Rapid Characterization of Paucibacillary TB Along Tex/Mex Border
Condition: Mycobacterium Tuberculosis
MeSH terms: Tuberculosis; Mycobacterium Infections
Study type: Observational

Summary: 
      This study will test a method of detecting tuberculosis-causing bacteria that are resistant
      to current medication treatments. Blood samples will be collected from patients from 3 sites
      and 3 mainly Hispanic populations in Texas, Mexico, and Colombia. Up to 780 males and
      females, ages 18-85 years, will participate. The study population will consist of 390 people
      with any of 3 forms of tuberculosis (TB) and 390 people who are either healthy or with a
      disease initially thought to be one of these 3 forms of TB but then ruled out. Volunteers
      will only be contacted, invited to participate and interviewed at the beginning of their
      evaluation for possible TB.The study team will follow up with the health department to
      determine if the volunteer was indeed diagnosed with TB, and with the laboratory to determine
      the results of TB tests at diagnosis and during the course of treatment.
    

Detailed description: 
      Global challenges to tuberculosis (TB) control are multidrug resistance TB (MDR-TB) and the
      increased susceptibility of populations such as elderly, those with HIV infection, type 2
      diabetes and other immunosuppressive chronic diseases. The first primary study objective is
      to examine the potential of the investigators' new DNA extraction/qPCR protocol as a
      non-invasive tool to study pathogenesis in a range of paucibacillary specimens. The
      investigators will evaluate their DNA extraction/qPCR assays prospectively in specimens from
      patients with paucibacillary TB, including extra-pulmonary TB (EPTB) and smear-negative
      pulmonary TB. Investigators will determine the number of mycobacterial genomes, presence of
      intact mycobacteria, and precise location within plasma, PBMCs or PMNs in blood, or other
      fluid or cells in a range of specimens. The second primary study objective is to standardize
      and validate a qPCR assay for early detection of Mycobacterium tuberculosis (MTB) drug
      resistance directly from specimens. The investigators will further establish the feasibility
      of using this highly sensitive assay to determine the ratio of Rifampin (RIF)-resistant to
      RIF-susceptible bacteria in a given specimen. The investigators will adapt a simple and
      effective method, similar to their qPCR technology, for detection of mutations in the rpoB
      gene. MTB-positive specimens, identified by either qPCR or direct smear, will be screened for
      RIF resistance using molecular beacons as probes in qPCR. The concordance between the
      molecular beacon-qPCR assays and resistance phenotype from culture will be established. The
      investigators will then utilize the capacity of qPCR to quantitate ratios of RIF-resistant to
      -sensitive mycobacteria in a clinical specimen. The investigators hypothesize that current
      assays are limited to indicating "presence" of drug susceptibility but in the patient the
      situation is more complex, with dynamic mixtures of resistant and sensitive bacteria,
      depending on local exposure to drugs. Developing a tool that detects minor populations of
      drug-resistance cells will open new avenues of investigation to help understand development
      of resistance and treatment failures. Primary study outcomes include: anticipation that the
      qPCR in blood WBCs will provide substantially improved sensitivity and precision
      (mycobacterial species information) in the diagnosis of paucibacillary TB, specifically
      tuberculous lymphadenitis, pleural TB and smear-negative (early) pulmonary TB, when compared
      with standard microbiological and clinical diagnosis; anticipation that molecular beacon-qPCR
      will predict RIF-resistance with 100% sensitivity and at least 86% sensitivity in their study
      site, providing a new tool for early suspicion of MDR, and hence, prompt modification in the
      treatment schedule of the patient; and investigators will learn about the biology of
      emergence of RIF resistance in a population of mycobacteria from serial patient specimens.
      Specimens will be collected from patients from 3 sites, all with predominantly Hispanic
      populations, located in South Texas, adjacent northeast Mexico, and Colombia. A maximum of
      780 males and females, ages 18-85 years, will be recruited. The study population will consist
      of 390 people with tuberculosis (62 with TB lymphadenitis, and at most 164 with pleural TB
      and 164 with smear-negative pulmonary TB) and 390 controls (either healthy controls or with a
      disease initially thought to be one of the three forms of TB described for cases, but then
      ruled out). Subjects will have 1 study related visit. Patients will only be contacted,
      invited to participate and interviewed at the beginning of their evaluation for possible TB.
      The study team will follow-up with the health department to determine if the patient was
      indeed diagnosed with TB, and with the laboratory to determine the results of serial direct
      smear, culture and sensitivity at diagnosis and during the course of treatment.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Studies will be conducted in the population from the TExas-Mexico border, and in Colombia.
        Participants are TB suspects, or controls.
      
Biospecimen description: 
      Blood from participants will be collected, and DNA extracted from white blood cells. These
      are expected to also contain DNA from M. tuberculosis- that will be the research question
    
Keywords: tuberculosis, paucibacillary, mycobacteria, Mexico, Colombia