[New recommendations for contact tracing in tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*1.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

[New recommendations for contact tracing in tuberculosis. German Central Committee against Tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

[False-positive interferon-gamma test?]. / Falsch-positiver Interferon-gamma-Test?

M. tuberculosis specific interferon-gamma tests have been established lately as an important additional instrument in the diagnosis of the latent tuberculosis infection (LTBI). In several studies these tests had a higher specificity compared to the tuberculin skin test (TST). In this report we describe the case of a woman without increased risk for LTBI and with discordant results for the interferon-gamma tests QuantiFERON-TB Gold In-Tube and T-SPOT.TB and for the TST. The findings suggest repeated false-positive results of the QuantiFERON-TB Gold In-Tube test.

[The Tuberculosis Rapid Assay from DiaVita - No Alternative to the Tuberculin Skin Test]. / Der Tuberkulose-Schnelltest von DiaVita - keine Alternative zum Tuberkulinhauttest.

New methods for diagnosing active tuberculosis (TB) and/or latent tuberculosis infection have been offered increasingly during recent years, also in Germany. The Tuberculosis Rapid Assay ('Tuberkulose Schnelltest [TB-ST]') from DiaVita is a serologic test method aiming to detect, within a few minutes, tuberculosis-specific antibodies in whole blood or serum of tuberculosis patients. Due to a lack of data, it is, however, hardly possible to assess this test on a scientific basis. With a relatively high specificity (according to DiaVita over 95 %) but inadequate sensitivity (approximately 60 - 80 %), particularly in paucibacillary types of TB, we consider this method of limited value for routine testing. If active TB is strongly suspected, a positive test result may corroborate the tentative diagnosis, whereas a negative test result is not helpful for differential diagnosis considering the great number of false-negative test results to be expected. The greatest value of the test seems to be in bacteriologically confirmed TB, in which however there may be no need for additional diagnostics. The test has not been evaluated, and in our opinion is probably unsuitable for detecting latent TB infection. Data is also lacking for a number of patient groups in urgent need of a reliable alternative to the tuberculin skin test (e. g., immunocompromised patients, children). It is not clear whether this method will find a place in routine TB diagnostics. We therefore cannot recommend this test as a routine diagnostic tool for TB at present.

[Future supply of tuberculin in Germany]. / Zukünftige Tuberkulinversorgung in Deutschland.

The manufacturers of the only tuberculin available up to now in Germany for intradermal TB tests according to Mantoux, Chiron Vaccines Behring, in 2004 unexpectedly stopped the production of the tuberculin Behring GT (GT="gereinigtes Tuberkulin"-purified protein derivative tuberculin). Only residual stocks were sold during the preceding months. The stocks of GT 10 were already depleted at the beginning of 2005, while there are small supplies left of GT 100 and GT 1000. As a temporary solution, Chiron Vaccines Behring is offering to import the Italian tuberculin Biocine PPD 5 IE lyophil produced by Chiron S.r.l. in Siena. As this is not licensed for sale in Germany, it is necessary to obtain an exceptional prescription (Einzelverordnung) according to section sign 73 (3) of the Federal Law Relating to the Manufacture and Distribution of Medicine (Arzneimittelgesetz, AMG). In the long term, Chiron Vaccines Behring plan to secure the supply of tuberculin in Germany by importing, starting in the summer of 2006, the tuberculin produced by Chiron Vaccines Evans in the UK (PPD Evans). However, these plans involve changing over to a different type of tuberculin twice within a very short period of time. Another problem is the unresolved issue of bioequivalence. Besides the above-mentioned tuberculins produced by Chiron Vaccines, a further possibility would be the import of the tuberculin PPD RT23 SSI of the Statens Serums Institute (Copenhagen/Denmark), which is recommended by the World Health Organization (WHO) as the standard tuberculin and which has already been introduced in several European countries, or of other tuberculins such as Tubersol (PPD CT68), which is used in the US. Together with the Robert Koch Institute (RKI) and the Paul Ehrlich Institute (PEI), the German Central Committee against Tuberculosis (DZK) is striving to find a solution, in view of the urgent need for an uninterrupted supply of tuberculin in Germany for diagnostic purposes and contact tracing. A uniform tuberculin should be used in all German regions as a basis to secure a standardized testing procedure and national comparability of test results. The estimated annual requirement for Germany is two million tuberculin test doses. The Statens Serum Institute is currently evaluating the possibility of licensing PPD RT23 SSI in Germany. Chiron Vaccines Behring communicated that it is not aiming to have the Biocine tuberculin licensed for Germany but intends to apply for a license for the tuberculin PPD Evans. Sanofi Pasteur MSD at this point does not intend to have a tuberculin like Tubersol (PPD CT68) licensed for Germany. Until a licensed tuberculin is again available in Germany, it would be very useful if, especially in settings where stocks of tuberculin are essential (e.g. public health services or hospital dispensaries), an exceptional import license could be obtained.

[Mendel-Mantoux tuberculin test with GT 1 in the public health office]. / Tuberkulintest nach Mendel-Mantoux mit GT 1 im Gesundheitsamt.

Within the German Public Health Service, the recommendation of the German Central Committee für Combatting Tuberculosis to use the intracutaneous tuberculin test according to Mendel-Mantoux as a standard test has led to demands for additional investigations on sensitivity and specificity of different tuberculin doses. In routine everyday work of the Public Health Office of the German provincial capital Stuttgart the Mendel-mantoux tuberculin test with tuberculin GT 1 Behring was examined in respect of sensitivity and incidence of excessive reactions and compared to a former study with GT 5. 2,592 persons for whom the tuberculin test was prescribed according to the German infectious diseases law were tested for tuberculosis by the Stuttgart Public Health Office between May and October 1998, using the Mendel-Mantoux test with GT 1 Behring. Of these, 202 persons did not return for checking the result. The 2390 checked persons were 28.4 years old on the average, the majority being female (59.0% against 41.0% males) and of German nationality (59.6% against 40.1% other nationals). A positive reaction was seen in 16.2% (induration > or = 6 mm), in 7.2% Germans against 29.6% other nationals. In 51% of the positive results the indurations had a diameter of more than 10 mm, in 12.6% more than 15 mm, 9 probands, i.e. 0.4% of all tested persons, had an excessive reaction (formation of blisters with local necrosis). Especially among the other nationals, the share of strongly positive results (> 15 mm) did not decrease to the same extent as did the share of positive results as a whole. 94 persons belonging to the surrounding of a bacillary index case got a second test with GT 10. Of these, 30 (31.9%) had a positive reaction. The use of a low tuberculin concentration (GT 1) for the intracutaneous test according to Mendel-Mantoux cannot be recommended. The sensitivity is significantly lower than with GT 5 which leads to seeming tuberculin conversions (because of the low sensitivity of GT 1) without avoiding excessive reactions. For tuberculin surveys in areas adjacent to bacillary index cases, the intracutaneous test according to Mendel-Mantoux should be performed with the usual dose (GT 10) as a standard test. For other purposes, the multipuncture-stamp test may be sufficient.