Tuberculosis

Question 1

What causes tuberculosis infection?

Answer 1

Tuberculosis infection is caused by a bacterium called tubercle bacilli.

Question 2

What is the name of the bacterium responsible for tuberculosis?

Answer 2

The bacterium responsible for tuberculosis is called Mycobacterium tuberculosis.

Question 3

Besides Mycobacterium tuberculosis, what other bacteria can cause tuberculosis-like infections?

Answer 3

Non-tuberculous (atypical) mycobacteria can also cause tuberculosis-like infections.

Question 4

How is tuberculosis transmitted?

Answer 4

Tuberculosis is primarily spread through the inhalation of droplets released by coughing individuals with pulmonary tuberculosis.

Question 5

What happens when the tuberculosis bacillus is inhaled into the lung?

Answer 5

Macrophages ingest the bacillus, and the bacilli replicate within the endosome.

Question 6

How can tuberculosis spread to other parts of the body?

Answer 6

Tuberculosis can spread through various routes, including the bloodstream (haematogenous), lymphatics to hilar lymph nodes and other lymph nodes, and direct extension to adjacent structures (e.g., pericardium).

Question 7

What percentage of tuberculosis cases primarily affect the lungs?

Answer 7

Approximately 80% of tuberculosis cases affect the lungs.

Question 8

Who is at risk of tuberculosis?

Answer 8

Various risk factors include deprivation (homelessness, malnutrition, overcrowding, vitamin D deficiency), alcohol abuse, prisons, immunocompromise (diabetes mellitus, HIV, steroid use), the elderly, and contact with high-risk groups (certain jobs, travel to areas of high incidence).

Question 9

What are the clinical presentations of pulmonary tuberculosis?

Answer 9

Clinical presentations of pulmonary tuberculosis include a productive cough (not improving with standard antibiotics), haemoptysis, chest pain, fever, night sweats, fatigue, and weight loss.

Question 10

What are some manifestations of the initial hypersensitivity response to tuberculosis infection?

Answer 10

The initial hypersensitivity response to tuberculosis infection can present with erythema nodosum (painful red nodules on the shins) and phlyctenular conjunctivitis (inflammation of the conjunctiva).

Question 11

How does the body respond to tuberculosis infection, and what are the different ways the disease may progress?

Answer 11

The body responds to tuberculosis infection by forming granulomas, which are collections of immune cells. The disease can progress in various ways, such as latent tuberculosis infection (asymptomatic), active pulmonary tuberculosis, miliary tuberculosis (spread throughout the body), extrapulmonary tuberculosis (affecting other organs), or tuberculosis reactivation (when latent infection becomes active).

Question 12

What is the pathogenesis of tuberculosis?

Answer 12

The pathogenesis of tuberculosis involves the inhalation of Mycobacterium tuberculosis (MTB) bacilli into the lungs. The bacilli are taken up by macrophages, which form granulomas. Within the granulomas, the bacteria can remain dormant or cause active disease, leading to tissue damage and the potential for dissemination.

Question 13

What are the characteristics of pulmonary MTB?

Answer 13

Pulmonary MTB accounts for the majority of tuberculosis cases (55%). It is associated with a higher risk of infection transmission. Cavitatory disease, characterized by the formation of cavities within lung tissue, is more infectious. In the lungs, there is a Ghon focus, which is a granuloma with central caseation and fibrosis. Over time, the Ghon focus may calcify and contain few dormant bacteria.

Question 14

Describe the characteristics of MTB bacillus.

Answer 14

The MTB bacillus is an aerobic bacterium that requires oxygen to survive. It has a slow growth rate, dividing every 16-20 hours. It has a cell wall but lacks a phospholipid outer membrane. It stains weakly positive with Gram stain but retains stains after treatment with acids, leading to its classification as an acid-fast bacillus.

Question 15

What diagnostic methods are used for pulmonary MTB?

Answer 15

Diagnosis of pulmonary MTB can be achieved through various methods, including chest X-ray (which often shows upper lobe involvement), sputum culture (three early morning samples), bronchoalveolar lavage (if sputum is not available), Mantoux (Tuberculin test), and Interferon gamma release assay (IGRA)/T-spot test. These tests rely on the host’s cellular immune response to MTB infection.

Question 16

What are the microbiological diagnostic methods for MTB?

Answer 16

Microbiological diagnosis of MTB includes sputum or bronchoalveolar lavage (BAL) samples, Ziehl-Neelsen (ZN) stain for microscopy, TB cultures (which take 6-8 weeks to confirm diagnosis and determine drug sensitivities), and nucleic acid amplification tests to identify the MTB complex and distinguish it from non-tuberculous infections. PCR can also be used to detect Mycobacterial DNA in various specimens such as pleural fluid, CSF, urine, etc.

Question 17

What are the stains used for MTB?

Answer 17

The stains commonly used for MTB include the Ziehl-Neelsen (ZN) stain, which shows bright red bacilli against a blue background, and the auramine-rhodamine stain, which utilizes fluorescence microscopy.

Question 18

What does the histology of MTB show?

Answer 18

The histology of MTB typically reveals granulomatous inflammation with a rim of lymphocytes and fibroblasts. Central infected macrophages, also known as giant cells, are present. Central necrosis, known as caseation, is observed. There is also secretion of cytokines, such as IFNγ, which activate macrophages to kill the bacteria. Acid-fast bacilli (AFBs) may be visualized within the granulomas.

Question 19

What is the Mantoux/Tuberculin test?

Answer 19

The Mantoux test, also known as the tuberculin test, is a cutaneous immune response test. It involves the intradermal injection of purified protein derivative (PPD) from Mycobacterium tuberculosis. The size of the reaction, measured after 48-72 hours, is graded based on the size of induration. It requires the ability of circulating memory T-lymphocytes to mount a delayed hypersensitivity reaction.

Question 20

What are the limitations of the Mantoux test?

Answer 20

The Mantoux test may yield false-positive results in individuals who have received the Bacillus Calmette-Guérin (BCG) vaccine and false-negative results in severely ill or immunosuppressed individuals. It can also cross-react with other Mycobacterial antigens, leading to non-specific results.

Question 21

What is the IGRA/T-spot test?

Answer 21

The IGRA (interferon gamma release assay) or T-spot test is an in-vitro test that measures T-cell activation by Mycobacterium tuberculosis antigens. Blood samples for the test must be analyzed within a few hours. It is more specific than the Mantoux test and correlates better with the degree of exposure to TB. However, it cannot differentiate between latent infection and active disease.

Question 22

What are the diagnostic methods for tuberculosis?

Answer 22

The diagnosis of tuberculosis involves considering the patient’s history of contact with smear-positive TB, presence of signs and symptoms suggestive of TB, abnormal chest X-ray findings, positive tuberculin test or positive T-spot test, culture of Mycobacterium tuberculosis, and always considering an HIV test.

Question 23

What is primary TB?

Answer 23

Primary TB refers to the active form of tuberculosis that occurs soon after the initial infection. It accounts for approximately 1-5% of cases, where the bacilli overcome the immune system shortly after infection.

Question 24

What is latent TB?

Answer 24

Latent TB infection is the majority of cases where individuals have been infected with Mycobacterium tuberculosis but do not have active disease. It represents immune memory of exposure to TB. Approximately 2-23% of individuals with latent TB infection may progress to reactivation disease.

Question 25

What is the difference between latent and active pulmonary TB?

Answer 25

Most people infected with TB have latent TB infection, meaning they are asymptomatic and not infectious. About 90% of those with latent TB will never become ill with TB, unless they are HIV positive. However, about 10% will progress to active TB, which is symptomatic and infectious. The risk of progressing to active TB is highest within the first 1 to 2 years of infection and decreases gradually over time.

Question 26

How does active TB occur?

Answer 26

Active TB can occur through two mechanisms: reactivation of latent TB (when the dormant bacteria become active again) or reinfection with a new strain of Mycobacterium tuberculosis.

Question 27

What are some differential diagnoses for TB?

Answer 27

Differential diagnoses for TB include conditions that present with bilateral hilar lymphadenopathy and B symptoms (fever, night sweats, weight loss), such as sarcoidosis and lymphoma.

Question 28

What are some sites of extrapulmonary TB?

Answer 28

Extrapulmonary TB can occur in various sites, including lymph nodes, central nervous system (CNS), bones (Pott’s disease of the spine), genitourinary system, gastrointestinal (GI) tract, and can also manifest as disseminated disease known as miliary TB.

Question 29

What are some characteristics of TB lymphadenitis?

Answer 29

TB lymphadenitis may worsen initially during treatment, which is known as a paradoxical reaction. It can also lead to the formation of sinus tracts with chronic discharge and the development of cold abscesses.

Question 30

What are the common symptoms associated with disseminated miliary TB?

Answer 30

Common symptoms of disseminated miliary TB include fevers, sweats, weight loss, and malaise. Respiratory symptoms are most common, but gastrointestinal (GI) or central nervous system (CNS) symptoms may also occur. GI symptoms can include abdominal pain, diarrhea, and abnormal liver function tests. CNS symptoms may manifest as headache, confusion, or altered mental state.

Question 31

What are some examples of extrapulmonary TB sites?

Answer 31

Extrapulmonary TB can occur in various sites, including the pericardium, eye, skeleton, genitourinary system, gastrointestinal (GI) tract, and central nervous system (CNS). Tuberculous meningitis is a form of CNS involvement, and it can be diagnosed by finding TB in the cerebrospinal fluid (CSF). Extrapulmonary TB is more common in individuals co-infected with HIV.

Question 32

What is the mortality rate associated with extrapulmonary TB, particularly in HIV co-infected individuals?

Answer 32

The mortality rate of extrapulmonary TB can range from 15% to 40% even with treatment. This rate is higher in HIV co-infected individuals.

Question 33

What is the standard quadruple therapy for tuberculosis (TB) using first-line drugs?

Answer 33

The standard quadruple therapy for TB consists of an initial phase of 2 months, which includes the drugs isoniazid, rifampicin, pyrazinamide, and ethambutol. This is followed by a continuous phase of 4 months, which includes isoniazid and rifampicin. However, for central nervous system (CNS) TB, specifically TB meningitis, treatment is extended to 12 months.

Question 34

What are the potential side effects of drug treatment for MTB?

Answer 34

The potential side effects of drug treatment for MTB include:

Pyrazinamide: Hepatotoxicity, joint pain, nausea, and vomiting.
Rifampicin: Hepatotoxicity, reddish color to the urine and tears.
Isoniazid: Hepatotoxicity, fever, peripheral neuropathy, and optic neuritis.
Ethambutol: Peripheral neuropathy, optic neuropathy, and gout.
All drugs: Nausea and skin rashes.

Question 35

What are the treatment duration and drugs used for CNS TB (TB meningitis)?

Answer 35

The treatment duration for CNS TB, specifically TB meningitis, is 12 months. The drugs used in the treatment regimen are the same as the standard quadruple therapy, including isoniazid, rifampicin, pyrazinamide, and ethambutol.

Question 36

What is multi-drug resistant TB (MDRTB)?

Answer 36

Multi-drug resistant TB refers to TB that is resistant to at least two of the most effective first-line anti-TB drugs: isoniazid and rifampicin. It occurs primarily due to the failure of treatment with first-line drugs, often due to lack of compliance. MDRTB poses a significant public health risk and is associated with higher mortality rates compared to drug-susceptible TB.

Question 37

What are some key points about MDRTB?

Answer 37

Majority of MDRTB cases are from Africa or the Indian sub-continent.
Rates of MDRTB have increased in the UK due to immigration.
MDRTB accounts for approximately 10% of all TB deaths worldwide.
Patients with MDRTB must be isolated to prevent transmission.
Outbreaks of MDRTB in hospitals and prisons can lead to high mortality.
Management of MDRTB requires specialized expertise and experience.
Treatment for MDRTB involves a prolonged course of second-line drugs, which may be required for up to 24 months. In some cases, third-line drugs may also be necessary.

Question 38

When is treatment for latent TB recommended?

Answer 38

Treatment for latent TB is recommended in various situations, including screening for latent TB among close contacts of an index case, pre-employment screening for healthcare workers, for certain individuals entering the UK (such as “looked after children”), and for those who will undergo immunosuppressive biologics treatment (e.g., rheumatoid arthritis, Crohn’s disease, psoriasis). The recommended treatment duration is 3 months of rifampicin and isoniazid or 6 months of isoniazid alone.

Question 39

How can the spread of TB be prevented?

Answer 39

The prevention of TB spread involves several strategies, including BCG vaccination, contact tracing, and directly observed therapy. These measures aim to identify cases, trace their contacts, and ensure appropriate treatment to prevent further transmission.

Question 40

Who should receive BCG vaccination?

Answer 40

BCG vaccination is typically offered to infants aged 0-4 weeks in specific situations:

Infants born in high-incidence areas with a TB incidence rate greater than 40 per 100,000.
Infants with a parent or grandparent born in a high-incidence area.
Infants with a family history of TB within the last 5 years. BCG vaccination reduces the risk of TB meningitis and miliary TB.

Question 41

What is contact tracing in the context of TB?

Answer 41

Contact tracing involves identifying the index case (patient with TB) and tracing their close contacts, such as household members. If any of these contacts test positive, the tracing extends to other family members, school or work contacts, and so on.

Question 42

How are contacts screened during contact tracing?

Answer 42

Contacts are typically screened using a chest X-ray (CXR) and an interferon-gamma release assay (IGRA). If the CXR is normal but the IGRA is positive, latent TB treatment is recommended. If the CXR is abnormal, and there are symptoms, along with a positive IGRA result, 6-month TB treatment is usually prescribed.

Question 43

What is directly observed therapy (DOT)?

Answer 43

Directly observed therapy is a strategy used to ensure treatment compliance in individuals with tuberculosis (TB). It involves a designated person, such as a healthcare worker or family member, directly observing the patient taking their medication. DOT is particularly important for certain individuals, including children who need supervision to swallow tablets and adults with factors such as alcoholism, chaotic lifestyle, previous TB, or mental health problems.

Question 44

How is directly observed therapy implemented?

Answer 44

Directly observed therapy can be conducted in various settings, including hospitals, via video calls, or at local pharmacies. The recommended frequency is daily administration of tablets. If daily administration is not feasible, three times a week can be considered. Ensuring compliance through DOT is crucial to avoid poor treatment outcomes and the development of multi-drug resistance TB.

Question 45

What are some monitoring methods for TB treatment?

Answer 45

During TB treatment, monitoring may include baseline blood tests, such as liver function tests, to assess the impact of the medication on liver health. Additionally, the Ishihara test, which evaluates color vision, may be performed to detect any potential adverse effects of the medication on vision. Regular monitoring of liver function tests throughout the treatment course is important.