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 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 design	Observational cross sectional
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	Hospital, Laboratory
Study type	Diagnostic
Participant information sheet	No participant information sheet available
Scientific title	Clinical application of whole genome sequencing in multidrug-resistant tuberculosis patients in Tanzania
Study acronym	CWGSMDRT-TB
Study objectives	Whole 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) studied	Application of whole genome sequencing in multidrug resistance tuberculosis patients
Intervention	This 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 type	Device
Pharmaceutical study type(s)	Not Applicable
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Illumina hiseq
Primary outcome measure	The efficacy of the diagnostic tests including drug susceptibility testing (DST), line probe assay and GeneXpert measured against the Gold standard (Culture).
Secondary outcome measures	Whole genome diagnostic efficacy will be measured against the gold standard test (culture). The measurement will be sensitivity and specificity.
Overall study start date	01/10/2020
Completion date	01/11/2024

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	80 Years
Sex	All
Target number of participants	153
Key inclusion criteria	1. 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 criteria	Does not meet inclusion criteria
Date of first enrolment	01/10/2021
Date of final enrolment	01/11/2024

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

Tanzania Commission for Science and Technology
Research council

P.O. BOX 4302
Dar es Salaam
11101
Tanzania

Phone	+255 784687178
Email	dg@costech.or.tz
Website	https://www.costech.or.tz
"ROR"	https://ror.org/03e04g978

Funders

Funder type

Government

European and Developing Countries Clinical Trials Partnerships

No information available

Results and Publications

Intention to publish date	31/12/2024
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Stored in non-publicly available repository, Available on request
Publication and dissemination plan	Planned publication in peer reviewed and high impact journal. presentations in Biannual EDCTP scientific Forum and local scientific conferences.
IPD sharing plan	The 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)