How do I interpret the results of a Mantoux (tuberculin skin) test in patients with varying risk factors, including those with human immunodeficiency virus (HIV) infection or impaired immune status?

Mantoux Test Interpretation for Practicing Doctors

Interpret the Mantoux test by measuring only the transverse diameter of induration (not erythema) at 48-72 hours, then apply risk-stratified cutoffs: ≥5 mm for high-risk patients (HIV-infected, close TB contacts, immunosuppressed, or those with fibrotic chest X-ray changes), ≥10 mm for moderate-risk groups (foreign-born from high-prevalence countries, healthcare workers, injection drug users, residents of congregate settings), and ≥15 mm for persons with no risk factors. 1

Proper Test Administration and Reading Technique

Timing

• Read the test between 48-72 hours after intradermal injection when induration reaches maximum size 1
• Tests read after 72 hours underestimate true induration size and should be avoided 2, 3

Measurement Technique

• Measure only the palpable induration (hard, raised swelling), never erythema (redness) alone 1, 2, 3
• Record the transverse diameter perpendicular to the long axis of the forearm in millimeters 1
• Perform measurement in good light with the forearm slightly flexed at the elbow 2, 3
• Record absence of induration as "0 mm," not "negative" 2
• Trained personnel must perform the reading—patient self-reading is unacceptable 1, 3, 4

Risk-Stratified Interpretation Cutoffs

≥5 mm Induration = Positive 1, 2, 4

• HIV-infected persons (regardless of CD4 count) 1, 4, 5
• Recent close contacts of persons with active pulmonary or laryngeal TB 1, 4, 5
• Persons with fibrotic changes on chest radiograph consistent with prior TB 1, 4, 5
• Organ transplant recipients 1, 4
• Immunosuppressed patients receiving ≥15 mg/day prednisone equivalent for ≥1 month 1, 4
• Patients on TNF-blocking agents 1

≥10 mm Induration = Positive 1, 2, 5

• Foreign-born persons from high TB prevalence countries 1, 5
• Injection drug users (HIV-seronegative) 1, 5
• Healthcare workers and mycobacteriology laboratory personnel 1, 2
• Residents and employees of high-risk congregate settings (prisons, nursing homes, homeless shelters) 1, 2, 5
• Persons with medical conditions increasing TB risk: diabetes mellitus, silicosis, chronic renal failure, hematologic malignancies, gastrectomy, intestinal bypass, chronic malabsorption, carcinomas preventing adequate nutrition 1, 5
• Recent converters: ≥10 mm increase within 2 years for age <35 years 1, 5
• Children <4 years old 1, 5

≥15 mm Induration = Positive 1, 2, 5

• Persons with no known risk factors for TB 1, 2, 5
• Recent converters age ≥35 years: ≥15 mm increase within 2 years 5

Special Populations and Critical Considerations

HIV-Infected and Immunocompromised Patients

• Use ≥5 mm cutoff regardless of CD4 count 1, 4
• False-negative rate is 25% even in active TB due to anergy 1, 4
• HIV-infected persons with latent TB have 5-10% annual risk of progression to active disease without treatment 1
• Anergy testing is NOT recommended—it lacks standardization, has poor reproducibility, and shows no documented benefit in screening programs 1, 4
• Even anergic HIV-infected patients can sometimes respond to PPD while not responding to control antigens 1

BCG-Vaccinated Persons

• Prior BCG vaccination is NOT a contraindication to tuberculin skin testing 3, 4, 6
• BCG-induced reactivity typically wanes over time and is unlikely to persist >10 years 2
• A positive TST in BCG-vaccinated persons should be interpreted as M. tuberculosis infection, especially in those from high-prevalence countries or with increased risk 2, 3, 4
• The size of reaction does not reliably distinguish BCG effect from true TB infection 2
• The larger the reaction, the greater the probability of true TB infection 6

False-Negative Results

False-negative reactions occur more frequently in: 1

• Infants and young children
• Early infection (<6-8 weeks after exposure)
• Recent viral vaccination
• Recent viral or bacterial infections
• Overwhelming or disseminated TB
• Immunosuppressive conditions (HIV, malignancy)
• Treatment with immunosuppressive drugs (high-dose corticosteroids, TNF inhibitors)

False-Positive Results

• Prior BCG vaccination, especially post-infancy or repeat vaccination 1
• Infection with nontuberculous mycobacteria 1

Mandatory Follow-Up Actions

For Any Positive TST 4

1. Obtain chest radiograph to exclude active pulmonary TB
2. Perform clinical evaluation for TB symptoms: cough >3 weeks, hemoptysis, fever, night sweats, weight loss 1, 4
3. Obtain sputum samples (3 specimens on different days) if symptoms present or radiograph abnormal 1, 4

Skin Test Conversion

• Defined as ≥10 mm increase in induration within a 2-year period, indicating recent infection 2, 3, 5
• Requires evaluation for active TB and consideration for preventive therapy 5

Common Pitfalls to Avoid

1. Measuring or recording erythema instead of induration—only induration counts 1, 2, 3, 4
2. Accepting patient self-reading—trained personnel must read all tests 1, 3, 4
3. Dismissing positive results in BCG-vaccinated individuals—interpret as true infection when risk factors present 3, 4
4. Reading tests after 72 hours—this underestimates true size 2, 3, 4
5. Relying on anergy testing in HIV/immunocompromised patients—this is no longer recommended 1, 4
6. Using a single cutoff for all patients—interpretation must be risk-stratified 1, 2, 3
7. Failing to recognize the boosting phenomenon—repeat testing can restore waned reactivity, not induce new reactivity 1

Test Performance Characteristics

• Sensitivity: 95-98% in clinically well persons with previously treated TB 1
• Specificity: Decreased by BCG vaccination and nontuberculous mycobacterial exposure 1
• Studies show significant underreading by healthcare professionals—median reading of 10 mm for actual 15 mm induration, with 93% incorrectly classifying a known converter as negative 7