Alveolar echinococcosis

from Wikipedia, the free encyclopedia
Classification according to ICD-10
B67.5 Echinococcus multilocularis infection [alveolar echinococcosis] of the liver
B67.6 Echinococcus multilocularis infection in multiple and other locations
B67.7 Echinococcus multilocularis infection, unspecified
ICD-10 online (WHO version 2019)

The alveolar hydatid disease is an emerging but still rare parasitic disease of humans. It is caused by the larval stage of the fox tapeworm ( Echinococcus multilocularis ) and is usually fatal if left untreated. Humans represent a false intermediate host , since the development cycle of the fox tapeworm does not go beyond them.

In addition to alveolar echinococcosis, there are other human diseases caused by echinococci; cystic echinococcosis is transmitted by dog tapeworms and represents around 90 percent of human echinococcosis cases worldwide. The causative agents of polycystic echinococcosis , which occurs very rarely in South and Central America, are Echinococcus vogeli , a parasite of native wild dogs, and E. oligarthra , the main host that attacks felids .

Pathogen

Alveolar echinococcosis is caused by an infection with the first larval stage of the fox tapeworm ( Echinococcus multilocularis , syn. E. alveolaris ). With a length of only a few millimeters, the fox tapeworm is a very small representative of the tapeworms , of which individual species can be several meters long. Its distribution area extends over the temperate to cold-temperate climatic zones of the northern hemisphere. In Europe, its distribution center is in Central Europe, especially in parts of Germany, Austria, Switzerland and France, where there are island-like areas with very high population density within large areas with little or no frequency. Since the end of the 20th century, there has been an expansion, particularly towards Western Europe and Eastern Europe.

As the main host, the fox tapeworm primarily infects members of the Vulpes genus , in Central Europe, Asia and North America the red fox ( Vulpes vulpes ) and in the circumpolar regions the arctic fox ( Vulpes lagopus ). In North America the coyote ( Canis latrans ) plays an important role as a host and in China the domestic dog . Small mammals, especially voles , which are the most common intermediate hosts in Germany, serve as intermediate hosts. In humans, it is a false intermediate host, since the life cycle of the parasite expires with the death of its host.

Occurrence

The occurrence of alveolar echinococcosis is linked to the geographical distribution of the fox tapeworm , apart from the possibility of entering patients who are already infected . Diseases only occur in different regions of the northern hemisphere , namely in Central Europe, the USA, Central Asia, Siberia, China and Japan. The spread of the fox tapeworm observed since the end of the 20th century is followed by alveolar echinococcosis, which is considered an emerging infectious disease .

The highest disease rate ever recorded worldwide was 6.2 percent between 2000 and 2002 in a series of 3200 participants in Sêrxü, a district in the Chinese province of Sichuan . The prevalence in the examined villages fluctuated between 0 and 14.3 percent. The population of the region is exposed to a combination of several risk factors; locally strongly fluctuating numbers of observed rodents are used as an explanation for the extremely fluctuating number of sick people from village to village in a small area.

In other regions, including Central Europe, the disease is very rare. As part of a survey by the European Echinococcus Register, eight states of the European Union (at the time Belgium, Germany, France, Greece, Great Britain, Italy, the Netherlands and Austria) as well as Switzerland, Poland, the Czech Republic and Turkey for the period from 1982 to 2000 only 559 cases of alveolar echinococcosis were found. Almost all local (autochthonous) cases were reported from Germany (132), Austria (54), Switzerland (118) and France (235), these are countries in which the fox tapeworm has always been common in certain areas. In Germany, a large proportion of illnesses that were not known to have occurred because there was no obligation to report the illness during the period under review and the recording was based on voluntary reports from treating doctors. In 2015, 44 cases were reported for Germany, in 2016 there were 26, in 2017 there were 36 cases of illness, and in 2018 49 cases were reported.

In Switzerland, where human echinococcosis had to be reported until 1997, only 494 cases of alveolar echinococcosis were known over a period of 50 years, from 1956 to 2005. The number of new cases per 100,000 inhabitants per year fluctuated between 0.10 and 0.15 between 1956 and 2000 and rose to 0.26 between 2001 and 2005. A high number of unreported cases can be ruled out for the first few decades, as the progress in diagnostics during the observation period only resulted in earlier diagnoses. The increase followed at a distance of around 15 years, the assumed incubation period, and the increase in the fox population observed in Switzerland and throughout Central and Eastern Europe.

transmission

The infectious tapeworm eggs are excreted with their faeces by infected main hosts , primarily foxes and dogs, but to a lesser extent also by domestic cats. The eggs survive in the environment for a long time; they are microscopic with a diameter of 30 to 40 µm and cannot be seen in everyday life. Humans can only become infected with the pathogen by swallowing fox tapeworm eggs. This includes the possibility of ingesting eggs with contaminated food or when eating with dirty hands, but inhaling contaminated dust, for example during haymaking, is also seen as a possible cause of infection. According to the Robert Koch Institute , however, thrown up dust is hardly infectious, or not at all, because if you inhale the parasite would not be activated by the gastric environment, which is very important for the oncosphere (larva), and tapeworm eggs are very sensitive to dehydration.

It is assumed that in most cases it is only a long-term exposure that leads to the infection, and not a single intake of the tapeworm eggs . A transmission of the disease from person to person is not possible.

As part of the above-mentioned study by the European Echinococcus Register on cases of disease in Europe, information on possible risk factors could be evaluated for 210 of the 559 patients . Around 22 percent of the patients were farmers, and 46 percent of the patients who did not work in agriculture did gardening or similar activities in their free time. 70 percent of the patients have been owners of dogs or cats, at least in the past. Only seven percent of the sick had neither farmed nor gardened nor kept pets.

A case-control study carried out in 2004 with 40 German patients, mostly from rural areas in southern Germany, supported these findings. In the endemic areas of southern Germany, farmers are at a higher risk of disease than those in other professions. The hay harvest, especially in the vicinity of water, carries a particularly high risk. Owning your own garden increases the likelihood of illness only when growing vegetables. Consumption of unwashed fruit, including berries, vegetables or mushrooms, with the exception of eating unwashed strawberries and chewing grass, has not been associated with an increased risk. Of the possible activities in the forest, an increased risk of infection could only be assigned to the collection of wood.

Keeping dogs and, to a lesser extent, cats also increased the likelihood of disease. For dog owners, keeping poaching dogs, unattended exercise in the garden or deworming at irregular intervals were more common among patients than in the control group. The keeping of domestic cats roaming free or chasing mice was also more common among patients. It was calculated that agricultural activity was the probable cause for two thirds, but consumption of unwashed fruit and vegetables for only 25 percent of the cases examined.

Studies on the risk factors for disease have only been conducted since the end of the 20th century. Their results partly contradict each other. In Austria, for example, hunters and owners of domestic cats were found to have an increased risk of disease, but not for farmers and dog owners. In Alaska , tundra home dwelling and dog ownership, particularly outside tethered dogs, have been associated with higher disease rates. The consumption of raw vegetables, berries and mushrooms has not been linked to diseases in either Austria or Alaska. In Japan, pig and cattle breeding and the drinking of spring water were identified as risk factors, while the German study found no association between illnesses and drinking water from natural sources. A study of Chinese cases showed that the risk of illness increased with a larger number of dogs kept in the past and with the extent of contact with the animals; other risk factors here were work in agriculture, drinking water supply and fox hunting.

Clinical picture

Alveolar echinococcosis; Finn infestation on the left side of the liver of a person

incubation period

The incubation period for alveolar echinococcosis is five to 15 years until clinical symptoms appear. An early diagnosis is possible using serological methods.

course

After ingesting oncospheres ("eggs"), these pass through the stomach and penetrate the wall of the small intestine . They reach the liver via the portal vein within three to four hours, and less often in the spleen, bile, lungs or brain. There they attach, grow into a primary cyst, and begin to spread by budding. On the surface of the comparatively small primary cyst, daughter cysts about the size of a hazelnut, the fins of Echinococcus multilocularis , form, which infiltrate the infected organ. The infection can spread to other organs in a metastatic manner via the blood ( hematogenous ) and lymphatic system ( lymphogenous ) . The clinical picture corresponds to that of a malignant (malignant) tumor and, if left untreated, leads to death in over 90% of cases within ten years after a gradual course.

The visual appearance of the foci of the disease is a collection of small bubbles filled with necrotic tissue and a jelly-like substance. One speaks here of an alveolar (vesicle-like) echinococcosis, to differentiate it from the cystic echinococcosis in the case of an infection by the dog tapeworm , in which the budding of the primary cyst takes place inwards and the new formation gives the impression of a single large bubble.

Symptoms

At the beginning of the infection there are hardly any symptoms that would raise suspicion of the disease. Even after many years, only unspecific signs appear at first, fatigue, abdominal discomfort and jaundice . At this stage of the disease, the larval tissue in the body has usually already reached a considerable size.

Complications

The possible complications are various sequelae of the destruction of liver tissue, the space-occupying growth and the spread in the patient's body. Inflammations of the bile ducts ( cholangitis ), jaundice due to disturbed bile outflow from the liver ( obstructive icterus ), gallstones (cholelithiasis), sepsis , portal hypertension ( portal hypertension , with the possible further consequences of esophageal varices , portal vein thrombosis and chronic Budd-Chiari syndrome ) have become known. , thrombosis of the lower vena cava ( inferior vena cava ), amyloidosis (a disorder of protein budget), glomerulonephritis (inflammation of the glomeruli), metastasis, chronic and acute liver failure (hepatic failure), and biliary fistula ( Fistula bronchobiliaris ). Cysts that enter the bloodstream through the budding of the parasite can cause an embolism either immediately or by growing in an awkward location such as the lungs or heart.

diagnosis

The early detection of the infection can be realized with serological tests ( IFT and PHA) before any symptoms appear. The serological differentiation between E. granulosus and E. multilocularis is usually possible using ELISA . Cross-reactions with other tapeworms are also possible.

Furthermore, imaging methods such as ultrasound examination , computed tomography and magnetic resonance tomography are used both for the diagnosis and for the assessment of the course of an alveolar echinococcosis . With these methods, however, it is only possible to monitor the course of the disease with a considerable delay through successive examinations to assess the change in size of parasitic damage. Liver damage, on the other hand, is characterized by the different activity of individual areas, which can be determined with the help of [18F] -fluoro-deoxyglucose positron emission tomography (FDG-PET).

If the liver is infected, other round nodules that take up space, such as an amoebic abscess (pus caused by amoeba ), must be excluded.

therapy

Early diagnosis and early, consistently performed therapy can lead to a complete cure.

Treatment options include chemotherapy , surgery, and palliative care ; usually a long-term treatment with is benzimidazole - derivatives essential. For this purpose, albendazole and mebendazole are currently officially approved in Germany. So far, this drug therapy has mostly been necessary for life because, according to the current state of knowledge, the above-mentioned substances only have a parasitostatic effect in the vast majority of cases. H. they only inhibit the growth of the parasites , but do not cause them to die. The drugs mentioned can have serious side effects, which is why benzimidazole therapy is stopped in about ten percent of cases. Since therapy failure also occurs in around 16 percent of cases, new therapeutic approaches are urgently needed.

Since in alveolar echinococcosis the parasite infestation is very often only found years after the infection, many patients are already inoperable at the initial diagnosis. Here, only long-term treatment can prevent the progressive worsening of the disease and extensive organ damage.

With FDG-PET , an improved follow-up is possible, since the parasitic activity can be determined at any time. This makes it possible to temporarily or permanently interrupt the benzimidazole therapy in approx. 25% of the patients.

prevention

The rarity of the disease and its long incubation period make individual and public measures of prevention difficult. Personal hygiene is the only recommended precautionary measure for people with an increased risk of the disease, such as people who work in agriculture and dog owners, there is no vaccination protection. At the level of state health protection, measures are being taken in the endemic areas to push back the fox tapeworm; in regions and states that are not affected, attempts are being made to prevent the pathogen from immigrating.

Individual prevention

When dealing with mice-catching pets such as dogs or cats, hygiene is the best protection against infection for humans. After touching the fur with the hands, for example by stroking them, they should not be brought to the mouth unwashed, especially if the fur has been touched in the anus region. Dogs and cats kept near fox populations should be dewormed regularly .

To prevent transmission through contaminated food, it should be washed thoroughly or heated sufficiently before consumption. In the agriculture employed persons wearing gloves when handling soil, plants and wood is recommended. As long as the inhalation of infectious material cannot be ruled out as a route of infection, the possible risk can be reduced by wearing dust protection masks when working in a dusty environment.

The World Organization for Animal Health (OIE) recommends decontamination using heat when handling infectious material ; hot water with a temperature of at least 85 ° C is described as very effective. For work equipment, freezing with a core temperature of −80 ° C for 48 hours or −70 ° C for 4 days is recommended, alternatively heating to 70 ° C for 12 hours is possible. Chemical disinfection is unreliable.

Reporting requirement

In 2001, when the Infection Protection Act came into force, human echinococcosis became notifiable in Germany . It is the direct or indirect detection of Echinococcus sp. (also of the fox tapeworm) not subject to notification by name according to Section 7 (3) of the Infection Protection Act (IfSG). The microbiological laboratories and pathologists who have diagnosed echinococcosis through histopathological or serological examinations (cf. § 8 , § 10 IfSG) are obliged to report to the Robert Koch Institute . In the event of a positive laboratory finding, treating general practitioners and clinicians must provide additional information to confirm the diagnosis, such as x-rays, but they are not obliged to report their own diagnosis independently of the laboratory. As a result, the Robert Koch Institute and the health authorities are not aware of all cases of alveolar echinococcosis; In a statistical study over the period from 2003 to 2005, the proportion of unreported cases in Germany was estimated at 67 percent.

In Austria, there has been a notification requirement since 2004 under the Epidemic Act 1950 and the Ordinance on Notifiable Communicable Diseases . In Austria, namely suspicion, illness and deaths on fox tapeworm (Echinococcus multilocularis) notifiable (according to § 1 1 para. Numeral 1 Epidemics Act 1950). Doctors and laboratories, among others, are obliged to report ( Section 3 Epidemic Act 1950).

In addition, it is a disease that must be monitored by the member states of the European Union according to the EU guideline for the monitoring of zoonoses and zoonotic pathogens of November 17, 2003.

In Switzerland, there has been no reporting requirement for human echinococcosis since 1997.

Control of the fox tapeworm

It is considered impossible to completely eliminate the fox tapeworm in an endemic area . However, deworming the foxes with the help of prepared bait can reduce their parasite load and the number of worm eggs released into the environment. The life cycle of the fox tapeworm is maintained in a region even if only one percent of the intermediate hosts are infected. Therefore, the control of the fox tapeworm requires continued treatment of the main hosts. Where control measures are carried out, they are most effective before the start of the cold season, as worm eggs excreted in cool weather remain infectious for a particularly long time and the infection rate of intermediate hosts increases more sharply.

Travel restrictions

In response to the spread of the fox tapeworm, which has been observed for several decades, several states that are currently or suspected to be free of fox tapeworm have introduced restrictions on imports from potential primary hosts. For this reason, Great Britain, Ireland, Malta, Sweden and Finland require a certificate of recent deworming when crossing the border with pets such as dogs or domestic cats . For a transitional period, these regulations are in line with European Union law . States that officially declare themselves free from the fox tapeworm can make indefinite regulations of this type. Norway has made use of this as far as the mainland is concerned. Sweden and Finland are striving to prove that they are free from the fox tapeworm in order to be able to follow the example.

history

Ancient and Middle Ages

The infestation of the intestines of animals and humans with tapeworms has been known since the early days, and many indigenous peoples are familiar with herbal remedies to alleviate the symptoms associated with a worm infestation. The clinical pictures caused by echinococci in their intermediate hosts were already known in antiquity. The Talmud mentions cysts in the bowels of sacrificed animals, Hippocrates described in the 4th century BC. Water-filled tumors in the lungs of cattle, sheep and pigs, and that after a water-filled liver bursts, the abdominal cavity fills with water and the (human) patient dies. In the 2nd century AD, Galen interpreted Hippocrates' aphorism as a description of the rupture of a hydatid cyst. Up until modern times, there have been occasional reports on the clinical pictures caused by cyst-forming tapeworms, without parasites being recognized as the cause or even the connection between the worms of the intestine and the cysts.

Pathogen biology

The genus Echinococcus was established in 1801 by Karl Asmund Rudolphi . The experimental feeding of infected intermediate hosts to dogs and other main hosts, as well as eggs isolated from the feces of dogs to pigs did not lead to the discovery until the middle of the 19th century that tapeworms go through a multi-stage development cycle with a host change. The life cycle of the dog tapeworm ( Echinococcus granulosus ) with the sheep as intermediate host was described by Carl von Siebold in 1853 and 1854. The first zoological description of the fox tapeworm was provided by Rudolf Leuckart in 1863, but its role as a causative agent of alveolar echinococcosis remained unrecognized.

Cystic echinococcosis

From the end of the 17th century, the animal nature of some of the "bubbles" discovered in human and animal tissue was recognized, and in 1782 Johann August Ephraim Goeze described the similarity of the scolici of the echinococci with the "heads" of the well-known tapeworms. These findings did not reach widespread use. On February 17, 1863, the Berlin doctor Bernhard Naunyn punctured a large liver cyst of a patient and successfully infected a dog with the dog tapeworm ( Echinococcus granulosus ) with the liquid obtained . Then the development cycle of the dog tapeworm was described by Rudolf Leuckart , the development of cystic echinococcosis in humans was explained.

Description of alveolar echinococcosis

In 1852 and 1854, the Munich physician Ludwig von Buhl described a liver tumor that differed from the previously known tumor forms and consisted of numerous small blisters filled with a gelatinous mass. He called the new formation "alveolar colloid" and viewed it as a form of degenerated tissue, but the cause of the disease remained hidden from him. Ernst Zeller published his dissertation in Tübingen in 1854 under the title "Alveolar Colloid of the Liver". He did see echinococci in some of the vesicles, but did not draw the correct conclusions from his observation. In the same year, Wilhelm Meyer wrote the dissertation “Two Forms of Cancer of Carcinoma” in Zurich, in which he referred to the disease as “gelatinous cancer”. It was not until the Würzburg doctor Rudolf Virchow recognized the new “alveolar colloid” or “gelatinous cancer” in 1855 after intensive microscopic examinations as a parasitic phenomenon. Like Zeller, he was fortunate to have seen protoscolices in the examined tissue, unlike in most cases . Virchow drew the correct conclusions from his observation and recognized the cause of the new formation. Based on the (unilocular) "Echinococcus", which has long been known as a worm disease, he named the disease "multilocular ulcerating echinococcal tumor of the liver" and published a detailed report on the symptoms, the course and the pathological findings of the disease.

Ludwig von Buhl congratulated Virchow in a letter and mentioned that Carl von Siebold had sent him a sample of a tumor of the same type from an animal liver. This communication led Virchow to be the first to recognize the zoonotic character of echinococcosis. Only because of the identification of the pathogen's species he failed, he thought it was a dog tapeworm. In 1875, Fritz Morin took the view in his doctoral thesis that the two diseases were caused by different pathogens, but he could not prevail with his view. The new disease was, also against the background of the judgment that the generally recognized and esteemed Virchow had given, merely as a freak of nature, as a degenerate form of infection with the dog tapeworm.

Identification of the pathogen

Until the 1950s, it was considered certain that alveolar and cystic echinococcosis are caused by dog ​​tapeworm, which for unknown reasons can cause various clinical pictures. It was not until 1955, after investigations by Robert L. Rausch and Everett L. Schiller in Alaska and Hans Vogel in Germany, that the fox tapeworm was established as the causative agent of alveolar echinococcosis.

Trivia

During the criminal proceedings against the former chairman of the State Council of the GDR, Erich Honecker , the defendant's ability to stand trial was questioned by his defense counsel and the proceedings were called for. The defendant has a malignant tumor in the right lobe of the liver and will most likely not see the end of the trial, as it is inhumane to negotiate against a dying person. In fact, a computed tomography in the Berlin Charité found a space-occupying process about five centimeters in size in the right lobe of the liver. Advised by the physician Julius Hackethal , the Berlin lawyer Hanns-Ekkehard Plöger, representing a joint plaintiff, the mother of Michael Bittner , who was shot on the Berlin Wall in 1986 , claimed that Honecker did not suffer from liver cancer, but "only" from a fox tapeworm.

Individual evidence

  1. ↑ a b c d e Erwin Kuntz and Hans-Dieter Kuntz: Parasitic infections and the liver. In: Erwin Kuntz and Hans-Dieter Kuntz: Hepatology. Principles and Practice. 2nd edition. History, Morphology, Biochemistry, Diagnostics, Clinic, Therapy . Springer Verlag, Berlin, Heidelberg 2006, ISBN 978-3-540-28976-0 , pp. 485-504.
  2. ↑ Erwin Kuntz and Hans-Dieter Kuntz: Parasitic infections and the liver. In: Erwin Kuntz and Hans-Dieter Kuntz: Hepatology. Principles and Practice. 2nd edition. History, Morphology, Biochemistry, Diagnostics, Clinic, Therapy . Springer Verlag, Berlin, Heidelberg 2006, ISBN 978-3-540-28976-0 , pp. 485-504, here p. 497.
  3. ↑ Dennis Tappe, August Stich and Matthias Frosch: Emergence of Polycystic Neotropical Echinococcosiss. In: Emerging Infectious Diseases , Volume 14, No. 2, 2008, pp. 292-297, PMC 2600197 (free full text).
  4. ↑ Article Echinococcus. In: Heinz Mehlhorn : Encyclopedic Reference of Parasitology. Biology, Structure, Function. Springer Verlag, Berlin, Heidelberg, New York 2001, ISBN 3-540-66239-1 , p. 410.
  5. ↑ a b J. Eckert u. a. (Ed.): WHO / OIE Manual on Echinococcosis in Humans and Animals: a Public Health Problem of Global Concern. Office International des Epizooties (OIE), Paris 2002, ISBN 92-9044-522-X . (PDF, 5.6 MB, accessed December 17, 2013)
  6. ↑ Tamás Sréter u. a .: Echinococcus multilocularis: An Emerging Pathogen in Hungary and Central Eastern Europe? In: Emerging Infectious Diseases. Volume 9, No. 3, 2003, pp. 384-386, PMC 2958538 (free full text).
  7. ↑ a b c Li Tiaoying et al. a .: Echinococcosis in Tibetan Populations, Western Sichuan Province, China. In: Emerging Infectious Diseases. Volume 11, No. 12, 2005, pp. 1866-1873, PMC 3367622 (free full text).
  8. ↑ a b Petra Kern u. a .: European Echinococcosis Registry: Human Alveolar Echinococcosis, Europe, 1982-2000. In: Emerging Infectious Diseases. Volume 9, No. 3, 2003, pp. 343-349, PMC 2958541 (free full text).
  9. ↑ Alexander Schweiger et al .: Human Alveolar Echinococcosis after Fox Population Increase, Switzerland. In: Emerging Infectious Diseases , Volume 13, No. 6, 2007, pp. 878-882, PMC 2792858 (free full text).
  10. ↑ a b c d e Petra Kern u. a .: Risk Factors for Alveolar Echinococcosis in Humans. In: Emerging Infectious Diseases. Volume 10, No. 12, 2004, pp. 2088-2093, PMC 3323393 (free full text).
  11. ↑ Ursus-Nikolaus Riede and Martin Werner: Color Atlas of Pathology . Thieme, Stuttgart, New York 2004, ISBN 3-13-127781-5
  12. ↑ S. Reuter u. a .: Pericystic Metabolic Activity in Alveolar Echinococcosis: Assessment and Follow-Up by Positron Emission Tomography . In: Clinical Infectious Diseases . Vol. 29, Iss. 5, 1999, pp. 1157-1163, doi: 10.1086 / 313438 , online
  13. ↑ Wissenschaft.de: Blueberries, wild garlic and dogs: where the fox tapeworm really lurks. In: Wissenschaft.de. May 30, 2007, accessed September 8, 2019 .
  14. ↑ Federal Food Safety and Veterinary Office: Parasitic pathogens in food and drinking water . In: admin.ch , accessed on February 12, 2020.
  15. ^ Office International des Epizooties (ed.): Manual of Diagnostic Tests and Vaccines for Terrestrial Animals (Mammals, Birds and Bees). Sixth Edition, Volume 1, pp. 175-189, Office International des Epizooties (OIE), Paris 2008, ISBN 978-92-9044-718-4 Online PDF 11.2 MB, accessed December 16, 2013.
  16. ↑ a b K. Alpers u. a .: Zoonotic infections in humans. In: Federal Health Gazette - Health Research - Health Protection. Volume 47, number 7, July 2004, pp. 622-632, ISSN  1437-1588 , doi: 10.1007 / s00103-004-0867-7 ( PDF, 340 kB ( Memento of the original from December 18, 2013 in the Internet Archive ) Info : The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this note. , Accessed on December 17, 2013) @1@ 2Template: Webachiv / IABot / www.rki.de
  17. ↑ Pernille Jorgensen u. a .: Underreporting of Human Alveolar Echinococcosis, Germany. In: Emerging Infectious Diseases. Volume 14, No. 6, 2008, pp. 935-937, PMC 2600310 (free full text).
  18. ↑ without author: Notifiable communicable diseases in Austria. In: Hygiene Monitor. Volume 12, No. 6 + 7, 2006, p. 2 (PDF, 2,350 kB, accessed on December 17, 2013) ( Memento of the original from November 23, 2006 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / universimed.com
  19. ↑ Peter Deplazes, Daniel Hegglin: Fox tapeworm: In Switzerland, significantly more people get alveolar echinococcosis. In: FVO magazine. Issue 3/2007, pp. 2-4 PDF ( Memento from December 17, 2013 in the Internet Archive ) (210 kB, accessed on December 17, 2013)
  20. ↑ K. Takumi, J. van der Giessen: Transmission dynamics of Echinococcus multilocularis; its reproduction number, persistence in an area of ​​low rodent prevalence, and effectiveness of control. In: Parasitology. Volume 131, No. 1, July 2005, pp. 133-140, ISSN  0031-1820 . PMID 16038404 .
  21. ↑ Pierre Burlet, Peter Deplazes, Daniel Hegglin: Age, season and spatio-temporal factors affecting the prevalence of Echinococcus multilocularis and Taenia taeniaeformis in Arvicola terrestris. In: Parasites & Vectors. 2011, Article 4: 6, doi: 10.1186 / 1756-3305-4-6 . PMC 3033848 (free full text).
  22. ↑ Helene Wahlström et al. a .: Combining information from surveys of several species to estimate the probability of freedom from Echinococcus multilocularis in Sweden, Finland and mainland Norway. In: Acta Veterinaria Scandinavica. 2011, 53 (9), doi: 10.1186 / 1751-0147-53-9 , PMC 3049754 (free full text).
  23. ^ Karl Asmund Rudolphi: Observations on the intestinal worms . In: Archive for Zoology and Zootomy , Volume 2, 1801, pp. 1–65, Online PDF 3.0 MB, accessed on December 24, 2013.
  24. ↑ a b c d e f David I. Grove: A History of Human Helminthology. CAB International, Wallingford (UK) 1990, ISBN 0-85198-689-7 , pp. 319-353.
  25. ^ A b Rudolf Leuckart: General Natural History of Parasites. With special consideration of the species parasitic in humans . CF Winter'sche Verlagshandlung, Leipzig and Heidelberg 1879, pp. 94–117 Online , accessed on December 24, 2013.
  26. ↑ a b c Dennis Tappe and Matthias Frosch: Rudolf Virchow and the Recognition of Alveolar Echinococcosis, 1850. In: Emerging Infectious Diseases , Volume 13, No. 5, 2007, pp. 732-735, PMC 2738454 (free full text).
  27. ↑ Rudolf Leuckart: The human parasites and the diseases originating from them. , 2 volumes, CF Winter'sche Verlagshandlung, Leipzig and Heidelberg 1863, Volume 1, pp. 328–389 Online , digitized version of Volume 1 in the Bayerische Staatsbibliothek, accessed on December 25, 2013.
  28. ↑ a b Rudolf Virchow: The multilocular, ulcerating echinococcal tumor of the liver . In: Negotiations of the Physikalisch-Medicinische Gesellschaft zu Würzburg , Volume 6, 1855, pp. 84–95, ISSN  0931-6507 Online PDF 785 kB, accessed on December 21, 2013.
  29. ↑ Herbert Auer, Horst Aspöck: The cystic and the alveolar echinococcosis - the most dangerous helminthoses of Central Europe . In: Denisia. Volume 6, (= catalogs of the Upper Austrian State Museum. New series no. 184). 2002, pp. 333–353, ISSN  1608-8700 (PDF, 2.7 MB, accessed on December 17, 2013)
  30. ↑ Rainer Frenkel: When death overlaps life . In: Die Zeit , No. 2, January 8, 1993, p. 5 Online , accessed December 25, 2013
  31. ↑ Uwe Wesel: The Honecker trial. About the rule of law, its embarrassments and its difficulties . In: Kritische Justiz , 1993, Issue 2, pp. 198–206 Online PDF 850 kB, accessed on December 25, 2013.

Web links