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In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany.Die Tuberkulose ist in Deutschland eine seltene, überwiegend gut behandelbare Erkrankung. Weltweit ist sie eine der häufigsten Infektionserkrankungen mit ca. 10 Millionen Neuerkrankungen/Jahr. Auch bei einer niedrigen Inzidenz in Deutschland bleibt Tuberkulose insbesondere aufgrund der internationalen Entwicklungen und Migrationsbewegungen eine wichtige Differenzialdiagnose. In Deutschland besteht, aufgrund der niedrigen Prävalenz der Erkrankung und der damit verbundenen abnehmenden klinischen Erfahrung, ein Informationsbedarf zu allen Aspekten der Tuberkulose und ihrer Kontrolle. Diese Leitlinie umfasst die mikrobiologische Diagnostik, die Grundprinzipien der Standardtherapie, die Behandlung verschiedener Organmanifestationen, den Umgang mit typischen unerwünschten Arzneimittelwirkungen, die Besonderheiten in der Diagnostik und Therapie resistenter Tuberkulose sowie die Behandlung bei TB-HIV-Koinfektion. Sie geht darüber hinaus auf Versorgungsaspekte und gesetzliche Regelungen wie auch auf die Diagnosestellung und präventive Therapie einer latenten tuberkulösen Infektion ein. Es wird ausgeführt, wann es der Behandlung durch spezialisierte Zentren bedarf.Die Aktualisierung der S2k-Leitlinie „Tuberkulose im Erwachsenenalter“ soll allen in der Tuberkuloseversorgung Tätigen als Richtschnur für die Prävention, die Diagnose und die Therapie der Tuberkulose dienen und helfen, den heutigen Herausforderungen im Umgang mit Tuberkulose in Deutschland gewachsen zu sein.

As part of tuberculosis control and the WHO end-TB strategy, contact persons of tuberculosis patients in Germany are examined for a possible infection with latent tuberculosis (LTBI). Activation of LTBI contributes a considerable proportion of newly reported tuberculosis cases in low-incidence countries such as Germany. Therefore, the aim is to detect cases of LTBI and, through chemopreventive treatment of these cases, prevent future, post-primary, active tuberculosis.In Germany, the rate of LTBI among contact persons of people diagnosed with active tuberculosis is not systematically recorded. The aim of the present work was to close this data gap for Cologne, a major city in Germany with a TB incidence of around 9/100,000 in the past years. The study further aimed to describe risk factors for LTBI and to reevaluate the standard inclusion criteria for contact investigation for tuberculosis under routine conditions in Germany. For the period 07/2012 to 12/2016, the retrospective cohort study examined the rate of LTBI diagnoses among contact persons of those with pulmonary tuberculosis notified at the Cologne public health department, as well as factors that increase the LTBI infection risk of contact persons. The diagnosis of latent tuberculosis was made when the interferon-gamma release assay (IGRA) was positive and there were no signs of active tuberculosis. The study included contact persons who cumulatively had a previously defined minimum total contact time with a tuberculosis patient, who were at least 5 years old at the time of the study and who were registered in Cologne. Statistical evaluation was carried out descriptively as absolute and relative frequency with a significance level of p ≤ 0.05. The analytical evaluation was carried out with univariate and multivariate logistic regression. Of a total of 3862 IGRA examinations among contact persons, 2834 cases met the inclusion criteria. A median of seven contact persons per index patient was reported. 12.5 % ​​of the study group tested positive for LTBI. In contact persons of microscopically open index patients, the positivity rate was 11.4 %, in culturally open but microscopically negative index patients, it was 14.3 %. Factors associated with a higher risk of LTBI included male sex (OR = 1.95), age ≥ 50 years (OR = 1.8) and household exposure (OR = 2.37). Using the German standard criteria, the positivity rate of IGRA testing and the diagnosis of LTBI among contacts in the present study was 12.5 %, which is lower than in other similar studies. Factors identified in the cohort for an increased risk of LTBI confirm known constellations. The significantly higher positivity rate among contact persons of microscopically negative but culturally positive index patients (p = 0.033) underscores the need to conduct a detailed contact examination of individuals of this group as well. Im Rahmen der Tuberkulosekontrolle und der End-TB-Strategie der WHO werden in Deutschland Kontaktpersonen von Tuberkulosepatienten auf eine mögliche latente Tuberkulose-Infektion (LTBI) untersucht. Die Aktivierung einer LTBI trägt einen erheblichen Anteil der neugemeldeten Tuberkulose-Fälle in Niedrig-Inzidenz-Ländern wie Deutschland bei. Deshalb ist es ein Ziel, Fälle von LTBI zu entdecken und durch chemopräventive Behandlung zukünftige, postprimäre, aktive Tuberkulosen zu verhindern. In Deutschland wird die Rate von LTBI unter Kontaktpersonen von an Tuberkulose Erkrankten nicht systematisch erfasst. Ziel der vorliegenden Arbeit ist es, diese Datenlücke für die Stadt Köln zu schließen. Die TB-Inzidenz in Köln betrug in den letzten Jahren ca. 9/100 000 Einwohner. Im Weiteren werden Risikofaktoren für eine LTBI beschrieben und die geltenden Einschlusskriterien für die Umgebungsuntersuchung bei Tuberkulose unter Routinebedingungen in Deutschland reevaluiert. Die retrospektive Kohortenstudie untersucht für die Periode 07/2012 bis 12/2016 die Rate an LTBI-Diagnosen unter Kontaktpersonen von an Lungentuberkulose erkrankten Personen im Zuständigkeitsbereich des Kölner Gesundheitsamtes sowie Faktoren, die das LTBI-Infektionsrisiko von Kontaktpersonen erhöhen. Im Rahmen der Studie wurden die Risikofaktoren Geschlecht, Alter, Art der Exposition (häusliches Umfeld/Arbeitsplatz) sowie die Kontagiosität des Indexpatienten auf ihren Einfluss auf das Infektionsrisiko bei latenter Tuberkulose berücksichtigt.Die Diagnose der latenten Tuberkulose wurde bei einem positiven Interferon-gamma Release Assay und fehlenden Zeichen einer aktiven Tuberkulose gestellt. In die Untersuchung wurden Kontaktpersonen eingeschlossen, die kumulativ eine zuvor definierte Mindestgesamtkontaktzeit zu einem Tuberkulosepatienten hatten, zum Untersuchungszeitpunkt mindestens 5 Jahre alt und in Köln gemeldet waren. Die statistische Auswertung erfolgte deskriptiv als absolute und relative Häufigkeit bei einem Signifikanzniveau von p ≤ 0,05. Die analytische Auswertung wurde mit univariater und multivariater logistischer Regression durchgeführt. Die Variablen, die sich in der Deskription als signifikant herausgestellt hatten, wurden zunächst univariat auf einen signifikanten Einfluss geprüft und bei statistisch signifikantem Ergebnis in das multivariate Modell eingeschlossen. Von insgesamt 3862 IGRA-Untersuchungen unter Kontaktpersonen erfüllten 2834 Fälle die Einschlusskriterien. Im Median wurden 7 Kontaktpersonen pro Indexpatient gemeldet. 12,5 % des Untersuchungskollektives wurden positiv auf LTBI getestet. Bei Kontaktpersonen mikroskopisch offener Indexpatienten lag die Positivitätsrate bei 11,4 %, bei kulturell offenem, aber mikroskopisch negativem Indexpatient bei 14,3 %. Außerdem konnte gezeigt werden, dass das männliche Geschlecht (OR = 1,95), Alter ≥ 50 Jahre (OR = 1,8) und die Exposition im Haushalt (OR = 2,37) das LTBI-Infektionsrisiko erhöhten. Unter Anwendung der DZK-Kriterien lag die Positivitätsrate der IGRA-Testung und die Diagnosestellung LTBI unter Kontaktpersonen in der vorliegenden Untersuchung mit 12,5 % niedriger als in anderen ähnlichen Studien. Die in der Kohorte identifizierten Faktoren für ein erhöhtes Risiko einer LTBI bestätigen bekannte Konstellationen. Die signifikant höhere Positivitätsrate unter Kontaktpersonen mikroskopisch negativer, aber kulturell positiver Indexpatienten (p = 0,033) unterstreicht die Notwendigkeit, auch in dieser Gruppe eine ausführliche Kontaktuntersuchung durchzuführen.

Tuberculosis is an often underestimated infectious disease which can lead to manifest infections even after years of latency. Pulmonary manifestations are by far the most frequent, although any other organ can be equally affected.A 95-year old patient presented with a localized painful swelling of the right foot for further investigation. Despite her advanced age there were no pre-existing medical conditions, except for a club foot existing since early childhood.On physical examination we found a hyperemic fluctuant swelling of 5 cm diameter at the arch of the right foot. The X-ray showed a complete destruction of the regular osseous structures from the upper ankle joint to the proximal metatarsal bones.Intraoperatively the suspicion of an abscess was confirmed and material was obtained for microbiological investigation. Liquid cultures grewTuberculosis, primary or reactivated, should always be considered as a potential cause of unclear infections; especially in patients with anticipated immunosenescence.Die Tuberkulose ist eine oft unterschätzte Infektionskrankheit, welche auch nach jahrelanger Latenz reaktiviert werden kann. Sowohl die primäre als auch die postprimäre Form manifestieren sich am häufigsten pulmonal, jedoch kann auch jedes andere Organ befallen werden.Eine 95-jährige Patientin wurde zur Abklärung einer lokal begrenzten, schmerzhaften Schwellung des rechten Fußes aufgenommen. Trotz des fortgeschrittenen Alters bestanden keine Vorerkrankungen.Klinisch bestand am rechten Fußrücken eine 5 cm große fluktuierende hyperämische Schwellung ohne Fistelung. Radiologisch zeigte sich eine komplette Destruktion regulärer Strukturen vom Bereich des rechten oberen Sprunggelenks bis zu den Basen der Ossa metatarsalia.Intraoperativ stellte sich der Befund als Abszess dar, aus welchem kulturell der Nachweis von Mycobacterium tuberculosis gelang. In der Magnetresonanztomografie konnte eine Osteomyelitis nicht ausgeschlossen werden. Die Dauer der antituberkulösen Standardtherapie wurde dementsprechend auf insgesamt 9 Monate festgelegt.Bei unklaren Infektionen sollte gerade bei Patienten in der Immunseneszenz immer auch die Möglichkeit einer primären oder postprimären Tuberkulosemanifestation bedacht werden.

Every year, medical personnel are sent abroad via relief organisations in order to provide humanitarian aid. The areas they are sent to are often countries with a high incidence of tuberculosis. The prevalence of latent tuberculosis infections (LTBI) and associated risk factors among returnees in Germany have not yet been systematically investigated. In a cross-sectional study (N = 95), medical personnel in Germany who had completed at least one foreign assignment were tested for LTBI with the Interferon-Gamma Release Assay in order to examine the LTBI prevalence among them. Relevant risk factors were assessed using a questionnaire. Statistical evaluation was carried out using cross-tables and multiple logistic regression. The LTBI prevalence in our sample was 12.63 %, 95 %CI (7.70 %; 23.89 %). The odds of LTBI increased with age (OR = 1.06, 95 %CI [1.01; 1.12], p-value = 0.021, per one life-year) and length of stay abroad (OR = 1.11, 95 %CI [1.03; 1.21], p-value = 0.009, per month). The study showed a higher LTBI prevalence among returnees after assignments abroad than among medical personnel in Germany after TB contact who had been investigated in previous studies. In order to be able to detect LTBI infections acquired abroad, routine testing before and after an assignment abroad seems to be necessary. Hilfsorganisationen senden medizinisches Personal ins Ausland, um dort humanitäre Hilfe zu leisten. Die Einsatzgebiete sind häufig Hochinzidenzländer für Tuberkulose. Deshalb wurde die Prävalenz einer Infektion mit In einer Querschnittsuntersuchung (n = 95) wurde die Prävalenz der latenten Tuberkuloseinfektion (LTBI) nach mindestens einem Auslandseinsatz bei medizinischem Personal aus Deutschland untersucht. Die Testung auf LTBI wurde mittels IGRA (Interferon-Gamma Release Assay) durchgeführt; relevante Risikofaktoren wurden mithilfe eines Fragebogens erfasst. Die statistische Auswertung erfolgte mit Kreuztabellen und multipler logistischer Regression. Die LTBI-Prävalenz in der Stichprobe betrug 12,63 %, 95 %-KI (7,70 %; 23,89 %) und stieg mit dem Alter (OR = 1,06, 95 %-KI [1,01; 1,12], p-Wert = 0,021, pro Lebensjahr) sowie der Länge der Auslandsaufenthalte (OR = 1,11, 95 %-KI [1,03; 1,21], p-Wert = 0,009, pro Monat). In unserer Studie war die LTBI-Prävalenz bei medizinischem Personal mit Auslandseinsätzen höher als in früheren Studien, in denen Beschäftigte nach Kontakt zu infektiösen Patienten oder Materialien untersucht wurden. Um im Ausland erworbene LTBI-Infektionen detektieren zu können, scheint eine Testung vor und nach einem Auslandseinsatz notwendig zu sein.

As part of the German TB control program, health authorities conduct investigations among contacts of patients with active tuberculosis based on the infection prevention legislation, to identify potential infections among these persons. The aim of this study was to analyze retrospectively procedures of the city health authority Cologne, in cases of newly diagnosed latent TB infection (LTBI) over a 5-year period.Data from the Cologne City Health Authority on contact investigations of TB cases between July 1Out of 3859 contact persons, 430 met the inclusion criteria: in 174/430 cases chemo-preventive therapy (CPT) was recommended and 65 (35.1 %) actually took the course of CPT; in 117 cases, no records of CPT were found in the files and 22/430 persons with LTBI developed active TB within the observation period.If the full potential of LTBI treatment on the basis of the recommendations of WHO's "End TB-Strategy" is to be realized, the present study reveals the need to continuously improve documentation and management of LTBI in this setting.Im Rahmen der Tuberkulosekontrolle führen Gesundheitsämter auf Grundlage des Infektionsschutzgesetzes (IfSG) in Deutschland Untersuchungen bei Kontaktpersonen von Tuberkulosepatienten durch, um eine mögliche Infektion bei diesen Personen zu identifizieren. Ziel dieser Untersuchung war es, die Maßnahmen des Kölner Gesundheitsamtes bei neu diagnostizierten Fällen von latenter Tuberkulose Infektion (LTBI) über einen Zeitraum von 5 Jahren retrospektiv zu analysieren.Daten des Kölner Gesundheitsamts von Untersuchungen bei Kontaktpersonen von Tuberkuloseerkrankten im Zeitraum 01.07.2012 bis 31.12.2016 wurden analysiert. Fehlende Zeichen einer aktiven Tuberkulose und ein positiver Interferon Gamma Release Assay bildeten die Basis zur Diagnose einer LTBI. Personen mit positiven Testergebnis, die zum Zeitpunkt der Untersuchung mindestens 16 Jahre und in Köln gemeldet waren, wurden mit in die Untersuchung eingeschlossen.Von insgesamt 3859 Kontaktpersonen erfüllten 430 Fälle die Einschlusskriterien: bei 174/430 Patienten wurde die Indikation für eine chemopräventive Therapie (CPT) gesehen, 65 LTBI-Patienten (35,1%) führten diese tatsächlich durch; bei 117 Patienten war in den Akten keine Angabe zur Durchführung einer Therapie vermerkt. 22/430 Personen mit LTBI entwickelten innerhalb des Untersuchungszeitraums eine aktive Tuberkulose.Um das Potenzial der chemopräventiven Therapie der LTBI im Hinblick auf die Empfehlungen der „End TB“-Strategie der Weltgesundheitsorganisation für Deutschland zu optimieren, unterstreichen diese Zahlen den Bedarf, Dokumentation und Management der latenten Tuberkulose weiter zu verbessern.

The majority of the people suffering from tuberculosis in Germany are migrants. The treatment of this demographic still presents certain challenges. Only up to a quarter to a fifth of tuberculosis cases in migrants is being diagnosed by the screening methods that were implemented by The German Protection against Infection Act (Infektionsschutzgesetz, IfSG). Reactivation of latent tuberculosis is the most common cause for tuberculosis in migrants. Easy access to health care is vital for the testing and treatment of latent tuberculosis in people with a high risk of reactivation. The level of infection risk, comorbidities and presentation of disease vary depending on the country of origin. Especially during migration people are more susceptible to somatic and mental maladies. Extrapulmonary tuberculosis is frequent in migrants and requires specific diagnostic approaches. Where risk factors for a multi-drug-resistant tuberculosis are present, this condition has to be actively excluded. To facilitate diagnosis and therapy of tuberculosis in migrants a high level of trust has to be established in the doctor-patient relationship. Therefore and despite of cultural and linguistic differences empathy and time are key. Patients need to be encouraged to complete their treatment rather than terminate it prematurely. To that end comorbidities have also to be diagnosed and treated, social and legal aspects have to be considered.

The incidence of tuberculosis decreases. However, clinical cases frequently raise questions, mainly in the context of contact tracing or when antimicrobial resistance is suspected. Empiric standard treatment consists of rifampin, isoniazid, ethambutol and pyrazinamide. This initial regimen aims to reduce the number of pathogenic germs while the consolidation therapy should eradicate the remaining pathogens. Treatment duration and adherence are crucial for cure. For the treatment of latent tuberculosis the traditional 6 to 9 months isoniazid regimen is still the treatment of choice. In complex cases such as tuberculosis in immunocompromised patients or if resistant tuberculosis is suspected, patients should be referred to a specialized center.

Infections with Mycobacterium tuberculosis (MTB) induce complex immune responses involving an orchestrated interplay of innate and adaptive immune mechanisms. Why the immune system fails to eradicate the pathogen and at best achieves control of infection in the latent stage, still remains an unsolved mystery even more than 100 years after the discovery of MTB by Robert Koch. This article provides an overview of the current state of the art in the constantly evolving field of tuberculosis (TB) immunology. This review focuses on a change of paradigm proposing that in the latent stage MTB is anything but dormant and that latent TB is not merely a state of bacterial stasis but a state of dynamic bacterial and immunological equilibrium. The understanding of these dynamics is crucial for the development of new drugs against MTB as well as vaccines that aim to provide effective protection against the disease.

Die Tuberkulose (TB) ist weltweit die häufigste Todesursache bei HIV-positiven Patienten. Die frühzeitige Identifizierung latent mit M. tuberculosis (MTB) Infizierter sowie die präventive Therapie sind entscheidend für die Reduktion der Morbidität und Mortalität bei HIV-Patienten. Ein Goldstandard für die Diagnostik der latenten Tuberkulose (LTB) ist bisher noch nicht etabliert. Bei bisher eingesetzten Tests wie dem Tuberkulin Hauttest (THT) wird vor allem bei immunsupprimierten Patienten eine niedrige Sensitivität beschrieben. In den letzten Jahren wurden neue Tests, die Interferon-Gamma-Release-Assays (IGRAs) entwickelt. Zur Abschätzung der Prävalenz der LTB in einer deutschen Großstadt wurden 192 HIV-Patienten mit einem IGRA, speziell dem T-SPOT.TB® (T-SPOT), sowie in 119 Fällen ebenfalls mit dem THT auf das Vorliegen einer LTB getestet. Als Ergebnis stellte sich eine anzunehmende LTB-Prävalenz von 20,7 % heraus, die bei Patienten aus TB-Hochendemiegebieten deutlich höher lag. Signifikante Risikofaktoren ließen sich jedoch weder für die Herkunft der Patienten, noch für Begleiterkrankungen oder den HIV-Status nachweisen. 3,2 % aller Patienten hatten ein indeterminantes Testergebnis. Der T-SPOT war im Gegensatz zum THT nicht vom Schweregrad der Immunsuppression abhängig: 20 % der Patienten mit < 100 CD4-positiven T-Lymphozyten (CD4-Zellen)/µl und 20,8 % der Patienten mit > 100 CD4-Zellen/µl waren T-SPOT positiv, allerdings traten bei Patienten mit weniger als 100 CD4-Zellen/µl mehr indeterminante Ergebnisse auf (Median der CD4-Zellzahl bei Patienten mit indeterminantem Ergebnis 54/µl und bei Patienten mit positivem oder negativem Ergebnis 286/µl, p = 0,003). Bei 112 Patienten, für die valide Ergebnisse in beiden Tests vorlagen, waren 23,2 % T-SPOT positiv und nur 11,6 % THT positiv. Beim THT zeigte sich eine Abhängigkeit zur CD4-Zellzahl. Obwohl nur sieben von 185 Patienten mit positivem Test (T-SPOT oder THT) eine präventive Therapie erhielten, entwickelte keiner der Patienten im Beobachtungszeitraum von über fünf Jahren eine aktive TB. Weitere große, prospektive Studien zur Optimierung des LTB- Screening mittels IGRA-Diagnostik und eine Überprüfung der Empfehlungen zur präventiven Therapie sind notwendig., Objective: Early detection of M. tuberculosis and preventive therapy are crucial to reduce morbidity and mortality in HIV-infected patients. However, a gold standard instrument for the diagnosis of latent tuberculosis (LTB) is lacking. Previous tests such as the tuberculin skin test (TST) are known for their low sensitivity, especially in immunocompromised patients. In recent years, new tools referred to as interferon-gamma release assays (IGRAs) have been developed. In this study, the test-performance of an IGRA, the T-SPOT.TB® (T-SPOT), was investigated in severely immunocompromised HIV-patients to detect LTB in a low-incidence country. Material and methods: The T-SPOT was performed on 192 HIV-positive patients at the Charité - Universitätsmedizin Berlin after written informed consent. Data about the immunological and virological status, concurrent other diseases, immunosuppressive therapy and demographic facts were drawn from the patients‘ medical records. 119 patients underwent an additional TST. In a follow up period of up to 66 months, clinical data and TB-status were reviewed. Results: Of 185 patients with valid T-SPOT results, 20.7 % were tested positive for LTB. The prevalence was higher in patients from high-TB-incidence countries, but as concerning HIV status or immunosuppressive therapy none of all examined factors were significantly associated with a positive test result. The proportion of positive results was equal regardless of the number of CD4-positive T-lymphocytes (CD4-cells): 20 % in patients with < 100 CD4-cells/µl and 20.8 % in patients with > 100 CD4-cells/µl were tested T-SPOT positive. 3.2 % of all patients received an indeterminate test result. However, there were more indeterminate results in patients with low CD4-cell count (CD4 median in patients with indeterminate results: 54/µl, CD4 median in patients with positive or negative results: 286/µl, p = 0.003). In 112 patients with valid results for T-SPOT and TST, there were 23.2 % with a positive T-SPOT results and 11.6 % with a positive TST. The proportion of positive TST results was low in patients with reduced CD4-cell count and increased with higher CD4-cell count. Of 43 patients with a positive test either with T-SPOT or TST, only seven received isoniazid as preventive therapy, but none of the 43 patients developed active TB during follow up. Conclusion: One-fifth of the HIV-positive patients in a central European city are latently infected with M. tuberculosis (LTB), according to a positive T-SPOT result. The results show an excellent performance in severely immunocompromised patients, though there were more indeterminate results in patients with < 100 CD4-cells/µl. Further prospectively designed studies are needed to evaluate the risk of developing active TB and indications of preventive therapy have to be reconsidered.

Interferon-gamma release assays (IGRA) are well established for diagnosing latent tuberculosis infection in adults. Evidence for their diagnostic relevance in children is still insufficient. The aim of this study was to evaluate the sensitivity and specificity of IGRA compared to the tuberculin skin test (TST) in a local population of children and adolescents presenting to our lung clinic with a specialised outpatient department.Records from all patients evaluated for tuberculosis at our centre between 2009 and 2011 were analysed retrospectively. Complete data sets were available for 80 children and adolescents (age 3 months to 17 years) in the following diagnostic groups: active pulmonary tuberculosis (MTB, n = 13), latent tuberculosis infection (LTBI, n = 15) and controls with tuberculosis exposure (n = 40), non-tuberculous mycobacterial disease (NTM, n = 2) or other lung diseases (n = 10).All 13 patients with MTB were positive on both IGRA and TST. Among the LTBI patients, 14 /15 had a positive IGRA and 14 /15 a positive TST result. In the control group 0 /52 exceeded the IGRA cut-off, while three patients had a positive TST due to a cross reaction with BCG or NTM.IGRA and TST results are highly correlated in paediatric patients with active or latent tuberculosis. IGRA sensitivity was comparable to that of the TST with a higher specificity as expected. The importance of IGRA in the hospital setting to guide diagnostic algorithms in an unselected population should be further evaluated in prospective studies.

Health-care workers are regularly screened for tuberculosis. To date, there has been no systematic analysis of the results of such a screening. A TB network for company doctors was created when interferon-γ release assays (IGRAs) were introduced in order to systematically collate their experience with IGRAs in preventive check-ups.Data have so far been recorded from 2,028 preventive check-ups. There are also data from preventive check-ups in France (n=148) and Portugal (n=2,889) for the purposes of a combined analysis. QuantiFERON-TB® Gold In-Tube and the tuberculin skin test with RT23 were used in the three cohorts.The prevalence of latent tuberculosis infections (LTBI) is dependent on age and country. Among young health-care workers (25 years old), 3% had a positive IGRA in Germany, compared with 18% in Portugal. Among health-care workers aged 55 and over, 25% were positive in Germany and 45% were positive in Portugal. In the French cohort an increase from 23% to 33% was observed when the youngest and oldest age categories were compared. Active tuberculosis has so far been diagnosed in 12 health-care workers in Portugal, four of whom developed culturally confirmed TB within the first two years following a positive IGRA. The risk of progression subsequent to a positive IGRA was 0.2% per annum.There is a low prevalence of LTBI among young health-care workers. In them a positive IGRA following close contact with an infectious patient is likely to indicate recent infection. Apart from that, older infections appear to prevail, as the IGRA results depend greatly on age, and the risk of progression following a positive IGRA appears to be low in the study groups. A positive IGRA should therefore be interpreted with caution as an indication of the need for chemotherapy.

In the western industrialized world tuberculosis has receded from its peak with an annual mortality of 1 % some 150 to 250 years ago to currently 10 to 20 new cases annually per 100,000 population. The introduction of chemotherapy in the 1950s reduced case fatality from some 70 % to a small fraction. Nowadays, the indigenous elderly and immigrants from high-prevalence countries contribute most of tuberculosis morbidity in the industrialized world. In contrast, tuberculosis remains a major public health problem in most resource-constrained countries and has substantially increased in sub-Saharan Africa as a result of the impact of HIV infection. The World Health Organization estimates that each year over 9 million new cases emerge in the world. Because of weak infrastructures low-income countries continue to experience shortages in the drug supply, facilitating the emergence of strains resistant to first-line drugs which are difficult or impossible to treat. The primordial task for the international community is to assist in strengthening the necessary infrastructures and to help ensuring that patients have unrestricted and uninterrupted access to antituberculosis medications and antiretroviral drugs.

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.

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.

The commercially available interferon gamma release assays T-SPOT.TB and QuantiFERON-TB Gold/QuantiFERON-TB Gold In-Tube may be important, besides the direct detection with culturing, PCR or the Mantoux skin test, for the diagnosis of tuberculosis as a possible cause of uveitis. It is important to know the limitations of these tests to get a fast and reliable diagnosis which may necessitate initiation of causative treatment of the tuberculosis to prevent further damage to the eye and to avoid multi-drug resistant tuberculosis strains.