[Current epidemiology of tuberculosis in Germany]. / Aktuelle Epidemiologie der Tuberkulose in Deutschland.

BACKGROUND: In addition to malaria and HIV/AIDS, tuberculosis (TB) is one of the world's most important infectious diseases. Also in Germany tuberculosis still remains a relevant public health problem that needs special attention. OBJECTIVES: This article provides an overview of the tuberculosis epidemiology in Germany with emphasis on drug resistance and population groups that are predominantly affected. METHODS: Based on surveillance data provided in the notification system, the TB-situation in Germany is presented-particularly with respect to drug resistance, origin of patients (country of birth and nationality) and treatment outcome. RESULTS: Since 2009, the continuous decline in case numbers has slowed down and is now stagnating as observed in several other industrialized nations. Since 2007, the proportion of foreign-born patients has continuously increased and accounts for over half of all cases registered in Germany. Special attention deserves the current drug resistance situation: With a proportion of 3.4% in 2013, multidrug-resistant tuberculosis (MDR-TB) has increased significantly compared to the previous year (2.1%) and the rate is therefore higher than in many other European low-incidence countries. Particularly high levels of MDR-TB were observed among foreign-born patients originating from a former Soviet Union country. On average, treatment success was observed in 79% of the cases. Thus, Germany does not reach the WHO target of 85% treatment success. Stagnating case numbers together with the observed drug resistance trend clearly indicate the need for continued efforts in tuberculosis control in Germany including focused strategies for the most affected population groups.

Bacteriological confirmation of pulmonary tuberculosis in children with gastric aspirates in Germany, 2002-2010.

OBJECTIVE: To assess bacteriological confirmation of pulmonary tuberculosis (TB) in children using nucleic acid amplification tests (NAAT) and culture of gastric aspirates in Germany. DESIGN: We analysed 2002-2010 TB notification data to determine the use of gastric aspirates, NAAT and culture performance, including test agreement among pulmonary TB patients aged <15 years (grouped into <1, 1-4, 5-9 and 10-14 years). RESULTS: Gastric aspirates were used among 59% (769/1307) of the patients with available diagnostic information. For 454 patients, gastric aspirates were the only reported specimen, and both NAAT and culture were performed. Among these, culture was positive in 53% (95%CI 48-58), NAAT in 48% (95%CI 44-53) and either test in 63% (95%CI 59-68), with an overall test agreement of 74% (95%CI 70-78). Infants < 1 year had the highest positivity rate (79%, 95%CI 68-88, either test). Test agreement was the highest among 10-14 year olds (79%, 95%CI 67-89). CONCLUSIONS: Routine notification data document a wide use of gastric aspirates and high yield of both NAAT and culture for bacteriological confirmation of TB with gastric aspirates, particularly in infants. Imperfect test agreement supports the combined use of molecular assays and culture-whenever available-in the diagnosis of childhood TB.

The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009.

Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main organ affected is the lung. This might lead to underestimate extrapulmonary TB (EPTB) forms, where in addition to the lung other sites are affected by TB. In Germany, TB notification data provide the main site and the secondary site of disease. To gain an overview of all the different EPTB forms, we analysed German TB notification data between 2002 and 2009 using information on both main and secondary disease site to describe all individual EPTB forms. Further, we assessed factors associated with meningitis using multivariable logistic regression. Solely analysing the main site of disease, lead to one third of EPTB manifestations being overlooked. Case characteristics varied substantially across individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis as main or secondary site. Of those, 105 (25%) of the 415 with available information had died. Multivariable analysis showed that meningitis was more likely in children younger than five years and between five and nine years-old (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40­7.07 and OR: 2.65; 95% CI: 1.40­5.00), in females (OR: 1.42; 95% CI: 1.17­1.73), and in those born in the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI: 1.66­3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02­2.23). Overall, EPTB manifestations, including meningitis, which is often fatal, were underestimated by routine analysis. We thus recommend using all information on disease manifestation generated by surveillance to monitor severe forms and to transfer the gained knowledge to TB case management where awareness of EPTB is most important.

Tuberculosis surveillance and control in Germany - An application of the Berlin Declaration Monitoring and Evaluation Framework.

BACKGROUND: In 2007, the 'Berlin Declaration on Tuberculosis' (BD) was signed by the Ministers of the WHO European Region Member States (MS) to address the re-emerging threat of tuberculosis (TB) by fully implementing the Stop TB strategy. WHO Euro developed a Monitoring and Evaluation (M&E) Framework using programmatic and epidemiological indicators to follow-up the BD from 2013 onwards. Ahead of this, we explored the Framework performance for Germany, a low TB incidence country. METHODS: We selected from a surveillance perspective on five country-specific indicators asked for all MS. Information sources included guidelines, notification data and laboratory quality assurance results. RESULTS: As to national TB guidelines (indicator 1.1.1), up-to-date guidance documents are available. Regarding external quality assurance (3.2) proficiency testing confirms high quality of culture and drug-susceptibility testing. M/XDR-TB prevention and control is reflected by a 1.7% MDR-TB rate in 2010 with decreasing tendency (4.1.2). As to treatment success (5), the WHO target of 85% is reached for all age groups except the elderly ≥60 years. Germany disposes of an electronic case-based surveillance providing evidence for TB policy and practices (5.2.2). CONCLUSIONS: The selected M&E Framework indicators proved well applicable to a low-incidence country. The results show no specific gaps in TB surveillance and control in Germany.

[Legionella in drinking water : outcomes of an exchange of ideas on the prevention of waterborne legionellosis]. / Legionellen im Trinkwasserbereich : Ergebnisse eines Fachgespräches zur Prävention trinkwasserbedingter Legionellosen.

Although much is known about Legionella and the illness they cause, the relationship between their concentration in water and the risk of infection remains unclear. A comprehensive body of experience shows that the growth of Legionella in heated water distribution systems can be effectively controlled by following the preventive measures described in the generally acknowledged codes of practice. As orientation to trigger action, a technical action level of 100 colony-forming units in 100 ml water has found wide acceptance as the maximally tolerable concentration of Legionella in drinking water hygiene. However, this value as well as the concept for controlling the growth of Legionella in installations has developed historically. In part, the focus differs between drinking water hygiene and hospital hygiene. Also, there is no harmonized European approach for controlling Legionella. In spite of such differences, there are important international parallels in the assessment of the occurrence of Legionella, in experience with controlling them, and in recommendations for prevention. There is a need particularly for adequate studies to clarify the risk of infection as well as for the publication of existing data and experience showing the efficacy of measures for prevention, disinfection and system upgrading. Such data are necessary to support evidence-based prevention of Legionella infections and to create a better epidemiological data base in Germany. One chance for reaching this target would be to improve practices in diagnosis, reporting and central data evaluation-not only of illness, but including also data on Legionella occurrence. More frequent Legionella testing of pneumonia patients is a prerequisite for this, but particularly also for the rapid identification and removal of the source of infection. Further requirements include better training of planers, plumbers, and operators of drinking water installations about the approach to preventing Legionella contamination of drinking water installations described in standards and guidelines. The further development of practicable concepts for effective Legionella prevention requires good collaboration between public authorities responsible for drinking water and hospital hygiene on the federal and state levels and experts for the prevention of infection, hygiene, and sanitary installations.

[Epidemiology of Legionnaires' disease in Germany]. / Epidemiologie der Legionärskrankheit in Deutschland.

Legionnaires' disease (LD) is a severe form of pneumonia which is caused by bacteria of the genus Legionella. They are widespread in fresh water and can also colonize technical water systems where they might present an infection risk. Since 2001, notification of laboratory-confirmed LD is mandatory in Germany. From 2001-2009, a total of 3672 cases of LD were registered. During the first 7 years, case numbers increased (2001: 127; 2007: 536 cases) but have remained stable during the past 2 years (2008: 525; 2009: 503 cases). In 2009, 49.6% of cases were attributed to an infection in the community, 33.2% were travel associated, and 13.6% were nosocomial. The average case fatality rate between 2001 and 2009 was 6.5%. However, the case fatality rate of nosocomial cases was three times as high compared to cases with non-nosocomial exposure. The network for community-acquired Legionnaires' disease (CAPNETZ) estimates that there are 20,000 cases per year in Germany. Thus, the number of reported cases represents only a small proportion of the actually occurring cases. It is likely that specific LD-diagnostics are insufficiently used. Hence, physicians should test more patients with pneumonia for LD. In particular, because of the high case fatality, nosocomial pneumonia cases need to be tested; identified LD cases require rigorous investigational and corrective action. In order to obtain evidence-based data on the relationship of water contamination and the risk for LD, it would be desirable, if (in addition to the patients' epidemiological data) the results of water texts relating to a given case were also reported systematically.

[Epidemiology of tuberculosis in the world and in Germany]. / Epidemiologie der Tuberkulose in der Welt und in Deutschland.

Tuberculosis (TB) remains one of the most important infectious diseases worldwide. The seemingly unstoppable spread of drug-resistant TB strains, particularly in the European region, make it a continuing threat even to industrialized nations such as Germany. Therefore, effective TB control measures must not be neglected despite declining case numbers in this country--on the contrary. Detailed knowledge of the epidemiological situation and of resistance rates must be the basis for effective control strategies and for the introduction or improvement of national TB and HIV control programmes. There is likewise a need for intensified long-term research into new antituberculous substances, simple and reliable diagnostic methods, and a highly protective vaccine.

[The current status of tuberculosis in Germany and impact of the global situation]. / Die aktuelle Tuberkulosesituation in Deutschland und die Auswirkungen der globalen Situation.

Tuberculosis (TB), like HIV/AIDS and malaria, belongs to the most frequent infectious diseases worldwide. About one-third of the world's population is infected with Mycobacterium tuberculosis (M. tuberculosis), and 5-10 % of those infected develop tuberculosis in the course of their lives. It is estimated that there were approx. 8.9 million new infections worldwide in 2004, representing an incidence of approx. 140/100,000. 3.9 million cases (62/100,000) were classified as smear positive. It is assumed that one smear-positive patient infects about 10-15 other people in the course of one year, and the infection risk is particularly high in HIV-positive persons. For Germany as a low-incidence country, the impact of growing global migration is a key point for future effective prevention of infection. Although the incidence of tuberculosis in Germany is decreasing according to the Robert Koch Institute, public health authorities should nevertheless consider the possible re-import of this infectious disease as a serious problem, in particular in view of the rising resistance rates.

Legionnaires' disease outbreak associated with a cruise liner, August 2003: epidemiological and microbiological findings.

Eight cases of Legionnaires' disease were identified among the 215 German passengers after a cruise to the Nordic Sea in August 2003. An unmatched case-control study was conducted to identify risk factors and the source of infection. In total, eight passengers fulfilled the case definition, one of these died. Forty-two passengers served as controls. The attack rate was 4%. The mean age was 60 years for cases and 62 years for controls. Prolonged exposure to the spa pool seemed to be a risk factor of infection (OR 4.85, P=0.09). Legionella pneumophila serogroup 1, monoclonal antibody (mAb) subgroup 'Knoxville' was isolated from clinical and environmental samples. DNA sequence-based typing revealed that these isolates were indistinguishable from each other. The investigation showed the importance of an interdisciplinary approach of microbiology and epidemiology as not all sites on the ship that tested positive for L. pneumophila actually posed a relevant risk for the passengers.

[Tuberculosis in Germany in 2001 and 2002]. / Die Tuberkulosesituation in Deutschland 2001 und 2002.

The implementation of the new law on infectious diseases in 2001 and the resulting notification of more detailed variables has led to a better knowledge about the epidemiology of tuberculosis (TB) in Germany. 7,515 new cases of active tuberculosis were notified to the Robert Koch Institute in 2001, and 7,684 cases in 2002, corresponding to an incidence of 9.1 (2001) and 9.3 (2002) per 100,000 inhabitants (as per 1 October, 2003). The slight increase in new cases in 2002 is most likely due to under-notification in 2001 because of the new system, considering that the previous decline over many consecutive years is continued according to the incidence for 2003 (8.7/100,000; n = 7,184). In 2001 as well as in 2002 42 % of new TB patients were born outside Germany, and those of foreign nationality have a five-fold higher incidence on the average than German citizens. The lung remains the most affected organ (80 %). 4,230 (2001) and 4,267 (2002) were cases of open, i. e., bacteriologically confirmed, pulmonary tuberculosis potentially contagious to their immediate contacts. The resistance rates are stable in the indigenous population, while patients coming from countries with high resistance rates reflect the situation in their countries of origin. Over two thirds of TB patients in Germany are hospitalized at some point during their disease. The treatment results (78 % on the average in 2001) do not reach the WHO target of 85 %. Approximately 7 % of TB patients in Germany still die because of this infectious disease.

An outbreak of Salmonella München in Germany associated with raw pork meat.

In summer 2001, an outbreak of Salmonella München occurred in Germany. We conducted descriptive epidemiology and hypothesis-generating interviews among case patients, two retrospective cohort studies, and a case-control study of suboutbreaks. We performed pulsed-field gel electrophoresis (PFGE) from selected patient isolates and a limited trace-back investigation for analytical purposes. Four states were consecutively affected: Saxonia (SX), Brandenburg (BB), Berlin (BE), and Baden-Württemberg (BW). Although hypothesis-generating interviews failed to identify a plausible food item, descriptive data and investigations of the suboutbreaks suggested pork meat as a probable source in three states (SX, BB, and BE) but not in BW. The PFGE profiles from isolates of case patients in the first three states were indistinguishable but differed from PFGE profiles of case patients in BW. Trace-back investigation suggested that contamination of pork meat occurred early in the rearing-production chain. This outbreak demonstrates how contamination early in the production process that can yield different end products may complicate multistate outbreaks. Investigation of suboutbreaks and use of the trace-back method as investigational tools may be useful adjuncts in solving the problem of multistate outbreaks.

[Survey among local health departments concerning the implementation of the new infectious disease reporting system]. / Befragung der Gesundheitsämter zur Umsetzung des Meldewesens nach dem Infektionsschutzgesetz.

The Infectious Disease Control Act enacted in Germany in January 2001 led to the establishment of a new reporting system for infectious disease. The implementation of this system was evaluated to identify opportunities for further improvement. In a survey of all German local health departments the following criteria were analyzed: resources (staff and technical equipment), information needs (satisfaction with current offers/further training requirements), data analysis (extent of local data analysis/feedback of national data), and acceptability (case definitions/electronic reporting). In local health departments, 11% of the staff were assigned to the infectious disease reporting system. Data were processed mainly by nonmedical staff (78.4%). A computer work-station is available for most staff members. One-third of the local health departments uses the RKI software "SurvNet@rki" for data transmission. All others use commercial software. Experience with the electronic reporting system was rated as very good/good by 47.1% of local health departments, as satisfactory by 44.5%, and as problematic by 8.4%. Most of the local health departments were satisfied with the offers of information provided by RKI (96.4%) and state health departments (83.7%), respectively. However, 49.1% of the local health departments saw a need for further education and training. The implementation of case definitions was supported by 95% of the local health departments, but transmission criteria were criticized. In summary, the new infectious disease reporting system in Germany was successfully implemented. However, the system could be improved through reduction of software problems concerning electronic data processing and transmission, expansion of current offers of in-formation and provision of special staff training programs, and revision of the case definitions concerning clearness and simpler handling.

Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial.

OBJECTIVE: Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. In addition. only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV-infected depressive patients was investigated. METHODS: In this open trial, amantadine was added to antidepressive and or mood-stabilizing compounds treating BDV-infected depressed patients (n = 25) with bipolar or major depressive disorders. Amantadine was given twice a day (100-300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM-D) and/or with an operationalized diagnostic criteria system (OPCRIT: version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples. RESULTS: The overall response rate of the amantadine augmentation in the BDV-infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity. CONCLUSION: Amantadine appears to show a remarkable antidepressive efficacy in BDV-infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.

Amantadine revisited: an open trial of amantadinesulfate treatment in chronically depressed patients with Borna disease virus infection.

Amantadinesulfate is a well known substance which has proven useful in the treatment and prophylaxis of viral infections, in treating symptoms of Parkinson's disease, cocaine dependence, and apathy in multiple sclerosis. It has also been reported as having mild antidepressive effects not sufficient to warrant its use as an antidepressant. Striking antidepressive effects in some patients have been attributed to its antiviral activity against human Borna disease virus (BDV) infection which is frequently seen in patients with depressive episodes. In this 8 to 12 week open study of oral amantadine in 30 depressed patients with various states of BDV infection we found a significant antidepressive response in 19 of 30. Peripheral BDV antigen indicating acute infection was cleared in both responders and non-responders, but only in responders peripheral infection was significantly reduced.