Abstract
Entamoeba histolytica is a protozoan parasite which infects approximately 50 million people worldwide, resulting in an estimated 70,000 deaths every year. Since the 1960s E. histolytica infection has been successfully treated with metronidazole. However, drawbacks to metronidazole therapy exist, including adverse effects, length of treatment, and the need for additional drugs to prevent transmission. All of these may decrease patient compliance and hence increase disease severity and spread of infection. In this study we identified the antimalarial drug mefloquine as possessing more potent, rapid, amoebicidal in vitro activity against E. histolytica trophozoites than metronidazole. We also showed that mefloquine could kill the cysts of a closely related reptilian parasite Entamoeba invadens unlike metronidazole. Additionally, mefloquine is known to possess a much longer half-life in human patients than metronidazole. This property, along with mefloquine’s rapid and broad action against E. histolytica position it as a promising new drug candidate against this widespread and devastating disease.
Author Summary Every year, around 70,000 people worldwide die from infection by the intestinal parasite Entamoeba histolytica, despite the widespread availability of the drug metronidazole as a treatment. Part of the reason for this may be due to issues with patients failing to comply with the full course of treatment for the drug, due either to unpleasant side-effects, to the somewhat long treatment period, or the need for a secondary drug to kill the transmissible life stage of the parasite. In this report we discovered that the antimalarial drug mefloquine killed E. histolytica more potently and more rapidly than metronidazole, and, importantly, also killed the transmissible cyst stage of another Entamoeba species used as a model system. These findings make mefloquine an excellent candidate for an alternative drug to the current standard, with a simpler course of treatment and a more effective strategy to reduce the spread of this disease.
