Current Organisation

Makerere University

Current Job Title

Lecturer

Biography

Publications

Project Title

Clinical evaluation of Novel Plasma Biomarkers for Stage Diagnosis and Treatment efficacy monitoring Among Sleeping Sickness Patients in Uganda

EDCTP Project Call

Career Development Fellowship (CDF)

Host Organisation

Project Objectives

1. To identify plasma biomarkers associated with either early or late stage T. b. gambiense disease using proteomics methods and compare with those previously identified for T. b. rhodesiense. 2. To determine the potential of plasma biomarkers identified using proteomics methods in discriminating between early and late stage patients for both T. b. rhodesiense and T. b. gambiense sleeping sickness. 3. To initiate the setup of a biomarker research team and laboratory at Makerere University.

Study Design

In this study, we propose to carry out a clinical validation of these novel plasma biomarkers as stage diagnostic markers. We shall conduct a retrospective study using archived samples from the trypanosomiasis biobank at Makerere University to assess disease staging potential. We shall select patient samples that were recruited at Lwala hospital (north Eastern Uganda) to represent Trypanosoma brucei rhodesiense cases and Omugo (West Nile) to represent T. b. gambiense cases. We shall use proteomics methods to find out if markers identified for T. b. rhodesiense also apply to T. b. gambiense. Clinical validation of identified markers will involve analysis as a single biomarker and as a panel of 2 or more analytes to determine the best predictor of late stage disease. Successful biomarkers identified from this study will form a basis for translation into field based dipstick assays for disease staging and inform policy regarding disease staging. This will greatly improve on patient management through the abolition of the mandatory requirement of an invasive lumber puncture that is painful and a discomfort to the patients. Furthermore, successful execution of this project will build capacity at Makerere University by offering critical skills to junior researchers to establish as research leaders. This work will also aid the creation or strengthening of existing networks and foster teams leading into joint grant writing to combat neglected tropical diseases.

Project Summary

Sleeping sickness progresses in two stages, the early stage with parasites in blood and the late stage in which parasite invade the central nervous system (CNS). Drug treatment for both early and late stage disease differs. Therefore, before treatment it is mandatory to determine the disease stage. However, the current staging criterion using cerebrospinal fluid (CSF) relies on an invasive lumber puncture that is also required to monitor treatment efficacy. Since initial disease diagnosis is done using blood, identification of plasma biomarkers to replace current staging and treatment efficacy evaluation criteria is paramount. Using proteomics methods, we have previously identified novel plasma biomarkers discriminating late stage from early stage patients for only T. b. rhodesiense. However, the clinical utility of these biomarkers is not yet known and not clear if these markers would apply to T. b. gambiense. In this study, we propose to carry out a clinical validation of these novel plasma biomarkers as stage diagnostic markers. We shall conduct a retrospective study using archived samples from the trypanosomiasis biobank at Makerere University to assess disease staging potential. We shall selectpatient samples that were recruited at Lwala hospital (north Eastern Uganda) to represent Trypanosoma brucei rhodesiense cases and Omugo (West Nile) to represent T. b. gambiense cases. We shall use proteomics methods to find out if markers identified for T. b. rhodesiense also apply to T. b. gambiense. Clinical validation of identified markers will involve analysis as a single biomarker and as a panel of 2 or more analytes to determine the best predictor of late stage disease. Successful biomarkers identified from this study will form a basis for translation into field based dipstick assays for disease staging and inform policy regarding disease staging. This will greatly improve on patient management through the abolition of the mandatory requirement of an invasive lumber puncture that is painful and a discomfort to the patients. Furthermore, successful execution of this project will build capacity at Makerere University by offering critical skills to junior researchers to establish as research leaders. This work will also aid the creation or strengthening of existing networks and foster teams leading into joint grant writing to combat neglected tropical diseases.

Results & Outcomes