Integrated Discovery and Development of Innovative TB Diagnostics ((CETR))

The long term goal of this project is to provide information critical to the development and use of a low-cost, point-of-care, rapid, simple, and highly accurate diagnostic tool that can help clinicians make a microbiological diagnosis in children who present with signs and symptoms suggestive of TB.

Specific aim 1: To identify the types of patient samples from which to best detect Mtb DNA in children with TB. We propose to obtain serial samples of sputum, blood, stool, and gastric and nasopharyngeal secretions from children with symptomatic TB and to use molecular methods to characterize the distribution of Mtb in these samples. The results of this study will allow us to identify the most promising sampling strategies for diagnosis of TB in children so that optimization of these easily-accessible samples for detection of Mtb nucleic acids can be addressed.

Specific aim 2: To determine whether cell free Mtb DNA can be detected in plasma and urine samples of children and adults with TB and to describe the host-related factors that alter the sensitivity of this assay. We propose to test serial urine and plasma samples for Mtb DNA fragments in two groups: (1) children with symptoms of TB and (2) adults with TB. Here, we will optimize sample volume sizes and of state-of-the-art sequencing tools to improve DNA recovery and detection. This study will help identify optimal samples and strategies for the non-invasive diagnosis of Mtb using urine.

Secondary aim: To create a bank of archived specimens for (1) optimization of Mtb DNA purification, extraction, and (2) use in future pediatric TB diagnostic research.

Study Overview

• Status: Completed
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Other: Observational cohort study

• Study Type: Observational
• Enrollment (Actual): 1450

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise (1) children (0-14 years) with symptoms of tuberculosis disease (TB) and (2) adults >18 years of age with a diagnosis TB. All participants will be recruited from Lima, Peru.

Description

Inclusion Criteria for aim 1:

Children must meet all of the following criteria at the time of enrollment to participate:

• Age < 15 years;
• Presents to a participating health center;
• Meets the Criteria for Enrollment of Children Into TB Diagnostic Evaluation Studies
• Has a history of contact with an adult with TB disease; and
• A guardian provides informed consent for minor to participate and, if age 8 to 14 years, the minor also provides assent.

Inclusion criteria for aim 2:

Inclusion criteria for children who participate in Aim 2 will be the same as for those for Aim 1. Adults who participate in Aim 2 must meet all of the following criteria at the time of enrollment to participate.

• Age ≥ 18 years;
• Presents to a participating health center;
• Is diagnosed with incident pulmonary TB;
• Has sputum smear microscopy results;
• Has not yet initiated tuberculosis treatment; and
• Is willing to receive a rapid HIV test.

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children and adults; Children with symptoms of TB and adults with smear-positive or smear-negative pulmonary TB.	Other: Observational cohort study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity for detection of Mtb, by sample type	For each type of biologic specimen, the proportion of samples in which Mtb could be isolated by DNA detection methods (sensitivity) relative to the standard of care (a combination of sputum smear, sputum culture, signs and symptoms).	Baseline

Collaborators and Investigators

• Sponsor: Harvard University Faculty of Medicine
• Investigators: Principal Investigator: Molly F. Franke, ScD, Harvard Medical School (HMS and HSDM)

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): February 28, 2020

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: October 1, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: pediatric; tuberculosis; diagnostic; cell-free DNA; molecular
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary
• Other Study ID Numbers: 5U19AI109755-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No