title: Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults.
abstract: 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 Plasmodium 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 Plasmodium 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 anti-inflammatory 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, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers 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 biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.
authors.affiliation: Vice-Chancellor's Office, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Yakhya
authors.initials: Y
authors.lastname: Dieye
authors.affiliation: Département d'Immunologie, Faculté de Médicine, de Pharmacie et d'Odontostomatologie, Université Cheikh Anta Diop de Dakar, Dakar, Sénégal; Unité d'Immunogénétique, Institut Pasteur de Dakar, Dakar, Sénégal.
authors.forename: Babacar
authors.initials: B
authors.lastname: Mbengue
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Shobha
authors.initials: S
authors.lastname: Dagamajalu
authors.affiliation: Service de Réanimation, Hôpital Principal de Dakar , Dakar , Sénégal.
authors.forename: Mouhamadou Mansour
authors.initials: MM
authors.lastname: Fall
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Mun Fai
authors.initials: MF
authors.lastname: Loke
authors.affiliation: Département Génie Chimique et Biologie Appliquée, École Supérieure Polytechnique, Université Cheikh Anta Diop de Dakar , Dakar , Sénégal.
authors.forename: Cheikh Momar
authors.initials: CM
authors.lastname: Nguer
authors.affiliation: Unité d'Immunogénétique, Institut Pasteur de Dakar , Dakar , Sénégal.
authors.forename: Alassane
authors.initials: A
authors.lastname: Thiam
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia.
authors.forename: Jamuna
authors.initials: J
authors.lastname: Vadivelu
authors.affiliation: Département d'Immunologie, Faculté de Médicine, de Pharmacie et d'Odontostomatologie, Université Cheikh Anta Diop de Dakar, Dakar, Sénégal; Unité d'Immunogénétique, Institut Pasteur de Dakar, Dakar, Sénégal.
authors.forename: Alioune
authors.initials: A
authors.lastname: Dieye
keywords: Cerebral; Cytokine; Inflammation; Malaria; Plasmodium falciparum