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Francisella tularensis

The causative agent of tularemia is a fine, gram-negative rod that can be cultivated from infected tissue samples. Tularemia has long been observed in Switzerland, particularly associated with contact to infected hares and other animals (hunting, slaughter). Since 2012, a significant increase in cases of the disease has been observed in Switzerland and Europe, from around 10 in 2007 to around one hundred in 2017. Francisella tularensis is a contagious zoonosis that can be transmitted in various ways (a zoonosis is a disease or infection that can be transmitted naturally from vertebrates to humans). In addition to contact with infected animals or their environment, tick or insect bites are an important route of transmission. Francisella tularensis was detected in Ixodes ricinus ticks in Switzerland as early as 2000.

Pathogen

Francisella tularensis is a facultative intracellular, gram-negative, partly coccobacillary appearing rod. The species Francisella tularensis comprises four subspecies. The most virulent subspecies, Francisella tularensis subsp. tularensis, is found in North America, while the subspecies Francisella tularensis subsp. holarctica is found throughout the northern hemisphere and is the most important subspecies in Europe. Due to its very low minimal infectious dose, bacterial cultures must be handled in a biosafety level 3 laboratory.

There is no proven clinical relevance to date for the subspecies Francisella tularensis subsp. mediasiatica (Central Asia) and Francisella tularensis subsp. novicida.

Epidemiology

Francisella spp. are zoonotic pathogens having a very broad host spectrum; they can infect more than 100 species (animals, arachnids, insects). In highly susceptible animals (rodents, hares, rabbits) the disease manifests itself as fever, apathy, dyspnoea and death due to septicaemia. The pathogen is widespread in the northern hemisphere. Humans become infected with Francisella tularensis by inhaling aerosols and dust (e.g. hay, soil), drinking contaminated water (fresh water), handling infected animals, eating infected meat, bites/bites from infected arthropods (mosquitoes, ticks, horseflies).

In Switzerland, vector-borne transmission by the tick species Ixodes ricinus is considered the most important route of infection. The infection rate of ticks with Francisella tularensis has been known since 2000 and remains low at 0.02%.

The incidence of tularemia in Switzerland has been remarkable for 20 years. The number of reported cases is rising steadily and currently amounts to 150 per year. Tick bites are cited as an important cause for this. It is not yet clear whether other vectors such as mosquitoes of the genus Aedes or ticks of the genus Dermacentor are contributing to this increase, as is the case in Finland for mosquitoes (especially Aedes cinnereus).

Clinical manifestation

The clinical picture of tularemia depends on the route of transmission, the pathogen’s virulence, the host’s immune system and the point in time of diagnosis. In general, the duration of the disease is relatively short. Tularemia manifests itself unspecifically with symptoms such as fever, chills, headache and malaise. A distinction is made between the following forms:

  • The most common form is the ulceroglandular form, in which the pathogens are transmitted via a bite/sting; regional lymph node swelling and a painless ulcer develop at the site of entry
  • In the glandular form, there are no ulcers at the entry site
  • In the oculoglandular form, the conjunctiva is the portal of entry; the pathogens are transmitted mechanically with the fingers from infectious sources
  • The oropharyngeal form occurs when the pathogens are ingested with water or food and is associated with pharyngeal lymphadenopathy
  • The pneumonic form occurs as a result of inhalation of the bacteria and is the most severe form
  • The typhoid form manifests with fever, chills, headache, hepato- and splenomegaly; no clear portal of entry is recognizable

Therapy

Local manifestations are treated with fluoroquinolones or tetracyclines. Systemic infections are primarily treated with aminosides.

Vaccination

No vaccination against tularaemia is available in Switzerland.

Diagnostics

Francisella tularensis is easy to cultivate, but is often not detected during routine examinations of superficial wounds due to its somewhat slower growth. If it is suspected, it is important to inform the laboratory accordingly so that the cultures can be incubated prolonged and the necessary safety precautions (BSL-3) can be taken. In the case of pulmonary or systemic manifestations, the pathogens are easier to detect in blood cultures. Ulcer biopsies are also well suited for cultural detection. The culture makes it possible to monitor possible antibiotic resistance; however, these are very rare.

Molecular biological detection is the method of choice, as the handling of bacterial cultures can be avoided. It detects the pathogen with high sensitivity within 24 hours of receiving the sample (Microbiology CHUV). A positive PCR result is important for the laboratory with regard to the safety 

measures to be taken for cultures from the same patient. Sequencing of the complete bacterial genome is carried out in rare cases, usually using cultured isolates.

Serology is the simplest but also the least reliable diagnostic method for Francisella tularensis. It depends very much on the quality of the tests used. In general, the sensitivity is rather low, in favour of a high specificity of 95-98% (confirmatory tests). Confirmation of a case requires the detection of IgG seroconversion; this approach avoids false, isolated IgM-positive results due to various non-specific cross-reactions. IgG antibodies usually become detectable 10-20 days after infection. The persistence of IgG antibodies and cross-reactivity with Brucella spp. and Yersinia spp. complicate the interpretation of serological tests, regardless of the test system used (agglutination, immunofluorescence or ELISA).

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