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Tackling the TB Epidemic

Tuberculosis is a contagious disease with high mortality worldwide. Approximately one-third of the world's population is presently infected, including 10-15 million people in the United States alone.

While the organism is dormant in up to 90% of infected individuals, M. tuberculosis is currently responsible for almost 3 million deaths per year worldwide. An HIV-infected individual has a significantly higher incidence of active disease, adding to the global burden. The rise in tuberculosis disease rates has been accompanied by the emergence of strains resistant to one or more of the commonly used therapeutic drugs. To counter this worldwide epidemic, NIAID supports biomedical research in tuberculosis to better understand the disease process, improve diagnostic tools, and encourage the development and testing of new drugs and vaccines.

In order to better understand the transition from initial infection to active disease, NIAID sponsors research to examine the complex interaction between the tuberculosis-causing organism and its human host. Tuberculosis specific factors involved with establishing infection are being identified. Disease could not occur, however, without a susceptible host environment and elucidating these factors is a focus of NIAID research. In addition to causing disease immediately upon infection, M. tuberculosis can remain dormant within an individual for many years creating an immense reservoir of potential disease worldwide. NIAID sponsors research to elucidate the process by which M. tuberculosis enters, maintains, and emerges from dormancy. When coupled with HIV infection, the probability of active tuberculosis infection increases and the overall course of the disease accelerates. This synergistic effect is a current area of NIAID research.

In addition to understanding the disease process, NIAID also sponsors research to improve the diagnosis of active tuberculosis. The current diagnostic tools available to identify active tuberculosis are slow and unreliable especially among HIV-infected patients. Newer diagnostic tools that are rapid, detect low numbers of organisms, identify drug resistant strains and have improved reliability are under development.

Once active tuberculosis disease has been identified, the current treatment is a multiple drug regimen for over 6-9 months. This therapeutic course is difficult for public health agencies to administer and is ineffective against drug-resistant strains. In recognition of the inadequate treatment of tuberculosis worldwide, NIAID has developed research areas to improve the medical management of tuberculosis. In order to facilitate the develpment of new and faster acting drugs for the treatment of tuberculosis, NIAID is supporting resources to screen candidate tuberculosis antibiotics and to test the effectiveness of existing drugs with HIV/tuberculosis co-infections. A major area of emphasis for future generations is research to support development of vaccine candidates for the prevention of the tuberculosis infection. Browse to a report from an NIAID TB vaccine workshop.

Due to improper and incomplete implementation of prescribed drug regimens, the emergence of resistance remains a concern.  To fight the resurgence of tuberculosis in the form of drug resistant strains, the NIAID's efforts include the TAACF as a service to investigators.

Since the latter part of 1994, the TAACF has actively pursued compounds for screening from academia, government agencies, and industry.  The ongoing efforts of the TAACF continually reward the scientific community with valuable data on potential drug candidates with activity against tuberculosis.

Strategies for Mycobacterial Drug Development

Analogs of existing agents - SAR

  • Improved therapeutic index
  • Activity against drug-sensitive strains
  • Improved bioavailability

Broad screening

  • Novel mode of action
  • Activity against MDR-TB

Target-directed

  • Mycobacterial-specific targets, e.g., lipoarabinomannan, lipoarabinogalactan, mycolic acids

Goals of the Program

New anti-TB drugs for use against MDR-TB

  • New mechanisms of action

New anti-TB drugs that are more potent, selective and quicker-acting

  • Decrease overall treatment time
  • Reduce amounts of drug to be taken
  • Bactericidal activity

New anti-TB drugs that can be used effectively in a drug cocktail

Facilitate early-stage drug development

Encourage the development of research ideas relating to anti-mycobacterial drug development

  • New drugs
  • Mechanism of action
  • Molecular biology
  • New targets

Provide the basis for pharmaceutical company involvement in the development of anti-mycobacterial drugs