Tuberculosis

Investigators: Xiaobo Yu, Ph.D., Mitch Magee, Ph.D., Garrick Wallstrom, Ph.D. and Jennifer Viloria

Collaborators: Robert N. Husson, M.D. (Harvard Medical School), Jacqueline M. Achkar, M.D., M.S. (Albert Einstein College of Medicine), Tuofu Zhu (University of Washington School of Medicine), Sanjeeva Srivastava, Ph.D. (IIT Bombay)


 

Disease Background

Who gets it?
What are the symptoms?
How do we detect it now?
How is it currently treated?
What are the current challenges?
  • 1/3 of the world’s population is infected with Mycobacterium tuberculosis(Mtb).
  • Co-infection of HIV decreases the ability to detect TB infection
  • TB infection is often the cause of death for people infected with HIV.
  • TB treatment is complicated and time-consuming and relies on accurately diagnosing the infection. 
  • Current diagnostics tests have low sensitivity and specificity.
    • Skin test often results in False-positives
    • Sputum test has a low sensitivity: 50% in immunocompetent persons and even less in HIV+/TB+ patients
  • TB treatment is complicated and time-consuming and relies on accurately diagnosing the infection. 
  • In order to interrupt this cycle of infection-transmission, we have to improve the current diagnostic capabilities, especially for difficult to diagnose patients like those co-infected HIV.

 


 


 

Our Approach

Mycobacterium tuberculosis (Mtb) infects approximately one-third of the world’s population, and an estimated 9.4 million people develop active tuberculosis (TB) each year.  The poor detection rate of TB cases, especially in developing countries, promotes this level of ongoing transmission. In resource-poor regions, direct microscopic examination of sputum smears for acid fast bacilli (AFB) provides the prime diagnostic tool. However, the AFB smear test exhibits poor sensitivity at approximately ~50% in immunocompetent persons, and is even less sensitive in HIV+ TB+ patients. In order to interrupt this cycle of infection-transmission, we need improvements in rapid diagnostic capabilities for difficult to diagnose patients like those co-infected HIV.

We are assessing the detection of antibody biomarkers produced in response to active TB to add as an adjunct to the current diagnostic armamentarium. To accomplish this, we are analyzing sera from well-defined patient and control groups, and screen these sera on a unique and novel protein array platform, which allows for display of the complete proteome of Mtb on a microarray. The screen of a complete representative proteome using patient and control sera will allow us to delineate a smaller set of target proteins which we will validate using an acquired set of independent samples obtained in cross-sectional studies of TB suspects.  We predict that the validation study will yield a select set of ~30 candidate proteins that could serve to detect antibody biomarkers in TB patients.  The antigen-antibody interaction provides the foundation for many diagnostics and our goal is to find and delineate the most sensitive and specific Mtb proteins that react with patient antibodies. The successful completion of this program will provide new and improved strategies for detecting TB rapidly and sensitively.