Tuberculosis Flashcards
What microbe is an obligate aerobe, rod shaped, slender, and slightly curved, non-motile, heat sensitive, and intracellular?
Mycobacterium tuberculosis
What media do you grow MTB from?
Middlebrooks or Lowenstein-Jensen
How do you describe MTB after 3-4 weeks of growth?
“Ruff, buff, and tuff”
What is the only reservoir for MTB? Who does it usually affect?
Humans; usually affects young adults, needs 10 bacilli to initiate infection
What kind of exposure is needed for TB infection?
prolonged, usually in crowded conditions
What are some possible complications of MTB?
Infants and immunocompromised individuals: hematogenous dissemination may result in meningitis and other symptoms
Older: failure of immune system, possible reactivation of latent infection
How do many children become infected?
By caregivers
What is the probability of infection for healthy individuals with no risk factors?
10% over lifetime
What is the probability of infection for individuals with HIV?
10% per year
How does mycolic acid act as a virulence factor?
Prevents dehydration and may resist H2O2
What factor is responsible for serpentine “cords” of cells in virulent strains of MTB?
Mycoside
How do sulfatides have their effect as a virulence factor in MTB?
Prevent phagolysosome production and promote intracellular growth
Which virulence factor inhibits cell mediated immunity (perhaps by interfering with macrophage activation by IFN-gamma) and scavenges ROI?
Lipoarabinomannan (LAM)
What is produced in the host by immunogenesis of MTB?
Caseous necrosis within granuloma, cavity formation in lungs, hematogenous spread of bacilli
What is the reason for immediate clearance of TB?
alveolar macrophages are able to clear bacteria
What are the four potential outcomes for TB?
1) immediate clearance
2) primary disease
3) latent infection
4) endogenous reactivation/secondary disease
What is the pathogenesis behind primary diease of MTB?
Enters alveolar macrophages and multiply, produce acute inflammatory reaction, exudative lesions form, and resembles bacterial pneumonia, all of which results in dev’t of primary or rapidly progressive disease
What are the two cytokines that are originally signaled in primary TB infection?
IL-12 and TNF alpha
Where do live macrophages take up and transport MTB particles to?
Perihilar lymph nodes, leads to lymphadenopathy
What causes sensitization?
When macrophages present MTB protein antigens to T-cells.
What are sensitized T Cells responsible for?
Turning on cell-mediated immunity which multiply and return to site of infection.
What releases IFN gamma? What does IFN-gamma do?
Sensitized T Cells; attracts and activates macrophages which will actively destroy intracellular MTB
How do activated macrophages actively destroy intracellular MTB?
by producing lytic enzymes and ROI and RNI, generates granuloma and tubercle formation. Local tissue destruction results in caseous necrosis
What is in an MTB granuloma or tubercle?
caseous necrosis surrounded by viable MTB cells, more macrophages, multinucleated giant cells, collagen fibers.
What causes cavitary lesions in the lungs?
multiple granulomas and caseous necrosis coalesce, which limits the amount of O2 and eventually the TB die
What is the Ghon Focus and Ghon Complex of primary MTB?
Focus: middle or lower zone of lung
Complex: Focus+perihilar lymph nodes form a fibrotic or calcified granuloma
What marks the onset of latent TB infection?
When CMI contains “persistent” MTB cells, which form very low activity. If granuloma contain viable MTB in low pH and low O2, they enter a spore-like state
What causes the reactivation of LTBI? When can it occur?
Impairment of CMI, HIV is most important cause. 2 years to decades after primary infection
How does TB become airborne?
Caseous necroses liquify and discharge TB bacilli into bronchi
What is miliary TB?
Hematogenous dissemination of MTB to the tissue surrounding BV, Millet-seed sized granulomas form and organ & system function lost due proliferation of MTB. May form Choroid granulomas
What is Pott disease?
miliary MTB present in vertebral bodies, causes chronic back pain and untreated results in destruction of vertebrae and permanent disability
What is the Xpert MTB/RIF system?
Analyzes 2 ml of sputum samples to look for rifampin resistance in two hours!
Which mycobacterium is a weakly G+ aerobic bacilli, acid fast (strongly), and ubiquitous?
M avium and intracellulare, doubles in half the time as MTB
What does the colony of MAC look like?
small, flat, translucent, smooth, occasionally pale yellow
NO CORDING or clustering
also grows well on Middlebrook agar
How does MAC enter the body?
Either inhalation or ingestion, NO PERSON-TO-PERSON, does not require patient isolation
What is the leading cause of NTM infection? #2?
HIV (opportunistic); mycobacterium kansasii found in tap water in the southeastern and southern US
HIV negative individuals may conduct pulmonary MAC if there are what other preexisting conditions?
Elderly men with COPD (fibrocavitary)
Elderly women with bronchiectasis due to repressed couching, aka Lady Windermere’s syndrome (fibronodulary)
What is the clinical manifestation of MAC in children (1-4)?
Lymphadenitis in unilateral cervical lymph nodes
Are MAC infections due to reactivation?
No, always new infection starting in the GI tract. Looks like MTB, but you differentiate with diarrhea in addition to fever, weight loss, and night sweats.
How is diagnosis of MAC made?
Sterile isolation of MAC, CRX, PCR to determine 16S rRNA sequence of pathogen
What is the DOC for MAC in both HIV+ and HIV- infections?
Combo of clarithro or azithro + ethambutol + rifambin (check LFTs)
What should be done for a year following MAC treament in HIV negative pts?
continuation of sputum cultures for 1 year
How do you treat an HIV+ patient with no MAC infection but with exposure?
Chemoprophylaxis (in pts with CD4 100
How do you treat an HIV+ infection with MAC infection?
Begin tx and then ART 2 weeks later, don’t flip around or it causes IRIS
