Mycobacterium

Tuberculosis,Leprosy

Mycobacterium tuberculosis

a) Description

b) Pathogenesis

  1. bacilli inhaled as droplet nuclei
  2. in human,bacilli are engulfed by alveolar macrophages in which they replicate to form the initial lesion known as Ghon Focus or Tubercles
  3. some bacilli are carried in phagocytic cells to the lymph nodes where additional foci of infection develop
  4. both formation of tubercles and the enlarged lymph nodes are known as primary complex
  5. within 10 days of infection,clones of antigen specific T lymphocytes are produced and release lymphokines which activate macrophages and cause them to form a compact cluster or granuloma around the foci of infection
  6. the centre of the granuloma contains a mixture of necrotic tissue and dead macrophages,which from its cheese-like appearance and consistency is referred to as caseous lesion
  7. the macrophages in the granuloma consume oxygen and the resulting anoxia and acidosis in the centre of the lesion kills most of the tubercle bacilli
  8. granuloma formation is usually sufficient to limit the primary infection but not all bacilli are destroyed. Some remain in a poorly understand dormant form from which when reactivated,cause post primary disease
  9. sometimes the tubercle lesions liquefy and form air-filled tuberculous cavities. From these cavities,the bacteria can spread to new foci of infections throughout the body. This spreading is often called miliary tuberculosis
  10. reactivation may occur spontaneously or after an inter-current illness or other condition that lowers the host's immune responsiveness
  11. reactivation often occurs in the upper lobes of the lungs
  12. the same process of granuloma formation occurs but the necrotic element of the reaction causes tissue destruction and the formation of large areas of caseation termed tuberculomata
  13. proteases liberated by activated macrophages cause softening and liquefaction of the caseous material and an excess of tumour necrosis factor and other immunological mediators cause the wasting and fevers characteristic of the disease
  14. the interior of the tuberculoma is acidic and anoxic and contains few viable tubercle bacilli
  15. eventually,however,the expanding lesion erodes through the wall of a bronchus,the liquefied contents are discharged and a well-aerated cavity is formed
  16. once the cavity is formed,large number of bacilli gain access to the sputum and the patient becomes an open or infectiousm case
  17. reactivation tuberculosis is particularly likely to occur in immunocompromised individuals including the elderly,transplant recipients and those who are HIV positive

c) Laboratory Diagnosis

d) Treatment

Divided into three phases :-

  1. during the first week or two,the large no, of actively replicating bacilli in cavity walls are killed,principally by isoniazid but also by rifampicin and ethambutol. As a result,the patient rapidly ceases to be infectious
  2. in the following few weeks,the less active bacilli within macrophages,caseous material and dense acidic,inflammatory lesions are killed by rifampicin and pyrazinamide
  3. in the continuation phase,any remaining dormant bacilli are killed by rifampicin during their short bursts of metabolic activity. Any rifampicin-resistant mutants that start to replicate are killed by isoniazid

e) Control

Mycobacterium leprae

a) Description

b) Pathogenesis

  1. the principal target cell is the schwann cell and the resulting nerve damage is responsible for the main clinical features of leprosy which are anaesthesia and muscle paralysis
  2. repeated injury to and infections of the anaesthetic extremities leads to their gradual destruction
  3. first sign of leprosy is a non-specific or indeterminate skin lesionwhich often heals spontaneously
  4. if the disease progresses,its clinical manifestation is determined by the specific immune responsiveness of the patient to the bacillus and there is a distinct immunological spectrum with hyper-raective tuberculoid (TT) leprosy at one pole and anergic lepromatous (LL) leprosy at the other. The intermediate position on the spectrum are classified as border-line tuberculoid (BT),mid-borderline (BB) or borderline lepromatous (BL)
  5. the nasal bones are also involved in leprosy and their destruction may lead to collapse of the nose
  6. blindness is another common and tragic complication of untreated leprosy

c) Laboratory diagnosis

d) Treatment

e) Control

Glossary