What is MDR-TB?
a. At least isoniazid (INH) and rifampin (RIF) resistant
b. Increasing prevalence worldwide
d. Mortality >80% in HIV+
e. Nosocomial outbreaks
f. XDR-TB also resistant to fluoroquinolones & aminoglycosides
What is TB Transmission like?
a. Respiratory pathogen
b. Crowded conditions enhance transmission
c. Single organism can cause infection
d. Each TB case likely to infect TB to 3-10 other contacts
e. Transmission to household contacts
1) smear (+) case: 50%; 2) smear (-) case: 5%
What is the natural history of tuberculosis?
It is normally latent (non-infective/no symptoms) in immunocompetent, but active (infectious) in immunosupppressed people.
a. 1 disease progression in very young, elderly & immunosuppressed
b. 2 disease/reactivation of latent infection in immunocompetent
c. 10% lifetime risk of disease progression in immunocompetent persons
d. 5% risk of disease progression in first 2 yr. after infection in immunocompetent
e. 10% annual risk of disease progression with HIV co-infection
f. Untreated active disease at 5 years
50% dead, 20% alive with disease, only 30% “cured”
What are the 3 essential ways to diagnose TB?
Medical history (specifically if they ever could’ve been exposed to TB)
Look for classic symptoms of TB (Pulmonary issues that are slow progressing and chronic)
Look for systemic symptoms of TB
What tests exist to diagnose TB?
- Skin testing-inflammation when exposed to TB shows latent TB is there. Won’t detect atypical mycobacteria. (latent)
- QuantiFERON Gold test (newly FDA approved, CDC-recommended alternative)-Looks at same thing as skin testing, but more specific-tests for IFN-gamma in response to TB antigen. Won’t detect atypical mycobacteria. (latent)
- AFB smear (active along with the rest)
- Culture and identification
- Histology and special stains
- DNA probes
- PCR
- Chest X-Ray
What are the priority guidelines for tuberculosis control?
- IDENTIFY ACTIVE CASES
- ISOLATE suspected or identified cases
- Proper TREATment
- EVALUATE CONTACTS
- CHEMOPROPHYLAXIS of latently infected persons to prevent disease progression
How is TB treated?
- Multiple drugs are necessary
- Combination of isoniazid (INH) plus rifampin (RIF) most effective
- Long term compliance absolutely necessary/DOT considered standard of care (watch them take pill)
- Need susceptibility results to rule out drug resistance
What are the treatment regimens for active TB?
- Regimens for TB (daily or 2-3 times/week options available)
Drugs
Duration (mos.)
INH RIF PZA ETB-2
INH RIF-4
INH RIF PZA STM-2
INH RIF-4
INH RIF-9 months
How do you decide who should be treated chemoprophylactically in order to avoid active disease from latent?
Induration Risk Examples
5 mm-High risk-HIV+ or equiv. immunosupp., HH contacts, x-ray c/w old TB
10 mm-moderate risk-Recent converters, IVDU, other
15 mm-low risk-No exposure or progression risks
What things put you at risk for going from latent to active?
HIV+, PPD converter (not positive on test to positive conversion) in past 2 years, abnormal chest x-ray,
How does TNF blockade increase risk of active TB? What does the CDC recommned in that situation?
Type 1 immunity is essential to prevent active TB. Type 1 immunity requires TNF. TNF inhibitors (infliximiab, etanercept) are used to fight the inflammation involved in RA, Chron’s disease, psoriasis, etc. However, b/c they block TNF, they lead to increased risk for active TB.
CDC recommends:
- Screen for latent TB prior to anti-TNF treatment (consider TST >5mm +)
- Treat for latent vs active TB prior to anti-TNF treatment
- Maintain high index of suspicion for TB during anti-TNF treatment
What is MAC? Where is it seen? How is it treated?
B. Mycobacterium avium-intracellulare complex (MAC)
- Commonly seen in advanced AIDS patients
- Chronic pulmonary disease in elderly with COPD (esp. if on steroids)
- Combination treatment with 3-5 drugs including (relatively resistant)
- Primary prophylaxis in AIDS patients with CD4<50-100 (azithromycin 1200 mg/wk)
What is the difference between the tuberculoid and lepromatous form of mycobacterium leprae?
Tuberuloid-acid fast bacilli are rare, cell mediated immunity is high, antibody titers are low, and nerve damage is high.
Lepromatous-acid fast bacilli are many, cell mediated immunity is low, antibody titers are high, and nerve damage is low.
