accumulate at the site of injection and result in palpable induration. This response requires 24 to 48 hours and has been termed delayed-type hypersensitivity. Delayed hypersensitivity develops 2–10 weeks after initial infection and persists for many years, although reactivity may wane with advancing age.
In the early 1900s, tuberculin testing consisted of a series of graduated doses of tuberculin. Any reaction to any dose was considered a positive test, and testing was used largely to eliminate tuberculosis as a diagnostic possibility in sick patients. In the 1920s and 1930s, the decreasing prevalence of tuberculosis resulted in decreased transmission of the infection to younger age groups and tuberculin was suggested as a method of diagnosing the infected state rather than the disease. The use of a series of skin tests with graduated doses of tuberculin was impractical, and in 1941, Furcolow and colleagues(12) reported a dose of 0.0001 mg discriminated patients with tuberculosis from others with the greatest accuracy. This amount of tuberculin was five times the usual starting dose with the graduated regimen and was said to contain 5 tuberculin units (TUs). This 5-TU dose has become the standard for tuberculin testing in the United States. Newly manufactured batches of tuberculin are currently bioassayed, and the 5-TU standard is the amount of material which produces results equal to those produced by 0.0001 mg of PPD-S. Other doses of tuberculin, such as “first strength” (1 TU) and “second strength” (250 TU) represent the smallest and largest doses of tuberculin that were administered in the abandoned graduated tuberculin testing method. These doses have been commercially available in the past, but they are not standardized by bioassay and have no use in diagnostic tuberculin testing programs.
Although induration is generally accompanied by erythema, results using erythema are less precise and repeatable than those measuring induration, and measurement of induration is the standard. The injection is usually administered on the volar surface of the forearm, and induration is measured 48 to 72 hours following administration. Variation in tests administered simultaneously to both forearms averages about 15 percent and variability in measuring induration among experienced observers is similar. Although interobserver variability may be decreased by using the ballpoint pen method of Sokal,(13) most studies are based on palpation by experienced observers. Even with experienced observers, there is a tendency for clustering around predetermined cut-points and this can be