Tuberculosis

Tuberculosis (TB) is an infectious disease caused by the mycobacterium tuberculosis bacteria. It is a small rod shaped bacteria (a bacillus). It has a waxy coating that makes gram staining ineffective. They are resistant to the acids used in the staining procedure. This property is called acid-fastness. Therefore, the TB bacteria are described as acid-fast bacilli. They require a special staining technique using the Zeihl-Neelsen stain. This turns TB bacteria bright red against a blue background.

TOM TIP: A common exam question involves a patient coughing up sputum that grows acid-fast bacilli that stain red with Zeihl-Neelsen staining. This is mycobacterium tuberculosis and the diagnosis is TB.

 

TB is more prevalent in non-UK born patients (i.e. from South Asia), those who are immunocompromised (i.e. HIV) and those with close contacts with TB. Multi-Drug Resistant TB (MDR TB) are strains that are resistant to more than one TB drug making them very difficult to treat.

 

Disease Course

The TB bacteria are very slow dividing with high oxygen demands and this makes them difficult to culture and treat. It is mostly spread by inhaling saliva droplets from infected people. It then spreads through the lymphatics and blood. Granulomas containing the bacteria form around the body.

Active TB is where there is active infection in various areas within the body. In the majority of cases the immune system is able to kill and clear the infection. The immune system may encapsulate sites of infection and stop the progression of the disease and this is referred to as latent TB. When latent TB reactivates this is known as secondary TB. When the immune system is unable to control the disease this causes a disseminated, severe disease and is referred to as miliary TB.

The most common site for TB infection is in the lungs where they get plenty of oxygen. Extrapulmonary TB is where it infects other areas:

  • Lymph nodes. A “cold abscess” is a firm painless abscess caused by TB, usually in the neck. They do not have the inflammation, redness and pain you would expect from an acutely infected abscess.
  • Pleura
  • Central nervous system
  • Pericardium
  • Gastrointestinal system
  • Genitourinary system
  • Bones and joints
  • Cutaneous TB affecting the skin

 

Risk Factors

  • Known contact with active TB
  • Immigrants from areas of high TB prevalence
  • People with relatives or close contacts from countries with a high rate of TB
  • Immunosuppression due to conditions like HIV or immunosuppressant medications
  • Homeless people, drug users or alcoholics

 

BCG Vaccine

The BCG vaccine involves an intradermal infection of live attenuated (weakened) TB. It offers protection against severe and complicated TB but is less effective at protecting against pulmonary TB.

Prior to the vaccine patients are tested with the Mantoux test and given the vaccine only if this test is negative. They are also assessed for the possibility of immunosuppression and HIV due to the risks related to a live vaccine.

BCG vaccine is offered to patients that are at higher risk of contact with TB:

  • Neonates born in areas of the UK with high rates of TB
  • Neonates with relatives from countries with a high rate of TB
  • Neonates with a family history of TB
  • Unvaccinated older children and young adults (< 35) who have close contact with TB
  • Unvaccinated children or young adults that recently arrived from a country with a high rate of TB
  • Healthcare workers

 

Presentation

Tuberculosis usually presents with a history of chronic, gradually worsening symptoms. Most cases are of pulmonary TB (around 70%) but they often have systemic symptoms.

Typical signs and symptoms of TB include:

  • Lethargy
  • Fever or night sweats
  • Weight loss
  • Cough with or without haemoptysis
  • Lymphadenopathy
  • Erythema nodosum
  • Spinal pain in spinal TB (also known as Pott’s disease of the spine)

 

Investigations

Tuberculosis can be very difficult to diagnose. The bacteria grows very slowly in a culture compared with other bacteria. It also can’t be stained with traditional gram stains and requires specialist stains like the Ziehl-Neelsen stain.

There are two tests for an immune response to TB caused by previous, latent or active TB. These are the Mantoux test and interferon‑gamma release assay. In patients where the active disease is suspected a chest xray and cultures are used to support the diagnosis.

 

Mantoux Test

The Mantoux test is used to look for a previous immune response to TB. This indicates possible previous vaccination, latent or active TB.

This involves injecting tuberculin into the intradermal space on the forearm. Tuberculin is a collection of tuberculosis proteins that have been isolated from the bacteria. The infection does not contain any live bacteria.

Injecting the tuberculin creates a bleb under the skin. After 72 hours the test is “read”. This involves measuring the induration of the skin at the site of the injection. NICE suggest considering an induration of 5mm or more a positive result. After a positive result they should be assessed for active disease.

 

Interferon-Gamma Release Assays (IGRAs)

This test involves taking a sample of blood and mixing it with antigens from the TB bacteria. In a person that has had previous contact with TB the white blood cells have become sensitised to those antigens and they will release interferon-gamma as part of an immune response. If interferon-gamma is released from the white blood cells then this is considered a positive result.

The IGRA test is used in patients that do not have features of active TB but do have a positive Mantoux test to confirm a diagnosis of latent TB.

 

Chest Xray

  • Primary TB may show patchy consolidation, pleural effusions and hilar lymphadenopathy
  • Reactivated TB may show patchy or nodular consolidation with cavitation (gas filled spaces in the lungs) typically in the upper zones
  • Disseminated Miliary TB give a picture of “millet seeds” uniformly distributed throughout the lung fields

 

TOM TIP: Disseminated miliary TB gives quite a characteristic appearance on a chest xray. This makes it a popular spot diagnosis in exams so it is worth looking at some pictures and remembering this.

 

Cultures

Performing a bacterial culture and collecting a sample of the bacteria is very useful prior to starting treatment. This allows testing the bacteria for resistance to antibiotics. Unfortunately cultures can take several months to grown an organism. Treatment is usually started whilst waiting for the culture results.   

There are several ways to collect cultures:

  • Sputum. 3 samples should be collected and tested. If they are not producing sputum then hypertonic saline can be used to induce sputum that can be collected. They might require bronchoscopy with lavage to collect sputum samples.
  • Mycobacterium blood cultures. These require special blood culture bottle.
  • Lymph node aspiration or biopsy

 

Nucleic Acid Amplification Test

Nucleic acid amplification testing is a way of looking for the DNA of the TB bacteria. It is tested on a sample containing the bacteria (i.e. sputum sample). It provides information about the bacteria faster than a traditional culture but is only used where having this information would affect treatment or they are at higher risk of developing complications (i.e. in HIV).

 

Management of Latent TB

Otherwise healthy patients do not necessarily need treatment for latent TB. Patients at risk of reactivation of latent TB can be treated with either:

  • Isoniazid and rifampicin for 3 months
  • Isoniazid for 6 months

 

Management of Acute Pulmonary TB

Management of active TB is coordinated by a specialist TB service with an MDT approach.

RIPE is the mnemonic used to remember the treatment for TB. It involves a combination of 4 drugs used at the same time:

  • RRifampicin for 6 months
  • I Isoniazid for 6 months
  • PPyrazinamide for 2 months
  • EEthambutol for 2 months

 

TOM TIP: Remember that isoniazid causes peripheral neuropathy and pyridoxine (vitamin B6) is usually co-prescribed prophylactically to help prevent this. An exam question might ask “they are started on R, I, P and E, what should also be prescribed?” The answer would be pyridoxine.

 

Other Management Considerations

  • Test for other infectious diseases (HIV, hepatitis B and hepatitis C).
  • Test contacts for TB.
  • Notify Public Health of all suspected cases.
  • Patients with active TB should be isolated to prevent spread until they are established on treatment (usually 2 weeks). In hospital negative pressure rooms are used to prevent airborne spread. Negative pressure rooms have ventilation systems that actively remove air to prevent it spreading out on to the ward.
  • Management and followup should be guided by a specialist MDT.
  • Treatment is slightly different for extrapulmonary disease and often includes using corticosteroids.
  • Individualised drug regimes are required for multidrug‑resistant TB.

 

Side Effects of Treatment

Rifampicin can cause red/orange discolouration of secretions like urine and tears. It is a potent inducer of cytochrome P450 enzymes therefore reduces the effect of drugs metabolised by this system. This is important for medications such as the contraceptive pill.

Isoniazid can cause peripheral neuropathy. Pyridoxine (vitamin B6) is usually co-prescribed prophylactically to reduce the risk of peripheral neuropathy.

Pyrazinamide can cause hyperuricaemia (high uric acid levels) resulting in gout.

Ethambutol can cause colour blindness and reduced visual acuity.

Rifampicin, isoniazid and pyrazinamide are all associated with hepatotoxicity

TOM TIP: A common exam question starts with “a patient has recently started treatment for tuberculosis. They noticed … Which medication is most likely to be implicated?” It is worth remembering the common side effects to help you answer these questions. They start feeling numbness or unusual sensations in their fingertips or feet: isoniazide (“I’m-so-numb-azid”). They noticed difficulty recognising colours: ethambutol (“eye-thambutol”). They noticed their urine or tears are orange or red: rifampicin (“red-an-orange-pissin’”).

 

Last updated April 2019
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