What are the next steps after a positive tuberculin skin test (TST) for tuberculosis (TB)?

Next Steps After a Positive Tuberculin Skin Test for TB

The immediate priority after a positive TST is to rule out active tuberculosis disease through chest radiography and clinical evaluation before initiating treatment for latent TB infection (LTBI). 1

Step 1: Rule Out Active TB Disease

• Obtain a chest radiograph to identify any evidence of active pulmonary tuberculosis, including cavitary lesions, infiltrates, or other abnormalities consistent with active disease 1
• Perform a thorough clinical evaluation assessing for TB symptoms including productive cough, fever, night sweats, weight loss, hemoptysis, and duration of symptoms 1
• Collect sputum specimens (if pulmonary symptoms are present) for acid-fast bacilli (AFB) smear microscopy, mycobacterial culture, and drug susceptibility testing 1, 2
• Obtain HIV testing as HIV co-infection fundamentally changes treatment approach and duration 2

A negative TST does not exclude active TB disease, but a positive TST supports the diagnosis when clinical and radiographic findings are consistent with TB 1

Step 2: Determine Treatment Category

If Active TB Disease is Confirmed or Highly Suspected:

Initiate a four-drug regimen immediately consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for the initial 2-month intensive phase, followed by isoniazid and rifampin for at least 4 additional months 1, 2, 3

If Active TB is Ruled Out (LTBI Confirmed):

Proceed with LTBI treatment using one of the preferred regimens below 1, 4

Step 3: LTBI Treatment Regimens (When Active TB is Excluded)

The preferred treatment for LTBI is 9 months of daily isoniazid, though shorter rifamycin-based regimens are acceptable alternatives 1, 4, 5

Preferred Regimens:

• Isoniazid for 9 months (daily or twice weekly with directly observed therapy) - reduces TB risk by up to 90% when completed 1, 4, 6
• Rifampin with or without isoniazid for 4 months - equivalent efficacy to 6 months of isoniazid 1, 6
• Isoniazid plus rifapentine weekly for 3 months under direct observation 6, 7

Regimen to Avoid:

• Rifampin plus pyrazinamide for 2 months should NOT be used due to unacceptably high rates of severe hepatotoxicity and death 1, 6

Step 4: Special Populations Requiring Priority Treatment

High-risk individuals warrant aggressive LTBI treatment regardless of age 1, 4:

• HIV-infected persons (TST ≥5mm) - require minimum 12 months of therapy if using isoniazid 4
• Recent contacts of infectious TB cases (TST ≥5mm) 1, 4
• Recent converters (≥10mm increase within 2 years for age <35; ≥15mm for age ≥35) 4
• Persons with fibrotic chest radiograph changes suggesting old healed TB (TST ≥5mm) - require 12 months isoniazid or 4 months isoniazid plus rifampin 4
• Children younger than 5 years who are contacts of infectious cases 1

Step 5: Window Period Prophylaxis for High-Risk Contacts

Children <5 years and immunocompromised contacts with initially negative TST should receive treatment during the 8-12 week window period 1:

• Start LTBI treatment immediately after ruling out active TB, even with negative initial TST 1
• Repeat TST 8-12 weeks after last exposure to the infectious case 1
• If second TST is positive (≥5mm): continue full course of LTBI treatment 1
• If second TST remains negative in immunocompetent children with no ongoing exposure: discontinue treatment 1
• If second TST remains negative but patient is immunocompromised (HIV-infected): complete full course of LTBI treatment 1

Step 6: Baseline and Monitoring Requirements

Before Starting Treatment:

• Baseline liver function tests are indicated for HIV-infected persons, pregnant women, persons with history of liver disease, regular alcohol users, and those at risk for chronic liver disease 2
• Document baseline symptoms and educate about hepatotoxicity warning signs 2

During Treatment:

• Monthly clinical monitoring assessing for symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice, dark urine) 2
• Discontinue isoniazid immediately if:
  • Aminotransferases >5 times upper limit of normal in asymptomatic patients 5
  • Aminotransferases >3 times upper limit of normal with symptoms 5
  • Bilirubin above normal range 8

Step 7: Directly Observed Therapy (DOT) Priorities

DOT should be prioritized for the highest-risk LTBI patients 1:

1. Children younger than 5 years
2. HIV-infected contacts
3. Other contacts with risk factors for progression to TB disease
4. Contacts with documented skin test conversion
5. Contacts of patients with positive sputum AFB smears and cavitary disease on chest radiograph

Common Pitfalls to Avoid

• Never initiate LTBI treatment without first ruling out active TB disease through chest radiography and clinical evaluation, as single-drug therapy for active TB leads to drug resistance 1, 2
• Do not use rifampin-pyrazinamide combination for LTBI due to severe hepatotoxicity risk 1, 6
• Do not assume negative TST excludes active TB in symptomatic or high-risk patients 1
• Do not neglect HIV testing as it fundamentally alters treatment duration and monitoring 2
• For patients over age 35, carefully weigh hepatotoxicity risk against TB risk, though treatment is still recommended for those with additional risk factors 4