Same Day Diagnosis of Extrapulmonary TB (TB Serositis and TB Meningitis).

Study Overview
=================
Brief Summary
-----------------
Extrapulmonary TB (EPTB) accounts for nearly 30% of TB cases in HIV endemic settings, such as South Africa. The diagnosis of extrapulmonary TB is complicated by the poor performance of Gene Xpert and TB Culture in extrapulmonary fluid (30-50% sensitive), as well as the poor specificity of ADA. We can therefore not reliably use these tests to diagnose EPTB as effectively as we use them in sputum samples. The current best practice for diagnosing pleural TB is to perform a pleural biopsy, which is both invasive and costly. A rapid, easy to use test is needed to allow accurate and fast diagnosis of EPTB. Interferon-gamma is released at high concentrations in extrapulmonary fluid in active EPTB. Antrum Biotech has developed the IRISA-TB assay (validated and SAHPRA licenced) for the diagnosis of EPTB. The study will assess the real-world performance of IRISA-TB compared to ADA, Gene Xpert, and TB Culture when used to diagnose EPTB. We will evaluate IRISA-TB's performance in the following patient groups: Suspected TB pleural effusion (n= 650) Suspected TB pericardial effusion (n= 280) Suspected TB peritonitis (n= 200) Suspected TB meningitis (n = 1040) As part of our evaluation, we will ask clinicians who treat these patients to provide their feedback on IRISA-TB. We will ask them to indicate to what extent the IRISA-TB test helped them to make treatment decisions. Finally, we will conduct an economic assessment to determine the true cost of diagnosing and treating EPTB to the health system and patients, and we will determine how IRISA-TB could potentially result in cost savings.

Official Title
-----------------
Same Day Diagnosis of Extrapulmonary TB (TB Serositis and TB Meningitis).

Conditions
-----------------
Tuberculosis, Extrapulmonary

Intervention / Treatment
-----------------
* Diagnostic Test: IRISA-TB


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female participants 18 years and over attending health care facility with symptoms of TB. Serosal or CSF fluid sample provided to NHLS with sufficient volume to perform SOC tests + 1ml. Patients in whom extrapulmonary TB is part of the treating clinicians' differential diagnosis. Exclusion Criteria: Volunteers who refuse to sign informed consent and/or provide clinical details (Proxy consent will be obtained for participants who are incapacitated, with a follow up consent when they have recovered their capacity to consent) Patients with current significant history of substance or alcohol abuse that may impact study visits. Patients who are unable to communicate by telephone or who do not have a current active traceable contact number. Patients not willing to undergo an HIV test. Patients whose fluid sample volumes are insufficient to perform standard of care testing in addition to IRISA-TB Positive sputum GXP within 2 weeks prior to serosal fluid or CSF sampling.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with suspected extrapulmonary tuberculosis<br>Patients with pleural, pericardial, or peritoneal effusions due to suspected extrapulmonary tuberculosis and those with suspected TB meningitis. | Diagnostic Test: IRISA-TB<br>* ELISA-based assay that detects interferon-gamma concentrations in extrapulmonary fluid in active TB.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test-specific performance outcomes | Comparison of sensitivity, specificity, accuracy, predictive values, likelihood ratios, number needed to treat (NNT) and indeterminate rate for the various diagnostic assays (IRISA-TB, ADA, Gene Xpert, TB Culture) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Empiric treatment rates for extrapulmonary TB | Clinicians will be asked to indicate whether IRISA-TB made an impact on treatment decisions. Empiric treatment rates for extrapulmonary TB are high due to poor performance of current diagnostics. | 24 months | 
| Cost effectiveness | Determining the true cost to the health system of various diagnostic strategies. | 24 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tuberculosis, Interferon-gamma, Tuberculosis diagnostics