24 Questions
What is the primary site of reactivation of M. tuberculosis?
Granulomas in the lungs
What percentage of active TB cases are extrapulmonary in immunocompetent individuals?
15-20%
Which of the following is NOT a common symptom of TB?
Headache
What is the purpose of the Xpert MTB/RIF assay?
To diagnose rifampicin resistance and MDR-TB
What is the primary reason for a false negative result in the Mantoux skin test?
Immunocompromised status
What is the main difference between the Mantoux skin test and the Interferon Gamma Release assay (IGRA)?
The type of sample required
Which of the following is a risk factor for reactivation of M. tuberculosis?
Severe stress
What is the term for the spread of M. tuberculosis to other parts of the body through the bloodstream?
Haematogenous spread
What is the primary mode of transmission of TB from person to person?
Inhalation of droplets in the air containing bacteria from an infected person
What is the result of the inflammatory response during primary TB infection?
Formation of a caseous centre surrounded by macrophages and lymphocytes
What percentage of individuals with latent TB infection will go on to develop active infection?
5-10%
What is the primary function of sulfolipids produced by M. tuberculosis during primary infection?
Inhibiting the fusion of phagocytic vesicles with lysosomes
What is the result of the granuloma undergoing fibrosis and calcification during latent TB infection?
The bacteria persist but do not multiply
What is the consequence of the destruction of macrophages and phagocytes during primary TB infection?
Tissue damage due to the release of degradative enzymes and reactive oxygen species
What is the expected outcome for individuals with latent TB infection?
Most individuals will remain asymptomatic and non-contagious
What is the role of macrophages during primary TB infection?
To phagocytose M. tuberculosis and initiate an inflammatory response
What is the primary function of interferon gamma in detecting Mycobacterium tuberculosis?
It indicates exposure to Mycobacterium tuberculosis
What is the duration of treatment for respiratory TB?
6-12 months
What is the term for TB that is resistant to multiple antibiotics?
Extensively drug-resistant TB (XDR-TB)
What is the purpose of contact tracing in TB prevention?
To identify individuals who have been exposed to TB
What is the difference between latent and active TB infection?
Latent TB is not contagious, while active TB is
What is the purpose of IGRA testing?
To diagnose latent TB infection
What is the advantage of BCG vaccination in preventing TB?
It reduces the risk of severe TB infection
What is the significance of a negative IGRA test result in individuals who have received BCG vaccine?
It indicates that the individual is not infected with TB
Study Notes
Reactivation
- Mainly occurs in lung granulomas, but can happen at any site
- Causes caseation necrosis, leading to cavities where bacteria grow
- Large numbers of bacteria present in the lungs, shed during sneezing or coughing
- Haematogenous spread to other parts of the body, leading to miliary tuberculosis (especially in immunocompromised individuals)
Reasons for Reactivation
- Immunocompromised status (e.g. medication, infection, HIV)
- Elderly
- Severe stress
- Malnutrition
- Alcoholism
- Migration
Extrapulmonary TB
- Accounts for 15-20% of active TB cases in immunocompetent individuals
- Accounts for 50-60% of active TB cases in HIV-positive individuals
- Can affect various organs, including:
- Meninges (meningitis)
- Kidneys (sterile pyuria)
- Liver (hepatitis)
- Lumbar vertebrae (Pott's disease)
- Miliary Tuberculosis (normally in immunocompromised individuals)
Common Symptoms of TB
- Fever
- Night sweats
- Cough
- Haemoptysis
- Chest pain
- Weakness
- Weight loss
Diagnosis
- Chest X-ray
- Sputum sample (Ziehl-Neelsen stain)
- Sputum culture (Lowenstein Jensen culture)
- Bronchoalveolar lavage (culture)
- PCR
- Xpert MTB/RIF (diagnoses rifampicin resistance and takes approximately 90 minutes)
Skin Test for Diagnosis of TB
- Mantoux skin test
- Intradermal injection of purified protein derivative
- Measure size of area of induration after 48-72 hours
- Positive result may be due to infection, non-TB mycobacteria, latent infection, or vaccination with BCG
- False negative could be due to immunocompromised status
Blood Test
- Interferon Gamma Release assay (IGRA)
- Detects evidence of exposure to Mycobacterium tuberculosis
- Specific to Mycobacterium tuberculosis
- Indicator of latent infection as well as active infection
- IGRA test does not distinguish between latent and active infection
- Negative in subjects who have received BCG vaccine
Treatment
- Can be between 6-18 months
- Respiratory TB: 2 months treatment (killing phase) with Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol
- Patient may be non-infectious in 2-3 weeks
- 4 months treatment (kill remaining bacteria and stop relapse) with Rifampicin and Isoniazid
- Longer treatments may be needed for resistant bacteria
Antibiotic Resistance
- Resistant to first line antibiotic (Rifampicin/Isoniazid)
- Treatment no longer than 6 months
- MDR-TB: resistant to 2 first line antibiotics
- Add a second line antibiotic (e.g. Fluoroquinolone)
- XDR-TB: resistant to first and second line antibiotics
- High mortality
Notification
- TB is a notifiable disease
- Contract tracing
- Outcome
Prevention of TB
- Vaccination
- Reporting
- Contact tracing
- Chest X-ray (for pulmonary TB)
BCG Vaccine
- Live attenuated strain of Mycobacterium bovis (Bacillus Calmette Guerin)
- BCG vaccination was routine in the UK due to high TB death rate
- With better diet, living conditions, and knowledge, TB was almost eradicated by the 1980s
Transmission
- Person-to-person by inhalation of droplets containing bacteria from cough, sneeze, or spit of infected person
Infection
- Primary disease: granuloma formation
- Mycobacterium tuberculosis is phagocytosed by alveolar macrophages
- M.tuberculosis survive in macrophages by producing sulfolipids
- Inflammatory response causes lymphocytes and macrophages to migrate to the area, forming a granuloma
Latency
- Granuloma may undergo fibrosis and calcification
- Bacteria may persist but not multiply
- Affected individuals may be asymptomatic or have mild flu-like illness
- Once latent, most people remain non-symptomatic and are not contagious
- 5-10% go on to active infection and are contagious
Learn about the process of tuberculosis reactivation, its occurrence in granulomas, and the reasons behind it, including immunocompromised individuals.
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