Introduction: Tularemia was first described as a plague-like disease of rodents in 1911, and 1921 in humans. The disease remains widely enzootic in North America, Europe and northern Asia, ticks, mosquitoes and biting flies have been implicated as vectors in transmission to humans and animals. Contaminated hay, water, infected animals and carcasses as well as aerosolized particles have been documented as sources of infection. Francisella tularensis is one of the most infectious bacteria known, requiring inoculation of as few as 10 organisms to cause infection. F. tularensis has long been considered as a potential biological weapon, it was one of the agents studied by the Japanese Imperial Army during occupation of Manchuria (1932-1945). By the late 1960, United States stockpiled F. tularensis in weaponized form; there are reports that strains weaponized by the Soviet Union in the 1990s were engineered to be resistant to antibiotics and vaccines. Live attenuated vaccines were developed in both countries, however volunteer studies showed poor protection against virulent aerosol challenges. The vaccine is currently under review by the FDA.

The Organism: Francisella tularensis is a tiny, gram-negative coccobacillus. Two major subspecies (biovars) exist: type A, which is highly virulent and is the most common isolate in North America, and type B (palaearctica), which is relatively avirulent, and is thought to cause all cases of tularemia in Europe and Asia. F .tularensis is a facultative intracellular bacterium, which can multiply within macrophages.

Transmission: Most cases occur by bites of infective arthropods (June through September), but also by contact with infected animals during farm activities, hunting and butchering. Laboratory workers are especially vulnerable, either by accidental inoculation or by inhaling aerosolized organisms. Person to person spread has not been documented.

Clinical manifestations and epidemiology: The incidence of tularemia in the U.S. declined since 1950s; between 1985 and 1992 there were 1409 cases and 20 deaths reported to the CDC (the reporting requirement of tularemia cases has been re-instated in 2001). The cases occurred predominantly in the mid-Western states. The ulceroglandular form of tularemia, which results from handling of infected carcass or arthropod bite, presents as a cutaneous papule, which becomes pustular and ulcerates over a few days. Typically, there is regional lymphadenopathy; even with antibiotic treatment the affected nodes may become fluctuant and rupture. Tularemia pneumonia may be a result of hemotogenous spread or a consequence of inhaling aerosolized organisms, a postulated method of a bioweapon attack. The largest outbreak of inhalational tularemia occurred in 1966 in Sweden, involving more than 600 patients in an extensive farming area. The onset of disease is usually abrupt after 3 to 5 days following exposure, with high fever, headache, chills and rigors, and generalized body aches. A pulse-temperature dissociation has been observed in as many as 42% of patients. Cough frequently occurs with or without objective signs of pneumonia; radiologic evidence of pneumonia is seen only in 25% to 50% of patients in the early stages of infection. Pulmonary infection can rapidly progress to severe pneumonia and death.

Laboratory diagnosis: If only routine microbiologic screening techniques for bacterial pathogens are followed, it is likely that identification of F. tularensis will be missed or delayed for several days or weeks. Therefore, an alert clinician must trigger suspicion of tularemia. F .tularensis is a fastidious organism, which requires cysteine supplementation for growth in most laboratory media. It is non-motile, has a thin capsule, and is mostly non-fermenting, utilizing glucose as the primary source. In smears the organisms are often difficult to visualize, and appear as mostly single cell, tiny, gram-negative rods. F. tularensis grows slowly in culture at 37 deg C, and need to be observed for 10 days for evidence of growth. Chocolate agar (CHAB) is the preferred growth medium, although the organism will grow on cysteine heart and Thayer-Martin agar. On CHAB plates, the colonies appear greenish-white, dense and have an opalescent sheen after 48-72 hours. There is little or no hemolysis. Identification can be challenging using typical phenotypic tests; F. tularensis does possess a characteristic fatty acid profile, which is the method utilized in our laboratory. Antigen detection assays, such the use of fluorescent-labeled antibodies, ELISA, and immunoblotting, as well as DNA-based assays (PCR) can be used for detection of F. tularensis in tissue specimens by reference laboratories. Serologic methods also exist, however serum antibody titers in tularemia do not reach diagnostic levels until 10 days or longer from the onset of symptoms.