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Treasure trove of data from Ulm helps in the understanding of community-acquired pneumonia

CAP, community-acquired pneumonia, is a common type of pneumonia that mainly affects young and old people. In Germany, around 800,000 people contract CAP every year and almost one third has to be admitted to hospital – exceeding the number of admissions due to cardiac infarction or stroke. Experts estimate that the costs arising from the treatment of CAP are more than 500 million euros per year. Around six to eight per cent of all CAP cases are fatal, making CAP the sixth most frequent cause of death in Germany. The CAPNETZ competence network, which up until recently was funded by the German government, is gradually shedding light on a hitherto little known disease.

CAP is the most common infectious disease in the world. In the USA, between two and three million CAP cases are diagnosed every year. This makes community-acquired pneumonia the most frequent cause of infection-related deaths in developed countries. Streptococcus pneumoniae is the most common cause of lower respiratory tract infections worldwide. The disease has an estimated incidence of between 1 and 11 people out of 1000 worldwide, affecting between 68 and 114 people out of 1000 in nursing homes.

CAP
Pneumonia in non-immunocompromised patients caused by pathogens in private or professional environments, i.e. in people who have not recently been hospitalised, is referred to as community-acquired pneumonia (CAP). This includes pneumonia that is diagnosed within two days of hospitalisation. In two thirds of all CAP cases, chronic-obstructive pulmonary diseases, advanced age (65 years or more), smoking, chronic liver and kidney diseases, diabetes mellitus, a previous influenza infection as well as aspiration-predisposing factors are regarded as the major risk factors for CAP.

An excellent database is now available for research

Streptococcus pneumoniae is the major cause of community-acquired pneumonia in Germany. © Tim Pietzcker/Ulm University Hospital

Prior to the establishment of CAPNETZ, reliable data on the pathogen spectrum, the resistance of the pathogens, the course of disease and effective outpatient treatment were not available. Nor was there any reliable data on the application of international recommendations on the diagnosis and therapy of CAP in Germany and on the interaction of pathogens with the host cells.

In order to rectify this situation, the CAPNETZ competence centre was established on the initiative of doctors from Berlin, Hanover and Ulm and was initially funded by the German Federal Ministry of Education and Research. Despite the federal funding coming to an end, the work has continued since 1st February 2010 thanks to the establishment of a foundation. For Heike von Baum, infectiologist and head of the Division of Hospital Hygiene at Ulm University Hospital, the continuation is evidence that CAPNETZ has generated important and excellent data, the acquisition and analysis of which merited the continuation of the project.

Since 2002, CAPNETZ has been pursuing a systematic and interdisciplinary approach, involving a broad range of research groups from all relevant areas of medicine: GPs, clinicians, microbiologists, virologists, epidemiologists and computer specialists. Around 7,000 CAP sufferers in Germany have been registered in order to obtain and compare clinical and microbiological data. Under the management of Heike von Baum, these data have been collected and are maintained in a central material- and database in Ulm.

Better prospects for patients

Radiological evidence: the photo shows inflamed lungs. The CAPNETZ competence centre brings together groups from all medical areas in order to acquire Germany-specific data. © CAPNETZ

The researchers and doctors from Ulm are focusing on gaining a detailed understanding of the pathogens and obtaining insights into the risk factors that lead to the disease. According to von Baum, the data acquired by CAPNETZ represent one of the largest studies worldwide. The study is characterised by identical microbiological standards, takes also into account critical seasons (autumn and winter) and a period of many years. In addition, the data were collected in all German regions, and hence do not underlie geographic particularities. "The Ulm data collection is not only a lively source for research work, but has also considerably improved the prospect of individual patients receiving appropriate treatment," said Heike von Baum.

The data were acquired from adult individuals (aged 18 upwards) who had not previously been hospitalised or treated with antibiotics for at least six weeks. The study excluded special cases, TB patients and children because of the completely different pathogen spectrum. "The strict diagnosis that is also as comprehensive and standardised as possible transforms the data collection into a treasure trove that identifies all known pathogens, both atypical and viral ones," explains Heike von Baum.

The diagnostic methods used involve the conventional cultivation of the bacterial pathogens on culture plates, a urine antibody test for the detection of pneumococcae and legionellae, a molecular biological examination in which DNA is isolated from respiratory material and analysed for the presence of atypical pathogens (those that do not grow on standard culture plates) and viruses. In addition to these methods, serological examinations were used to provide further information.

The CAPNETZ data provide the first reliable information on other pathogens in Central Europe. The data show that more than 90 per cent of all community-acquired pneumonia types are caused by bacteria, in particular by Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. Severe pneumonias are often caused by Staphylococcus aureus, Klebsiella pneumoniae and Legionella pneumophila (which have recently led to a number of Legionella infections in the Ulm area).

CAPNETZ's next objective is to obtain more data from outpatient treatment, since the majority of data up until now has been obtained from hospitalised patients. In Germany, pneumococcae have also been identified as the major cause of community- and hospital-acquired pneumonia. This is in line with other worldwide data.

A pathogen affects mainly young people

In a CAPNETZ study involving more than 4,500 patients, Heike von Baum found that Mycoplasma pneumoniae is one of the most frequent pathogens that lead to CAP (6.7 per cent of all CAP patients), mainly affecting younger patients who have a limited number of or no other diseases. In the majority of cases, this type of CAP is very mild. The majority of CAP patients were treated on an outpatient basis, since the course of the disease was less serious than in hospitalised patients. In addition to Chlamydiphila pneumoniae, M. pneumoniae is therefore the only bacterial pathogen that affects the respiratory tract, and that most frequently occurs in young adults under the age of forty. Von Baum and her colleagues therefore do not believe that the double treatment of patients with mild CAP, which also counteracts atypical pathogens, should be used as standard therapy for such cases. However, researchers are convinced that such patients need to be treated with antimicrobials that target pneumococcae.

Legionellae – no longer a distant danger

Legionellae bacteria recently led to the deaths of five elderly people in the Ulm area. © Tim Pietzker/Ulm University Hospital

In 2008, von Baum and her colleagues found that Legionnaires’ disease was no longer a disease restricted to the Mediterranean area. Based on the CAPNETZ data, the authors calculated that around 30,000 cases of Legionnaires’ disease occur in Germany every year. Legionella pneumonia was detected in 3.8 per cent of non-hospitalised and hospitalised patients. It is worth noting that the diagnostic methods used were unable to detect other subtypes. At the beginning of 2010, the researchers’ assumptions were confirmed by Legionella infections that occurred in the Ulm area where five people died from a disease caused by Legionella pneumophila, and several dozen people became infected. A large water cooling system in the centre of Ulm was identified as the source of the infection.

Not yet a resistance problem

Heike von Baum does not anticipate the danger of multiresistant pathogens arising in Germany, as occurred in Spain as a result of the uncontrolled use of antibiotics, leading to major problems due to penicillin-resistant pneumococcae. Many CAPNETZ findings were included in the S-3 (i.e. evidence-based) guideline, which provides recommendations for GPs and also recommends the use of certain therapies, including the use of certain antibiotics. “The severity score is of great practical help, especially for general practitioners. Using the slightly modified and simplified CAPNETZ score, simple clinical examinations provide information as to which patients need to be hospitalised and which patients can be treated on an outpatient basis.

Patients are the greatest beneficiaries of the success

In addition to a broad range of insights obtained in basic research, reliable data are now available on the pathogens that cause CAP as well on the incidence of CAP in Germany. Von Baum also believes that these data can be transferred to the situation in Central Europe as a whole. Thanks to CAPNETZ, it has been possible to publish guidelines based on rational fundamentals. Von Baum is sure that the recommendations on the diagnosis and the prescription of suitable drugs are gradually leading to a successful outcome. The data obtained in the CAPNETZ competence centre, which is the only project in Central Europe to provide information about the incidence of community-acquired pneumonia cases caused by Legionella, were also highly applicable to the treatment of the recent cases of Legionnaires’ disease in Ulm.

Von Baum also highlighted that the CAPNETZ activities have now reached a phase in which certain therapies are being reconsidered in order to ensure optimal and timely treatment. The CAPNETZ researchers have got plenty to work on in the future. For example, they are planning to look into the genetic predisposition of patients to certain infectious diseases, geographic particularities and the question as to which pneumococcae subtypes cause which diseases.

Literature:

  • von Baum/Welte et al.: Mycoplasma pneumoniae pneumonia revisited within the German Competence Network for Community-acquired pneumonia (CAPNETZ), BMC Infection Diseases 2009, 9:62, doi:10.1186/1471-2334-9-62)

  • Von der Poll/Opal: Pathogenesis, treatment, and prevention of pneumococcal pneumonia, in: Lancet, Vol. 374, 31/10/2009, p. 1543ff.)

  • Von Baum/Ewig, et al.: Community-acquired Legionella Pneumonia: New Insights from the German Competence Network for Community Acquired Pneumonia, Clinical Infectious Diseases, 2008, 46: 1356-64, doi: 10.1086/586741

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