The tuberculin skin test is the most useful test for the diagnosis of past or present tuberculous infection. The Mantoux test is more reliable than multiple-puncture tests, such as the tine test. PPD is available in three strengths:
- the first strength contains 1 tuberculin unit (TU),
- the intermediate strength contains 5 TU, and
- the second strength contains 250 TU.
Only the 5-TU strength should be used for screening.
The tuberculin skin test result should be interpreted 48 to 72 hours after injection; the diameter of induration (not erythema) determines the interpretation. Until recently, a single standard was used to interpret the tuberculin skin test in all people:
- 0 to 4 mm was negative,
- 5 to 9 mm was doubtful, and
- 10 mm or greater was positive.
As noted earlier, authorities such as the Centers for Disease Control and Prevention (CDC) now recommend that different skin test criteria be applied to different population groups to provide a more accurate assessment of risk.
The current CDC criteria for skin test positivity include the following:
- Induration of 5 mm for patients who are:
- HIV-positive,
- have undergone solid-organ transplantation,
- receiving immunosupressive therapy including TNF antagonists or the equivalent of 15 mg/d of prednisone for more than 1 month,
- very likely to have TB, such as close contacts of documented cases and patients with chest x-ray films that strongly suggest TB.
- Induration of 10 mm for members of high-incidence populations, such as:
- immigrants from countries where tuberculosis is endemic (particularly those who have immigrated within 5 years);
- injection-drug users;
- residents or employees of high-risk coagreggate settings (hospitals, nursing homes, homeless shelters, correctional facilities);
- patients with medical conditions predisposing to active TB, such as silicosis, diabetes, chronic renal insufficiency, leukemia or lymphoma, or cancer of the head or neck;
- persons who have undergone gastrectomy or jejunoileal bypass or whose weight is 10% or more below their ideal body weight;
- and children younger than 4 years of age.
- Induration of 15 mm for persons with no identifiable risk factors.
Repeated tuberculin skin tests can produce a booster effect, but only among patients already infected with TB. Among hospital employees or other populations who may undergo repeated skin testing, a booster effect can be mistaken for tuberculin conversion. Confusion can be avoided by repeated testing of persons with negative or doubtful skin test results 1 week later; any increase in the diameter of induration at 1 week can be attributed to the booster effect. In contrast, increased reactivity that occurs at 1 year, but not at 1 week, should be attributed to newly acquired infection.
False-negative reactions (anergy) have been documented in up to 20% of patients with TB, particularly those who are:
- immunocompromised by HIV infection,
- overwhelming or advanced disease,
- malnutrition, or
- debility.
In addition to immunologic incompetence of the host, other causes of false-negative skin test results are:
- mishandling of the antigen and
- faulty injection technique.
Tuberculin should never be transferred from one container to another, and skin tests should be administered as soon as possible after the syringe is filled. Subcutaneous rather than intradermal injection may result in false-negative reactions. Because tuberculin sensitivity develops 2 to 10 weeks after initial infection, results of early skin tests may be negative in newly infected persons.
Although tuberculin skin testing is highly specific, false-positive reactions may also occur, usually because of cross-reactivity with atypical mycobacterial antigens acquired environmentally. This may cause intermediate skin test reactions in people who have not been exposed to M. tuberculosis, hence the requirement for larger areas of induration when a low-risk population is screened.