Latent TB

Tuberculosis (TB) is an infectious disease and accounted for 1.6 million deaths in 2017. It is caused by Mycobacterium tuberculosis (Mtb) and is typically treated by administering a combination of antibiotics (isoniazid, rifampin, pyrazinamide, ethambutol) for several months. Although curable, due to the long periods of treatment, patient noncompliance is high, especially in developing countries where resources are limited.

The World Health Organisation estimates that about 25% of the world's population have latent TB, with a 5-15% lifetime risk of those individuals falling ill with the disease due to re-growth of the dormant, non-replicating (NR) Mtb residing in their tissues. Persons infected with latent TB do not display any symptoms of the disease and the only way to determine whether they have the infection is by carrying out a TB blood test, or through a positive reaction to a tuberculin skin test. Additionally, they're not infectious. However, those with compromised immune systems (e.g. individuals with HIV) have a greater risk of developing active TB.

Similar to active TB, patients with NR latent TB are treated with a course of antibiotics for several months. Therefore, there is a need for the development of potent, short-term therapies to eliminate dormant bacilli and help to reduce the global burden caused by TB. In this regard, several new small molecules with activity against NR Mtb have been reported in the literature in recent years. These include:

• Oxazolidinones
• Hydrazones
• Oxathiazolones
• Oxyphenbutazone – NSAID