by Lauren Whitehead, University of Aberdeen

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. While TB may seem to be a disease of the past in developed nations, it still kills 1.7 million people annually. It is also the leading killer of people who are HIV-positive. Worldwide, it is thought that 1 in 4 people harbour an inactive (latent) TB infection. Therefore, despite the advances in TB prevention and treatment, complete eradication of this deadly disease is still a global concern.

Figure 1: Digitally coloured scanning electron microscope image of Mycobacterium tuberculosis (Image credit: NIAID/CDC)

TB seems to have always been waiting in the wings ready to pounce on the vulnerable throughout human history. Ancient Greek philosophers, like Hippocrates, referred to the devastating nature of the lung lesions plaguing young adults as Phthisis. These have also been described in Egyptian mummies. During the middle ages, TB was called the “King’s evil” and in the 18^th century, TB referred to as consumption, killed one in four people! It also claimed the lives of the famous artist Modigliani and the author of ‘Animal farm’, George Orwell.

In 1882, Robert Koch identified the tubercle bacillus as the causative agent of TB, although the infectious nature, pathology and progression of TB disease had already been illustrated by others.

M. tuberculosis has mastered the art of immune manipulation to aid its survival in the human host. It has the ability to subvert the killing mechanism of the immune cell clean-up crew (the macrophages), and to not only survive within these cells but also multiply. The immune system responds by sending in more cells to fight the bacteria and eventually quarantines the region, creating a cheese-like structure called a granuloma. This, as you can imagine, makes breathing quite difficult.

M. tuberculosis grows incredibly slowly. So slow that it takes about 3 weeks of incubation before single colonies are visible on a culture plate. In comparison, E. coli colonies are visible after just an 18 hour incubation. This is one of the reasons why TB antibiotics that target bacterial growth need to be taken for so long.

TB treatment

Sanatoria were popular throughout the 18^th century as fresh air and good nutrition was thought to improve the lungs. In reality, these countered the conditions in which TB thrives; crowded environments with poor ventilation affecting individuals with a weakened immune system. With the introduction of antibiotics, TB can be successfully treated with a regime of 4 antibiotics over 6 months. However, the length of treatment, complex dosing regime, serious drug-drug interactions and unpleasant side effects of these drugs means treatment adherence can be poor. As a result, drug resistance is on the rise. Multi-drug resistant (MDR) and extensive-drug resistant (XDR) strains have reared their heads in countries such as South Africa. MDR-TB is resistant to the two most powerful antibiotics, rifampicin and isoniazid, while XDR-TB is resistant to these drugs plus a fluoroquinolone and at least one injectable second-line drug. The remaining drug options are significantly less effective and have more side effects. As such, mortality rates are as high as 60%.

Figure 2: Sanatorium at Saranac Lake, USA.

Vaccination

The BCG (Bacille Calmette-Guérin) vaccine, developed from heat killed M. bovis in 1921, is extremely successful in the prevention of childhood TB meningitis. It may also have additional protective effects against other infections through trained innate immunity. Unfortunately, the BCG vaccine does little to protect individuals from adult pulmonary TB infection. Currently, a global TB vaccine initiative is testing several candidates for the prevention of TB.  Some of which show great promise for future eradication of TB disease.

Further Reading:

• World Health Organisation. Global tuberculosis report. (2018)
• Centres for Disease Control and Prevention Website https://www.cdc.gov/tb/

About the author:

Lauren Whitehead is a final year PhD student at the University of Aberdeen investigating the role of C-type lectin receptors in rheumatoid arthritis. Her main interest is infectious disease and immunology. In her rare spare time, Lauren enjoys walking in the hills of Scotland and indulging in a glass of wine, cuddled up on the couch with her Labrador.