Tuberculosis Flashcards
Trends in TB
• Worldwide trends
o Infects 1/3 of world’s population
o Most cases occur in SE Asia, sub-Saharan Africa, and Eastern Europe
• National trends
o Greatest number of TB cases:
• In foreign-born persons from high prevalence countries
• Racial/ethnic minorities (African-Americans)
• Certain populations (living in congregate settings like corrections, long term care facilities)
• Wisconsin Trends
o 70 cases in 2011 (>40% were in Milwaukee county)
o >50% cases were in persons born outside U.S.
Transmission of TB
o Humans are only natural reservoir for M. tuberculosis
o Spread person-to-person by aerosols
o Equally affects males and females
Populations with increased risk of TB
- Elderly
- Infants
- Immunocompromised (especially with HIV = TB is leaded killer)
Patients at high risk:
• AFB smear positive (because need 10^5 organisms for positive test)
• Cavitary lung disease (~10^9-10^12 organisms)
• Laryngeal disease
• Cough and fail to cover mouth
• Procedures that increase aerosolization
• Untreated disease
Describe the structure and properties of TB
• Structure
o Unusual waxy coating on cell surface
o Made of mycolic acid (>60%)
• High lipid content = impermeable to usual stains (Gram stain)
o Also includes: sulfolipids, LAM (lipoarabinomannan)
• Properties
o Intracellular pathogen
o Ingested by macrophages but not killed
o Inhibits phagolysosome fusion → prevents acidification of vacuole → can multiply within macrophages
o Obligate aerobe
o Slow growing (24 hour generation time)
o Resistant to drying and common disinfectants
Virulence mechanisms of TB
o Key virulence = ability to multiply in macrophages
o Cell wall components disrupt phagosome-lysosome interactions → interfere with oxidative killing
o LAM induces macrophages → produce TNF-α → fever, weight loss, tissue damage
o Increases IL-10 production → immuosuppression
o Cord factor = surface glycolipid only in virulent strains
• Triggers TH1 response, enhances macrophage survival
Describe the transmission of tuberculosis infection
o Reservoir: people with cavitary lung lesions with large amounts of M. tuberculosis
o Into environment via coughing or sneezing
o Transferred when another person inhales aerosolized droplet nuclei
o Small droplet nuclei (1-5 μm) may reach alveoli in mid to lower lobes → infection
• Likelihood of infection depends on: o Number of organisms expelled into air o Concentration of organisms in air (influenced by room size, ventilation) o Length of time exposed o Immune status of exposed person
Describe the pathogenesis of tuberculosis infection
o Primary TB/ TB infection = response in person who has not been previously infected
• Inhaled droplet nuclei (containing bacilli) are deposited in lung
• Some bacilli are taken up by alveolar macrophages:
Outcome:
• Myobacteria can multiply in macrophages and alveolar spaces
• Circulating macrophages can carry organisms to distant sites (lymph nodes, bloodstream) → antigen is presented to helper T cells
• Silent bacteremia = carries organisms to body sites
• Results:
• Unrestrained replication in initial and metastatic foci
• Elicits CMI response
• Activated T cells circulate → Delayed type hypersensitivity
o Surround bacilli
o Form granulomas
o Stop further multiplication and spread
Granuloma fates:
o Most heal through fibrosis an calcification
• Bacilli slowly die
o Well-oxygenated sites = bacilli may remain viable even if walled off
• Source of disease later on
o At primary sites in lung and regional nodes:
• Central necrosis lesion, surrounded by macrophages and T cells (Ghon complex/ primary complex)
• Visible on chest x-ray
- Overall = infected by not infectious to others (Latent TB infection)
- 10% chance over lifetime infection will proceed to disease (if not treated with chemoprophylaxis)
- Highest risk is within first 2 years (50% of cases occur)
Active disease (symptoms present)
• Due to a compromise of CMI = dormant bacilli begin to replicate
• Can manifest at one site or as a disseminated disease
• Reactivation often occurs in upper, well-oxygenated lobes of lung
• Lesions become necrotic, caseate, and liquefy
• Form cavities → can erode through bronchial walls
• Visible on chest x-ray
• Person is infectious to others
Signs and symptoms of TB infection
From intense cellular response
• Release of many cytokines (especially IL-1 and TNF-α)
• Cough (possible producing blood-tinged sputum)
• Weight loss
• Night sweats
• Fever and chills
Extrapulmonary TB
o From contiguous spread or lymphohematogenous dissemination from lung Results in TB in extrapulmonary site: • Bones and joints • Pleura • Lymphatic system • GU tract • CNS • GI tract More common in children and immunocompromised
Disseminated TB (military TB)
o Serious form
o Spread via blood to multiple sites throughout body
o Organs are seeded with millet-like lesions
o Commonly seen in people co-infected with HIV; young children
o High mortality if not quickly diagnosed and treated
Explain the significance of co-infection with HIV and the mycobacteria involved.
TB = most common HIV-associated opportunistic disease
o Major cause of death of people with HIV/AIDS
HIV = strongest risk factor for latent TB to progress to active disease
o HIV modifies clinical TB presentation
o Increased frequency of radiographically and atypical pulmonary TB, extrapulmonary and disseminated disease
Complicated treatment of TB/HIV
o Many drug-drug interactions
o Development of IRIS (Immune Reconstitution Inflammatory Syndrome:
• Improvement of CD4 cells
• Able to react to TB
• Result: pathologically inflammatory response
At risk for developing Mycobacterium avium complex (MAI, or MAC)
o Mycobacterial disease
o Caused by mycobacteria in environment (water, soil, food)
o Usually only infects birds
o Rarely causes disease in normal individuals
o Acquired primarily through respiratory tract; also through GI tract
o Widespread dissemination throughout body
• Especially liver, spleen, bone marrow, and intestines
o In HIV patients = results in chronic wasting disease
• Nonspecific symptoms
• Persistent fever, night sweats, fatigue, weight loss
• Intestinal involvement → abdominal pain and chronic watery diarrhea
o Diagnose with blood cultures
o Treatment: second-line anti-TB drugs
Discuss why young children need to be identified soon after contact with an individual who has active disease, including predisposing factors.
• Increased risk of developing severe disease (weeks to months of infection)
• Predisposing factors:
o Close contact with adult with active TB
o Close contact with high-risk adult
o Foreign-born or travel to TB-prevalent country
o Chronic conditions:
• Diabetes
• Malnutrition
• HIV
• Increased risk for developing TB meningitis
• Leads to deafness, blindness, paralysis, mental impairments
• Immunodeficiency
List the laboratory tests available to diagnose M. tuberculosis.
Acid-Fast Stain (Ziehl-Neelsen stain, Auramine-Rhodamine stain) Nucleic acid amplification Culture Drug susceptibility testing TB skin testing TB blood tests (IGRA)
Acid-Fast Stains
o To detect acid fast bacilli = need 5,000-10,000 bacili/ml
o Only 50-80% patients with TB have a positive smear
o If positive smear = assumed to have infectious TB
Ziehl-Neelsen stain
• Acid-fast because retain carbol fuschsin stain even after decolorizing with acid alcohol
• Appear = magenta rods on blue background
Auramine-Rhodamine Stain
• Fluorescent dye followed by acid decolorization
• Mycobacteria fluoresce bright yellow
Nucleic acid amplification
(M. tuberculosis direct test)
o Available for respiratory specimens
o Detects TB genetic material
o Performed on:
• All smear-positive specimens
• Specimens from patients with symptoms of clinical TB (even if smear-negative)
o Advantages:
• Results within 24 hours
o Disadvantages:
• Low sensitivity in smear-negative patients
• No viable organisms available for susceptibility testing
• Not applicable in resource limited stings
o A negative test does not exclude TB diagnosis
