Tuberculosis Flashcards
What is the NICE definition of Tuberculosis?
TB is an infection caused by the mycobacterium complex, mainly Mycobacterium tuberculosis (TB) and more rarely mycobacterium bovis and africanum. Which is affected by 2 billion people worldwide whom which not all have symptoms.
A smallrod-shapedbacteria (abacillus). M. tuberculosis bacteria are very slow dividing andhave high oxygen requirements, making them difficult toculturein a lab.
What are the risk factors of TB?
Arrived or returned from a high prevalence country within last 5 years
Born in a high prevalence country
Lives with people who have active TB
Have close contact with people diagnosed with active TB, e.g. school or work
Smoker, excess alcohol, IV drug users
Homeless, Malnutrition, Lack of access to treatment
Recently been in prison
How is TB transmitted?
-Air Borne Droplet – cough, sneeze
-90% of children are non infectious
- TB cannot be acquired from individuals with latent TB
Incubation period 2-10 weeks
- Infectious period – sputum smear positive or laryngeal TB
- Non infective within 2 weeks of appropriate treatment
What is the disease course of TB?
Immediate clearanceof the bacteria (in most cases)
Primary active tuberculosis(active infection after exposure)
Latent tuberculosis(presence of the bacteria without being symptomatic or contagious)
Secondary
tuberculosis(reactivation of latent tuberculosis to active infection)
What happens when the immune system can’t control the infection?
Disseminatedandseveredisease can develop, referred to asmiliary tuberculosis.
What is the pathophysiology of primary infection from TB?
- Primary Infection & Ghon Focus 📍
Entry: TB is transmitted via airborne droplets and reaches the alveoli, usually in the mid-to-lower lung lobes (subpleural region).
Macrophage Invasion:
Alveolar macrophages engulf TB bacteria.
However, TB evades destruction by preventing phagosome-lysosome fusion.
The bacteria replicate inside macrophages, leading to a localized inflammatory response.
Granuloma Formation (Ghon Focus):
The immune system forms a granuloma to “wall off” the infection.
This central caseous necrotic lesion is called the Ghon focus.
What is latent TB?
Latent tuberculosisis present when the immune systemencapsulatesthe bacteria and stops the progression of the disease. Patients with latent tuberculosis have no symptoms and cannot spread the bacteria. Most otherwise healthy patients with latent tuberculosis never develop an active infection. When latent tuberculosisreactivates, and an infection develops, usually due toimmunosuppression, this is calledsecondary tuberculosis.
What occurs after gohn focus formation after primary infection of TB?
Ghon Complex Formation
Lymphatic Spread: Some TB bacteria drain to regional lymph nodes, particularly the hilar lymph nodes.
Hilar Lymphadenopathy: The infected lymph nodes also develop granulomas and caseous necrosis.
Ghon Complex = Ghon Focus (lung lesion) + Hilar Lymphadenopathy
Seen in Primary TB:
Often asymptomatic, but may cause mild fever or cough.
In most people with intact immunity, the TB bacteria are contained at this stage, leading to latent TB.
What happens to the Ghon complex overtime?
Fibrosis & Calcification: Over time, the Ghon Complex undergoes fibrosis and calcification, forming the Ranke Complex.
Ranke Complex = Healed, calcified Ghon Complex (evidence of past TB infection).
TB remains dormant within these calcified granulomas but can reactivate years later if immunity weakens (e.g., HIV, diabetes, immunosuppressive therapy).
How does TB progress to active or military TB?
If the immune system fails to contain TB at the Ghon Complex stage, the granulomas break down, allowing TB to:
Reactivate (Secondary TB) → Usually in the upper lobes (better oxygen supply).
Disseminate (Miliary TB) → TB spreads via the bloodstream to multiple organs, causing widespread granulomas.
What is the pathophysiology of TB?
Ghon Focus → Initial lung lesion with caseous necrosis.
Ghon Complex → Ghon Focus + Hilar Lymphadenopathy.
Ranke Complex → Healed, fibrotic and calcified Ghon Complex (latent TB).
Active or Miliary TB → Reactivation or widespread dissemination if immune defenses fail.
What is systemic Military TB/extrapulmonary TB?
Miliary TB occurs when TB bacteria, instead of being contained in the lungs, enter the bloodstream (via the hilar lymph nodes or directly from the lungs) and spread to various parts of the body.
This leads to the formation of small granulomas in the liver, spleen, bone marrow, kidneys, brain, and other organs.
Similar to primary TB, the body attempts to contain the infection by forming granulomas at the sites of infection.
The granulomas in miliary TB are small, numerous, and scattered (resembling millet seeds).
What are the systemic symptoms of systemic military TB?
Fever (often high and persistent)
Night sweats
Weight loss (cachexia)
Fatigue
How does sytemic miliary TB affect other organs?
Kidneys: Sterile pyuria
Meninges of Brain: TB meningitis (headache, confusion, stiff neck).
Lumbar vertebrae: Potts disease
Adrenal glands: Addison’s disease
Liver: Hepatitis
Cervical Lymph nodes: Lymphadenitis in neck
Hepatomegaly/splenomegaly: Swelling of the liver and spleen.
Pancytopenia (low blood cell counts).
Hepatomegaly/splenomegaly: Swelling of the liver and spleen.
What are the typical signs and symptoms of TB?
Cough
Haemoptysis (coughing up blood)
Lethargy/fatigue
Fever or night sweats /Night sweats –
Weight loss
Lymphadenopathy
Erythema nodosum(tender, red nodules on the shins caused by inflammation of the subcutaneous fat)
Spinal pain inspinal tuberculosis(also known asPott’s disease of the spine)
Wha are the late signs of TB?
Haemoptysis
Chest pain
Hoarse voice
What are the investigations according to NICE?
- Resp/CVS -Examination & Obs
- Mantoux test:
Involves injectingtuberculininto theintradermalspace on the forearm. Tuberculin is a collection oftuberculosis proteinsisolated from the bacteria. It does not contain any live bacteria.
The infection creates ablebunder the skin. After 72 hours, the test is “read”. This involves measuring the induration of the skin at the injection site. An induration of5mm or moreis considered a positive result. - Interferon-Gamma Release Assays (IGRA):
IGRA involves mixing a blood sample withantigensfrom theM. tuberculosisbacteria. After previous contact withM. tuberculosis,white blood cellsbecomesensitisedto thebacteria antigensand will releaseinterferon-gammaon further contact. A positive result is wheninterferon-gammais released during the test. - Chest X-ray:
– signs of cavitation, pleural effusion, mediastinal or hilar lymphadenopathy, parenchymal infiltrates mainly in upper lobes - Microbiology testing:
Sputum Smear and Culture:
- 3 consecutive samples especially if chest x-ray suggestive of TB.
- Samples should be spontaneously produced, one preferable to be early morning
- Collect sputum samples to detect Mycobacterium tuberculosis through acid-fast bacilli (AFB) smear microscopy and culture.
Nucleic Acid Amplification Tests (NAATs):
- Utilize PCR-based methods to rapidly identify TB DNA in clinical specimens.
Drug Susceptibility Testing: Determine the sensitivity of the isolated TB strain to standard anti-TB medications.
What is a bronchoalveolar lavage?
Bronchoalveolar lavage (BAL) is a procedure that is sometimes done during a bronchoscopy. It is also called bronchoalveolar washing. BAL isused to collect a sample from the lungs for testing. During the procedure, a saline solution is put through the bronchoscope to wash the airways and capture a fluid sample. This is done for symptomatic patients along with sputum testing for MCS.
How is TB identified in culture?
Culturing Mycobacterium tuberculosis (MTB) is the gold standard for TB diagnosis, as it allows for definitive identification and drug susceptibility testing. However, due to the slow growth of TB bacteria, results can take several weeks. Thus treatment should start without waiting for results if symptomatic.
Positive result:
-Acid-Fast Bacilli (AFB) Staining
Ziehl-Neelsen stain
- MTB appears as red, rod-shaped bacteria against a blue background.
What are the different types of samples that can be collected for TB suspected patients?
Sputum (most common for pulmonary TB)
Bronchoalveolar lavage (BAL) (if sputum is not available)
Pleural fluid, cerebrospinal fluid (CSF), urine, or tissue biopsy (for extrapulmonary TB)
Blood culture (for disseminated/miliary TB)
What is caseous necrosis?
Caseous necrosis (TB lymphadenitis) is a form of tissue death (necrosis) that has a cheese-like appearance. It is most commonly associated with tuberculosis (TB). If there is no caseous it will be more likely be sarcoidosis.
-Soft, friable, and white/yellow tissue that resembles cottage cheese.
-Occurs due to chronic inflammation and immune response against Mycobacterium tuberculosis.
-The body’s macrophages try to kill the bacteria but fail to fully digest them, leading to persistent inflammation and tissue destruction.
-Surrounded by granulomas
-Found in Pulmonary TB (in Ghon focus, Ghon complex, and Ranke complex)
What is the management of latent TB?
Treatment Regimens:
Options include:
- Isoniazid for 6 months.
- Rifampicin for 4 months.
- Isoniazid and Rifampicin for 3 months.
Hepatotoxic & Liver function needs to be assessed
Target Groups: Prioritize treatment for individuals under 65 with latent TB, especially those at high risk of progression to active disease.
What is the management of active TB?
Initial Phase (2 months): Administer a combination of four antibiotics: Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. (RIPE)
Continuation Phase (4 months): Continue with Isoniazid and Rifampicin.
Directly Observed Therapy (DOT): Consider DOT to ensure adherence, especially for individuals at risk of non-compliance.
Patient kept in negative pressure rooms, use of N-95 face masks
Treatment success determined by completion of course and negative sputum smear, combinations may change depending on drug sensitivities/allergies
Treatment much longer in Multi-Drug Resistant (MDR) TB, and includes combination of 6 sensitive organism
When is DOT offered?
- have a current risk or history of non-adherence;
- have previously been treated for tuberculosis;
- have a history of homelessness, drug or alcohol misuse;
- are in prison or a young offender institution, or have been in the past 5 years;
- have a major psychiatric, memory or cognitive disorder;
- are in denial of the tuberculosis diagnosis;
- have multi-drug resistant tuberculosis;
- request directly observed therapy after discussion with the clinical team;
are too ill to self-administer treatment
What are the adverse drug reactions?
Rifampicin - > can turn urine (sweat& tears) red- four hours after a dose hepatitis, thrombocytopenic purpura, flu syndrome, can affect hormonal contraceptives
Isoniazid -> Hepatitis, peripheral neuropathy (pyridoxine (vitamin B6) is co-prescribed to help prevent this)
Pyrazinamide -> Hepatitis, arthralgia, hyperuricaemia
Ethambutol -> Retro Bulbar neuritis, arthralgia
What is the management of Multi-drug resistant TB and XTR TB?
MDR-TB is resistant to Isoniazid (INH) and Rifampicin (RIF), while XDR-TB is MDR-TB plus resistance to Fluoroquinolones and at least one second-line injectable drug (e.g., Amikacin, Kanamycin, or Capreomycin).
Surgical management of MDR and extensively drug resistant (XTR) TB
Unilateral disease (localized and resectable) → May undergo lobectomy or pneumonectomy.
Bilateral apical disease → Usually managed medically unless severe complications arise.
– only in cases where patients have good lung function & not responded to medical management
What are the general measures of TB?
Good respiratory hygiene
Smoking cessation/ reduced alcohol in take
Psychological support – depression/anxiety
How was TB prevented in the UK?
Bacillus Calmette–Guérin(BCG) Vaccination
- involves anintradermalinjection oflive attenuated(weakened)Mycobacterium bovisbacteria (a close relative ofM. tuberculosisthat does not cause disease in humans). This creates an immune response, providing lasting immunity againstM. tuberculosiswithout causing infection. The vaccine protects against severe and complicated TB but less againstpulmonary TB.
- BCG vaccine school vaccination programme ceased in 2005
- offered in patients at increased risk (areas of high prevalence with TB; close contact)
- vaccine doesn’t protect against infection but prevents more serious disease e.g miliary/meningeal TB
What are the other management options to consider?
Testing for other infectious diseases (e.g.,HIV,hepatitis Bandhepatitis C)
Testingcontactsfor tuberculosis
NotifyingUK Health Security Agency(UKHSA) of suspected cases
Isolating patientswithactive tuberculosisto prevent spread (usually for at least 2 weeks of treatment)
Aspecialist MDTguides management and follow-up
Individualised regimes are required formultidrug‑resistanttuberculosisandextrapulmonary disease
In hospitals,negative pressure roomsare used to prevent airborne spread. Negative pressure rooms have ventilation systems that actively remove air to prevent it from spreading onto the ward.
What is the screening test?
Before vaccination, patients are tested with theMantoux testand only given the vaccine if this test is negative. They are also assessed for the possibility ofimmunosuppressionandHIVdue to the risks related to alivevaccine.
Mantoux testing – tuberculin test or IGRA – positive results -> chest Xray
