Cytauxzoonosis caused by Cytauxzoon felis was first reported in the USA in 1976; since then, it has become an important emerging infectious disease in domestic cats. Cytauxzoon spp are protozoan parasites classified within the family Theileriidae, along with Theileria spp and Gonderia spp. More recent molecular characterizations of these organisms have resulted in some dispute about the taxonomic status of Cytauxzoon spp, but its multiplication by schizogony in mononuclear phagocytes (macrophages), rather than lymphocytes as for Theileria spp, is a strong argument for maintaining its classification in a separate genus.
Etiology and Transmission
Cytauxzoon felis has been reported in domestic cats in Missouri, Arkansas, Florida, Georgia, Louisiana, Mississippi, Oklahoma, Kansas, Texas, Kentucky, Tennessee, North Carolina, South Carolina, and Virginia. The domestic cat has been considered an aberrant or dead-end host given the acute and fatal course of disease; however, there are reports of domestic cats surviving natural infection with and without treatment. The bobcat (Lynx rufus) is the natural host, typically experiencing subclinical infection and maintaining chronic parasitemia. C felis infection has been reported in several other wild felids, such as cougars and panthers, in the absence of overt disease; however, a few lions and tigers have been reported to succumb to illness.
Recent studies demonstrated that C felis can be transmitted by the lone star tick, Amblyomma americanum. The distribution of this tick parallels the distribution of cytauxzoonosis in domestic cats much more closely than does the distribution of the other competent vector, the American dog tick, Dermacentor variabilis. Cytauxzoonosis is typically diagnosed during April through September, which correlates with climate-dependent seasonal tick activity. Cats living near heavily wooded, low-density residential areas, particularly those closest to natural or unmanaged habitats where both ticks and bobcats may be in close proximity, are at the highest risk of infection. Experimental infections have been induced with parenteral injection (subcutaneously, intraperitoneally, and intravenously) of tissue homogenates from acutely infected cats. However, infection was not induced when these tissues were administered intragastrically or when noninfected cats were housed together with infected cats in the absence of arthropod vectors.
After transmission from the tick into the domestic cat, the parasite undergoes two major stages: schizogony (asexual reproduction) and merogony. First, sporozoites infect WBC (mononuclear phagocytes) and undergo schizogony to form schizonts. Schizont-infected WBC have been detected ∼12 days after experimental infection and increase in size from 15 μm to as much as 250 μm in diameter. They are most commonly detected in lymph node, spleen, liver, lung, and bone marrow but have been documented in many organs and are occasionally seen on blood smears. Schizont-infected WBC are the principal cause of disease and death, and they are found predominantly lining and often occluding blood vessels. These “parasitic thrombi” result in ischemia and tissue necrosis.
Schizont-infected WBC then rupture and release piroplasms (merozoites), which infect RBC. The piroplasms in RBC are fairly innocuous with parasitemias ranging from 1–4% on average; however, higher parasitemias (>10%) have been documented. During acute infection, the detection of merozoite-infected RBC is variable and has been correlated with a rise in body temperature and decline in leukocytes. Survivors typically remain chronically parasitemic, and at least one cat has been shown experimentally to be solidly immune to subsequent infections. Chronic parasitemia has been established via inoculation with merozoite-infected RBC. These chronically parasitemic cats did not develop overt clinical disease but were not immune to subsequent challenge with infection of sporozoites/schizonts, suggesting that the schizogonous tissue phase is required for establishment of immunity in domestic cats.
Clinical Findings and Lesions
Onset of clinical signs for cats infected with C felis usually occurs 5–14 days (∼10 on average) after infection by tick transmission. Nonspecific signs include depression, lethargy, and anorexia. Fever and dehydration are the most common findings on a physical examination; body temperature rises gradually and can reach as high as 106°F (41°C). Other findings include icterus, lymphadenomegaly, and hepatosplenomegaly. In extremis, cats are often hypothermic, dyspneic, and vocalize as if in pain. Without treatment, death typically occurs within 2–3 days after peak in temperature.
At necropsy, splenomegaly, hepatomegaly, enlarged lymph nodes, and renal edema are usually observed. The lungs show extensive edema and congestion with petechial hemorrhage on serosal surfaces and throughout the interstitium. There is progressive venous distension, especially the mesenteric and renal veins and the posterior vena cava. Hydropericardium is often seen with petechial hemorrhage of the epicardium.
When first described, mortality of C felis infection was reported to be nearly 100%. A study of C felis in northwestern Arkansas and northeastern Oklahoma indicated survival of natural infection in 18 cats with and without treatment; these cats seemed less sick initially, did not have temperatures >106°F, and never became hypothermic. Similar sporadic reports in other areas exist. Some hypotheses for survival of these cats include atypical route of infection, innate immunity in certain cats, increased detection of carriers, decreased virulence with strain attenuation or occurrence of a new strain, dose of infectious inoculum, and timing and type of treatment.
The most common abnormalities on CBC include leukopenia with toxic neutrophils and thrombocytopenia with a normocytic, normochromic anemia seen at later stages. The most common biochemical abnormalities are hyperbilirubinemia and hypoalbuminemia, but these may vary depending on the organ systems affected by parasitic thrombosis and ischemia with tissue necrosis. Other less consistently detected abnormalities include increased liver enzyme concentrations and azotemia.
Rapid diagnosis requires microscopic observation of piroplasms or schizonts. Observation of piroplasms on blood smears is variable; they are seen in association with increasing body temperature and typically become apparent ∼1–3 days before death. There are anecdotal reports of a higher level of sensitivity when blood is collected from smaller vessels (eg, ear vein prick) to prepare blood smears. On a well-prepared, well-stained (eg, Wright's Giemsa, Giemsa, Diff-Quik) blood smear, when detectable, merozoites may range from 1 to 4% on average with extremely high percentages (>10%) reported. They are pleomorphic and may be round, oval, anaplasmoid, bipolar (binucleated), or rod-shaped; however, the round (1.0–2.2 μm in diameter) and oval (0.8–1.0 μm × 1.5–2.0 μm) piroplasm forms are most common. They are pale centrally and contain a small, magenta, round to crescent-shaped nucleus on one side. Once the parasitemia is >0.5%, Maltese cross and paired piriforms may be seen. Careful observation is needed to exclude Mycoplasma haemofelis, Howell-Jolly bodies, stain precipitate, and water artifact.
The schizont tissue stage precedes the formation of the RBC phase. Occasionally, schizonts may be observed in peripheral blood smears, particularly at the feathered edge, and may be mistaken at low power for large platelet clumps. In the absence of detection of RBC piroplasms or schizonts on blood smear, a rapid diagnosis should be pursued by performing fine needle aspiration of a peripheral lymph node, spleen, or liver to identify schizonts cytologically. These phagocytes are 15–250 μm in diameter, contain an ovoid nucleus with a distinctive, prominent, large, dark nucleolus. The cytoplasm is often greatly distended with numerous small deeply basophilic particles representing developing merozoites.
In the absence of these observations, a diagnostic PCR test with greater sensitivity and specificity than microscopy is offered by the Vector Borne Disease Diagnostic Laboratory at North Carolina State University. This test is recommended in suspect cases in which the parasite is not observed, as well as for confirmation following identification of piroplasms or schizonts.
Treatment and Control
Historically, attempts to treat this disease with a variety of antiparasitic drugs (parvaquone, buparvaquone, trimethoprim/sulfadiazine, sodium thiacetarsamide) have met with little success. Six of 7 cats were successfully treated with diminazene aceturate (not approved in the USA) or imido-carb dipropionate (2 mg/kg, IM, 2 injections 3–7 days apart). Most recently, a case series (n = 22) reported survival of 64% of cats treated with a combination of atovaquone (15 mg/kg, PO, tid for 10 days) and azithromycin (10 mg/kg, PO, sid for 10 days) and supportive care.
Supportive care, including IV fluid therapy and heparin (100–200 U/kg, SC, tid), should be instituted in all cases. Nutritional support via an esophageal or nasoesophageal feeding tube is recommended and also facilitates the administration of oral medications (atovaquone and azithromycin). Oxygen therapy and blood transfusions should be administered when necessary. Anti-inflammatory drugs may be warranted in cases with unrelenting fever; however, the use of NSAID is contraindicated in cats with azotemia or dehydration. Once a diagnosis is achieved and treatments have begun, minimal stress and handling are recommended. Recovery, including resolution of fever, is often slow and may take as long as 5–7 days. Patients that survive have a complete clinical recovery, including the resolution of hematologic and biochemical abnormalities within 2–3 wk. Some survivors remain persistently infected with piroplasms and may represent a reservoir of infection.
Routine application of a tick preventive is recommended; however, disease has occurred in cats despite this treatment. Keeping cats from areas likely to be infested with the tick vector (ie, indoor only) is considered the best method of prevention.
Last full review/revision July 2011 by Jaime Tarigo, DVM, DACVP