SUMMARY

Signs and Symptoms: Ulceroglandular tularemia presents with a local ulcer and regional lymphadenopathy, fever, chills, headache and malaise. Typhoidal tularemia presents with fever, headache, malaise, substernal discomfort, prostration, weight loss and a non-productive cough.

Francisella tularensis, the causative agent of tularemia, is a small, aerobic non-motile, gram-negative cocco-bacillus. Tularemia (also known as rabbit fever and deer fly fever) is a zoonotic disease which humans typically acquire after contact of their skin or mucous membranes with tissues or body fluids of infected animals, or from bites of infected deerflies, mosquitoes, or ticks. Less commonly, inhalation of contaminated dusts or ingestion of contaminated foods or water may produce clinical disease. Respiratory exposure by aerosol would cause typhoidal or pneumonic tularemia. F. tularensis can remain viable for weeks in water, soil, carcasses, and hides, and for years in frozen rabbit meat. It is resistant for months to temperatures of freezing and below. It is rather easily killed by heat and disinfectants.

Francisella tularensis was weaponized by the United States in the 1950's and 1960's during the U.S. offensive biowarfare program, and other countries are suspected to have weaponized this agent. This organism could potentially be stabilized for weaponization by an adversary and theoretically produced in either a wet or dried form. It could then theoretically be delivered against U.S. forces in a similar fashion to the other bacteria discussed in this handbook.

After an incubation period varying from 1-21 days (average 3-5 days), presumably dependent upon the dose of organisms, onset is usually acute. Tularemia may appear in several forms in man depending upon the route of inoculation: ulceroglandular, glandular, typhoidal, oculoglandular, pharyngeal, and pneumonic tularemia. In humans, as few as 10 to 50 organisms will cause disease if inhaled or injected intradermally, whereas approximately 10⁸ organisms are required with oral challenge.

Identification of organisms by staining ulcer fluids or sputum is generally not helpful. Routine culture is difficult, due to unusual growth requirements and/or overgrowth of commensal bacteria. Isolation represents a clear hazard to laboratory personnel and should only be attempted in BL-3 laboratory. The diagnosis can be established retrospectively serologically. A fourfold rise in the tularemia tube agglutination or microagglutination titer is diagnostic of infection. A single convalescent titer of 1:160 or greater is diagnostic of past or current infection. Titers are usually negative the first week of infection, positive the second week in 50-70 percent of cases and reach a maximum in 4-8 weeks.

Standard Precautions are recommended for healthcare workers. Streptomycin (1 gm every 12 hours IM for 10-14 days) is the treatment of choice. Gentamicin 3-5 mg/kg/day parenterally for 10-14 days is also effective. Tetracycline and chloramphenicol treatment are effective as well, but are associated with significant relapse rates. Although laboratory related infections with this organism are very common, person-to-person spread is unusual and respiratory isolation is not required.

Vaccine: A live, attenuated tularemia vaccine is available as an investigational new drug (IND). It is given by scarification. This vaccine has been administered to more than 5,000 persons without significant adverse reactions. It is of proven effectiveness in preventing laboratory acquired tularemia as well as in experimentally exposed human volunteers. As with all vaccines, the degree of protection depends upon the magnitude of the challenge dose; vaccine-induced protection could be overwhelmed by extremely high doses.