Immunopathogenesis of falciparum malaria: implications for adjunctive therapy in the management of severe and cerebral malaria

Despite optimal antimalarial treatment and advances in malaria eradication, the mortality rate associated with severe malaria due to Plasmodium falciparum infection, including cerebral malaria (CM), remains unacceptably high. This suggests that strategies directed solely at parasite eradication may be insufficient to prevent neurological complications and death in all cases of CM. Therefore, there is an urgent need to develop innovative adjunctive therapeutic strategies to effectively reduce CM-associated mortality. CM pathogenesis is believed to be due, in part, to an aberrant host immune response to P. falciparum, resulting in deleterious consequences, including vascular activation and dysfunction. Development of effective and affordable therapeutic strategies that act to modulate the underlying host-mediated immunopathology should be explored to improve outcome. In this article, we summarize immunomodulatory therapies that have been assessed in clinical trials to date, and highlight novel and promising treatment strategies currently being investigated to address this major global health challenge.