Cytauxzoonosis in Cats

Cytauxzoon felis, an apicomplexan parasite, is transmitted to domestic cats primarily by the lone star tick (Amblyomma americanum). Transmission of C felis by the American dog tick (Dermacentor variabilis) has been reported in cats under experimental conditions; D variabilis is considered a less effective vector.

The domestic cat has been considered an aberrant or dead-end host of C felis because of the acute and fatal course of disease. However, there are reports of domestic cats surviving natural infection with and without treatment. The natural host for C felis is the bobcat (Lynx rufus). Bobcats typically experience subclinical infection followed by a chronic parasitemia. Rare cases of fatal cytauxzoonosis in bobcats have been reported. Reservoir hosts (asymptomatic carriers) include bobcats and domestic cats that survive infection. Cytauxzoonosis has been reported in several other wild felids in the USA and other countries, with both fatal and nonfatal outcomes. Infection has been reported in cougars, panthers, and tigers in the USA, in addition to two suspected but unconfirmed cases in cheetahs.

C felis or closely related Cytauxzoon sp infections of wild felids reported in other countries include:

• lions

• jaguars

• pumas

• ocelots

• Iberian lynx

• meerkats

• European wild cats

• an Asiatic wildcat

In the early 1980s, interspecies transmission of C felis was investigated to identify additional potential natural and aberrant hosts among 91 wildlife, laboratory, and domestic farm animals. Bobcats and domestic cats were the only animals confirmed to be susceptible to C felis.

Cytauxzoonosis is typically diagnosed during April through September, which correlates with climate-dependent seasonal tick activity of the lone star tick vector, A americanum. Infection can occur earlier in the spring or later in the fall depending upon the climate. Cats living near heavily wooded, low-density residential areas particularly close to natural or unmanaged habitats where both ticks and bobcats may be in close proximity are at highest risk of infection. Experimental infections have been induced with parenteral injection of tissue homogenates (SC, IP, and IV) 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, suggesting that oral and "cat-to-cat" transmission does not occur. One recent study failed to document perinatal transmission of C felis from 2 chronically infected dams to 14 healthy kittens, suggesting that vertical transmission may not occur commonly, if at all.

After C felis transmission from a tick into the cat, sporozoites infect macrophages and undergo schizogony (asexual reproduction) to form schizonts, which increase dramatically in size from ~15 mcm to up to ~250 mcm in diameter. Schizonts 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. Schizonts form “parasitic thrombi” occluding blood vessels that result in widespread ischemia, tissue necrosis, and death.

When schizonts rupture they release piroplasms (merozoites), which infect RBCs. Piroplasms in RBCs are innocuous, and parasitemia ranges from 1%–4% on average; however, higher parasitemias (ie, >10%) have been documented. During acute infection, detection of piroplasms in RBCs on blood smear examination is variable and has been correlated with an increase in body temperature and a decrease in leukocytes. Cats that survive acute cytauxzoonosis remain chronically parasitemic and clinically asymptomatic. Several survivors of the acute stage have been shown to be solidly immune to subsequent infections.

• Depression, lethargy, and anorexia

• Fever and dehydration

• Splenomegaly, hepatomegaly, lymph node enlargement, pulmonary edema

Onset of clinical signs for cats infected with C felis usually occurs 5–14 days (~10 on average) after infection by tick transmission, which has been documented to occur as early as early as >36-48 hours after infestation. Nonspecific signs such as depression, lethargy, and anorexia are the most common presenting problems. Fever and dehydration are the most common findings on physical examination; body temperature can increase to 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 the peak in temperature. Necropsy findings include splenomegaly, hepatomegaly, enlarged lymph nodes, renal edema, pulmonary edema/congestion/serosal surface petechiation, progressive venous distention, and often hydropericardium with epicardial petechiation.

• Leukopenia with toxic neutrophils and thrombocytopenia with a normocytic, normochromic anemia seen at later stages

• Microscopic observation of piroplasms or schizonts in blood

• Fine-needle aspiration of lymph node, spleen, or liver to identify schizonts

Cytauxzoon felis piroplasms, blood smear, cat

Image

Courtesy of Dr. Jaime L. Tarigo.

Cytauxzoon felis schizonts, cat

Image

Courtesy of Dr. Jaime L. Tarigo.

The most common abnormalities on the CBC in animals with cytauxzoonosis 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 may vary depending on organ systems affected by parasitic thrombosis and ischemia with tissue necrosis. Other, less consistently detected abnormalities include increased liver enzyme concentrations and azotemia. DIC was identified in 5/5 cats with acute cytauxzoonosis in one study. Among the commonly available diagnostic tests, prolonged prothrombin time and activated partial thromboplastin time, thrombocytopenia, and elevated D-dimers supported a diagnosis of DIC.

On blood smears, rapid diagnosis requires microscopic observation of piroplasms or schizonts. Observation of piroplasms in RBCs on blood smears is variable; they are seen in association with increasing body temperature and typically become apparent approximately 1–3 days before death. On a well-prepared, well-stained blood smear, when detectable, piroplasms may be seen ranging in 1%–4% of RBCs on average, with extremely high percentages (ie, >10%) reported in some cases. Piroplasms are round to oval and range from ~0.8-2.2 mcm in diameter, They have a pale center and contain a small, magenta, round to crescent-shaped nucleus on one side. Less commonly, pleomorphic piroplasms are seen (anaplasmoid, bipolar/binucleated, rod shaped, paired piriforms, and Maltese cross morphology).

Blood smears must be examined carefully to exclude Mycoplasma haemofelis, Howell-Jolly bodies, stain precipitate, and water artifact. The presence of schizonts in tissues occurs before the presence of piroplasms in RBCs. Occasionally, schizonts may be seen in peripheral blood smears, particularly at the feathered edge, and may be mistaken for large platelet clumps at low power.

In the absence of detection of piroplasms or schizonts on a blood smear, a rapid diagnosis can be pursued by performing fine-needle aspiration of a peripheral lymph node, spleen, or liver to identify schizonts cytologically. Schizonts are 15–250 mcm in diameter and contain an ovoid nucleus containing a prominent, large, dark nucleolus. The cytoplasm is often greatly distended, with numerous small, deeply basophilic particles representing developing piroplasms. If piroplasms or schizonts are not identified microscopically, a diagnostic PCR test with greater sensitivity and specificity than microscopy can be done. This test is recommended in suspect cases in which the parasite is not observed, as well as to confirm identification of piroplasms or schizonts.

• Combination therapy with atovaquone (15 mg/kg, PO, three times daily) and azithromycin (10 mg/kg, PO, once daily) for 10 days

• Supportive care, including IV fluids and nutritional support

Combination therapy with atovaquone (15 mg/kg, PO, three times daily for 10 days) and azithromycin (10 mg/kg/day, PO, for 10 days) is recommended. Atovaquone is available in capsule form through veterinary compounding pharmacies and in liquid form in some human and veterinary pharmacies on a limited basis. Treatment should be started as quickly as possible; in C felis endemic areas, stocking compounded atovaquone for initial dosing may be considered. A combination tablet product containing atovaquone and proguanil HCl is available, however, this combination has reportedly caused significant adverse GI effects in some dogs.

Attempts to treat cytauxzoonosis with a variety of other antiparasitic drugs (parvaquone, buparvaquone, trimethoprim/sulfadiazine, sodium thiacetarsamide, diminazene aceturate, imidocarb dipropionate) have been met with little or substantially less success than combinatorial atovaquone and azithromycin therapy and may have greater adverse side effects.

Supportive care with IV fluid therapy and heparin (100–200 U/kg, SC, three times daily) should also be instituted. Nutritional support via an esophageal or nasoesophageal feeding tube is recommended, and also facilitates administration of oral medications (eg, atovaquone and azithromycin). Oxygen therapy and blood transfusions should be administered as necessary. Anti-inflammatory drugs may be warranted in cases with unrelenting fever; however, the use of NSAIDs is contraindicated in cats with azotemia or dehydration.

Once a diagnosis is achieved and treatments have begun, minimal stress and handling are recommended. Providing a quiet/dark environment within the cage may be helpful.

Recovery, including resolution of fever, is often slow and may take as long as 5–7 days. Cats that survive have a complete clinical recovery, including resolution of hematologic and biochemical abnormalities within 2–3 weeks. Some survivors remain persistently infected with piroplasms and may represent a reservoir of infection.

Routine use of a tick preventive is recommended to prevent cytauxzoonosis; however, disease has occurred in cats despite using topical agents alone. Two acaracidal approaches have shown promising results for prevention of infection with C felis by ticks. In one study, a tick-repellent collar for cats containing imidacloprid 10%/flumethrin 4.5% prevented A americanum ticks from attaching, feeding, and transmitting C felis in 10 cats infested with infected ticks after application of the collar. In the same study, ticks attached and fed on 10 of 10 control cats not treated with a collar, and 9 of the 10 control cats were infected with C felis. Exclusion of cats from areas likely to be infested with the tick vector (ie, indoor only) is still considered the best method of prevention.

Another recent study assessed the efficacy of a topical acaracide containing selamectin (6 mg/kg) plus sarolaner (1 mg/kg) formulated in combination to prevent infestation with A americanum ticks and transmission of C felis. Seven of 8 untreated control cats tested positive for C felis post-infestation, however none of the 8 treated cats tested positive. Application of the product for 3 months in a row resulted in >94.7% efficacy against infestation with A americanum. The authors suggested that the product may be most helpful in the prevention of C felis transmission if cats are not allowed into risky environments until several days after application.

Also see pet health content regarding cytauxzoonosis in cats.