*(X)MicroB Bacteria Mycobacterium (2)*Mycobacterium tuberculosis (MTB) Flashcards
Characterize (2) : Mycobacterium tuberculosis
(1) Acid fast
(2) Obligate aerobe
(Facultative intracellular vs. M. leprae which is OBLIGATE intracellular)
Are patients with LBTI symtomatic?
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Are patients with LBTI infectious?
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Are patients with LBTI symtomatic?
NO
Are patients with LBTI infectious?
ALSO NO
But its a different story if latent TB bacilli reactivate and cause active TB
DOT in TB treatment refers to […]
DOT in TB treatment refers to Directly observed treatment (DOT) - making sure ppl take their medicine (compliance)
impt in TB. esp MDR-TB bc you dont want it to spread. and you have to complete your regimen
How does the chest X ray (CXR) in pulmonary TB commonly presents as?
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How does the chest X ray (CXR) in pulmonary TB commonly presents as?
- Lobar
- Diffused
- Cavitation
- Nodules
- lymph node enlargement
Lobar pneumonia can also be strep pneumonia.
How does Tuberculin Skin Testing (TST) work? Which type of hypersensitivity? (IMPT!!)
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What does a positive TST result mean?
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What can a false positive TST result be due to?
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What can a false negative TST result be due to?
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What are the advantages of using IGRAs(Interferon-Gamma Release Assays) over TST?
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How does Tuberculin Skin Testing (TST) work? Which type of hypersensitivity? (IMPT!!)
Injecting Purified Protein Derivatives (PDD) from killed MTB and measuring the size of induration after 48-72 hours. Induration is caused by type 4 hypersensitivity
What does a positive TST result mean?
Exposure and Infection to MTB (now or sometime in the past)
- Active TB
- Latent TB
- Cured/exposure to environmental mycobacteria (NTM – non tuberculous mycobacteria)
What can a false positive TST result be due to?
- Test not specific
- BCG vaccine
What can a false negative TST result be due to?
- Anergy (steroid use, malnutrition, AIDS, etc)
What are the advantages of using IGRAs(Interferon-Gamma Release Assays) over TST?
measures interferon-gamma levels in whole blood in respose to SPECIFIC tb antigens
- Specific for MTB
- NO CROSS-REACTIVITY with BCG vacination
- NO CROSS-REACTIVITY with other mycobacterial contamination (NTM)
- Single visit to the clinic
- 24h turnaround
Tests for latent TB or past exposure to TB.
48 hours is the time taken for type 4 (delayed) hypersensitivity to occur (APC presentation to T cells + T cell release cytokines to attract macrophages + macrophage migrate to injection site)
Check out “clinical micobiology made ridiculously simple 6e” page 144 to have a full understanding.
HH: “The concept of the test is that the higher risk a person is for having tuberculosis infection, the smaller the size of the induration needs to be!”
LTBI reactivation:
- […]% of latent TB reactivates
- 80% of latent infection reactivate within the first […]
LTBI reactivation:
- 10% of latent TB reactivates
- 80% of latent infection reactivate within the first two years
MTB is one of the two major acid-fast organisms. What is the other one?
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MTB is one of the two major acid-fast organisms. What is the other one?
Nocardia
Mycobacteria are rods with waxy lipid-laden cell walls which prevents effective staining (resist decolouration) using Gram stain techniques (hence “acid-fast”)
This is ZN stain btw.
“Acid fastness is a physical property that gives a bacterium the ability to resist decolorization by acids during staining procedures. This means that once the bacterium is stained, it cannot be decolorized using acids routinely used in the process.”
THIS IS THE REASON WHY acid fast bacterias retain the color of the stain after an acid wash
MTB mode of spread:
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MTB mode of spread:
Respiratory droplets (depends on infectivity of carrier and duration of contact)
Sputum AFB smear positive – […] infectious TB
Sputum AFB smear negative, culture positive – […] infectious TB
Sputum AFB smear positive – highly infectious TB
Sputum AFB smear negative, culture positive – less infectious TB
Staining for MTB:
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Staining for MTB:
Need acid-fast stain (Ziehl Neelsen stain)
Can’t do normal gram stain effectively.
The most common site of TB reactivation in the lungs is the […]
The most common site of TB reactivation in the lungs is the upper lobes (apices)
Due to high ventilation but poor perfusion in the apical regions of the lung, leading to higher oxgen tension.
MTB is an aerobic bacterium, hence the high PaO2 in upper lobes is more ideal for reactivation
The pathologic features of TB are the result of the degree of hypersensitivity and the local concentration of antigen
- Small antigen load + high tissue hypersensitivity
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The pathologic features of TB are the result of the degree of hypersensitivity and the local concentration of antigen
- Small antigen load + high tissue hypersensitivity
- well formed granuloma containining MTB.
- healing with fibrosis. encapsulation and scar formation
- usually this case for immunocompetent ppl - High antigen load + low tissue hypersensitivity
- Caseating (cheesy) granuloma due to poor organization of immune cells & incomplete necrosis
- Tend to liquify and produce tuberculous cavity with high number of MTB, bronchogenic spread
- usually immunocompromised ppl
Vaccine for TB known as
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What are da limitations of this vaccine?
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Vaccine for TB known as
BCG (Bacille Calmette-Guerin)
What are da limitations of this vaccine?
- live attenuated (cannot give to HIV/immunocompromised)
- Does NOT prevent infection, but prevents progression to clinical disease
- prevents serious TB (like miliary or meningitis), but not pulmonary
- does not prevent latent from reactivating
- low efficacy in preventing adult TB in high endemicity area
What are the 3 types of active (symtomatic + clinical signs) TB disease?
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What are the 3 types of active (symtomatic + clinical signs) TB disease?
- Active primary TB
- Post primary TB (reactivation of LTBI/reinfection)
- Miliary TB (disseminated haematogenous TB w multiorgan involvement)
What are the common possibilities of progression following primary MTB infection?
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What are the common possibilities of progression following primary MTB infection?
- LTBI
- Seeding to apical-posterior areas of the lung (pulmonary TB/reactivation of TB)
- Miliary TB (lymphohaemotogeneous dissemination of TB to MANY organ) (seen in very young, very old, HIV and immunocompromised)
What are the important biochemical tests that suggest active TB?
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What are the important biochemical tests that suggest active TB?
- ADA (adenosine deaminase) in pleural fluid (T cell activation)
- Renal TB –> Sterile pyuria (increase wbc in urine)
- TB meningitis– > White cell, protein, glucose in CSF
Sterile pyuria in TB = red and white blood cells in urine, but no bacteria seen by gram stain or grow in culture (MTB takes weeks to grow and are acid fast).
What are the most likely clinical manifestation of TB?
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What are the most likely clinical manifestation of TB?
- Pulmonary TB (85% in sg)
- Pleuritis (pleural cavity)
- Lymphadenitis (cervical LN, Peyer’s patches)
What are the risk factors that contributes to developing active TB from LTBI?
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What are the risk factors that contributes to developing active TB from LTBI?
- Recent infection due to close contact with active TB patient
- Infancy, 15-25 y/o (no idea why), old age
- Immunosuppresion (HIV/AIDS, bone marrow transplant, immunosuppressants, poorly controlled DM)
What are the symptoms and signs of active TB?
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What are the symptoms and signs of active TB?
Alarm-bell symptomps, but non specific :(
Reason why it is a differential for infection of any organ system
What are the tests for active TB? (IMPT!)
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What are the tests for active TB? (IMPT!)
Early morning sputum (AT LEAST 2)
- Sputum culture (Loweinstein-Jensen medium/MGIT)
- Sputum smear (ZN stain)
- PCR
Culture is the gold standard but its slow (1-8 weeks) and expensive
MGIT = Mycobacteria Growth Indicator Tube
What are the two accepted albeit imperfect tests for latent TB Infection (LTBI)?
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Why are they imperfect?
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What are the two accepted albeit imperfect tests for latent TB Infection (LTBI)?
- **TST (Tuberculin Skin Test/Mantoux Test) **
- IGRA (Interferon Gamma Release Assay)
Why are they imperfect?
- both depends on cell mediated immunity (memory T-cell response)
- Neither can accurately distinguish LTBI and active TB
For suspected pulmonary TB:
What is Ghon focus and Ghon complex?
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What is Ghon focus and Ghon complex?
Ghon focus = a calcified tubercle in the middle or lower lung zone
Ghon/Ranke complex = a Ghon focus + perihilar lymph node calcified granulomas
What is MDR-TB? What is it resistant to?
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What is XDR-TB? What is it resistant to?
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How does drug resistance arise???
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What is MDR-TB? What is it resistant to?
Multi-Drug Resistant TB
- Resistance to Rifampicin and Isoniazid (RIPE)
What is XDR-TB? What is it resistant to?
Extensively-Drug Resistant TB
- Resistance to Rifampicin and Isoniazid (RIPE) + a fluoroquinolone (2nd line) + a 2nd line injectable drug (capreomycin/kanamycin/amikacin)
How does drug resistance arise???
- Primary (person to person)
- Secondary (poor compliance with anti-TB medications, hence need for DOT)
“Resistance is a man-made amplification of a natural phenomenon”
Resistance arises spontaneously: we select for it with drugs.
Got some other drug resistance types here~
Note: INH = another name for Isoniazid, RIF = another name for rifampicin
What is the FASTEST way to detect TB and its drug resistance? how long it takes?
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What is the FASTEST way to detect TB and its drug resistance? how long it takes?
PCR yo!!! 1 day only ezpz
This is impt because MDR-TB evades RIPE. So your infected guy doesn’t go around infecting other ppl for 2 months while RIPE has no effect on him.
What the heck is Mycobacterium tuberculosis complex (MTB complex)???
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What the heck is Mycobacterium tuberculosis complex (MTB complex)???
a genetically related group of Mycobacterium species that can cause tuberculosis in humans or other living things
Don’t need to identify the sub-species in the clinics.
When will a patient with TB clinically declared non-infectious?
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When will a patient with TB clinically declared non-infectious?
- Generally after 2 weeks of effective treatment in drug-sensitive TB
- Other supporting signs – 3 consecutive AFB smear negative specimens, clinically improved
- More stringent criteria for MDR TB
Why is Drug Susceptibility Testing so important in the diagnosis of TB?
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Why is Drug Susceptibility Testing so important in the diagnosis of TB?
- Early choice of appropriate treatment
- Rapid determination of drug resistance
- Adequate management of patients (isolation, etc)
Determination of rifampicin resistance is critical! Resistance to rifampicin invalidates the 6 months RIPE course
