82
Brief Communications and Case Reports
3 Kouyoumdjian AO, McDonald JJ: Association of congenital adrenal neuroblastoma with multiple anomalies,
including an unusual oropharyngeal cavity (imperforate
buccopharyngeal membrane?). Cancer 4:784-788, 195 1
4 Latshaw W K Veterinary Developmental Anatomy, pp.
87-126. BC Decker, Philadelphia, PA, 1987
5 Longacre JJ: Congenital atresia of the oropharynx. Plast
Reconstr Surg 8:341-348, 1951
6 Saperstein G: Congenital abnormalities of internal organs
and body cavities. Vet Clin North Am 9: 1 15-1 25, 1993
Vet Pathol 33:1, 1996
7 Seghers MJ: Une malformation rare: I’imperforation oropharyngienne. Acta Paediatr Belgica 20: 130-1 37, 1966
Request reprints from Dr. I. W. Smoak, Department ofAnatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, 4700
Hillsborough Street, Raleigh, NC 27606 (USA).
Vet Pathol33532-86 (1996)
Fatal Cytauxzoonosis in a Captive-reared White Tiger (Panthera tigris)
M. M. GARNER,
N. P. LUNG,S. CITINO,E. C. GREINER,
J. W. HARVEY,
AND B. L. HOMER
Abstract. Fatal (Panthera tigris) cytauxzoonosis was diagnosed in a 7-year-old female white tiger. The tiger
presented with a 2-day history of anorexia and lethargy. She was mildly dehydrated, with a temperature of
105.2 F and a hematocrit of 26%. Over the next day, icterus developed, and her physical condition progressed
to recumbency, coma, and death. Hematologic findings obtained shortly before death included icteric plasma,
severe thrombocytopenia, mild anemia, hematuria, and parasites consistent with Cytauxzoonfelis in circulating
erythrocytes. Gross necropsy findings included generalized icterus, generalized petechiae and ecchymoses, splenomegaly, and peribronchial edema. Histologic changes included large numbers of intravascular macrophages
containing developmental stages of Cytauxzoon felis that partially or completely occluded blood vessels in the
lung, spleen, liver, and bone marrow. Except for an experimental infection of a bobcat, fatal cytauxzoonosis
has not previously been diagnosed in felids other than domestic cats. These findings raise questions regarding
the pathogenicity of this organism in felids and may impact husbandry and interstate transfer of captive large
cats.
Key words: Cytauxzoon felis; cytauxzoonosis; tigers.
Cytauxzoonosis is an uncommon but uniformly fatal disease of domestic cats (Felis domesticus) caused by Cytauxzoon felis, a protozoan in the family Theileridae, which
also includes the genera Theileria and Gonderia.’ Members
of this family have erythrocytic and extraerythrocytic phase^.^
Within this family, Cytauxzoon is unique in that schizogony
occurs within mononuclear phagocytes, whereas the schizont
stages of Theileria and Gonderia occur in lymphocyte^.^ Naturally occurring cases of cytauxzoonosis in the United States
have been confined to states in the southeast and midwest
and along the Gulf Coast.’ Cytauxzoonfelis has been transmitted experimentally between bobcats (Felis rufus) and cats
by the American dog tick, Dermacentor variabilis.‘ The bobcat is believed to be the reservoir host for C. felis, and only
one experimentally infected bobcat has been reported to develop fatal disease.’O Additional cases of clinical disease attributed to this organism have not been reported in felids
other than domestic cats. In this report, we describe a case
of fatal cytauxzoonosis in a captive adult white tiger (Panth-
era tigris).
A 7-year-old captive-born female white tiger housed at a
private breeding facility in northern Florida had a 2-day
history of anorexia and lethargy. Following chemical immobilization on day 3 of illness, two female lone star ticks
(Amblyommaamericanum) were removed from the inguinal
skin. On clinical examination, the tiger was mildly dehydrated, with a temperature of 105.2 F and a hematocrit of
26% (normal = 3O.4-42.6Yo4).Splenic enlargement was noted
on palpation and abdominal radiographs. Over the next day,
icterus developed and the tiger’s physical condition rapidly
progressed to recumbency, coma, and development of petechiae on the oral mucous membranes, with profuse bleeding from injection and venipuncture sites. Four serial CBCs
obtained during the last 2 days of life were similar and not
progressive; averaged values revealed mild nonregenerative
anemia (hematocrit = 27.7%), moderate leukopenia (leukocytes = 4,025/pl; normal = 8,100-1 5,9O0/pl4)with neutropenia (2,10O/pl; normal = 2,800-1 1,8O0/pl4)and lymphopenia (7OO/pl; normal = 1,300-1 ,9O0/pl4),severe thrombocytopenia (estimated <2,OOO/pl; normal = 1 1 1,000447,0O0/pl4),positive plasma fibrin split products test, and
the presence of piroplasmic ring forms of C.felis in approx-
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Vet Pathol 33:1, 1996
Brief Communications and Case Reports
Fig. 1. Blood film; white tiger. Piroplasm ring forms of
C.felis within the cytoplasm of erythrocytes. (The occurrence
of spherocyte-like erythrocytes at the feathered edge of the
film is a normal finding in felids.) Wright-Geimsa stain. Bar
= 5.0 um.
imately 5% of circulating erythrocytes (Fig. 1). Serum chemistry values obtained shortly before death revealed hyperbilirubinemia (3.5 mg/dl; normal = 0.1-0.3 mg/d14), hypoglycemia (26 mg/dl; normal = 8 1.9-1 56.1 mg/d14), and hypoproteinemia (4.6 g/dl; normal = 6.5-7.9 g/d14).By routine
enzyme-linked immunosorbent assay, the tiger was negative
for feline leukemia virus (FeLV) antigen and negative for
antibodies to feline immunodeficiency virus (FIV) at the time
of illness and 1 year prior to illness. Cytauxzoonfelis organisms were not observed during blood film examination 2 and
3 years earlier. By day 4 of illness, the tiger had not recovered
from the previous day’s chemical immobilization and died
soon after percutaneous hepatic biopsy samples were obtained. Necropsy was immediately performed.
Gross necropsy findings included mild dehydration, generalized icterus, generalized petechiae and ecchymoses, severe abdominal sanguineous effusion attributed to postbiopsy hepatic hemorrhage, moderate splenomegaly, peribronchial edema, severe bilateral hip dysplasia, and mild atrophy
of the skeletal muscles of the hind limbs. Additional ticks
were not observed on the carcass.
Selected tissues were fixed in 10% buffered formalin, processed in paraffin blocks, sectioned at 5 pm, and stained with
hematoxylin and eosin (HE). Formalin-fixed specimens of
spleen were divided into 1-mm3sections, immersed in 2.5%
glutaraldehyde in 0.1 M phosphate buffer, postfixed in 2%
osmium tetroxide, and embedded in epoxy resin. Ultrathin
sections stained with uranyl acetate and lead citrate were
examined with a Hitachi H-7 electron microscope at 75 kV.
The primary histologic lesion was the presence of large
numbers of intravascular mononuclear phagocytes containing cytoplasmic developmental stages of C. felis in brain,
heart, lung, liver, kidney, spleen, lymph node, and bone marrow. These cells were often in close contact with the endothelium and partially or completely filled small arteries, veins,
and capillaries. The infected phagocytes were enlarged up to
three times normal size, and the cytoplasm was filled with
developing stages of the parasite. The infected cells usually
83
had a large oval displaced nucleus and a single large nucleolus. Depending on the developmental stage, organisms had
a variable appearance. Low numbers of phagocytes contained
early stages of schizogony, characterized by an amorphous
vacuolar or slightly granular cytoplasmic appearance. In the
most commonly observed form, the phagocyte cytoplasm
became filled with numerous round to oval 4-7-pm lightly
basophilic spherical structures that often contained one or
two small distinct basophilic nuclei. Occasionally, infected
cells contained large numbers of 1-2-pm oblong basophilic
bodies arranged in small clusters (merozoites). In this stage,
the host cell occasionally had evidence of degeneration, characterized by nuclear swelling, pyknosis or karyorrhexis, and
cytoplasmic eosinophilia. Many infected cells contained developing schizont and merozoite stages (Fig. 2). In the lung,
greatly expanded zones of edematous connective tissue surrounded most of the bronchi and bronchioles. Numerous
small veins and venules filled with infected mononuclear
phagocytes were observed in these areas, and fewer infected
cells occasionally filled the lumina of alveolar capillaries (Fig.
3). Splenic enlargement was attributed to hyperplasia of the
mononuclear phagocyte system, with large numbers of parasitized mononuclear phagocytes within the red pulp and
large blood vessels. Lymphoid cellularity was reduced markedly in the red and white pulp. Bone marrow contained large
numbers of parasitized phagocytes within the extravascular
and intravascular marrow spaces, accompanied by moderate
myeloid and erythroid hypoplasia and occasional erythrophagocytosis. Megakaryocytes numbers were normal to
slightly increased with orderly maturation in the bone marrow and were also low within the splenic red pulp. Large
numbers of parasitized mononuclear phagocytes were in central veins and sinusoidal Kupffer cells of the liver and within
venules of the meninges and brain.
Ultrastructural examination of formalin-fixed spleen revealed most developing stages of C.felis within the cytoplasm
of infected mononuclear phagocytes, although early and
merozoite stages were rare and residual bodies were not observed. Most commonly, infected cells contained large numbers of multinucleated syncytial forms. Fission of nuclei within
the syncytium and budding of merozoites from the external
surface of the syncytium were observed occasionally (Fig. 4).
Merozoites contained a single slightly eccentric nucleus, a
polar ring, apical cytoplasmic rhoptries, and mitochondria.
Developing parasites greatly expanded the cytoplasm of the
host cell and displaced the cell nucleus and cytoplasmic organelles. The morphology of the parasite at each stage of
development within infected mononuclear phagocytes was
identical to that described in phagocytes of infected domestic
cat~.~lJ~
The pathogensis of feline cytauxzoonosis is obscure. Investigators have hypothesized that release of toxic by-products associated with the development of schizonts and merozoites in infected phagocytes contributes to pyrexia and
cellular necrosis.* Polysystemic occlusion of blood vessels
results in congestion and tissue anoxia and could also contribute to cellular necrosis and toxemia.* Although degenerative changes were detected in the infected phagocytes,
tissue necrosis was not observed in this tiger and does not
appear to be a significant feature of the experimental or nat-
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84
Brief Communications and Case Reports
Vet Pathol 33:1, 1996
Fig. 2. Lung, peribronchial venule; white tiger. Lumen of the venule is filled with enlarged mononuclear phagocytes
that contain developing schizonts (large arrow) and merozoites (curved arrow) of C. felis. Note eccentric, occasionally
pyknoytic nuclei of host cell. A parasitized cell is also in an alveolar capillary (small arrow). HE. Bar = 50 pm.
ural disease in domestic cats. Congestion and edema of numerous tissues have been attributed to impaired venous
drainage due to occlusion of vascular lumina by infected
mononuclear phagocytes.8 This phenomenon most likely
caused the peribronchial edema in the tiger. Leukopenia,
anemia, and thrombocytopenia were detected, as reported
in infected domestic cat^.^.^ Anemia in cats infected with C.
felis is believed to be caused primarily by phagocyt~sis.~
Bilirubinemia and icterus result from increased erythrocyte destruction.IZIn this tiger, mild nonregenerative anemia and
lack of a regenerative erythroid response in the marrow suggest that anemia and the presence of the erythrocytic form
of the parasite occurred late in the clinical course of disease.
The tiger may not have been anemic long enough for a regenerative response to be detected in the bone marrow. The
finding of erthrophagocytosis in the marrow is consistent
with the proposed mechanism for the development ofanemia
in infected cats. There was minimal evidence of impaired
hematopoiesis in the bone marrow of the tiger. The apparent
erythroid hypoplasia may have been relative to the presence
of large numbers of infected phagocytes and moderate myeloid hyperplasia. Excluding hemorrhage attributed to hepatic biopsy shortly before death, blood loss due to hemorrhage was mild and probably did not contribute significantly
Fig. 3. Lung, bronchus; white tiger. Penbronchial edema (astenck) and numerous venules filled with phagocytes infected with C. felis in the adjacent parenchyma. One involved venule has prominent perivascular edema (arrow). HE. Bar
= 1.0 mm.
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Vet Pathol 33:1, 1996
Brief Communications and Case Reports
85
Fig. 4. Spleen, mononuclear phagocyte; white tiger. Cytoplasm of phagocyte contains numerous developmental stages
of Cytauxzoon. Some syncytia (s) have merozoites budding from outer membrane (arrows), and mature merozoites (open
arrow) are free in the cell cytoplasm. Uranyl acetate and lead citrate stain. Bar = 1.O pm.
to the anemia. Dehydration was mild but may have masked generalized disease and not a preexisting condition. Immua slightly more severe anemia. The anemia in part may have nosuppression was therefore not necessarily involved in the
been due to anemia of chronic inflammatory disease asso- pathogenesis of the C.felis infection in this tiger; some tigers
ciated with the hip dysplasia.
may be susceptible to clinical cytauxzoonosis. Cytauxzoon
Hemorrhage was attributed to thrombocytopenia. Throm- felis has not previously been reported in tiger blood and was
bocytopenia was accompanied by a slight increase in bone not seen in blood smears from two Bengal tigers housed near
marrow megakaryocytes and the appearance of low numbers this patient. Experimental C.felis infectivity studies have not
of megakaryocytes in the spleen, suggestive of a regenerative been performed in tigers.
response to platelet consumption or destruction. ThromboCytauxzoonfelis has been transmitted experimentally becytopenia due to consumption, such as in disseminated in- tween bobcats and domestic cats by The American dog tick.'
travascular coagulation (DIC), was considered possible be- There are no documented cases of transmission of this parcause of the increased fibrin split products detected in the asite by lone star ticks, the ticks found on the tiger prior to
peripheral blood prior to death; however, histologic features death; however, these ticks can serve as a host for the related
of DIC, such as the occurrence of fibrin thrombi in pulmo- protozoan Theileria cervi.? One of us (E. C. Griener) has
nary and glomerular capillaries, were not detected. Although collected these ticks from the breeding facility. It is also posphagocytized platelets were not observed histologically or in sible that the parasite was transmitted by another type of
blood smears, intravascular immune-mediated destruction tick not detected antemortem or at necropsy. Cytauxzoon
of platelets was a possible cause for the severe thrombocy- felis has been recognized in erythrocytes ofbobcats,6cheetahs
topenia. Widespread attachment of platelets to endothelium (Acinonyxj u b a t u ~ ) and
, ~ ~ a Florida panther (Felis concolor
activated or damaged by infected phagocytes is also a possible coryi).2 Only one fatal case attributed to Cytauxzoon infecmechanism of platelet removal.
tion has been reported in a bobcat.* Experimental tick-borne
No examinations of immune function were performed on transmission of the organism from infected bobcats to dothis tiger. There was no history of birth control implants or mestic cats results in fatal cytauxzoonosis in the cats, sugrecent administration of immunosuppressive drugs. Infec- gesting that the bobcat is a reservoir host and the domestic
tion by FeLV and FIV are common viral causes of immu- cat is an accidental host.' A suspension of mononuclear cells
nosuppresion in domestic cats, but these infections were ruled from an infected, asymptomatic panther experimentally inout serologically as possible underlying infections in this ti- oculated into a domestic cat produced fatal cytauxzoonosis
ger. In addition, a heritable basis for immunosuppression in the cat,2but transfusion of cheetah blood containing Cywould be unlikely in an adult tiger with no prior history of tauxzoon-like organisms failed to produce fatal disease in a
disease attributable to immunosuppression. Although lymph domestic cat.I4 Because blood transfusions from infected
nodes were not examined histologically, there was marked asymtomatic donors may produce parasitemia without
lymphoid depletion in the spleen, possibly due to disruption death9J0and tissue homogenate inoculums from donors with
of lymphoid tissue by infected phagocytes or a response to clinical disease are always fatal,9 it is likely that fatal trans-
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Brief CommunicatioIns and Case Reports
86
fusions require the presence of circulating schizont stages in
infected mononuclear phagocytes.
The tiger of this report was housed for 5 years in a fenced
outdoor enclosure bordered on three sides by a densely wooded area known to support wild bobcats subclinically infected
with C. felis. Other large cats at this facility included Bengal
tigers, cheetahs, Florida panthers, and Texas cougars (Felis
concolor). Low numbers of ticks had been noticed on many
of the cats, including two Bengal tigers housed with the white
tiger. In addition to the wild bobcats, one Texas cougar and
three Florida panthers in the facility had evidence of erythrocytic piroplasms, consistent with C. felis, in peripheral
blood. Because of the difficulty in detecting low parasitemias
in subclinically infected cats, it is possible that more subclinically infected large cats are present at this facility. Tickborne transmission of the parasite probably occurred while
the tiger was on the premises.
The occurrence of fatal cytauxzoonosis in a white tiger has
significant implications regarding management of nondomestic cats in breeding facilities or zoological exibits. Because the circumstances necessary for development of clinical
disease in nondomestic cats are not clear and because feral
cats, bobcats, and other large breeds of cats may occur in
facilities where interaction is possible via the tick vector,
cytauxzoonosis should be considered as a potential problem
for cats housed in these facilities. Although in the United
States, the disease has been confined to the southeast, Midwest, and Gulf Coast, interstate transfer of large cats carrying
the erythrocytic stages of Cytauxzoonfelis provides a source
of infection for susceptible cats in tick-infested areas in other
parts of the country. Monitoring of peripheral blood in cats
destined for interstate transfer is recommended.
3
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7
8
9
10
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12
Acknowledgements
We thank Drs. D. Forrester, R. Isaza, and C. Buergelt for
their critical reviews of the manuscript.
References
13
14
1 Blouin EF, Kocan AA, Glenn BL, Kocan KM, Hair JA:
Transmission of Cytauxzoonfelis Kier, 1979 from bobcats, Felis rufus (Schreber), to domestic cats by Dermacentor variabilis (Say). J Wildl Dis 20:241-242, 1984
2 Butt MT, Bowman D, Barr MC, Roelke ME: Iatrogenic
transmission of Cytauxzoonfelis from a Florida panther
Vet Pathol 33:1, 1996
(Felix concolor coryi) to a domestic cat. J Wildl Dis 27:
342-347, 1991
Cowell RL, Panciera RJ, Fox JC, Tyler RD: Feline cytauxzoonosis. Compend Cont Ed Pract Vet 10:73 1-735,
1988
Flesness NR. Average Physiologic Values. International
Species Information System (ISIS), Apple Valley, MN,
1992
Franks PT, Harvey JW, Shields RP, Lawman MJP: Hematological findings in experimental feline cytauxzoonosis. J Am Anim Hosp Assoc 24:395-401, 1988
Glenn BL, Kocan AA, Blouin E F Cytauxzoonosis in
bobcats. J Am Vet Med Assoc 183:1155-1158, 1983
Hazen-Karr CG, Kocan AA, Kocan KM, Hair JA: The
ultrastructure of sporogeny in Theileria cervi (Bettencourt et al., 1907) in salivary glands of female Amblyomma americanum (L.) ticks. J Parasitol 73: 1182-1 188,
1987
Kier AB, Wagner JE, Kinden DA: The pathology of
experimental cytauxzoonosis. J. Comp Pathol 97:4 15432, 1987
Kier AB, Wagner JE, Morehouse LG: Experimental
transmission of Cytauxzoon felis from bobcats (Lynx
rufus) to domestic cats (Felis domesticus). Am J Vet Res
43~97-101, 1982
Kier AB, Wightman SR, Wagner JE: Interspecies transmission of Cytauxzoonfelis. Am J Vet Res 43: 102-105,
1982
Kocan AA, Kocan ISM, Blouin EF, Mukolwe SW: A
redescription of schizogeny of Cytauxzoon felis in the
domestic cat. Trop Vet Med Curr Issues Perspect 653:
161-167, 1992
Schalm OW, Jain NC, Carroll EJ: Veterinary Hematology, 3rd ed. Lea and Febiger, Philadelphia, PA, 1985
Simpson CF, Harvey JW, Lawman MJP, Murray J, Kocan AA, Carlisle JW: Ultrastructure of schizonts in the
liver of cats with experimentally induced cytauxzoonosis.
Am J Vet Res 46:384-390, 1985
ZinMe JG, McDonald SE, Kier AB, Cippa SJ, Small PJ:
Cytauxzoon-like organisms in erythrocytes of two cheetahs. J Am Vet Med Assoc 179:1261-1262, 1981
Request reprints from Dr. M. Gamer, Phoenix Central Laboratory, 11620 Airport Road, Suite 100, Everett, WA 982043742 (USA).
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