History

In May 2006, a 1-year-old 3.41-kg (7.50-lb) neutered male domestic shorthair cat was evaluated at a veterinary hospital in Georgia because of sudden onset of inappetence and lethargy.

Clinical and Gross Findings

Physical examination revealed icterus, tachycardia, tachypnea, and high rectal temperature (40.4°C [104.7°F]). A CBC and serum biochemical analysis revealed anemia (Hct, 24%; reference interval, 30% to 45%), high serum total bilirubin concentration (9.2 mg/dL; reference interval, 0.08 to 0.3 mg/dL), and high BUN concentration (51 mg/dL; reference interval, 17 to 30 mg/dL). The cat was dehydrated (percentage dehydration unknown). Given the hematologic and physical examination abnormalities, fluid therapy; administration of enrofloxacin, doxycycline, and prednisone; and nutritional support were instituted. The following day, the cat was severely icteric and laterally recumbent. Owing to rapidly worsening clinical signs, the owners opted to euthanize the cat; a postmortem examination was conducted at the University of Georgia College of Veterinary Medicine.

At necropsy, the cat was diffusely icteric. The spleen was dark red and enlarged, with a meaty consistency and rounded margins. The liver was diffusely brownish yellow. The lungs were abnormally heavy, wet, and noncollapsing; multifocal, pinpoint to coalescing, red foci were present on the pleural surface and extended into the pulmonary parenchyma (Figure 1).

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Photograph of the thoracic and abdominal cavities of a neutered male domestic shorthair cat that was euthanized after becoming moribund following a sudden onset of inappetence, dehydration, and lethargy the preceding day. Notable lesions detected during necropsy included icterus, noncollapsing lungs with multiple widespread foci of hemorrhage, brownish-yellow liver, and splenomegaly.

Citation: Journal of the American Veterinary Medical Association 240, 2; 10.2460/javma.240.2.159

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Histopathologic Findings

Various tissue samples, including samples of lungs, liver, spleen, and brain, were processed for histologic examination. Alveoli were distended with edema fluid and small amounts of fibrillar eosinophilic material (fibrin). Alveoli were multifocally filled with erythrocytes. Numerous blood vessels, including alveolar septal capillaries, were filled with enlarged monocytes (20 to 30 μm in diameter), which contained intra-cytoplasmic, basophilic, granular structures consistent with Cytauxzoon felis merozoites (0.75 to 2 μm in length; Figure 2). In the liver, monocytes containing similar merozoites were predominantly observed within hepatic sinusoids and the portal vasculature. A few central veins were filled with similar monocytes. Severe canalicular cholestasis was present, and several bile ductules were filled with bile. There was mild hepatocellular vacuolation. Portal areas were occasionally infiltrated by lymphocytes and plasma cells. Additional findings included splenic congestion and infiltration of the red pulp by numerous infected monocytes similar to those in lungs and liver. In the CNS, numerous blood vessels within the meninges and choroid plexus contained parasitized monocytes. Rarely, blood vessels within the neuroparenchyma contained infected monocytes.

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Photomicrograph of a section of lung from the cat in Figure 1. Notice the medium-caliber vessel that contains engorged monocytes filled with 0.75- to 2-μm-long, basophilic, granular structures consistent with Cytauxzoon felis merozoites. Adjacent capillaries and smaller vessels contain similar parasitized monocytes. H&E stain; bar = 200 μm.

Citation: Journal of the American Veterinary Medical Association 240, 2; 10.2460/javma.240.2.159

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Morphologic Diagnosis

Widespread moderate to severe intravascular monocytosis, with intracytoplasmic protozoal merozoites consistent with C felis; moderate, diffuse, pulmonary edema, with petechial to ecchymotic hemorrhages; icterus; and severe, intrahepatic, canalicular cholestasis.

Comments

For the cat of this report, histologic examination of various tissue sections confirmed the diagnosis of cytauxzoonosis. Cytauxzoon felis is a tick-transmitted protozoal parasite, which causes a sporadic and fulminating disease in felids.^1–5 Cytauxzoon felis is endemic in the southeastern United States but its presence in the mid-Atlantic and Gulf Coast states has also been reported.^2–5 Cytauxzoonosis develops in cats primarily in March through September, with peak incidences in spring and fall.^2,3,6

The geographic distribution of C felis typically follows the natural range of the North American bobcat (Lynx rufus), the presumed natural reservoir for this protozoan.^1,2,4,5,7 Bobcats are persistently parasitemic and typically clinically unaffected carriers of C felis.^2,8,9 Florida panthers (Puma concolor coryi) may serve as an additional reservoir host.

Clinical signs of cytauxzoonosis in a naïve felid develop soon following tick transmission of C felis from a reservoir host.³ Characteristic clinical signs include anorexia, anemia, signs of depression, dyspnea, icterus, and pyrexia (body temperature ranging from 39.5° to 41.7°C [103° to 107°F]).^1–3,6,9 The monocytic phase of the parasite is chiefly responsible for the clinical signs associated with C felis infection.^2,3 This phase is initiated by tick transmission of sporozoites, which invade host monocytes and undergo schizogony.^3–5 Schizonts undergo binary fission to yield numerous basophilic, granular structures (merozoites), which fill monocytes and cause them to enlarge (Figure 3).^1,2,4,5,7,10 Parasitized monocytes appear to be adherent and have a reduced ability to undergo diapedesis.¹ As a result, they accumulate and potentially occlude blood vessels.^{1,5,8,10–12} Widespread vascular occlusion is accompanied by release of vasoactive mediators from parasitized mononuclear cells and results in splenic congestion and pulmonary edema and congestion with petechial hemorrhages.^2,3 Engorged monocytes may also act as thrombi and promote a shock-like state through local release of inflammatory mediators and cyto-toxic effects on the endothelium.^2,3,13 Despite severe clinical signs, parasitemia is rarely detectable during the monocytic phase, although intramonocytic parasites may be observed in heart blood samples and fine-needle aspirates of spleen, lungs, liver, lymph nodes, and bone marrow.^1,2,6

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Illustrative photomicrograph of an impression smear of a lymph node from a different C felis-infected cat with similar lesions to those seen in the cat in Figure 1. Notice the enlarged monocyte with prominent nucleolus and numerous intracytoplasmic, variably sized, basophilic granular structures consistent with C felis merozoites. Modified Wright stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 240, 2; 10.2460/javma.240.2.159

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The erythrocytic phase of the disease begins 1 to 3 days following the monocytic phase with rupture of enlarged monocytes and release of merozoites into the blood-stream.^2,4,5,10 Free merozoites are taken up by erythrocytes to produce a late-stage, potentially cytologically detectable parasitemia.^2,4,5 Microscopic examination of Wright- or Giemsa-stained blood smears may reveal intraerythrocytic protozoa (piroplasms); these often form a single basophilic signet ring, which is diagnostic for cytauxzoonosis.^2,4,7,10 However, even during the erythrocytic phase, parasitemia is only cytologically evident in 50% of cases.^1,12 Negative results of blood smear examination do not necessarily indicate an absence of infection; they may reflect a low sensitivity of the technique for detection of low-level parasitemias⁴ or indicate that the blood sample may have been collected from a cat that was in the monocytic phase of cytauxzoonosis.^2,10 Specific PCR analysis is a more sensitive means of identifying C felis carriers that have no clinical signs and low-level parasitemias; however, very low parasite loads may yield inconsistent results, thereby requiring repeated PCR testing of some cats.⁴

Sudden-onset anemia develops as a result of immune-mediated destruction of parasitized erythrocytes.^2,12 Erythrophagocytosis increases bilirubin load to the liver and exhausts the ability of hepatocytes to conjugate bilirubin. As a result, bilirubin moves into the peripheral vasculature and results in icterus. Bilirubinemia also leads to bile accumulation within canaliculi and to cholestasis. Because of the combination of multiorgan failure and anemia, the illness in cats typically lasts a week and culminates in death.^2,4,11 At necropsy, gross findings of splenomegaly, yellowish-brown liver, and noncollapsing lungs with petechial hemorrhages further support a diagnosis of cytauxzoonosis.¹ For the cat of this report, the splenomegaly was likely attributable to a combination of the euthanasia solution used and C felis infection.

Although postulated as a highly fatal disease in domestic cats, recent reports^2,4,6,9,10 indicate that there are numerous unaffected carriers as well as individuals that survive natural or experimental C felis infection with or without treatment. Cytauxzoon felis strains of lesser virulence, immune responses conferring protection from disease, or improved treatment strategies are speculated reasons for improved survival rates.^3,6,8,10 To date, no published medical treatment has been consistently successful in treating this disease.⁸ Treatments with antiprotozoal drugs, such as diminazene aceturate and imidocarb diproprionate, have had some success in reducing clinical signs in affected cats, especially in combination with IV fluid therapy and oral administration of enrofloxacin.^2,4,5,10 A treatment trial comparing imidocarb diproprionate administration with combined azithromycin and atovaquone treatment in cats with cytauxzoonosis has revealed greater promise for the latter combined treatment.¹⁴ Heparin is often administered in conjunction with antiprotozoal medications to prevent disseminated intravascular coagulation, a common sequela of the erythrocytic phase.² Unfortunately, persistently parasitemic survivor or carrier cats may serve as reservoirs.^4,6,9

Several diseases are associated with clinical signs similar to those of cytauxzoonosis. In an anemic and icteric cat, infection with Mycoplasma haemofelis, Toxoplasma gondii, or feline infectious peritonitis virus and cholangiohepatitis are differential diagnoses. Mycoplasmosis may be differentiated from cytauxzoonosis on the basis of the absence of pyrexia and type of anemia. Cytauxzoon felis infection generally causes a normocytic, normochromic, nonregenerative anemia, whereas M haemofelis infection typically induces a strongly regenerative hemolytic anemia.^2,12 Toxoplasma gondii infection contrasts with C felis infection in that it is typified by necrosis of major organs. The noneffusive form of feline infectious peritonitis is grossly typified by ocular lesions and pyogranulomas of multiple organs, whereas the effusive form may include development of ascites or thoracic effusion with polyserositis, which is characterized by small white necrotic plaques on the surface of multiple organs. In contrast to C felis infection, cholangiohepatitis is not associated with anemia. During postmortem examination of an anemic and icteric cat, microscopic examination of impression smears of the liver, spleen, and lungs and smears of heart blood that have been stained with Romanowsky, Giemsa, or Wright stain can provide useful information for identifying a causative agent. Detection of characteristic C felis merozoites within monocytes in an impression smear expedites the diagnosis (Figure 3).^2,10 A thorough necropsy is still recommended, however, to detect the presence of concurrent disease or other factors important to the owner of the cat.