HC extra: Mycobacterial infections (tuberculosis)

Mycobacterium tuberculosis epidemiology

Mycobacterium tuberculosis is characterized by:

• Droplet nuclei
• Alveolar macrophage
• Intracellular survival
• Spread to lymph nodes
• Hematogenous spread
• T-cell immunity → latent stage
• Reactivation

In regions such as southern Africa, 50% of patients with TB have HIV. HIV affects the CD4 cells, which increases the chance of getting TB enormously.

Pathogen and pathogenesis

Mycobacterium tuberculosis can have 6 different clinical manifestations:

• Latent
  • Many patients don't have symptoms but are carriers
• Subclinical
  • Cannot only be transmitted during forceful coughs
• Limited disease
  • Pneumonia in 1 lung lobe
• Extensive disease
  • Pneumonia in both lungs
• Multi-organ
  • Spread by macrophages migrating everywhere in the body
  • For example masses in the abdomen
• Miliary TBC
  • Very rare
  • Granulomas all over the body
    • The granulomas are visible as speckles
    • The necrosis breaks through to the vessel wall → the bacteria are spread via the blood stream

Diagnosis and treatment

Testing:

TB can be diagnosed clinically or via diagnostic tests:

• Clinical
  • Complaints
    • Cough for longer than 2 weeks
    • Fever, night sweats, weight loss
    • Depends on organ involvement
  • Physical examination
• Diagnostic tests
  • Radiography: never specific for TBC
  • Histology: unusual
    • Granulomas
    • Central necrosis
      • Looks like cottage cheese
    • Multinucleate giant cells
  • Microbiological tests: essential for a correct diagnosis
    • Acid fast staining
      • For example Ziehl-Neelsen
      • The cell wall has a high content of complex lipids → mycolic acids
      • Acid fast bacteria stay pink, non-acid fast bacteria become blue after decoloring
    • PCR
    • Culture
      • Takes 2 weeks to 2 months until the bacteria have grown
    • Antibiotic susceptibility testing
    • Genotyping
  • Indirect
    • Tuberculin skin test
      • A small amount of antigens is injected → the T-cell response is measured
      • Positive mantoux test → the T-cells respond in the skin
      • These tests are not specific for TBC
    • Interferon gamma release assay

1. A small amount of blood is put in 1 positive and 1 negative control tube
2. Antigens specific for mycobacterium tuberculosis are put in the tube
3. If the cells have produced the cytokine interferon g, the person has been exposed to mycobacterium tuberculosis in the past or present

Therapy:

The treatment of TBC depends on whether it is active or latent. Multiple drugs are prescribed → a patient has to take at least 2 drugs at the same time:

• Active TBC → treatment has to be a combination of:

• Isoniazide
  • For 6-9 months
• Rifampicin
  • For 6-9 months
• Pyrazinamide
  • For 2 months
• Ethambutol
  • For 2-9 months

• Latent TBC → it is acceptable to treat with 1 or 2 drugs:
  • Isoniazide
  • Rifampicin
  • Isoniazide and rifampicin

It isn't necessary to remember the names of these drugs.

In case of multi-drug resistant TBC (MDR TB), patients are resistant to the 2 most used drugs against TBC. Some of these patients have to be isolated for many months, because they stay contagious for a very long time. Extensive drug resistant TBC (EDR TB) also exists. In this case, patients are resistant to almost every drug against TBC → these patients are very hard to treat.

Transmission

TBC can be transmitted from person to person. Droplet nuclei can stay in the air for hours, but the infectious dose is very low.

Prevention and control

Hospitals take several measures to prevent transmission:

• Coughing hygiene
• Aerogenic isolation
• Respiratory protection
  • For example an FFP2 mask → has very tiny pores that filter the mycobacterium tuberculosis

If someone has been diagnosed with TBC in the Netherlands, every person they have been in contact with, and again every person they have been in contact with, who have latent TBC, are treated. This way, TBC can be contained very well.

About 70% of TBC cases in the Netherlands is among first generation immigrants. The reason for this is thats in other countries TBC isn't contained as well.

Vaccination:

It is possible to be vaccinated against TBC. This vaccine is called Bacille Calmette Guerin (BCG), which is moderately effective against childhood TBC and not protective against adult pulmonary TBC.

Development of a new vaccine is slow. A number of people are working on the development of new vaccines.