The causative bacterium, Francisella tularensis, is a nonspore-forming, gram-negative coccobacillus antigenically related to Brucella spp. It is a facultative intracellular parasite that is killed by heat and proper disinfection but survives for weeks or months in a moist environment. It can be cultured readily on blood supplemented with cysteine but must be differentiated from other gram-negative bacteria on blood agar. The taxonomic status of Francisella has been revised and debated, but recent consensus establishes the subspecies F tularensis tularensis, associated with type A tularemia; F tularensis holarctica, which causes type B tularemia; and a third type, C, associated with F novicida, which has low virulence and is less common than the other two. Type A has been found predominantly in North America and is more virulent; in people, the mortality rate may be as high as 30% if untreated. Type B is less virulent and occurs in both the Old and New Worlds.
Among domestic animals, clinical infection of tularemia has been reported in sheep, cats, dogs, pigs, and horses. Cats are at increased risk because of predatory behavior on small mammal hosts and appear to have an increased susceptibility, whereas cattle appear to be resistant. Little is known of the true incidence and spectrum of clinical disease in domesticated animals. Important wild animal hosts for F tularensis tularensis include cottontail and jackrabbits, whereas the most common vectors are the ticksDermacentor andersoni (the wood tick), Amblyomma americanum (the lone star tick), D variabilis (the American dog tick), and Chrysops discalis (the deer fly). Animal hosts of F tularensis holarctica are numerous, including lagomorphs, beaver, muskrat, voles, and sheep. Ticks, flies, fleas, and exposure to contaminated water sources are all associated with transmission of this subspecies, which has also been found to persist naturally in a water-associated amoeba.
Natural foci of infection exist in North America and Eurasia. Although found in every state except Hawaii, tularemia is most often reported in the southcentral and western USA (eg, California, Missouri, Oklahoma, South Dakota, and Montana).
Tularemia can be transmitted by aerosol, direct contact, ingestion, or arthropods. Inhalation of aerosolized organisms (in the laboratory or as an airborne agent in an act of bioterrorism) can produce a pneumonic clinical presentation. Direct contact with, or ingestion of, infected carcasses of wild animals (eg, cottontail rabbit) can produce the ulceroglandular, oculoglandular, oropharyngeal (local lesion with regional lymphadenitis), or typhoidal forms. Immersion in or ingestion of contaminated water can result in infection in aquatic animals. Ticks can maintain infection transstadially and transovarially, making them efficient reservoirs and vectors.
The most common source of infection for people and herbivores is the bite of an infected tick, but people who prepare or eat improperly cooked wild game are also at increased risk. Dogs, cats, and other carnivores may acquire infection from ingestion of an infected carcass. Case reports have implicated cats as a source of infection in people.
The clinical presentation of tularemia depends on the host species, subspecies of the bacteria, and route of infection. The incubation period is 1–10 days. Type A tularemia is particularly pathogenic for lagomorphs, with fatal infections also reported in cats and nonhuman primates. Sheep and cats may be subclinically infected or develop bacteremia, fever, and respiratory infection. Cats may also develop ulceroglandular or oropharyngeal disease, presumably through exposure to infected prey items. Clinical signs include:
Prostration and death may occur in a few hours or days. Sporadic cases are best recognized by signs of septicemia. Outbreaks in untreated lambs may have up to 15% mortality.
When individual animals present with consistent clinical signs of septicemic disease, generalized or acute lymphadenopathy, or pneumonia, tularemia must be considered a possible cause. Tularemia should also be ruled out when large numbers of sheep show typical signs during periods of heavy tick infestation or when large numbers of rodents or lagomorphs are found dead. Affected sheep should be evaluated for tularemia and tick paralysis, whereas the etiologic agents to consider in cats and small mammals should also include agents of plague and pseudotuberculosis.
When tularemia is suspected, laboratory personnel should be alerted as a precaution to reduce the risk of laboratory-acquired infection. The infective dose required to transmit this pathogen is extremely low; thus, risk of infection during necropsy or to laboratory personnel is significant, and special procedures and facilities are essential.
Diagnosis of acute infection of tularemia is confirmed by bacterial culture and identification of the bacterium, serology, or PCR. Organisms can be readily isolated from necropsy specimens by use of special media using stringent personal protection protocols. A direct or indirect fluorescent antibody test, or tube agglutination test with a single titer of ≥1:80, is presumptive evidence of exposure, whereas a 4-fold increase in antibody titer between acute and convalescent serum specimens confirms acute infection. PCR can be used to confirm infection rapidly.
Early treatment is important to minimize risk of fatality. Streptomycin, gentamicin, and tetracyclines are effective at recommended dosage levels. Gentamicin should be continued for 10 days. Because tetracycline and chloramphenicol are bacteriostatic, they should be continued for 14 days to minimize the risk of relapse.
Because of the substantial sylvatic (wildlife and tick) component of the Francisella life cycle, control involves reducing arthropod infestations and limiting exposure to wildlife, for example by keeping cats and dogs indoors. In some jurisdictions, tularemia in animals is reportable to public health authorities.
Tularemia is a possibly fatal disease of numerous hosts, including people, with highly variable presentation.
There are multiple subspecies of Francisella tularensis, with differing pathogenicity, ecologic cycles, and geographic distributions. Ticks and wildlife are major sources of risk to people and domestic animals.
An index of suspicion is necessary to diagnose and treat tularemia effectively.