Etiology and pathogenicity
The causative agent of tularemia is a pleomorphic, non-motile bacterium, Francisella tularensis. Three subspecies are distinguished: tularensis (North America, highest pathogenicity), holarctica (Eurasia), and mediaasiatica (Central Asia).
The pathogenicity of the bacterium is associated with its ability to undergo intracellular replication within macrophages, endothelial cells, and fibroblasts. Phagocytosis of the bacterium by phagocytes does not lead to its destruction, resulting in incomplete phagocytosis. The bacterial capsule protects against complement, and the surface protein AcpA (acid phosphatase) blocks the macrophage respiratory burst. Consequently, the phagosome fails to fuse with the lysosome. The microbe multiplies inside the cell for a long time, induces apoptosis, and escapes.
The endotoxin (lipopolysaccharide) of the tularemia bacillus is 1000 times less toxic than that of E. coli. Due to this, the interaction between the bacterium and the immune system causes only mild inflammatory changes. This allows the pathogen to persist for a long time and disseminate through the lymphatic system, forming productive granulomatous inflammation.
Epidemiology: reservoirs and transmission routes
Tularemia is a classic natural focal infection. The primary reservoir consists of animals of susceptibility group 1 (water rats, muskrats, hares, hamsters, voles). They suffer severe disease and die. An additional reservoir consists of blood-sucking insects. While horseflies and mosquitoes remain infectious for about two weeks after a bite, ixodid ticks retain the pathogen for life, transmitting it to their offspring (transovarially).
Humans belong to group 2: they are extremely susceptible to the infection, but bacteremia is mild. An infected person is not a source of transmission.
The transmission route determines the subsequent clinical form of the disease:
- Vector-borne: insect bites in summer.
- Contact: butchering carcasses, skinning, contact with contaminated hay.
- Aspiration (aerosol): inhalation of dust during agricultural work.
- Alimentary: consumption of water or food contaminated by rodents.
Clinical manifestations
The onset of the disease is always acute: chills, high fever, insomnia, myalgia and ossalgia (muscle and bone pain), hyperemia, and facial puffiness. Specific symptoms depend on the portal of entry:
- Ulceroglandular: an ulcer develops at the site of the insect bite, and regional lymph nodes enlarge to form a bubo.
- Glandular: lymphadenitis without a primary skin lesion. Lymph nodes in tularemia are moderately painful, not fused with surrounding tissues, and show no signs of periadenitis.
- Oculoglandular: involvement of the conjunctiva and regional lymph nodes.
- Oropharyngeal (tonsilloglandular): specific involvement of the tonsils.
- Pulmonary (thoracic): proceeds in a bronchitic or pneumonic variant.
- Gastrointestinal (abdominal): abdominal pain, involvement of mesenteric nodes.
- Generalized: septic, typhoid-like course.
Diagnostics, management, and microbial survival
The basis of the diagnosis is a well-taken epidemiological history (horsefly bites, staying at a dacha, contact with rodents). When tularemia is suspected, a general practitioner is obliged to refer the patient for hospitalization in an infectious diseases hospital; outpatient treatment is not performed.
The diagnostic workup includes CBC, urinalysis, bacteriological culture of bubo aspirate, serological and allergic tests for tularemia. Differential diagnosis is performed with cat-scratch disease (benign lymphoreticulosis), common lymphadenitis, and tuberculous lymphadenitis.
Francisella tularensis is extremely resistant to cold: it survives in water and soil for up to 6 months, and in frozen rodent carcasses for half a year. However, it is rapidly killed by heat: at 60°C within 5–10 minutes, and upon boiling within just 1–2 minutes.
Briefly: answers to topical questions
What diseases must the ulceroglandular form of tularemia be differentiated from?
The ulceroglandular form of tularemia must be differentiated from cutaneous anthrax and cutaneous plague.
Differences from cutaneous anthrax:
- Smaller ulcer size (no more than 0.5–0.7 cm).
- Raised and firm edges.
- Minimally painful.
Differences from cutaneous plague:
- Slow formation of elements.
- Low pain intensity.
- General condition of the patient is mildly impaired.
Which antibacterial drugs are the drugs of choice for etiotropic treatment of tularemia?
The drugs of choice for etiotropic treatment of tularemia are the following antibacterials (course duration — at least 2 weeks):
- Gentamicin (IM or IV).
- Amikacin (IM or IV).
- Streptomycin (IM or IV).
- Doxycycline (IM, IV, or oral).
- Rifampicin (IV or oral).
- Chloramphenicol (IV or oral, especially indicated for meningitis).
Aminoglycosides, macrolides, and fluoroquinolones are also drugs of choice.
Which specific serological reactions are used to confirm the diagnosis of tularemia?
To confirm the diagnosis of tularemia, the following serological reactions are used:
- Indirect hemagglutination assay (IHA) with a diagnostic titer of 1:100 and higher.
- Enzyme-linked immunosorbent assay (ELISA) with a diagnostic titer of 1:400.
- Agglutination test (AT).
- Immunofluorescence assay (IFA).
Which vaccine is used for specific prophylaxis of tularemia and what is the method of administration?
For specific prophylaxis of tularemia, a dry live tularemia vaccine is used (developed by B.Ya. Elbert and N.A. Gaysky). The basis of the vaccine is strain No. 15 of F. tularensis subspecies holarctica. The method of administration is a single percutaneous application.
Link between transmission route and clinical form: Tick bite — ulceroglandular. Ingested contaminated food — abdominal. Inhaled hay dust — pulmonary. Wherever the microbe enters, a local lymph node (bubo) will develop nearby.
Class and exam questions
Why is purulent inflammation poorly expressed in tularemia, while granulomas predominate?
This is because the bacterial endotoxin is 1000 times weaker than that of common enteric bacteria. It barely triggers an acute inflammatory response, giving the pathogen time to multiply covertly inside macrophages and form granulomas.
Is it necessary to isolate close contacts living with a patient with tularemia?
No, a person does not shed the pathogen into the environment in quantities sufficient to infect other people. However, the physician must explain transmission routes to relatives and the necessity of visiting a clinic if similar symptoms develop (since they may have been infected from the same source).
How dangerous is tularemia as a biological weapon?
It is extremely dangerous. Humans possess the highest susceptibility to aerosol transmission of tularemia, which can lead to mass outbreaks of the severe pulmonary form.
What else to study on this topic
- Features of the bacterial antigenic structure: transition of virulent S-forms to avirulent R-forms and loss of the Vi-antigen.
- Principles and regimens of etiotropic and pathogenetic therapy for various clinical forms of the disease.
- Indications for surgical treatment (management of suppurated tularemia bubo).
- Methods of specific (vaccination) and non-specific prophylaxis (deratization, disinsection) in natural foci.
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