RePORT India Partners:

  • Jawarharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
  • Boston Medical Center/Boston University School of Medicine, Boston, MA
  • Rutgers University New Jersey Medical School, Newark, NJ

 

Lead Investigators:

Parija S, Roy G, Sarkar S, Ellner J

 

Study Aims:

Aim 1. Identify biomarkers for risk of treatment failure in the TB case cohort of adults and children ≥ 6 years.

Aim 2. Identify biomarkers for risk of development of TB in the household contacts cohort.

Aim 3. In both cohorts, determine the impact of risk factors (diabetes mellitus, helminth infection, HIV, malnutrition, smoking, alcoholism, and anemia) on treatment outcome in pulmonary tuberculosis (PTB) and latent tuberculosis infection (LTBI) and define:

  1. The odds ratio for the occurrence of TB, LTBI, and TB treatment failure comparing those with and without co-morbidities.
  2. The impact of co-morbidities on transcriptomic risk profiles predictive of treatment failure and/or progression to active TB.

Aim 4.  Perform network analysis of the transcriptome profiles to define stages in the continuum between LTBI and PTB and their immunologic concomitants.

 

Overview of Study Design

This protocol will develop two cohorts: a cohort of patients with sputum smear positive pulmonary TB (PTB) and a second cohort of their household contacts (HHC). The clinical study will determine the impact of risk factors (diabetes mellitus, helminth infection, HIV, malnutrition, smoking, alcoholism, and anemia) on treatment outcomes in PTB and the association of these co-morbidities with the development of pulmonary TB (PTB) and latent TB infection (LTBI). The fundamental research focuses on the host transcriptome as a sensitive indicator of the replication of Mycobacterium tuberculosis (Mtb). The protocol will characterize diagnostic biomarkers that predict treatment failure in PTB and risk of TB in exposed HHC. These biomarkers and a network analysis of immune pathways will define stages of LTBI and PTB. The cohorts will provide descriptive data essential to local TB control including the prevalence of Mtb infection, HIV, drug resistance, and co-morbidities; and also will provide populations accessible for future trials of new TB diagnostics, treatments and preventive modalities including vaccines.

Study eligibility criteria for all study participants will incorporate health information collected by the existing TB Program and data collected as part of the study. We will utilize the RNTCP network of clinics to identify subjects. All TB cases presenting for smears to the District Microscopy Centers (DMCs) in Pondicherry and the Tamil Nadu districts of Villupuram and Cuddalore will be considered for study participation. Study eligibility criteria for all index cases will be based on health information that is collected by RNTCP as part of the routine TB care offered to all new TB cases. Household contacts will be enrolled subsequently. Enrollment of study households will be completed within 8 weeks of the initial index case evaluation; all study protocol activities will be completed within two years of the initial index case evaluation (up to 4 study visits to index cases, 2 visits to all household contacts including combined visit to index case and contacts at baseline, and an additional visit for TST+ controls at 24 months).

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