Flea-Associated Diseases in the Cat: Update on the Diagnosis and Treatment of Haemoplasmas and Rickettsia spp
Michael R. Lappin, DVM, PhD, DACVIM
Director, Center for Companion Animal Studies, Colorado State University, Fort Collins, CO, USA
The new names for Haemobartonella felis are Mycoplasma haemofelis (Mhf), 'Candidatus Mycoplasma haemominutum' (Mhm), and 'Candidatus M. turicensis'. Strains evaluated in the United States, Australia, and the United Kingdom are genetically similar.
In at least two studies of experimentally infected cats, Mhf is apparently more pathogenic than Mhm; all Mhf inoculated cats became clinical ill whereas Mhm inoculated cats were generally subclinically infected. Cats with chronic Mhm infection had more severe anemia and longer duration of anemia when experimentally infected with Mhf when compared to cats infected with Mhf alone.
In a recent study, we collected fleas from cats and attempted to amplify hemoplasma DNA from flea digests as well as the blood of the cat. The prevalence rates for Mhf in cats and their fleas were 7.6% and 2.2%, respectively. The prevalence rates for Mhm in cats and their fleas were 20.7% and 23.9%, respectively. Results from our collaborative study in Australia were similar (Barrs et al., 2008).
Ctenocephalides felis ingest Mhm and Mhf from infected cats when feeding. In one cat, we documented flea feeding to transfer Mhf. However, when we fed Mhf or Mhm infected fleas to cats, infection was not documented. In other studies, hemoplasmas have been transmitted experimentally by IV, IP, and oral inoculation of blood. Clinically ill queens can infect kittens; whether transmission occurs in utero, during parturition, or from nursing has not been determined.
Transmission by biting has been hypothesized. DNA of the hemoplasmas has been amplified from the mouths of cats, the salivary glands, and the tonsils. Thus, history of fighting in the past is a likely risk factor for feline hemoplasmosis. We are currently studying the role mosquitoes may play in the transmission of these agents.
Red blood cell destruction is due primarily to immune-mediated events; direct injury to red blood cells induced by the organism is minimal. Clinical signs of disease depend on the degree of anemia, the stage of infection, and the immune status of infected cats. Coinfection with FeLV can potentiate disease associated with Mhm. 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 have recurrence of clinical disease following periods of stress.
The anemia associated with hemoplasmosis is generally macrocytic, normochromic. Chronic non-regenerative anemia is unusual in cats with hemoplasmosis. Neutrophilia and monocytosis have been reported in some hemoplasma-infected cats.
Diagnosis is based on demonstration of the organism on the surface of erythrocytes on examination of a thin blood film or PCR assay. 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. Real time PCR to quantify hemoplasma DNA has now been titrated and can be used to monitor response to treatment.
Since hemoplasmosis and primary immune hemolytic anemia are difficult to differentiate, cats with severe, regenerative hemolytic anemia are often treated with glucocorticoids and antibiotics. Doxycycline has fewer side-effects than other tetracyclines in cats and so is preferred. I usually administer doxycycline as a flavored suspension (to avoid esophageal strictures) at 10 mg/kg, PO, every 24 hours for 7 days. If there is a positive response and the cat is tolerating the drug, I continue treatment for 14–28 days. If autoagglutination is evident, I generally prescribe prednisolone at 1 mg/kg, PO, every 12 hours for the first 7 days or until autoagglutination is no longer evident.
Tetracyclines utilized to date appear to lessen parasitemia and clinical signs of disease but probably do not always clear the organism from the body and so recurrence is possible. 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. Imidocarb administered at 5 mg/kg, IM, every 2 weeks for at least 2 injections was used successfully in the management of five naturally-infected cats that had failed treatment with other drugs. Blood transfusion should be given if clinically indicated. 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.
To attempt to prevent hemoplasma infections, it might be prudent to control fleas. Cats should be housed indoors to avoid other potential vectors and fighting. Blood donor cats should be screened by PCR assay prior to use.
Rickettsia spp. are obligate intracellular gram-negative bacteria that are divided into two distinct groups, the spotted fever group (SFG) and the typhus group. Cats can be infected by Rickettsia felis and have been shown to have antibodies against R. rickettsii. Rickettsia felis was originally detected in a commercial cat flea (Ctenocephalides felis) colony and has been shown to belong in the SFG. Fever, headache, myalgia, and macular rash in humans have been attributed to R. felis infection in several countries around the world. In addition, one person in Mexico developed neurological symptoms following R. felis infection, suggesting that the organism may be the cause of severe debilitating disease in some people. Recently, infected people and dogs have been found in Australia.
The organism has been detected in 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 C. felis collected from cats in the United Kingdom, France, Israel, New Zealand, Australia, Thailand, and the United States.
In recent study in our laboratory, we assayed 92 pairs of cat blood and flea extracts from Alabama, Maryland and Texas, using PCR assays that amplify a region of the citrate synthase gene (gltA) and the outer membrane protein B gene (ompB). Of the 92 pairs, 62 of 92 (67.4%) flea extracts and none of the cat blood samples were positive for R. felis DNA. We have now documented R. felis DNA in fleas from cats in Australia (Barrs et al., 2008). In another study, we showed R. felis and R. rickettsii antibody prevalence rates in cats in the USA with fever to be 5.6% and 6.6% respectively, but neither organism was amplified from blood. These results prove that cats are sometimes exposed 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. Prevention in cats and people should include flea control. Since cats are generally not PCR positive for these organisms in blood, it is not currently recommended by Colorado State University to test blood donor cats.
Administration of imidocloprid monthly to cats has been shown to block transmission of B. henselae. While this has not been proven to date with the hemoplasmas or Rickettsia, use of flea control products seems to be a reasonable recommendation.
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