76 Cytauxzoonosis

8/11/2019 76 Cytauxzoonosis

1/13

Infectious Diseases of the Dog and Cat, 3rd Edition

CHAPTER 76 Cytauxzoonosis

Craig E. Greene

James Meinkoth

A. Alan Kocan

ETIOLOGY AND EPIDEMIOLOGY

Cytauxzoon feliscauses a tick borne blood protozoal disease of domestic cats (Felis domesticus)and exotic

Felidae from several central, south central, and southeastern states in the United States (Fig. 76-1). This

distribution corresponds somewhat with the only known tick vector,Dermacentor variablis. Infection of domestic

cats results in a rapidly progressive, usually fatal, disease. The natural reservoir host appears to be the North

American bobcat (Lynx rufus), in which infection is usually exhibited as a persistent, but asymptomatic,

erythroparasitemia. Other wild cats may also harbor the organism. In a study of naturally exposed exotic cats inFlorida, the prevalence of asymptomatic infection for transplanted Texas cougars was 39% and for Florida

panthers was 35%.30

Fatal cytauxzoonosis was reported in a captive reared white tiger (Panthera tigris)at a

private breeding facility in northern Florida.10

Florida panthers (Puma concolor coryi)and a Texas cougar (P.

concolor stanleyana)at this facility were also suspected of being infected. In Germany, a captive Bengal tiger

(Panthera tigris)developed fatal cytauxzoonosis, presumably after contact with bobcats imported from North

America.16

The organism has previously been recognized in the erythrocytes of cheetahs (Acinonyx jubatus).33

Iatrogenic transmission from a Florida panther to a domestic cat has been reported.4Cytauxzoonosis, caused by

similar organisms as evaluated by light microscopy, was first described in African ungulates. Electron microscopic

examination of a natural, fatal case of African cytauxzoonosis in a tsessebe calf (Damaliscus lunatus)showed the

size and appearance similar to those described for C. felis.17

Organisms genetically similar to C. felishave been

identified in cats in Spain,6

South Africa,1

and in a Pallas cat (Otocolobus manul)from Mongolia.18

Thereforethis disease may be more widespread than was previously recognized. Reservoir hosts and vectors will need to be

determined for these newly recognized foci of infection.

Cytauxzoonhas been classified in the order Piroplasmida and family Theileriidae. This family has both an

erythrocytic and a leukocytic, or tissue, phase. In the case of C. felis, the tissue phase consists of large schizonts

that develop within macrophages, whereas Theileria, a more familiar genus of this family, has its exoerythrocytic

phase primarily within lymphocytes. The Babesiidae, a related family, is characterized by having only or primarily

an erythrocytic (piriform) phase in the mammalian host that is indistinguishable from the erythrocytic form in

Cytauxzoon. Although no serologic cross reactivity has been reported between C. felisand the South African

parasites Theileria taurotragiandBabesia felis, RNA gene sequence analysis links C. felis, Babesia equi, and

Babesia rodhainito both the theilerias and babesias, with some suggestion that these three organisms be

reclassified within a separate family.1,7

In the life cycle of C. felis, schizonts develop primarily within mononuclear phagocytes, first as indistinct

vesicular structures within the cytoplasm of infected cells and later as large, distinct, nucleated schizonts that

actively undergo division by schizogony and binary fission (Fig. 76-2).22

The phagocytes line the lumens of

vessels within almost every organ and become huge and numerous, often occluding the vessel similar to a

thrombus. Multiplication of schizonts within host cells is observed ultrastructurally to be true schizogony, without

76

76.1

CHAPTER 76 Cytauxzoonosis Page 1 of 13


2/13


host cell division. Later in the course of the disease, schizonts develop buds (merozoites) that separate and

eventually fill the entire host cell. The host cell probably ruptures, releasing the merozoites into the blood or tissue

fluid. Merozoites appear in macrophages 1 to 3 days before they are observed in erythrocytes. These organisms

then invade uninfected erythrocytes and produce late stage parasitemias that are detected on examination of blood

films, usually 1 to 3 days before death.20

Fig 76-1 Map of distribution by state of reported cytauxzoonosis in the United

States, along with overlapping distribution of the tick and reservoir host.

(Courtesy University of Georgia, Athens, Ga.)

The apparently sporadic occurrence, short course of illness, and usually fatal nature of the disease indicate that the

domestic cat is likely an incidental dead end host. However, at least two cats with naturally occurring infectionsand two experimentally inoculated, untreated cats have survived.

13,28,32In contrast, the schizogenous phase is

limited and transient in infected bobcats that usually develop a nonfatal erythroparasitemia and serve as potential

carriers.3Infection rates as high as 60% in clinically healthy, wild-trapped bobcats has been reported.

12However,

fatal disease has been reported sporadically in some bobcats.3,21,29

717



3/13


Ticks likely are the natural vector for Cytauxzoonbecause most cases have been associated with the presence of

ticks on the hosts. Tick (Dermacentor variabilis)transmission from wild caught, splenectomized bobcats with

parasitemia to two splenectomized domestic cats resulted in the fatal form of the disease. Conversely,

subinoculation of blood from bobcats to cats appeared to transmit only the erythrocytic piroplasm stage resulting

in asymptomatic parasitemia.2The fatal form of the disease with extraerythrocytic stages develops only, or

primarily, after tick transmission of the organism or inoculation of schizont-containing tissues from fatally

infected cats. In the white tiger that developed naturally occurring fatal disease in Florida, two female Lone Star

ticks (Amblyomma americanum)were present on the inguinal skin.10

Deceased.

PATHOGENESIS

The prepatent period of natural infection is between 2 to 3 weeks. Rapid, intravascular multiplication of the tissue

phase of the parasite is responsible for the severe clinical illness seen in domestic cats, most likely the result of

mechanical obstruction of blood flow, especially through the lungs. By-products of tissue parasites may be toxic,

pyrogenic, and vasoactive. The blood phase may induce destruction and phagocytosis of erythrocytes, although

erythroparasitemia in the absence of schizogenous development is of little clinical significance. Disseminated

intravascular coagulation (DIC) has been a complication based on laboratory findings in naturally infected

cats.10,13

Infected cats appear to die from a shocklike state.

CLINICAL FINDINGS

In the naturally occurring disease, affected cats develop nonspecific clinical signs that lead to a rapid course of

illness and death, usually in fewer than 5 days. Most cats are presented from March through September, and

geographic clusters of infection may be observed. Access to an outdoor, wooded environment or tick exposure is

typically noted. Anorexia, dyspnea, lethargy, dark urine, dehydration, depression, icterus and pallor, anemic heart

murmur, capillary refill time greater than 2 seconds, and fever (39.4 to 41.6 C [103 to 107 F]) have been

observed (Fig. 76-3). Some cats vocalize as if in pain. Hypothermia, recumbency, and coma are clinical findings

in terminally ill cats.

Clinical signs in experimentally induced cytauxzoonosis have been similar to those in naturally occurring cases.

Incubation periods have varied from 5 to 20 days, probably attributable to type and dose of inoculum, method of

cryopreservation, and individual cat response. After a febrile period (39.9 to 40.1 C [103.8 to 104.2 F]), the

temperature may become subnormal, and the cat may have difficulty breathing. Parasitized erythrocytes are

observed late in the disease, during the febrile episode. Cats usually die 2 or 3 days after the temperature peak, and

the entire course of clinical illness usually takes less than a week.

DIAGNOSIS

Cytauxzoonosis should be considered in the differential diagnosis when a cat that is allowed access to tickinfested, wooded areas becomes depressed and develops high temperature and possibly anemia and jaundice.

Confusion with hemotrophic mycoplasmosis (formerly haemobartonellosis) is most frequent (see Chapter 31).

Generally, cytauxzoonosis can be suspected when anemia is mild relative to the degree of icterus. Instead of the

strongly regenerative anemia typical of hemolysis, the anemia of cytauxzoonosis is normocytic, normochromic,

and nonregenerative. The leukocyte count may be variable, but a profound leukopenia or thrombocytopenia, or

both, are present, particularly late in the course of disease. High serum concentrations of total bilirubin and

76.2

76.3

76.4



4/13


bilirubinuria are common findings. Other clinical chemistry changes are variable and less specific but include low

serum concentrations of albumin, cholesterol, and potassium and high serum glucose and alanine aminotransferase

activity.15

Although serum urea nitrogen and ammonia concentrations and hepatic enzyme activities may be

elevated in febrile or comatose animals, they may not be elevated earlier in the course of disease. Along with

thrombocytopenia, prolonged activated coagulation, activated partial thromboplastin time (APTT), and

prothrombin time tests and increased fibrin split products will be present in cats with DIC.10,13,14

Cats with

cytauxzoonosis do not always have prolongation of all coagulation values; the APTT, in conjunction with

thrombocytopenia, is usually most consistently elevated. 717



5/13


Fig 76-2 Life cycle of C. felis. A, Free merozoites, released from schizonts, (B)

enter circulating erythrocytes by endocytosis and (C)undergo replication

in a variety of forms. The circulating parasitized erythrocytes are ingestedby the tick and (D)are released into the gut. E, These differentiate into

macro- and micro-gamonts which unite to form a zygote. This

differentiates into an ookinete which replicates by asexual reproduction

and finally penetrates the gut wall and migrates to the salivary gland. F,

Once there, asexual reproduction by merogony results in salivary

infection, (G)via budding of organisms from the cell surface. H, During

feeding, the organism is inoculated by the tick and enters mononuclear

phagocytes. I, Within the phagocytes, replication by schizogony and

binary fission leads to large parasitized cells that often occlude the blood

vessel lumen. Merozoites engorge the cell until it ruptures releasing themerozoites into the blood and the cycle continues (Courtesy University

of Georgia, Athens, Ga.)

718



6/13


Fig 76-3 A, Cat showing paleness from Cytauxzooninfection. B, Serum (glass tube,

top left)and urine (syringe, bottom right)show high bilirubin content.

(Courtesy University of Georgia, Athens, Ga.)

Definitive diagnosis is most commonly made by demonstrating the erythrocyte phase (piroplasms) in Wright's or

Giemsa stained thin blood films. The piroplasms within erythrocytes appear as round signet ringshaped bodies,

1 to 1.5m in diameter; bipolar oval safety pin forms, 1 2 m; tetrad forms; or anaplasmoid round dots, less

than 0.5 m in diameter (Fig. 76-4). All forms may occur in a single blood film, the signet ringshaped organisms

being most characteristic. A single cell usually contains only one parasite, but pairs and tetrads (Maltese crosses)

are observed occasionally. The nucleus of the piroplasm is round to elongated and stains purple to dark red. The

cytoplasm stains light blue or may appear as an indistinct clearing of the erythrocyte adjacent to the nucleus. The

erythrocytic stage of Cytauxzoonmay appear similar to other hemoparasites. The prominent, well-defined nuclear

area of C. felispiroplasms allows differentiation from the ring form of hemotrophic mycoplasmas. Piroplasms of

some smallBabesiaspp., such asB. felis, and Theileriaspp. are morphologically indistinguishable from those of

C. felis. However, these organisms have not yet been reported to infect domestic cats in the United States.

The number of parasitized cells varies from cat to cat and with the stage of the disease, increasing as the disease

progresses. The development of schizogenous tissue phases, which is responsible for clinical signs of disease,

precedes the appearance of piroplasms in the peripheral blood by a few days. Therefore some cats examined early

in the course of disease may not be parasitemic on initial evaluation. The number of parasites in peripheral blood

smears may increase dramatically in a 24-hour period; therefore reevaluation may be helpful when cytauxzoonosis

is suspected despite a negative blood smear. When quantitated, the percentage of parasitized erythrocytes during

illness ranges from 0.5% to 4%. In terminally ill, moribund cats, parasitemia has been higher. The number of

nucleated erythrocytes and erythrocytes with Howell-Jolly bodies may increase slightly.

If the parasitemia is absent or low, the schizogenous tissue phase may be found in Wright's or Giemsa stained

aspirates or impression smears of spleen, lung, liver, bone marrow, or lymph node.9Phagocytes containing

tissue-phase schizonts are sometimes found on the feathered edge of a peripheral blood smear. Schizonts are firstrecognized as basophilic areas within the cytoplasm of macrophages (Fig. 76-5). As the developing schizont

enlarges to fill the cytoplasm of the macrophage completely, the parasitized host cell enlarges greatly and

develops a large, prominent nucleolus (Fig. 76-6). As the schizont matures, the purple nuclei of developing

merozoites can be seen within the basophilic schizont (Fig. 76-7).

719



7/13


Fig 76-4 Feline erythrocytes infected with characteristic, signet ring-shaped

Cytauxzoonpiroplasms. The large, clearly evident nuclear area allows the

organisms to be differentiated from hemotrophic Mycoplasmaorganisms(Wright-Giemsa, 330).

Thoracic radiographs may show a bronchointerstitial pulmonary pattern, presumably related to the schizogony

occurring in the pulmonary tissues.25

Endotracheal washings from one cat had a mixed cell pattern of

macrophages, eosinophils, neutrophils, and lymphocytes, in decreasing order. Intracellular schizonts were

observed in pulmonary macrophages.

In cats that die, histologic confirmation should be made from standard formalin fixed tissues (lung, lymph node,

spleen, liver, heart, brain) sent to a veterinary pathology laboratory for parasite evaluation because hemotrophic

mycoplasmosis and babesiosis do not have a tissue stage. A direct fluorescent antibody test for the detection of the

tissue phase31

and a microfluorometric immunoassay system for the detection of the serum antibody to C. felis5

have been developed; however, neither test is commercially available. Polymerase chain reaction (PCR) has been

used to document and follow infection in cats that survived infection, and it may become commercially

available.27,1a

In one treated cat, the PCR results were positive 18 months after treatment, although no organisms

were detected on blood smear examination.27

Because of the usually rapidly progressive nature of the disease,

such tests are not needed in most routine cases.

719

720



8/13


Fig 76-5 Impression smear from a feline liver showing a macrophage contains a

developing Cytauxzoonschizont. The early schizont (outlined by

arrowheads)appears as a lobulated basophilic area within the cytoplasmof the host cell. A large, prominent nucleolus is present in the host cell

nucleus (long arrow)(Wright-Giemsa, 165).

Fig 76-6 Two schizont-containing macrophages in an impression smear of felinespleen. The host cells are greatly enlarged as can be seen by comparison

with the numerous small lymphocytes and plasma cells (arrows)in the

background (Wright-Giemsa, 66.)



9/13


PATHOLOGIC FINDINGS

Gross findings in domestic cats include dehydration; pallor; icterus; hydropericardium; hydrothorax; enlarged,

edematous, and hemorrhagic lymph nodes; accentuated hepatic lobular pattern; intraabdominal venous distention;

splenomegaly; and petechial and ecchymotic hemorrhages on the serosal surfaces of abdominal organs and lungs

(Fig. 76-8). The lungs are frequently congested and edematous, often with petechiae throughout (Fig. 76-9).

The characteristic lesion on histologic examination of feline cytauxzoonosis is the accumulation of a large number

of parasitized mononuclear phagocytes containing schizonts in various stages of development. These cells are

particularly prevalent within the lumens of veins of the lungs, liver, lymph nodes, and spleen, making these vessels

appear partially or completely occluded (Fig. 76-10). Minimal inflammatory reaction is present in affected tissues.

Spleen and lymph node should be used for tissue impression films, which should be stained with Wright's or

Giemsa stain.

Fig 76-7 Higher magnification of cell in Fig. 76-6. The host nucleus (outlined by

arrowheads)with an enlarged nucleolus is visible. The developedschizont completely fills the cytoplasm and the nuclear material of the

developing merozoites is evident (small arrows)(Wright-Giemsa, 330).

THERAPY

Preliminary attempts to treat cats that have either naturally or experimentally induced disease have had very

limited success. The domestic cat as an unnatural host appears highly susceptible to this organism. Some evidence

for more recent adaptation exists in that cats are being presented for clinical illness rather than at postmortem.13,27

Strains from different geographic areas may also vary in virulence. Since 1997, an increasing number of cats from

a limited geographic area in northwestern Arkansas and northeastern Oklahoma have survived natural infection,

most without receiving any specific, potentially effective antiprotozoal treatment.27

These cats appear to be

immune to subsequent challenge with virulent C. felis.26

In most other reports, even with the most effective drugs,

76.5

76.6



10/13


the mortality is extremely high. Of the recovered cats, supportive care is essential. Supportive diuresis with

isotonic intravenous fluids and adjunctive heparin is necessary to control concomitant DIC.14

Parvaquone, sodium thiacetarsemide, buparvaquone, and tetracycline appear to be ineffective. One cat treated with

fluids, enrofloxacin, and tetracycline survived, although therapy was likely not related to survival in this animal.32

This cat came from the area in northeastern Oklahoma in which survivors have subsequently been commonly

reported and may in fact represent an early infection with a less virulent strain. Most success in treatment has been

with the carbanilide compounds, diminazene, or imidocarb. Imidocarb is commercially available in the United

States (see Drug Formulary, Appendix 8).14

The drug is given as two injections within a 1- to 2-week interval.

Parasympatholytic drugs such as atropine or glycopyrrolate should be given before treatment to counteract

potential parasympathetic side effects. Morphologic examination of the organisms in blood smears showed a

degenerating appearance within 48 hours after drug therapy was instituted. Enrofloxacin has also been used in a

limited number of cats, in combination with the carbanilides; however, its efficacy has not been substantiated.

Recommended dosages for these drugs are listed in Table 76-1. Within the first week following treatment, the cat

develops a hemolytic anemia, presumably as a result of destruction of dying organisms in infected erythrocytes.

Cats that recover subsequently have an increase in their erythrocyte neutrophil and platelet counts. Blood

transfusions may be required in cats that have the most severe hemolytic anemia following treatment.

Fig 76-8 Gross lesions in a cat experimentally infected with C. felisinclude a

greatly enlarged spleen and a slightly enlarged liver with rounded edges

and distended veins.

720

721



11/13


Fig 76-9 Petechial and ecchymotic hemorrhages throughout the lungs of a cat

that died from cytauxzoonosis. (Courtesy Oklahoma State University

Veterinary Pathobiology Teaching Set, Stillwater, Okla.)

Table 76-1 Therapy for Cytauxzoonosis

DRUGa

DOSEb ROUTE INTERVAL DURATION (DAYS)

Heparin 100150 U/kg SC 8 hours As needed

Atropine 0.04 mg/kg IV, IM, SC 24 hours 1c

Glycopyrrolate 0.0050.01 mg/kg IV, IM, SC 24 hours 1c

Enrofloxacind 5.0 mg/kg PO, SC 12 hours 710

Imidocarb dipropionate5.0 mg/kg IM 14 days 14

Diminazene aceturate 2.0 mg/kg IM 7 days 7

SC,Subcutaneous; IV,intravenous; IM,intramuscular; PO,by mouth.

a See Drug Formulary, Appendix 8, for specific information on each drug. Adjunctive isotonic fluid

therapy is extremely important for this disease. See text.

b Dose per administration at specified interval.

c Given once, 15 minutes before injection of imidocarb or diminazene.

d The efficacy of this drug alone for cytauxzoonosis is uncertain. Use of imidocarb or diminazene is

recommended instead or in combination. Higher dosages of enrofloxacin previously used have been

associated with retino toxicity.



12/13


Fig 76-10 Section of lung from a cat with cytauxzoonosis. Schizont-containing

macrophages completely line the endothelial surface and nearly

occlude the lumen of a large vessel. The enlarged nucleoli of host cellnuclei are visible in some cells (arrowheads). Developing organisms can

be seen as a faint granular appearance to the cytoplasm of some of the

cells (arrow)(H and E stain, 66).

PREVENTION

A conscientiously applied ectoparasite control program and confinement indoors during tick season may be

beneficial in preventing cytauxzoonosis because all naturally occurring cases have involved cats that were free toroam in wooded, tick infested areas. See Chapter 94for more extensive information on tick control.

Suggested Readings*

* See the CD-ROM for a complete list of references.

6. Criado-Fornelio, A, Gonzalez-del-Rio, Buling-Sarana, A, et al.: The expanding universe of piroplasms.

Vet Parasitol. 119, 2004, 337345.

14. 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. 215, 1999, 497500.

18. Ketz-Riley, CJ, Jazson, MV, Van den Bussche, R, et al.: An intraerythrocytic small piroplasm in wildcaught Pallas cat (Otocolobus manul)from Mongolia.J Wild Dis. 39, 2003, 42430.

25. Meier, HT, Moore, LE: Feline cytauxzoonosis: a case report and literature review.J Am Anim Hosp

Assoc. 36, 2000, 493496.

721

722

76.7

76.8



13/13


27. Meinkoth, J, Kocan, AA, Whitworth, L, et al.: Cats surviving natural infection with Cytauxzoon felis:

18 cases (1997-1998).J Vet Intern Med. 14, 2000, 521525.


76 Cytauxzoonosis

Documents

Transcript of 76 Cytauxzoonosis