The organism is a small, non-motile, Gram-negative, facultatively intracellular, aerobic coccobacillus, measuring 0.2 μm x 0.3–0.7 μm. Within the species, there are two predominant sub-species: F. tularensistularensis or Type A is more virulent than F. tularensis palaearctica or Type B. The organism can survive for up to several weeks in the natural environment
F. tularensis tularensis is found in North America, while F. tularensis palaearctica occurs in Asia, Europe and North America.
Many wild animals, especially rabbits, hares, voles, muskrats and beavers, as well as some hard ticks. The disease has been reported in many other animals, including various rodents, birds, reptiles, amphibians and marine mammals. It is also found in soil and water.
Mode of transmission
Tularaemia is primarily a disease of a wide variety of wild mammals and birds. Humans become infected mainly through the bite of arthropods, particularly ticks and mosquitoes, and through the skin, conjunctival sac or oropharyngeal mucosa, by direct contact with infected animals or animal materials and by ingestion of contaminated food or water or inhalation of contaminated dust or aerosols. F. tularensis is easily transmitted by aerosols and inhalation of only a few organisms is likely to cause infection. Person-to-person transmission has not been documented.
The incubation period varies from 1 to approximately 14 days, averaging 3–5 days.
Clinical manifestations depend on the route of entry and the virulence of the agent. Infection through the skin or conjunctiva usually produces an ulceroglandular form, with an indolent ulcer at the site of entry and painful swelling of local lymph glands, which may suppurate. In some cases the site of entry is inconspicuous, there being only local lymph gland involvement.
Infection resulting from ingestion is characterized by a painful pharyngitis and associated cervical lymphadenitis.
Rarely, an intestinal form may develop with infection of the mesenteric nodes, and characterized by abdominal pain, diarrhoea and vomiting. Both forms are usually accompanied by an abrupt onset of fever, accompanied by chills, malaise and joint and muscle pain. Ulceroglandular tularaemia caused by virulent strains, if untreated, has a case-fatality rate of about 5% and lasts 2–4 weeks, with a convalescent period of up to 3 months.
Depending on the site in the respiratory system at which infection occurs, inhalational tularaemia may take the form of a primary pneumonia or of tracheitis and bronchitis. The initial manifestation, however, may be influenza-like without evident signs of respiratory involvement.
Pleuropulmonary tularaemia with a virulent strain has a high case-fatality rate (40–60%) if untreated. The organism may enter the bloodstream, causing systemic illness, often severe. Untreated sepsis with the more virulent Type A strain is often fatal. Systemic illness without apparent site of primary infection is commonly termed “typhoidal tularaemia”.
Direct microscopic examination of clinical specimens showing small, poorly staining Gram-negative bacteria may suggest the diagnosis, and be supported by direct fluorescent antibody staining. Other supportive tests include PCR and antigen-capture ELISA methods. Confirmation is obtained by culturing the organism in cysteine-rich media, such as cysteine-enriched broth, thioglycolate broth, or cysteine heart blood agar, and by detecting diagnostic antibody titres to F. tularensis
The organism is extremely infectious and poses a substantial risk of laboratory-acquired infection unless handled according to stringent safety guidelines. Biosafety Level 2 practices, equipment and facilities are recommended for routine handling of clinical specimens from humans or animals. Biosafety Level 3 practices, equipment and facilities, including the use of a negative pressure biosafety cabinet, are recommended for all manipulations of cultures and any procedures posing a risk of aerosolization, such as centrifugation.
There is no requirement for quarantine of patients or immunization of contacts. Standard precautions are indicated where there are open lesions and discharges from ulcers, including autoclaving, incineration or disinfection of discharges and contaminated materials.
Prophylaxis and therapy
Live attenuated vaccines applied intradermally have proved effective in preventing or attenuating infection by the cutaneous and inhalatory routes. Vaccines of this type have been used to reduce the risk of tularaemia in populations living in endemic regions of the former Soviet Union and, although not approved or available for general use in the USA. At present, tularaemia vaccine supplies are available in the Russian Federation only, but the vaccine may be available outside the Russian Federation in the future, if necessary. Attempts to develop improved vaccines are under way in a number of countries.
For antimicrobial prophylaxis, oral administration of doxycycline or ciprofloxacin is recommended for a 14-day period following the last day of exposure. For therapy, streptomycin is the recommended antimicrobial of choice, and is administered parenterally at 15 mg/kg twice daily for 10 days, but not to exceed 2 g per day.
Parenteral gentamicin, doxycycline or ciprofloxacin are recommended alternatives to streptomycin. Patients beginning treatment with parenteral doxycycline or ciprofloxacin can switch to oral antimicrobial administration when clinically indicated.
Recommended duration of administration of gentamicin or ciprofloxacin for treatment of tularaemia is 10 days.
Doxycycline, however, is bacteriostatic, and treatment should continue for 14–21 days to avoid relapse. Chloramphenicol has been used to treat tularaemia, but there is a higher rate of primary treatment failure and relapse with its use than with the antimicrobials noted above.