Barbara Hauer

Empfehlungen zur Therapie, Chemoprävention und Chemoprophylaxe der Tuberkulose im Erwachsenen- und Kindesalter

Seit der Veröffentlichung der Empfehlungen des DZK zur medikamentösen Therapie der Tuberkulose (TB) 2001 sowie zur Chemoprävention der latenten tuberkulösen Infektion (LTBI) 2004 sind verschiedene neue internationale Empfehlungen erschienen. Diese sind in die jetzigen Empfehlungen, welche sowohl die Therapie der aktiven Tuberkulose als auch die präventive Behandlung darstellen, integriert, wobei Deutschland-spezifische Adaptationen betont werden. Jeweils gesondert wird das aktuelle Vorgehen bei Mono-, Polyund Multiresistenzen oder Medikamentenunverträglichkeiten, bei kindlicher Tuberkulose, bei verschiedenen Formen der extrapulmonalen Tuberkulose, bei LTBI sowie in speziellen Situationen wie HIV-Infektion, Nierenoder Leberinsuffizienz, Infektion nach BCG-Instillation bei Harnblasenkarzinom oder bei Auftreten von unerwünschten Arzneimittelwirkungen vorgestellt. Folgende Aspekte weichen von den früheren Empfehlungen ab: Die Dreifachtherapie der sogenannten vollsensiblen Minimaltuberkulose wird bei Erwachsenen nicht mehr empfohlen. Bei der Dosierung von Ethambutol für Erwachsene wird 15mg/kg Körpergewicht als ausreichend angesehen. Für die Therapie der multiresistenten Tuberkulose (MDR-TB) werden vier Zweitrangmedikamente (zusätzlich ggf. Pyrazinamid) empfohlen. Die Dauer der Behandlung einer MDR-TB sollte wenigstens 20 Monate betragen, wobei ein injizierbares Medikament (Initialphase) mindestens über acht Monate gegeben werden sollte. Ciprofloxacin und Ofloxacin spielen bei der Behandlung der Tuberkulose keine Rolle mehr. Außerdem wird empfohlen, jedem Tuberkulosepatienten einen HIV-Test anzubieten, um ggf. eine antiretrovirale Therapie zu ergänzen und die antituberkulöse Therapie entsprechend zu modifizieren. Abstract !Several new international recommendations have been published since the German Central Committee against Tuberculosis (DZK) published its recommendations for drug treatment of tuberculosis (TB) in 2001 and for chemoprevention of latent tuberculosis infection (LTBI) in 2004. These international publications have been integrated in the present new recommendations which describe both the treatment of active TB and preventive treatment, pointing out specific adaptations for Germany. Separate sections deal with the current management of mono-, poly-, and multiresistance or drug intolerance, of TB in children, of different forms of extrapulmonary TB, of LTBI and of special situations such as HIV infection, renal or hepatic insufficiency, infection following BCG instillation in bladder cancer or in case of adverse drug reactions. The following aspects differ from the previous recommendations: A three-drug regimen for the so-called fully susceptible minimal TB is no longer recommended in adults. A dosage of 15 mg/kg body weight of ethambutol for adults is regarded as sufficient. Four secondline drugs (supplemented by pyrazinamide, where appropriate) are recommended for multidrug-resistant tuberculosis (MDR-TB). MDR-TB should be treated over a period of at least 20 months, with an injectable drug administered for a minimum of 8 months (initial phase). Ciprofloxacine and ofloxacine are no longer used to treat TB. It is also recommended to offer an HIV test to all TB patients to complement antiretroviral therapy, if necessary, and to adapt the antituberculous therapy accordingly.

Empfehlungen für das Tuberkulosescreening vor Gabe von TNF-α-Inhibitoren bei rheumatischen Erkrankungen

Due to the increased risk of tuberculosis (TB) under treatment with TNF-alpha-inhibitors for rheumatoid arthritis and other autoimmune diseases, precautionary measures are required before initiating TNF-alpha-inhibitor therapy. Patients should have active TB ruled out and screening for latent TB infection should be performed. The screening should include chest X-ray, complete medical history, and the administration of a highly specific Interferon-gamma-Release Assay (IGRA). As tuberculin skin test (TST) results can be expected to be either false-positive or false-negative in these patients, the TST, as commonly performed in the past, is recommended only for exceptional situations. For chemopreventive treatment of latent TB infection (LTBI), isoniazid is usually given for 9 months.

Neue Empfehlungen für die Umgebungsuntersuchungen bei 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.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Empfehlungen für das Tuberkulose-Screening vor Gabe von TNF-α-Inhibitoren bei rheumatischen Erkrankungen

Due to the increased risk of tuberculosis (TB) under treatment with TNF-alpha inhibitors for rheumatoid arthritis and other autoimmune diseases, precautionary measures are required before initiating TNF-alpha-inhibitor therapy. Patients should have active TB ruled out and screening for latent TB infection should be performed. The screening should include chest X-ray, complete medical history, and the administration of a highly specific interferon-gamma-release assay (IGRA). (In the future, the reimbursement of IGRA tests under an analogue procedure code is expected to be formalized by the application of a code specific to the TB-IGRA procedure.) As tuberculin skin test (TST) results can be expected to be either false-positive or false-negative in these patients, the TST, as commonly performed in the past, is recommended only in exceptional situations. For chemopreventive treatment of latent TB infection (LTBI), isoniazid is usually given for 9 months.

Recommendations for tuberculosis screening before initiation of TNF-α-inhibitor treatment in rheumatic diseases.

Due to the increased risk of tuberculosis (TB) under treatment with TNF-alpha inhibitors for rheumatoid arthritis and other autoimmune diseases, precautionary measures are required before initiating TNF-alpha-inhibitor therapy. Patients should have active TB ruled out and screening for latent TB infection should be performed. The screening should include chest X-ray, complete medical history, and the administration of a highly specific interferon-gamma-release assay (IGRA). (In the future, the reimbursement of IGRA tests under an analogue procedure code is expected to be formalized by the application of a code specific to the TB-IGRA procedure.) As tuberculin skin test (TST) results can be expected to be either false-positive or false-negative in these patients, the TST, as commonly performed in the past, is recommended only in exceptional situations. For chemopreventive treatment of latent TB infection (LTBI), isoniazid is usually given for 9 months.

Drug-Resistant Tuberculosis: A Worldwide Epidemic Poses a New Challenge

BACKGROUND Although the incidence of tuberculosis (TB) in Germany is now declining, the world as a whole faces the threat of a catastrophe that will also affect the industrialized nations. The main reason, aside from TB/HIV co-infection, is the increase of resistant TB strains. The situation is already serious because of the spread of multidrug-resistant TB, i.e., TB that is resistant to the two most important antituberculous drugs, and is being further aggravated by resistance to second-line drugs as well. METHOD Selective review of the literature. RESULTS There are an estimated half a million cases of multidrug-resistant TB worldwide, and so-called extensively resistant TB (XDR-TB), with additional resistance to defined second-line drugs, is now prevalent in more than 45 countries. An accurate assessment of the situation is hampered by a widespread lack of laboratory capacity and/or proper surveillance. The problem is mainly due to inappropriate treatment, which may have many causes, but is theoretically avoidable. Aside from programmatic weaknesses, a lack of diagnostic and therapeutic tools causes difficulties in many countries. DISCUSSION Only rapid and internationally concerted action, combined with intensified research efforts and the support of the affected nations, will be able to prevent the development of a situation that will no longer be manageable even with 21(st)-century technology.

S2k-Leitlinie: Tuberkulose im Erwachsenenalter

Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany.

Empfehlungen zur Diagnostik und Therapie nichttuberkulöser Mykobakteriosen des Deutschen Zentralkomitees zur Bekämpfung der Tuberkulose (DZK) und der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP)

Nontuberculous mycobacterioses comprise a group of diseases caused by mycobacteria which do not belong to the Mycobacterium (M.) tuberculosis complex and are not ascribed to M. leprae. These mycobacteria are characterized by a broad variety as to environmental distribution and adaptation. Some of the species may cause specific diseases, especially in patients with underlying immunosuppressive diseases, chronic pulmonary diseases or genetic predisposition, respectively. Worldwide a rising prevalence and significance of nontuberculous mycobacterioses can be recognized. The present recommendations summarise actual aspects of epidemiology, pathogenesis, clinical aspects, diagnostics - especially microbiological methods including susceptibility testing -, and specific treatment for the most relevant species. Diagnosis and treatment of nontuberculous mycobacterioses during childhood and in HIV-infected individuals are described in separate chapters.

Higher Rate of Tuberculosis in Second Generation Migrants Compared to Native Residents in a Metropolitan Setting in Western Europe

Background In Western Europe, migrants constitute an important risk group for tuberculosis, but little is known about successive generations of migrants. We aimed to characterize migration among tuberculosis cases in Berlin and to estimate annual rates of tuberculosis in two subsequent migrant generations. We hypothesized that second generation migrants born in Germany are at higher risk of tuberculosis compared to native (non-migrant) residents. Methods A prospective cross-sectional study was conducted. All tuberculosis cases reported to health authorities in Berlin between 11/2010 and 10/2011 were eligible. Interviews were conducted using a structured questionnaire including demographic data, migration history of patients and their parents, and language use. Tuberculosis rates were estimated using 2011 census data. Results Of 314 tuberculosis cases reported, 154 (49.0%) participated. Of these, 81 (52.6%) were first-, 14 (9.1%) were second generation migrants, and 59 (38.3%) were native residents. The tuberculosis rate per 100,000 individuals was 28.3 (95CI: 24.0–32.6) in first-, 10.2 (95%CI: 6.1–16.6) in second generation migrants, and 4.6 (95%CI: 3.7–5.6) in native residents. When combining information from the standard notification variables country of birth and citizenship, the sensitivity to detect second generation migration was 28.6%. Conclusions There is a higher rate of tuberculosis among second generation migrants compared to native residents in Berlin. This may be explained by presumably frequent contact and transmission within migrant populations. Second generation migration is insufficiently captured by the surveillance variables country of birth and citizenship. Surveillance systems in Western Europe should allow for quantifying the tuberculosis burden in this important risk group.