J. Paul Woods,     Guelph, Ontario, Canada

Epidemiology

C. felis was first recognized in 1976 in southwestern Missouri. It now has been reported in the south central, southeastern, mid-Atlantic, and Gulf Coast states of the United States (Web Figure 84-3). The pattern of geographic distribution probably is affected by the availability of both reservoir hosts (wild bobcats) and arthropod vectors (Dermacentor variabilis, Amblyomma americanum). The natural life cycle of C. felis is not completely understood. The domestic cat was presumed to be an accidental terminal host in which C. felis caused predominantly a rapidly fatal disease, but recent findings of asymptomatic infected cats have led to the possibility that domestic cats serve as an additional reservoir for C. felis. In contrast, bobcats (Lynx rufus) are the presumed reservoir hosts acting as persistent carriers of the organism and usually developing only mild or subclinical infection. There is a paucity of information on blood parasites of free-ranging cats, however, and Cytauxzoon has been reported in bobcats only since 1982, so questions remain as to whether this is a new disease of felids or only a newly identified disease. Mountain lions (Felis concolor) from Florida and Texas also have been reported to carry the organism. There has been a correlation of disease with tick interchange among wild and domestic felids, with ticks presumably transmitting the organism between cats by feeding. In addition to D. variabilis (American dog tick), A. americanum (Lone Star tick) recently has been demonstrated experimentally to be a competent vector for Cytauxzoon. Both tick species are common in the southeastern and midwestern United States where the majority of C. felis infections have been identified. Transstadial transmission occurs in ticks but transovarial transmission has not been demonstrated. However, cytauxzoonosis may be more widespread than previously recognized because cytauxzoonosis-like diseases have been reported in domestic cats in Zimbabwe and Spain, in Pallas’s cats (Otocolobus manul) in Mongolia, and in a lion (Panthera leo) in Brazil. Experimental studies have revealed no zoonotic or agricultural risk for C. felis.

Feline cytauxzoonosis is highly seasonal, occurring in spring to early fall; the highest incidence is in early spring to early summer, which correlates with the peak activity of competent tick vectors. Outdoor cats with access to wooded environments are at greatest risk of infection, presumably because of increased exposure to tick vectors. In endemic areas there is a large variability in the incidence of disease between relatively short distances. In fact, there are hyperendemic foci as suggested by detection of infection in more than one cat in multicat households, a phenomenon likely due to common exposure to tick populations rather than direct cat-to-cat transmission. Cytauxzoonosis has been reported most commonly in middle-aged cats, but it can occur in cats of any age, with no sex or breed predilections. A recent report suggested young male cats to be at higher risk. A previous study screening for C. felis in feral cats in the southeastern United States reported a prevalence of 0.3% with an estimated prevalence range of 0% to 0.8%. However, recent studies of feral cats and “high-risk” cats (e.g., cats cohabiting with a cat previously diagnosed with cytauxzoonosis) using more sensitive real-time polymerase chain reaction (PCR) testing have reported prevalence of up to 20% to 40%.

Pathogenesis

The limited information available from investigations of C. felis reveals a complex pathogenesis. Experimental studies demonstrate that the clinical disease in domestic cats depends on exposure to the schizogonous tissue phase of C. felis. Inoculation with schizont homogenate induces disease, whereas inoculation with only erythrocyte-phase piroplasms results in erythroparasitemia without schizont development and without clinical signs of disease. Cats exposed to infected D. variabilis develop both schizogonous phases and erythroparasitemia and become ill with cytauxzoonosis. Piroplasms cannot progress through their natural life cycle without passing through the tick host. Thus the ticks are not just mechanical vectors but also are necessary to complete the C. felis life cycle. As noted earlier, transstadial but not transovarial transmission has been demonstrated in ticks. Oral and contact exposure does not result in disease; therefore close contact between cats without tick vectors does not pose a risk of disease transmission.

After infection, the organism undergoes schizogony, an asexual reproductive phase, in mononuclear phagocytic cells associated with vessels of almost every organ. As the schizonts (see Web Figure 84-2) undergo schizogony and binary fission, macrophages lining the blood vessels enlarge tremendously and occlude venules in liver, spleen, lung (Web Figure 84-4), and lymph nodes, which result in a thrombuslike mechanical obstruction of blood flow and tissue hypoxia. The schizont is associated with clinical disease, and the greater the schizont burden the more severe the clinical illness. Infected domestic cats have extensive schizont burdens, whereas mildly affected bobcats have a limited and transient schizogonous phase. The tissue phase also is suspected to release toxic, pyrogenic, and vasoactive products that contribute to clinical manifestations. The schizogonous tissue phase, detectable by 12 days after infection, is responsible for the venous congestion, thrombotic disease, and organ failure that leads to death in most cats within 3 weeks of infection.