Tuberculosis, Leprosy Flashcards
What stain is commonly used to identify M. tuberculosis? Why?
Acid-Fast stain; Mycolic acid content of cell walls
What is the natural host and reservoir of Mycobacterium Tuberculosis?
Humans
What type of oxygen processing capibilities do M. tuberculosis have?
They are obligate aerobes;
What is the significance of the pathogenicity of M. tuberculosis in guinea pigs?
This pathogenicity helps to differentiate between a Mycobacterium tuberculosis infection and atypical mycobacterium infection
What are some important structural components of M. tuberculosis?
- Mycolic acids - acid-fastness
- Phosphatides - Caseation necrosis
- Cord factor (trehalose dimycolate) - virulence, microscopic serpentine appearance
- Phtiocerol dimycocerosate: lung pathogenesis
M. tuberculosis transmission?
Inhalation of infected aerosols
Describe the pathogenesis of TB dissemination
- TB enters lung via inhaled particles
- Bugs spread to hilar lymph nodes (Ghon Complex)
- Bugs are coughed up in sputum (can pass infection) and are swallowed causing GI infection
- Bugs disseminate through blood stream causing Meningitis and Miliary TB (small foci) throughout the body (skeletal, genitourinary)
- Body attempts to wall of infection forming granulomas
Describe the TB pathogenesis in immunocompetent hosts
- Immunocompetent - Cell mediated immunity - Macrophages engulf bacteria. Some macros are activated by CD4 Th1 cells and can kill the bacteria; CD8 suppressor T cells lyse other infected macros forming caseating granulomas (“tubercules”)
What is the role in TNF in TB pathogenesis?
TNF plays an important role in maintaining latency. Patients receiving TNF-Alpha antagonists may reactivate
What is the Ghon complex?
A lesion involving the lung parenchyma and a hilar node
What is the difference betwixt proliferative and exudative TB lesions?
Proliferative - bacillary load is small and host cellular-immune responses dominate
Exudate lesions - large numbers of bacilli are present and host defenses are weak.
What is scrofula? What is it caused by? Tests? Tx?
(Generally) unilateral, painless, cervical adenitis caused by TB or M. scrofulaceum; PPD and fine-needle aspiration; Surgery considered after AB Tx started
What are risk factors for TB infection?
- Crowded environments
- HIV
- Immunosuppression - Uncontrolled HIV, Steroids, IFNgamma deficiency, TNF-Alpha Antagonists, Age <5 yo
Classic TB presentation?
Cough, Night Sweats, Weight Loss, Fever, Chest pain, Hemoptysis
This patient has TB. Describe the lung findings
CXR showing cavity formation associated with advanced infection and high bacterial load
What is the most effective procedure for obtaining cutures for suspected TB infection?
Fiberoptic bronchoscopy (Bronchoalveolar Lavage)
What is the general rate of renal TB in a patient with primary TB infection? What tests are performed to determine genitourinary TB? What findings on urinalysis are suggestive of systemic/urogenital TB?
Most common site for extrapulmonary infection and almost always reaches the kidneys; Intravenous urography (best option), Sterile pyuria
What is the most sensitive test for detecting the extent of leptomeningeal TB disease?
MRI with gadolinium enhancement
The following patient has systemic TB infection. What does the MRI show? Describe it.
Pott’s Disease; Spinal infection demonstrating destruction of vertebral body with epidural compression.
A lung is shown at autopsy. What is the Dx? Describe the pathogenesis.
Miliary TB
- Hematogenous spread of TB resulting in many tiny noncalcified foci of infection
- “Millet seeds” on CXR
- Generally associated with primary infection
Describe the special considerations in the Dx and Tx of pediatric TB
- TB in child indicates recent transmission: Track it!
- Infection in unusual sites: Middle Ear, Skin, Ocular Structures
- Tests: Gastric aspirates used due to pediatric inability to forcefully expel sputum
- Tx: Begin Tx ASAP if TB is suspected
Describe the TB PPD test and the findings for an IC’ed patient, patient with risk factors, and an immunocompentent patient. What is the major thought process when reading a PPD?
- Tuberculin units injected into dermis
- Reading PPD is a judgement call, consider the RFs, not the size
What are important lab tests for Dx TB?
- Sputum - very SPECIFIC but not very sensitive (acid fast stain)
- Urinalysis and urine culture - for those with GU complaints
- Cultures needed for AB resistance testing
- Molecular tests (rRNA probe and PCR)
What is problematic with culturing and testing AB resistance of suspected TB?
Takes 3-4 wks to culture and therefore determining AB resistance can take forever
Describe the process of treating a patient with TB
- Isolation - in a negative pressure room; All contacts should wear high-efficiency masks for the first two weeks
- Tx: 4-drug regimen - Isoniazid, rifampin, pyrazinamide, ethambutol/streptomycin (used once TB is know to be fully susceptible)
How long is the Tx for pulmonary TB? TB in ICed? Those with CNS involvement?
- 3-6 months
- 9-12 months
- 9-12 months
What are MDR and XDR TB?
Multidrug resistant and Extremely Drug resistant TB
What do we do with noncompliant patients who have TB?
Directly Observed Tx
What preventative measures do we have to stop TB?
- Strong CMI makes TB latent - no longer contagious
- BCG vaccine - live attenuated M. bovis - not all that effective
Describe the acid-fast stain process
- Carbolfuchsin stain
- Acid/alcohol decolorization
- Methylene blue counterstain
- Acid-fast positive bbugs hold carbolfuchsin during decolorization
How long should a patient with TB be isolated?
At least two weeks
What is Quantiferon?
INF-gamma release assay Dx tool for determining if a person houses TB and is not affected by the BCG vaccination
What is atypical mycobacteria? What disease do they cause? What are typical PPD/TST findings? What is the lethality in guinea pigs?
Environmentally acquired bugs that do not cause TB or leprosy, usually have a negative PPD and TST, and are less aggressive. NOT lethal in guinea pigs
What are the typical presentations in humans of atypical mycobacteria?
- Immunocomps - generally cutaneous infection in adults and scrofula in children
- IC’ed - Systemic disease
What are the group 1 atypical mycobacteria?
Photochromogens - form pigment in light
- M. kansaii - most lethal, environmental, lung disease
- M. marinum - most common, found in fresh and salat water, forms ulcerating granulomas on skin
What are the group 2 atypical mycobacteria? What is it a typical cause of? Tx?
M. scrofulaceum
- Produces pigment when grown in light OR dark
Most common cause of scrofula in children
Fix by surgical removal of affected nodes
What are the group 3 atypical mycobacteria? What disease do they normally cause? Issue with Tx?
M. avium and M. intracellulare (NO pigment); Cause pulmonary disease indistinguishable from TB in severely immunocompromised patients; Severely drug resistant
What are the group 4 atypical mycobacteria and their typical presentation?
Rapidly growing mycobacteria
- M. fortuitum and M. chelonei - Cause problems in IC
- M. abscessus - Chronic lung infections
- M. smegmatis - normal flora under foreskin
- What are the major issues with M. leprae culturing?
- What are the reservoirs?
- Preferable growth environment?
- Can’t be cultured and doubling time is 14 days
- Humans (major), armadillos (minor)
- 30C for growth (periphery of humans)
What is another name for Leprosy?
Hansen disease
- What is the mechanism of transmission?
- What is the most common sequel of exposure?
- Mechanism unknown
- 90% result in asymptomatic seroconversion
What are the two presentations of Leprosy? Describe each
- Tuberculoid - Strong CMI (CD4 and Th1) response that contains the bug
- Lepromatous - Poor CMI response w/ useless Th2 response and nonprotective antibodies
What are the typical responses of the Lepromatin test on a person with tuberculoid leprosy? Lepromatous?
In Tuberculoid, the test has a positive result because the body was able to mount a response. In Lepromatous, there is no cellular response and therefore a negative Lepromatin test.
What is nerve damage generally caused by in M. leprae infections?
The bacteria and the cell-mediated response
What are typical findings on exam of a patient with leprosy?
- Tuberculoid - Hypoesthesia, skin lesions, peripheral neuropathy, hypopigmented macules, Positive Lepromatin
- Lepromatous - Extensive bilateral symmetric cutaneous nodules, eye infection, loss of nasal cartilage, “leonine facies”, Negative Lepromatin Test
What is the main use of the Lepromatin test?
Determine patient’s ability to raise immune response; It is NOT diagnostic of exposure
What labs tests are used for suspected Leprosy?
- Skin smear/biopsy - lipid-laden macros (“foam cells”)
- Acid-fast stain
What are the Tx for Tuberculoid and Lepromatous leprosy? For pediatric patients with suspected exposure
- Tuberculoid: Dapson + Rifampin 2 yrs
- Lepromatous: Dapsone, Rifampin and Clofazimine >2 yrs until bugs are gone
- Peds: Dapsone
In a pregnant patient with erythema nodosum leprosum, what medicine should be avoided? Why?
Thalidomide because it is a major teratogen
