Mycobacterium Tuberculosis

• Tuberculosis is the world’s most spreading disease and developing drug resistance.

Epidemiology of M.Tuberculosis

1. Mycobacterium tuberculosis is the causative agent.
2. It is estimated that 20% to 43% of the world’s population suffers from TB.
3. In the USA, 15 million people are infected (Old statics).
4. TB occurs in :
   1. Poor community is considered to be the disease of poor people.
   2. Malnourished people.
   3. Homeless.
   4. Overcrowded community.
   5. Substandard housing.

Mode of the spread of tuberculosis: 

1. This is an airborne disease.
2. This occurs in various forms and modes.
3. 1. Primary TB = Clinically and radiologically is silent.
   2. Latent TB = Do not have active disease and can not spread the disease to others.
   3. Active TB = 10% of the latent TB develop active TB when not given treatment.
   4. Progressive primary TB = 5 % of the primary active TB with signs and symptoms.
4. This is thought that 90% of the disease is a reactivation of latent TB.

Microbiology of Mycobacterium Tuberculosis:

1. These are acid-fast bacilli.
   1. These are rods shape and grow in cords.
   2. The growth is very slow on special media.
2. They get gram stain but are very weak, which is gram stain positive.
3. These are non-motile, obligatory aerobes and intracellular organisms.
4. Humans are the only reservoir.

Pathogenesis of Mycobacterium Tuberculosis:

1. Mycobacterium tubercle bacilli cause damage by invading the macrophagic cells by Type IV hypersensitivity reaction.
2. This bacteria leads to caseating necrosis and granuloma formation.

3. There are multinucleated giant cells, Langhans’ type cells.
4. TB  bacteria consists of slightly curved or straight rods.
   1. It cannot be stained by the gram’s stain but are acid-fast.
   2. These are nonmotile and without spores.
   3. Pathogenic bacteria are slow-growing and may take 4 to 6 weeks.
5. The common types are :
   1. Mycobacterium tuberculosis.
   2. Mycobacterium bovis.
   3. others are Runyon group 1 to IV.

Sign and Symptoms of Mycobacterium Tuberculosis:

1. The patient will have the following:
   1. Malaise.
   2. Anorexia.
   3. Weight loss.
   4. Fever.
   5. Night sweating.
   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.

Clinically the possibilities of tuberculosis are:

1. TT (Manteaux test) positive cases, and these cases may be inactive asymptomatic people.
2. Primary tuberculosis shows the Ghon complex.
   1. 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. There may be cavity formation in the lung.
   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 organs, including the bones.
5. Extra-pulmonary may involve CNS and leads to chronic meningitis.
   1. There may be the formation of tuberculoma in the brain.
   2. There may be the involvement of the skin.
6. TB is very common in AID patients.
   1. In AID patients, TT may be negative due to compromised immune systems.

Laboratory diagnosis of 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.
      

      TB bacilli

TB Acid-fast bacilli

2. Sputum, three consecutive samples is 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 in case of negative sputum.
   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 the case may give a positive culture to T. bacilli.
   1. The sensitivity should be done once the culture is positive.
   2. The sensitivity should be done if the sputum culture is positive after the treatment for 2 months.
6. Needle biopsy of the pleura shows granulomas in 60 % of the cases.
7. Pleural fluid cultures are positive in < 25 % of the cases.
8. Radiology,  X-ray chest shows small homogenous opacity.

Mantoux test or Tuberculin test (TT).

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

7. Other specimens that can also be used are:
   1. Urine. The first-morning clean catch is collected for three consecutive days.
   2. Stool. This should be collected in a clean, sterile container.
   3. Blood. Lysed centrifuged blood is used for culture.
8. Niacin test. Mycobacterium produces Niacin. Commercially available kits can test this.

Preventive measures for Mycobacterium Tuberculosis

1. This disease can be prevented by health workers.
2. If your TB test is positive, you have contact with the patient and may not have active disease.
3. Vaccination like BCG is helpful in preventing the disease.
   1. BCG is live attenuated bacteria.
   2. It is not available in the USA.

Treatment of Mycobacterium Tuberculosis

1. The following drugs are used in patients with tuberculosis:
   1. Isoniazid (INH).
      1. This is advised in TT-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.

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