A tuberculin test is a skin test with tuberculin , a preparation that is filtered from liquid mycobacteria cultures. When introduced into the skin, tuberculin causes a reaction with sensitized T-lymphocytes , which are formed on contact with tuberculosis pathogens. The test is therefore used to detect a previous or current tuberculosis infection. Old tuberculin was originally developed by Robert Koch as a tuberculosis remedy ( therapeutic ). However, it turned out to be unsuitable for this. In contrast, tuberculin as a diagnostic agent for tuberculosis has been extremely important for more than 100 years in the improved preparation of PPD (Purified Protein Derivatives) (see below ).
A test that was first presented in 1907 after the introduction of tuberculin was the Pirquet test. In 1907, Clemens von Pirquet discovered the tuberculin skin reaction named after him. With a pipette, tuberculin was applied to the degreased skin at two points 10 cm apart and then drilled into the skin ( scarified ). A third hole without tuberculin was placed in between as a negative control point in order to distinguish a non-specific reaction. There were several variants of the test procedure. If nodules (papules) with a diameter of more than 5 mm developed after 48 hours, the result was positive, a previous tuberculosis infection was to be assumed. The sample did not allow any conclusions to be drawn about the presence or activity of the tuberculosis.
Percutaneous sample according to Moro
Ernst Moro also presented his percutaneous sample in 1907. After rubbing the intact, pre-cleaned skin with a tuberculin ointment, eczema that developed after 48 hours was assessed as positive. Because of the uncomplicated, painless application, the otherwise unsafe test method was preferred for small children.
Conjunctival tuberculin test
The third test presented in 1907 was the conjunctival tuberculin test according to Woff-Eisner, in which a tuberculin solution was dropped onto the conjunctiva of one eye. After 6–12 hours, a more or less severe conjunctivitis developed in the positive case. Because of its complications, the method was rarely used.
A plaster soaked with tuberculosis was stuck to a sanded area of skin.
Plaster sample after Hamburger
According to Hamburger, a tuberculin-coated plaster was stuck on above the left nipple and removed after 24 hours. The test was read after 48 hours. Until the 1970s, it was preferred for screening tests in kindergartens and schools.
A simplified way of carrying out this was to apply the tuberculin to the inside of a forearm with a commercially available stamp (Tinetest ® , Tubergen ® -Test). It was visible there as a point. The test could be read between the fourth and seventh day after the injection and was considered positive if a palpable papule at least 2 mm in diameter was found - reddening alone was not sufficient. The disadvantage of this method was its relatively low specificity and sensitivity . The production of stamp tests was therefore stopped in 2005. The test is no longer available in Germany and its neighboring countries because it is no longer approved by the BfArM (or corresponding authorities abroad).
The Heaf test was a British variant of the stamp test. At least six tuberculin-wetted spines sitting on a plastic or metal plate were pressed into the superficial skin with the instrument of the Heaf Multiple Puncture Apparatus. In the event of a positive response, the extent of the reaction was divided into four grades three to ten days after application and clinically assessed. The production of the Heaf test was stopped in 2005.
Current standard and developments
Mendel-Mantoux intracutaneous test
The Mendel - Mantoux test (internationally the term Mantoux test is more common) is used for a more precise examination . 2 TU ( tuberculin units ) - 0.1 ml - Tuberculin RT23 from the Staten Serum Institute in Copenhagen (approved in Germany since September 2005) are injected strictly intracutaneously into the uppermost skin layer ( epidermis ) on the volar side of the forearm. After the injection, the test site should not be rubbed or exposed to excessive UV radiation. The test is read after 48 hours at the earliest, or better after 72 hours, and is considered an indication of a tuberculosis infection in healthy persons exposed to tuberculosis if a hardened swelling ( induration ) larger than 5 mm is evident. The interferon gamma tests that are now available can also help clarify the question of a tuberculosis infection more precisely. Because the amount of tuberculin is administered much more precisely, it is more reliable than the stamp test.
Assessment of the Mendel-Mantoux test
Usually the assessment is adapted to the clinical situation. If the defense is weakened, the cut-off for the positive failure is shifted downwards into the area of 5 mm or more transverse diameter of a palpable induration. In healthy adolescents and adults without prior BCG vaccination and without current exposure, the cut-off is usually 10 mm transverse diameter. The assessment is carried out according to national guidelines, which may vary slightly and sometimes take additional criteria into account. In Germany, the guidelines of the German Central Committee for Combating Tuberculosis (DZK) are used. The current guideline can be found under point 3.5.2 in the publication: New guidelines for environmental examinations in tuberculosis.
The provisionally designated C-TB test of the Staten Serum Institute SSI in Denmark in 2014 has completed clinical trial phase III with excellent results. In contrast to the biologically obtained PPD, the mixture of the C-Tb test is genetically engineered with defined antigens. As a result, increases in specificity and also in sensitivity are to be expected, which would make the C-TB test in series examinations a reliable and inexpensive alternative to gamma interferon tests. The European approval of the C-TB test is expected in 2017.
A positive reaction can occur not only with or after tuberculosis, but also after infections with other so-called atypical mycobacteria and after previous tuberculosis vaccination with the BCG vaccine as a so - called cross - reactivity . In the case of blooming or fulminant tuberculosis or severe immune deficiency, the tuberculin test can be negative despite the disease. This condition is known as anergy . The test cannot indicate or quantify the level of activity of the disease.
The conventional tuberculin test is still an important tool for making diagnoses and, when used as a tuberculin survey, it enables the assessment of the contamination of various population groups. Its interpretation and prognostic value are based on data that has existed for over a hundred years. Because of the cross-reactivity, the tuberculin test does not differentiate between the defined tuberculosis pathogens and so-called atypical mycobacteria. A newer test procedure with a somewhat more specific Tb antigen detection and thus reduced cross-reactivities was introduced in Germany in 2005, see γ-interferon test , and can increase the informative value of the tuberculin test . Due to its ubiquitous availability and its resource-saving application, the improved tuberculin test will be able to maintain its clinical value.
- Thomas Hirtl: The tuberculin. (= Gesund series in Vienna ). Literas Universitätsverlag, 2000, ISBN 3-85429-167-1 .
- Tomas Hirtl: The tuberculin. Literas Universitätsverlag, Vienna 2000, pp. 65f.
- Tomas Hirtl: The tuberculin. Literas Universitätsverlag, Vienna 2000, p. 66ff.
- Tomas Hirtl: The tuberculin. Literas Universitätsverlag, Vienna 2000, p. 66.
- Tomas Hirtl: The tuberculin. Literas Universitätsverlag, Vienna 2000, p. 68.
- Tomas Hirtl: The tuberculin. Literas Universitätsverlag, Vienna 2000, pp. 68f.
- General Practice Notebook - a UK medical reference Heaf test - General Practice Notebook .
- A. Detjen et al.: Immunological diagnosis of tuberculosis - γ-interferon test. In: Monthly Pediatrics. 2006; 154, pp. 152-159.
- K. Magdorf: childhood tuberculosis. In: Monthly Pediatrics. 2006; 154, pp. 124-132.
- German Central Committee to Combat Tuberculosis: New Guidelines for Environmental Investigations in Tuberculosis. In: Pneumology. 2011; 65, pp. 359–378, online publication May 10, 2011 295 359..378 ( Memento of the original from August 26, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , Pneumologie.de.
- Homepage of the SSI: New tuberculosis skin test - SSI is developing a new and improved skin test to diagnose M. Tuberculosis infections, and has achieved excellent results to date, accessed August 21, 2014 New tuberculosis skin test - Statens Serum Institut.