Tuberculosis Flashcards
First part of the immune system to interact with TB bacilli
Alveolar macrophages
Ghon focus
Giant cell granuloma
Ghon complex
Regional lymph nodes filled with granulomas, visible on X-ray, MRI, CT
Miliary tuberculosis
Tiny foci of granuloma, often appears in lungs, form of disseminated primary infection
This form of TB tends to be lifelong
Characteristic of the disease are tubercles found in many organs, including the liver, spleen, kidneys, brain, and meninges. aseation and cavitation are less frequent than in secondary TB.
Characteristic staining used to detect Mycobacterium tuberculosis
Acid-fast
Constitutional symptoms of tuberculosis
fever, weight loss, and drenching night sweats.
Mycobacterium leprae
- slow-growing, acid-fast bacillus that is the causative agent of leprosy
- illness that ranges between two polar forms: tuberculoid (strong immune response with few organisms) and lepromatous (minimal immune response with immense numbers of organisms)
“atypical mycobacteria”
Mycobacteria other than M. tuberculosis
Unusual properties of mycobacteria
acid fast, are unusually resistant to drying, and grow slowly compared with most other bacteria.
mycolic acid
The most abundant wax within the M. tuberculosis membrane, which confers the property of acid-fastness to the bacteria
How acid-fast staining works
Stain w/ fuchsin
Treat with 3% HCl in EtOH
Wrinse
Only mycobacteria should retain the stain, appearing as slender red rods
Best ways to kill mycobacteria
- Mycobacterial antiboitics
- Heat (Pasteurization of products kills any hiding mycobacteria!)
Pasteurization
60oC, 30 minutes
The generation time of M. tuberculosis is ___ compared with ___ for most bacterial pathogens
The generation time of M. tuberculosis is 15 to 20 hours compared with less than 1 hour for most bacterial pathogens
Nearly all persons coinfected with ___ and M. tuberculosis will eventually develop active tuberculosis
Nearly all persons coinfected with HIV and M. tuberculosis will eventually develop active tuberculosis
Mycobacterium avium complex
- organism is often found in water and soil and is generally harmless to immunocompetent individuals
- May infect individuals with advanced HIV or AIDS
- Colonizes GI tract, then disseminates
- Fever, malaise, wasting
- Diarrhea, abdominal pain, spleen and liver symptoms, retroperitoneal lymphadenopathy
Air in a room occupied by a person with pulmonary TB may remain infectious even . . .
air in a room occupied by a person with pulmonary TB may remain infectious even after the person has left the room
TB infection rarely occurs outdoors because ___
TB infection rarely occurs outdoors because ultraviolet light kills M. tuberculosis
M. tuberculosis utilizes ___ as a means of transport to other body sites.
M. tuberculosis utilizes macrophages moving through the lymphatics as a means of transport to other body sites.
The most important consequence of lymphohematogenous dissemination of TB is . . .
The most important consequence of lymphohematogenous dissemination of TB is seeding of the lung apices
Reactivation of TB
- Occurs during periods of immunosuppression
- Lesions of latent TB become necrotic, undergo caseous necrosis, and eventually merge into larger lesions
- With time, the caseous lesions liquefy and discharge their contents into bronchi, creating a well-aerated cavity into which organism may proliferate and seeding new alveoli
- Caseous lesions also serve as sources of droplet nuclei to infect others
Caseous necrosis is ___.
Caseous necrosis is unstable
The material it produces tends to liquefy and discharge, especially within the bronchioles of the lung, producing a cavity and providing conditions in which bacteria multiply to very high numbers.
The uneasy equilibrium in the war between tuberculosis and macrophages
- Some macrophages successfully kill TB
- Some TB successfully kill macrophages
- Some macrophages capture the TB and wall it off, harboring dormant bacteria for years
Caseation and cavitation are phenotypes characteristic of. . .
. . . secondary TB. Usually not primary, primary progressive, or miliary.
In tubercular meningitis, . . .
. . . there are actually very few organisms in the CSF, but they are able to cause potent inflammation
tuberculin conversion
A newly positive TB PPD test after a history of negative tests
About __% of individuals with active TB have negative tuberculin tests.
About 15% of individuals with active TB have negative tuberculin tests.
Many of these individuals are immunocompromised, hence the lack of conversion.
A false-positive tuberculin test may be caused by . . .
. . . exposure to an atypical mycobacterium
An even better test for TB than the PPD
IFNg release assay
Pott disease
- When M. tuberculosis affects vertebral bodies.
- patients present with chronic back pain
- Failure to diagnose and treat Pott disease can result in destruction of vertebrae and permanent disability
Initial diagnostic approach for TB
- Careful history
- Sputum culture
- Chest X-ray
The gold standard for TB diagnosis
Culture
Radiometric culture techniques
Accelerate the diagnosis by early detection of radioactive CO2 released by organisms metabolizing 14C-labeled palmitic acid, providing results within 7 to 14 days. as opposed to the usual ~6 weeks
Mycobacteria which may mimic TB but result in much less severe infections
- Mycobacterium avium complex
- Mycobacterium kansasii
Persons with pulmonary TB usually become noncontagious within ___ of therapy if the organisms are sensitive to the drugs administered
ersons with pulmonary TB usually become noncontagious within 2 weeks of therapy if the organisms are sensitive to the drugs administered
Drugging TB
- Requires multiple drugs to prevent development of resistance for active TB
- isoniazid (INH), rifampin, pyrazinamide (PZA), and ethambutol
- chemoprophylactic on-site treatment of seroconverters detected via PPD with single dose of isoniazid
Why are vaccines against TB no good?
TB requires a cell-mediated immune response, antibodies just bounce right off its waxy coat!
Studies of M. leprae are difficult because . . .
. . . the organism cannot be continuously grown in vitro
phenolic glycolipid
- A surface lipid of M. leprae, may provide a defense against oxidative killing
- To kill M. leprae, macrophages must be efficiently activated by CD4 T cells
Leprosy bacilli grow best at . . .
Leprosy bacilli grow best at low temperatures
Tuberculoid leprosy
- characterized by red blotchy lesions with localized anesthesia on face, trunk, extremities
- organisms grow and cause thickening in nerve sheaths. These thickened nerves can be felt through the skin, a characteristic of leprosy
- patients usually demonstrate delayed-type hypersensitivity to lepromin
*
Lepromatous Leprosy
- can reduce or suppress specific T cells produced by the host that activate infected macrophages
- In lepromatous leprosy, there is little or no delayed-type hypersensitivity to lepromin
- Both skin and nerves may be involved
- With time, the loss of local sensation leads to inadvertent, traumatic lesions of the face and extremities. These may become secondarily infected, resulting in additional disfigurement.
___ are at extremely high risk for primary progression of infection after an initial TB exposure and for disseminated disease.
Children under the age of four are at extremely high risk for primary progression of infection after an initial TB exposure and for disseminated disease.
Their presentations may be more subtle than in adults and classic symptoms may not be present. All household contacts should be investigated for TB, even without symptoms.
To treat TB, the classic course is. . .
4 drugs for 2 months,
followed by 2 drugs for 4 months
When giving someone with reactivated TB an immunosuppressive treatment for a chronic autoimmune condition (like Lupus or sarcoidosis), . . .
. . . it is fine to have them on an anti-TNF, as long as they are on antimycobacterials.
Sensitivity of different TB tests
Smear and stain: 5,000-10,000 cfu/mL
Gene Xpert (PCR technique): 150 cfu/mL
Culture: 10 cfu/mL
Generally speaking, someone with a positive TB smear is probably ___ while someone with a negative TB smear is probably not.
Generally speaking, someone with a positive TB smear is probably contagious while someone with a negative TB smear is probably not.
IFNg RA and PPD are for ___ TB.
IFNg RA and PPD are for latent TB.
Their results for active TB are uninterpretable.
If you are unsure whether to treat someone that is at high risk for having developed TB but does not display symptoms and has negative tests . . .
. . . just start them on isoniazid and repeat testing in a week or two.
The four drugs given for TB
RIPE
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
Children and TB
Children <4 are at risk high for developing TB
Generally speaking for HIV patients, if ____, PPD and IFNg release assay are reliable. If ____, they should not be trusted.
Generally speaking for HIV patients, if CD4>200, PPD and IFNg release assay are reliable. If CD4<200, they should not be trusted.
