Project Title

Clinical application of whole genome sequencing in multidrug resistance tuberculosis patients in Tanzania (CWGSMDRT-TB)

Project Objectives

General objectives To describe the incidence of drug resistance mutations in MDR-TB patients in northern Tanzania, establish epidemiological associations and evaluate the clinical application of this approach Specific objectives To describe drug susceptibility against first and second line antituberculosis drugs To identify molecular markers associated with drug resistance M. tuberculosis in this population isolates To describe associations between drug resistance genotype and clinical outcome To determine the genetic relatedness of drug resistance M. tuberculosis isolates

Host Organisation

EDCTP Project Call

Career Development Fellowship (CDF)

Study Design

case control study

Project Summary

The TMA2018CDF-2363 study is hosted at the Commission for Science and Technology (COSTECH) and conducted in collaboration with Kibong’oto Infectious Diseases Hospital (KIDH) and Muhimbili University of Health and Allied Sciences (MUHAS). The study intends to determine the clinical application of whole genome sequencing in multidrug resistance tuberculosis patients. The study hypothesizes that whole genome sequencing of multidrug resistance tuberculosis (TB) (MDR-TB) strains will improve diagnosis and treatment of TB in Tanzania while providing stringent strain discrimination. The study enrolls 153 multidrug resistance tuberculosis patients attending health services at TB dedicated Kibong’oto Hospital, northern Tanzania. WGS and bioinformatics analysis will be performed to determine mutations that predict phenotypic resistance to anti-TB drugs. Immunological tests are performed to assess an association between types of drug resistance (DR), alone or in combination and TB progression/severity. Patient’s clinical information and outcomes are obtained and compared to phenotypic and genetic data. This study will provide an insight into the role of WGS in clinical management of patients and the role of DR genes in progression and severity to TB infection. In the second year of the reporting period, about 45 MDR-TB patients have been recruited after consenting to take part in the study, making a total of 103 MDRT patients since last year. The inclusion criteria for study participants included MDRTB patients aged ≥18 years, confirmed as MDR-TB using DST, MTB/RIF assay GeneXpert® (Cepheid, Sunnyvale, CA, USA), GenoType MTBDRplus (Hain Life science, GmbH, Nehren) with willingness to provide sputum samples for laboratory analysis. All study participants were recruited after interviewing the participants using semi-structured questionnaires. All participants were interviewed using semi-structured questionnaire to capture both demographical and clinical information. Demographical information such as age, sex, marital status etc. are collected on daily basis. Further clinical information such as culture results, Immunological status in terms of viral load are taken only from TB patients co-infected with HIV in order to assess the level of immunity. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the action so far. The study has not yet achieved its full potential to impact the wider society due to delay of reagents and consumables for DNA extraction and MIC test. The full potential of the study will be achieved in third year of the project after results from minimum inhibitory concentration (MIC) test and whole genome sequencing are compared and be used by clinicians for informed decision making in management of MDRTB patients.

Current Organisation

Tanzania Commission for Science and Technology

Current Job Title

Director of Research

Biography