Cytauxzoonosis

CAPC Recommends

• Cytauxzoonosis should be considered for any cat presenting with high fever, lethargy, icterus, respiratory signs (such as dyspnea or tachypnea), elevated lymph nodes and anemia.
• Mortality is often high despite treatment. The current recommended treatment protocol is intravenous fluids, blood transfusions and a combination of atovaquone and azithromycin (see Treatment guidelines) with aggressive supportive care.
• Reduce the risk of infection through effective year-round tick control and keeping cats indoors if possible. Remove ticks promptly when found.

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 recent research suggests that feral, domestic cats may play a larger role in maintaining the parasite than previously thought.
  

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

• Clinical signs usually develop about 10 days after a tick bite. Cats with cytauxzoonosis may present with:
  • high fever
  • dyspnea
  • tachypnea
  • depression
  • dehydration
  • anorexia
  • anemia
  • icterus
• The condition often rapidly progresses to hypothermia, recumbency, coma, and death. Severe morbidity and high mortality are commonly seen.
• Cats that present with hypothermia or respiratory distress have a very poor prognosis.
• 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. 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 acute cytauxzoonosis.
• Cats that survive acute infection are lifelong subclinical carriers.

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.
• The reported prevalence of C. felis in subclinically infected domestic cats in the United States ranges from 0% to 25.8% (Kansas).
• The prevalence of C. felis in bobcats can be very high with reports ranging from 0% to 80%.
  

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. However, the local and systemic immune response may also play a role in the development of severe disease.
• 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, hyperbilirubinemia, and hypoalbuminemia. Bilirubinuria is also a common finding.
• 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. Levels of circulating parasitemia vary especially post-treatment. Therefore, submission of whole blood for testing prior to treatment is key to accurate diagnosis.
• 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.
• No treatment protocol is consistently effective for the treatment of cytauxzoonosis.
• Currently, the recommended treatment for feline cytauxzoonosis is a combination of atovaquone (15 mg/kg PO q 8h for 10 days) and azithromycin (10 mg/kg PO q 24h for 10 days). Survival rates using this combination therapy combined with aggressive supportive care are 60% when initiated promptly.
• Imidocarb diproprionate, following premedication with atropine or glycopyrrolate, has also been historically used for treatment. However, this treatment protocol has largely fallen out of favor due to reduced efficacy and inconsistent results.
• Aggressive supportive care measures are necessary in all cases if cats are to recover from severe disease. It is also advised to minimize stress and handling while treating infected cats.
• No treatment protocol is currently available for eliminating C. felis in chronically infected cats.

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.
• Currently, some commercial products have demonstrated high efficacy in preventing C. felis transmission from infected ticks.
• 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.
• C. felis infection is limited to members of the cat family and poses no risk to dogs, or other species of animals.

Public Health Considerations

Cytauxzoon felis is not known to infect people.

Selected References

• 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.
• Haber MD, Tucker MD, Marr HS, Levy JK, Burgess J, Lappin MR, Birkenheuer AJ. 2007. The detection of Cytauxzoon felis in apparently healthy free-roaming cats in the USA. Vet Parasitol 146: 316-320.
• Levine, J. F., et al. 2008. Treatment of feline cytauxzoonosis with a combination of atovaquone and azithromycin. JVIM, 22(6), 1292-1298. DOI: 10.1111/j.1939-1676.2008.0174.x
• Nagamori Y, Slovak JE, Reichard MV. 2016. Prevalence of Cytauxzoon felis infection in healthy free-roaming cats in north-central Oklahoma and central Iowa. J Feline Med Surg Open Rep 2.
• 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.
• Reichard MV, Thomas JE, Arther RG, Hostetler JA, Raetzel KL, Meinkoth JH, Little SE. 2013. Efficacy of an imidacloprid 10%/flumethrin 4.5% Collar (Seresto®, Bayer) for preventing the transmission of Cytauxzoon felis to domestic cats by Amblyomma americanum. Parasitol Res 112: S11-S20.
• Reichard MV, Rugg JJ, Thomas JE, Allen KE, Barrett AW, Murray JK, Herrin BH, Beam RA, King VL, Vatta AF. 2019. Efficacy of a topical formulation of selamectin plus sarolaner against induced infestations of Amblyomma americanum on cats and prevention of Cytauxzoon felis transmission. Vet Parasitol 270: S31-S37.
• Rizzi TE, Reichard MV, Cohn LA, Birkenheuer AJ, Taylor JD, Meinkoth JH. 2015. Prevalence of Cytauxzoon felis infections in healthy cats from enzootic areas in Arkansas, Missouri, and Oklahoma. Parasit Vectors 8: 13.
• Shock BC, Murphy SM, Patton LL, Shock PM, Olfenbuttel C, Beringer J, Prange S, Grove DM, Peek M, Butfiloski JW, Hughes DW, Lockhart JM, Bevins SN, VandeWoude S, Crooks KR, Nettles VF, Brown HM, Peterson DS, Yabsley MJ. 2011. Distribution and prevalence of Cytauxzoon felis in bobcats (Lynx rufus), the natural reservoir, and other wild felids in thirteen states. Vet Parasitol 175: 325-330.
• Weerarathne P, Sanders TL, Kao Y, Cotey SR, Place JD, Fairbanks WS, Miller CA, Reichard MV. 2023. High prevalence of Cytauxzoon felis in bobcats (Lynx rufus) across Oklahoma and occurrence in West Texas, USA. J Wildl Dis 59: 432-441.
• Wikander YM, Anantatat T, Kang Q, Reif KE. 2020. Prevalence of Cytauxzoon felis infection-carriers in Eastern Kansas domestic cats. Pathogens 9: 854.