TuberculosisStool4TBNCT05047315
Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV
An observational study of Tuberculosis and Diagnoses Disease, run by Barcelona Institute for Global Health at 3 sites in 3 countries.
Trial summary
Stool4TB aims to evaluate an innovative stool-based qPCR diagnostic platform (with the capacity to become a POC diagnostic tool) in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the extremely large TB case detection gap by improving TB confirmation… Read more about this study
- Who is it for?
- Ages 0 to 8 yearsHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, Diagnoses Disease
- How many people
- 1,967 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 1 Dec 2021to 30 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 8 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Our proposed diagnostic evaluation will be performed in three high TB/HIV burden settings in populations where the tests are intended to be used (presumptive adult pulmonary TB cases and presumptive intrathoracic pediatric TB cases). The study will enroll presumptive TB cases within two study groups: 1. Children less than 8 years of age (irrespective of HIV status) 2. Adults living with HIV (>15 years of age), irrespective of immunological status.
Who may be able to join
- Pediatric Cohort
- <8 years of age
- Identified with suspected PTB defined as follows:
- A child with ≥1 of the following criteria:
- <!-- -->
- Persistent unremitting cough (or cough significantly worse than usual in child with chronic lung disease including HIV-related) of >2 weeks duration, unresponsive to a course of appropriate antibiotics (when clinically indicated)
Show all 18Show fewer
- Poor growth documented over the preceding 3 months [clear deviation from a previous growth trajectory and/or documented crossing of centile lines in the preceding 3 months and/or; weight-for-age, or weight-for-height Z-score of ≤2 in the absence of information on previous/recent growth trajectory AND not responding to nutritional rehabilitation (or to antiretroviral therapy if HIV-infected)]
- Persistent unexplained lethargy or reduced playfulness/activity reported by the caregiver.
- Persistent (>1w) unexplained fever (>38C), reported by a guardian or objectively recorded at least once;
- In infants 0-60 days, also: unresponsive neonatal pneumonia or unexplained hepatosplenomegaly OR sepsis-like illness (all other more common causes excluded and/or not responding to appropriate therapy/ broad-spectrum antibiotics/antivirals).
- OR
- 2) Any duration of cough/ wheeze/ acute pneumonia with ≥1:
- TB exposure. Either: i) Documented/Reported exposure to a known TB source case (regardless of smear status) in previous 12months OR ii) immunological evidence: positive IGRA or positive TST (defined as >5mm in HIV infected or severely malnourished, >10 otherwise)
- Chest radiograph suggestive of TB.
- Adult Cohort (WHO definition of a HIV-positive presumptive TB case)
- > 15 years of age
- Confirmed HIV infection (ELISA or molecular)
- Presenting at any health facility with any of the following: cough, fever, night sweats or unintentional weight loss (any duration).
Who cannot join
- Participants will be excluded (both from study groups) if:
- Receiving TB treatment for >72 hours in previous 2 weeks
- History of TB treatment in the last year
- Refusal to provide consent for study participation or HIV testing when status is unknown
- Severe illness resulting in unstable condition
- Absolute contra-indication to any of sampling procedures required by the study (ie: acute severe asthma, pertussis syndrome etc.)
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
Mozambique1 site
Centro de investigação de Saúde de Manhiça
Manhiça, Maputo Province, 1929
About this study
Stool4TB aims to evaluate an innovative stool-based qPCR diagnostic platform (with the capacity to become a POC diagnostic tool) in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the extremely large TB case detection gap by improving TB confirmation rates in children and people living with HIV (PLHIV).
Read the detailed description
Tuberculosis (TB) continues to be a leading cause of morbidity and mortality among children and people living with HIV (PLHIV). Despite significant progress in TB diagnostics, improvement of childhood TB diagnosis continues to be a major challenge and is a key pillar of the WHO "End TB Strategy". TB laboratory confirmation is particularly challenging in children and PLHIV given the difficulty in obtaining sputum samples, and the pauci-bacillary nature of disease. In consequence, bacteriological confirmation of pulmonary TB in young children and immunosuppressed PLHIV remains disappointingly low. Inability to bacteriologically confirm TB, results in both i) under diagnosis which leads to worse outcomes including increased mortality and ii) over or under diagnosis, and poor resource allocation. Given the limitations of currently available sputum-based diagnostic tests in these vulnerable populations, there is a need to develop new tools and identify easy to collect non-respiratory specimens which, combined, could improve bacteriological confirmation. Preliminary data suggest that a new platform, an innovative stool homogenization and DNA isolation method, adds value to existing sputum-based diagnostics by increasing the rates of bacteriological confirmation, and could also be useful as a monitoring tool for treatment response. This platform has the potential to be adapted to a point of care (POC) diagnostic and thus easily implemented in resource-constrained basic health care centres.
Objective: The aim of this project is to evaluate the diagnostic performance of the stool bead-based real-time quantitative PCR (qPCR) platform for TB diagnosis in children and PLHIV. This will be evaluated in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the large TB case detection gap by improving TB confirmation rates in children and PLHIV, while proving feasible and acceptable.
Primary objective:
- Evaluate the diagnostic accuracy of a stool-based real-time quantitative PCR for detecting DNA of Mycobacterium tuberculosis (MTB qPCR), compared to a composite reference standard (sputum and stool Xpert Ultra, sputum culture and urine TB-LAM).
Secondary objectives:
- Evaluate the diagnostic accuracy of the stool-based Mtb qPCR to individual sputum and stool Xpert Ultra, urine LAM, sputum smear and sputum culture (MGIT) results using a consensus clinical case definition as the reference standard.
- Evaluate the usefulness of the quantitative stool-based MTB qPCR platform as a tool to monitor treatment response for children and PLHIV.
- To create a biorepository of well characterized pediatric samples at each of the study sites to support the future development and evaluation of novel biomarker research.
Methodology: This is a prospective diagnostic evaluation study with a nested longitudinal cohort evaluation. During a 30-month recruitment period, people with presumptive TB will consecutively enroll being part of two study groups: Children less than 8 years of age, irrespective of HIV status (N=1295) and adults living with HIV, irrespective of immunological status (N=650). Sixty extra people will take part as healthy (asymptomatic) controls. After clinical, radiological and bacteriological evaluation, TB cases will be treated according to national guidelines. Participants diagnosed with TB will be followed up for 6 months since treatment initiation in order to assess treatment response and outcomes. A clinical case definition will be established as a reference standard and defined as any participant in whom a decision is made to start ATT (TB cases will be classified as confirmed or unconfirmed). Specifically, children will be classified into 3 distinct pediatric endpoint categories (confirmed TB, unconfirmed TB and Unlikely TB) based on bacteriological, radiological and clinical criteria, following international consensus guidelines.
- Conditions
- Tuberculosis, Diagnoses Disease
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Adult | Adults >15 with confirmed HIV status and presumptive TB | |
| Pediatric | Children <8 years of age with presumptive TB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic performance qPCR test in stool samples
Diagnostic performance (Sensitivity, specificity, negative and positive predictive value) of the qPCR test in stool samples with respect to:
- bacteriologically confirmed tuberculosis as a composite gold standard of any of the other tests positive (including induced sputum and gastric aspirate Xpert Ultra and MGIT culture, stool Ultra or TB-LAM in urine)
- clinical reference standard case definition (S. Graham et al.; CID 2015).
Measured: 2 months
Secondary outcomes (2)
Comparison of diagnostic performance
Diagnostic performance of the qPCR test in stool compared to each of the other microbiological confirmation tests separately with respect to:
- bacteriologically confirmed tuberculosis as a composite excluding index/comparator).
- clinical l reference standard case definition (S. Graham et al.; CID 2015).
Measured: 2 months
Monitor response to TB treatment
Ability of qPCR test in stool to monitor response to TB treatment, by comparing the change in readout over time while receiving TB treatment to that of Xpert Ultra in sputum and in stool.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2021
- Study start1 Dec 2021
- Primary completion17 Dec 2024
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,967 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barcelona Institute for Global Health
- Sponsor type
- University, hospital or other
- Collaborators
- Makerere University, Amsterdam Institute for Global Health and Development, Centro de Investigacao em Saude de Manhica, Baylor Eswatini Clinical Centre of Excellence (COE), Research Center Borstel, Fundação Manhiça, Baylor College of Medicine
- Responsible party
- Sponsor
- Investigators
- Alberto L García-Basteiro, MD, PhD, Principal investigator, Barcelona Institute for Global HealthElisa López Varela, MD, PhD, Study director, Barcelona Institute for Global Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05047315
- Sponsor's protocol ID
- RIA2018D-2511
- Acronym
- Stool4TB
- Status last verified
- Mar 2026
- First submitted
- 8 Sep 2021
- Last updated
- 6 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kasule GW, Hermans S, Acacio S, Kay A, Nsubuga JK, Fernandez-Escobar C, Shiba N, Carratala-Castro L, Semugenze D, Mwachan P, Munguambe S, Ehrlich J, Lopez-Varela E, DiNardo AR, Cobelens F, Lange C, Joloba M, Mandalakas AM, Ssengooba W, Garcia-Basteiro AL; Stool4TB Global Partnership. Performance of stool Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis among adults living with HIV: a multicentre, prospective diagnostic study. Lancet Microbe. 2025 Jul;6(7):101085. doi: 10.1016/j.lanmic.2025.101085. Epub 2025 Apr 4.
PubMed 40194533Carratala-Castro L, Ssengooba W, Kay A, Acacio S, Ehrlich J, DiNardo AR, Shiba N, Nsubuga JK, Munguambe S, Saavedra-Cervera B, Manjate P, Mulengwa D, Sibandze B, Ziyane M, Kasule G, Mambuque E, Sekadde MP, Wobudeya E, Joloba ML, Heyckendorf J, Lange C, Hermans S, Mandalakas A, Garcia-Basteiro AL, Lopez-Varela E; Stool4TB Global Partnership. A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation. BMC Infect Dis. 2024 Feb 21;24(1):233. doi: 10.1186/s12879-023-08708-9.
PubMed 38383310
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV
- ClinicalTrials.gov ID
- NCT05047315
- Acronym / sponsor ID
- Stool4TB / RIA2018D-2511
- Conditions
- Tuberculosis, Diagnoses Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,967 participants (actual)
- Lead sponsor
- Barcelona Institute for Global HealthUniversity, hospital or other
- Collaborators
- Makerere University, Amsterdam Institute for Global Health and Development, Centro de Investigacao em Saude de Manhica, Baylor Eswatini Clinical Centre of Excellence (COE), Research Center Borstel, Fundação Manhiça, Baylor College of Medicine
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 17 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stool4TB aims to evaluate an innovative stool-based qPCR diagnostic platform (with the capacity to become a POC diagnostic tool) in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the extremely large TB case detection gap by improving TB confirmation rates in children and people living with HIV (PLHIV).
Detailed description
Tuberculosis (TB) continues to be a leading cause of morbidity and mortality among children and people living with HIV (PLHIV). Despite significant progress in TB diagnostics, improvement of childhood TB diagnosis continues to be a major challenge and is a key pillar of the WHO "End TB Strategy". TB laboratory confirmation is particularly challenging in children and PLHIV given the difficulty in obtaining sputum samples, and the pauci-bacillary nature of disease. In consequence, bacteriological confirmation of pulmonary TB in young children and immunosuppressed PLHIV remains disappointingly low. Inability to bacteriologically confirm TB, results in both i) under diagnosis which leads to worse outcomes including increased mortality and ii) over or under diagnosis, and poor resource allocation. Given the limitations of currently available sputum-based diagnostic tests in these vulnerable populations, there is a need to develop new tools and identify easy to collect non-respiratory specimens which, combined, could improve bacteriological confirmation. Preliminary data suggest that a new platform, an innovative stool homogenization and DNA isolation method, adds value to existing sputum-based diagnostics by increasing the rates of bacteriological confirmation, and could also be useful as a monitoring tool for treatment response. This platform has the potential to be adapted to a point of care (POC) diagnostic and thus easily implemented in resource-constrained basic health care centres.
Objective: The aim of this project is to evaluate the diagnostic performance of the stool bead-based real-time quantitative PCR (qPCR) platform for TB diagnosis in children and PLHIV. This will be evaluated in the high TB and HIV burden settings of Mozambique, Eswatini and Uganda, under the hypothesis that it will narrow the large TB case detection gap by improving TB confirmation rates in children and PLHIV, while proving feasible and acceptable.
Primary objective:
- Evaluate the diagnostic accuracy of a stool-based real-time quantitative PCR for detecting DNA of Mycobacterium tuberculosis (MTB qPCR), compared to a composite reference standard (sputum and stool Xpert Ultra, sputum culture and urine TB-LAM).
Secondary objectives:
- Evaluate the diagnostic accuracy of the stool-based Mtb qPCR to individual sputum and stool Xpert Ultra, urine LAM, sputum smear and sputum culture (MGIT) results using a consensus clinical case definition as the reference standard.
- Evaluate the usefulness of the quantitative stool-based MTB qPCR platform as a tool to monitor treatment response for children and PLHIV.
- To create a biorepository of well characterized pediatric samples at each of the study sites to support the future development and evaluation of novel biomarker research.
Methodology: This is a prospective diagnostic evaluation study with a nested longitudinal cohort evaluation. During a 30-month recruitment period, people with presumptive TB will consecutively enroll being part of two study groups: Children less than 8 years of age, irrespective of HIV status (N=1295) and adults living with HIV, irrespective of immunological status (N=650). Sixty extra people will take part as healthy (asymptomatic) controls. After clinical, radiological and bacteriological evaluation, TB cases will be treated according to national guidelines. Participants diagnosed with TB will be followed up for 6 months since treatment initiation in order to assess treatment response and outcomes. A clinical case definition will be established as a reference standard and defined as any participant in whom a decision is made to start ATT (TB cases will be classified as confirmed or unconfirmed). Specifically, children will be classified into 3 distinct pediatric endpoint categories (confirmed TB, unconfirmed TB and Unlikely TB) based on bacteriological, radiological and clinical criteria, following international consensus guidelines.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adult | – | –Adults >15 with confirmed HIV status and presumptive TB |
| Pediatric | – | –Children <8 years of age with presumptive TB |
Who may qualify
- Ages
- 0 to 8 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Our proposed diagnostic evaluation will be performed in three high TB/HIV burden settings in populations where the tests are intended to be used (presumptive adult pulmonary TB cases and presumptive intrathoracic pediatric TB cases). The study will enroll presumptive TB cases within two study groups: 1. Children less than 8 years of age (irrespective of HIV status) 2. Adults living with HIV (>15 years of age), irrespective of immunological status.
Key inclusion criteria (18 listed)
- Pediatric Cohort
- <8 years of age
- Identified with suspected PTB defined as follows:
- <!-- -->
- OR
Key exclusion criteria (6 listed)
- Receiving TB treatment for >72 hours in previous 2 weeks
- History of TB treatment in the last year
- Refusal to provide consent for study participation or HIV testing when status is unknown
- Severe illness resulting in unstable condition
- Absolute contra-indication to any of sampling procedures required by the study (ie: acute severe asthma, pertussis syndrome etc.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic performance qPCR test in stool samples
Time frame: 2 months
Diagnostic performance (Sensitivity, specificity, negative and positive predictive value) of the qPCR test in stool samples with respect to: 1. bacteriologically confirmed tuberculosis as a composite gold standard of any of the other tests positive (including induced sputum and gastric aspirate Xpert Ultra and MGIT culture, stool Ultra or TB-LAM in urine) 2. clinical reference standard case definition (S. Graham et al.; CID 2015).
2 secondary outcomes
Comparison of diagnostic performance
Time frame: 2 months
Monitor response to TB treatment
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2026.
- Derived from this study: PubMed 40194533Kasule GW, Hermans S, Acacio S, Kay A, Nsubuga JK, Fernandez-Escobar C, Shiba N, Carratala-Castro L, Semugenze D, Mwachan P, Munguambe S, Ehrlich J, Lopez-Varela E, DiNardo AR, Cobelens F, Lange C, Joloba M, Mandalakas AM, Ssengooba W, Garcia-Basteiro AL; Stool4TB Global Partnership. Performance of stool Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis among adults living with HIV: a multicentre, prospective diagnostic study. Lancet Microbe. 2025 Jul;6(7):101085. doi: 10.1016/j.lanmic.2025.101085. Epub 2025 Apr 4.
- Derived from this study: PubMed 38383310Carratala-Castro L, Ssengooba W, Kay A, Acacio S, Ehrlich J, DiNardo AR, Shiba N, Nsubuga JK, Munguambe S, Saavedra-Cervera B, Manjate P, Mulengwa D, Sibandze B, Ziyane M, Kasule G, Mambuque E, Sekadde MP, Wobudeya E, Joloba ML, Heyckendorf J, Lange C, Hermans S, Mandalakas A, Garcia-Basteiro AL, Lopez-Varela E; Stool4TB Global Partnership. A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation. BMC Infect Dis. 2024 Feb 21;24(1):233. doi: 10.1186/s12879-023-08708-9.
- Individual participant dataSharing planned: Undecided
Related trials for Tuberculosis
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Paradoxical Tuberculosis Reactions in Patients Without HIV Infection
Tuberculosis
Not yet recruitingPhase 2
Re-evaluating the Duration in Children of TB Treatment
Tuberculosis
RecruitingPhase 1/2
A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV
Tuberculosis
Active, not recruitingPhase 3
Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Patients
Tuberculosis, MDR
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alberto L García-Basteiro, MD, PhD principal investigator
Barcelona Institute for Global Health
Elisa López Varela, MD, PhD study director
Barcelona Institute for Global Health
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis and Diagnoses Disease, run by Barcelona Institute for Global Health at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Eswatini, Mozambique, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic performance qPCR test in stool samples (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05047315, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026.