Association of extra-pulmonary tuberculosis with age, sex and season differs depending on the affected organ.

SETTING: Data from tuberculosis (TB) cases in Germany who are continuously monitored for the purposes of epidemiological surveillance and disease control. OBJECTIVE: To examine the distribution of age, sex, place of birth, seasonality and recurrence of TB disease in different types of TB organ manifestations, with particular focus on lymph nodes and pleura. DESIGN: All TB cases reported to the Berlin State Office for Health and Social Affairs (LAGeSo) in Berlin, Germany, between 2001 and 2012 were analysed. RESULTS: Significant differences with regard to seasonal variation as well as age and sex distribution were seen when comparing pleural TB and TB of the extrathoracic lymph nodes, the predominant types of extra-pulmonary TB. EPTB was generally more prevalent in patients born outside Europe. In contrast to a previous study, an increase in recurrent TB was not observed in EPTB when compared to pulmonary TB cases. CONCLUSION: Significant differences in TB organ manifestation in association with season, sex and age suggest different pathophysiological mechanisms of disease development. Future studies might provide further insight into the mechanism of TB development and may therefore be of help in the prevention and treatment of EPTB.

Autochthonous dengue virus infection in Japan imported into Germany, September 2013.

In September 2013, dengue virus (DENV) infection was diagnosed in a German traveller returning from Japan. DENV-specific IgM and IgG and DENV NS1 antigen were detected in the patient's blood, as were DENV serotype 2-specific antibodies. Public health authorities should be aware that autochthonous transmission of this emerging virus may occur in Japan. Our findings also highlight the importance of taking a full travel history, even from travellers not returning from tropical countries, to assess potential infection risks of patients.

[Tinea corporis]. / Tinea corporis.

Between February 2011 and April 2012, an outbreak caused 55 episodes of Tinea corporis in a Berlin kindergarten. According to the case definition Tinea corporis was confirmed in 2 cases, 16 cases were dermatologically probable, 24 cases were suspicious, whereas 13 cases were viewed as improbable. 48% (n=32/67) of all children had at least one episode of disease. Of those aged 4-6 years 76% (n=29/38) were affected, compared with 10% (n=3/29) of those younger than 4 years. Despite comprehensive hygienic measures being taken, the outbreak could not be quickly controlled. To stop the outbreak the immediate cooperation of public health service and medical staff, kindergarten employees, parents and children was necessary. The timely involvement of dermatologists along with a uniform treatment approach turned out to be of major importance. The recommended long treatment duration over several weeks affected adherence to treatment. Overall, the extended treatment in the kindergarten of affected skin areas of children proved to be the most effective measure for the control of the outbreak.

Giardiasis in kindergartens: prevalence study in Berlin, Germany, 2006.

In Germany, an increase of notified giardiasis was observed between 2002 (n = 3,101) and 2007 (n = 3,651) with 62% of cases acquired in Germany. The highest incidence was reported in 1- to 5-year-olds (2001-2007, 11.5/100,000 on average) and Berlin is one of the most affected states (17.5/100,000). We performed a cross-sectional study in five Berlin kindergartens differing in socioeconomic status and migrant proportion in order to estimate the prevalence and investigate routes of transmission among children under 6 years of age. Stool samples were screened for Giardia lamblia and Cryptosporidium parvum using microscopical and antigen detection. Giardia-positive samples underwent PCR and subtyping. Two hundred two children participated (mean age 3.4 years). We found three girls (1.5%) who tested positive for G. lamblia genotype-A3, all clustering in one kindergarten (prevalence 5.5%). No common source was identified. Two children were symptomatic. Possible dog-to-child transmission was established for one of the symptomatic cases. All contact-tracing results were negative. Other microscopically detected parasites (Blastocystis hominis, Endolimax nana cysts, Entamoeba coli cysts and Iodamoeba bütschlii cysts) were found in 4% of children. In summary, a substantial level of Giardiasis may be prevalent in some of Berlin's kindergartens, despite standard hygienic measures being followed. The relatively high prevalence in one kindergarten indicates the need for further studies to identify risk factors for children, which may help to guide possible interventions and strategies. Giardiasis should be considered as a differential diagnosis in children with unclear gastrointestinal symptoms. Additional education and training on proper toilet and food hygiene may further reduce the possibility of child-to-child transmission.

[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.

[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.

[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.

[Latent tuberculosis infection: recommendations for preventive therapy in adults in Germany]. / Latente tuberkulöse Infektion: Empfehlungen zur präventiven Therapie bei Erwachsenen in Deutschland. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

The immunologic mechanisms of latent tuberculosis (TB) infection are complex and hitherto not completely understood. The lifelong risk of an immunocompetent individual of developing active TB after infection with M. tuberculosis is 5-10 % and highest during the first two years after infection. Various factors may considerably increase the risk of developing active TB, e. g., immunosuppressive disease or immunosuppressive medication. However, the development of active TB may be avoided by preventive chemotherapy, the therapy of choice being isoniazid over a 9-month period. Alternative treatment regimens may be indicated in special cases, but it must be borne in mind that the efficacy of these regimens has not been studied sufficiently while they seem to be less well tolerated than isoniazid monotherapy. The tuberculin skin test is still the only sufficiently documented method to detect latent infection with M. tuberculosis which is also suitable for routine application. This test today should be performed exclusively as described by Mendel and Mantoux. Its sensitivity and specificity depend on the prevalence of tuberculosis infection. It should therefore be restricted to individuals at increased risk of latent TB infection. When interpreting the tuberculin skin test, it is necessary to know whether an individual belongs to one of the defined risk groups or has an elevated risk of developing active TB. Among the risk groups are individuals who may have been infected recently with M. tuberculosis (contacts of contagious TB patients) or in whom other factors increase their risk of developing active TB. The indication for chemotherapy for latent TB infection must be based on a careful individual risk-benefit analysis and, besides patient compliance, requires full information of the patient and careful monitoring during therapy. Before initiating treatment, active TB must always be excluded by the proven methods.

[Recommendations for personal respiratory protection in tuberculosis]. / Empfehlungen zur Anwendung von Atemschutzmasken bei Tuberkulose - Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

These recommendations of the German Central Committee against Tuberculosis give an overview of the current scientific knowledge on the tuberculosis risk of health service employees and on the risk of infection in individual areas of work. The efficacy of face masks and their benefit in tuberculosis control is discussed. There are no reliable data on the efficacy of face masks in preventing infection with M. tuberculosis, nor can such data be expected in the near future, due to the complex interaction of infection-preventing measures. As rapid case finding, isolation, and immediate, effective treatment of infected patients already greatly diminish the risk of transmission, we consider face masks to be of limited use in reducing this risk. However, they may be beneficial in certain areas of work and in certain situations, particularly in the presence of elevated aerosol concentrations. The benefit of face masks depends largely on their correct application. The choice of a particular type of mask requires knowledge of the current epidemiological situation, and a competent assessment of the risk in the area of work for which it is chosen, taking into account the closeness of contact with potentially infectious tuberculosis 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.

Strategies against multidrug-resistant tuberculosis.

The rise of multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis showing resistance to at least isoniazid and rifampicin, is a serious threat to tuberculosis control in some high prevalence countries and may have some impact on low prevalence regions as well. The World Health Organization estimates that 50 million people worldwide are infected with MDR-TB, and that, in the year 2000, 273,000 (3.1%) MDR-TB cases were among the 8.7 million new tuberculosis cases. In 1998, the highest MDR-TB rates among new cases and the highest combined (new and previously treated cases) MDR-TB rates were found in Estonia (14.1 and 18.1%), Henan province in China (10.8 and 15.1%), Latvia (9.0 and 12.0%), and Ivanovo Oblast (9.0 and 12.3%) and Tomsk Oblast (6.5 and 13.7%) in the Russian Federation. The risk factors for MDR-TB are previous treatment or relapse, originating from "hot spot" areas, a history of imprisonment, homelessness and possibly also human immunodeficiency virus. The treatment of multidrug-resistant tuberculosis is difficult due to side-effects and a treatment duration of up to 3 yrs, which is expensive and often unsuccessful. Therefore, strategies for the treatment and prevention of multidrug-resistant tuberculosis are urgently required. This requires functioning tuberculosis control programmes (directly observed treatment short course), and, in some high prevalence countries, the introduction of second-line drugs on the basis of appropriate susceptibility testing (directly observed treatment short course-Plus). Only the future will show whether this "ticking time bomb" can be defused.