Mycobacterium tuberculosis-Epidemiology, Pathogenesis, and Treatment

Mycobacterium tuberculosis-Epidemiology, Pathogenesis, and Treatment

Introduction

  • M. tuberculosis is gram-positive rods, aerobic, non-motile, non-spore-forming, intracellular bacteria.
  • It has fastidious growth requirements, growth is enhanced by CO2 (5%-10%), divides slowly (up to 8 weeks), because of the complex cell wall.
  • The common culture medium is Lowenstein- Jensen (composed with homogenized egg in the base nutrient), colonies appear after 3-6 weeks, they are rough, dry & light brownish yellow color colonies.
Mycobacterium tuberculosis colonies on Lowenstein- Jensen medium
Mycobacterium tuberculosis colonies on Lowenstein- Jensen medium
  • Cell Structure – It is rich in lipids, with hydrophobic exteriors which provide resistance against various disinfectants,  stains, acids & alkalis.
  • It is different from  a typical gram-positive cell wall structure :
    • In the plasma membranes, phosphatidylinositol mannosidises, proteins, and lipoarabinomannan (LAM) are anchored.
    • LAM has a functional association with the O-antigenic lipopolysaccharide that exists in bacteria.
    • Porins and Transport protein span across the cell wall.
    • The proteins have biological significant antigens, triggers the host’s cellular immune response, also used for diagnosis purposes as purified protein derivatives (PPDs).
The cell wall of Mycobacterium tuberculosis

Pathogenesis

  • M. tuberculosis can cause lifelong infection, it affects the respiratory tract.
  • When exposed, M. tuberculosis enters the respiratory airways & penetrates the alveoli, gets phagocytosed by alveolar macrophages.
    •  Bacteria prevents phagosome fusions with lysosomes (by blocking early endosomal autoantigen 1(EEA1).
    • Instead phagosome fuse with intracellular vesicles (permit access to nutrients & replication).
  • Macrophage secretes interleukin-12(IL-12) & tumor necrosis factor-α (TNF-α), in response to the infection.
  • Cytokines  increasing localized inflammation ( recruits T cells, NK cells, required interferons)
  • People who have decreased productions of cytokines (IL-12 & TNF-α) or defects in cytokines receptors are at major risk of mycobacterial infections.
  • Fused macrophages / Langhans giant cells/epithelial cells, with mycobacterium, form a necrotic mass (present in core) surrounded by a thick wall of macrophages & NK T cells, CD4 & CD8 which is completely called a granuloma.
    • It prevents the further spread of the infection.
    • Less antigenic burden leads to the formation of the small granuloma with minimal tissue damage.
    • More bacteria are present, large necrotic granulomas are formed, encapsulated within fibrins which provide resistance against macrophage killing. (Bacteria can remain in a dormant stage and reinfect when the host immune system is weakened (old age or disease- called Reactivation).

Epidemiology

  • The natural reservoirs are humans and primates.
  • The mode of transmission is by person-to-person contact (by inhaling infectious droplets).
  • According to WHO, 1/3 rd of the population is infected by the disease tuberculosis.
  • The mortality rate per year is 2 million / yr and new cases are 9 million worldwide.
  • The highest incidence includes regions such as sub-Saharan Africa, Eastern Europe & Southeast Asia.
  • People susceptible to disease caused by M.tuberculosis are drug & alcohol abusers, HIV patients, also health care workers.

Sign & Symptoms

  • The primary infection of tuberculosis is majorly asymptomatic or clinical symptoms like fever & malaise occur.
  • The infiltrates in the lung (mid-zone) & enlarged lymph nodes can be observed by radiographs. It occurs in Pulmonary tuberculosis.
  • The symptoms include dry cough (main), as a disease progresses there is sputum production, mixed with blood (known as hemoptysis), fever, sweating, malaise, fatigue, & weight loss comes along with the further disease progression
  • The disease can also involve other organs such as bone, kidneys, brain, meninges & bowel.
  • The untreated progressive disease usually takes 2-5 yrs to cause death but is rapid in HIV  or immunocompromised patients.

Diagnosis

  • A very common diagnostic test to find out the exposure to the organism is the Tuberculin test (test for PPD) & Interferon -γ  release, these are sensitive markers.
  • Detection can be done by using microscopic observation of clinical specimens (sputum) smeared with Ziehl- Neelsen procedure.
Rod shape mycobacterium can be observed by the acid-fast staining method
  • Molecular probes are quite helpful in the diagnostic procedure.

Treatment

  • M. tuberculosis is susceptible to various effective antimicrobial agents as follows:

First Line Drug

Second Line Drug

Isoniazid (Disrupts mycolic acid) Para-Aminosalicylic acid
Ethambutol (affects LAM element in the cell wall) Ethionamide
Rifampin Cycloserine
Pyrazinamide Fluoroquinolones (e.g., ciprofloxacin & ofloxacin)
Streptomycin (Inhibits cell wall synthesis) Kanamycin
  • Second lines drugs are used in combinations with the first lines drugs if resistance or toxicity prevails.
  • The oral chemotherapy treatment (Isoniazid & Ethambutol) of the disease, is usually continued for 18- 24 months.
  • The time period of treatment is shortened by 6 months by using isoniazid, rifampin & pyrazinamide.
  • For prevention, the BCG vaccine (Bacillus Calmette-Guerin) is available.

References & Sources

  • https://quizlet.com/155098300/mmi-unit-3-flash-cards/
  • https://www.researchgate.net/publication/8666585_Tuberculosis_A_problem_with_persistence
  • https://quizlet.com/57381644/pathogenic-microbiology-test-3-note-cards-flash-cards/
  • https://www.sciencedirect.com/topics/medicine-and-dentistry/blue-rubber-bleb-nevus-syndrome

Also Read:

Leave a Comment