Mycobacterium Tuberculosis (TB)

What sample is needed for the diagnosis of Tuberculosis?

1. For pulmonary tuberculosis, you can advise sputum for AFB staining.
2. A chest X-ray may also help.
3. A lymph node biopsy may be done to see granulomatous inflammation.
4. You may see granulomas in the bone biopsy.
5. Examination of the CSF.

How would you discuss the epidemiology of M. tuberculosis?

1. Tuberculosis is the world’s most widespread disease and a developing drug-resistant disease.
2. Mycobacterium tuberculosis is the causative agent.
3. It is estimated that 20% to 43% of the world’s population suffers from TB.
4. In the USA, 15 million people are infected (Old statistics).
5. TB occurs in :
   1. Poor communities suffer, and these are considered to be diseases of poor people.
   2. Malnourished people.
   3. Homeless.
   4. Overcrowded community.
   5. Substandard housing.

What is the mode of spread of tuberculosis?

1. This is an airborne disease.
   1. Coughing.
   2. Speaking.
   3. Sneezing.
2. This occurs in various forms and modes.
3. Primary TB = Clinically and radiologically, it is a silent disease.
   1. A characteristic lesion is a Ghon focus.
   2. Usually present in the peripheral lower part of the upper lobe or upper part of the lower lobe.
   3. This complex may become calcified and fibrotic.
4. Latent TB = Do not have active disease and can not spread the disease to others.
5. Active TB = 10% of latent TB develop active TB when not given treatment.
6. Progressive primary TB = 5% of the primary TB develop active TB with signs and symptoms.
7. It is thought that 90% of the disease is a reactivation of latent TB.

What is the Microbiology of Mycobacterium Tuberculosis?

1. These are acid-fast bacilli.
   1. These are rod-shaped and grow in cords.
   2. The growth is very slow on special media.
2. They stain Gram-positive but weakly.
3. These are non-motile, obligate aerobes and intracellular organisms.
4. Humans are the only reservoir.

What is the pathogenesis of Mycobacterium Tuberculosis?

1. Mycobacteria are engulfed by macrophages, and in them, they survive and multiply.
   1. These phagocytic cells ingest the mycobacteria and carry them via lymphatics to the local hilar lymph nodes.
   2. In the lymph nodes, a type IV hypersensitivity reaction (Cell-mediated immune response) takes place.
2. Mycobacterium tuberculosis bacilli cause damage by invading macrophages via a type IV hypersensitivity reaction.
3. This bacterium leads to caseating necrosis and granuloma formation.

4. Multinucleated giant cells, Langhans’ type cells, are present.
5. TB  bacteria consist of slightly curved or straight rods.
   1. Gram stain does not stain them, but they are acid-fast.
   2. These are nonmotile and without spores.
   3. Pathogenic bacteria are slow-growing and may take 4 to 6 weeks.
6. The common types are :
   1. Mycobacterium tuberculosis.
   2. Mycobacterium bovis.
   3. Others are Runyon group 1 to IV.

What are the components of a granuloma?

1. Granuloma consists of:
   1. Central caseous necrosis.
   2. Langhans giant cells. These consist of multiple nuclei in a horseshoe shape.
   3. Formation of epithelioid cells.
   4. There are surrounding lymphocytes.

What are the signs and Symptoms of Mycobacterium Tuberculosis?

1. The patient will have the following:
   1. Malaise.
   2. Anorexia.
   3. Weight loss.
   4. Fever.
   5. Night sweats.
   6. A chronic cough is a common presentation of pulmonary TB.
   7. Blood-streaked sputum is common.
   8. The patient may have hemoptysis.
   9. Rarely are patients asymptomatic.
   10. In advanced disease:
       1. There may be clubbing of nails.
       2. Enlarged lymph nodes in the neck.
       3. The patient may develop pleural effusion.

What are the possibilities of Mycobacterium tuberculosis infection?

1. TT (Mantoux test) positive cases, which may be inactive and asymptomatic.
2. Primary tuberculosis shows the Ghon complex.
   1. In primary tuberculosis, the disease is mostly insidious.
   2. There is a lesion in the lung and involvement of the lymph nodes.
3. Secondary tuberculosis involves the upper lobe of the lung because of the higher oxygen concentration.
   1. This is usually seen in impaired immunity.
   2. Cavity formation may occur in the lungs.
   3. Sputum smears are AFB-positive.
   4. The disease is contagious.
4. Miliary tuberculosis is a widespread disease.
   1. It involves the lungs, CNS, kidneys, and GI tract.
   2. It may involve any organ, including the bones.
5. Extra-pulmonary TB may involve the CNS and lead to chronic meningitis.
   1. A tuberculoma may form in the brain.
   2. The skin may be involved.
6. TB is very common in AIDS patients.
   1. In AIDS patients, TT may be negative due to compromised immune systems.

What are the complications of tuberculosis?

1. Primary tuberculosis in the lungs.
2. Involvement of the kidneys.
3. Involvement of the neighboring part of the lungs.
4. Pleural effusion.
5. Involvement of the meninges.
6. Brain abscess.
7. Involvement of the intestines.
8. Peritonitis.
9. Skin infection

How would you diagnose Mycobacterium Tuberculosis?

1. Definite diagnosis depends upon the demonstration of T. Bacilli by:
   1. Culture.
   2. Culture on solid media needs 12 weeks.
   3. Culture on liquid media needs several days.
   4. PCR by DNA or RNA amplification method.

2. Sputum, three consecutive samples are recommended for:
   1. Fluorochrome staining with rhodamine-auramine.
   2. AFB stain or Ziehl-Neelsen stain.
   3. An early morning specimen is recommended.

3. Bronchoscopy is advised for bronchial washing if sputum is negative.
   1. Transbronchial lung biopsy increases the diagnostic yield.
4. Gastric aspiration. An early morning sample is an alternative to bronchoscopy.
5. Blood culture: 15% of cases may indicate a positive culture for T. bacilli.
   1. Assess sensitivity once the culture is positive.
   2. Assess sensitivity if the sputum culture is positive after 2 months of treatment.
6. Needle biopsy of the pleura shows granulomas in 60% of cases.
7. Pleural fluid cultures are positive in <25% of cases.
8. Radiology: The chest X-ray shows a small homogeneous opacity.
9. Other specimens that can also be used are:
   1. Urine. Collect the first-morning clean catch for three consecutive days.
   2. Stool. Collect this in a clean, sterile container.
   3. Blood. Lysed, centrifuged blood is used for culture.
10. Niacin test. Mycobacterium produces Niacin. Commercially available kits can test this.

How will you describe the significance of the Mantoux test or Tuberculin test (TT)?

1. The Mantoux test (TT) will not distinguish between latent and active TB.
2. Inject 0.1 mL (5 tuberculin units) of PPD intradermally.
3. The best site is the volar surface of the arm.
4. Inject with a 27 G needle.
5. Read after 48 to 72 hours for induration (thickening of the injected area).
6. After infection, it takes 2 to 10 weeks for the immune response to PPD to develop.

What are the preventive measures for Mycobacterium Tuberculosis?

1. Health workers can prevent this disease.
2. If your TB test is positive, you have had contact with the patient and may not have active disease.
3. Vaccination, such as BCG, helps prevent the disease.
   1. BCG is a live attenuated bacterium.
   2. It is not available in the USA.

How would you treat Mycobacterium Tuberculosis infection?

1. The following drugs are used in patients with tuberculosis:
   1. Isoniazid (INH).
      1. This is advised in TB-positive people.
      2. This is also given prophylactically in AIDs patients.
   2. Combination of drugs like:
      1. Isoniazid.
      2. Rifampicin.
      3. Pyrazinamide.
      4. Ethambutol.
   3. Isolation is also important to stop the spread of the disease.
   4. Steroids are contraindicated in these patients because there may be reactivation of tuberculosis.

What is the outcome of tuberculosis?

1. There is a steady decline in the incidence of tuberculosis because of the:
   1. Specific preventive measures.
   2. Improvement in social conditions.
   3. Use of the BCG vaccine in the prevalent area.
   4. Use of isoniazid for 1 year with a close contact person.

Questions and answers:

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