Tuberculosis

Question 1

what bacteria causes TB?

Answer 1

myobacterium tuberculosis

Question 2

where is TB common?

Answer 2

B is endemic to many parts of Asia, Africa, South America and eastern Europe and was common in the UK until the 1950s

Question 3

what is the pathogenesis of TB?

Answer 3

Transmitted by aerosol inhalation and causes pulmonary infection, then
spreads via haematogenous spread to any site in the body.

Initial infection can be asymptomatic. Can lie dormant for many years without causing symptoms (latent TB), then reactivate later in life to form active infection.

It is common for people immigrating to the UK from endemic areas to experience reactivation after their arrival.

The exact reason for this is unknown. Vitamin D deficiency is being researched as a cause.

Question 4

what is the lifetime reactivation risk of TB?

Answer 4

Lifetime reactivation risk is estimated at 10-15% (Usually due to immunosuppression, advancing age, or HIV infection)

Question 5

how can TB be classified?

Answer 5

TB can be classified as active or latent. Active TB is then classified by the site affected (pulmonary, pericardial, abdominal, miliaryetc)

Question 6

what is latent TB`?

Answer 6

By definition, latent TB is asymptomatic and is identified by screening

screening involves CXR and measurement of interferon gamma (quantiFERON or T spot)

Question 7

what is quantiFERON?

Answer 7

Assesses the amount of interferon gamma released by T cells when they are exposed to proteins found on mycobacteria.

Pre-exposed cells release more interferon

It does not differentiate between active and latent TB.

It is not used to diagnose active TB and can also be negative during infection.

Patients with immunosuppression may not release interferon gamma causing false negatives.

Question 8

what is the T spot test?

Answer 8

similar principle to quantiFERON test, but rather than testing whole blood the lymphocytes are isolated and tested directly.

Theoretically meaning if there is a deficiency of lymphocytes the quantiFERON might be indeterminate but the t spot may be positive.

A POSITIVE INTERFERON GAMMA TEST DOES NOT MEAN THE PATIENT HAS ACTIVE TB AND A NEGATIVE INTERFERON GAMMA TEST DOES NOT MEAN THAT A PATIENT DOESN’T HAVE ACTIVE TB

Question 9

who is screened with interferon gamma tests?

Answer 9

used in asymptomatic patients with risk factors for latent TB:

• Immigrants from high prevalence countries
• Healthcare workers
• HIV positive patients
• Patient starting on immunosuppression

Question 10

how is latent TB treated?

Answer 10

3 months rifampicin and isoniazid or 6 months rifampicin alone

• Treatment reduces risk of reactivation needs to be balanced against the risk of
  hepatotoxicity.
• Pts aged > 35 are at increased risk of hepatotoxicity. Current guidelines advise against treating latent TB in these patients unless they have other risk factors (HIV or work as a healthcare worker).

Question 11

what are the common symptoms of active TB?

Answer 11

• non resolving cough
• unexplained persistent fever
• drenching night sweats
• weight loss

Question 12

what imaging can be done into active TB?

Answer 12

CXR: Mediastinal lymphadenopathy or a cavitating pneumonia or pleural effusion among other signs

CT: Lymphadenopathy. Nodes with central necrosis are more suggestive.Lesions in viscera can also be seen

MRI – can show leptomeningeal enhancement in TB meningitis

Question 13

what is the gold sample culture for diagnosis?

Answer 13

Culturing the bacteria is the gold standard for diagnosis

If possible treatment should be delayed until adequate samples have been taken

Culture can take 6 weeks so ATT (Ethambutol, Pyrazinamide, INH, Rifampicin) is usually started after samples taken

Question 14

how is pulmonary TB identified?

Answer 14

sometimes can be identified from sputum samples or induced sputum (sputum taken after a nebuliser of 7% hypertonic saline).

If TB can be seen on a sample using simple microscopy it is said to be ‘smear positive’. This implies a high bacterial load and high infectivity. ATT can be started immediately as there is a high chance it will culture.

If a sputum sample is ‘smear negative’ then we usually proceed to bronchoscopy +/- EBUS (endobronchial ultrasound guided biopsy) of pulmonary lymph nodes.

Once these samples are taken we start ATT

Question 15

how is meningeal TB identified?

Answer 15

lumbar puncture for TB culture and TB PCR

Question 16

how is lymph node TB identified?

Answer 16

core biopsy of lymph node (FNA is not adequate)

Question 17

how is pericardial TB identified?

Answer 17

ideally pericardiocentesis – often not practical

Question 18

how is GI TB identified?

Answer 18

colonoscopy and bowel biopsy/ Ultrasound guided omentum biopsy

Question 19

what can be seen on histology of tissue affected by TB?

Answer 19

caseating/necrotising granulomatous inflammation

Question 20

why do TB symptoms get worse a the start of treatment?

Answer 20

Increase in inflammation as bacteria die causing worsening symptoms. Usually occurs at the start of treatment

paradoxical reaction

Question 21

if TB is affecting sites where additional swelling cannot be tolerated (e.g. meningeal/spinal/pericardial TB) what can be given to help?

Answer 21

steroids can be given at the start of treatment

paradoxical reaction as giving ATT treatment straight away can make it worse

Question 22

what are the features of TB meningitis/CNS TB?

Answer 22

All patient with military TB should have a lumbar puncture to exclude TB meningitis

The symptoms can be varied. Initially can be subtle with just personality change and headache, then becomes meningitic and finally comatose over several weeks.

It is usually more insidious onset than viral/bacterial meningitis.

MRI will show leptomeningeal enhancement

LP will show high protein, low glucose, and lymphocytosis

If a patient has TB meningitis then the paradoxical reaction to ATT can be fatal. They are therefore given steroids when starting treatment. The treatment is also longer (12 months).

Question 23

what are the features of pericardial TB?

Answer 23

Pericardial TB can result in a pericardial effusion and in tamponade. Signs include pericardial rub or kussmaul’s sign.

Paradoxical reaction can result in tamponade.

Duration of treatment is 6 months. Steroids are given at the start of treatment

Question 24

what is are the features of disseminated/miliary TB?

Answer 24

Miliary TB has a characteristic appearance on CXR/CT. It is widespread throughout the patient and is often found in multiple sites including CNS/bone marrow/pericardium.

All patients with miliary TB should have neuroimaging (CT/MRI head) +/- lumbar puncture to exclude CNS involvement.

Treatment for military TB shouldn’t be delayed whilst awaiting biopsies

ATT is usually started as soon as it is determined whether or not there is CNS
involvement

Question 25

what are the features of MDR TB?

Answer 25

Consider in patients who have had incomplete treatment for TB previously

Usually seen in patients from abroad

Treatment is specialised and is based on sensitivities.

Treatment regimen is usually decided by consultant

Infection control is paramount, especially for MDR TB and these patient should be managed in a negative pressure room and staff should wear masks/PPE when dealing with them.

Question 26

how is active TB treated?

Answer 26

Standard ATT (Anti-TB Therapy) is used for all sites of TB except for CNS TB.

Standard ATT consists of:

2 months (intensive phase)
Rifampicin +Isoniazid + Ethambutol + Pyrazinamide (available as a combined tablet called RIFATER) 

plus pyridoxine (vitamin b)

Then

4 months (continuation phase)

Rifampicin and isoniazid (combined tablet RIFINAH)

plus pyridoxine

Question 27

what of the ADRS of the 4 ATT drugs?

Answer 27

1) Rifampicin
- causes urine/tears to turn orange (reverses when rifampicin stops)
- Drug induced hepatitis +
2) Isoniazid
- Peripheral neuropathy (reduced by giving pyridoxine)
- Colour blindness
- Drug induced hepatitis ++
3) Ethambutol
- optic neuropathy/ reduced visual acuity
4) Pyrazinamide
- drug induced hepatitis +++

Question 28

how is active TB managed before and during treatment?

Answer 28

Before treatment: measure baseline LFT and visual acuity (if using ethambutol)

During treatment: monitor LFTS

If LFTS derange treatment can either be stopped and the drugs gradually reintroduced once they have normalised, or a “liver friendly” regimen can be given (e.g. amikacin, levofloxacin and ethambutol) but the treatment duration is longer (up to 24 months)

Question 29

what is the process of contact tracing with TB?

Answer 29

Once a patient has been diagnosed they should be referred to the TB nurses

They will perform contact tracing and will test household contacts with either

CXR or QuantiFERON testing and will treat any latent TB

Usually if household contacts were going to catch TB it would be before the patient was admitted so visitors are allowed – unless they have resistant TB

Question 30

how is infection control done with TB?

Answer 30

Patients with non-resistant pulmonary TB should be nursed in a side room.

After 2 weeks of treatment patients are generally considered non-infectious to immunocompetent individuals.

If the ward also manages immunocompromised patients, then patients with respiratory TB need to be nursed in a side room until discharge regardless of whether they are smear positive or negative

Smear positive patients can still be discharged home but would need to quarantine themselves at home until they have completed 2 weeks of treatment.

NICE guidance is that staff do NOT need to wear masks/aprons unless MDR TB is suspected or they are performing an aerosol generating procedure such as giving a nebuliser.

Patients with smear positive TB DO need to wear a mask when leaving their room until they have completed 2 weeks of treatment.