TB - Cross Flashcards
What type of stain is best used to detect mycobacterium tuberculosis?
Acid fast stain
What property of M. tuberculosis allows it to stain like it does?
Mycolic acid
What is mycolic acid and where is it found?
fatty acid found in the cell wall
Virulent strains are associated with what (think virulence factor)? Where does the name come from?
Cord factor, due to virulent strains growing in a cord-like pattern
Avirulent strains do not have cord factor
Cord factor MOA?
inhibits macrophage maturation and induces TNF-alpha release
Besides cord factor, what is another virulence factor important to M.tuberculosis? MOA?
Sulfatides (surface glycolipids) inhibit phagolysosomal fusion
Cell wall of mycobacterium has what 4 components?
Mycolic acids, glycolipids, arabinogalactans, free lipids
Risk factors predisposing to TB. List as many
- prison (crowded conditions)
- immigrant from high burden country
- malnourished
- alcoholism
- poverty
- debilitating illness
- AIDS
- Elderly
- Certain disease: DM, Hodgkin lymphoma, CKD, malnutrition, immunosuppression; RA on TNF alpha antagonist
What is the critical mediator that allows macrophages to contain the infection?
IFN-gamma
Most important determinant of whether overt TB disease occurs?
Adequacy of cell mediated immunity
Pathogenesis. Initially, MTB enters what cells via what process?
Enters macrophages via phagocytosis
Pathogenesis. After MTB has entered macrophage via phagocytosis, what occurs?
It will inhibit the formation of the phagolysosome, allowing bacteria to replicate
Pathogenesis. After phagolysosome has been inhibited by TB, what cytokine is produced and what does it do?
After phagolysosome inhibited, IL-12 is produced, stimulating a T-helper response. IFN-gamma is then produced via Th1 cells, enabling macrophages to contain the infection (forming a granuloma)
Pathogenesis. Activated macrophages secrete what factors? What is there role?
Activated macrophages secrete TNF-alpha and cytokines that recruit more monocytes
Primary infection defined as?
Transmission from active case to susceptible host
Primary infections are asymptomatic or symptomatic?
asymptomatic, 95% of cases
Only evidence of primary infection is?
fibrocalcific nodule at site of infection
Secondary infection defined as?
When viable organisms remain dormant for years, reactivate to produce secondary infection (active disease)
Secondary infection usually involves what location of lungs? Why?
apices of lungs. MTB is an obligate aerobe and there is better O2 content at apex of lung
Cavitation occurs frequently in primary or secondary infection?
secondary
Erythema nodosum? Prognosis good or bad? Why? Is it specific for TB?
Indicative of good prognosis. Sign of good cell mediated immunity/ hypersensitivity response. Not specific for TB
What tests should be done to diagnose TB?
Which is the initial test?
List the time it takes for each one
Acid fast stain on sputum (initial test)
Lowenstein Jensen solid agar - 3-6 weeks
Culture in liquid media - 2 weeks
PCR or nucleic acid amplification - rapid
What test should NOT be done to diagnose TB
Culture on blood agar, it will not grow
PCR or nucleic acid amplification better for smear positive or smear negative specimens?
Smear positive (initially sputum will come back smear positive or negative)
What is the 1st line choice of antibiotics for TB?
RIPE Rifampin Isoniazid Pyrazinamide Ethambutol
Miliary/Disseminated TB requires RIPE treatment for how long?
9-12 months
Miliary TB pathophysiology. What occurs?
TV invasion into bronchus or lymphatics causes spread of TB throughout the lungs (and potentially elsewhere in the body). Lungs specifically look like millet seeds on CXR, hence the name
What subset of patients are at high risk for miliary TB?
HIV patients
What other organs are commonly infected in military TB?
Kidneys, Liver, bone marrow, spleen
What is the most common extra pulmonary site of miliary TB?
Kidneys
Miliary TB spreading to vertebrae = ?
Pott Disease
RA patients on antagonists of what cytokine are at increased risk for TB?
RA patients on TNF-alpha antagonists. If TNA-alpha not induced, granulomas won’t form and patient will have disseminated TB = death
Once susceptibility is confirmed, which therapy from RIPE can be discontinued
Ethambutol
Multidrug resistant TB is most commonly resistant to what drugs? What subset of patients are more likely to be MDR-TB patients?
Isoniazid and Rifampin, AIDS patients
TB and HIV. What is a important risk factor?
Low CD4 count, can’t produce Th1 cells, no IL-12.
TB and HIV. Sputum culture statistics?
Increased frequency of false negative sputum smears
TB and HIV. Granuloma frequency?
Absence of granulomas in tissues
TB and HIV. Compare cavitation/bronchial damage as compared to healthy non HIV patients.
HIV patients have reduced immune response, therefore decreased cavitation/bronchial damage and fewer acid fast bacilli in sputum
Purified protein derivative (PPD) test can be false positive for MTB if?
Patient has been exposed to other mycobacterium (such as mycobacterium avium)
What latent TB test is only specific to MTB?
IGRA - IFN gamma release assay
Which latent TB test is the gold standard?
IGRA - IFN gamma release assay
How can you get a false positive with the PPD test?
If patient has been immunized with BCG vaccine
If patient has BCG vaccine or a non tuberculosis mycobacterium infection, what will happen to the IGRA?
Nothing, there are no false positives with BCG or NTB infections
What is one case where the PPD and IGRA test can have a false negative? Why? What is this called?
HIV patients, can produce false negative due to lack of immune response, sometimes called anergy
Whats is the treatment for latent TB?
Isoniazid for 9 months; Isoniazid and Rifapentine for 3 months
If patient tests positive for Latent TB, what is your next step?
Make sure they do not have an active disease. Obtain a CXR and do a workup before you put them on medication for latent TB
Bacillus Calmette-Guerin (BCG) vaccine used against TB contains a strain from which mycobacterial species?
Mycobacterium bovis
BCG vaccine is limited in U.S to who?
young children in close contact with individuals with active TB and military personnel
BCG vaccine is contraindicated in what patients?
Immunocompromised patients
BCG vaccine is also used to treat what cancer?
Bladder cancer
Adverse effect of Rifampin
Orange-red secretions (tears,urine, saliva) will stain contact lenses
Toxicity associated with Rifampin
Hepatotoxicity
Isoniazid associated with 2 types of toxicity based on what characteristic?
Slow acetylators of INH - neuropathy
Fast acetylators of INH - hepatotoxicity
Pyrazinamide adverse effect?
hyperuricemia - leading to gout
Ethambutol toxicity?
Ocular toxicity
