Severe and Cerebral Malaria Investigated Through Host Metabolomics

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT02451904

Collaborator

Chittagong Medical College and Hospital (Other)

840

Enrollment

Location

Actual Duration (Months)

31.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Malaria	Other: Observation

Study Design

Study Type:

Observational

Actual Enrollment :

840 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Microvascular and Metabolic Dysregulation in the Pathogenesis of Severe and Cerebral Malaria Investigated Through Host Metabolomics

Actual Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Sep 1, 2017

Actual Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Severe/Cerebral Malaria Intensive monitoring	Other: Observation
Uncomplicated Malaria Intensive monitoring	Other: Observation
Sepsis Intensive monitoring	Other: Observation
Acidosis Intensive monitoring	Other: Observation
Encephalitis Intensive monitoring	Other: Observation
Healthy Individuals Monitoring	Other: Observation

Outcome Measures

Primary Outcome Measures

Characterisation of patterns of metabolic dysregulation in severe malaria [4-6 weeks]
Interrelationship between disturbances in metabolic pathways associated with acidosis and cerebral malaria

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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:

Heart rate > 90 beats per minute;
Respiratory rate > 20 breaths per minute, a PaCO2 of < 32 mmHg, or the use of mechanical ventilation for an acute respiratory process;
Tympanic temperature > 38°C or < 36 °C;
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:

Peripheral venous bicarbonate < 15 mmol/L
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