INF1 - E. TUBERCULOSIS-COVERED Flashcards
1
Q
what causes TB
A
- 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
2
Q
where do you get mycobacterium bovis from
A
- raw, unpasteurised milk and dairy products from infected cows
- similar infection to TB
3
Q
what does TB look like and made of
A
- 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
4
Q
how to identify mycobacterium tuberculosis
A
- Ziehl-Neelsen stain (acid-fast stain)
- growth on selective culture media/biochemical tests
- PCR
5
Q
pathogenicity and virulence of mycobacteria tuberculosis relating to the cell wall
A
- 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
6
Q
pathogenicity and virulence of mycobacteria tuberculosis relating to cell entry
A
- 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)
7
Q
what social factors contribute to TB
A
- immigration from high endemic prevalence areas
- poverty
- alcoholism
- close contact with large groups
- IV drug use
8
Q
what age groups are at risk of TB
A
- very young
- elderly (reactivation of existing, dormant infection)
9
Q
what immunocompromised subjects are at risk of TB
A
- HIV
- gamma interferon (chronic granulomatous disease)
- severe combined immune deficiency
- immunosuppression ie - transplant patients
10
Q
what is primary TB
A
- 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
11
Q
what is post-primary TB
A
- 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
12
Q
what is military/spreading TB (extra-pulmonary)
A
- 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
13
Q
what are the differences between TB infection and TB disease in lungs
A
- 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
14
Q
what samples to take for identification
A
- sputum if productive
- bronchoscopy alveolar lavage (BAL)
- pleural biopsy/fluid
15
Q
what tests to take for diagnosis
A
- 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
16
Q
what is the drug regime for sensitive TB
A
4 drugs for 2 months then
2 months for 4 months
17
Q
what is the drug regime for resistant TB
A
5-6 drugs for up to 2 years
18
Q
why is combination therapy used
A
to target different parts of the organism
19
Q
what are first line drugs for TB and what do they target
A
- 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)
20
Q
what are second line drugs for TB
A
- cycloserine
- ciprofloxacin
- clarithromycin
- amikacin
- streptomycin
21
Q
problems with TB treatment
A
- liver toxicity due to high doses for long time
- multiple therapy
- prolonged treatment
- drug interactions (anti-HIV drugs)
- compliance (may need DOTS)
22
Q
why is TB re-emerging
A
- HIV/AIDS
- travel to and from countries where TB is endemic
23
Q
what vaccine is available for TB
A
- Bacille Calmette-Guerin vaccine (BCG)
live attenuated mycobacteria (M.bovis) - not lifelong protection
