Did You Know That Up to 80% of Cat Fleas Carry Human or Pet Pathogens?

A number of feline flea borne disease agents can be zoonotic. The most risk is from Bartonella spp., Rickettsia felis, and Yersinia pestis. Coxiella burnetii DNA has also be amplified from fleas. The purpose of this proceedings is provide an update on the diagnosis and management of clinical abnormalities associated with Bartonella spp, and Rickettsia spp. infections of cats. Please also see the AAFP reports on feline bartonellosis and zoonoses guidelines www.catvets.com.

Bartonellosis

A number of Bartonella spp. including B. henselae, B. clarridgeiae, B. koehlerae, B. quintana and B. bovis have been cultured or amplified from client-owned cats with fever. Fever following experimental inoculation with B. henselae has been documented in a number of studies including a recent study in our laboratory where the CSU-1 strain of B. henselae induced significant fever in three of six cats after exposure to infected C. felis (Bradbury et al, 2010). None of the six cats administered imidacloprid-moxidectin in that study became infected or febrile. However, not all strains or Bartonella spp. induce fever in all cats; for example in the imidacloprid-moxidectin study, cats inoculated with the same strain intravenously failed to develop fever. Whether fever will occur during Bartonella spp. infection is likely a complex interaction that is influenced by both host and organism factors. Lymphadenopathy, endocarditis, myocarditis, and hyperglobulinemia are other well documented manifestations of bartonellosis in cats (Whittemore et al, 2012).

As B. henselae, B. clarridgeiae, B. koehlerae are transmitted by fleas, bacteremia and antibody positive rates can be very high. For example, serum antibodies were detected in 93% of cats housed in a North Carolina shelter and Bartonella spp. DNA was amplified from the blood of > 50% of cats housed in an Alabama shelter. The majority of these cats were thought to be normal which emphasizes that fever from bartonellosis cannot be documented by test results alone. In one study of pair matched cats with or without fever, serum Bartonella antibodies detected by ELISA or Western blot immunoassay were not correlated to the presence of fever (Lappin et al, 2009). In addition, serum antibody test results are negative in between 3 and 15% of bacteremic cats. Thus, if a cat with fever is to be evaluated for Bartonella spp. infection the combination of blood culture or PCR assay on blood, and serologic testing will detect the greatest number of cats that are currently or previously infected (www.dlab.colostate.edu; www.galaxydx.com). Febrile cats that are seronegative and negative for Bartonella spp. in blood by culture or Bartonella spp. DNA in blood are unlikely to have the organism as the cause of fever.

If fever or other clinical signs from bartonellosis is suspected in a cat, administration of doxycycline or a fluoroquinolone is generally effective. Doxycycline at 10 mg/kg, PO, daily for 7 days as the initial therapeutic trial has been recommended by some veterinarians. If a positive response is achieved, continue treatment for 2 weeks past clinical resolution of disease or for a minimum of 28 days. If a poor response is achieved by day 7 or doxycycline is not tolerated and bartonellosis is still considered a valid differential diagnosis, fluoroquinolones are appropriate second choices. In experimental or field studies, administration of enrofloxacin or orbifloxacin have led to rapid resolution of fever in cats with presumed bartonellosis. Azithromycin is now considered contraindicated because of rapid induction of resistance (Biswas et al, 2010). The new veterinary fluoroquinolone, pradofloxacin (Veraflox, Bayer Animal Health) is the least likely to cause resistant strains of B. henselae and so may be the preferred quiniolone for the treatment of this syndrome (Biswas et al, 2010). Flea control with imidocloprid containing compounds (Advantage Multi and Seresto collar; Bayer Animal Health) has been shown to block transmission of B. henselae amongst cats by Ctenocephalides felis (Lappin et al, 2013).

The clinical manifestations of bartonellosis in people are more extensive than just catscratch disease, peliosis hepatis, bacillary angiomatosis, and valvular endocarditis. It is now apparent that immune-competent individuals can develop a number of Bartonella spp.–associated chronic inflammatory syndromes and Bartonella spp. infections are an occupational risk for veterinary health care providers (Breitschwerdt et al, 2007; Lantos et al, 2014; Oteo et al, 2017). For example, Bartonella spp. infection was commonly confirmed in people with rheumatic symptoms in a Lyme disease–endemic region (Maggi et al, 2012). Bartonella henselae may have contributed to the death of 2 veterinarians (Breitschwerdt et al, 2015). Veterinarians or others commonly exposed to cats or fleas that develop chronic inflammatory diseases should have Bartonella spp. on the list of differential diagnoses.

Feline Hemoplasmosis

Hemolytic anemia, with or without fever, are the most common abnormalities associated with infection by Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’, or ‘Candidatus M. turicensis’. In multiple studies of experimentally infected cats, M. haemofelis is apparently the most pathogenic species. Dual infection with hemoplasmas may potentiate pathogenesis of disease. In one study, cats with chronic ‘Candidatus Mycoplasma haemominutum’ infection had more severe anemia and longer duration of anemia when experimentally infected with M. haemofelis when compared to cats infected with M. haemofelis alone. In one abstract, our research group reported an association between M. haemofelis and fever in cats without anemia. Clinical signs of disease depend on the degree of anemia, the stage of infection, and the immune status of infected cats. Direct transmission may occur with the hemoplasmas and so the agents should be on the differential list for cats with a history of fighting (Dean et al, 2008).

Diagnosis of hemoplasmosis is based on demonstration of the organism on the surface of erythrocytes on examination of a thin blood film or by PCR assay results. Organism numbers fluctuate and so blood film examination can be falsely negative up to 50% of the time. The organism may be difficult to find cytologically, particularly in the chronic phase. Thus, PCR assays are the tests of choice due to sensitivity.

Doxycycline is often administered as a flavored suspension (to avoid esophageal strictures) at 10 mg/kg, PO, every 24 hours for a minimum of 7 - 10 days. In cats intolerant of doxycycline, enrofloxacin given at 5 mg/kg, PO, every 24 hours for 14 days was tolerated by cats and is equally effective or more effective than doxycycline. Administration of marbofloxacin or orbifloxacin gives similar results. Azithromycin was not effective for the treatment of hemoplasmosis in one study (Westfall et al, 2001). Pradofloxacin (Veraflox®; Bayer Animal Health) is the only drug proven to eliminate M. haemofelis infection in experimentally inoculated cats (Dowers et al, 2009). Most drug protocols have failed to eliminate infection and so at this time there is no clinical utility to repeat PCR testing. The owners should be warned that recurrences may occur but are unusual.

Feline Rickettsiosis

Rickettsia spp. are obligate intracellular gram negative bacteria that are divided into the spotted fever group and the typhus group. Cats can be infected by Rickettsia felis and have been shown to have antibodies against R. rickettsii. Rickettsia felis DNA has been amplified from C. felis, C. canis, and Pulex irritans; these fleas have a worldwide distribution. Ctenocephalides felis is a biological vector for R. felis; the organism can be transmitted transovarially and transtadially within the flea. Rickettsia felis DNA has been amplified from fleas collected from dogs or cats around the world including including Australia, France, Israel, New Zealand, Thailand, the United Kingdom, and the United States.

Fever, headache, myalgia, and macular rash in human beings have been attributed to R. felis infection around the world (Angelakis et al, 2016). Rickettsial infection is suspected to a cause of fever in cats but this has not been well documented. While we have commonly amplified R. felis from C. felis (67.4% of flea extracts in one study), we have not amplified the organism from the blood of healthy cats or cats with fever. However, in one study of cats with fever, we showed R. felis and R. rickettsii antibody prevalence rates in cats in the USA to be 5.6% and 6.6%, respectively but neither organism was amplified from blood (Bayliss et al, 2009). These results prove that cats are sometimes exposed to spotted fever group organisms but further data are needed to determine significance of diseases associations. Because clinical illness in cats has not been documented, optimal treatment is unknown. However, based on results in dogs, doxycycline or a fluoroquinolone would be logical choices.

Yersinia Pestis (Feline Plague)

Yersinia pestis is the facultatively anaerobic gram-negative coccobacillus that causes plague. The organism is maintained in a sylvan life cycle between rodent fleas and infected rodents, including rock squirrels, ground squirrels, and prairie dogs. However, it has been shown that C. felis can be a competent vector, but transmission was less efficient than by a rodent flea in one experimental study (Eisen, 2008). Both cats and dogs are susceptible to infection. Antibodies against Y. pestis have also been detected in serum of nondomestic felids. Clinical disease is recognized most frequently from spring through early fall, when rodents and rodent fleas are most active. However, a recent unpublished case in Colorado was diagnosed in December of a mild winter. Most of the cases in human beings and cats in the United States have been documented in Colorado, New Mexico, Arizona, California, and Texas. Of the cases of human plague diagnosed from 1977 to 1998, 23 (7.7%) resulted from contact with infected cats (Gage et al, 2000).

Cats and dogs are infected after being bitten by infected rodent fleas, after ingestion of bacteremic rodents, or after inhalation of the organism. After ingestion, the organism replicates in the tonsils and pharyngeal lymph nodes, disseminates in the blood, and results in a neutrophilic inflammatory response and abscess formation in infected tissues. The incubation period is 2 to 6 days after a flea bite and 1 to 3 days after ingestion or inhalation of the organism. Outcomes in experimentally infected cats include death (6 of 16 cats; 38%), transient febrile illness with lymphadenopathy (7 of 16 cats; 44%), or inapparent infection (3 of 16 cats; 18%) (Gasper et al, 1993).

Bubonic, septicemic, and pneumonic plague can develop in infected human beings, dogs, and cats. Bubonic plague is the most common form of the disease in cats, but individual cats can show clinical signs of all three syndromes. Most infected cats or dogs are allowed outdoors and have a history of hunting. Anorexia, depression, cervical swelling, dyspnea, and cough are common presenting complaints; fever is detected in most infected cats. Unilateral or bilateral enlarged tonsils, mandibular lymph nodes, and anterior cervical lymph nodes are detected in approximately 50% of infected cats. Cats or dogs with pneumonic plague commonly have respiratory signs and may cough. In a series of 62 suspected dog cases, the most common clinical signs were included fever (100%), lethargy (97%), and anorexia (77%); only 23% of the dogs had lymphadenopathy (Nichols et al, 2013).

Supportive care should be administered as indicated for any bacteremic animal. Cervical lymph node abscesses should be drained and flushed with the clinician wearing gloves, a mask, and a gown. Parenteral antibiotics should be administered until anorexia and fever resolve. Optimal antibiotics for treatment of plague in infected cats in the United States are unknown. Streptomycin administered intramuscularly at 5 mg/kg q12h was used historically but is not widely available. Cats treated with gentamicin intramuscularly or intravenously at 2 to 4 mg/kg q12-24h, or enrofloxacin intramuscularly or intravenously at 5 mg/kg q24h, have resolved clinical signs. Chloramphenicol administered orally or intravenously at 15 mg/kg q12h can be used in cats with central nervous system signs. Antibiotics should be administered orally for 21 days after the cat has survived the bacteremic phase; doxycycline at 5 mg/kg q12-24h is an appropriate choice. In one study 90.9% of cats treated with antibiotics survived, whereas only 23.8% of untreated cats survived (Eidson et al, 1991). In a dog case series, 73% of the 62 suspect cases were treated with antibiotics and 97% of the dogs survived (Nichols et al, 2013). The prognosis is believed to be worse for the pneumonic form of Y. pestis infection. A recent case seen at the authors institution developed a consolidated lung lobe and died after lobectomy.

Summary

Fleas on dogs and cats around the world are potential sources of zoonotic agents. When working with pets with heavy flea infestations, veterinarians should wear gloves or wash their hands carefully.

Selected References

• Angelakis E, Mediannikov O, Parola P, et al. Rickettsia felis: the complex journey of an emergent human pathogen. Trends Parasitol. 2016; 32: 554-564
• Bayliss DB, Morris AK, Horta MC, et al. Prevalence of Rickettsia species antibodies and Rickettsia species DNA in the blood of cats with and without fever. J Feline Med Surg. 2009;11:266-270.
• Biswas S, Maggi RG, Papich MG, et al. Comparative activity of pradofloxacin, enrofloxacin, and azithromycin against Bartonella henselae isolates collected from cats and a human. J Clin Microbiol. 2010;48:617-618.
• Bland DM and Hinnebusch BJ. Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia pestis by the Cat Flea, Ctenocephalides felis. PLoS Negl Trop Dis. 2016; 10(2): e0004413. DOI: 10.1371/journal.pntd.0004413.
• Bradbury CA, Lappin MR. Evaluation of topical application of 10% imidacloprid-1% moxidectin to prevent Bartonella henselae transmission from cat fleas. J Am Vet Med Assoc. 2010;236:869-873.
• Breitschwerdt EB, Maggi RG, Chomel BB, Lappin MR. Bartonellosis: an emerging infectious disease of zoonotic importance to animals and human beings. J Vet Emerg Crit Care (San Antonio). 2010;20:8-30.
• Breitschwerdt EB. Did Bartonella henselae contribute to the deaths of two veterinarians?. Parasit Vectors. 2015;8:317
• Eidson M, Thilsted JP and Rollag OJ. Clinical, clinicopathologic, and pathologic features of plague in cats: 119 cases (1977-1988). J Am Vet Med Assoc. 1991; 199: 1191-1197.
• Gasper PW, Barnes AM, Quan TJ, et al. Plague (Yersinia pestis) in cats: description of experimentally induced disease. J Med Entomol. 1993; 30: 20-26.
• Gracia MJ, Marcén JM, Pinal R, Calvete C, Rodes D. Prevalence of Rickettsia and Bartonella species in Spanish cats and their fleas. J Vector Ecol. 2015;40:233-239.
• Kassem AM, Tengelsen L, Atkins B, et al. Notes from the field: plague in domestic cats - Idaho, 2016. MMWR Morb Mortal Wkly Rep. 2016; 65: 1378-1379.
• Lantos PM, Maggi RG, Ferguson B, et al. Detection of Bartonella species in the blood of veterinarians and veterinary technicians: a newly recognized occupational hazard?. Vector Borne Zoonotic Dis. 2014;14(8):563‐570.
• Lappin MR. Breitschwerdt E, Brewer M, et al. Prevalence of Bartonella species DNA in the blood of cats with and without fever. J Fel Med Surg 2009;11:141-148.
• Lappin MR, Davis WL, Hawley JR, et al. A flea and tick collar containing 10% imidacloprid and 4.5% flumethrin prevents flea transmission of Bartonella henselae in cats. Parasites & Vectors 2013, 6:26.
• Lappin MR, Elston T, Evans L, et al. 2019 AAFP Feline Zoonoses Guidelines. J Feline Med Surg. 2019;21(11):1008‐1021.
• Lappin MR, Tasker S, Roura X. Role of vector-borne pathogens in the development of fever in cats: 1. Flea-associated diseases. J Feline Med Surg. 2020;22(1):31‐39.
• Maggi RG, Mozayeni BR, Pultorak EL, et al. Bartonella spp. bacteremia and rheumatic symptoms in patients from Lyme disease-endemic region. Emerg Infect Dis. 2012;18(5):783‐791.
• Oteo JA, Maggi R, Portillo A, et al. Prevalence of Bartonella spp. by culture, PCR and serology, in veterinary personnel from Spain. Parasit Vectors. 2017;10(1):553. Published 2017 Nov 7. doi:10.1186/s13071-017-2483-z
• Pennisi MG, Egberink H, Hartmann K, et al. Yersinia pestis infection in cats: ABCD guidelines on prevention and management. J Feline Med Surg. 2013; 15: 582-584.
• Psaroulaki A, Chochlakis D, Ioannou I, Angelakis E, Tselentis Y. Presence of Coxiella burnetii in fleas in Cyprus. Vector Borne Zoonotic Dis. 2014;14:685-687.
• Whittemore JC, Hawley JR, Radecki SV, et al. Bartonella species antibodies and hyperglobulinemia in privately owned cats. J Vet Intern Med. 2012;26:639-444.