Evaluation of Four Stool Processing Methods Combined With Xpert MTB/RIF Ultra for Diagnosis of Intrathoracic Paediatric TB (TB-Speed - Stool Processing)

NCT04203628 | Completed

• 1 other identifier: C19-34
• Study Type: interventional
• Target: 215
• Locations: 2 countries
• Sites: 3

Brief Summary

There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations. Therefore, in this study, the investigators propose to evaluate the accuracy of different promising stool processing methods in the same population within the same study with an adapted design. Furthermore, no study has so far evaluated for stool testing the new Xpert MTB/RIF Ultra cartridge that has a lower level of detection than the previous Xpert MTB/RIF cartridge. The investigators propose to evaluate the accuracy of Xpert MTB/RIF Ultra (Ultra) performed on stool samples collected from children with presumptive TB and processed using four different processing methods (Standard sucrose flotation method, optimized sucrose flotation method, SPK, and SOS) against bacteriological results from respiratory specimens and to perform a head-to-head comparison of the diagnostic accuracy and feasibility of these different methods in Uganda and Zambia. The selection of processing methods was based on accuracy results, degree of simplification allowing their introduction at PHC level, and finding from the TB-Speed in-vitro stool processing study. The standard sucrose flotation method is kept to assess if results obtained with the optimised sucrose-flotation method in our in-vitro study can be reproduced in-vivo

Conditions

Tuberculosis

Keywords

Tuberculosis; Child; Diagnosis; Method; Laboratory

Outcome Measures

Primary Outcomes (1)

• Sensitivity and sensibility of Ultra on stool

  Sensitivity and specificity of Ultra on stool using TB culture reference standard (LJ and MGIT) in two respiratory samples (two sputums or two gastric aspirates according the age of the child).

  8 weeks

Secondary Outcomes (11)

• Per-protocol analysis of diagnostic accuracy of Ultra on stool using TB culture reference standard

  8 weeks

• Head-to-head comparisons

  8 weeks

• Sensitivities and specificities of each sampling method

  8 weeks

• Proportion of Ultra "trace" results in stools out of the number of stools tested with Ultra

  8 weeks

• Proportion of Ultra semi-quantitative results "very low"; "low"; "medium" and "high" in stool

  8 weeks

Study Arms (2)

Prospective cohort

EXPERIMENTAL

Any child with presumptive TB will be proposed to participate in the study. If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies. For children identified from the routine practice, the nurse will collect 2 respiratory samples (sputum or GA) in consecutive children with presumptive TB to be tested using Ultra as done in routine care, record symptoms and refer the child for clinical exam and for chest X-ray. For the purpose of the study, 2 stool samples will be collected to be tested with Ultra. In addition, for study purpose the two respiratory samples will be tested with Mycobacterial culture as this test is not routinely prescribed for TB diagnosis in the study sites

Diagnostic Test: Xpert MTB/Rif Ultra on stool samples; Diagnostic Test: Xpert MTB/Rif Ultra on respiratory sample

Enrichment cohort

EXPERIMENTAL

Any child with presumptive TB and a positive Xpert result from one respiratory sample (NPA, IS or GA) will be proposed to participate in the study. If the child is enrolled in the TB-Speed SAM or HIV studies, the study nurse will collect 2 stool samples then collect information about the clinical examination, chest X-ray, HIV-testing and the mycobacterial culture results as soon as they are available, from the data collected in the TB-speed records since all these procedures are already performed in these studies For children identified from the routine care, once enrolled, samples collected as routine practice will be tested with mycobacterial culture in addition to Xpert. If needed an additional respiratory sample will be collected (sputum or GA) and tested with Mycobacterial culture. The nurse will also record symptoms, refer the child for clinical exam and for chest Xray, and collect stool samples. HIV-testing will be offered for children with unknown HIV-status

Diagnostic Test: Xpert MTB/Rif Ultra on stool samples

Interventions

Xpert MTB/Rif Ultra on stool samples DIAGNOSTIC_TEST

The Xpert MTB/Rif Ultra will be performed on stool samples processed using four different processing methods: * Standard sucrose flotation method * Optimized sucrose flotation * Stool processing kit (SPK) * Simple One-step method (SOS)

Enrichment cohort; Prospective cohort

Xpert MTB/Rif Ultra on respiratory sample DIAGNOSTIC_TEST

The Xpert MTB/Rif Ultra will be performed on gastric aspirate or expectorated sputum

Prospective cohort

Eligibility Criteria

• Age: Up to 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children \< 15 years old
• Presumptive intra-thoracic TB based on at least one criterion among the following:
• Persistent cough for more than 2 weeks
• Persistent fever for more than 2 weeks
• Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age \< 2)
• Failure of broad-spectrum antibiotics for treatment of pneumonia
• Suggestive CXR features
• OR History of contact with a TB case and any of the symptoms listed under point 2 with shorter duration (\< 2 weeks) if the child is HIV infected or presents with SAM.
• Signed informed consent by parent or guardian and assent signed by children ≥ 7 years old
• Children \< 15 years old
• Presumptive TB based on at least one criterion among the following:
• Persistent cough for more than 2 weeks
• Persistent fever for more than 2 weeks
• Recent failure to thrive (documented clear deviation from a previous growth trajectory in the last 3 months or Z score weight/age \< 2)
• Failure of broad-spectrum antibiotics for treatment of pneumonia

You may not qualify if:

• \> 5 days of antituberculosis treatment in the last 3 months
• History of tuberculosis preventive therapy in the last 3 months
• Confirmed extrapulmonary TB only

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• UNITAID: collaborator

Study Sites (3)

Mbarara Regional Hospital

Mbarara, Uganda

Location

Lusaka University Teaching Hospital

Lusaka, Zambia

Location

Arthur Davidson Children Hospital

Ndola, Zambia

Location

Related Publications (1)

• Lounnas M, Masama EN, Beneteau S, Kasakwa K, Kaitano R, Nabeta P, Ruhwald M, De Haas P, Tiemersma EW, Nduna B, Nicol MP, Eyangoh S, Wobudeya E, Mwanga-Amumpaire J, Chabala C, Marcy O, Bonnet M; TB-Speed Stool Study Group. Centrifuge-free stool processing methods for Xpert MTB/RIF Ultra tuberculosis diagnosis in children in Uganda and Zambia: an observational, prospective, diagnostic accuracy study. Lancet Microbe. 2025 Aug;6(8):101055. doi: 10.1016/j.lanmic.2024.101055. Epub 2025 Jun 23.

  PMID: 40570871 DERIVED

Related Links

• TB-Speed project official website

MeSH Terms

Conditions

Tuberculosis; Disease

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Maryline Bonnet, MD, PhD

  Institut de Recherche pour le Développement (IRD) Montpellier, France

  PRINCIPAL INVESTIGATOR

• Olivier Marcy, MD, PhD

  University of Bordeaux, France

  PRINCIPAL INVESTIGATOR

• Eric Wobudeya, MD, PhD

  MU-JHU Care Ltd, Kampala, Uganda

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Enrolment will have 2 stages. During stage 1 (prospective cohort stage), all consecutive children with presumptive TB enrolled in the TB-Speed HIV or TB-Speed SAM or seen in routine care if ineligible for those two studies will be proposed to participate in the study until we reach the number needed for the evaluation of specificity. All children with presumptive TB will have at least two respiratory samples collected (ES or GA) tested with Ultra and mycobacterial culture. The cohort will be closed once the sample size of presumptive TB children with two negative Ultra results from respiratory samples will be reached. During the 2nd phase (enrichment phase), only children with presumptive TB who are Xpert positive on at least one respiratory sample will be proposed to participate in the study in order to complement the number of confirmed TB cases required for the evaluation of the sensitivity.

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 18, 2019
• Study Start: January 13, 2020
• Primary Completion: February 7, 2022
• Study Completion: February 7, 2022
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Access to data will be given after the publication of the main study results based on global data.
• Access Criteria: Data can be requested by members or partners of the TB-Speed consortium or by external research groups. They can be used for secondary analyses of the TB-Speed project, country specific analyses, contribution to individual data meta-analysis and analyses that are not related to the research thematic of TB-Speed project. The request for access to data will need to be sent to the Publication Committee accompanied by a concept paper describing the objectives of the analysis/study, how the data will be used, the list of data or material requested and how the original contributors will be credited. Once the application is approved, data will be released under a data and/or material sharing agreement that secures the term of use.

Locations

UG (1); ZA (2)