Flea-associated illnesses in cats

Ctenocephalides felis commonly infests cats in many areas of the United States and is associated with a variety of clinical syndromes.1 In small kittens, a heavy infestation can cause anemia, particularly if they are concurrently infected with the common parasite Ancylostoma tubaeforme or Ancylostoma braziliense.2 Repeated flea exposure can result in flea-bite hypersensitivity, one of the most common flea-associated syndromes.3, 4 Because C. felis ingests feline blood, a number of blood-borne infectious agents, including Bartonella quintana, Bartonella koehlerae, Bartonella henselae, Bartonella clarridgeiae, Rickettsia felis, Wolbachia pipientis, 'Candidatus Mycoplasma haemominutum,' Mycoplasma haemofelis, and feline leukemia virus (FeLV), have been grown or amplified by polymerase chain reaction (PCR) assays from C. felis or its feces.5-18 Ctenocephalides felis is a vector for some of these infectious agents. And because some of these agents are human pathogens, the American Association of Feline Practitioners (AAFP) recommends continual flea control to potentially reduce the risk of exposure.19 This article will provide a brief update on Bartonella and Mycoplasma species infections in cats.

Bartonella species infections

Bartonella henselae

is the most common cause of cat scratch disease as well as bacillary angiomatosis and bacillary peliosis, which are common disorders in people with acquired immunodeficiency syndrome (AIDS).19-21 People with cat scratch disease develop a variety of clinical signs, such as lymphadenopathy, fever, malaise, weight loss, myalgia, headache, conjunctivitis, skin eruptions, and arthralgia. Bacillary angiomatosis is a diffuse disease resulting in vascular cutaneous eruptions. Bacillary peliosis is a diffuse systemic vasculitis of the parenchymal organs. Most cases of cat scratch disease are self-limiting, but some cases may take several months to resolve completely. Cats can also be infected with

B. clarridgeiae

, an organism that has been associated with cat scratch disease.22

Based on seroprevalence studies in cats, exposure to Bartonella species is very common and varies by region in the United States.23 The organism is transmitted by fleas, so prevalence is highest in cats from states where fleas are common.6, 9 Bartonella henselae survives in flea feces for days after it's passed by infected C. felis.8, 10 In a recent study, we collected fleas from cats and attempted to amplify Bartonella species DNA from flea digests as well as cat blood (Lappin MR, Unpublished data, 2005). The prevalence rates for B. henselae infection in cats and their fleas were 34.8% and 22.8%, respectively. The prevalence rates for B. clarridgeiae infection in cats and their fleas were 20.7% and 19.6%, respectively.

Clinical signs

Most cats with positive

Bartonella

antibody titers,

Bartonella

species cultured from the blood, or organismal DNA amplified from the blood by PCR assay are clinically normal.

However, Bartonella species infection in cats has also been associated directly and indirectly with clinical manifestations such as fever, lethargy, lymphadenopathy, uveitis, gingivitis, and neurologic diseases. How often cats become ill from Bartonella species infections is unknown and more information is needed.

For example, the association of B. henselae infection and uveitis in cats was first made in an individual uveitis case that ultimately responded to doxycycline therapy.24 We subsequently found Bartonella antibody production and DNA in the aqueous humor of cats previously presumed to have idiopathic uveitis.25 A recent series of feline ocular disease cases thought to be caused by bartonellosis were responsive to antibiotic therapy.26 Thus, it appears likely that Bartonella species causes ocular disease in some cats. However, it can be difficult to determine which cats have been exposed and which cats are diseased. In a recent study, the prevalence rates for Bartonella species antibodies in feline sera were not significantly different for cats with and without ocular disease.27 It's also unclear why some cats develop Bartonella uveitis and others do not. For example, we failed to induce Toxoplasmagondii or Bartonella species uveitis when we inoculated Bartonella intravenously into cats with chronic toxoplasmosis.28

Testing for Bartonella infection

Blood culture, PCR assay on blood, and serology can all be used to test cats for

Bartonella

infection. Culture-negative or PCR-negative cats probably aren't a source of flea, cat, or human infection even if they test antibody-positive. However, bacteremia can be intermittent, and false-negative culture or PCR results do occur, limiting the predictive value of a single battery of tests. False-positive results can also occur with PCR assays, and positive results don't necessarily indicate that the organism is alive.

While serologic testing can help determine an individual cat's exposure, both seropositive and seronegative cats can be bacteremic, limiting the diagnostic utility of serologic testing. Therefore, testing healthy cats for Bartonella species infection with any test isn't currently recommended.19, 29 Instead, I generally only evaluate cats with suspected clinical bartonellosis for Bartonella species infection.

If the results of the Bartonella species tests are negative in a clinically ill cat, the organism likely isn't the cause of the clinical syndrome unless the infection was peracute and serologic testing was used as the diagnostic test. If the Bartonella test results are positive, keep the agent on the differential list, but exclude other causes of the clinical syndrome.

Treatment

Administering doxycycline, tetracycline, amoxicillin-clavulanate, erythromycin, or enrofloxacin can limit bacteremia but does not cure infection in all cats and has not been shown to lessen the risk of cat scratch disease.19 Thus, treatment is generally recommended for clinically ill cats.19

I use a flavored doxycycline suspension (to avoid the esophageal strictures associated with doxycycline tablets) at 10 mg/kg orally once a day for seven days as an initial therapeutic trial. If the response is positive, I continue treatment for two weeks past clinical disease resolution or for a minimum of 28 days. If doxycycline is not tolerated or the cat is not responding at Day 7, I usually prescribe a different drug if I still think bartonellosis is a valid differential diagnosis. I generally consider azithromycin or a fluoroquinolone as a second choice.26 In my experience, Bartonella infection is not the cause of illness in Bartonella-positive cats that have failed to respond to two drugs with presumed anti-Bartonella activity.

Preventing Bartonella infection

The following guidelines are adaptations of recommendations for people infected with human immunodeficiency virus (HIV) and for other cat owners by the Centers for Disease Control and Prevention and the AAFP to lessen the likelihood of acquiring

Bartonella

species infections from cats.19, 29

• If a family member is immunosuppressed and a new cat is to be acquired, adopt a healthy cat older than 1 year.

• Declawing is generally not advised, but immunosuppressed people should avoid cat bites and scratches.

• Cat-associated wounds should be washed promptly and medical advice sought.

• Cats should not be allowed to lick open wounds on immunosuppressed people.

• Flea control should be maintained.

Mycoplasma species infections

The large and small forms of

Haemobartonella felis

are gram-negative, epicellular parasites of feline erythrocytes that have been reclassified as mycoplasmas. The new name for the large form (Ohio isolate) is

Mycoplasma haemofelis

.30 The proposed name for the small form (California isolate) is

'Candidatus

Mycoplasma haemominutum.'31 Strains evaluated in the United States and the United Kingdom are genetically similar.32 A potentially pathogenic, genetically distinct strain was

recently amplified from a clinically ill cat in Switzerland.33 In at least two studies of experimentally infected cats,

M. haemofelis

was apparently more pathogenic than '

Candidatus

M. haemominutum'; all

M. haemofelis

-inoculated cats became clinically ill, whereas '

Candidatus

M. haemominutum'-inoculated cats were generally subclinical.34, 35 Cats with chronic '

Candidatus

M. haemominutum' infection had more severe and longer durations of anemia when experimentally infected with

M. haemofelis

than cats infected with

M. haemofelis

alone.35

In a recent study, we collected fleas from cats and attempted to amplify Mycoplasma species DNA from flea digests as well as cat blood (Lappin MR, Unpublished data, 2005). The prevalence rates for M. haemofelis infection in cats and their fleas were 7.6% and 2.2%, respectively. The prevalence rates for 'Candidatus M. haemominutum' infection in cats and their fleas were 20.7% and 23.9%, respectively. In addition, fleas ingest 'Candidatus M. haemominutum' and M. haemofelis from infected cats when feeding.17, 18 In one cat, flea feeding was documented as transferring M. haemofelis. In other studies, Mycoplasma species have been transmitted experimentally by intravenous, intraperitoneal, and oral inoculation of blood.36 Clinically ill queens can infect kittens whether transmission occurs in utero, during parturition, or during nursing. Transmission by biting has been hypothesized. Red blood cell destruction is due primarily to immune-mediated events; organism-induced direct injury to red blood cells is minimal.

Clinical signs

Clinical signs of disease depend on the degree of anemia, the stage of infection, and the immune status of infected cats.36-38 Coinfection with FeLV can potentiate disease associated with '

Candidatus

M. haemominutum'.38 Clinical signs and physical examination abnormalities associated with anemia are most common and include pale mucous membranes, depression, inappetence, weakness, and, occasionally, icterus and splenomegaly. Fever occurs in some acutely infected cats and may be intermittent in chronically infected cats. Evidence of coexisting disease may be present. Weight loss is common in chronically infected cats. Cats in the chronic phase can be subclinically infected only to suffer recurrences following periods of stress.

Testing for Mycoplasma infections

The anemia associated with

Mycoplasma

species infections is generally macrocytic and normochromic but may be macrocytic and hypochromic if coinfections leading to chronic inflammation exist. Neutrophilia and monocytosis have been reported in some infected cats. Diagnosis is based on results of PCR assay or blood film examinations showing the organism on erythrocyte surfaces. Because organism numbers fluctuate, blood film examination can be falsely negative up to 50% of the time.39 The organism may be difficult to find cytologically, particularly in the chronic phase. Thus, the more sensitive PCR assays are the test of choice. Primers are available that amplify a segment of the 16S rRNA gene common to both

Mycoplasma

species.39 Real-time PCR assays that quantify mycoplasmal DNA have now been titrated and can be used to monitor treatment responses.40 Clinically ill cats that are positive for either

Mycoplasma

species should be treated with a drug with presumed anti-

Mycoplasma

activity.

Treatment

Because

Mycoplasma

species infections and primary immune hemolytic anemia are difficult to differentiate, both antibiotics and glucocorticoids are often used to treat cats with severe, regenerative hemolytic anemia.

Doxycycline is preferred by most clinicians because it causes fewer side effects in cats than other tetracyclines and can be administered once daily. As with Bartonella infection, I administer a flavored doxycycline suspension at 10 mg/kg orally once a day for seven days. If the response is positive and the cat tolerates the drug, I continue treatment for 28 days. If autoagglutination is evident, I generally prescribe prednisolone (1 mg/kg orally b.i.d.) for the first seven days or until autoagglutination is no longer evident. The tetracyclines appear to lessen parasitemia and the clinical signs of disease but do not consistently clear the organism from the body, so recurrence is possible.34

Enrofloxacin administration (5 mg/kg orally once a day) for 14 days was tolerated by doxycycline-intolerant cats and is equally or more effective than doxycycline.40, 41 Azithromycin was not effective for treatment of Mycoplasma species infection in one study.35 Imidocarb dipropionate administered at 5 mg/kg intramuscularly every two weeks for at least two injections was used to successfully manage five naturally-infected cats that had failed treatment with other drugs.42 Minocycline could be considered in resistant cases but there are no published efficacy data. Blood transfusions should be given if clinically indicated.

Preventing Mycoplasma infection

To prevent

Mycoplasma

species infections, appropriate flea control should be maintained. Cats should be housed indoors to avoid vectors and fighting with other cats. Donated blood from cats should be screened for both

Mycoplasma

species using PCR assays, which are now widely available.43

Dr. Michael Lappin is the Kenneth W. Smith professor in Small Animal Clinical Veterinary Medicine in the Department of Clinical Sciences at the College of Veterinary Medicine & Biomedical Sciences at Colorado State University in Fort Collins, Colo.

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