Active clinical trials for "Malaria, Cerebral"

Malaria remains one of the most common life-threatening illnesses in the tropics with a dramatic toll of more than one million deaths each year. A majority of malaria cases are non-complicated and only few evolve towards severe malaria resulting from the combination of parasite-specific virulence factors and host inflammatory responses. Cerebral malaria (CM) kills more than 1 million African children each year. CM carries a fatality rate of about 20% in adults, higher in children, despite timely and adequate chemotherapy. Moreover, the more rapid clearance of parasitaemia with new antimalarial drugs is not associated with improved survival, suggesting the potential interest for adjunctive therapies in the early phase of the disease. Cerebral malaria leading to seizure and coma is associated with severe intracranial hypertension caused by brain-swelling. Recent imaging and post-mortem findings in adult cerebral malaria have confirmed the presence of diffuse cerebral oedema with thalamic and cerebellar white matter hypoattenuation, diffuse petechial hemorrhages and symmetric ischemic changes involving the thalamus and the cerebellum. However, the nature of the pathogenetic processes leading to cerebral malaria is incompletely understood but mechanisms linking cytokines with endothelial cells activation in the cerebral microvasculature have been recently stressed. The effect of new neuroprotective therapies has not yet been investigated, although the manifestations of cerebral malaria partly share features with neurological stroke or acute non-specific neurological disorders. The hormone erythropoietin (EPO) is probably one of the more enthusiastic drugs in this area. EPO is as a member of type I cytokine superfamily with multiple functions, including a prominent role for erythropoiesis and neuroprotection. Systematically administered EPO crosses the blood brain barrier via the abundant expression of EPO receptors at brain capillaries, and acts as an anti-apoptotic and cytoprotective cytokine. Moreover, EPO prevents inflammation by inhibiting pro-inflammatory cytokines including TNFα, preserves endothelial cells integrity and prevents blood-brain barrier permeability. We propose a randomized clinical trial to investigate the safety and efficacy of EPO in patients presenting cerebral malaria and hospitalized at Gabriel Toure hospital, Bamako, Mali, to reduce the incidence of premature death in hospitalized patients.

Cerebral malaria is a life-threatening complication of Plasmodium falciparum infection in African children and nonimmune travellers despite availability of quinine, the current drug of choice. Several reports have suggested that raised intracranial pressure (ICP) is a major cause of death among children with cerebral malaria. Mannitol, an osmotic diuretic, effectively lowers ICP and is used to treat post traumatic raised ICP. There have been some case reports of reduction in mortality and morbidity in African children with cerebral malaria following administration of mannitol, but as these were not randomized controlled trials it is difficult to evaluate their significance. This study seeks to establish whether a single dose of intravenous mannitol given to children with cerebral malaria will significantly reduce the coma recovery time.

The purpose of this study is to see if children, who develop coma from malaria, are not making enough of a vitamin-like chemical, tetrahydrobiopterin (BH4), which is required for the brain to function normally. This information may help to identify new ways to treat malaria in the future. Study participants will include 512 children, ages 6 months to 6 years. Participants will be placed into one of 4 groups: well children; children with mild malaria; children without malaria, but with a medical problem involving the brain that requires a lumbar puncture for diagnosis (a procedure in which a needle is placed into an area surrounding the spinal cord and a sample of cerebral spinal fluid is removed); and children with a severe form of malaria affecting the brain called cerebral malaria. Study procedures will include blood samples, urine samples and lumbar puncture, only if necessary for diagnosis as part of standard practice procedures. Participants will be involved in study related procedures for up to 3 weeks.

The aim is to describe disease mechanisms of severe and cerebral malaria and identify new targets for adjunctive therapies. Despite treatment between 10-30% of patients with severe malaria die. Metabolic acidosis and cerebral malaria are major complications associated with mortality across all age groups. Still, their underlying pathogenesis remains incompletely understood. Using a metabolomics approach, this study aims to characterise the spectrum of acids accumulating during acidosis, and investigate patterns of metabolic dysregulation associated with coma and seizures.