12th January 2024

Background

Tuberculosis (TB) globally represents a leading cause of death by an infectious agent. TB is caused by Mycobacterium tuberculosis (MtB), an aerobic bacillus transmitted by the respiratory route. From the point of deposition of aerosols containing MtB onto lung alveolar surfaces, the progression of disease can have several outcomes, from patients who are able to clear the initial infection to those who have haematogenous spread of the infection throughout the body. TB is a notifiable disease in the UK.

Epidemiology

Globally, it is estimated that 1.5 million deaths per year are caused by TB, with approximately 10 million incident cases per year. In the UK, the incidence of TB has been slowly reducing over recent years, currently standing between 4000-5000 cases per year. Approximately 300 deaths per year in the UK are caused or contributed to by TB.

Stages of TB disease

TB has human-to-human transmission by the respiratory route. Individuals with active respiratory TB produce aerosol droplets containing MtB when coughing, sneezing or speaking. If others inhale these infectious droplets, they lodge in the lung alveoli and bacilli are taken up by resident macrophages. From this point the progression of disease can have several outcomes, largely determined by the host immune response. An unknown proportion of individuals appear able to completely clear the infection, suggesting they are protected by as-of-yet-unknown immune mechanisms. For some individuals, primary infection leads to active TB (primary progressive tuberculosis), when the replication of bacilli cannot be effectively suppressed by the innate immune system. In most healthy individuals, MtB infection causes little or no symptoms as the immune system acts to wall off the bacteria in granulomas, which limit further replication and spread and form latent TB infection. Most individuals will remain with their infection in latency lifelong; however, for some, the infection can later become active (reactivation). Miliary TB occurs when there is massive lymphohematogenous dissemination of the bacilli to the lungs and other organs, which results in the formation of millet seed-sized tuberculous foci.

Risk factors

There are a number of factors which increase an individual’s risk of TB infection. These include:

• Being born in a high prevalence area, such as India, Pakistan, Romania, Bangladesh etc.
• Being in close contact with someone with active respiratory TB, e.g. living in the same household or working in close proximity.
• Having a comorbid condition, such as HIV, diabetes mellitus or occupational lung disease
• Taking immunosuppressive drugs
• Having a history of excessive alcohol, injecting drug users, and smokers
• Having a low socioeconomic status, with individuals using homeless hostels and shelters and people living in prison, particularly at risk.

Given the above, anyone with confirmed or suspected TB should be offered testing for HIV. Furthermore, as anti-tumour necrosis factor (TNF)-alpha biologic therapies have been shown to increase risk of reactivation of latent TB, any patient being offered these medications should be tested for TB before their commencement.