Diagnostic Innovations for Pediatric Tuberculosis in Bolivia
1 other identifier
observational
1,220
1 country
1
Brief Summary
Pediatric tuberculosis (TB) continues to pose diagnostic challenges in low- and middle-income countries with high rates of TB disease, due to the well-described impact of paucibacillary disease in children, and current TB culture and polymerase-chain reaction tests are of limited usefulness due to cost, restricted availability, and poor sensitivity in specimens available from younger children. Our team of experts from Tulane, Johns Hopkins University, Universidad Peruana Cayetano Heredia, and Asociación Benéfica Prisma have confronted all of these challenges through more than 25 years of collaboration in Peru and Bolivia. Our goal is to directly address the challenges of TB in children by evaluating a new diagnostic approach developed by MPI Tony Hu at Tulane University using a CRISPR-mediated TB assay (CRISPR-TB) optimized to detect circulating Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA), and used to analyze cryopreserved serum in pilot studies from adults and children with presumptive TB, their asymptomatic household contacts, and a cohort of symptomatic children living with HIV (CLHIV) at high risk for TB. Results from symptomatic adult cohorts yielded a pooled sensitivity of 93%; specificity of 93%; positive predictive value of 95%; and negative predictive value of 92%. In limited pilot studies in CLHIV CRISPR-TBD results accurately identified all confirmed TB (13/13) and most children with unconfirmed TB (80%; 52/65). We propose to enroll 200 presumptive TB cases and an equal number of well control subjects in each of 2 study populations (test population and validation population) identified through clinics associated with the "Dr. Mario Ortiz Suarez" Children's Hospital in Santa Cruz, Bolivia. We will determine the distribution of cfDNA concentrations in peripheral blood in a "test population" composed of two age-based groups of children (2 months-6 years, 7-14 years) with respiratory disease grouped by likelihood of TB based on the NIH consensus case definitions (confirmed TB, unconfirmed TB, and unlikely TB) and in age-matched controls grouped by presence of latent TB infection (LTBI), with cfDNA measured serially in time among TB cases receiving antibiotic therapy. We will also validate standard ranges of quantitative cfDNA established for clinical subgroups of children with TB disease or LTBI in an independent validation cohort. An additional aim will determine the correlation between quantitative cfDNA and quantitative imaging-based TB scores based on evidence of disease in the lung, the primary target organ in TB disease, by (1) chest radiograph, measured by computer-aided analysis using the CAD4TB v7 system, and by (2) lung ultrasound, performed with a portable/low-cost probe assisted by machine learning algorithms for automatic interpretation. These biomarkers will be tested as potential cofactors that may be combined with cfDNA levels in peripheral blood, to improve the detection of TB disease in children. The results of this study will be the first step in a process to find a path to allow detection of the many "unconfirmed" TB cases and ideally make the diagnosis of pediatric TB in reach for low resource settings where it is so critically needed.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Apr 2024
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 27, 2023
CompletedFirst Posted
Study publicly available on registry
November 2, 2023
CompletedStudy Start
First participant enrolled
April 15, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2028
September 5, 2025
September 1, 2025
3.5 years
October 27, 2023
September 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cell free DNA level
Cell free DNA level
Baseline and 2 months post treatment for TB cases on therapy
Secondary Outcomes (1)
CAD4TB score
At presentation for case grou
Study Arms (4)
Presumptive pediatric TB cases-- Test population
Inclusion criteria: Children ages 2 months to 14 years with symptomatic disease and suspicion of TB (based on Bolivian Ministry of Health guidelines). Exclusion criteria (prior treatment for TB in 12 mo, current treatment for TB, weight \< 2.5 kg., instability, positive COVID-19 test) Study subgroups are determined in part based on the results of diagnostic tests and on clinical response. A. Confirmed TB * Symptomatic by case definition from the 2015 NIH Expert Panel * Positive culture or positive Xpert MTB/RIF from at least one sample. B. Unconfirmed TB- * Symptomatic and clinical/radiographic evaluation consistent with TB, by case definition from the 2015 NIH Expert Panel * Negative M. tuberculosis culture and negative Xpert MTB/RIF from all samples. C. Unlikely TB--- * Symptomatic BUT clinical/radiographic eval does NOT meet criteria for Unconfirmed TB, per clinical definition-2015 Expert Panel * Negative culture and negative Xpert MTB/RIF from all specimens.
Control group--Test population
Well Children Control Group-One for each child in groups A-C above, age matched for paired case. * Well children presenting for reasons other than respiratory diseases, and not symptomatic for TB. * Clinical and radiographic evaluation (if performed) NOT suggestive of TB, and NOT diagnosed or treated for TB during the follow-up period (minimum 8 weeks). * Divided into 2 subgroups based on presence or absence of LTBI (by Quantiferon Gold assay).
Presumptive pediatric TB cases-- Validation population
Inclusion criteria: Children ages 2 months to 14 years with symptomatic disease and suspicion of TB (based on Bolivian Ministry of Health guidelines). Exclusion criteria (prior treatment for TB in 12 mo, current treatment for TB, weight \< 2.5 kg., instability, positive COVID-19 test) Study subgroups are determined in part based on the results of diagnostic tests and on clinical response. A. Confirmed TB * Symptomatic by case definition from the 2015 NIH Expert Panel * Positive culture or positive Xpert MTB/RIF from at least one sample. B. Unconfirmed TB- * Symptomatic and clinical/radiographic evaluation consistent with TB, by case definition from the 2015 NIH Expert Panel * Negative M. tuberculosis culture and negative Xpert MTB/RIF from all samples. C. Unlikely TB--- * Symptomatic BUT clinical/radiographic eval does NOT meet criteria for Unconfirmed TB, per clinical definition-2015 Expert Panel * Negative culture and negative Xpert MTB/RIF from all specimens.
Control group--Validation population
Well Children Control Group-One for each child in groups A-C above, age matched for paired case. * Well children presenting for reasons other than respiratory diseases, and not symptomatic for TB. * Clinical and radiographic evaluation (if performed) NOT suggestive of TB, and NOT diagnosed or treated for TB during the follow-up period (minimum 8 weeks). * Divided into 2 subgroups based on presence or absence of LTBI (by Quantiferon Gold assay).
Interventions
Test for TB infection
Test for HIV infection
TB culture by MODS
Chest imaging test by traditional X ray
Chest imaging test by ultrasound
Blood test for TB infection
Eligibility Criteria
Children from clinic population in Santa Cruz Bolivia
You may not qualify if:
- prior treatment for TB within the past year,
- current treatment for prevention of TB,
- weight \< 2.5 kg., or
- clinical instability,
- positive COVID-19 diagnostic test
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tulane Universitylead
- Asociacion Benefica Prismacollaborator
- Universidad Peruana Cayetano Herediacollaborator
- Johns Hopkins Bloomberg School of Public Healthcollaborator
Study Sites (1)
Hospital de Ninos "Mario Ortiz Suarez"
Santa Cruz, Bolivia
Biospecimen
Plasma samples
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- PROSPECTIVE
- Target Duration
- 2 Months
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
October 27, 2023
First Posted
November 2, 2023
Study Start
April 15, 2024
Primary Completion (Estimated)
October 1, 2027
Study Completion (Estimated)
October 1, 2028
Last Updated
September 5, 2025
Record last verified: 2025-09