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JanneLaine

Tularaemia

Essentials

  • There are several forms of tularaemia. In the most common, ulceroglandular form the patient has fever, lymphadenopathy and an ulcerated skin lesion (picture 1) at the site of a mosquito bite or a scratch.
  • Begin treatment immediately if the symptoms are typical and the point of time of the disease onset matches with tularaemia. Diagnosis can be confirmed with serology.

Transmission

  • There is no certainty about the natural reservoir of tularaemia. Small rodents and hares are the most likely candidates. Natural water contaminated by tularemia appears to play an important role in the disease cycle.
  • The infection is transmitted by
    • mosquitoes (clearly most important vector in Finland, for example)
    • other blood-sucking arthropods (horse-flies, black flies, ticks)
    • handling of a sick animal
    • inhalation of infected aerosols
    • ingestion of contaminated water or food
    • ingestion of meat from an affected animal (even after freezing the meat)
  • Incubation period is 1-14 days (usually 3-5 days)
  • The total number of human cases in Europe is about 800 annually, with most cases between July and November http://www.ecdc.europa.eu/en/tularaemia/facts http://www.ecdc.europa.eu/sites/default/files/documents/AER-tularaemia-2019.pdf. In some European countries (e.g. Finland and Sweden) tularemia is more common and recurrent outbreaks take place every few years http://helda.helsinki.fi/items/54f1e5a2-ba52-40e5-b9d0-2a5a23b8ba28, while in some other European countries tularemia does not occur (Iceland, Ireland, UK).
  • The milder type B tularaemia (Francisella tularensis holarctica) encountered in Europe is not associated with significant mortality. Type A (Francisella tularensis tularensis) found in North America leads to death in 1-2% of the infected persons.

Symptoms

  • There are several different disease forms. General symptoms like fever, chills, headache and malaise are seen in all of these.
    • The ulceroglandular form (90% of the cases) causes fever, a small infected skin lesion as well as swelling and tenderness of regional lymph nodes (picture 2).
    • The glandular form (5-10%) causes fever and lymphadenopathy but no skin lesions. Lymphadenopathy is usually local.
    • The oculoglandular form causes granulomatous conjunctivitis with regional lymphadenopathy.
    • In pneumonic tularaemia the patient may have a dry cough, dyspnoea and thoracic pain, but respiratory symptoms may be absent. Chest x-ray shows infiltrations, pleural fluid or hilar lymphadenopathy.
    • The oropharyngeal form (2-4%) causes tonsillitis, pharyngitis and cervical lymphadenopathy.
    • The typhoidal form (5-15%) causes severe systemic symptoms (fever, fatigue and weight loss) and possibly enlargement of the liver and spleen.
  • Rash (picture 3) has been reported in up to 20% of the patients.
  • Liver enzyme concentrations may be increased and the liver enlarged.
  • Peritonitis, meningitis and osteomyelitis are rare symptoms.
  • CRP increases moderately; ESR is increased.
  • Anaemia
  • Duration of the disease varies from a few days to some weeks.

Diagnosis

  • Treatment is begun on the basis of the clinical picture. The assessment should take into account whether the timing is typical for tularemia and whether the patient has been exposed to tularemia (mosquito bites).
  • Diagnosis is usually confirmed by serology. The antibody titre rises first 1-3 weeks after onset of fever. Paired sera samples are taken at 2-3 week intervals. A rise in the antibody titre is an indication of a recent infection. The diagnosis is certain if there is a fourfold rise in the titre.
  • There is also a PCR test that can quickly detect infection. However, the availability of this test is limited. Suitable samples for PCR testing include secretion from an inflamed mosquito bite site or a piece of tissue from a diseased area.
  • In special cases, Francisella tularensis can be cultivated from a tissue sample, from the wall of an abscess or from pus. Cultivation is demanding, its availability is limited, and negative culture result cannot be considered as exclusive. The laboratory must be informed about the possibility of tularaemia because there is a risk of laboratory transmission. Cultivation is performed in a BSL-3 level safety laboratory.

Treatment

  • Ciprofloxacin is the recommended antibiotic therapy Fluoroquinolones in the Treatment of Tularaemia (dose 500 mg twice daily for adults), or, alternatively, doxycycline (100 mg twice daily). Levofloxacin (500 mg once daily) may be used instead of ciprofloxacin. Gentamicin (5 mg/kg/day in adults divided into one or two doses) can also be used as treatment. The duration of treatment is usually 10-14 days.
  • There is no clear consensus on the choice of antibiotics for pregnant women. Severe tularaemia, on the other hand, can compromise the course of pregnancy. However, aminoglycosides (tobramycin or gentamicin) are considered the first-line treatment. Azithromycin also has in vitro efficacy and case reports on its use have been published. However, its efficacy is considered uncertain and resistance has been observed in Europe.
  • Even if ciprofloxacin is not officially approved for paediatric use, it has been used in verified cases of tularaemia for children as well. The dose is 20-30 mg/kg daily divided into two doses. The adult dosage must not be exceeded even if the dose calculation based on body weight would indicate a higher dose!
  • Beta-lactam antimicrobials are ineffective.

    References

    • Maurin M, Gyuranecz M. Tularaemia: clinical aspects in Europe. Lancet Infect Dis 2016;16(1):113-24. [PubMed]
    • Rossow H, Ollgren J, Klemets P ym. Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study. Epidemiol Infect 2014;142(10):2207-16. [PubMed]