Abstract: The present disclosure provides for methods of addressing the devastating effects of malaria infection by mosquito-borne Plasmodium parasites. The methods include the administration of an effective amount of at least one pro-apoptotic agent and the administration of an effective amount of at least one p53 activator. The at least one pro-apoptotic agent can be administered concurrently with, prior to, or subsequent to the at least one p53 activator. The at least one pro-apoptotic agent and/or at least one p53 activator can be administered concurrently with, prior to, or subsequent to exposure of a hepatocyte (in vivo or in vitro) by a Plasmodium parasite. In some embodiments, the administration of the at least one pro-apoptotic agent combined with the administration of the at least one p53 activator results in clearance of hypnozoite stage of P. vivax or P. ovale, and thus prevents relapse of symptoms and disease from the infection of these parasites.