Tularemia (rabbit fever, deerfly fever) is caused by the gram-negative bacterium Francisella tularensis. It was identified more than 60 years ago in infected ground squirrels in California, and in 1914, the first described human case occurred in a restaurant worker in Cincinnati.

Of the five recognized subspecies of F. tularensis, only two are considered clinically significant in humans. Of these, F. tularensis subsp. tularensis is highly infective for rabbits, humans, and cats. F. tularensis subsp. holarctica is more often associated with rodents and aquatic mammals (muskrats, mice, beaver, prairie dogs, voles, water voles) than rabbits and humans. F. tularensis subsp. novicida is found in the United States, Australia, and Canada, and can cause tularemia-like illness, but is less infectious.

Tularemia most commonly affects lagomorphs (rabbits and hares) and rodents, whereas infections in birds, fish, amphibians, and reptiles are relatively rare. Tularemia has been observed in pet monkeys and nonhuman primates housed in zoos and laboratories (squirrel monkeys, black and red tamarins, talapoins, and lowland gorillas). Carnivores require high doses of the bacterium to become infected, although wild carnivores may serve as reservoirs of the bacteria. In 2005, antibodies to F. tularensis were detected in 32% of coyotes and 38% of raccoons in Nebraska.

While domestic animals and humans are usually considered accidental hosts, outbreaks occurring in sheep in the United States, Canada and Russia have resulted in high mortality. Outbreaks also have been identified in commercially bred mink, beaver, and fox. A 2006 serological survey of 91 privately owned, healthy cats in New York and Connecticut determined that 12% of the cats had antibodies to F. tularensis. Dogs appear to be more resistant, but may serve as reservoir hosts.

The annual number of reported human cases of tularemia in America is ~100-200. Since 1990, more than half have come from Arkansas, Missouri, South Dakota, and Oklahoma in association with high insect vector activity and rabbit hunting. Tularemia is endemic on Martha's Vineyard, Massachusetts, with outbreaks in 1978 and 2000.

The bacteria can survive in mud, soil, decaying animal carcasses, or water for long periods of time (weeks to months). Infection can be transmitted by arthropod (tick and deerfly) bites, inhalation of aerosolized bacteria, eating or drinking contaminated food or tissues, and handling infected animals or tissues. Ticks are the most important vectors of F. tularensis, transferring the bacterium between rabbits, hares, and rodents and serving as a reservoir. Deerflies, horseflies, mosquitoes, sucking lice, and biting flies may also transmit the bacteria from one animal to another or to humans.

Sheep and domestic cats can be sources of infection for humans. Human tularemia cases have occurred from shearing infected sheep, following direct contact with infected cats, and through cat bites or scratches from infected cats. Wild-caught prairie dogs, destined for sale in 2002 as exotic pets in the United States and Europe died in large numbers at a commercial holding facility in Texas. Cannibalization of carcasses by other prairie dogs was believed to play a major role in propagating the infection. Fourteen of 20 exposed personnel reported symptoms consistent with tularemia. Tularemia has been reported in a human patient following kidney transplantation from an infected organ donor. Veterinarians, wildlife handlers, farmers, sheep handlers and shearers, hunters, trappers, meat handlers, cooks, landscapers, and laboratory workers are at higher risk of exposure and disease.

F. tularensis is one of the most infectious pathogens. Known doses as low as 10 colony-forming units can cause infection. The bacterium is classified as a Category A agent by the World Organization for Animal Health due to its ease of spread, potential for high mortality rates and use in bioterrorism, major public health impact, and potential for inducing public panic and social disruption.