EDCTP Project Call

EDCTP-AREF Preparatory Fellowships (PF)

Project Objectives

Pulmonary Tuberculosis (TB) is a devastating disease that affects almost 10 million people and kills 1.8 million annually around the world. Mycobacterium tuberculosis (M. tuberculosis) the causative agent of TB can become MDR-TB, which complicates the patient’s condition and affects the disease course with very poor prognosis. Low bioavailability of anti-tuberculosis drugs postulated to be one of the causes of MDR-TB. Variation of anti-tuberculosis drugs bioavailability can be owing to polymorphisms of some drug transporters genes that control drugs absorption and secretion. Some of these gene polymorphisms are widely prevalent among Sub-Saharan African populations and some are not investigated. We aim to determine the pharmacokinetic of rifampicin in Sudanese patients with pulmonary tuberculosis and MDR-TB. In addition, determine the effect of these transporters’ gene polymorphisms on the bioavailability of the rifampicin. Moreover, determine whether rifampicin exposure is associated with decrease rate of sputum conversion and development of MDR-TB or not?

Study Design

We propose a piloting cohort that follow-up 70 patients with pulmonary tuberculosis who diagnosed according to American thoracic criteria. These patients’ sputum will be examined also by GeneXpert to rule-out any possibility of rifampicin resistance or MDR at the time of diagnosis. DNA sequencing for M. tuberculosis will also be done to make sure there is no secondary infections by another MDR-TB bacteria. After 2, 5 and 6 months of starting the anti-tuberculosis drugs, sputum microscopy and culture will be done to differentiate those who developed MDR-TB and those who are drug susceptible. Blood will be collected from the patients to isolate DNA. Genotyping will be done in selected transporters’ gene by PCR-RFLP and for others by DNA sequencing. Blood samples will be collected at 1, 3 and 8 hours from taking the drugs just once for rifampicin assay. Pharmacokinetic analysis and population model will be done at University of Cape Town in collaboration with Professor Helen McIlleron and Dr.Paolo Denti. Patients will be recruited from Bashier University hospital which is affiliated to the Fellow’s Home organisation. A bigger sample size study will be conducted based on the findings of this study with building of a simulation model that tested against higher rifampicin doses for those who have risky allele. A superiority clinical trial will be embarked based on the studies finding that increase the dose for better clinicals outcomes. The study will have direct policy and clinical implications that hinting to better clinical and epidemiological outcomes for pulmonary tuberculosis.

Project Summary

ulmonary Tuberculosis (TB) is a devastating disease that affects almost 10 million people and kills 1.8 million annually around the world. Mycobacterium tuberculosis (M. tuberculosis) the causative agent of TB can become MDR-TB, which complicates the patient’s condition and affects the disease course with very poor prognosis. Low bioavailability of anti-tuberculosis drugs postulated to be one of the causes of MDR-TB. Variation of anti- tuberculosis drugs bioavailability can be owing to polymorphisms of some drug transporters genes that control drugs absorption and secretion. Some of these gene polymorphisms are widely prevalent among Sub-Saharan African populations and some are not investigated. We aim to determine the pharmacokinetic of rifampicin in Sudanese patients with pulmonary tuberculosis and MDR-TB. In addition, determine the effect of these transporters’ gene polymorphisms on the bioavailability of the rifampicin. Moreover, determine whether rifampicin exposure is associated with decrease rate of sputum conversion and development of MDR-TB or not? We propose a piloting cohort that follow-up 70 patients with pulmonary tuberculosis who diagnosed according to American thoracic criteria. These patients’ sputum will be examined also by GeneXpert to rule-out any possibility of rifampicin resistance or MDR at the time of diagnosis. DNA sequencing for M. tuberculosis will also be done to make sure there is no secondary infections by another MDR-TB bacteria. After 2, 5 and 6 months of starting the anti-tuberculosis drugs, sputum microscopy and culture will be done to differentiate those who developed MDR-TB and those who are drug susceptible. Blood will be collected from the patients to isolate DNA. Genotyping will be done in selected transporters’ gene by PCR-RFLP and for others by DNA sequencing. Blood samples will be collected at 1, 3 and 8 hours from taking the drugs just once for rifampicin assay. Pharmacokinetic analysis and population model will be done at University of Cape Town in collaboration with Professor Helen McIlleron and Dr.Paolo Denti. Patients will be recruited from Bashier University hospital which is affiliated to the Fellow’s Home organisation. A bigger sample size study will be conducted based on the findings of this study with building of a simulation model that tested against higher rifampicin doses for those who have risky allele. A superiority clinical trial will be embarked based on the studies finding that increase the dose for better clinical outcomes. The study will have direct policy and clinical implications that hinting to better clinical and epidemiological outcomes for pulmonary tuberculosis.

Host Organisation

Current Organisation

Current Job Title

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