Tuberculosis (TB)

Tuberculosis (TB) is an infection caused by bacteria of the Mycobacterium complex, predominantly Mycobacterium tuberculosis and more rarely Mycobacterium bovis or africanum. Almost all cases in the UK are infected by inhaling the bacterium in respiratory droplets that are released when a person with infectious active pulmonary or laryngeal TB cough.

• Active disease describes where there is evidence of symptomatic or progressive disease of the lung and/or other organs.
  • Active pulmonary TB is the most common presentation, accounting for 54.4% of all cases in the UK in 2017.
  • Active extrapulmonary TB presents with symptoms specific to the site involved, such as the central nervous system (typically the meninges), peripheral lymph nodes, bones and joints, pericardium, skin, gastrointestinal and genitourinary systems.
• Latent disease is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens, with no evidence of clinically active TB (the person is asymptomatic and not infectious).
  • There is a 5–10% lifetime risk of progression to active (symptomatic) disease if, for example, the person becomes immunocompromised or has intercurrent illness.
  • Multiple longitudinal epidemiological studies indicate that the majority of TB disease occurs soon after initial infection, with disease rarely occurring more than two years after infection.

Risk Factors

Risk factors for tuberculosis (TB) infection include:

• Being born in high prevalence areas (defined as more than 40 cases per 100,000 population per year).
• Children less than 5 years of age.
• Close contact with a person with active pulmonary or laryngeal TB
• History of untreated or inadequately treated active TB infection.
• Comorbid conditions including HIV, diabetes mellitus, end-stage chronic kidney disease receiving renal replacement therapy, previous gastrectomy or jejunoileal bypass surgery, occupational lung disease (for example silicosis), haematological malignancy, history of solid organ transplantation, and malnutrition.
• Immunosuppressive drugs
• Under-served groups e.g. people using homeless hostels, shelters, and day centres, and people living in prison or detention centres
• History of excessive alcohol, injecting drug users, and smokers.

Clinical Features

Suspect active TB in any person who is at high risk of developing TB and has general symptoms of weight loss, fever, night sweats, anorexia, or malaise.

• Consider pulmonary involvement if the person has a persistent productive cough, which may be associated with breathlessness and haemoptysis (usually late features).
• Consider extrapulmonary involvement (especially in children, people from countries with a high prevalence of TB, and people with HIV), if they have organ-specific symptoms and signs, such as:
  • Lymphadenopathy (typically painless lymph node swelling with a rubbery texture, often affecting the cervical or supraclavicular lymph node chains) — may suggest lymphatic TB.
  • Bone or joint pains, back pain, and joint swelling — may suggest joint or spinal TB.
  • Abdominal or pelvic pain, constipation, bowel obstruction — may suggest genitourinary or gastrointestinal TB.
  • Sterile pyuria — may suggest renal TB.
  • Headache, vomiting, irritability, confusion, cranial nerve abnormalities — may suggest TB meningitis.
  • Skin lesions — for example, erythema nodosum (a hypersensitivity reaction triggered by TB infection); lupus vulgaris (painful nodular lesions affecting the face) may suggest cutaneous TB.
  • Breathlessness, chest pain, or ankle swelling — may suggest TB pericarditis.
• Be aware that children may present with non-specific symptoms and signs, such as poor weight gain, faltering growth, fatigue, or persistent fever.

Investigations

• Chest X-ray
  • This may show signs of cavitation, pleural effusion, mediastinal or hilar lymphadenopathy, or parenchymal infiltrates, mainly in the upper lobes.
• Respiratory samples (x 3)
  • Ideally, specimens should be spontaneously-produced, deep cough sputum samples, with preferably one early morning sample, for microscopy for acid-fast bacilli, Mycobacteria culture, and specialist molecular tests/drug sensitivity testing, depending on local laboratory protocols.
• Other investigations
  • Consider additional investigations depending on the likely site of disease e.g. joint or spinal plain x-rays; abdominal, renal tract, or lymph node ultrasound scans; early morning urine samples for dipstick testing, microscopy (looking for sterile pyuria) and Mycobacteria culture; echocardiogram (pericardial disease); CT scans of the chest, central nervous system, or bones/joints.

Management

Specialist assessment

• Rapid diagnostic nucleic acid amplification tests (NAATs) for the Mycobacterium tuberculosis complex may be used on primary specimens if there is clinical suspicion of TB and the person has HIV, or a rapid diagnosis and information about mycobacterial species is needed, or contact tracing of large numbers of people may be needed.
• Alternative sampling and imaging techniques may be needed such as sputum induction, bronchoscopy and lavage, gastric aspiration, organ-specific aspiration or biopsy, and CT or MRI scans.

Specialist management

• If a diagnosis of active TB is suspected on the basis of clinical features, specialist treatment should be started without waiting for the culture results:
  • Antibiotic drug treatment with combination regimens — usually 6 months of isoniazid (with pyridoxine) and rifampicin, supplemented in the first 2 months with pyrazinamide and ethambutol. Treatment success is usually defined by completion of therapy with negative follow-up sputum smears. People with active TB of the central nervous system require a prolonged treatment regimen. Drug susceptibility testing may result in the modification of treatment regimens.
  • Treatment of multidrug-resistant (MDR) TB — this is more complex than standard treatment, often involving prolonged treatment (for 18–24 months) with at least six drugs to which the mycobacterium is likely to be sensitive. Treatment is often less efficacious and more poorly tolerated due to increased adverse effects.
  • Surgical management of MDR and extensively drug-resistant (XDR) TB — candidates for surgery may include people with potentially resectable unilateral disease (or apical bilateral disease in selected cases), with adequate lung function who have not responded to medical treatment.

The side effects of the commonly used antituberculous drugs include:

• Rifampicin: orange urine, purple tears, hepatitis, induced liver enzymes
• Isoniazid: hepatitis, peripheral neuropathy
• Pyrazinamide: hepatitis, photosensitivity, gout
• Ethambutol: optic neuritis
• Streptomycin: ototoxic, nephrotoxic

Contact Tracing

People who have been in contact with a person with active pulmonary or laryngeal TB should have screening for latent TB arranged through the local multidisciplinary TB team. High-risk contacts who need contact tracing include:

• All household members.
• Close contacts (such as partner, house visitors, and close workplace contacts) if the person with TB has a positive sputum smear result.
• Casual contacts (such as most work colleagues) if the index person with TB is particularly infectious (known transmission to close contacts), or if casual contacts are at increased risk of infection (such as immunocompromised people).

The results of specialist screening tests to identify latent tuberculosis (TB) infection should be interpreted taking into account the person's immune status, history of exposure to TB and the Bacillus Calmette-Guérin (BCG) vaccination, and other risk factors. Tests include the Mantoux test and the interferon gamma release assay (IGRA) test.

If a test for latent TB infection is positive:

• The person should be assessed for active TB, and if there is no evidence of active infection on the basis of symptoms and chest X-ray, the person should be treated for latent TB infection by the local multidisciplinary TB team to prevent progression to active disease. Drug regimens are usually either three months of isoniazid (with pyridoxine) and rifampicin, or six months of isoniazid (with pyridoxine).

Complications

• Reduced quality of life
• Transmission to others
• Drug resistance
• Post-TB bronchiectasis, chronic obstructive pulmonary disease, and aspergillomas (occur in residual lung cavities)
• Post-TB cor pulmonale/respiratory failure (may result from lung cavitation, scarring, and fibrosis)
• Death