17th February 2025

Mycobacterium tuberculosis (TB)

Symptoms of TB

TB is a multi-organ infection caused by the bacterium Mycobacterium tuberculosis. Whilst the key manifestations tend to be pulmonary, systems such as the CNS, GI tract and musculoskeletal system may also be involved.

The main symptoms of pulmonary TB include weight loss, fevers, cough, fatigue and haemoptysis. Due to this array of symptoms, malignancy will also be high on the list of differentials.

Other symptoms such as confusion, joint or bone pain or abdominal pain may be evidence of extrapulmonary involvement; this is more prevalent in the immunosuppressed. Symptoms of extrapulmonary tuberculosis are dependent on the systems involved. Tuberculomas, which are firm masses formed in tuberculosis, may exert mass effects in areas where they arise. A spinal tuberculoma may produce a spinal deformity, alongside pain and if not treated, sensory and motor dysfunctions. Pericardial tuberculosis can result in constrictive pericarditis, which may be fatal.  Tuberculosis of the central nervous system can present as TB meningitis with the usual symptoms of pain, fever, confusion and neck stiffness.

The rates of tuberculosis in the UK tend to be highest in cities with high immigrant populations, such as London, but it is also more common in immunosuppressed or homeless populations.

Investigations in TB

Aside from history taking and examination, primary investigations for TB include a chest radiograph and three respiratory cultures. Respiratory cultures should be early morning samples from a deep cough. Zeihl-Neelsen staining (an acid-fast bacilli test) is used but can be falsely negative, particularly with HIV. Bronchoalveolar lavage can be used to obtain samples in non-productive patients or if cultures are negative with high clinical suspicion.

In HIV-positive patients, rapid diagnostic nucleic amplification tests can be used to assess for active TB infection. This may be used for rapid diagnosis but cannot be used to exclude TB.

A chest X-ray may show lymphadenopathy, especially around the hilar regions, but it may also look normal. In some cases of disseminated tuberculosis, a chest X-ray may show miliary TB, where there are diffusely spread nodules throughout the chest. CT chest may show cavitation, which can become infiltrated with fungal diseases such as an aspergilloma.

A positive Mantoux test or positive interferon-gamma release assay (IGRA) can be used to demonstrate latent TB. An interferon-gamma release assay cannot distinguish between latent or active TB. 

Extrapulmonary TB is investigated according to the site of suspected involvement. CNS involvement warrants a CT head or spine and lumbar puncture to assess for cavitation, meningitis or tuberculoma. Lymphadenopathy may be assessed with a fine needle tissue biopsy. Pericardial TB warrants an echocardiogram and possible pericardiocentesis with specimen sampling. Joint involvement requires an ultrasound scan and aspiration of joint fluid.

Patients starting anti-TNF-alpha treatment, e.g. infliximab, should be tested for TB prior to commencing treatment.

Treatment of TB

The standard treatment regimen for active TB in the UK is 6 months of rifampicin and isoniazid, with the addition of pyrazinamide and ethambutol for the first 2 months. Pyridoxine (vitamin B6) should be prescribed alongside isoniazid for the entire duration of its usage to minimise the risk of neuropathy.

For CNS involvement, TB treatment should consist of 12 months of rifampicin and isoniazid (with pyridoxine), with the first 2 months supplemented by pyrazinamide and ethambutol. Patients with CNS involvement should be offered 4-8 weeks of corticosteroids at the start of treatment.

Multidrug-resistant TB will require extended courses of antibiotics based on resistance patterns. 

The Bacillus Calmette-Guérin (BCG) vaccine has resulted in substantially reduced mortality from TB worldwide and is still recommended in countries of high prevalence, although currently, in the UK, it is only offered to high-risk populations.

Common side effects of the TB medications are as follows:

• Rifampicin: potent cytochrome P450 inducer; red/orange discolouration of bodily fluids; hepatotoxicity
• Isoniazid: peripheral nerve damage
• Pyrazinamide: gout
• Ethambutol: optic neuritis