Prospective Evaluation of Novel Diagnostics for Tuberculosis in KwaZulu-Natal, South Africa

Study Overview
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Brief Summary
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Tuberculosis (TB) infects nearly two billion people and has become the leading infectious cause of mortality worldwide, due in part to inadequate diagnostic and prognostic tests. Older diagnostic tools, such as acid-fast staining, and newer diagnostic tests, such as nucleic acid amplification, are either insensitive, expensive, or not suitable for use at the clinical point-of-care. Therefore, novel diagnostic tests are needed to diagnose active TB disease among adults, people living with HIV (PLHIV), and children in TB-endemic countries. In this project, the investigators will conduct clinical evaluation studies of emerging TB diagnostic tests among (1) hospitalized adults, (2) ambulatory adults in outpatient clinics, and (3) children <12 years suspected of having active TB disease. the investigators will also maintain a biorepository of well-characterized clinical specimens that can be used for either retrospective validation of TB diagnostic tests, establishing a reference LAM test, or to share with partners developing novel TB diagnostics, including new LAM antibodies. The project will be coordinated at the University of Washington, and conducted in partnership with clinical research partners in South Africa, including Umkhuseli Innovation and Research Management (UIRM) and the National Health Laboratory Service (NHLS). The project team is well-equipped to serve as a central clinical research site to evaluate new and emerging point-of-care TB diagnostics, particularly novel urinary LAM assays, at the on-site TB Diagnostics Research Laboratory at Edendale Hospital in KwaZulu-Natal, South Africa.

Official Title
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Prospective Evaluation of Novel Diagnostics for Tuberculosis in KwaZulu-Natal, South Africa

Conditions
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Tuberculosis

Participation Criteria
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Eligibility Criteria
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Phase I 1. Eligibility for hospitalized and ambulatory adults: ≥16 years old Positive Xpert MTB/RIF Ultra test (TB-positive cohort) or no suspicion of clinical TB (TB-negative cohort) Have a documented HIV test result or agrees to test for HIV Have NOT received IPT within prior 3 months Have NOT received anti-TB treatment for more than 24 hours Willing/able to provide written informed consent Phase II: Eligibility for hospitalized adults: ≥16 years old Admitted to inpatient medical ward <72 hours Have a documented positive HIV test Have NOT received IPT within prior 3 months Have NOT received anti-TB treatment for more than 24 hours Willing/able to provide written informed consent Study population description: Eligibility for Xpert+ adults (hospitalized and attending outpatient clinics) ≥16 years old Have a documented HIV test result or agrees to test for HIV Positive Xpert MDR/RIF Ultra test documented. Have NOT received anti-TB treatment for more than 24 hours Willing/able to provide written informed consent 3) Eligibility for children children <12 years of age suspected of having active TB disease by clinical team Have a documented HIV test result or agrees to test for HIV Have not had IPT within 3 months Have not received anti-TB treatment for more than 24 hours within the prior 5 days Parent or guardian is willing/able to provide written informed consent

Ages Eligible for Study
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Minimum Age: 12 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adults - inpatient<br> | |
| Adults- ambulatory<br> | |
| Children<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Classified with TB Case Definition | TB positive: A person with a positive Xpert MTB/RIF test or TB culture on any bodily fluid specimen that was obtained/tested within 5 days of enrollment. Probable TB: A person with compatible symptoms, signs, histopathological specimens and imaging for TB, but without a positive TB culture or Xpert test on any specimen; empirically initiated on TB treatment. TB negative: A person with a primary hospital diagnosis other than TB, who has no clinical suspicion for TB, and no diagnostic TB testing ordered by the treating team. TB negative (TB excluded): A person with all reference microbiological testing for TB returning negative, including negative Xpert, negative TB culture, other investigations for TB negative (e.g. histopathology, imaging) and either clinical improvement in the absence of anti-TB therapy or alternate diagnosis determined. In addition, no incident TB diagnosis made (including empiric anti-TB treatment initiation) within the 2 months following enrollment. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with TB Treatment Outcome | Confirmed TB: Bacteriological confirmation obtained: culture or Xpert MTB/RIF from at least one specimen. Probable TB: Bacteriological confirmation not obtained AND at least 2 of the following: Symptoms/signs suggestive of TB (as defined) Chest radiograph or abdominal ultrasound consistent with TB Close TB exposure or immunologic evidence of M. tuberculosis infection Positive response to anti-TB treatment (requires documented positive clinical response on TB treatment) TB negative/unlikely: Bacteriological confirmation NOT obtained AND criteria for unconfirmed tuberculosis NOT met. | 2 Month, 6 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urine-Lam, Diagnostics