Feline cytauxzoonosis (Cytauxzoon felis)

©F. Dean Dailey, DVM; Pauline M. Rakich, DVM, PhD; and Kenneth S. Latimer, DVM, PhD. Cytauxzoonosis in Cats:  An Overview. Veterinary Clinical Pathology Clerkship Program. http://www.vet.uga.edu/vpp/clerk/Dailey/index.php

Introduction

Cytauxzoonosis is a serious, often fatal, protozoal disease affecting domestic cats in the south central and south-eastern portions of the United States. The causative organism, Cytauxzoon felis, is classified in the Order Piroplasmida, Family Theileridae. Because of the rapid onset of severe clinical illness and high mortality (historically greater than 95%) associated with this disease in domestic cats, they likely serve as accidental dead-end hosts.¹ The natural reservoir host of C. felis is the North American bobcat (Lynx rufus). In most instances, bobcats remain asymptomatic when infected by C. felis; however, fatal infection also has been observed in this species. Ticks are believed to be the natural vector for this organism. Experimentally, an Ixodid tick (Dermatocentor variablis) has been shown to transmit C. felis from bobcats to domestic cats, causing the clinical signs associated with cytauxzoonosis.⁵ As expected, Cytauxzoonosis is seen more often during the summer months (May through September) when ticks are more likely to be found. Cats with access to the outdoors (especially wooded areas) are at higher risk of coming into contact with infected ticks and acquiring this disease.⁴

Life cycle of C. felis

Organisms in the genus Cytauxzoon have two stages in their life cycles: an erythrocytic piroplasm and a leukocytic or tissue phase.⁷ The leukocytic phase begins when C. felis organisms infect mononuclear phagocytes. The organisms infecting these cells undergo asexual reproduction forming schizonts.⁶ As these leukocytes become engorged with schizonts, they line the lumens of veins in many of the organs of the body, causing obstruction of blood flow. Obstruction of blood flow and ischemia are responsible for many of the clinical signs associated with this disease.⁵ Subsequently, the schizonts develop into merozoites which eventually cause host cell rupture and enter the blood. These intravascular merozoites infect variable numbers of erythrocytes. The parasitemia seen on the stained blood smear often represents a late stage of disease. Infected cats typically die within a few days after the onset of parasitemia.⁵

Clinical Signs of Disease

The clinical signs observed in cats with Cytauxzoonosis are non-specific and usually include acute lethargy, depression, and anorexia. Infected cats also often exhibit icterus, mucous membrane pallor, and dehydration.^1-8 As the disease progresses, mild to severe dyspnea becomes apparent with concomitant radiographic evidence of moderate to severe bronchointerstitial pulmonary disease.⁶ Less frequently, renomegaly, splenomegaly, and hepatomegaly have been identified on physical examination.⁴ A fever may be present that ranges in severity from 103-107ºF. Febrile episodes usually coincide with the onset of parasitemia as observed on stained blood smears.² Hypothermia, recumbency, and coma generally are signs of terminal disease.

Pathological Changes

Several changes in the complete blood count are commonly seen in cats with Cytauxzoonosis. These abnormalities may include leukopenia with a left shift and toxic changes of neutrophils, thrombocytopenia, and a normocytic, normochromic, non-regenerative anaemia. The anaemia coincides with the parasitemia. The rapidly developing anaemia is believed to be due to an immune-mediated destruction of parasitized erythrocytes. Accelerated removal or destruction of infected erythrocytes occurs rapidly (usually within 1 to 3 days), before signs of erythrocyte regeneration are observed.² Abnormal hemostasis may be present from disseminated intravascular coagulation.³ Common abnormalities in the biochemical profile may include hyperbilirubinemia, hyperglycaemia, hypoalbuminemia, hypokalemia, and increased activity of alanine aminotransferase. In many cases, marked bilirubinuria is observed.

Diagnosis of Cytauxzoonosis is made by identifying piroplasms within erythrocytes in the stained blood smear. These erythroparasites may appear as round to oval "signet rings" (1-1.5 µm in diameter); bipolar, oval, "safety pin" forms (1-2 µm in diameter); tetrad forms; or anaplasmoid round "dots" (less than 0.5 µm in diameter) (Fig. 1). The anaplasmoid form may appear as single organisms or as multiple organisms resembling chains.¹ Microscopically, the piroplasms have a small, peripherally-located nucleus that stains dark red to purple with a off white to light blue cytoplasm when using Giemsa stain.¹ The number of erythrocytes parasitized with C. felis varies among cats and with the stage of disease. However, the percentage of affected erythrocytes usually is low.⁶ Infrequently, large mononuclear phagocytes containing developing merozoites can be seen at the feathered edge of peripheral smears. These parasite-laden macrophages may measure 75 µm in diameter.¹

When detection of parasitized erythrocytes is difficult in the stained blood smear, fine-needle aspirates of the spleen, lymph nodes, or bone marrow may provide a diagnosis. In these cases, the large, merozoite-laden macrophages may be readily observed.⁴ Other methods used to diagnose cytauxzoonosis in cats include a direct fluorescent antibody test for detection of the tissue phase of the parasite and a microfluorometric immunoassay system to detect serum antibody to the organism. However, these tests are largely experimental and generally are not available commercially.⁵

Cytauxzoon felis is a relatively new pathogen in the United States. It was first reported in Missouri in 1976. Parasitism with this organism has sometimes been overlooked or the parasite had mistakenly been identified as another organism, such as Hemobartonella felis (Fig. 2). However, the two parasites are easily distinguishable: H. felis organisms are located extracellularly within invaginations of the plasma membrane. In stained blood films, these organisms generally appear as thin rings, rods, or chains.¹ In contrast, C. felis organisms are located intracellularly and appear as "signet rings" or safety pins (one organism that cannot be differentiated from C. felis by blood smear evaluation is Babesia felis; however, this organism is exotic to the United States). Another factor that can complicate detection of parasitemia is improper Romanowsky (Wright, Giemsa, Leishman, or Diff-Quik) staining technique (Fig. 3). In this situation, unwanted stain precipitate may obscure hemoparasites.

Because of the extremely rapid course of illness associated with cytauxzoonosis, a diagnosis is often made by post-mortem examination. Grossly, dehydration, generalized pallor, and/or icterus may be observed^1,3,4 Other common findings at necropsy include enlarged, oedematous, and reddened lymph nodes; distended abdominal veins (especially splenic, mesenteric, and renal veins); petechial and ecchymotic haemorrhages of abdominal organs, heart, and lungs; large dark spleen; and congested, oedematous lungs.^1,5

Impression smears of affected tissues are usually diagnostic. Large mononuclear phagocytes (engorged with schizonts and developing merozoites) are readily identified within tissue imprints (Fig. 4).¹ On histopathology, schizont-containing macrophages are prominent within the lumens of larger blood vessels, especially in tissue sections of lung, spleen, and liver (Fig 5). These parasite-laden macrophages may be identified free within the lumen or attached to wall of the vessel, often appearing to occlude the vessel (Fig. 6).⁵ Despite the severity of infection, very few signs of inflammation are evident histologically.⁴

Fig. 4. Fine-needle aspirate, spleen, cat, cytauxzoonosis, Wright-Leishman stain. Large macrophage with innumerable Cytauxzoon felis merozoites.

Treatment

Historically, diagnosis with cytauxzoonosis has a very poor prognosis. Until recently, this disease was considered to be almost 100% fatal despite attempted treatment.² A current study has suggested that treatment with certain antiprotozoal drugs may control or eliminate cytauxzoonosis in cats. Seven of eight treated cats survived and cleared C. felis infections when treated with either diminazene aceturate or imidocarb dipropionate (along with aggressive supportive care).³ This small clinical study suggests that effective treatment may be possible for a disease that has been refractory to treatment for decades. In contrast, another study reported 18 cases of cytauxzoonosis in cats from Oklahoma and Arkansas in which the cats recovered without antiprotozoal therapy (although some cats remained parasitemic and could be a potential source of infection for naive cats).⁷ Experience (KSL, PMR) at The University of Georgia indicates that cytauxzoonosis in cats has been increasing in frequency with a greater distribution of the parasite. In previous decades, most cases of cytauxzoonosis occurred in the Brunswick, Georgia area. More recently, cats with the disease have been observed within the greater Atlanta metropolitan area. However, the parasite seems to be adapting to domestic cats because the disease course is sometimes less severe and more protracted. As the parasite continues to adapt to domestic cats as hosts, more animals may be expected to survive infection. Regardless, the fact remains that many of the cats that develop cytauxzoonosis do not survive. Therefore, cat owners should be educated that the disease may be prevented by tick control and restricting animals from tick infested areas during the warmer months of the year.

1. Cowell RL, Panciera RJ, Fox JC, et al. Feline cytauxzoonosis. Comp Cont Edu 10:731-736, 1988

2. Franks PT, Harvey JW, Shields RP, et al. Hematological findings in experimental Feline cytauxzoonosis. J Am Vet Med Assoc 24:395-401, 1987.

3. Greene CE, Latimer K, Hopper E, et al. Administration of diminazene aceturate or imidocarb dipropionate for treatment of cytauxzoonosis in cats. J Am Vet Med Assoc 214:497-500, 1999.

4. Hoover JP, Walker DB, Hedges JD. Cytauxzoonosis in cats: Eight cases (1985-1992). J Am Vet Med Assoc 205:455-460, 1994.

5. Kier AB, Greene CE. Cytauxzoonosis. Infectious Diseases of the Dog and Cat, 2nd ed. Greene, C.E. (ed). W.B. Saunders and Co., 1998, pp. 470-473.

6. Meier HT, Moore LE. Feline cytauxzoonosis: A case report and literature review. J Am Vet Med Assoc 36:493-496, 2000.

7. Meinkoth J, Kocan AA, Whitworth L, et al. Cats surviving natural infection with Cytauxzoon felis: 18 cases (1997-1998). Vet Intern Med 14:521-525, 2000.

8. Walker DB, Cowell RL. Survival of a domestic cat with naturally acquired cytauxzoonosis. J Am Vet Med Assoc 206:1363-1365, 1995.