Evaluating a New Stool Based qPCR for Diagnosis of Tuberculosis in Children and People Living With HIV

NCT05047315 | Completed

• 1 other identifier: RIA2018D-2511
• Study Type: observational
• Target: 1,967
• Locations: 3 countries
• Sites: 3

Brief 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 rates in children and people living with HIV (PLHIV).

Conditions

Tuberculosis; Diagnoses Disease

Outcome Measures

Primary Outcomes (1)

• 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: 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 months

Secondary Outcomes (2)

• Comparison of diagnostic performance

  2 months

• Monitor response to TB treatment

  6 months

Study Arms (2)

Adult

Adults \>15 with confirmed HIV status and presumptive TB

Pediatric

Children \<8 years of age with presumptive TB

Eligibility Criteria

• Age: 0 Years - 8 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• Pediatric Cohort
• \<8 years of age
• Identified with suspected PTB defined as follows:
• A child with ≥1 of the following criteria:
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• 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)
• 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).
• \) 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Barcelona Institute for Global Health: lead
• Makerere University: collaborator
• Amsterdam Institute for Global Health and Development: collaborator
• Centro de Investigacao em Saude de Manhica: collaborator
• Baylor Eswatini Clinical Centre of Excellence (COE): collaborator
• Research Center Borstel: collaborator
• Fundação Manhiça: collaborator
• Baylor College of Medicine: collaborator

Study Sites (3)

Baylor Eswatini Clinical Centre of Excellence (COE)

Mbabane, Eswatini

Location

Centro de investigação de Saúde de Manhiça

Manhiça, Maputo Province, 1929, Mozambique

Location

Makerere University

Kampala, Uganda

Location

Related Publications (2)

• 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.

  PMID: 40194533 DERIVED

• Carratala-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.

  PMID: 38383310 DERIVED

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Alberto L García-Basteiro, MD, PhD

  Barcelona Institute for Global Health

  PRINCIPAL INVESTIGATOR

• Elisa López Varela, MD, PhD

  Barcelona Institute for Global Health

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2021
• First Posted: September 17, 2021
• Study Start: December 1, 2021
• Primary Completion: December 17, 2024
• Study Completion: June 30, 2025
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

ES (1); UG (1); MO (1)