What is considered a positive PPD (Purified Protein Derivative) result and what is the recommended treatment for latent tuberculosis infection (LTBI)?

From the Guidelines

A positive PPD result is determined based on individual risk factors, with 5 mm or more considered positive for immunocompromised individuals, 10 mm or more for those with increased TB risk, and 15 mm or more for healthy individuals. The interpretation of PPD results varies based on the risk factors of the individual being tested, as outlined in the guidelines from the American Thoracic Society 1 and the Centers for Disease Control and Prevention 1.

Key Considerations for PPD Interpretation

• For individuals with HIV infection, recent close contacts of persons with infectious TB, or those with other immunosuppressive conditions, an induration of 5 mm or more is considered a positive result 1.
• For those with increased risk of TB, such as recent immigrants from high-prevalence countries, injection drug users, or residents of high-risk congregate settings, 10 mm or more of induration is considered positive 1.
• For healthy individuals with no known risk factors for TB, 15 mm or more of induration is considered a positive result 1.

Treatment of Latent Tuberculosis Infection (LTBI)

The recommended treatment for LTBI, as per the World Health Organization guidelines for low TB burden countries 1, includes:

• Isoniazid (INH) 300 mg daily for 6-9 months, with 9 months preferred for optimal efficacy.
• Alternative regimens such as rifampin 600 mg daily for 4 months, or a 3-month regimen of weekly isoniazid (900 mg) plus rifapentine (900 mg).
• For those who cannot tolerate isoniazid, a 4-month regimen of rifampin plus pyrazinamide is available but carries a higher hepatotoxicity risk.
• All patients on these medications should be monitored for side effects, particularly liver toxicity, with baseline liver function tests recommended before starting treatment 1.
• Vitamin B6 (pyridoxine) 25-50 mg daily is typically added to isoniazid regimens to prevent peripheral neuropathy.

From the FDA Drug Label

Persons with human immunodeficiency virus (HIV) infection (≥ 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection. Close contacts of persons with newly diagnosed infectious tuberculosis (≥ 5 mm) Recent converters, as indicated by a tuberculin skin test (≥ 10 mm increase within a 2-year period for those < 35 years old; ≥ 15 mm increase for those ≥ 35 years of age). All infants and children younger than 4 years of age with a > 10 mm skin test are included in this category. Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (≥ 5 mm). Intravenous drug users known to be HIV-seronegative (> 10 mm). Persons with the following medical conditions that have been reported to increase the risk of tuberculosis (≥ 10 mm): Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly Children who are less than 4 years old are candidates for isoniazid preventive therapy if they have > 10 mm induration from a PPD Mantoux tuberculin skin test persons under the age of 35 who a) have none of the above risk factors (1-6); b) belong to none of the high-incidence groups; and c) have a tuberculin skin test reaction of 15 mm or more, are appropriate candidates for preventive therapy.

A positive PPD result is considered to be:

• ≥ 5 mm for persons with HIV infection, close contacts of persons with newly diagnosed infectious tuberculosis, and persons with abnormal chest radiographs
• ≥ 10 mm for recent converters, infants and children younger than 4 years of age, intravenous drug users, and persons with certain medical conditions
• ≥ 15 mm for persons under the age of 35 with no risk factors and no high-incidence group membership The recommended treatment for latent tuberculosis infection (LTBI) is:
• 12 months of isoniazid
• 4 months of isoniazid and rifampin, concomitantly, for certain candidates 2

From the Research

Definition of a Positive PPD Result

• A positive PPD (Purified Protein Derivative) result is typically defined as an induration of 10 mm or greater in diameter for the general population 3.
• However, for individuals with HIV infection, a reduced cutoff value of 5 mm or greater in diameter is often used to compensate for loss of sensitivity 4, 3.
• Some studies suggest that an even lower cutoff value of 2 mm or greater in diameter may be more appropriate for HIV-infected individuals to reduce misclassification 3.

Treatment of Latent Tuberculosis Infection (LTBI)

• The treatment of LTBI is an important component of TB control and elimination 5.
• Recommended treatment regimens for LTBI include:
  • Once-weekly isoniazid plus rifapentine for 3 months
  • Daily rifampin for 4 months
  • Daily isoniazid plus rifampin for 3-4 months
  • Daily isoniazid for 6-9 months 5
• Isoniazid monotherapy is efficacious in preventing TB disease, but rifampin- and rifapentine-containing regimens are shorter and have similar efficacy, adequate safety, and higher treatment completion rates 5, 6.
• The choice of treatment regimen should be based on individual patient factors, such as age, co-morbidities, and potential drug interactions 6.

Factors Affecting PPD Test Results

• HIV infection can affect the results of PPD testing, with a higher risk of false-negative results due to skin test anergy 4, 3.
• The risk of skin test anergy increases with decreasing CD4+ lymphocyte count 3.
• Other factors, such as age and history of previous police arrest, may also be associated with PPD positivity or anergy 3.