How do I perform and interpret a Mantoux tuberculin skin test for screening latent Mycobacterium tuberculosis infection in at‑risk individuals?

Performing and Interpreting the Mantoux Tuberculin Skin Test

Test Administration

The Mantoux test must be administered intradermally using 0.1 mL of purified protein derivative (PPD) tuberculin to produce a visible wheal at the injection site. 1

Critical Technical Requirements

• Inject intradermally (not subcutaneously) to create a distinct "wheal" or bleb measuring 6-10 mm in diameter at the injection site 1
• Use the volar surface of the forearm as the standard injection site 2
• If significant leakage occurs or the injection is administered subcutaneously (no wheal formation), repeat the test immediately at another site at least 5 cm away 1
• The test is safe during pregnancy and should not be delayed in pregnant women with TB risk factors 3

Reading and Interpretation

Return in 48-72 hours to measure transverse diameter of induration (not erythema) in millimeters using the palpation method. 4, 1

Common Pitfall to Avoid

Measure only the induration (firm, raised area), not the surrounding erythema (redness). If erythema >10 mm is present without induration, the injection was likely too deep and retesting is indicated. 1

Interpretation Criteria Based on Risk Stratification

The interpretation threshold depends entirely on the individual's TB risk profile, not a single universal cutoff:

≥5 mm Induration is Positive in High-Risk Groups:

• HIV-infected persons 5, 2
• Recent close contacts of persons with active pulmonary TB 5, 2
• Persons with fibrotic changes on chest radiograph consistent with prior TB 5, 2
• Organ transplant recipients and other immunosuppressed patients (receiving equivalent of ≥15 mg/day prednisone for ≥1 month) 2
• Patients initiating anti-TNF therapy 6

≥10 mm Induration is Positive in Moderate-Risk Groups:

• Recent immigrants (<5 years) from high TB prevalence countries 5, 2
• Injection drug users 5, 2
• Residents and employees of high-risk congregate settings (prisons, nursing homes, homeless shelters) 5, 2
• Mycobacteriology laboratory personnel 2
• Children <4 years of age 5
• Persons with clinical conditions that increase TB risk: diabetes mellitus, chronic renal failure, silicosis, gastrectomy, jejunoileal bypass, malignancies, weight loss >10% 2

≥15 mm Induration is Positive in Low-Risk Groups:

• Persons with no known TB risk factors 5, 2

Special Considerations

BCG Vaccination

A positive tuberculin skin test in BCG-vaccinated persons should be interpreted as indicative of TB infection, particularly in persons from high TB prevalence countries. 6, 2 History of BCG vaccination is not a contraindication to PPD testing, and the larger the reaction, the greater the probability of true TB infection rather than BCG effect. 1 In BCG-vaccinated individuals, interferon-gamma release assays (IGRAs) are preferred due to higher specificity. 7, 6, 4

Recent Exposure and Conversion

• A negative test obtained <8 weeks after exposure is unreliable for excluding infection 2
• Repeat testing at 8-10 weeks after exposure ends is required 2
• Skin test conversion is defined as an increase of ≥10 mm within 2 years, indicating recent infection requiring treatment 2

Immunosuppressed Patients

The tuberculin skin test has reduced sensitivity in patients on immunosuppressive medications (corticosteroids >1 month, thiopurines or methotrexate >3 months) or with chronic illnesses. 6, 4 For patients on immunomodulators with an initial negative TST, perform a booster test 1-2 weeks later, as this identifies an additional 8-14% of latent TB cases. 6 Any TST ≥5 mm should be considered positive for latent TB in immunosuppressed patients. 6

Post-Test Evaluation

All persons with positive tuberculin skin test results require chest radiography to exclude active TB disease before initiating treatment for latent TB infection. 2, 8

Screening Algorithm Before Testing

Before performing the TST, screen for TB symptoms: cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, and fatigue. 7, 8 Individuals with any TB symptoms or radiological abnormalities require full evaluation for active TB disease, not just LTBI testing. 7, 8

Treatment Initiation

• If chest radiograph is normal and no symptoms are present, initiate treatment for latent TB infection 8
• Preferred regimens include 3 months of weekly rifapentine plus isoniazid, 4 months of daily rifampin, or 3 months of daily isoniazid plus rifampin 8
• For children, 9 months of isoniazid remains the only recommended regimen 5, 8
• In HIV-infected patients, treat all positive TST results after excluding active disease 8

Anergy Testing

Anergy testing is no longer routinely recommended in conjunction with TST, even in HIV-infected persons, due to poor standardization and lack of demonstrated benefit. 9 The practice was abandoned because only approximately 5% of immunocompetent persons with positive tests progress to disease, and preventive therapy for anergic HIV-infected persons showed no apparent benefit. 6, 9