The pathological bases of immunomodulatory therapy in malaria

Abstract

Objectives The objectives of this review are an attempt to analyse the potential bases for immunomodulary therapy in malaria. Malaria is a major cause of suffering and death and one of the most important problems of public health in vast areas of the world, mainly due to the severe forms of Plasmodium falciparum infection. Epidemiology According to the World Health Organization, it is currently estimated that a total of 350 to 500 million clinical cases occur annually, which cause something between 1.1 and 1.3 million deaths every year. Pathogenesis The hyperactivation of the immune system, with enhanced production of cytokines, mainly TNF, has an important role in the complex pathogenesis of the disease. Enhanced sequestration of parasitized erythrocytes within the small vessels of major organs is a central feature of P. falciparum infection. The increased production of pro-inflammatory cytokines and nitric oxide, followed by the up-regulation of endothelial cell adhesion molecules, influences the progression of cerebral lesions. Immunomodulation Therefore, different approaches have been attempted to downmodulate the hyperactive immune system in malaria, including the administration of cytokines or anti-cytokine antibodies, antibodies against molecules of adherence, drugs that reduce the excessive synthesis of reactive oxygen species, and drugs with pleiotropic action on the immune system. The impact of these immunomodulatory therapies on the course of malaria has reached variable success. Application We submitted this subject to a critical assessment and it was proposed ways to take advantage of immunomodulatory drugs, associated to anti-parasite therapy, to reduce the morbimortality of malaria.