Lecture 8.2 - Mycobacterium Tuberculosis

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Questions and Answers

What is the primary site of reactivation of M. tuberculosis?

Skin lesions

Liver

Granulomas in the lungs (correct)

Lymph nodes

What percentage of active TB cases are extrapulmonary in immunocompetent individuals?

15-20% (correct)

40-50%

25-30%

5-10%

Which of the following is NOT a common symptom of TB?

Cough

Weakness

Headache (correct)

Fever

What is the purpose of the Xpert MTB/RIF assay?

To diagnose rifampicin resistance and MDR-TB Signup and view all the answers

What is the primary reason for a false negative result in the Mantoux skin test?

Immunocompromised status Signup and view all the answers

What is the main difference between the Mantoux skin test and the Interferon Gamma Release assay (IGRA)?

The type of sample required Signup and view all the answers

Which of the following is a risk factor for reactivation of M. tuberculosis?

Severe stress Signup and view all the answers

What is the term for the spread of M. tuberculosis to other parts of the body through the bloodstream?

Haematogenous spread Signup and view all the answers

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 Signup and view all the answers

What is the result of the inflammatory response during primary TB infection?

Formation of a caseous centre surrounded by macrophages and lymphocytes Signup and view all the answers

What percentage of individuals with latent TB infection will go on to develop active infection?

5-10% Signup and view all the answers

What is the primary function of sulfolipids produced by M. tuberculosis during primary infection?

Inhibiting the fusion of phagocytic vesicles with lysosomes Signup and view all the answers

What is the result of the granuloma undergoing fibrosis and calcification during latent TB infection?

The bacteria persist but do not multiply Signup and view all the answers

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 Signup and view all the answers

What is the expected outcome for individuals with latent TB infection?

Most individuals will remain asymptomatic and non-contagious Signup and view all the answers

What is the role of macrophages during primary TB infection?

To phagocytose M. tuberculosis and initiate an inflammatory response Signup and view all the answers

What is the primary function of interferon gamma in detecting Mycobacterium tuberculosis?

It indicates exposure to Mycobacterium tuberculosis Signup and view all the answers

What is the duration of treatment for respiratory TB?

6-12 months Signup and view all the answers

What is the term for TB that is resistant to multiple antibiotics?

Extensively drug-resistant TB (XDR-TB) Signup and view all the answers

What is the purpose of contact tracing in TB prevention?

To identify individuals who have been exposed to TB Signup and view all the answers

What is the difference between latent and active TB infection?

Latent TB is not contagious, while active TB is Signup and view all the answers

What is the purpose of IGRA testing?

To diagnose latent TB infection Signup and view all the answers

What is the advantage of BCG vaccination in preventing TB?

It reduces the risk of severe TB infection Signup and view all the answers

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 Signup and view all the answers

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

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Description

Learn about the process of tuberculosis reactivation, its occurrence in granulomas, and the reasons behind it, including immunocompromised individuals.