Diagnostics, Global Health, Tuberculosis
Conditions
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTOral swab molecular testing
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.
DIAGNOSTIC_TESTAutomated Cough Sound Analysis
Cough sounds can be collected through a mobile phone and tablet, and then analyzed with machine learning algorithms to predict TB.
DIAGNOSTIC_TESTAutomated Lung Sound Analysis
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.
OTHERChest X Ray Computer Aided Detection
Several artificial intelligence algorithms have been developed to predict TB, though this has not yet been validated in children.
Sponsors
University of California, San Francisco
Instituto Nacional de Saúde, Mozambique
National Referral Hospital
University of Cape Town
Johns Hopkins University
Elizabeth Glaser Pediatric AIDS Foundation
National Institute of Allergy and Infectious Diseases (NIAID)
University of California, Irvine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 65 Years
Healthy volunteers
Yes
Inclusion criteria
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: 1. Completed preventive or active TB treatment within the past 12 months (to increase TB prevalence and reduce false-positive results, respectively); 2. 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); 3. Are unable to return for follow-up visits; or 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion with positive index test result among participants with tuberculosis (TB) | 2 years | 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) |
| Proportion with negative index test result among participants without tuberculosis (TB) | 2 years | 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) |
Countries
Mozambique, South Africa, Uganda
Contacts
CONTACTDevan Jaganath, MD
CONTACTBrittney Sweetser, MPH
PRINCIPAL_INVESTIGATORAdithya Cattamanchi, MD, MAS
University of California, Irvine
PRINCIPAL_INVESTIGATORNilesh Bhatt
Elizabeth Glazer Pediatric AIDS Foundation
Outcome results
None listed