Tuberculosis (TB)

Question 1

Background

Answer 1

Caused by mycobacterium.
Various forms of TB but transmission only from active forms. Infected cough or sneeze release droplets of bacterium bacilli, droplets can stay in the air for hours especially in poor ventilated/enclosed places.

Summarised pathophysiology:
Bacilli inhaled. Immune system activated, M TB antigens bind to receptors on macrophages and activated T helper cells release interferon gamma. Bacilli ingested by alveolar macrophages. Cytokines get inflammatory cells making granuloma. 80% infected immune system kills TB. NOT KILLED REMAIN DORMANT IN GRANULOMA AS LATENT TB. IF granuloma breaks bacteria multiply = ACTIVE TB.

TB STAGES:
EXPOSURE -> LATENT TB -> ACTIVE TB -> DEATH.

Question 2

Risk factors

Answer 2

Risk factors differ by stage:

EXPOSURE:
- High number of new cases
- Highly dense population
- Large family size

DEVELOPING LATENT TB:
- Poor air circulation
- Poor ventilation

LATENT TB BECOMING ACTIVE TB:
- HIV +
- Age less than 5
- Excessive alcohol
- IVDU - IV drug use
- Had organ transplant
- Haematological maligancy
- On CHEMO
- Diabetic
- CRF or using dialysis
- Treated with anti TNF or biologics
- Had gastrectomy

TB PROGRESS/PROGNOSIS:
- HIV+
- Untreated/poor TB treatment
- Late diagnosis
- Old age
- Poor nutrition
- Disease site
- Co morbidities

Question 3

Signs and Symptoms

Answer 3

In general:
weight loss, fever, night sweats, anorexia, malaise, SOB, chest pain, haemoptysis (blood cough).
* pulmonary TB - persistent productive cough
* Lymphadenopathy = LYMHPHATIC TB
* Bone/joint pains, back pain, joint swelling = Joint/skeletal TB
* Abdominal or pelvic pain, constipation, bowel obstruction = GI TB
* Urinary symptoms (dysuria, haematuria, and increased urinary frequency) = genitourinary TB
* Sterile pyuria = Renal TB
* Headache, vomiting, irritability, confusion, cranial nerve abnormalities = TB meningitis
* Skin lesions = Cutaneous TB
* Breathlessness, chest pain, or ankle swelling = TB pericarditis
* Ocular inflammation or visual disturbances = Ocular TB RARE

Question 4

Diagnosis

Answer 4

FOR ACTIVE TB
Suspect TB more likely in people with in following high risk groups:
- Contacts of person infected with TB
- Immunocompromised (Diabetic, HIV ppl, Renal failure etc)
- Ppl from countries with HIGH TB
- Ppl with socioeconomic factors that put them at more risk (homeless, IVDU, Alcoholics)

• Pulmonary TB can be found via Chest X-RAY BUT
• Best is to grow culture of M TB.
• Culture not possible then use clinical features, radiology, treatment response.
• If suspected extrapulmonary TB joint/spinal X-RAY.

FOR LATENT TB
Either tuberculin skin test (TST) OR interferon gamma release assay (IGRA)

TST:
- known as Mantoux test
- Protein made from M. TB - its injected in to skin. A local delayed hypersensitive reaction can occur if infected.
- Disadvantages: Need to come in again for results, could have FALSE POSITIVE via previous vaccination. Takes 2-3 days for results.

IGRA:
- Blood test more specific for M. TB because antigens are used that are present in M. TB - so no false positives
- Infected ppl WBCs releases interferon gamma when they are mixed with the antigens in M. TB.
- Faster result

• Both tests can be offered to severely immunocompromised.

If Latent TB positive:
* Asses for active TB
* IF NO ACTIVE TB treat them for latent TB. regimes usually:
- 3 months rifampicin AND isoniazid (+Pyridoxine) OR
- 6 months isoniazid (+ Pyridoxine)

Question 5

Treatment

Answer 5

ACTIVE TB:
2 phases
INTIAL PHASE (2 months) - reduce bacterial population asap and prevent drug resistance.
Rifampicin
Isoniazid (+ Pyridoxine)
Pyrazinamide
Ethambutol
Start b4 culture results if sure of TB diagnosis.

CONTINUATION PHASE (4 months)
Rifampicin
Isoniazid (+ Pyridoxine)
Can be 10 months for active TB of CNS with or without spine.

• Phases can be modified if resistance occurs
• Pyridoxine gives to prevent isoniazid induced neuropathy.

Dosing regimens:
Supervised OR Unsupervised
* Supervised used if thought patient will have poor adherence. Supervised is intermittent (not given every day of the week). Usually 3 times a week
* Combo pills can be used reduce pill burden and better adherence.

Extrapulmonary TB additional treatments:
CNS TB - initial 2 months continuation 10 months. Initial High dose dexamethasone or prednisolone should be give at the same time as TB drugs then slowly withdrawn over 4 to 8 weeks.
PERICARDIAL TB - + Initial high dose of prednisolone same time as TB drugs then slowly withdrawn over 2 to 3 weeks.

LATENT TB:
* Treatment Should be offered to all <65 with latent TB and been in close contact to infected person.
* Severely immunocompromised should be tested for latent TB and offered treatment if positive.
* New NHS employee from other countries should be offered testing if positive they should be treated.

People <65 years Inc. HIV ppl offer:
- 3 months isoniazid (+ Pyridoxine) AND rifampicin OR
- 6 months isoniazid (+ Pyridoxine)
* 35 - 65 only offered if hepatotoxicity is not a issue.
* <35 where hepatoxicity is a concern after LFT test and risk factors then offer 3 months treatment (above).

Question 6

DRUG RESISTANT TB Treatment

Answer 6

DRTB - resistance to 1 drug
MDRTB - resistant to at least isoniazid and rifampicin
XDRTB - resistant to isoniazid and rifampicin, plus any fluoroquinolone and at least 1 of 3 injectable 2nd line drugs

Resistance to isoniazid:
- INITIAL = R, P, E - 2 months
- CONTINUATION = R + E - 7 months (10 for extensive disease)

Resistance to pyrazinamide:
- INTIAL = R, I (+ Pyridoxine), E - 2 months
- CONTINUATION = R, I (+ Pyridoxine) - 7 months

Resistance to ethambutol:
- INTIAL =R, P, I (+ Pyridoxine) - 2 months
- CONTINUATION = R + I (+ Pyridoxine) - 4 months

Resistance to rifampicin:
- Offer treatment with minimum 6 anti tuberculosis drugs mycobacterium is sensitive to.

MDRTB:
SAME AS RIFAMPICIN