Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and Assessing Diagnostics At POC for TB in Children (ADAPT for Kids)

Study Overview
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Brief Summary
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Every year there are an estimated 230,000 childhood deaths from TB. There is an urgent need for novel tests for TB diagnosis in children under 15 years. The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies seek to reduce the burden of TB worldwide by evaluating faster, simpler, and less expensive TB triage and diagnostic tests for use in children.

Detailed Description
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The Rapid Research in Diagnostics Development for TB Network (R2D2 Kids) and the Assessing Diagnostics at Point-of-care for Tuberculosis in children (ADAPT for Kids) studies will rigorously assess promising, point-of-care (POC) TB diagnostic tests in clinical studies conducted among children at settings of intended use. There is an urgent need for novel tests for TB diagnosis in children under 15 years because of the challenge of obtaining sputum samples from children and the low sputum bacillary burden among children with TB even when a sample is obtained. This creates delays in diagnosis and treatment initiation, and is a major contributor to the 230,000 childhood deaths from TB each year. Therefore, a non-sputum biomarker-based test has been ranked among the highest priority target product profiles for new TB diagnostics. If inexpensive and simple to perform, such a diagnostic tool could have significant impact by facilitating rapid diagnosis and TB treatment in children. The studies will evaluate the sensitivity and specificity of novel diagnostic tests in children in reference to NIH consensus definitions for childhood TB. In addition, the usability and acceptability of the novel TB diagnostic tests will be assessed through direct observations and surveys of routine health workers.

Official Title
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Rapid Research in Diagnostics Development for Tuberculosis Network (R2D2 Kids) and Assessing Diagnostics At Point-of-care for Tuberculosis in Children (ADAPT for Kids)

Conditions
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Tuberculosis, Diagnostics, Global Health

Intervention / Treatment
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* Diagnostic Test: Oral swab molecular testing
* Diagnostic Test: Automated Cough Sound Analysis
* Diagnostic Test: Automated Lung Sound Analysis
* Other: Chest X Ray Computer Aided Detection


Participation Criteria
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Eligibility Criteria
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Participant eligibility criteria: Participants will include children (age <15 years) who present to care with: A. 2 or more of the following: Unexplained cough for any duration TB contact or tuberculin skin test or interferon gamma release assay positive Abnormal chest X-ray (any abnormality) OR B. Any one of criteria A AND any one of the following: Unexplained weight loss OR unexplained failure to thrive OR Severe Acute Malnutrition Unexplained fever ≥2 weeks Unexplained lethargy or reduced playfulness ≥2 weeks The study will exclude participants who: Completed preventive or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively); Have taken any medication with anti-mycobacterial activity for any reason for greater than 3 days at the time of enrollment (to reduce false-negatives); Are unable to return for follow-up visits; or Whose parents/guardians are unwilling to provide informed consent or who are unwilling to provide assent if applicable (age determined by local IRB) Assessment of the usability of novel TB tests: The study will also include health workers at each clinical site who are 1) aged ≥18 years and 2) involved in routine TB testing (collecting specimens for or performing TB tests). Personnel who are unwilling to provide informed consent will be excluded.

Ages Eligible for Study
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Maximum Age: 65 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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evaluation of various novel TB triage and diagnostic tests<br>The investigators will conduct evaluation of novel TB triage and diagnostic tests in a cohort of children with presumed TB. The investigators aim to enroll 250 participants per year at each of three enrollment sites for evaluation of various novel TB triage and diagnostic tests and 30 health workers to assess test usability. Novel test evaluations will be conducted on a rolling basis as new tests ready for field evaluation are identified. | Diagnostic Test: Oral swab molecular testing<br>* Swab-based testing provides a non-invasive approach to collect respiratory specimens for TB testing. Data in adults suggests that swab-based testing could be valuable when sputum collection is not feasible or available.<br>Diagnostic Test: Automated Cough Sound Analysis<br>* Cough sounds can be collected through a mobile phone and tablet, and then analyzed with machine learning algorithms to predict TB.<br>Diagnostic Test: Automated Lung Sound Analysis<br>* Lung sounds can be collected with a non-invasive digital stethoscope, and then saved on a tablet or phone and analyzed by machine learning algorithms to predict TB.<br>Other: Chest X Ray Computer Aided Detection<br>* Several artificial intelligence algorithms have been developed to predict TB, though this has not yet been validated in children.<br>* Other names: Artificial Intelligence algorithm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion with positive index test result among participants with tuberculosis (TB) | Sensitivity - Number with positive index test result/(Number with positive or negative index t test result) among participants with TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results) | 2 years | 
| Proportion with negative index test result among participants without tuberculosis (TB) | Specificity - Number with negative index test results/(Number with positive or negative index t test result) among participants without TB. TB will be defined based on a microbiological reference standard (sputum mycobacterial culture results) | 2 years |