Tuberculosis
Tuberculosis (TB) is an infectious disease. In humans almost all cases are caused by the bacterium Mycobacterium tuberculosis (MTB). MTB has a unique cell wall that doesn't take up Gram staining, and as a result, M. tuberculosis can appear weakly Gram-positive. Acid-fast stains such as Ziehl–Neelsen, or fluorescent stains such as auramine are used instead to identify MTB with a microscope. The physiology of M. tuberculosis is highly aerobic and requires high levels of oxygen.
In about 5–10% of individuals, the infection progresses rather than being contained (progressive primary TB), potentially affecting the CNS, lymph nodes, bones, genitourinary system, or disseminating via the bloodstream as miliary TB.
Latent TB occurs when bacilli remain dormant. It is asymptomatic and non-infectious, but detectable via tuberculin skin testing (TST) or interferon-gamma release assays (IGRA). Around one-third of the global population has latent TB.
There is a 5–10% lifetime risk of reactivation of latent TB, more commonly seen in immunocompromised individuals (e.g. HIV). This typically presents as post-primary TB, often in the lung apices, with potential for local or distant spread.
The body's defence against TB depends heavily on T-cell-mediated immunity. Effective T-cell responses can contain the infection within granulomas, leading to a latent state. However, if immunity declines (due to ageing, HIV, malignancy, infection, or immunosuppressive therapies) the risk of reactivation increases, potentially resulting in active disease.
Investigations and diagnosis
Microscopy: The Ziehl-Neelsen (ZN) stain is used to identify acid-fast bacilli in sputum. It is quick but less sensitive than other methods.
Sputum mycobacteria culture: Three samples required. Depending on the media results can take up to 8 weeks.
Nucleic acid amplification tests (NAATs): These detect M. tuberculosis DNA and provide faster results than cultures. NICE recommends using NAATs when rapid diagnosis will affect management, particularly in HIV-positive individuals or where significant contact tracing is anticipated.
NICE advise imaging investigations. A CXR is advised in all patients plus further imaging depending on the suspected site.
Initial phase (2 months):
Treatment is extended to 12 months for TB involving the brain or spine. Corticosteroids may be used to reduce inflammation in these cases.
Infection control measures include use of respiratory protection like N95 masks and patient isolation. The TB team will usually organise contact tracing and testing.
HIV co-infection: Patients with HIV are at increased risk of TB. NICE recommends routine testing for HIV in all TB patients and vice versa. Co-infected individuals may need longer or adjusted regimens, as well as prophylactic therapy.
Directly observed therapy (DOT): For individuals at risk of non-adherence such as those with substance misuse or unstable housing. DOT involves a healthcare provider supervising the intake of medication.
Latent TB: NICE advises treatment for latent TB in people under 65 with risk factors for progression. Options include 3 or 6 month regimens depending on the specific drugs used.
Transmission
Tuberculosis is primarily transmitted via aerosolised droplets when individuals with active pulmonary or laryngeal TB cough, sneeze or speak. Once inhaled, Mycobacterium tuberculosis (MTB) establishes infection in the lungs, particularly in the alveolar spaces, where it may remain latent or progress to active disease.Pathophysiology
Mycobacterium tuberculosis is inhaled and engulfed by alveolar macrophages, but it can evade destruction by escaping the phagolysosome, allowing it to multiply within the cytoplasm. Some bacilli travel to regional lymph nodes, forming additional infection sites. Together with the initial lung focus, this forms the primary complex. The immune response leads to granuloma formation, tissue destruction, and systemic symptoms such as fever and weight loss, often with lung cavitation. and granuloma formation.In about 5–10% of individuals, the infection progresses rather than being contained (progressive primary TB), potentially affecting the CNS, lymph nodes, bones, genitourinary system, or disseminating via the bloodstream as miliary TB.
Latent TB occurs when bacilli remain dormant. It is asymptomatic and non-infectious, but detectable via tuberculin skin testing (TST) or interferon-gamma release assays (IGRA). Around one-third of the global population has latent TB.
There is a 5–10% lifetime risk of reactivation of latent TB, more commonly seen in immunocompromised individuals (e.g. HIV). This typically presents as post-primary TB, often in the lung apices, with potential for local or distant spread.
The body's defence against TB depends heavily on T-cell-mediated immunity. Effective T-cell responses can contain the infection within granulomas, leading to a latent state. However, if immunity declines (due to ageing, HIV, malignancy, infection, or immunosuppressive therapies) the risk of reactivation increases, potentially resulting in active disease.
There is a 5–10% lifetime risk of reactivation of latent TB
Clinical features
TB presents a wide range of clinical manifestations. Patients often exhibit site specific features and systemic features. Systemic features include:- Fever
- Unintentional weight loss
- Night sweats (often described as drenching)
- Anorexia
- Malaise
- Clubbing
| Site | Notes |
|---|---|
| Pulmonary | The most common form, presenting with a persistent cough, haemoptysis, pleuritic chest pain, |
| Kidneys | May present with sterile pyuria and haematuria |
| Spine (Pott’s disease) | Associated with back pain and potential spinal deformity |
| Gastrointestinal tract | Symptoms may include abdominal pain, diarrhoea, or intestinal obstruction |
| Central nervous system | Can lead to tuberculous meningitis, with features such as headache, neck stiffness, and confusion |
| Miliary TB | A disseminated form due to haematogenous spread. It can cause widespread organ involvement, even in the absence of active lung infection |
Investigations and diagnosis
Microscopy: The Ziehl-Neelsen (ZN) stain is used to identify acid-fast bacilli in sputum. It is quick but less sensitive than other methods.
Sputum mycobacteria culture: Three samples required. Depending on the media results can take up to 8 weeks.
Nucleic acid amplification tests (NAATs): These detect M. tuberculosis DNA and provide faster results than cultures. NICE recommends using NAATs when rapid diagnosis will affect management, particularly in HIV-positive individuals or where significant contact tracing is anticipated.
NICE advise imaging investigations. A CXR is advised in all patients plus further imaging depending on the suspected site.
CXR is a useful diagnostic tool but normal CXR does not exclude the disease. Diagnosis is typically confirmed by sputum culture for acid fast bacilli.
Management
The standard treatment for active TB consists of:Initial phase (2 months):
- Isoniazid
- Rifampicin
- Pyrazinamide
- Ethambutol
- Isoniazid
- Rifampicin
Treatment is extended to 12 months for TB involving the brain or spine. Corticosteroids may be used to reduce inflammation in these cases.
Infection control measures include use of respiratory protection like N95 masks and patient isolation. The TB team will usually organise contact tracing and testing.
Special considerations
HIV co-infection: Patients with HIV are at increased risk of TB. NICE recommends routine testing for HIV in all TB patients and vice versa. Co-infected individuals may need longer or adjusted regimens, as well as prophylactic therapy.
Directly observed therapy (DOT): For individuals at risk of non-adherence such as those with substance misuse or unstable housing. DOT involves a healthcare provider supervising the intake of medication.
Latent TB: NICE advises treatment for latent TB in people under 65 with risk factors for progression. Options include 3 or 6 month regimens depending on the specific drugs used.
TB is a notifiable disease