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''Cytauxzoon felis'' is a
protozoal Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
organism transmitted to domestic cats by
tick bite Ticks (order Ixodida) are parasitic arachnids that are part of the mite superorder Parasitiformes. Adult ticks are approximately 3 to 5 mm in length depending on age, sex, species, and "fullness". Ticks are external parasites, living by ...
s, and whose
natural reservoir In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and rep ...
host is the
bobcat The bobcat (''Lynx rufus''), also known as the red lynx, is a medium-sized cat native to North America. It ranges from southern Canada through most of the contiguous United States to Oaxaca in Mexico. It is listed as Least Concern on the IUC ...
. ''C. felis'' has been found in other wild
felid Felidae () is the family of mammals in the order Carnivora colloquially referred to as cats, and constitutes a clade. A member of this family is also called a felid (). The term "cat" refers both to felids in general and specifically to the dom ...
species such as the
cougar The cougar (''Puma concolor'') is a large Felidae, cat native to the Americas. Its Species distribution, range spans from the Canadian Yukon to the southern Andes in South America and is the most widespread of any large wild terrestrial mamm ...
, as well as a
white tiger The white tiger or bleached tiger is a leucistic pigmentation variant of the Mainland tiger. It is reported in the wild from time to time in the Indian states of Madhya Pradesh, Assam, West Bengal, Bihar, Odisha, in the Sunderbans region and ...
in captivity. ''C. felis'' infection is limited to the family
Felidae Felidae () is the family of mammals in the order Carnivora colloquially referred to as cats, and constitutes a clade. A member of this family is also called a felid (). The term "cat" refers both to felids in general and specifically to the ...
which means that ''C. felis'' poses no
zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
(transmission to humans) risk or agricultural (transmission to farm animals) risk. Until recently it was believed that after infection with ''C. felis'', pet cats almost always died. As awareness of ''C. felis'' has increased it has been found that treatment is not always futile. More cats have been shown to survive the infection than was previously thought. New treatments offer as much as 60% survival rate.


Terminology

''Cytauxzoon felis'' belongs to the order
Piroplasmida Piroplasmida is an order of parasites in the phylum Apicomplexa. They divide by binary fission and as sporozoan parasites they possess sexual and asexual phases (sexual reproduction occurs in the tick gut). They include the tick parasites ''Ba ...
and the family
Theileriidae Theileriidae is a family of parasites in the order Piroplasmida. It includes the genus ''Theileria ''Theileria'' is a genus of parasites that belongs to the phylum Apicomplexa, and is closely related to ''Plasmodium''. Two ''Theileria'' speci ...
. ''C. felis'' is related to ''
Theileria ''Theileria'' is a genus of parasites that belongs to the phylum Apicomplexa, and is closely related to ''Plasmodium''. Two ''Theileria'' species, ''T. annulata'' and ''T. parva'', are important cattle parasites. ''T. annulata'' causes tropical ...
spp''. of African
ungulate Ungulates ( ) are members of the diverse clade Ungulata which primarily consists of large mammals with hooves. These include odd-toed ungulates such as horses, rhinoceroses, and tapirs; and even-toed ungulates such as cattle, pigs, giraffes, cam ...
s. It is not a
bacterium Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
, not a
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
, and not a
fungus A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...
, but is instead a
protozoan Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
that infects the blood cells of cats.


Epidemiology

The first case of ''C. felis'' was documented in
Missouri Missouri is a U.S. state, state in the Midwestern United States, Midwestern region of the United States. Ranking List of U.S. states and territories by area, 21st in land area, it is bordered by eight states (tied for the most with Tennessee ...
in 1976, and in the past it was believed to be limited to south central and southeastern
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
. There have been more cases popping up in the mid-Atlantic region in the United States, and even as far north as
Pennsylvania Pennsylvania (; ( Pennsylvania Dutch: )), officially the Commonwealth of Pennsylvania, is a state spanning the Mid-Atlantic, Northeastern, Appalachian, and Great Lakes regions of the United States. It borders Delaware to its southeast, ...
and
North Dakota North Dakota () is a U.S. state in the Upper Midwest, named after the Native Americans in the United States, indigenous Dakota people, Dakota Sioux. North Dakota is bordered by the Canadian provinces of Saskatchewan and Manitoba to the north a ...
in bobcats. There has not been any age or sex predilection made, but intact animals have shown more prevalence in some studies; in particular intact males. In studies it is unclear if the sex predilection is due to the increased roaming of intact animals or another reason. The most common seasons for the disease to become apparent are spring and summer and appear to affect outdoor cats the most often. The reason that outdoor cats get infected more is due to the increased exposure to ticks. Ticks are also active in spring and summer.


Symptoms and signs

Most infected cats have been healthy before a very sudden onset of severe disease. The course of clinical disease is often swift with clinical signs of
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
and inappetence within 5 to 20 days after the tick bite. Cats develop a high fever, but the temperature may become low before death. Other clinical findings can be:
dehydration In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, icterus (
jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...
),
enlarged liver Hepatomegaly is the condition of having an enlarged liver. It is a non-specific medical sign having many causes, which can broadly be broken down into infection, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdomi ...
and spleen,
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
, pale mucus membranes,
respiratory distress Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
or
bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...
, and tick infestation (although ticks are not often found on infected cats since cats typically groom ticks off their fur). Signs of disease seen on blood work include
hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
,
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
, increased or decreased
white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
numbers, icterus, and elevated
liver enzymes Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...
. Death usually follows the onset of clinical signs within a few days. However, more recent studies show not all cats develop clinical signs after infection, and some cats survive the infection.


Life cycle and transmission

The life cycle for ''Cytauxzoon felis'' has not been completely described. Bobcats become persistent carriers of the organism after they develop mild or subclinical infection and then serve as the reservoir host. ''C. felis'' is transmitted by the Lone star tick (''
Amblyomma americanum ''Amblyomma americanum'', also known as the lone star tick, the northeastern water tick, or the turkey tick, or the "Cricker Tick", is a type of tick indigenous to much of the eastern United States and Mexico, that bites painlessly and commonly ...
'') that feeds on an infected bobcat then transmits the organism to another bobcat, or to a pet cat. Many other types of ticks may feed on the cats, but the only other tick that has been shown to transmit the organism is the American dog tick (''
Dermacentor variabilis ''Dermacentor variabilis'', also known as the American dog tick or wood tick, is a species of tick that is known to carry bacteria responsible for several diseases in humans, including Rocky Mountain spotted fever and tularemia (''Francisella tul ...
'') but only in a research setting. In the past, domestic cats were thought to always die from infection so they were considered terminal hosts or "dead end hosts". Now there have been documented cases of cats that get sick and survive the infection and even those that never show clinical signs at all. Cats cannot catch the infection from another cat directly without being bitten by a tick. The life cycle of the protozoa has a tissue phase and an
erythrocytic Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
(red blood cell) phase. The organism goes through
asexual reproduction Asexual reproduction is a type of reproduction that does not involve the fusion of gametes or change in the number of chromosomes. The offspring that arise by asexual reproduction from either unicellular or multicellular organisms inherit the fu ...
phase that is called
schizogony Fission, in biology, is the division of a single entity into two or more parts and the regeneration of those parts to separate entities resembling the original. The object experiencing fission is usually a cell, but the term may also refer to how ...
which occurs in the mononuclear phagocytic cells. In the tissue phase, the macrophage cells that are infected often clog
venules A venule is a very small blood vessel in the microcirculation that allows blood to return from the capillary beds to drain into the larger blood vessels, the veins. Venules range from 7μm to 1mm in diameter. Veins contain approximately 70% of t ...
in organs such as the liver, spleen, lungs, and lymph nodes. It is this phase that is associated with clinical disease if the schizonts are numerous. Schizonts next form merozoites that break out of the
macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
cells and infect the red blood cells (erythrocytes). The erythrocytic disease is not as important for clinical disease, but is often used to diagnose ''C. felis'' because
piroplasm Piroplasmida is an order of parasites in the phylum Apicomplexa. They divide by binary fission and as sporozoan parasites they possess sexual and asexual phases (sexual reproduction occurs in the tick gut). They include the tick parasites ''Ba ...
s (erythrocytes that have phagocytized
merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
s) can be seen on a
peripheral blood smear A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the ...
under the microscope. It is not clear why some cats become clinically affected with ''C. felis'' while others never show any signs. There are speculations about resistance in some cats, and speculations about different strains of ''C. felis'' with differing virulence. There is not enough information to prove any of these theories, but cats in the same household or same regions can have drastically different clinical presentations. Some studies even show multi-cat households have had one cat die and another be persistently infected. When cats survive infection they have persistent
parasitemia Parasitemia is the quantitative content of parasites in the blood. It is used as a measurement of parasite load in the organism and an indication of the degree of an active parasitic infection. Systematic measurement of parasitemia is important in ...
which shows up in the blood as piroplasms, but these cats do not have the tissue phase again and therefore do not again show the clinical illness.


Diagnosis

One way to diagnose ''C. felis'' is by taking blood and performing a peripheral blood smear to look for the erythrocytic piroplasms. The erythrocytic piroplasms are usually shaped like signet rings and are 1 to 1.5 µm. Not all cats that are infected will have the piroplasms on their blood smear, especially if they are early in disease course. Another method of diagnosing infection in sick cats is to take needle aspirates of affected organs and find the schizonts inside mononuclear cells in the tissues; examination of tissue is also useful for the diagnosis after cats have died. Blood samples can be sent away for
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...
(PCR) testing to confirm infection. Other diseases that might resemble cytauxzoonosis should be ruled out. A major rule-out for ''C. felis'' is ''
Mycoplasma haemofelis ''Mycoplasma haemofelis'' (formerly ''Haemobartonella felis'') is a gram-negative epierythrocytic parasitic bacterium. It often appears in bloodsmears as small (0.6μm) coccoid bodies, sometimes forming short chains of three to eight organisms. ...
'' (formerly known as ''Haemobartonella felis''); clinical signs can be similar to cytauxzoonosis and the organism may be confused on the peripheral smear. Because it causes similar signs in outdoor cats during the spring and summer,
tularemia Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium ''Francisella tularensis''. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat infe ...
is another disease the veterinarian may want to rule out. Other laboratory tests are often abnormal in sick cats. The CBC of an infected cat often shows a
pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood coun ...
, or a decrease in red blood cells, white blood cells, and
platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
s; in some cases there is not a decrease in all three values. Clotting tests may be prolonged. Increased liver enzymes are common, and
electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...
disturbances,
hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200  mg/dL), but symptoms may not start to become noticeable until even ...
, and acid-base disturbances can also be observed.


Treatment and prevention

The preventative measure of keeping cats inside in areas with high infection rates can prevent infection. Approved tick treatments for cats can be used but have been shown not to fully prevent tick bites. The most often used treatments for cytauxzoonosis are
imidocarb dipropionate Imidocarb is a urea derivative used in veterinary medicine as an antiprotozoal agent for the treatment of infection with ''Babesia'' (babesiosis Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukary ...
and a combination of
atovaquone Atovaquone, sold under the brand name Mepron, is an antimicrobial medication for the prevention and treatment of ''Pneumocystis jirovecii'' pneumonia (PCP). Atovaquone is a chemical compound that belongs to the class of naphthoquinones. Atovaq ...
and
azithromycin Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumon ...
. Although imidocarb has been used for years, it is not particularly effective. In a large study, only 25% of cats treated with this drug and supportive care survived. 60% of sick cats treated with supportive care and the combination of the
anti-malarial drug Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young c ...
atovaquone and the antibiotic azithromycin survived infection. Quick referral to a veterinarian equipped to treat the disease may be beneficial. All infected cats require supportive care, including careful fluids, nutritional support, treatment for complications, and often
blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
. Cats that survive the infection should be kept indoors as they can be persistent carriers after surviving infection and might indirectly infect other cats after being themselves bitten by a vector tick.


References


External links


Cytauxzoonosis - The Merck Veterinary Manual





Cytauxzoonosis - WSAVA 2002
{{Taxonbar, from=Q779053 Parasites of cats Zoonoses Veterinary protozoology