many areas (1). Reports of CQ-resistant P. vivax also have begun to emerge from Asia and South America (2). In response to the problem of CQ resistance, the quinolinemethanol mefloquine has been widely deployed and used for the prevention and treatment of malaria in areas where CQ is no longer effective. However, resistance to this drug has emerged in many malarious regions (3–8). Although the older quinolinemethanols quinine and quinidine remain useful in areas of CQ and mefloquine resistance, these drugs have been losing efficacy, and cases of cross-resistance among the different quinolines have been described (9–16).