INF1 - E. TUBERCULOSIS-COVERED

Question 1

what causes TB

Answer 1

• mycobacterium tuberculosis
  (tuberculosis - refers to type of lesion, tubercle formed in response to infection with mycobacteria)
• affects lymph nodes and lungs but can affect other parts of body
• HIV/AIDS/immunocompromised at risk of being infected the most

Question 2

where do you get mycobacterium bovis from

Answer 2

• raw, unpasteurised milk and dairy products from infected cows
• similar infection to TB

Question 3

what does TB look like and made of

Answer 3

• rod shaped
• mycolic acid in cell wall
• small amount of peptidoglycan
• lipids, glycolipids and sugars - arabinogalactan, lipoarabinomannan, PIM (pathogenicity factors)
• slow-growing due to mycolic acid
• mycolic acid affects:
  acquisition of nutrients
  uptake of antibiotics/disinfectants
• obligate aerobe: needs oxygen rich part of body ie - upper lung
• survives inside macrophages so acts as an obligate parasite

Question 4

how to identify mycobacterium tuberculosis

Answer 4

• Ziehl-Neelsen stain (acid-fast stain)
• growth on selective culture media/biochemical tests
• PCR

Question 5

pathogenicity and virulence of mycobacteria tuberculosis relating to the cell wall

Answer 5

• mycolic acid: immune evasion
  impermeable/resistance to antimicrobials/biocides
• cord factor (trehalose 6,6’ dimycolate)
  glycolipid which causes TB to grow in serpentine cords, linked with virulent strains
  toxic to mammalian cells, inhibitor of neutrophil migration
• antigen 85 complex
  bind host tissues via molecules, ie - fibronectin
  involved in tubercle formation

DOESN’T PRODUCE MANY TOXINS

Question 6

pathogenicity and virulence of mycobacteria tuberculosis relating to cell entry

Answer 6

• binds to mannose receptors on macrophages and live inside macrophage - immune privileged site (can replicate in tissue)
  factors inhibit phagolysosome function and hence it survives
  damage of innate immune responses
• cytokines can be released eg - tumour necrosis factor alpha
• excessive production of TNF-alpha - symptoms of wasting (loss of muscle mass)

Question 7

what social factors contribute to TB

Answer 7

• immigration from high endemic prevalence areas
• poverty
• alcoholism
• close contact with large groups
• IV drug use

Question 8

what age groups are at risk of TB

Answer 8

• very young
• elderly (reactivation of existing, dormant infection)

Question 9

what immunocompromised subjects are at risk of TB

Answer 9

• HIV
• gamma interferon (chronic granulomatous disease)
• severe combined immune deficiency
• immunosuppression ie - transplant patients

Question 10

what is primary TB

Answer 10

• inhaled micro-droplets containing mycobacteria tuberculosis
• taken up by alveolar macrophages , not activated initially, bacteria can replicate
• t-cells induce a cell-mediated response to infection (inhibits phagolysosomes)
• small foci of inflam (walls of bacteria) induced by bacteria with spontaneous healing - form a granuloma
• ghon focus: mycobacteria can’t proliferate in this lesion but may persist and reactivate later in life
• often clinically silent (not active), not regarded as infectious or a case of TB
• active with symptoms is regarded as infectious/contagious and is a case of TB
• most cases, cell-mediated, T-cell responses and uninfected macrophages wall off and destroy infected macrophages - form caseous granulomas which leave fibrotic, calcified scares (Ghon focus/complex)
• lesions may contain few direct organisms which can lead to reactivation of the disease if not treated
• some cases can lead to infectious disease (more so if immunocompromised
• symptoms: persistent fever, night sweats, weight loss due to inflam response, persistent dry cough/wheezy cough, fluid of lungs, shortness of breath, chest pains, fatigue
• can affect lymph nodes near lung/airways causing obstruction - cough (lung can’t repair)
• pulmonary TB = lungs
• extra-pulmonary TB = lymph nodes, skin, CNS, bones, joints

Question 11

what is post-primary TB

Answer 11

• reactivation due to a weakened cell-mediated immune system
• rupture of granulomata (tubercles) release mycobacteria that establish more lesions
• no spontaneous healing of granulomata, causing cavities and extensive damage to lung tissue, airways, blood vessel (irreversible)
• fever, night sweats, weight loss (due to cytokine TNF-alpha)
• cough may produce purulent sputum, maybe with blood
• pulmonary TB - infectious TB

Question 12

what is military/spreading TB (extra-pulmonary)

Answer 12

• disseminated TB with spread of bacteria from ruptured tubercles/granuloma to blood (in the macrophages) and reaching many tissues
• Tuberculous meningitis
  children with primary TB
  adults with extensive TB in other parts of body
  AID patients
  immunosuppressed
• Renal TB
  may present as a UTI
  can form abscess in kidney - damage
• TB of joints and bones
  affects cartilage with caseation lesions, spread to adjacent bones causing damage
  spine - deformity - Pott’s disease

Question 13

what are the differences between TB infection and TB disease in lungs

Answer 13

• chest x-ray shows lesion in disease
• sputum smears and cultures positive in disease
• symptoms like cough, fever, weight loss in disease
• infectious before treatment in disease
• defined as a case of TB in disease

Question 14

what samples to take for identification

Answer 14

• sputum if productive
• bronchoscopy alveolar lavage (BAL)
• pleural biopsy/fluid

Question 15

what tests to take for diagnosis

Answer 15

• Mantoux test
• X-ray (granuloma/tubercle lesions)
• microscopy of sputum, BAL, bronchial brushings
  (Ziehl-neelsen stain, PCR)
• Culture
• Take prophylaxis if positive after Mantoux test

Question 16

what is the drug regime for sensitive TB

Answer 16

4 drugs for 2 months then
2 months for 4 months

Question 17

what is the drug regime for resistant TB

Answer 17

5-6 drugs for up to 2 years

Question 18

why is combination therapy used

Answer 18

to target different parts of the organism

Question 19

what are first line drugs for TB and what do they target

Answer 19

• rifampicin: inhibits RNA synthesis in ribosome
• isoniazid: inhibits cell wall synthesis (blocks mycolic acid)
• pyrazinamide: disrupts plasma membrane and energy metabolism
• ethambutol: inhibits cell wall synthesis (blocks arabinogalactan)

Question 20

what are second line drugs for TB

Answer 20

• cycloserine
• ciprofloxacin
• clarithromycin
• amikacin
• streptomycin

Question 21

problems with TB treatment

Answer 21

• liver toxicity due to high doses for long time
• multiple therapy
• prolonged treatment
• drug interactions (anti-HIV drugs)
• compliance (may need DOTS)

Question 22

why is TB re-emerging

Answer 22

• HIV/AIDS
• travel to and from countries where TB is endemic

Question 23

what vaccine is available for TB

Answer 23

• Bacille Calmette-Guerin vaccine (BCG)
  live attenuated mycobacteria (M.bovis) - not lifelong protection