Severe and Cerebral Malaria Investigated Through Host Metabolomics

Severe/Cerebral Malaria: * Any P. falciparum parasitaemia detected by asexual stages on a peripheral blood-slide or a positive rapid diagnostic test in combination with one or more Modified WHO Criteria for Severe Malaria (Hien et al, 1996) * \< 24 hours after treatment commencement with either parenteral artemisinin or quinine * Age \> 12 years * Full informed written consent obtained Uncomplicated malaria: * Any level of Plasmodium parasitaemia, detected by asexual stages on a peripheral blood-slide or a positive rapid diagnostic test without any of the complications of severe malaria stated above. * Age \> 12 years * Full informed written consent obtained Sepsis: * Clinical signs of infection in combination with any two of the following signs: 1. Heart rate \> 90 beats per minute; 2. Respiratory rate \> 20 breaths per minute, a PaCO2 of \< 32 mmHg, or the use of mechanical ventilation for an acute respiratory process; 3. Tympanic temperature \> 38°C or \< 36 °C; 4. White-cell count of \> 12x109/L or \< 4x109/L, or a differential count showing 10% immature neutrophils ; * Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria * \[As bacterial culture is not routinely available at the study site, positivity of cultures is not required\] * Age \> 12 years * Full informed written consent obtained Acidosis: * Clinical suspicion of metabolic acidosis in combination with any of the following: 1. Peripheral venous bicarbonate \< 15 mmol/L 2. Peripheral venous base excess \< -3 mmol/L * Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria; and not meeting any of the inclusion criteria for sepsis as stated above. * Age \> 12 years * Full informed written consent obtained Encephalitis: * GCS \< 11/15 * Documented fever \> 38°C * Onset of symptoms \< 2 weeks, with an indication a lumbar puncture as part of the diagnostic work up * Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria * Age \> 12 years * Full informed written consent obtained Healthy volunteers: * No chronic or acute disease * No fever in the past 2 weeks * Age \> 16 years * Full informed written consent obtained Exclusion Criteria: * Known pre-existing chronic medical conditions including advanced hepatic disease.