Tularemia

from Wikipedia, the free encyclopedia
Classification according to ICD-10
A21.- Tularemia
A21.0 Ulceroglandular tularemia
A21.1 Oculoglandular tularemia
A21.2 Pulmonary tularemia
A21.3 Gastrointestinal tularemia

Abdominal tularemia

A21.7 Generalized tularemia
A21.8 Other forms of tularemia
A21.9 Tularemia, unspecified
ICD-10 online (WHO version 2019)

Tularemia is an often fatal infectious disease in free-living rodents and rabbits caused by the bacterium Francisella tularensis (formerly Pasteurella tularensis ). The disease is a zoonosis and can be transmitted to humans. In Germany it is one of the notifiable animal diseases .

Since the symptoms (with the primary effect at the point of entry and involvement of the regional lymph nodes) resemble that of the plague and the disease very often affects hares and wild rabbits , it is often referred to as rabbit plague . Other names are rodent plague , lemming fever , Parinaud disease and deer fly fever .

history

The disease was first described in 1911 by the American physician George W. McCoy . In 1912 he and Charles W. Chapin succeeded in isolating the pathogen from a species of squirrel in California . Between 1919 and 1928 Edward Francis dealt with the disease in great detail and named it after the town of Tulare in California / USA . The pathogen's scientific name was also named after it. Tularemia was first documented in Europe in 1931, on the Baltic coast of central Sweden. Between 1936 and 1950 the Soviet scientists H. A. Gaiski, B. Y. Elbert, Somov and Chatenever succeeded in developing a vaccine against tularemia.

During the Second World War , epidemics with more than a hundred thousand infections were reported on the Eastern European front . Former Soviet bioweapons researcher Ken Alibek from the Soviet Biopreparat agency suspects that the epidemics were the result of Francisella tularensis being used as a biological weapon .

In the 1950s and 1960s, the US military developed weapon systems designed to distribute the bacterium as an aerosol . In 1969 a panel of experts from the World Health Organization estimated that such a distribution of 50 kilograms of F. tularensis over a city of 5 million people would result in 250,000 incapacitated and 19,000 dead. In 1997, scientists at the American CDC estimated the cost of such an attack to be 5.4 billion US dollars per 100,000 people exposed to the agent.

The largest documented tularemia outbreak occurred in a farm area in Sweden from 1966 to 1967 and affected approximately 600 patients. Most of these had become infected with the milder type B by inhalation when moving infected hay and responded well to tetracycline , so that no deaths were recorded.

Pathogen

Colonies of Francisella tularensis

The causative agent of tularemia is the highly contagious bacterium Francisella tularensis (formerly also: Pasteurella tularensis ). It is a very small, gram-negative , cocoid , spore-free , difficult to cultivate rod that is assigned to the γ-proteobacteria . Francisella is the only genus in the Francisellaceae family, order Thiotrichales. It comprises a total of 4 species ( F. tularensis , F. philomiragia , F. novicida and F. noatunensis ). The bacterium is destroyed by heat and conventional disinfectants , but is resistant to cold . As little as 10 to 50 bacteria as aerosol can infect a person. The pathogen can persist in frozen rabbit meat for up to three years and in soil and water for several weeks.

There are two known variants:

  • Francisella tularensis biovar tularensis (type A) in North America, which is responsible for more dangerous courses.
  • Francisella tularensis biovar palaearctica (type B) with worldwide distribution.

Animals such as hares, beavers and ticks serve as reservoir hosts .

distribution

In October 2005, nine hunters and drivers were infected with tularemia during a hunt for hares in the Darmstadt-Dieburg district . Almost all of them had been involved in gutting or felling; they had not noticed any signs of disease in the animals. Another hunter who died about four weeks later was believed to be the cause of death because he had shown typical symptoms. In Bavaria, on November 6, 2018, it became known that nine hunters were infected with the rabbit plague.

Shortly after the Second World War, the disease was much more common in Germany, presumably because of the higher rabbit and rabbit population at the time and the greater use of these animals for human consumption. Around 100 to 200 cases were registered each year during this time.

Route of infection

Blood-sucking ectoparasites have been identified as vectors for the pathogen, i.e. parasites living on the body surface , such as. B. mosquitoes , fleas , lice , bed bugs , mites or ticks . The parasites are found on wild rabbits (such as hares and wild rabbits ) and rodents ( rats , mice , squirrels ), less often on wild fowl , foxes or farm and domestic animals ( sheep , pigs , cattle , dogs , cats , hamsters ).

Transmission:

  • through direct and indirect contact with infectious rodents (also: hunting , skinning or slaughtering )
  • indirectly via the blood-sucking ectoparasites mentioned as vectors
  • over mud or contaminated water
  • By inhaling dust containing pathogens (contaminated hay , silage , soil, dust), whereby only a few bacteria lead to disease
  • by consuming insufficiently heated meat containing pathogens.

Human to human transmissions are not known.

Course of the disease and symptoms

Tularemia is different in animals and humans.

Animal tularemia

After parasites transmit the pathogen to the rodents , septicemia occurs after two to three days, i.e. a systemic infection due to the permanent presence of the pathogen in the bloodstream. The animals are noticeable for their weakness, apathy (until they fail to escape), fever and increased breathing frequency. The lymph nodes and spleen are enlarged. Most animals perish within four to thirteen days. Chronic infections are fatal after 14 to 60 days.

Domestic dogs seem to be largely resistant to the pathogen. In rare cases, an outbreak of the disease with fever , swelling of the liver , spleen and lymph nodes , jaundice , runny nose, bronchopneumonia and ulcers on the skin and mucous membranes can occur. Domestic cats also seem to be less receptive. They can experience fever, swelling of the lymph nodes, unwillingness to eat, emaciation and weakness. If infectious material was fed experimentally several times, the animals died after 10 to 50 days.

Tularemia in humans

Tularemia can be transmitted from living or dead animals to humans, usually through direct contact (e.g. via small skin defects). According to Section 7 of the Infection Protection Act in Germany, it is a reportable zoonosis in the event of indirect or direct evidence of the pathogen . The course of the disease in humans is severe and often life-threatening (the mortality rate is reported to be around 33% without treatment), which is why early diagnosis is of the utmost importance. The disease is very rare in Central Europe. In Germany, a total of 15 and 10 cases were reported in 2008 and 2009, 20 cases in 2013 and 21 cases in 2014, which corresponds to an incidence of around 0.01 per 100,000. In the autumn of 2018, several hunters fell ill with rabbit plague after hunting hares in Bavaria. Several people close to the hunters were also affected. Due to the rarity of the disease, the exact anamnesis (animal contact) usually provides the decisive clue for the suspected diagnosis.

The incubation period in humans is between one and ten days. The infection can occur through contact with infected animals or through insect bites (mosquitoes, ticks). Depending on the entry point of the pathogen (skin wound, through the mouth, inhalation as an aerosol), different disease manifestations occur, as listed below.

External (localized) forms

Lesion in human tularemia
  • Ulceroglandular (cutanoglandular) tularemia - the most common form of tularemia (75–85%) that begins with a sudden rise in fever. It formed ulcers (primary lesions) at the entry point with regional, often purulent inflammation of the lymph nodes .
  • oculoglandular tularemia ( parinaud conjunctivitis ) - the portal of entry on the conjunctiva of the eye can be recognized by a yellowish nodule, the lymph nodes in front of the ear and in the throat are swollen. In addition, there is very painful conjunctivitis .
  • Glandular tularemia - no portal of entry can be seen and ulcer formation is absent.
  • glandulo- pharyngeal or oropharyngeal tularemia - this form is found mainly in children. Ulcers develop in the oral cavity and throat , and the lymph nodes in the corner of the jaw are swollen.

Inner (invasive) forms

The internal form of tularemia occurs when the pathogens are inhaled or reach internal organs via the bloodstream. It is then a highly febrile, dangerous disease with a significantly higher mortality rate than the external forms.

  • intestinal tularemia - transmission likely through the consumption of insufficiently heated meat from infected animals. Symptoms include pharyngitis , nausea, vomiting, diarrhea, and abdominal pain.
  • thoracic (pulmonary) tularemia - second most common; preferably affects the lungs and then manifests itself as pneumonia , i.e. pneumonia. Patients suffer from cough with sputum , shortness of breath and pain in the chest .

diagnosis

Samples for pathogen detection should, if possible, be taken before antibiotic therapy. The direct detection of pathogens by culturing on cysteine ​​or cystine-enriched, blood-containing culture media (e.g. cysteine ​​heart blood agar) from blood, tissue samples (liver, spleen) or smears is not always successful, but should be attempted in every case. Isolates should be transferred from the routine laboratory to one of the special laboratories listed below for further characterization.

Since strains of F. tularensis have been described as being resistant to antibiotics, resistance testing of the cultivated pathogens should be carried out as standard. Since it is a highly infectious pathogen, further diagnostics, in particular subtyping and virulence and resistance testing, should be reserved for special laboratories.

Nucleic acid detection methods (e.g. various PCR methods) and antigen detection (e.g. immunofluorescence microscopy, ELISA ) are also available as direct pathogen detection .

The infection can be diagnosed indirectly through the detection of serum antibodies against the pathogen. A single high titer or an increase in the titer indicate a previous infection. Various methods such as ELISA, Western blot, immunofluorescence and agglutination tests can be used for the detection of antibodies.

therapy

Treatment consists of giving antibiotics . Streptomycin is the most effective . Alternatively, doxycycline or gentamicin can be used. The pathogens are also sensitive to other tetracyclines , macrolides such as erythromycin or azithromycin and chloramphenicol and ciprofloxacin . Compared to penicillin and sulfonamides , however, there is a resistance .

forecast

The internal form of tularemia in humans is a serious, life-threatening disease which, when treated, is fatal in approx. 5% of cases. Without antibiotic treatment, mortality can be over 30%. With a mortality of 10 to 35%, the virulence of American forms of tularemia is higher than that of the European strains.

In dogs, the prognosis is good with timely treatment. However, treatment is controversial because of the high risk of infection for the owner.

prophylaxis

There is a live attenuated vaccine (USA, CIS ), which is currently not available in Germany.

Drug prophylaxis after probable exposure (e.g. in the laboratory): Doxycycline or ciprofloxacin for 14 days should be started quickly (if possible within 24 hours after exposure). If a possible exposure is only considered after the occurrence of illness, all suspected exposed persons should carry out fever monitoring for 21 days (after the suspected exposure). Those who develop a flu-like illness or fever during this period should receive therapy as described above. Surviving the disease leaves a long-term immunity .

Reporting requirement

In Austria, tularemia is notifiable in the event of suspicion, illness or death in accordance with Section 1 (1) number 1 of the 1950 Epidemic Act . Doctors and laboratories, among others, are obliged to report this ( Section 3 Epidemics Act).

In Switzerland there is an obligation to notify the attending physician in the event of a positive laboratory analysis result. This results from the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Annex 1 or Annex 3 of the Ordinance of the FDHA on the reporting of observations of communicable diseases in humans .

literature

  • H. Krauss, A. Weber, M. Appel, B. Enders, A. v. Graevenitz, HD Isenberg, HG Schiefer, W. Slenczka, H. Zahner: Zoonoses. Infectious diseases that can be transmitted from animal to human. 3rd completely revised and expanded edition. Deutscher Ärzte-Verlag, Cologne, 2004, ISBN 3-7691-0406-4 .
  • H. Krauss, A. Weber, M. Appel, B. Enders, A. v. Graevenitz, HD Isenberg, HG Schiefer, W. Slenczka, H. Zahner: Zoonoses. Infectious Diseases Transmissible from Animals to Humans. 3. Edition. ASM Press American Society for Microbiology , Washington DC 2003, ISBN 1-55581-236-8 .
  • H. Krauss, A. Weber, B. Enders, HG Schiefer, W. Slenczka, H. Zahner: Zoonoses. ACATAP, Damascus, Syria 2001. (Arabic)
  • Tularemia, rabbit plague (Francisella tularensis). In: Federal Health Gazette . Robert Koch Institute 2001.
  • Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , p. 251 f.
  • Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9-223, here: pp. 216-218.

Web links

Individual evidence

  1. ^ McCoy GW. A plague-like disease of rodents. Public Health Bull 1911; 43: 53-71.
  2. ↑ A. Tärnvik1 and L. Berglund, Tularaemia . Eur Respir J 2003; 21: 361-373.
  3. ^ McCoy GW, Chapin CW. Bacterium tularense, the cause of a plaguelike disease of rodents. Public Health Bull 1912; 53: 17-23.
  4. ↑ a b c D. T. Dennis et al .: "Tularemia as a Biological Weapon" . In: Journal of the American Medical Association . tape 21 , no. 285 , 2001, p. 2763-2773 , PMID 11386933 .
  5. ↑ AF Kaufmann, MI Meltzer, GP Schmid: The Economic Impact of a Bioterrorist Attack: Are Prevention and Postattack Intervention Programs Justifiable? In: Emerging Infectious Diseases . tape 3 , no. 2 , 1997.
  6. ↑ Bavaria: Nine hunters apparently got sick with rabbit plague. Spiegel Online, November 7, 2018, accessed November 7, 2018 .
  7. ↑ a b Katrin Hartmann: Tularemia. In: Peter F. Suter, Hans G. Nobody (Hrsg.): Internship at the dog clinic. 10th edition. Paul-Parey-Verlag, Stuttgart 2006, ISBN 3-8304-4141-X , p. 312.
  8. ↑ In: Marian C. Horzinek et al. (Ed.): Diseases of the cat. 4th edition. Enke, 2005, ISBN 3-8304-1049-2 , p. 184.
  9. ↑ Epidemiological Bulletin (pdf) of the Robert Koch Institute, April 19, 2010 / No. 15 with annual statistics of notifiable infectious diseases in 2008 and 2009.
  10. ↑ Epidemiological Bulletin No. 31 of the Robert Koch Institute. (PDF) Robert Koch Institute , August 4, 2014, accessed December 4, 2014 .
  11. ↑ Epidemiological Bulletin No. 3 of the RKI , January 19, 2015.
  12. ↑ Confirmed: Hunter in Nabburg fell ill with rabbit plague . In: BR24 . ( br.de [accessed on November 12, 2018]).
  13. ↑ Case report on tularemia after a cat bite : AN Weinberg, JA Branda: A 29-Year-Old Woman with Fever after a Cat Bite. In: N Engl J Med . 2010; 363, pp. 1560-1568, October 14, 2010.
  14. ↑ Case report: E. Capka, M. Roch, M. Ritter, U. Stölzel: 23-year-old patient with a sore throat and progressive lymph node swelling - a rare form of rabbit plague. In: The internist. Volume 51, No. 6, pp. 784-787, doi: 10.1007 / s00108-009-2547-z .
  15. ↑ Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 9-223, here: p. 131 ( Tularemia (typhoid form) ).
  16. ↑ RKI - Infectious Diseases AZ - Tularemia. Retrieved June 15, 2020 .