Evaluation of a Urinary Biomarker Assay for Diagnosis and Test of Cure for Tuberculosis

Dr. Jeff Tornheim is PI of this study.

METHODS

This study will make use of biorepository samples from the Cohort for TB Research by the Indo-US Medical Partnership (CTRIUMPh). CTRIUMPh, funded by the US NIH and Indian Department of Biotechnology, is an academic collaboration between Johns Hopkins University, Byramjee Jeejeebhoy Medical College, Pune, India and the National Institute of Research in TB, Chennai, India wherein prospective cohorts of adults and children with pulmonary and EPTB have been established at two Indian sites.10 To date, 880 TB patients have been enrolled, including 628 pulmonary TB patients (109 <15 years old) and 249 extrapulmonary TB patients (69 <15 years old). Of these, 50 participants at BJMC were HIV-positive, including 9 children <15, the majority of whom have CD4 counts >100. CTRIUMPh participants completed 24 months of follow up with urine samples collected before, during, and after treatment for storage in a biorepository. In addition, CTRIUMPh enrolled the household contacts of active TB patients in a second cohort. These household contacts were evaluated for active TB and latent tuberculosis infection (LTBI, defined aspositive interferon gamma release assay or tuberculin skin test >5) at the time of enrollment, then are followed for 24 months with serial testing to evaluate incident LTBI or active TB. These control participants also have urine samples collected at the time of enrollment and throughout their follow-up, which are available for the proposed study.

STUDY DESIGN

We will conduct a case-control diagnostic study nested within the CTRIUMPh cohort study using stored urine samples to identify positive results by the urine FujiLAM, conventional LAM, and the LAM and ESAT-6 nanocage assays. Samples have been collected from patients at multiple time points during treatment, and we will evaluate samples at enrollment (start of treatment), 2 months into treatment, and at the end of treatment (6 months). All participants are classified by site of disease (pulmonary or extrapulmonary) and pediatric patients are classified by standardized, published criteria distinguishing “confirmed TB” (positive culture or nucleic acid amplification test, e.g. Xpert MTB/RIF) from “unconfirmed TB” (absence of microbiologic confirmation and a combination of clinical, radiographic, epidemiologic, and immunologic findings with response to empiric TB treatment).9