Project Title

Research Capacity Strengthening Programme for Emerging and Re-emerging Infectious Diseases Control in Tanzania

EDCTP Project Call

Senior Fellowship (SF)

Project Objectives

Primary Objective • To assess the differences in changes of hearing thresholds in MDR-TB patients using NAC at a dose of 900mg daily or 900mg twice a day in combination with the aminoglycoside based regimen and compare with patients using the standard aminoglycoside based regimen. Secondary objectives • To assess the effect of NAC at a dose of 900mg daily or 900mg twice a day on pharmacokinetics of second-line anti-TB drugs • To assess safety and tolerability of patients on NAC at a dose of 900mg and 900 mg twice a day in combination with second-line anti-TB regimen • To characterize molecular mechanisms of drug-resistance in MTB from MDR-TB patients using TAC • To assess the effect of NAC on clearance of MTB using molecular bacterial load (MBL) Assay in MDR-TB patients

Study Design

Phase 2b randomized double-blind clinical trial

Project Summary

Background: Tanzania, one of the sub-Saharan African countries with endemic tuberculosis (TB) and Human Immunodeficiency Virus (HIV) is confronting emerging and re-emerging infectious disease threats such as multidrug-resistant tuberculosis (MDR-TB), dengue, chikungunya amidst the shortage of healthcare workers including medical researchers. Health research capacity strengthening (HRCS) has been recommended as one of the best approaches for the developing world in improving the ability to tackle epidemics. Aims and objectives: To conduct a clinical trial focused in TB/HIV patients that will not only answer an important scientific question of direct patient benefit but with additional components of establishing a clinical trial unit with capacity for laboratory scientists, research trialists, and a rapid response infrastructure. Methods: Through research aims proposed in the programme, the senior fellow will conduct a Phase 2b double-blind randomized controlled trial to evaluate the otoprotective efficacy, safety and tolerability of N-acetylcysteine in combination in adult subjects treated with kanamycin containing regimens for MDR-TB in Tanzania. In addition, trial participants will provide sequential sputum specimens to determine elimination of MTB in sputum using the molecular bacterial load (MBL) assay. The effect of second-line susceptibility will be determined by rt-PCR of MTB resistance determining regions as identified by the MTB specific TaqMan Array Card (TAC) platform on the elimination of MTB on the sputum. In addition, TAC results will be compared to conventional phenotypic drug susceptibility results and isolate with discordant results between TAC and the phenotypic tests will be interrogated by Whole Genome Sequencing (WGS) (on the Illumina MiSeq) platform. In the research described, next generation of scientists will be mentored at Master and Ph.D. levels. Likewise, mentees will acquire hands-on research skills in clinical trials and cutting-edge molecular diagnostic research. This will create a critical mass of experts and a functional clinical trial unit (CTU). Relevancy to EDCTP scope: The proposed programme will support the capacity strengthening of the Senior Fellow as African research leader using the train-the-trainer model. Two young investigators and two junior researchers at Ph.D. and Master degree levels respectively will be mentored during the conduct of proposed clinical trial activities. Expected impact: Researchers in this project will be designing and conducting clinical trials ( meeting the International Conference on Harmonisation – Good Clinical Practice (ICH-GCP) standards) and investigating infectious diseases pathogens using cutting-edge molecular diagnostics. The team will continuously thrive and address the challenges of infectious diseases threats in the country.

Host Organisation

Sites

Current Organisation

Kibong'oto Infectious Diseases Hospital

Current Job Title

Physcian cum Scientist

Biography