Performance Evaluation of TB Breath- and Cough-testing Platforms

Study Overview
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Brief Summary
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This will be a prospective, multicentre study conducted to evaluate the diagnostic accuracy of two TB breath-based technologies independently of the manufacturers. Assay error and failure rates and device operational characteristics will also be assessed during this study. Participants will be enrolled in this study in line with FIND sample banking activities. Results from index tests will not be used to make clinical decisions. Participation in this study will not alter the standard of care.

Official Title
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Performance Evaluation of Two Diagnostic Technologies for TB Detection Based Upon Breath Testing

Conditions
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Pulmonary TB, Diagnoses Diseases

Intervention / Treatment
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* Device: Rapid Biosensor Systems (RBS) TB Breathalyser
* Device: eNose AeonoseTM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms suggesting pulmonary TB, i.e. persistent cough (generally > 3 weeks or as per local definition of TB suspect) and at least one other finding listed below: Persistent cough Fever Malaise Recent weight loss Night sweats Contact w/ active case Hemoptysis Chest pain Loss of appetite Other [specify] Provision of informed consent to sample collection, banking and HIV and breath-based assay testing Production of adequate quantity of sputum (sputum induction whenever possible) Adult age (>18 years old) Exclusion Criteria: Participants receiving any anti-tuberculosis medication, including fluoroquinolone and aminoglycosides in the 60 days prior to enrolment. Participants with ONLY extra-pulmonary disease will be excluded. Participants for whom complete follow-up and a clear final diagnosis are judged to be difficult (e.g. residents elsewhere or about to move).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adults with pulmonary TB symptoms<br>All patients will be tested with both the reference and index TB diagnostic tests. Index test results will not be used to inform case management. All samples must be collected before the patient starts any form of TB treatment. Patients will be randomized to receive either the TB Breathalyser or AeonoseTM on Day 1, and will be tested with the remaining breath-test on Day 2. A follow-up evaluation will be required after 8 weeks for all patients who do not have microbiologic confirmation of TB (smear or culture). Two additional breath samples may also be collected upon follow-up. | Device: Rapid Biosensor Systems (RBS) TB Breathalyser<br>* Rapid Biosensor Systems (RBS) recently developed a portable, non-invasive, rapid TB diagnostic 'Breathalyser' capable of diagnosing TB in patient breath samples collected while patients cough (Figure 1). The TB Breathalyser comprises a disposable, single-use sample collection tube and a multi-use reader. At the bottom of the collection tube is a glass bio-sensor coated with a biochemical sensor that is formulated to react with TB bacilli. Patients cough into the collection tube after nebulization with 0.9% saline solution. Following sample collection, the tube is placed into the reader, where a diode laser interrogates the biochemical coating in the sample collection tube and reports the presence of TB bacilli. The entire process takes about two minutes.<br>Device: eNose AeonoseTM<br>* The eNose Company has also developed a hand-held, non-invasive rapid TB diagnostic 'electronic nose' (AeonoseTM) for TB detection based upon analysis of exhaled breath. After the device has been calibrated, the patient is instructed to breathe into the device through a mouthpiece for 5 minutes. Within the device is a micro-hotplate, metal-oxide sensor which behaves as a semiconductor at high temperature. Redox-reactions occurring at the sensor surface result in changes in resistance, with results read and interpreted by a phone application to confirm the presence of MTB.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological TB Diagnosis | TB diagnosed by AFB smear microscopy or by one of two MGIT (liquid) or LJ (solid) cultures on enrollment or follow-up sputum sample | 8 weeks |