Tularemia is a bacterial disease that affects > 250 species of wild and domestic mammals, birds, reptiles, fish, and humans. It is listed as a category A bioterrorism agent because of the potential for fatality, airborne dissemination, and societal disruption if released. Clinical signs depend on the host species, subspecies of bacteria, and route of infection. Diagnosis is confirmed by bacterial culture, serological testing, or PCR assay. Antimicrobial treatment can be effective if begun early.
Etiology of Tularemia in Animals
Francisella tularensis is a non–spore-forming, gram-negative, facultatively intracellular coccobacillus that causes tularemia and is antigenically related to Brucella spp. The pathogen is inactivated by heat and disinfectants routinely used for hospital infection control; however, it survives for weeks or months in a moist environment.
F tularensis can be cultured readily on blood supplemented with cysteine but must be differentiated from other gram-negative bacteria on blood agar. Four subspecies of F tularensis exist:
F tularensis subsp tularensis (type A; divided into type A1 and type A2)
F tularensis subsp holarctica (type B)
F tularensis subsp mediasiatica
F tularensis subsp novicida
Disease in humans and animals is primarily caused by F tularensis subsp tularensis and F tularensis subsp holarctica. F tularensis subsp tularensis is found predominantly in North America and is more virulent; in humans, the mortality rate may be as high as 30% if untreated. F tularensis subsp holarctica, which is less virulent, is predominantly found in Europe but can also be found in North America.
Epidemiology and Transmission of Tularemia in Animals
Among domestic animals, tularemia has been reported in sheep, cats, dogs, pigs, and horses. Cats may be at increased risk because of their predatory behavior, whereas cattle appear to be resistant. Little is known of the true incidence and spectrum of clinical disease in domesticated animals.
Important wildlife hosts for F tularensis subsp tularensis include cottontail rabbits and jackrabbits, whereas the most common vectors are the ticks Dermacentor andersoni, Amblyomma americanum, and D variabilis and the deer fly Chrysops discalis.
Animal hosts of F tularensis subsp holarctica are numerous, including lagomorphs, beavers, muskrat, voles, and sheep. Ticks, flies, and fleas all may transmit this subspecies, which can also be acquired through exposure to contaminated water containing amoebas harboring this bacterium.
Although found in every state except Hawaii, tularemia is most often reported in the central, north-central, and western US (eg, California, Missouri, Oklahoma, South Dakota, and Montana), with an additional focus in Massachusetts, especially Martha's Vineyard. Disease has also been described in a number of dogs from New Mexico. Type A1 is found in the central and south-central regions of the US and is associated with cats, ticks, and lagomorphs. Type A1 is more virulent than type A2, which is found in the western US.
Tularemia can be transmitted by aerosol, direct contact, ingestion, or arthropod bites. 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 wildlife carcasses (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 (passing the pathogen from one life stage to the next) and transovarially, making them efficient reservoirs and vectors.
The most common source of F tularensis infection for humans and herbivores is the bite of an infected tick (approximately half of all cases follow tick bites); however, people who prepare or eat improperly cooked wild game are also at increased risk. Large outbreaks have been documented after exposure to organisms in the environment (ie, airborne or waterborne transmission). Pneumonic tularemia has been described after activities such as lawn mowing in tick-infested areas. Dogs, cats, and other carnivores may acquire infection from ingesting or even mouthing an infected carcass.
Zoonotic Risk of Tularemia in Animals
Tularemia is a zoonotic disease. Case reports have implicated cats as a source of infection for humans. Human-to-human transmission does not seem to occur.
Clinical Findings of Tularemia in Animals
The clinical presentation of tularemia depends on the host species, subspecies of bacteria, and route of infection. The incubation period is 1–10 days. F tularensis subsp tularensis is particularly pathogenic for lagomorphs; fatal infections have also been reported in cats and nonhuman primates. Sheep, cats, and dogs may be subclinically infected or can develop bacteremia, fever, and respiratory infection. Cats may also develop ulceroglandular or oropharyngeal disease, presumably through exposure to infected prey. Clinical signs of tularemia include the following:
tachycardia and tachypnea
cough
vomiting and diarrhea
oral ulceration
lymphadenopathy and hepatosplenomegaly
fever
Obtundation and death may occur in a few hours or days, although chronic infections with mild clinical signs, such as persistent lymphadenopathy, can also occur.
Lesions
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.
Diagnosis of Tularemia in Animals
Bacterial culture
Serological testing
PCR assay
Tularemia should be considered in endemic regions where there are clinical signs consistent with bacteremia, generalized or acute lymphadenopathy, or pneumonia. Tularemia must also be ruled out when large numbers of sheep develop illness during periods of heavy tick infestation or when large numbers of lagomorphs are found dead.
In regions where both plague and tularemia occur, plague is an important differential diagnosis in dogs and cats with clinical signs consistent with tularemia, as both diseases have similar clinical signs.
To decrease the risk of laboratory-acquired infection, laboratory personnel should be alerted when plague or tularemia is under consideration. When inhaled, as few as 10 F tularensis organisms are sufficient to cause disease in humans; thus, risk of transmitting infection during necropsy or to laboratory personnel is high, and special procedures and facilities are essential to prevent this.
Diagnosis of tularemia is confirmed by bacterial culture, serological testing, or PCR assay. (See F tularensis micrograph.)
Dr. Kari Lounatmaa.
Organisms can be readily isolated from necropsy specimens by use of special media; however, access to a laboratory that performs biosecurity level 3 procedures is required. A direct or indirect fluorescent antibody test, or a 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 collected 3 weeks apart confirms acute infection.
PCR assays are also offered by some veterinary diagnostic laboratories for rapid detection of Francisella.
Treatment and Control of Tularemia in Animals
Antimicrobials (if begun early)
Decreased exposure to wildlife and ticks
Early treatment of tularemia is important to minimize risk of fatality and decrease human exposure. Companion animals suspected of having tularemia should be treated as plague/tularemia suspects and moved to an isolation ward for treatment. High-density (N95) masks should be worn if affected animals have evidence of pneumonia, and extreme care should be taken to avoid bites or needle-stick injuries.
Aminoglycosides, tetracyclines, or fluoroquinolones have activity against F tularensis, with aminoglycosides (amikacin or gentamicin) being the treatment of choice. Gentamicin (5–8 mg/kg, IV or SC, every 24 hours) or amikacin (10–15 mg/kg, IV or SC, every 24 hours) is recommended for the first 72 hours to decrease the risk of human exposure. Treatment is recommended for 2–3 weeks.
Alternatively, doxycycline (5–10 mg/kg, PO, every 24 hours for 3–8 weeks) and marbofloxacin (2.75–5.5 mg/kg, PO, every 24 hours for 3–8 weeks) may be given for at least 3 weeks to avoid relapse.
Prevention of tularemia involves decreasing arthropod infestations and limiting predation and other exposure to wildlife. In some jurisdictions, tularemia in animals is reportable to public health authorities. Animal owners should inform their healthcare provider of a diagnosis of tularemia in their animal(s) should these animals develop illness. They should also be directed to online resources developed by the World Organisation for Animal Health (WOAH) and the CDC.
Key Points
Tularemia is a potentially fatal disease of numerous host species, including humans, with clinical signs that can include fever, lymphadenopathy, oral ulcerations, pneumonia, and hepatosplenomegaly.
Multiple subspecies of Francisella tularensis exist, with differing pathogenicity, ecological cycles, and geographical distributions. Ticks and wildlife are major sources of risk to humans and domestic animals. Outbreaks have been described in sheep in association with tick exposure. Only a few organisms are required to cause disease in humans after inhalation.
A high index of suspicion is required for efficient diagnosis and successful treatment of tularemia, which is important for decreasing risk for zoonotic transmission.
For More Information
Tularemia. World Organisation for Animal Health.
Tularemia. Centers for Disease Control and Prevention.
Sykes JE, Chomel BB, Nordstoga AB. Tularemia. In: Sykes JE, ed. Greene's Infectious Diseases of the Dog and Cat. 5th ed. Elsevier; 2023:916-924.
Also see pet owner content on tularemia in cats, dogs, and horses.
