Dr Lizzie Youens BSc(Hons) BVSc MRCVS 

Imagine a five-year-old domestic longhaired female cat is brought into your veterinary clinic with a two-day history of lethargy and inappetence. Your patient has no medical history apart from routine vaccinations and is not up to date with preventative parasite treatment. The patient has outdoor access but also spends time indoors. There is no known access to toxins, and the cat has no other symptoms. No vomiting, diarrhea, coughing, sneezing or changes in urination habits have been observed at home. The food has not been changed recently, and there is no history of travel.

On examination, the cat is quiet but alert. The mucous membranes are pale. The patient is tachypnoeic (respiratory rate 50 breaths/minute) and tachycardic (heart rate 220 bpm). She has a temperature of 103.2^oF. Lymph node and abdominal palpation is normal. 

Most veterinarians will likely agree that the list of differential diagnoses is fairly long: inappetence and lethargy are common symptoms in any sick cat. So which diagnostic tests do you choose to carry out? And does your geographic location affect your diagnostic pathway and process?

Vector-borne disease is becoming more prevalent across the United States and is a concern for both animal and human health. With varying climates and habitats, as well as differing distributions of human and animal populations, veterinarians should be vigilant for vector-borne pathologies, including hemoparasites. 

Read on to learn more about feline hemoparasites, their diagnostic clues, and their geographical variations. 

What is a feline hemoparasite?

Hemoparasites, or erythroparasites, are organisms which live within the blood cells of a host. They are often transferred between hosts via a vector, such as a tick or fly. Hemoparasites can be bacteria or other microorganisms such as rickettsiae, protozoa, or nematodes. 

Examples of feline hemoparasites seen in the United States include:

• Babesia
• Dirofilaria immitis
• Cytauxzoon felis
• Mycoplasma haemofelis and Mycoplasma haemominutum 
• Hepatozoon felis
• Trypanosoma cruzi

Geographic prevalence

When considering vector-borne disease, the geographic location of the pet and any history of travel are hugely important. The prevalence of hemoparasites varies according to region, mostly due to climate and vector differences. 

D. immitis is an excellent example of how prevalence of disease varies according to location. The Companion Animal Parasite Council (CAPC) compiles data on feline heartworm antibody and antigen cases across the USA and uses these statistics to produce maps displaying prevalence. A large study of 25,000 cats nationwide found that 15.9% tested antibody positive for heartworm (Piche et al., 1998). There is a marked increase in cases in the Southeastern U.S., the Mississippi River Valley, and Texas. 

Another hemoparasite with a fairly strict geographical distribution is Trypanosoma cruzi. This zoonotic trypanosome is endemic in parts of South and Central America. In the U.S.A., only localized areas in the southern states are affected (CAPC). Cats in Louisana have been implicated as a potential reservoir for this disease as tested animals have shown significant levels of serum antibody to it. To date there are no reported feline cases in the United States. (Greene)

Some hemoparasites have a broader distribution and are more affected by season than region. Cytauxzoonosis, for example, is seen primarily in the southeastern and south-central states where the resovior host and vector populations overlap. However the resovior host, lynx, is present throughout the United States, and disease from these areas is not ruled out. However, cases are almost all concentrated between March through September, as this is when the tick vector (Dermacentor varibilis & A. americanum) is active (Reichard et al., 2008). 

The availability of vectors will play a large role in the prevalence of disease. Mycoplasma haemofelis, for example, is spread through biting, blood-sucking parasites which include fleas, but also potentially through a bite from an infected cat. As fleas are the most common ectoparasite in the U.S, often present year-round (Blagburn & Dryden, 2008), it makes sense that feline hemoplasmosis commonly occurs all over the country and throughout the seasons (Sykes et al., 2008). Conversely, diseases spread via a tick vector will depend on the prevalence of tick species, the season, and the exposure of animals to ticks (Stich et al., 2014).

Detecting hemoparasites in cats

Veterinarians presented with a sick animal will naturally start their diagnostic pathway with a full history — including travel status and parasite preventatives — and a clinical examination. They will then commonly progress to establishing a minimum database including a complete blood count (CBC), biochemistry profile, and urinalysis. 

Many clues can be established from these initial tests. The longhaired cat mentioned in the introduction, for example, was found to be tachycardic and tachypnic, as well as severely anemic (PCV 14%). The anemia was regenerative, with polychromasia and nucleated RBCs seen on smear. The patient also had an elevated bilirubin, which can be elevated with hemolysis, hepatic disease and cholestasis. As the results showed normal ALT, AST, GGT and ALKP, hemolysis appeared a likely cause of the anemia. Albumin levels were also normal, which would usually decrease in cases of hemorrhage. The differential diagnosis for hemolytic anemia include primary immune mediated disease as well as infectious causes including Cytauxzoon felis and feline haemoplasmas, FIP, feline retrovirus, heinz body hemolytic anemia, and congenital disorders such as pyruvate kinase deficiency and red cell fragility of Abysian and Somali cats.

The clinical findings, including hemolysis, fever, and a lack of parasite prevention, would give a  suspicion for hemoparasitic disease and therefore warrant further diagnostics in this area.

In cases which are presenting with classic symptoms of hemoparasitic disease, such as fever, lethargy, and hematological concerns such as anemia, relevant testing for vector-borne disease would be recommended. The clinician should use knowledge of the relevant parasites in their area, alongside their clinical findings, to prioritize specific testing. 

Serology testing to identify specific antibodies is available for certain parasites, such as Trypanosoma cruzi, Babesia spp. and D. immitis. ELISA (enzyme-linked immunoassay) and IFA (indirect fluorescent antibody). However, antibody testing is not foolproof: cross-reactivity can occur (such as with T. cruzi and Leptospira spp.) and false negatives can occur if the test is run too early and antibodies are not yet present. 

Alternatively, PCR (polymerase chain reaction) tests may be available, which can be more specific as they look for the presence or absence of the organism’s DNA in each sample. PCR testing is commonly used for Mycoplasma spp., but also for Babesia and D. Immitis. 

Accurate assessment of a blood smear is often an essential tool for parasite diagnosis. Definitive diagnosis of Babesia, for example, relies upon the identification of piroplasms in erythrocytes on a stained smear. It’s important to remember that organisms like M. hemofelis are variably present on a smear based on the stage of disease (Ettinger).Similarly, C. felis testing requires identification via a smear, as serology is not available and recent PCR tests have shown relatively high levels of both false negatives and positives. Since some pathogens are variably present in the peripheral blood, fine needle aspirate of lymph nodes or the spleen may highlight infectious agents more reliably such as in the case of cytauxzoonosis. (Greene)

Diagnosis of heartworm in cats can also pose challenges. It has been found that 15-25% infected with adult worms are antibody negative (Venco et al., 2015), whereas up to 90% of antibody-positive cats have no mature worms present (Browne et al., 2005). With antigen testing, only mature female worms are detected, and around a third of adult heartworm infections in cats are composed only of male worms and would therefore go undetected. Heat treatment may improve this technique (Little et al., 2014). Identifying microfilariae can also be problematic: less than 20% of cats with adult worm infections have microfilariae present (Venco et al., 2015). The American Heartworm Society has various guidelines to navigate this tricky diagnostic path, as well as information about incidence and prevalence of the parasite. 

Prevention

An awareness of the prevalence of parasitic disease and the availability of vectors seasonally are important when considering prevention as well as diagnosis. Due to the high prevalence of vectors, parasites and clinical disease levels, as well as potential risks to human health, the AAHA have feline specific guidelines for annual care. These include screening for infectious and zoonotic disease as well as discussion of parasite prevention at annual wellness exams. 

Conclusion?

So what of the lethargic five-year-old cat mentioned above? Well, after it was found to be severely anemic, further investigations proceeded. The anemia was regenerative, with significant polychromasia and nucleated cells. Bilirubin levels were elevated, but liver enzymes were within normal values, as was albumin, indicating that the anemia may have a hemolytic cause rather than hepatic, cholestatic, or hemorrhagic. A blood smear and PCR testing confirm the diagnosis of Mycoplasma haemofelis. The patient was treated with doxycycline for three weeks and made a good recovery. 

Vector-borne disease is a rising global concern and affects both animal and human health. Veterinarians play an important role in the prevention, diagnosis, and treatment of feline disease caused by hemoparasites, so we should remain vigilant for potential cases amongst our patients. 

References

Atkins CE. 2017. Canine and Feline Heartworm Disease. In Textbook of Veterinary Internal Med, Ettinger SJ, Feldman ED, Côté, (eds), Elsevier, St Louis, Mo, pp. 1316-1344

Browne LE, Carter TD, Levy JK, Snyder PS, Johnson CR. 2005. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs. AJVR 66(9):1544-1549

Blagburn BL, Dryden MW. Biology, Treatment, and Control of Flea and Tick Infestations. Vet Clin North Am Small Anim Pract 39: 1173-1200, 2009

Little SE, Raymond MR, Thomas JE, et al. 2014. Heat treatment prior to testing allows detection of antigen of Dirofilaria immitis in feline serum. Parasit Vectors Jan 13;7:1

Piche CA, Cavanaugh MT, Donoghue AR, Radecki SV. 1998. Results of antibody and antigen testing for feline heartworm infection at Heska Veterinary Diagnostic Laboratories. In Recent Advances in Heartworm Disease: Symposium ’98, Seward L (ed), American Heartworm Society, Batavia, IL pp. 139-143

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

Stich, R., Blagburn, B., Bowman, D., Carpenter, C., Cortinas, M., Ewing, S., Foley, D. & Foley, J. (2014) ‘Quantitative factors proposed to influence the prevalence of canine tick-borne disease agents in the United States.’ Parasites & Vectors 7(417)

Sykes, J., Terry, J., Lindsay, L. & Owens, S. (2008) ‘Prevalences of various hemoplasma species among cats in the United States with possible hemoplasmosis’ J Am Vet Med Assoc 232(3)

Venco L, Marchesotti F, Manzocchi S. 2015. Feline heartworm disease: a ‘Rubik’s-cube-like’ diagnostic and therapeutic challenge. J Vet Cardiology 17: S190-S201

Greene, Infectious Diseases of the Dog and Cat (2012). 4th Ed. Elsevier