Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

Abstract

Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively.

Aspartyl Proteinases of Eukaryotic Microbial Pathogens: From Eating to Heating

“…Plasmepsin II is actively produced at the disease-critical blood stage of infection. As recently highlighted [46], upon infection with P . falciparum , the host immune system produces pro-inflammatory cytokines, including IL-1β, which activates endothelial cells that in turn produce CXCL10, a chemo-attractant for mononuclear leukocytes.…”

Dynamic interactions ofPlasmodiumspp. with vascular endothelium

“…76,77 These inflammatory mediators are identified mostly by measuring circulating levels using various immunoassays, or more recently by transcriptomics. Very few of the mediators have been studied functionally in relation to the infection, and as a result, the elevated levels do not distinguish between whether a particular inflammatory mediator actually contributes to disease pathology or merely serves as a biomarker of severity.…”

Fatal Cerebral Malaria with Multi-Organ Dysfunction and Oleander Poisoning

“…According to the most established hypotheses, CM usually results due from the sequestration of infected erythrocytes (IEs) which binds to host endothelial receptor leading to microvascular circulatory obstruction and clogging, whereas the decreased deformability of IEs, rosette formation by uninfected RBCs and clumping (via platelets). The inflammatory cytokine release then result in brain endothelial injury leading to tissue hypoxia, increased permeability and dysfunction of the blood-brain-barrier with intracranial hypertension and brain oedema [16,18,19]. The absolute cause of death however, in this case, may apparently be attributed to cerebral malaria along with acute multi-organ failures, however it may not be ruled out that the poisoning episode didn't aggravate his overall clinical condition.…”

“…More importantly, the coma can even persist along with other complications till several days, although peripheral parasitaemia may have cleared [2]. Pathogenesis of cerebral malaria is multi-factorial and a dynamic process where the present scientific understanding is argued to be incomplete; though advanced imaging techniques and newer diagnostic tools and biomarkers have started to pave the way forward [16,17]. According to the most established hypotheses, CM usually results due from the sequestration of infected erythrocytes (IEs) which binds to host endothelial receptor leading to microvascular circulatory obstruction and clogging, whereas the decreased deformability of IEs, rosette formation by uninfected RBCs and clumping (via platelets).…”