Cytauxzoonosis
Species
Cytauxzoon felis
Overview of Life Cycle  
Cats become infected with C. felis when feeding ticks inoculate sporozoites into the bite wound. The protozoa enter endothelial-associated mononuclear phagocytes and begin multiplying by binary fission. Large schizonts are ultimately produced. These rupture to release merozoites that enter erythrocytes.
Asexual reproduction of C. felis occurs in the felid host whereas sexual reproduction (gametogony) and production of infective sporozoites (sporogony) occurs in the tick vector.
Amblyomma americanum, the lone star tick, is considered the predominant vector of C. felis based on experimental infection studies and epidemiologic data. Historical studies indicate Dermacentor variabilis, the American dog tick, can also transmit C. felis to cats. Observed differences in vectorial capacity of different tick species may be due to pathogen strain differences, tick strain differences, or immune status of host.
Bobcats (Lynx rufus) are traditionally considered the main reservoir host of C. felis although other wild felids and domestic cats are also infected and may contribute to infection prevalence in ticks.
Stages
Large schizonts containing numerous merozoites develop within endothelial-associated macrophages.
Merozoites released from mature schizonts invade erythrocytes and are usually apparent within erythrocytes on stained blood smears from clinically affected cats in the late stages of disease.
Cytauxzoon felis within erythrocytes
Cytauxzoon felis schizonts within macrophages
Disease
Cats with cytauxzoonosis may present with high fever, dyspnea, depression, dehydration, anorexia, anemia, and jaundice that often rapidly progresses to hypothermia, recumbency, coma, and death. Severe morbidity and high mortality are commonly seen.
Cats often present with complications of disseminated intravascular coagulation and shock. Fatalities usually occur within one week of initial development of clinical disease.
Mortality appears to be dependent on which strain of C. felis is involved and how rapidly intensive nursing care is instituted. Even with outstanding supportive care, mortality rates with C. felis remain high (> 50%). However, because some cats do survive, treatment is recommended in all but the most moribund of patients.
Mild or subclinical infections with C. felis also occur in domestic cats, including those that have recovered from cytauxzoonosis.
Prevalence
Most cases of cytauxzoonosis in the United States are reported from the southeastern and south-central states between March and September, when the tick vectors are active. However, disease due to C. felis also occurs in the mid-Atlantic states and upper Midwest and on the West Coast.
Host Associations and Transmission Between Hosts
Cats become infected with C. felis upon inoculation of sporozoites by tick feeding.
Direct transmission from an infected to a naïve animal is unlikely but could occur following blood transfusion, iatrogenic inoculation with contaminated needles or surgical instrument, or by bite wounds. In these cases, only the erythrocytic form is likely to be transmitted, and thus severe clinical disease, which is associated with development of large schizonts inside macrophages, will not occur.
Prepatent Period and Environmental Factors
Piroplasms can be found in erythrocytes on stained blood smears 1 to 3 weeks following infection by tick feeding.
Exposure to a tick-infested environment is an important part of the history. Because disease may not develop for as long as 3 weeks after inoculation of organisms by ticks, attached ticks may or may not be present on cats at presentation.
Site of Infection and Pathogenesis
Ticks inoculate sporozoites of C. felis directly into the bite wound. Organisms first invade macrophages where they undergo schizongony. Released merozoites then invade erythrocytes in circulation.
The severe clinical disease seen in cats with cytauxzoonosis is thought to be primarily attributable to large schizonts within macrophages obstructing blood flow (particularly in the lungs) and leading to disseminated intravascular coagulation and shock.
A mild hemolytic anemia also may develop due to the erythrocytic stage.
Diagnosis
Clinical pathologic changes in cats with C. felis include non regenerative anemia, leukopenia, thrombocytopenia, elevated liver enzymes, and hypoalbuminemia.
Definitive microscopic diagnosis of C. felis infection relies on identification of piroplasms in circulating erythrocytes on blood smear; identification of large schizonts in splenic, lymph node, or bone marrow aspirates; or identification of large schizonts on impression smears from these organs or from the lung at necropsy.
Serology and culture isolation are not available for C. felis.
In recent years, molecular diagnosis of C. felis via polymerase chain reaction (PCR) of whole blood has become available. However, results should be interpreted with caution because the techniques used in different diagnostic laboratories vary. Amplification of related organisms by nonspecific primers may result in false-positive reactions. Conversely, apparent false-negatives may occur if extraction procedures fail to remove PCR inhibitors present in a blood sample or if the level of circulating parasitemia falls below the level of assay detection because of a normal decrease in circulating organisms or temporary suppression of infection following antiprotozoal treatment. To maximize the utility of molecular diagnostics, blood samples should be collected early in the course of clinical disease and before the initiation of chemotherapy and should be submitted to experienced diagnostic laboratories with stringent quality control measures in place.
Treatment
Mortality attributable to C. felis is often high despite therapy, although some strains are apparently less virulent.
Current research supports using a combination of atovaquone (15 mg/kg PO q 8h) and azithromycin (10 mg/kg PO q 24h) for the treatment of feline cytauxzoonosis and has been suggested to result in greater survival rates.
Imidocarb diproprionate (5 mg/kg IM, twice at 14-day intervals), following premedication with atropine or glycopyrrolate, can also be used for treatment. Decreasing the interval between injections to 7 days may improve survival. Hemolytic anemia is often exacerbated following initiation of imidocarb and, in severe cases, may necessitate a blood transfusion.
Some protocols recommend combining imidocarb diproprionate therapy with enrofloxacin (5 mg/kg PO or SC q12h for 10 days).
Aggressive supportive care measures are also necessary if cats are to recover from severe disease.
Control and Prevention
Vaccines are not available to prevent infection of cats by C. felis.
Cats should be kept indoors to avoid tick exposure. If cats cannot be kept indoors, then stringent adherence to routine application of effective acaricides and daily tick checks with prompt removal of all attached ticks is critical to prevent the disease and mortality associated with C. felis infection.
Tick infestations and resultant infection with C. felis can be prevented by avoiding tick-infested areas whenever possible and by modifying the habitat around the home through such basic measures as removing debris and keeping shrubbery and grass closely clipped to discourage both tick populations and the wildlife species that often harbor them from flourishing.
Public Health Considerations
Cytauxzoon felis is not known to infect people.
Selected References
Reichard MV, Baum KA, Cadenhead SC, Snider TC. 2008. Temporal occurrence and environmental risk factors associated with cytauxzoonosis in domestic cats. Vet Parasitol 152: 314-320.
Reichard MV, Edwards AC, Meinkoth JH, Snider TA, Meinkoth KR, Heinz RE, Little SE. 2010. Confirmation of Amblyomma americanum as a vector for Cytauxzoon felis to domestic cats. J Med Entomol. 47: 890-896.
Cohn LA, Birkenheuer AJ, Brunker JD, Ratcliff ER, Craig AW. 2011. Efficacy of atovaquone and azithromycin or imidocarb diproprionate in cats with acute cytauxzoonosis. J Vet Intern Med. 25(1): 55-60.
Species
Cytauxzoon felis
Overview of Life Cycle  
Cats become infected with C. felis when feeding ticks inoculate sporozoites into the bite wound. The protozoa enter endothelial-associated mononuclear phagocytes and begin multiplying by binary fission. Large schizonts are ultimately produced. These rupture to release merozoites that enter erythrocytes.
Asexual reproduction of C. felis occurs in the felid host whereas sexual reproduction (gametogony) and production of infective sporozoites (sporogony) occurs in the tick vector.
Amblyomma americanum, the lone star tick, is considered the predominant vector of C. felis based on experimental infection studies and epidemiologic data. Historical studies indicate Dermacentor variabilis, the American dog tick, can also transmit C. felis to cats. Observed differences in vectorial capacity of different tick species may be due to pathogen strain differences, tick strain differences, or immune status of host.
Bobcats (Lynx rufus) are traditionally considered the main reservoir host of C. felis although other wild felids and domestic cats are also infected and may contribute to infection prevalence in ticks.
Stages
Large schizonts containing numerous merozoites develop within endothelial-associated macrophages.
Merozoites released from mature schizonts invade erythrocytes and are usually apparent within erythrocytes on stained blood smears from clinically affected cats in the late stages of disease.
Cytauxzoon felis within erythrocytes
Cytauxzoon felis schizonts within macrophages
Disease
Cats with cytauxzoonosis may present with high fever, dyspnea, depression, dehydration, anorexia, anemia, and jaundice that often rapidly progresses to hypothermia, recumbency, coma, and death. Severe morbidity and high mortality are commonly seen.
Cats often present with complications of disseminated intravascular coagulation and shock. Fatalities usually occur within one week of initial development of clinical disease.
Mortality appears to be dependent on which strain of C. felis is involved and how rapidly intensive nursing care is instituted. Even with outstanding supportive care, mortality rates with C. felis remain high (> 50%). However, because some cats do survive, treatment is recommended in all but the most moribund of patients.
Mild or subclinical infections with C. felis also occur in domestic cats, including those that have recovered from cytauxzoonosis.
Prevalence
Most cases of cytauxzoonosis in the United States are reported from the southeastern and south-central states between March and September, when the tick vectors are active. However, disease due to C. felis also occurs in the mid-Atlantic states and upper Midwest and on the West Coast.
Host Associations and Transmission Between Hosts
Cats become infected with C. felis upon inoculation of sporozoites by tick feeding.
Direct transmission from an infected to a naïve animal is unlikely but could occur following blood transfusion, iatrogenic inoculation with contaminated needles or surgical instrument, or by bite wounds. In these cases, only the erythrocytic form is likely to be transmitted, and thus severe clinical disease, which is associated with development of large schizonts inside macrophages, will not occur.
Prepatent Period and Environmental Factors
Piroplasms can be found in erythrocytes on stained blood smears 1 to 3 weeks following infection by tick feeding.
Exposure to a tick-infested environment is an important part of the history. Because disease may not develop for as long as 3 weeks after inoculation of organisms by ticks, attached ticks may or may not be present on cats at presentation.
Site of Infection and Pathogenesis
Ticks inoculate sporozoites of C. felis directly into the bite wound. Organisms first invade macrophages where they undergo schizongony. Released merozoites then invade erythrocytes in circulation.
The severe clinical disease seen in cats with cytauxzoonosis is thought to be primarily attributable to large schizonts within macrophages obstructing blood flow (particularly in the lungs) and leading to disseminated intravascular coagulation and shock.
A mild hemolytic anemia also may develop due to the erythrocytic stage.
Diagnosis
Clinical pathologic changes in cats with C. felis include non regenerative anemia, leukopenia, thrombocytopenia, elevated liver enzymes, and hypoalbuminemia.
Definitive microscopic diagnosis of C. felis infection relies on identification of piroplasms in circulating erythrocytes on blood smear; identification of large schizonts in splenic, lymph node, or bone marrow aspirates; or identification of large schizonts on impression smears from these organs or from the lung at necropsy.
Serology and culture isolation are not available for C. felis.
In recent years, molecular diagnosis of C. felis via polymerase chain reaction (PCR) of whole blood has become available. However, results should be interpreted with caution because the techniques used in different diagnostic laboratories vary. Amplification of related organisms by nonspecific primers may result in false-positive reactions. Conversely, apparent false-negatives may occur if extraction procedures fail to remove PCR inhibitors present in a blood sample or if the level of circulating parasitemia falls below the level of assay detection because of a normal decrease in circulating organisms or temporary suppression of infection following antiprotozoal treatment. To maximize the utility of molecular diagnostics, blood samples should be collected early in the course of clinical disease and before the initiation of chemotherapy and should be submitted to experienced diagnostic laboratories with stringent quality control measures in place.
Treatment
Mortality attributable to C. felis is often high despite therapy, although some strains are apparently less virulent.
Current research supports using a combination of atovaquone (15 mg/kg PO q 8h) and azithromycin (10 mg/kg PO q 24h) for the treatment of feline cytauxzoonosis and has been suggested to result in greater survival rates.
Imidocarb diproprionate (5 mg/kg IM, twice at 14-day intervals), following premedication with atropine or glycopyrrolate, can also be used for treatment. Decreasing the interval between injections to 7 days may improve survival. Hemolytic anemia is often exacerbated following initiation of imidocarb and, in severe cases, may necessitate a blood transfusion.
Some protocols recommend combining imidocarb diproprionate therapy with enrofloxacin (5 mg/kg PO or SC q12h for 10 days).
Aggressive supportive care measures are also necessary if cats are to recover from severe disease.
Control and Prevention
Vaccines are not available to prevent infection of cats by C. felis.
Cats should be kept indoors to avoid tick exposure. If cats cannot be kept indoors, then stringent adherence to routine application of effective acaricides and daily tick checks with prompt removal of all attached ticks is critical to prevent the disease and mortality associated with C. felis infection.
Tick infestations and resultant infection with C. felis can be prevented by avoiding tick-infested areas whenever possible and by modifying the habitat around the home through such basic measures as removing debris and keeping shrubbery and grass closely clipped to discourage both tick populations and the wildlife species that often harbor them from flourishing.
Public Health Considerations
Cytauxzoon felis is not known to infect people.
Selected References
Reichard MV, Baum KA, Cadenhead SC, Snider TC. 2008. Temporal occurrence and environmental risk factors associated with cytauxzoonosis in domestic cats. Vet Parasitol 152: 314-320.
Reichard MV, Edwards AC, Meinkoth JH, Snider TA, Meinkoth KR, Heinz RE, Little SE. 2010. Confirmation of Amblyomma americanum as a vector for Cytauxzoon felis to domestic cats. J Med Entomol. 47: 890-896.
Cohn LA, Birkenheuer AJ, Brunker JD, Ratcliff ER, Craig AW. 2011. Efficacy of atovaquone and azithromycin or imidocarb diproprionate in cats with acute cytauxzoonosis. J Vet Intern Med. 25(1): 55-60.