Overview of Tularemia
Tularemia is a bacterial septicemia that affects >250 species of wild and domestic mammals, birds, reptiles, fish, and people. It is listed as a category A bioterrorism agent because of the potential for fatality, airborne dissemination, and societal disruption if released.
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, sheep are the most common host, but clinical infection has also been reported in cats, dogs, pigs, and horses. Cats are at increased risk because of predatory behavior 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 ticks Dermacentor 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 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 form. 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 form. 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 incubation period is 1–10 days. The most severely and commonly affected livestock species are sheep; Type A tularemia is particularly pathogenic for lagomorphs, and cats and nonhuman primates have been reported to be infected. The clinical presentation depends on host species, subspecies of the bacteria, and route of infection. 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 increased pulse and respiratory rates, coughing, diarrhea, and pollakiuria with lymphadenopathy and hepatosplenomegaly. 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.
The most consistent lesions are miliary, white to off-white foci of necrosis in the liver and sometimes in the spleen, lung, and lymph nodes. Organisms can be readily isolated from necropsy specimens by use of special media. 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.
Tularemia must be differentiated from other septicemic diseases (especially plague and pseudotuberculosis) or acute pneumonia. When large numbers of sheep show typical signs during periods of heavy tick infestation, tularemia or tick paralysis (see Tick Paralysis) should be suspected. Tularemia should be considered in cats with signs of acute lymphadenopathy, malaise, oral ulcers, and history of recent ingestion of wild prey.
Diagnosis of acute infection is confirmed by culture and identification of the bacterium, direct or indirect fluorescent antibody test, or a 4-fold increase in antibody titer between acute and convalescent serum specimens. A single titer of ≥1:80 by the tube agglutination test is presumptive evidence of prior infection. When tularemia is suspected, laboratory personnel should be alerted as a precaution to reduce the risk of laboratory-acquired infection. In some jurisdictions, tularemia in animals is reportable to public health authorities.
Streptomycin, gentamicin, and tetracyclines are effective at recommended dose 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. Early treatment is important to minimize risk of fatality. Because of the substantial sylvatic (wildlife and tick) component of the Francisella life cycle, control is limited to reducing arthropod infestation and to rapid diagnosis and treatment.