Cytokine response during non-cerebral and cerebral malaria:evidence of a failure to control inflammation as a cause of death in African adults

Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries.& Several species of the protozoan Plasrnodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasrnodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of antiinflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Senegal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biornarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria The levels of pro-inflammatory biornarkers were higher in the cerebral malaria than in the non-eerebral malaria patients. In contrast, the concentrat ons of anti-inflammatory cytokines were comparable in these two grouys. or lower in CM patients. Additionally, four pro inflammatory biorrlarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. adults Regsard fienrginogr an damage kidney failure was significantly associated with death organ cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.