[Death due to tuberculosis requiring treatment or an accompanying disease? A contribution to the lethality and mortality of tuberculosis in Germany]. / Tod an behandlungsbedürftiger Tuberkulose oder an Begleitkrankheiten? Ein Beitrag zur Letalität und Mortalität der Tuberkulose in Deutschland.

BACKGROUND: Tuberculosis (TB) is a curable disease. Nevertheless, patients in Germany also die of TB. Although mortality is decreasing, there are indications for an increase in lethality. This observation provided the impetus for a detailed analysis that sought to investigate the validity of the statistics on deaths caused by TB. METHOD: The study population consists of the 926 fatal cases that were classified either as "death from TB" or as "death due to other causes" out of the 6044 TB patients in the DZK study. For the analysis, health authorities were asked to provide additional information and such documents as the death certificate, the autopsy protocol and the final medical report. In 778 cases, there was at least one additional piece of information available. Three teams of two experts each conducted independent evaluations of the documents. RESULTS: Based on the findings of the experts, every second death caused by TB in 1997 and 1998 was not recorded correctly during the post-mortem examination. Every third TB death was not diagnosed during the patient's lifetime. Patients who died due to TB were, on average, older and more likely to be born in Germany. This indicates that age-related comorbidity among the native German population plays a relevant role. Yet, the unicausal death registration did not acknowledge comorbidity as a contributing factor to the fatal outcome. Pulmonary TB with positive microscopy and culture, miliary TB and meningeal TB were more common among the deaths due to TB than among the general study population, and led more often to a fatal outcome than other organ manifestations. However, the two groups did not differ with regard to multi-drug resistant TB. Alcohol abuse was a leading risk factor for death caused by TB in patients under 65 years. Patient's delay ranged from six to 34 days, and doctor's delay from eight to 46 days. For example, alcohol abusers, on average, visited a physician much later, but were diagnosed more rapidly after the first visit than patients who were not alcohol-dependent. A period of 32 - 200 days elapsed between diagnosis and death caused by TB. CONCLUSIONS: The post-mortem examination often missed TB as the cause of death. Many native German TB patients showed age-related comorbidity. Pulmonary TB with positive microscopy, miliary TB and meningeal TB led more often to a fatal outcome than other organ manifestations. Alcohol abuse was a leading risk factor for TB deaths in patients younger the 65 years. The average period between the onset of symptoms and the diagnosis was significantly longer than the one month generally considered acceptable. The experts could not confirm an increase in lethality for the period under investigation.

Demographic characteristics of patients with extrapulmonary tuberculosis in Germany.

The aim of the present study was to determine the demographics of patients with extrapulmonary tuberculosis in Germany. Data on 26,302 tuberculosis cases from a national survey carried out during the period 1996-2000 were analysed. The crude proportion of tuberculosis patients with extrapulmonary manifestations was 21.6%. Extrapulmonary tuberculosis was most likely among females, children aged <15 yrs and persons originating from Africa and Asia. Females tended to be more likely to have any form of extrapulmonary tuberculosis than males, except pleural tuberculosis. The strength of this association was strongest in the age range 25-64 yrs and less pronounced amongst the oldest patients. Children were particularly prone to the development of lymphatic and meningeal tuberculosis, whereas the likelihood of genitourinary tuberculosis increased with increasing age. Asian and African patients were generally more likely than persons from other areas to have lymphatic, osteoarticular, meningeal and miliary tuberculosis. The analysis shows important differences, by age, sex and origin, in the likelihood of a tuberculosis patient presenting with extrapulmonary tuberculosis. Since the relative contribution of the foreign-born to tuberculosis in low-prevalence countries is rising, extrapulmonary tuberculosis must be taken into account more often in the differential diagnostic work-up of these patients, particularly among those originating from Asia and Africa.

Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons.

BACKGROUND: BCG-vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection. METHODS: We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON-TB-Gold In Tube; QFT-G) during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. RESULTS: During a 6-month period, 309 contacts (mean age 28.5 +/- 10.5 years) from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8%) had received BCG vaccination and 84 (27.2%) had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000). For the TST, the positive response rate was 44.3% (137/309), whilst only 31 (10%) showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (kappa = 0.2, with 95% CI 0.14.-0.23), and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7-52.5). In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (kappa = 0.58, with 95% CI 0.4-0.68), increasing to 0.68 (95% CI 0.46-0.81), if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. CONCLUSION: The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

[Interferon-gamma assays -- description and assessment of a new tool in the diagnosis of tuberculosis]. / Interferon-gamma-Tests in der Tuberkulose-Diagnostik -- Aktueller Stand.

Up to now the diagnosis of latent tuberculosis infection (LTBI) was based solely on the tuberculin skin test. However, this method offers neither 100 % sensitivity nor -- and this is in particular due to its cross-reactivity with BCG and environmental mycobacteria -- a 100 % specificity. The demand in Germany for a more reliable in vitro test is currently enhanced by the change from the multipuncture test to the intradermal (Mendel-Mantoux) test and by the uncertainty resulting from the ceased production of the tuberculin previously used in Germany. The manufacturers of immunologic test methods such as the QuantiFERON-TB Gold In-Tube (ELISA assay) and the T SPOT-TB Test (ELISPOT assay), which are based on the Interferon-gamma (IFN-gamma) production of sensitized T lymphocytes, offer their products as possible alternatives. This article explains the function of the IFN-gamma tests and gives an overview of the most recent data, possible indications and the open scientific questions to be investigated by future clinical studies. Although the new test methods have the potential to eventually prevail as an additional helpful diagnostic tool, the authors consider a complete replacement of the tuberculin skin test as premature. The IFN-gamma tests may, however, prove already now to be a useful additional diagnostic method.

[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.

Isoniazid resistance among tuberculosis patients by birth cohort in Germany.

SETTING: Germany, 1997-2000. OBJECTIVE: To determine the prevalence of isoniazid resistance by year of birth among previously treated and untreated tuberculosis patients by country of birth. DESIGN: Univariate and multivariate analyses of data on 8658 cases from a nationally representative sample. RESULTS: The crude prevalence of isoniazid resistance was 2.4% and 9.9% among Germany-born patients respectively without and with a prior treatment history. Among those without a history, there was virtually no difference between quartiles of birth cohorts, while among those with, a large decrease from the oldest to the youngest was observed. Among foreign-born patients, the prevalence of isoniazid resistance increased from 3.8% to 11.8% from the oldest to the youngest among those without, and more than doubled from less than 20% to more than 40% among those with prior treatment. CONCLUSION: This analysis suggests a remarkably constant and low prevalence of isoniazid resistance among never treated Germany-born patients. In contrast, among the diverse group of foreign-born patients, the prevalence increases appreciably from the oldest to the youngest birth cohorts. This indicates that tuberculosis treatment policies in Germany have been sound and that great care is needed to prevent acquisition of additional resistance among foreign-born patients.

[The state of tuberculosis in Germany in 2000]. / Die Tuberkulosesituation in Deutschland 2000.

Tuberculosis is one of the leading infectious diseases globally besides HIV/AIDS and malaria. Around 8 million people per year develop active tuberculosis, of whom 2 million eventually die of the disease. Of special importance to Germany is the epidemiologic situation in the former Soviet Union, where new infections are rising steeply. This region is also a hot spot for the development of multidrug-resistant tuberculosis. In 2000, the WHO registered already 273 000 cases of multidrug-resistant tuberculosis worldwide. In Germany the tuberculosis situation is stable. 9 064 persons (910 less than 1999) had tuberculosis in the year 2000. 5 271 cases were tuberculosis of the respiratory tract with detection of Mycobacteria tuberculosis. In 2 264 cases registered as tuberculosis of the respiratory tract, Mycobacteria tuberculosis could not be detected. 1 529 persons developed extrapulmonary tuberculosis. The highest incidences were found among the elderly. One third of the tuberculosis patients were born outside Germany. Resistance to antituberculous drugs also increased slowly in Germany. A study of the DZK, although with small numbers, demonstrated an increase of multidrug-resistant tuberculosis from 1.2 % (1996) to 1.7 % (2000), which also influenced the treatment outcome. With rising resistance rates, the treatment success decreased from 77.5 % in fully susceptible to 59.5 % in multidrug-resistant cases.

[Sense and nonsense of exposure prophylaxis in communal club installations for children and adolescents -- a contribution to the implementation of the German Defence Against Infection law from a point of view of preventive paediatrics]. / Sinn und Unsinn der Expositionsprophylaxe in Kinder- und Jugendgemeinschaftseinrichtungen (KJGE) -- Ein Beitrag zu den Regelungen des section 34 Infektionsschutzgesetz aus Sicht der präventiven Pädiatrie.

The protection against infections in facilities of the community for infants and children, such as kindergarten, schools and training centres, results first of all from the vaccination practice and hygiene practices. Pertussis, varicella and tuberculosis are examples for this. In some cases the transient avoidance of contacts and the intensified integration of the parents could contribute to the prevention of an infection, e. g. strepptococcus A infections and head louses. The consequential realization of the recommendation of the STIKO (expert panel for vaccination guidelines; http://www.rki.de/GESUND/STIKO/STIKO.HTM) is one of the main pillars of protection by vaccination. Vaccine coverage may also be improved by including these paragraphs in the statutes of day nurseries. Before integration of children into such facilities it should be necessary to verify that there are no doubts about the health conditions. This could be confirmed by presenting the vaccination or check-up card.

Surveillance of tuberculosis in Europe. Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting on tuberculosis cases.

Consensus-based recommendations have been developed by a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis surveillance data in the countries of Europe. A uniform case definition and a minimum set of variables for reporting on each case have been agreed which, when collated on a national basis, will allow comparison of the epidemiology of tuberculosis in different European countries. The Working Group recommends that the case definition includes "definite" cases, where the diagnosis has been confirmed by culture (or supported by microscopy findings in countries where diagnostic culture facilities are not available), and "other than definite cases" based on a clinical diagnosis of tuberculosis combined with the intention to treat with a full course of antituberculosis therapy. Both "definite" and "other than definite" cases should be notified by physicians and, in addition, laboratories should be required to report "definite" cases. The minimum set of variables to be collected on each case of tuberculosis should include: date of starting treatment, place of residence, date of birth, gender, and country of origin, to characterize the patient. Recommended disease-specific variables include: site of disease, bacteriological status (microscopy and culture), and history of previous antituberculosis chemotherapy. The minimum set of variables should be collated on all patients and should be as complete as possible. Additional variables may be collected for individual, local or national purposes, but, in general, completeness of reporting on cases is likely to be better if the information requested is kept to a minimum. Timely reporting of cases is essential for appropriate public health action. Cases should be reported to the health authority at the local and/or regional level within 1 week of starting treatment. Individual-case based information should be reported to the national level by the local or regional level. Feedback to reporters is essential. At the national level, preliminary quarterly reports should be produced and final reports should be published annually.