Mycobacteria Flashcards
Myco TB transimssion
Respiratory droplets
What does TB look like?
Stains acid-fast - takes up carbylfuscin stain bc of high concentration of mycolic acid in cell wall. The waxy, fatty acids take up the dye and trap it (it doesn’t wash out)
Like leprae as well
Possible serpentine-like formation in TB
How do you culture TB?
It grows very slowly. 2-6 weeks for growth
Grow it on Lowenstein-Jensen medium
TB respiration
Obligate aerobe
Cord Factor
A virulence factor of Mycobacterium TB
Cell wall contains glycolipids that are involved in clumping of bacteria into a serpentine-like formation. The serpentine-like structure is Cord Factor. Without this, no virulence.
Cord Factor protects bacteria from being destroyed.
It elicits granuloma formation by increasing TNF-alpha and other inflammatory cytokines. This activates macrophages. Newly attracted macrophages wall off TB in the granuloma
Sulfatides
Virulence factor of Mycobacterium TB
Allows TB to survive inside macrophages. It prevents phagolysosome fusion leading to the sparing of TB from exposure to lysosomal hydrolysis.
Sulfatides accumulate in lysosomes and create incompetent secondary lysosomes that are unable to fuse.
What are the three different outcomes following a primary TB infection?
1) Healed latent infection
2) Systemic infection (Miliary TB)
3) Reactivation of TB
Primary infection by TB - general info
Lower of middle lobe of lungs
After it heals, the lesion becomes fibrotic and eventually calcifies (As do nearby lymph nodes). Together this forms the Ghon Complex.
Ghon Complex = Hilar lymphadenopathy + peripheral granulomatous lesion in middle or lower lung lobe (visible on CXR)
TB causes caseating granulomas
Granulomas are basically formed to wall off infection. Characterized by collection of activated macrophages called Langerhans Giant Cells.
In caseating granulomas, there’s a central area of caseating necrosis. Another name for granuloma surrounded by scar with central areas of necrosis = tubercle
Primary infection by TB - symptoms
Prolonged fever
Mostly in children in areas endemic to TB
Most cases of primary TB resolve, heal by calcification/fibrosis and become latent.
Primary TB infection induces a Positive PPD - tuberculin skin test (A wheal in the skin). Type 4 hypersensitivity.
(+) PPD in active infection, latent infection, or if Pt received BCG vaccine.
BCG Vaccine
Live attenuated vaccine for mycobacterium TB. It is not given to patients in the USA. It will induce a false (+) PPD test even if patient has never been exposed to TB
Miliary TB
Most cases of primary TB heal (fibrosis) and become latent. Some cases can progress systemically and cause bacteremia (Miliary TB)
TB can seed almost any organ in body in this case. It commonly infects bone, liver, lymphatics.
It can quickly progress to death
Presentation varies depending on infected organ.
“Fulminant, multi-organ failure in Pt (an immigrant) from endemic area” - keep TB on ddx
Reactivation of latent TB
Most people with latent TB do not reactive. Only seen in 5-10% of patients.
It is associated with a state of immunosuppression - HIV, old age, cancer.
Reactivation is caused by down regulation of TNF-alpha release. TNF-alpha is a pro-inflammatory cytokine that causes infection to be contained. Neutralizing this causes spread again.
If you want to start someone on a TNF-alpha inhibitor (like infliximab) you should first screen with PPD to make sure they’re not at risk for a reactivation
When TB reactivates, it normally affects the upper lobes.
3 classic reactivation symptoms are:
1) cough
2) night sweats
3) hemoptysis
Many patients experience cachexia (wasting) due to TNF-alpha produced in response to cord factor. TNF-alpha promotes wasting.
Remember: Reactivation is from within macrophages.
Reactivated TB can also affect skeleton and CNS
1) Pott’s Disease = When TB has infected spinal column
usually multiple vertebrae. Diminished bone w/ soft tissue swelling causing pain.
Can progress to abscess, spinal deformity, weakness (loss of support)
2) CNS involvement is seen in 10-15% of patients who reactivate. Manifests as meningitis or tuberculoma (cavitary lesion in brain)
TB Tx
TB is often resistant to multiple drugs and can become resistant to more drugs bc the treatment period is so long.
We use a 4 drug combo treatment: RIPE
R = Rifampin I = Isoniazid P = Pyrazinamide E = Ethambutol
Prophylaxis for patients who have latent TB:
Rifampin and Isoniazid - 9 month prophylaxis
What kind of environment does M. leprae prefer?
Thrives in cool temperature - explains why it loves extremities so much
What is the main reservoir for M. leprae?
In the USA it’s the armadillo
Another name for Leprosy
Hansen’s Disease
Tuberculoid Leprosy
One of the 2 distinct presentations of M. Leprae
Tuberculin response (like PPD)
Th1 response with cell-mediated immunity. The body can contain the bacteria within macrophages.
Main symptom in this leprosy is well-demarcated, hairless, hypoaesthetic skin plaque
Generally well-controlled
Lepromin skin test is positive - intradermal injection of bacterial antigens to test for presence of immune rxn
Lepromatous Leprosy
One of the 2 distinct presentations of M. Leprae
If body cannot fight off Tuberculoid leprosy, we get this one. This is classic leprosy.
Th2 mediated humoral response. These patients have an absent or weak Th1 response which prevents containment so bacteria are unable to be contained within the macrophages.
It has high chance of human-human spread (respiratory droplets?)
Symptoms:
Distal parts of extremities end to be cooler than core temp so extremities are preferred.
Symmetric glove and stocking neuropathy*
Numerous, poorly-demarcated raised lesions - can present all over body (mostly extensor surfaces). If you Bx these lesions you’d see large amounts of bacteria (If you Bx the lesion in tuberculoid leprosy you wouldn’t find much bacteria bc it’s well contained).
Causes profound facial deformity = leonine facies
- thickening of skin
- loss of eyebrows and eyelashes
- collapse of nose
- formation of nodular ear lobes
M. Leprae Tx
Multidrug therapy for long time (like TB)
Dapsone + Rifampin + Clofazimine for 2-5 years.
Deformities and neuropathies may not even be reversible
