CEREBRAL MALARIA: NEUROPATHOGENESIS AND INNOVATIVE THERAPEUTIC APPROACHES.

Cerebral malaria is the severe neurological complication and is the most frequent manifestation of falciparum malaria. It presents as unarousable coma and fever and include any degree of impaired consciousness, delirium, abnormal neurological signs and focal and generalized convulsions. Surviving patients may have an increased risk of neurological and cognitive deficits, behavioural difficulties and epilepsy making cerebral malaria a leading cause of childhood neurodisability in the region. The pathogenesis of neuro-cognitive sequelae is poorly understood as coma develops through multiple mechanisms of brain injury. Understanding of these mechanisms play vital role in developing appropriate neuroprotective interventions. Other distinguishing abnormalities include thrombocytopenia (60% of cases), hyperbilirubinemia (40%), anemia (30%) and elevated hepatic amino-transferase levels (25%). Neutrophilia with a marked increase in band forms (left shift) is present in the majority of cases. Additionally erythrocyte sedimentation rate, C-reactive protein and procalcitonin are almost invariably elevated except leukocyte count which is usually normal or low. Treatment for severe malaria comprises of primary treatment with either of oral antimalarials drugs like artemether/lumefantrine, atovaquone/proguanil, doxycycline, mefloquine followed by additional treatment and supportive care. Intravenous artesunate is considered as treatment of choice for cerebral malaria as it is found safe in infants, children and pregnant women in the second and third trimesters. Recently increased resistance to most of the existing drugs is observed and there is need for research on new drugs and drug combinations along with smart utilizations of existing antimalarials through nanotechnology based drug delivery systems. [ABSTRACT FROM AUTHOR]