Tuberculosis, Latent Infection

Essentials of Diagnosis

• Positive tuberculin skin test

• No evidence of active infection with tuberculosis (TB)

• History (knowingly or not) of exposure to Mycobacterium tuberculosis (MTB)

General Considerations

• Targeted skin testing used to identify

  • Persons at high risk for TB

  • Persons who would benefit from treatment of latent TB infection (LTBI)

• LTBI describes patients who have been infected with M tuberculosis but do not have active disease

• Individuals with LTBI have contained but not eradicated infection

• The importance of identifying and treating LTBI is to prevent reactivation disease

• LTBI is nontransmissible but may become active disease if a person's immune function becomes impaired

• Active TB will develop in approximately 6% of individuals with LTBI who are not given preventive therapy; half of these cases occur in the 2 years following primary infection

• Patients with primary infection require 2–10 weeks to manifest an immune response to skin testing

• Persons who have received bacillus Calmette-Guérin (BCG) vaccination may have a positive purified protein derivative (PPD) tuberculin test for the rest of their lives

• Resistance may be to single or multiple drugs

  • Drug-resistant TB is resistant to one first-line antituberculous drug, either isoniazid (INH) or rifampin (RIF)

  • Multidrug-resistant tuberculosis (MDR-TB) is resistant to INH and RIF, and possibly additional agents

  • Extensively drug-resistant tuberculosis (XDR-TB) is resistant to INH, RIF, fluoroquinolones and either aminoglycosides or capreomycin or both

Symptoms and Signs

• Patients are asymptomatic

• LTBI is uncovered by screening with the tuberculin skin test

• Any pulmonary or constitutional symptoms should prompt an evaluation for active disease prior to prophylactic treatment

Differential Diagnosis

• BCG vaccination

Laboratory Tests

• All patients with risk factors should be tested for HIV

Imaging Studies

• Chest radiograph is required to rule out active pulmonary TB

Diagnostic Procedures

• The Mantoux test is the preferred skin test (Table 9–13)

  • 0.1 mL of PPD containing 5 tuberculin units is injected intradermally on the volar forearm

  • At 48–72 hours, transverse width in millimeters of induration is measured

• False-positive tuberculin skin test reactions occur in patients previously vaccinated against MTB with BCG

• Prior vaccination with BCG does not alter the interpretation of the tuberculin skin test

• False-negative tests may result from

  • Improper technique

  • Concurrent infections

  • Malnutrition

  • Advanced age

  • Immunosuppression of any kind

  • Fulminant MTB infection

• Because of waning immunity, some patients with LTBI may have a negative skin test many years after exposure

• Two-step testing or "boosting"

  • Performed to reduce the likelihood that a boosted reaction will later be misinterpreted as a recent infection in individuals who will be tested repeatedly (health care workers)

  • A second test is performed 1–3 weeks after a negative test

  • If negative, the patient is uninfected or anergic; if positive, a "boosted reaction" (recovery of waned immune response) is likely and the patient has LTBI

• Anergy testing is not recommended to distinguish a true-negative test from anergy

Medications

• Treatment substantially reduces the risk that infection will reactivate and progress to clinical disease

• Patients in whom active disease is suspected should be treated with multidrug regimens until the diagnosis is confirmed or excluded

• Exposed persons who are skin-test–negative and HIV-negative may be observed without treatment or treated with 6 months of oral therapy

• INH

  • 9-month oral regimen (minimum of 270 doses administered within 12 months) is preferable to 6 months of therapy

  • Dosing options include a daily dose of 300 mg or twice-weekly doses of 15 mg/kg

  • Persons at risk for developing INH-associated peripheral neuropathy (diabetes mellitus, uremia, malnutrition, alcoholism, HIV infection, pregnancy, seizure disorder) should be given supplemental pyridoxine (vitamin B₆), 10–50 mg/day

• INH and RIF: A 3-month oral regimen of INH (300 mg/day) and RIF (600 mg).

• INH and rifapentine: A 3-month oral regimen of once weekly INH at 15 mg/kg and rifapentine at 15–30 mg/kg

• RIF

  • Patients who cannot tolerate INH can be considered for a 4-month oral regimen of RIF at 600 mg daily

  • HIV-positive patients receiving protease inhibitors or nonnucleoside reverse transcriptase inhibitors who are given RIF or rifapentine require management by experts in both TB and HIV disease

Therapeutic Procedures

• It is not necessary to routinely monitor liver chemistries unless there are abnormalities at baseline or clinical reasons to obtain the measurements

Follow-Up

• All contacts of persons with MDR-TB or extensively drug-resistant TB should be monitored for 2 years regardless of treatment

• Patients being treated for LTBI should be seen monthly to evaluate for evidence of active TB, side effects (eg, INH hepatitis), and adherence to treatment

Complications

• Development of active TB

• Drug toxicity

Prognosis

• Almost all properly treated patients with TB can be cured

• Relapse rates are < 5% with current regimens

• Treatment failure is most commonly due to medication nonadherence

When to Refer

• HIV-positive patients receiving antiretroviral therapy should be referred to TB and HIV experts if they are to receive RIF therapy

Prevention

• Close contacts of patients with active TB should be retested 10–12 weeks after a negative tuberculin skin test

• Despite a negative skin test, close contacts of patients with TB should consider treatment if they are immunosuppressed