Project title: Clinical application of whole genome sequencing in multidrug resistance tuberculosis ptients in Tanzania

Programme:                 EDCTP 2

Start Date:                    October 2020

End date:                      September 2024

Project Code:                TMA2018CDF-2363

Grant acronomy:          CWGSMDRTB

Brief summary describing the background and objectives of the observational clinical trial

TMA2018CDF-2363 research project, hosted at COSTECH will determine the clinical application of whole genome sequencing in multidrug resistance tuberculosis patients. The study will utilize whole genome sequencing of multidrug resistance tuberculosis (MDR-TB) in 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 (KIDH) and TB health clinics in Dar es Salaam. Whole genome sequencing (WGS) and bioinformatics analysis will be performed to determine mutations that predict phenotypic resistance to anti-TB drugs. 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 (drug resistance) DR genes in progression and disease outcome. It is conducted in collaboration with Kibong’oto Infectious Diseases Hospital and Muhimbili University of Health and Allied Sciences and University College London, United Kingdom.

Target number of participants: 153 multidrug resistance tuberculosis patients attending health services at TB clinical services at Kibong’oto and Dar es Salaam Health clinics.  

Host organization: Tanzania Commission for Science and Technology in collaboration with Kibong’oto Infectious Diseases Hospital, University College London and Muhimbili University of Health and Allied Sciences

Primary objective

To describe the incidence of drug resistance mutations in MDR-TB patients in Tanzania, establish epidemiological associations and evaluate the clinical application of this approach.

Secondary objective

To describe drug susceptibility against first and second line antituberculosis drugs

To identify molecular markers associated with drug resistance M. tuberculosis in these population isolates

To describe associations between drug resistance genotype and clinical outcome

To determine the genetic relatedness of drug resistance M. tuberculosis isolates

To determine the genetic relatedness and phylogenetic relationship of drug resistance M. tuberculosis isolates

Determination of the role of genotypic mutation alone or in combination in clinical outcome.

To monitor the microevolution events in drug resistance genes during antituberculosis therapy

Eligibility criteria:

List Inclusion criteria: Inclusion criteria will be TB patients aged ≥18 years, confirmed either as MDR-TB or non MDRTB using DST, Xpert® MTB/RIF assay GeneXpert® (Cepheid, Sunnyvale, CA, USA), GenoType MTBDRplus (Hain Life science, GmbH, Nehren) with willingness to sign a written informed consent and provide sputum samples for laboratory analysis.

List Exclusion criteria: TB patients aged <18 years, with non-confirmed MDR-TB or extensively drug-resistant tuberculosis (XDR-TB) and those who will refuse to sign a written informed consent will be excluded from the study.

Outcomes:

·         The research will have impact on understanding the molecular basis/biomarkers of drug resistance TB isolates from different regions in the country

·         Improve understanding of the role played by mutation alone or in combination in prediction of clinical manifestations/ diseases progression/ identifying patients at early stages of disease

·         Improvement in turnaround time (TAT) for informed decision making on course of infection control and improve patient treatment

Recruitment centres:    Kibong’oto Infectious Diseases Hospital & Health centres in Dar es Salaam

Ethical approval:           Tanzania National Institute for Medical Research (NIMR)

Finding sources:           European and Developing Countries Clinical Trials Partnerships (EDCTP)

Collaborators:               Tanzania Commission for Science and Technology (COSTECH)

                                    Muhimbili University of Health and Allied Sciences (MUHAS

                                    Kibong’oto Infectious Diseases Hospital (KIDH)

                                    University College London (UCL), University of London

Contact people:

1.     Dr Bugwesa Zablon Katale, Tanzania Commission for Science and Technology, P.O. BOX 4302, Dar es Salaam, Email: bugwesa.katale@costech,or.tz, Mobile: +255784687178,

2.     Prof Meck I Matee, Muhimbili University of Health and Allied Sciences, P.O.BOX 65001, Department of Microbiology and Immunology, Email: mateemecky@yahoo.com or mateemecky@gmail.com, Mobile: +255713081162

This project TMA2018CDF-2363 is part of the EDCTP2 programme supported by the European Union