Wendy Fleischman, DVM, DACVIM (SAIM)
Tularemia and plague are most commonly transmitted to domestic pets and people from May through October. According to the CO Department of Public Health and Environment, there has been only one case of feline tularemia confirmed in 2017, but it has been found in wildlife (8 rabbits and a fox) in at least four counties this year and there have been 82 human cases in the past 3.5 years in Colorado. In 2017 there have been 4 cats diagnosed with plague, 3 of them in our region: Boulder, Larimer, and Weld counties. The last of these cats was just diagnosed in June. Plague has also been found in a prairie dog and a flea pool in Larimer County as well as two foxes in Jefferson County. As these diseases are zoonotic, highly infectious, and potentially fatal, it is essential to be familiar with them and have them on the differential list for patients with compatible clinical signs.
Cause
Tularemia is caused by Francisella tularensis, a small gram negative, non-motile rod-shaped bacillus. It is a facultative, intracellular pathogen. There are four biovars, two of which occur in North America, including Colorado. The bacteria can infect a wide array of mammals including rabbits and other lagomorphs; mice, squirrels, voles, prairie dogs, muskrats, beavers, and other rodents; cats, dogs, sheep, pigs, horses, foxes, and bears. It can also infect birds, fish, amphibians, and insects.
Rabbits and, to a lesser extent, rodents are the most common source of infection in Colorado. Ticks serve as both a reservoir of infection and also as a vector of transmission. Infection can also be transmitted by fleas, lice, biting flies, and mosquitos. Cats and dogs most commonly become infected through ingestion of or contact with an infected animal or carcass. Infection can also be transmitted to domestic pets by infected vectors as noted previously.
The bacteria are hardy and can persist in soil, water, and carcasses for a prolonged period of time, thus infection through environmental exposure is possible. It can also cause infection through inhalation of aerosolized particles. Only a small dose of the bacterium is needed to cause infection. Cats are more susceptible to infection than dogs but both species may develop severe illness. Level of suspicion should be high for pets with compatible clinical signs who are allowed to roam and hunt. Once infected, the incubation period until clinical signs begin is typically between 1-10 days, but may be longer.
Presenting Symptoms
Clinical signs may range from mild to severe and are non-specific. Anorexia, lethargy, cough, nasal discharge, dyspnea, diarrhea, and/or vomiting may be reported by the client. A physical exam may demonstrate fever, lymphadenopathy, skin abscesses, uveitis, oral ulcers, and/or hepato/splenomegaly. Tularemia should be on the differential list in Colorado for any cat or dog that presents with fever and lymphadenopathy, especially cats that roam and hunt.
Diagnostics
Blood work may demonstrate a few non-specific abnormalities. CBC may demonstrate leukocytosis or leukopenia, anemia, and/or thrombocytopenia. Chemistry panel may demonstrate liver enzyme elevation, hyperbilirubinemia, hypoglycemia, and/or electrolyte derangements. Thoracic radiographs may demonstrate pulmonary infiltrates as tularemia has a pneumonic form, particularly in animals that became infected via inhalation of the pathogen. Abdominal US may demonstrate hepato and splenomegaly with microabscesses in the parenchyma.
Any cat or dog with clinical signs potentially consistent with tularemia should also be tested for plague, which we will discuss further in the next section. Samples should ideally be taken prior to initiating therapy with antibiotics. PCR can be performed on blood and/or aspirates of affected tissues such as lymph nodes or spleen. This can be done at the CSU Veterinary Diagnostic Lab or through the Colorado Department of Public Health and Environment (CDPHE) lab.
It is recommended that you contact the lab prior to obtaining and submitting samples to ensure correct sample acquisition and procedures for shipping. The CDPHE website has detailed instructions regarding appropriate sample acquisition. Serology via tube agglutination or ELISA is also available. It is important to recognize that seroconversion may take 2-3 weeks, thus serology performed in an acutely ill animal may be negative. Convalescent titers should be performed 2-3 weeks after the onset of illness. A four-fold titers rise in samples taken 10-14 days apart is considered consistent with infection. The bacteria can be cultured to confirm diagnosis but does not grow on standard media and may take a prolonged period of time to grow.
One should not attempt to culture F tularensis in-house as this poses a severe health risk to staff. The same is true of necropsy. Samples for culture can be submitted to CSU but it is recommended you contact the lab before doing so. Treatment should obviously not be withheld while diagnostic test results are pending.
Treatment
Treatment for domestic pets is extrapolated from human medicine and consists of antibiotics and supportive care as indicated. Parenteral antibiotic administration for the first 48 hours is preferred to avoid exposure to the patient’s oral mucous membranes during that time. After 48 hours of antibiotic therapy, the patient is considered non-infectious.
Based on the human experience, streptomycin and gentamicin are preferred. As streptomycin is not readily available, gentamicin is considered the treatment of choice. It is essential to monitor renal function during the administration of this medication and pre-existing renal disease is a contraindication to its use. Other antibiotics considered effective for tularemia are doxycycline, enrofloxacin or other fluoroquinolones, and chloramphenicol.
Patient Handling
Patients in the hospital with possible or confirmed tularemia should be kept in isolation with strict biohazard precautions taken to avoid infecting staff or other patients. This includes wearing gown, gloves, mask, and eye protection when handling the patient or collecting samples for diagnostic testing. Although hardy in the environment, F tularensis is relatively easily killed with routine disinfectants. Any materials used in the care of a patient with suspected tularemia should be thoroughly disinfected, autoclaved, or incinerated.
Cause
Plague is caused by Yersinia pestis, a gram-negative, non-motile rod-shaped coccobacillus. It is a facultative, intracellular pathogen. Rodents are the reservoir hosts for plague. Infection in a rodent population is transmitted by infected fleas. Plague can infect most mammals although susceptibility to infection varies by species. Transmission in pets most often occurs due to ingestion of an infected rodent or carcass. It can also be transmitted to cats and dogs by infected rodent fleas. Dog and cat fleas (Ctenocephalides spp) are considered poor vectors for plague. Exposure to an animal with the pneumonic form can lead to transmission via inhalation. The bacteria is sensitive to desiccation and heat but can survive in water, soil, and carcassess for weeks to months, thus environmental exposure represents another possible route of exposure. Once infected, the incubation period is usually less than one week.
Presenting Symptoms
Cats appear to be more susceptible to plague than dogs. As seen in humans, plague may present with three clinical forms in cats. The bubonic form is most common. Cats with this form demonstrate lethargy, anorexia, fever, and lymphadenopathy. In the septic form, cats may or may not demonstrate lymphadenopathy but may be profoundly ill with signs of sepsis or septic shock, including lethargy, fever, anorexia, vomiting, diarrhea, tachycardia, poor pulses, and hypotension. Either one of these forms may also be associated with the pneumonic form in which pulmonary involvement manifests with coughing, sneezing, nasal discharge, and/or dyspnea. The latter two forms are more likely to be fatal.
In dogs, clinical signs are more variable and often milder but can be severe and even fatal. It is important to note that the pneumonic form carries the highest risk of transmission to the veterinary staff.
Diagnostics
Potential blood work and radiographic abnormalities are similar to those noted previously for tularemia. Cats with the septicemic form of plague may also have evidence of hypotension, disseminated intravascular coagulation, multi-organ dysfunction, and/or acute respiratory distress syndrome. Thoracic radiographs should be performed in all cases where plague is considered possible as the potential human health ramifications of the pneumonic form are severe. Diffuse interstitial to coalescing infiltrates may be seen with the pneumonic form of plague.
As mentioned previously, any cat or dog with potentially consistent clinical signs should be tested for both diseases. The same samples being tested for tularemia can be tested for plague. Please refer to the Tularemia Diagnostics section for more information.
Unlike F tularensis, Yersinia pestis can also sometimes be identified on cytologic examination of infected fluid, including LN aspirates, sputum, blood, or CSF. Y pestis can also be more readily cultured than F tularensis. Again, extreme caution must be taken when collecting and submitting samples from patients suspected to have either of these diseases.
Patient Handling
Patients who are plague suspects or have confirmed plague must be strictly isolated with all precautions taken to contain spread of infection, as with tularemia. Additionally, a respirator should be worn with a patient suspected of having the pneumonic form of plague as there is a real hazard of transmission to humans due to aerosolized particles.
Some cats, particularly those with the septicemic and pneumonic forms, may require intensive 24-hour supportive care. Patients should be hospitalized and isolated for the first 2-4 days of treatment. After that time they are considered no longer infectious.
Treatment
Treatment for plague consists of antibiotic therapy as described for tularemia. In addition to the antibiotics noted previously, TMS can also be administered for plague. Duration of treatment is 10-21 days. Patients with possible or confirmed plague should be treated immediately for fleas as should any other animals in the household.
Owner Awareness & Prevention
Owners of patients with possible or confirmed tularemia or plague should be advised of its zoonotic nature. They should monitor other pets for clinical signs. If they themselves fall ill, they should seek medical evaluation and advise their doctor of the possibility of tularemia or plague. If tularemia or plague is confirmed, a course of prophylactic antibiotics, such as doxycycline, may be warranted for other exposed pets.
Prevention of these diseases in cats and dogs entails a restriction on roaming and hunting behavior and flea/tick prevention for all household pets. There is not a vaccine available for either of these diseases for domestic pets. The majority of human tularemia cases result from inhalation of aerosolized rabbit feces which are kicked up during mowing or gardening and from tick bites or other vector borne exposure. A minority of cases are due to contact with infected animals.
The majority of cases of plague in humans emanate from infected flea bites with the remaining cases due to contact with an infected carcass or infected animal. It is recommended that people with pets who roam in plague endemic areas not allow pets to reside in the bedroom or sleep in their bed as this serves as a common source for contact with fleas. Both tularemia and plague are reportable diseases and if suspected or diagnosed in a patient, should be reported immediately to the Colorado Department of Health.
*Both tularemia and plague are present in Colorado. Plague specifically has been identified in our region of Colorado in 2017. The likelihood of contracting these diseases is highest in the summer months.
*Cats who roam and hunt are at the highest risk for infection.
*Infection with tularemia or plague should be considered for any cat or dog that presents with fever, especially if they also demonstrate lymphadenopathy.
*Diagnosis can be achieved through the CDPHE lab or CSU DL.
*Antibiotic therapy should be initiated immediately after diagnostic sample acquisition.
*The patient should be kept in isolation and handled with strict biohazard precautionary measures until 2-3 days after initiation of appropriate antibiotic therapy.
References and further reading:
Berman-Booty LD, Cui J, Horvath SJ, Premanandan p: Pathology in practice. Tularemia. J Am Vet Med Assoc 2010 Vol 237 (2) pp. 163-5.
CO Department of Health and Environment Website www.colorado.gov/cdphe
Center for Disease Control Website www.cdc.gov
Green, CE. 2013. Infectious Diseases of the Dog and Cat. Elsevier Health Sciences.
Nichols MC, Ettestad PJ, VinHatton ES, Melman SD, Onischuk L, Pierce EA, and Aragon AS. Yersinia pestis infection in dogs: 62 cases (2003-2011). J Am Vet Med Assoc 2014, 244(10):1176-1180
Pennisi, M.G. et al. Francisella Tularensis Infection in Cats ABCD guidelines on prevention and management. J Fel Med Surg. 2013, 15: 585–587.
