Tuberculosis

Epidemiology

• U.S. prevalence of infection: 10-15 million people; worldwide prevalence: 2 billion people

• * incidence in U.S. from 1984-1992 due to HIV. poverty, homelessness. immigration

• Pt is more likely to develop TB disease If:

High-prevalence populations (more likely to be exposed to and infected with bacillus): immigrant from high-prevalence areas, homeless or medically underserved. resident or worker in jail or long-term care facility. HCW at facility w/ TB. close contact to Pt w/ active TB

High-risk populations (more likely to progress from infection — active disease): HIV © or other immunodeficiencies, chronic renal failure, diabetes mellitus. IVDA. alcoholics, malnourished, malignancy, s/p gastrectomy

Microbiology and natural history

• Transmission of Mycobacterium tuberculosis via small-particle aerosols (ie. droplet nuclei)

• 90% of infected normal hosts will never develop clinically evident disease. 10% will

• Localized disease: healing & calcification or progressive 1" TB

• Hematogenous spread: latent infection • reactivation TB or progressive disseminated TB

• Two-thirds of clinically evident disease due to reactivation in U.S.; risk 2%/y for first

2-3 y after infection Screening for prior infection

• Whom to screen: high-prevalence and high-risk populations (HIV © Pts should have PPD testing as part of initial evaluation and annually thereafter)

• How to screen: Mantoux tuberculin test (ie. purified protein derivative or PPD)

inject 5-TU (0.1 ml) intermed. strength PPD intradermally — wheal; examine 48-72 h

• How to interpret determine maximum diameter of induration by palpation

Size of reaction

Persons considered to have © test

>5 mm

HIV © or immunosuppressed (eg. prednisone 15 mg/d x >1 mo) Close contacts with Pt w/ active TB CXR c/w prior TB

>10 mm

All other high-risk populations

Recent conversion (t in induration by >10 mm in last 2 y)

Faulty application, anergy. acute TB (2-10 wk to convert), acute non-TB infections, malignancy

False ©

Improper reading, cross-reaction with atypicals, BCG vaccination (although usually <10 mm by adulthood)

Booster effect

T induration b/c immunologic boost provided by prior skin test in previously sensitized (ie. infected) individual. Test goes from 0-»

but does not represent true conversion due to recent infection. 2nd test is Pt s true baseline. Can be seen 1 y after initial skin test.

(NE/M 2002:347:1860)

• IFN-7 assays may be supenor for screening purposes b/c of T Sp (Lone« 200i.357.20l7; jama

2001:286:1740, Lancet 2006:367:1328. MMWR Dec 16.2005)

(NE/M 2002:347:1860)

• IFN-7 assays may be supenor for screening purposes b/c of T Sp (Lone« 200i.357.20l7; jama

2001:286:1740, Lancet 2006:367:1328. MMWR Dec 16.2005)

Clinical manifestations

• Primary tuberculous pneumonia: middle or lower lobe consolidation.

effusion. • cavitation

• Tuberculous pleurisy: can occur with primary or reactivation. Due to breakdown of granuloma with spilling of contents into pleural cavity and local inflammation. Pulmonary effusion pericardial and peritoneal effusions (tuberculous polyserositis).

• Reactivation tuberculous pulmonary dis.: apical infiltrate t volume loss - cavitation

• Miliary tuberculosis: acute or insidious: wide dissemination 2° hematogenous spread:

usually in immunocompromised, diabetic, alcoholic, elderly or malnourished Pts. Constitutional symptoms (fever, night sweats, weight loss) prominent. Pulmonary disease w/ small millet seed-like lesions (2-4 mm) on CXR or chest CT (latter more Se. but not present in everyone with miliary TB).

• Extrapulmonary tuberculosis: lymphadenitis, pericarditis, peritonitis, meningitis.

nephritis, osteomyelitis (vertebral Pott's disease), hepatitis, cutaneous

• Tuberculosis and HIV infection: HIV-infected and other immunosuppressed Pts at

T risk for reactivation and progressive primary infection. Risk of progression from infection to disease 8-10%/y.

Diagnostic studies for active TB (high index of suspicion is key!)

• Acid-fast smear (rapid diagnosis) and culture (more Se and allows susceptibility testing)

of sputum, bronchoscope alveolar lavage, pleura, or other clinical specimens

• PCR: 94-97% Se c/w smear; 40-77% Se c/w culture

• CXR: classically fibrocavitary apical disease in reactivation vs. middle & lower lobe consolidation in 1°TB, but distinction imperfect and HIV © strongly assoc. with non-apical disease, regardless of timing (jama 2005:293:2740)

Preventive therapy (jama 2005:293.2776)

• Appropriate prophylaxis reduces incidence of subsequent disease by 65-75%

• Treat Pts who are © based on screening guidelines listed above

• Rule out active disease in any Pt w/ suggestive s/s before starting INH

Scenario

Likely INH-sensitive HIV©

Regimen

INH 300 mg PO qd + pyridoxine 25 mg PO qd x 6-9 mo INH 300 mg PO qd • pyridoxine 25 mg PO qd x 9 mo

Contact case INH-resistant

RIF x 4 mo

Contact case known or suspected to have multi-drug resistant TB

No proven regimen: ? PZA • ETB. 1 PZA • FQ

(INH = »oniazid, RIF = rifampin. PZA = pyrazinamlde, ETB = ethambutol. FQ = fluoroquinolone)

(INH = »oniazid, RIF = rifampin. PZA = pyrazinamlde, ETB = ethambutol. FQ = fluoroquinolone)

• Monitor for hepatitis: if aminotransferases 5x normal (risk t w/ age; Chest 2005:128:116)

or symptomatic -» d/c current anti-TB medications and reevaluate

Treatment of active tuberculosis (Lancet 2003:361887; jama 2005:293:2776)

• Use regimens containing multiple drugs to which the organism is susceptible

• Promote adherence to therapy; directly observed therapy (DOT) cost effective for

Pts at high risk for nonadherence

• Screen for HIV in all Pts in whom initiating anti-TB Rx

Antituberculous Medications

Drug

Dose

Adverse effects

Isoniazid (INH)

300 mg PO qd

Hepatitis, peripheral neuropathy (prevented by concomitant pyridoxine). lupus-like syndrome

Rifampin (RIF)

600 mg PO qd

Orange discoloration of urine/tears, hepatitis. Gl upset, hypersensitivity, fever

Pyrazinamide (PZA)

25 mg/kg PO qd

Hepatitis, hyperuricemia, arthritis

Ethambutol (EMB)

15-25 mg/kg PO qd

Optic neuritis

Streptomycin (SM)

15 mg/kg IM qd

Ototoxicity, nephrotoxicity

Amikacin (AMK)

15 mg/kg IM qd

Ototoxicity, nephrotoxicity

Quinolone Moxifloxacin

400 mg PO qd

Gl upset

Antituberculous Regimens*

Scenario

Regimen

Pulmonary TB &4% INH-resist in community

(includes most of U.S.)

INH + RIF • PZA • (EMB) until suscepL known If sensitive to INH & RIF INH • RIF • PZA x 2 mos.

then - INH ♦ RIF x 4 mos If resistant, see next row

Drug-resistant TB

(INH-. RIF-.or multidrug-resistant)

Consult ID specialist

Extrapulmonary TB

Consult ID specialist

TB in HIV patient

Consult ID specialist

'Individualize duration based on host disease form, and rate of clinicai/microbiologic improvement.

'Individualize duration based on host disease form, and rate of clinicai/microbiologic improvement.

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