The present invention features a non-human animal model of malaria, e.g., Plasmodium, particularly Plasmodium falciparum. The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having anti-pathogenic activity against malaria.