The usefulness of whole genome sequencing in diagnosis and clinical management of drug-resistant tuberculosis patients in Tanzania

ISRCTN ISRCTN14635089
DOI https://doi.org/10.1186/ISRCTN14635089
Secondary identifying numbers NIMR/HQ/R.8a/Vol.IX/3600
Submission date
10/11/2023
Registration date
06/03/2024
Last edited
06/03/2024
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Drug-resistant tuberculosis (DR-TB) poses a significant challenge to global tuberculosis (TB) control efforts. Whole genome sequencing (WGS) which is based on genetic change of the TB causing bacteria (Mycobacterium tuberculosis) has been used in diagnosis and management of drug resistance TB patients in developed countries, but its incorporation into the detection of TB in developing countries is limited due to lack of expertise and financial capabilities. This study aims to determine the usefulness of WGS in detection and management of TB patients by comparing with currently used diagnostic tests such as growth of bacterial causing TB disease, GeneXpert test (currently used detection test for TB diagnosis in health centers).

Who can participate?
The participation in the study is voluntary and will involve TB patients who do not respond to treatments of at least isoniazid and rifampin, the two most potent TB drugs.

What does the study involve?
Patients receive treatments as per guidelines for the management of the disease in the country.

What are the possible benefits and risks of participating?
The study is non-invasive; hence risk is minimal based on the fact that only sputum sample on the spot is routinely required at the health centre.

Where is the study run from?
Tanzania Commission for Science and Technology in collaboration with Muhimbili University of Health and Allied Sciences and Kibong'oto Infectious Diseases Hospital, Moshi, Kilimanjaro region in the United Republic of Tanzania.

When is the study starting and how long is it expected to run for?
October 2020 to October 2024

Who is funding the study?
European and Developing Countries Clinical Trials Partnerships (EDCTP)

Who is the main contact?
Dr Bugwesa Katale
bugwesa2002@yahoo.co.uk
zablon.bugwesa@sacids.org
bugwesa.katale@costech.or.tz

Study website

Contact information

Dr Bugwesa Katale
Public, Scientific, Principal Investigator

Tanzania Commission for Science and Technology, P.O. BOX 4302
Dar es Salaam
14113
Tanzania

ORCiD logoORCID ID 0000-0002-3276-2603
Phone +255 784687178
Email zablon.bugwesa@sacids.org
Dr Bugwesa Katale
Public, Scientific, Principal Investigator

Tanzania Commission for Science and Technology, P.O. BOX 4302
Dar es Salaam
14113
Tanzania

Phone +255784687178
Email bugwesa.katale@costech.or.tz

Study information

Study designObservational cross sectional
Primary study designObservational
Secondary study designCross sectional study
Study setting(s)Hospital, Laboratory
Study typeDiagnostic
Participant information sheet No participant information sheet available
Scientific titleClinical application of whole genome sequencing in multidrug-resistant tuberculosis patients in Tanzania
Study acronymCWGSMDRT-TB
Study objectivesWhole genome sequencing of DR TB strains will improve the diagnosis and treatment of TB in Tanzania while providing stringent strain discrimination.
Ethics approval(s)

Approved 01/10/2020, National health Research Ethics Committee (NaTHREC) (3 Baraka Obama Drive, P.O. BOX 9653, 11101, Dar es Salaam, 12101, Tanzania; +255 222121400; hq@nimr.or.tz), ref: NIMR/HQ/R.8b/Vol.I/1099, 2021-617-NA-2021/109

Health condition(s) or problem(s) studiedApplication of whole genome sequencing in multidrug resistance tuberculosis patients
InterventionThis study is an observational clinical trial focusing on multidrug-resistant tuberculosis (MDRTB) patients at Kibong’oto Infectious Diseases Hospital in Moshi, Tanzania. The objective is to assess the efficacy of whole genome sequencing (WGS) in comparison to the existing diagnostic methods for detecting MDRTB in the country.

The participants in the trial will be MDRTB patients attending tuberculosis (TB) clinics, who have been initially diagnosed using Xpert MTB/RIF and subsequently confirmed through Line Probe Assays (LPA), specifically the GenoType MTBDRplus. Every second MDRTB patient seeking health services at the clinic will be included in the study.

The evaluation will involve comparing WGS with the current diagnostic tests, including culture, drug susceptibility testing, and GeneXpert. The goal is to determine the utility and effectiveness of WGS in detecting multidrug resistance in tuberculosis patients as compared to the standard diagnostic procedures currently in use.
Intervention typeDevice
Pharmaceutical study type(s)Not Applicable
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Illumina hiseq
Primary outcome measureThe efficacy of the diagnostic tests including drug susceptibility testing (DST), line probe assay and GeneXpert measured against the Gold standard (Culture).
Secondary outcome measuresWhole genome diagnostic efficacy will be measured against the gold standard test (culture). The measurement will be sensitivity and specificity.
Overall study start date01/10/2020
Completion date01/11/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit80 Years
SexBoth
Target number of participants153
Key inclusion criteria1. TB patients aged ≥18 years
2. 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)
3. Willingness to sign a written informed consent and provide sputum samples for laboratory analysis.
Key exclusion criteriaDoes not meet inclusion criteria
Date of first enrolment01/10/2021
Date of final enrolment01/11/2024

Locations

Countries of recruitment

  • Tanzania

Study participating centre

Kibong'oto Infectious Diseases Hospital & Muhimbili National Hospital
Private Bag, Siha, Moshi, Kilimanjaro
Dar es Salaam
25101
Tanzania

Sponsor information

Funders

Funder type

Government

European and Developing Countries Clinical Trials Partnerships

No information available

Results and Publications

Intention to publish date31/12/2024
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryStored in non-publicly available repository, Available on request
Publication and dissemination planPlanned publication in peer reviewed and high impact journal. presentations in Biannual EDCTP scientific Forum and local scientific conferences.
IPD sharing planThe dataset generated from the study will be stored at Tanzania Commission for Science and Technology repository and shared upon request.

Editorial Notes

13/11/2023: Trial's existence confirmed by National health Research Ethics Committee (NaTHREC)