Non-tuberculosis (TB) bacteria in patients with TB in Kampala, Uganda
| ISRCTN | ISRCTN14141535 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14141535 |
- Submission date
- 01/10/2021
- Registration date
- 17/03/2022
- Last edited
- 17/03/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English Summary
Background and study aims
The microbiota are complex communities of microbes that reside in mammals and play a significant role in health and disease including induction/function of the immune system. However, baseline information on their composition and potential role(s) in pulmonary tuberculosis (TB) in sub-Saharan Africa, is lacking.
TB is a bacterial infection spread through inhaling tiny droplets from the coughs or sneezes of an infected person. It mainly affects the lungs, but it can affect any part of the body, including the tummy (abdomen), glands, bones and nervous system.
The overall purpose of this proposal is to determine the composition of the microbiota in pulmonary TB in Kampala, Uganda, and examine its relationship with treatment- and immune-response in TB patients relative to their household healthy contacts without TB-infection and HIV-infection.
Who can participate?
Adults (18 years or older) newly diagnosed with TB
What does the study involve?
Participants will provide blood, stool, and sputum samples a number of times over a 2 year period.
What are the possible benefits and risks of participating?
Apart from the contribution of knowledge generation that could advance tuberculosis research in Africa, there are no direct benefits in participating in the study. There are very minimal risks of participating as we will use clinical specimens that are routinely collected during patient investigation. As we will collect a small amount of blood (i.e., 5 ml) from the participants, they may experience some pain in the course of phlebotomy.
Where is the study run from?
Makerere University College of Health Sciences (Uganda)
When is the study starting and how long is it expected to run for?
January 2019 to December 2026
Who is funding the study?
European and Developing Countries Clinical Trials Partnership (TMA2018CDF-2357)
Who is the main contact?
Dr David Kateete, davidkateete@gmail.com
Ms Geraldine Nalwadda, nalwaddageraldine@gmail.com
Contact information
Scientific
Makerere University College of Health Sciences
Upper Mulago Hill Road
Box 7072
Kampala
-
Uganda
 ORCID ID |
0000-0001-8075-3069 |
|---|---|
| Phone | +256704879922 |
| david.kateete@mak.ac.ug |
Public
Makerere University College of Health Sciences
Upper Mulago Hill Road
Box 7072
Kampala
-
Uganda
| Phone | +256414541830 |
|---|---|
| geraldine.nalwadda@mak.ac.ug |
Study information
| Study design | Longitudinal observational |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Community |
| Study type | Other |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Insight into the role of the microbiome in pulmonary tuberculosis in Kampala, Uganda |
| Study acronym | MTI-Plus |
| Study hypothesis | The microbiota/microbiome, complex communities of microbes in mammals, play a significant role in health and disease including induction/function of the immune system. However, baseline information on their composition and potential role(s) in pulmonary tuberculosis (TB) in sub-Saharan Africa, is lacking. The overall purpose of this proposal is to determine the microbiome composition in pulmonary TB in Kampala, Uganda, and examine its relationship with treatment- and immune-response in TB patients relative to their household healthy contacts without TB-infection and HIV-infection. |
| Ethics approval(s) | Approved 24/06/2020, Makerere University School of Biomedical Sciences Research Ethics Committee (SBS-REC, P.O. Box 7072 Kampala, Uganda; +256-414-532-204; biomedicalresearch62@gmail.com), ref: SBS-REC 780 |
| Condition | Investigation of the microbiome of patients with tuberculosis |
| Intervention | In the proposed project, we will investigate sputum, stool and blood samples from a total of 800 participants at baseline (day 0 before administering therapy), as well as months 2, 5, 12, 18 and 24 for microbial and cytokine profiles. Note, of the 800 participants, 500 will be pulmonary TB cases of whom 300 are expected to be HIV-positive (TB+/HIV+) while 200 will be HIV-negative (TB+/HIV-) given the HIV/TB co-infection rate of 40% in Uganda. We will investigate baseline samples (sputum, stool & blood) from 300 household contacts (i.e. the comparator group) of the 500 TB patients: Household contacts will be adults and healthy (i.e. HIV negative & TB negative with no signs of disease symptoms) family members of the 500 TB cases matched for age and gender. We will avail human microbiota profiles of patients from a TB endemic setting with high rate of HIV/TB coinfection, whose profiles could be used as a reference for similar settings in Africa. Overall, we will investigate sputum, stool and blood samples from each of the 800 participants (500 TB cases and 300 healthy controls i.e. household contacts), as outlined above. Each household will be visited by a study nurse who will identify the healthy contacts (aged 18 years and older). In each household, consented contacts will be screened for TB and HIV, and interviewed for information on demographic characteristics, history of illnesses and antibiotic treatment. Contacts found to have HIV and/or TB will not be recruited but the results will be provided to them via a counsellor at the TB clinic. Note that samples from each household contacts (n=300) will be collected as described for the TB cases (i.e. by an expert pulmonologist and/or study nurse) but only once at baseline. In other words, we will not follow-up healthy contacts since they won’t be on treatment for TB. On the other hand, more samples (sputum, stool and blood) will be collected from pulmonary TB patients (n=500) at months 2, 5, 12, 18 and 24. To obtain stool, participants will be provided with sterile containers for collecting samples before they take anti-TB drugs, and instructed to return samples to the TB clinic the following day. To prevent growth of bacteria, 2-β-mercaptoethanol (2%) will be added to the samples immediately after collection and transported in a cool-box to the Molecular Laboratory for DNA/RNA purification; the extracted DNA/RNA will be stored at -80°C in the biorepository. As well, 50 ml of blood will be drawn from each TB participant and immediately taken to the laboratory for preparation of serum/plasma and isolation of peripheral blood mononuclear cells (PBMCs). Samples (sputum, stool and blood) from each participant will be processed as below; please note that for healthy controls, samples will be taken only at baseline while for TB cases, samples will be collected at baseline (before treatment initiation) and during follow-up (months 2, 5, 12, 18 and 24). Following processing, we will store the remaining samples (serum/plasma, blood, stool and sputum) at the H3Africa Biorepository for a period of 5 years. |
| Intervention type | Other |
| Primary outcome measure | Microbiome composition and diversity measured from stool sample using the alpha and beta diversity indices in the 'R' statistical package at baseline (time 0) and at 2, 5, 12, 18, and 24 months |
| Secondary outcome measures | Cytokine profiles relative to the microbiome composition and diversity measured using serum/plasma, blood, stool and sputum samples using the ELISA assay at baseline (time 0) |
| Overall study start date | 01/01/2019 |
| Overall study end date | 01/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 800 |
| Participant inclusion criteria | New adult TB patients 18 years and older |
| Participant exclusion criteria | 1. Previously treated TB patients 2. Children |
| Recruitment start date | 01/10/2021 |
| Recruitment end date | 31/10/2024 |
Locations
Countries of recruitment
- Uganda
Study participating centre
Box 7072
Kampala
-
Uganda
Sponsor information
University/education
Upper Mulago Hill Road
Box 7072
Kampala
-
Uganda
| Phone | +256-414-532631- 4 |
|---|---|
| pro@admin.mak.ac.ug | |
| Website | http://mak.ac.ug/ |
"ROR" |
https://ror.org/03dmz0111 |
Funders
Funder type
Government
Private sector organisation / International organizations
- Alternative name(s)
- Le partenariat Europe-Pays en développement pour les essais cliniques, A Parceria entre a Europa e os Países em Desenvolvimento para a Realização de Ensaios Clínicos, The European & Developing Countries Clinical Trials Partnership, European and Developing Countries Clinical Trials, EDCTP
- Location
- Netherlands
Results and Publications
| Intention to publish date | 12/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Published as a supplement to the results publication |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication. |
Editorial Notes
21/10/2021: Trial's existence confirmed by Makerere University.
