Severe Malaria
Conditions
Keywords
Pathogenesis, Microvascular function, Metabolic dysregulation, Metabolomics
Brief summary
* 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.
Interventions
OTHERObservation
Sponsors
Chittagong Medical College and Hospital
University of Oxford
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterisation of patterns of metabolic dysregulation in severe malaria | 4-6 weeks | Interrelationship between disturbances in metabolic pathways associated with acidosis and cerebral malaria |
Countries
Bangladesh
Outcome results
None listed