Since the discovery of feline cytauxzoonosis in Missouri in the mid-1970s, the distribution of C felis has been expanding. C felis has been reported in domestic cats in Missouri, Arkansas, Florida, Georgia, Louisiana, Mississippi, Oklahoma, Texas, Kentucky, Kansas, Tennessee, North Carolina, South Carolina, Nebraska, Iowa, Virginia, and Illinois. Anecdotally, C felis infection has also been reported in Alabama and Ohio.
Etiology of 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.
Aberrant and Natural Hosts of Cytauxzoonosis in Cats
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:
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.
Risk Factors for Cytauxzoonosis in Cats
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.
Life Cycle and Pathogenesis of Cytauxzoonosis in Cats
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.
Clinical Findings and Lesions of Cytauxzoonosis in Cats
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.
Diagnosis of Cytauxzoonosis in Cats
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
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.
Treatment of and Recovery from Cytauxzoonosis in Cats
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.
A large case series of cats with acute cytauxzoonosis treated with atovaquone and azithromycin combination therapy and supportive care resulted in a survival rate of 64%. Atovaquone is a ubiquinone analog that binds cytochrome b. In one study, a C felis cytochrome b subtype (cytb1) was identified and associated with increased survival in cats treated with atovaquone and azithromycin. Future development of a rapid means to identify the cytb1 C felis subtype in infected cats may help better predict the likelihood of survival with treatment.
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 (41°C), and never became hypothermic. Similar sporadic reports in other areas exist. Some hypotheses for survival in these cats have included the following:
an 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
timing and type of treatment
Prevention of Cytauxzoonosis in Cats
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.
Cytauxzoonosis is a life-threatening infectious disease of domestic cats in the southcentral and southeastern United States caused by infection with Cytauxzoon felis, which is transmitted by the lone star tick, Amblyomma americanum.
Infected cats often present with depression, lethargy, anorexia, and fever as high as 106°F (41°C). Additional findings may include icterus, lymphadenopathy, hepatosplenomegaly, and dyspnea.
Diagnosis is by identification of Cytauxzoon piroplasms in a peripheral blood smear or schizonts in cytology of infected tissues and by PCR.
Recommended treatment includes a combination of atovaquone and azithromycin, heparin therapy, and supportive care with minimal stress/handling.
Two acaracidal products, have provided promising preliminary results in preventing transmission of C felis; however, additional studies are needed.