Lecture 1: Mycobacterium Flashcards
Which chronic lung disease puts people at a particularly high risk for tuberculosis?
Silicosis
Which critical mediator released from TH1 cells both in LN’s and the lung enables macrophages to contain M. tuberculosis infection?
IFN-γ
Which immune cells orchestrate the formation of granulomas and caseous necrosis seen in M. tuberculosis infection?
TH1
Macrophages activated by IFN-γ in M. tuberculosis infection differentiate into what?
“Epithelioid histiocytes” that aggregate to form granulomas; some may aggregate to form giant cells
Pt’s with RA treated with what type of drugs are at an increased risk for tuberculosis reactivation?
TNF antagonist
Which pattern of tuberculosis arises in a nonimmune host vs. previously sensitized host?
- Non-immune = primary TB
- Previously sensitized = secondary TB
Secondary pulmonary tuberculosis classically involves which area of the lungs?
APEX of one or both lungs
What are the systemic and pulmonary signs/sx’s associated with secondary tuberculosis?
- Remittent/low-grade FEVER + WEIGHT LOSS + Night sweats
- Fever appears late each afternoon and then subsides
- Sputum that at first is mucoid and later purulent; variable degree of hemoptysis
Which laboratory diagnostic test allows for more rapid diagnosis of M. tuberculosis?
PCR amplification of M. tuberculosis DNA
What remains the gold standard for confirming diagnosis of M. tuberculosis?
Culture
Primary tuberculosis almost always begins in which organ and what is seen morphologically as sensitization develops?
- Lungs –> bacilli implant in the distal airspaces of lower part of upper lobe or upper part of lower lobe
- Gray-white inflammation w/ consolidation, know as Ghon focus –> center of focus undergoes caseous necrosis
Ghon complex seen in primary TB is a combination of what?
Parenchymal lung lesion (Ghon focus)+LN involvement
Cell-mediated immunity typically controls the primary TB infection leading to what morphological change in the Ghon complex, which is often followed by what radiologically detectable change?
Ghon complex undergoes progressive fibrosis, followed by radiologically detectable calcification (Ranke complex)
Which subset of pt’s do NOT form the characteristic granulomas associated with primary TB and instead have macrophages loaded with many bacilli?
Immunocompromised
What is a risk factor in HIV infected pt’s before starting HAART which increases risk for developing tuberculosis?
Low CD4 count
Systemic miliary tuberculosis is most prominent in which organs/structures?
- Liver
- Bone marrow (osteomyelitis)
- Spleen
- Adrenals (Addison diseas)
- Meninges (tuberculous meningitis)
- Kidneys (renal tuberculosis)
- Fallopian tubes (salpingitis) and Epididymis
With progressive pulmonary tuberculosis, the pleural cavity is almost invariably involved, and what 3 complications may be seen here?
- Pleural effusions
- Tuberculous empyema
- Obliterative fibrous pleuritis
When the vertebrae are affected by isolated tuberculosis this is known as what?
Parapsinal “cold” abscesses in these pt’s may track along tissue planes and present how clinically?
- Pott disease
- Present as abdominal or pelvic mass
What is the most frequent presentation of extra-pulmonary tuberculosis (aka what is most often affected)?
Lymphadenitis
How does lymphadenitis and the presentation differ in HIV-negative vs. HIV-positive pt’s with active tuberculosis?
- HIV-negative = lymphadenitis tends to be unifocal and localized
- HIV-positive = tends to be multifocal disease w/ systemic sx’s, and either pulmonary or other organ involvement
Granulomatous inflammation leading to ulceration of the overlying mucosa and eventually healing strictures associated with intestinal tuberculosis is most often seen in which segment of the intestine?
Ileum
What is the stain, shape, motility and oxygen dependence of M. tuberculosis?
Weakly gram (+) rod, NON-motile, obligate aerobe
How is TB required and what is unique about this mode of transmission?
Aerosolized transmission; droplets can remain suspended for hours!
Which virulence factor of M. tuberculosis inhibits neutrophil migration and damages mitochondria; releases cachectin causing weight loss?
Cord factor
Which lobes of lung involved in primary TB?
Middle and lower lobes
Which virulence factor of M. tuberculosis inhibits the phagosome from fusing with the lysosome?
Sulfatides
A person with a postive PPD skin test is considered to have what?
Latent TB
A positive PPD skin test is defined as what?
Area of induration (hardness) that is greater than a pre-defined size after 48 hours!
A positive PPD skin test will be present in which 3 situations?
- Pt with active infection
- Pt with latent infection
- Pt who was cured of their infection
What is the BCG vaccine made from and why is it given; why you should be weary about it when giving a PPD test for TB?
- Made from M. bovis
- Given in high prevelnace areas for prevention of severe forms of disseminated TB in children
- May cause a false (+) PPD test
What is anergy and what may it be caused by?
- Anergic = lack normal immune response due to..
- Steroid use, malnutrition, AIDS, etc.
If the typical healing by fibrosis and/or calcification seen with primary TB does not occur and instead progresses to primary progressive TB what are 3 patterns of injury which may be seen?
- Primary caseous pneumonia
- Tuberculosis bronchopneumonia –> 2’ to bronchogenic spread
- Miliary tuberculosis –> 2’ to hematogenous spread
What is the common CXR finding for secondary TB?
APICAL and posterior segment involvement, pulmonary cavitation present
What is another name for the PPD test?
Mantoux skin test
In which 4 situations will an induration of ≥5mm be considered a positive PPD test?
- HIV
- Close contact w/ actively infected person
- CXR w/ fibrotic changes consistent w/ TB
- Immunosuppression (TNF-alpha inhibitors, chronic glucocorticoids, chemotherapy, and organ transplant)
What are 4 situations where an induration of ≥10mm is considered a positive result from a PPD test?
- Pt w/ clinical conditions that ↑ risk of reactivation: silicosis, DM, chronic renal failure w/ dialysis, malginancies, malnourished, IV drug abuse
- Children <4
- From country of high prevalence
- Residents/employees in high risk setting: jail, healthcare, mycobacterium labs, homeless shelters
What are 4 causes of false positive PPD tests?
- Previous BCG vaccine
- Infections w/ nontuberculosis mycobacterium
- Incorrect administration of TST
- Incorrect interpretation
What are 6 causes of false negative PPD test?
- Anergy
- Recent TB exposure (not enough time to generate response)
- Age <6 months
- Very old TB
- Recent live virus vaccine for infxn w/ virus (measles, chicken pox)
- Overwhelming TB infection
What is the initial staining used to screen for M. tuberculosis?
- Initial screen = Auramine-rhodamine stain (utilizes fluorescent microscopy)
Which 2 stains are confirmatory for TB?
- Ziehl-Neelsen stain
- Kinyon stain
XDR-TB (aka extremely drug resistant) is defined as resistance to what?
- Isoniazid
- Rifampin
- a Fluoroquinolone
- An injectable agent (such as an aminoglycoside)
What is the most common cause of fever of unknown origin in AIDS patients?
Mycobacterium Avium Complex (MAC)
How does mycobacterium avium complex present in AIDS patients?
Disseminated infection w/ fever, weight loss, hepatitis, and diarrhea
Which 2 immunocompetent patient populations may be affected by mycobacterium avium complex and what is seen in each?
- Upper lung cavitary disease in elderly smokers
- Middle and lower lung nodular and bronchiectatic disease in middle-aged female non-smokers
Which virulence factor of M. tuberculosis is used for Fe2+ acquisition?
Siderophore
Which drug is added to TB regimen for drug resistant forms?
Streptomycin
What is the most common extrapulmonary manifestation of M. tuberculosis?
Lymphadenitis –> Scrofula
If a pt showing no signs of pulmonary TB receives a PPD test with induration of 12mm and has a hx of BCG vaccination; what is the next best step in management of this pt?
Interferon-gamma release assay
What are 2 lab findings of the aspirate taken from a pleural effusion caused by TB; what stage of TB infection are pleural effusions most commonly associated with?
- Adenosine deaminase and IFN-gamma
- Associated with primary progressive TB
Mycobacterium kansasii is most commonly seen in whom; is endemic in which areas of the US?
- Older pt’s with underlying lung disease or long term smokers
- M>>W
- Endemic: Midwest and SW United States
What is the tx and duration for Mycobacterium kansasii?
Rifampin + isoniazid + ethambutol for at least 18 months!!!
