Cerebral Malaria Clinical Trial
Official title:
Randomized Trial of Erythropoietin to Prevent Death From Cerebral Impairment During Severe Malaria
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.
n/a
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