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Approximately, two billion people worldwide are infected with Mycobacterium tuberculosis (M. tb.), the etiologic agent
of tuberculosis (TB). A tenth of the infected individuals develop active disease. Active pulmonary TB is an inflammatory
disease and is increasingly viewed as an imbalance of host immune responses to M. tb. infection. The current frontline
diagnostic methods including sputum smear (SS) microscopy, and X-ray, are insensitive, inefficient, cumbersome or too
expensive. The most widely used test, SS microscopy (WHO standard), test has a low sensitivity. Therefore, there is an urgent
need for low cost, efficient, high-throughput and accurate diagnostic approaches. We have developed multiplex antibody
biomarker based TB diagnostic system in pre-clinical research in non-human primates and tested it in TB patients. Data on
immune biomarkers, microbiology, and CT imaging from proof-of-concept and subsequent field studies have shown that this
approach will enable a scalable, flexible and cost effective model for diagnostic applications. In addition, we have published
that 10 plasma cytokine/chemokine biomarkers representing host immune-responses in TB patients, are not only gender
biased but concentrations of some of these biomarkers (e.g., IP-10, MIG, IL-16, IFN-�± and G-CSF) progressively decreased in
patients which responded to anti-tuberculosis treatment (ATT) with a cocktail of several drugs (isoniazid, rifampin, ethambutol,
and pyrazinamide or streptomycin - WHO Standard). This decrease is strongly correlated with treatment success and can be
used for monitoring efficacy of therapy. This is important because ATT is a drawn out process (at least six months), and early
detection of patients who may not respond to therapy is important. One possible reason for not responding to ATT could be
due to infection with multi-drug resistant (MDR) strain of M. tb. The standard culture based drug sensitivity testing can take
several weeks. Therefore, there is a need for rapid molecular tests. A test, based on multiplex gene amplification (multiplex
PCR), of several M. tb. genes involved in drug resistance, and multiplex detection of the relevant gene mutations to detect
resistance against four TB drugs will also be discussed.
Biography
Imran H Khan completed his PhD in Molecular and Cellular Biology at Albert Einstein College of Medicine, USA. His research program has focused on “Infectious diseases, intracellular signaling pathways and molecular biology for over 15 years”. Since 2002, he has worked on developing highly efficient and high throughput multiplex approaches for infectious disease biomarkers (e.g., tuberculosis). His research includes simultaneous analysis of multiple key components of cell signaling pathways in a single reaction vessel. In addition, he has employed novel approaches to study disease related biomarkers (e.g., immune biomarkers) in bodily fluids (e.g., plasma/serum) by combining the power of multiplexing systems and computational modeling.