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ARRA Investments in Tuberculosis

Public Health Burden
Tuberculosis, or TB, is most commonly caused by the bacterium, Mycobacterium tuberculosis.  An infectious disease where the bacterium spreads from person to person through the air, TB is a major cause of death and disability worldwide.  One third of the world’s population is infected with TB, and each year over 9 million people around the world become sick from this disease.  Annually, nearly 2 million people die from a TB-related illness worldwide.  In 2008, 12,904 cases were reported in the United States.  TB is particularly dangerous for those who are infected with the human immunodeficiency virus; an estimated one third of the persons living with HIV infection are coinfected with TB.

Basic Research
Understanding the basic biology of the bacteria––Mycobacterium tuberculosis–– and how it interacts with humans is essential to expand our knowledge of the disease and provide a strong foundation for effective product development.  ARRA funds support a number of basic research projects, including those aimed at:
  • Investigating the role of a protein called TLR2 in controlling both protective and pathological features of the tuberculosis granuloma.1
  • Studying how the TB bacteria interact with a person’s immune system during early stages of infection.2
  • Using a large scale screening method to discover new antibodies for TB, the results of which may be useful in producing improved diagnostic tests for TB.3
  • Examining how the bacterium that causes TB hides from the immune system, which could offer insights into ways to engineer better vaccines against TB.4
Drug Development and Treatment
Current treatments for TB require those infected to take several medications for an extended period of time. This prolonged treatment regimen presents numerous challenges to our ability to adequately treat this highly infectious disease. People who do not take all the required medicines can become sick again and spread TB to others.  In addition, when people do not take all the prescribed medicines or skip times when they are supposed to take them, the TB bacteria evolve and become insensitive to the effects of the antibiotics.  Soon, the medicines no longer work against the disease.  If this happens, the person now has drug-resistant TB.  A better understanding of mechanisms of drug resistance coupled with the development of new prophylactic and therapeutic anti-TB regimens are crucially needed.  To this end, a variety of ARRA funded grants are exploring potential new treatments, including those aimed at:
  • Developing new anti-tuberculosis agents that will treat latent subpopulations of tuberculosis bacteria and shorten the required time of therapy.5
  • Identifying new inhibitors of a key TB target, InhA, which, if successful, will re-establish InhA as critical target in drug development.  Results of this research could inform current challenges related to drug resistant TB.6
  • Developing compounds that inhibit protein complexes of the tuberculosis bacterium, which may lead to new treatments for drug-resistant tuberculosis.7
  • Identifying compounds showing significant activity against multidrug- resistant (MDR) and extensively drug- resistant (XDR) tuberculosis strains.8
Vaccine Development and Evaluation
Bacille Calmette-Guérin (BCG), a vaccine for TB disease, is not widely used in the United States, but is often given to children in other countries where there is a high prevalence of TB.  Because BCG has variable effectiveness against adult pulmonary TB, and the vaccine is known to interfere with tuberculin skin test reactivity, causing confusing results, the vaccine is only recommended for very select people who meet specific criteria.  Therefore, a research priority is the development and testing of (an) effective new vaccine(s) for the prevention and control of TB.
  • ARRA funds are supporting investigators seeking to develop a new vaccine for tuberculosis using genetic manipulations of wild-type Mycobacterium tuberculosis.9
The development and implementation of rapid and sensitive diagnostics and tools to appropriately treat and monitor how individuals with TB respond to therapy are urgently needed if we are to control the spread of the disease and emergence of drug resistance.
  • ARRA funds support a project to develop a new diagnostic tool to rapidly identify patients with drug resistant TB. Early diagnosis of those individuals with drug resistant TB would allow clinicians to select the best and most appropriate treatment regime, leading to reduced morbidity and mortality rates.10

  1. 1R56AI084822-01 -- TLR2 and the Tubercle Granuloma -- Salgame, Padmini (NJ)
  2. 1R01AI073774-01A2 -- Regulation of Apoptotic Envelope Formation by MTB in the Host Macrophage -- Remold, Heinz (MA)
  3. 1R21AI082000-01 -- Proteome-wide Screen for M. tuberculosis antigens -- Husson, Robert (MA)
  4. 1R56AI081727-01 -- Regulation of ESX-1 Secretion and its Role in M. tuberculosis virulence -- Cox, Jeffery (CA)
  5. 2R01AI062415-05A1 -- Inhibitors of Latent M. tuberculosis -- Lee, Richard (TN)
  6. 3R01AI044639-09S1 -- Targeting InhA For Anti-TB Drug Discovery -- Tonge, Peter (NY)
  7. 1R56AI080618-01A1 -- Mycobacterial Proteasome Inhibitors -- Carl, Nathan (NY)
  8. 1RC1AI086677-01 -- Targeting MDR-TB -- Reynolds, Robert (AL)
  9. 3R01AI049534-07S1 -- Chracteristics of An M. Tuberculosis Derived Vaccine -- Jagannath, Chinnaswamy (TX)
  10. 1RC1AI087062-01 -- AFB Smears for Drug Resistance Detection and Surveillance in MTb. -- Alland, David (NJ)

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