ISSN 2398-2950      

Feline hepatozoonosis

ffelis
Contributor(s):

Gad Baneth

Albert Lloret


Introduction

  • Cause: domestic cats has been described to be infected by three species of Hepatozoon: Hepatozoon felis, H. silvestris and H. canis. Hepatozoon species are protozoa which infect vertebrates and are transmitted by hematophagous arthropods. There are currently more than 340 species in the genus Hepatozoon, with the majority of species described in reptiles and amphibians. The gamont stage of Hepatozoon is found in the blood of its vertebrae host and can often be seen in blood smears parasitizing white blood cells (neutrophils and monocytes).
  • Signs: the description of clinical signs associated with the different Hepatzooon spp. that infect cats is based on a small number of reported infections with clinical descriptions published in the veterinary scientific literature.
    • 1. Hepatozoon felis:
      • Hepatozoon felis develops mainly in striated muscles and the cardiac muscle of domestic cats. Infection with H. felis is frequently sub-clinical. In some cats systemic clinical signs were observed, but most of them were diagnosed of other diseases or coinfections. Clinical abnormalities that might be associated to H. felis infection include anemia and increased serum muscle enzyme activities of creatine kinase (CK) and lactate dehydrogenase (LDH). In some studies, detection of H. felis has been associated to cats suffering other diseases and/or immune-supression. However, a cat from Austria infected with H. felis in which other infectious diseases were not identified presented with poor body condition, lethargy, anorexia, icterus, a painful abdomen, fever, thrombocytopenia, leukopenia, and increased serum levels of symmetric dimethylarginine (SDMA) and bilirubin, suggesting that in rare instances might be a primary pathogen.
    • 2. Hepatozoon silvestris:
      • Hepatozoon silvestris was reported to be associated with a fatal lymphoplasmacytic and histocytic myocarditis in a cat from Switzerland that presented with weakness and anorexia and died shortly after presentation to a veterinary clinic. Diagnosis was made after necropsy and pathology studies.
    • 3. Hepatozoon canis:
      • No distinct clinical signs have been associated so far with H. canis infection of domestic cats.
  • Diagnosis: diagnosis of feline hepatozoonsis is possible by detection of Hepatozoon spp. gamonts in blood smears (neutrophils and monocytes), detection of meront stages in tissues (skeletal or myocardial muscles) by histopathology, or by PCR of blood or tissues (test of choice with high sensitivity).
  • Treatment: little data is available on the treatment of feline hepatozoonosis. Off label use of some drug combinations such as imidocarb dipropionate at 6 mg/kg subcutaneously twice with an interval of 14 days in combination with doxycycline monohydrate at 5 mg/ kg orally for four weeks has been reported to be effective in a cat that recovered from infection. Another cat that recovered clinically was treated with the combination of primaquine, an anti-malarial drug, at 2 mg/kg orally once, and oxytetracycline at 50 mg/kg twice daily.
  • Prognosis: sub-clinical infection with H. felis is widespread in domestic cats in some areas of the world and carries a good prognosis usually with no need for specific treatment. However, coinfections and/or immune suppression might increase the risk of showing clinical signs as well as poor prognosis. Severe clinical infection with possible fatal outcomes has been reported with H. felis and H. silvestris in a few cases.

Pathogenesis

Etiology

  • Hepatozoon species are protozoal parasites with a blood sucking arthropod final host and a vertebrate intermediate host. Hepatozoon spp. have been described in amphibians, reptiles, birds, marsupials and mammals. They are transmitted by ingestion of an arthropod host containing mature parasite oocysts by an intermediate vertebrate host. Hepatozoon species of dogs are transmitted by ingestions of their tick hosts by the dog, however, no known arthropod vectors have been identified as yet for the feline Hepatozoon spp. including H. felis and H. silvestris. Additional transmission pathways have been described in some Hepatozoon spp. including transplacental transmission during pregnancy and carnivorism of another infected intermediate vertebrate host. Transplacental transmission from the queen to its embryos has been suspected for H. felis but not proven definitively by experimental research.

Predisposing factors

General

  • Outdoor access of cats was found as a significant risk factor for H. felis infection in an epidemiological study from Israel. This supports the possibilities of transmission by ingestion of an infection arthropod vector or carnivorism and preying upon small mammals.
  • Co-infection with other infectious diseases has been reported in several clinical reports of H. felis infection and in a survey of cats with travel history from Germany. Infections reported include leishmaniosis Leishmaniasis, hemotrophic mycoplasmosis Feline infectious anemia, FIV Feline immunodeficiency virus disease, and FeLV Feline leukemia virus disease. Co-infection with another disease agent may worsen H. felis infection and allow the parasite to increase its proliferation and dissemination in the cat tissues. No significant association was found between H. felis and FIV infection in a survey of cats from Israel.

Pathophysiology

  • Two life forms of H. felis and H. silvestris have been described, the meront developmental stage in tissues, mostly in skeletal and myocardial muscles, and the gamont stage in blood leukocytes. Meronts have also been reported in other tissues including the spleen, pancreas and lungs. The meronts seen on histopathology are round to oval with a mean length and width of 39 by 35 µm for H. felis and surrounded by a thick membrane . Developing or fully mature merozoites can be seen within meronts. Some host inflammatory cells may be seen in tissues surrounding meronts by histopathology of infected tissues. Mature merozoites that release from tissue meronts invade blood neutrophils and monocytes, transform to gamonts in the cytoplasm of the leukocytes and circulate in the blood. The gamonts of H. felis are elongated spherical structures about 10.5 by 4.7 µm in size surrounded by a membrane and posses an acentric rounded nucleus .

Timecourse

  • Unknown.

Epidemiology

  • Surveys of Hepatozoon spp. infection in domestic cats describe variable rates of infection in different regions.
  • Hepatozoon felis DNA was amplified by PCR PCR (Polymerase chain reaction) from the blood of 55 of 152 (36%) surveyed cats in Israel. A significant association was found between infection and outdoor access but not with gender, age or FIV infection.
  • A study of 200 blood feline samples from Sao Luis in Brazil found only one cat infected with H. felis.
  • In a survey of 80 asymptomatic cats from the island of Maio in Cape Verde off the coast of Western Africa, H. felis was detected by PCR in 12 (15%) of the cats.
  • Out of 282 cats examined for Hepatozoon spp. infection in Greece, 72 (26 %) were positive by PCR for H. felis and 9 of them (13%) showed gamonts on their blood smear microscopic examination

Diagnosis

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Treatment

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Prevention

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Grillini M, Simonato G, Tesarin C, Dotto G, Traversa D, Cassini R, Marchiori E, Frangipane di Regalbono A (2021) Cytauxzoon sp. and Hepatozoon spp. in Domestic Cats: A Preliminary Study in North-Eastern Italy. Pathogens 10,1214 PubMed.
  • Morelli S, Diakou A, Traversa D, Di Gennaro E, Simonato G, Colombo M, Dimzas D, Grillini M, Frangipane di Regalbono A, Beugnet F, Halos L, Paoletti B, Di Cesare A (2021) First record of Hepatozoon spp. in domestic cats in Greece. Ticks Tick Borne Dis 12(1), 101580 PubMed.
  • Schäfer I, Kohn B, Volkmann M, Müller E (2021) Retrospective evaluation of vector-borne pathogens in cats living in Germany (2012-2020). Parasit Vectors 14(1), 123 PubMed.
  • Schäfer I, Kohn B, Nijhof AM, Müller E (2021) Molecular detection of Hepatozoon species infections in domestic cats living in Germany. J Feline Med Surg 1-7 PubMed.
  • Basso W, Görner D, Globokar M, Keidel A, Pantchev N (2019) First autochthonous case of clinical Hepatozoon felis infection in a domestic cat in Central Europe. Parasitol Int 72, 101945 PubMed.
  • Qurollo B (2019) Feline Vector-Borne Diseases in North America. Vet Clin North Am Small Anim Pract 49(4), 687-702 PubMed.
  • Kegler K, Nufer U, Alic A, Posthaus H, Olias P, Basso W (2018) Fatal infection with emerging apicomplexan parasite Hepatozoon silvestris in a domestic cat. Parasit Vectors 11(1), 428 PubMed.
  • Attipa C, Neofytou K, Yiapanis C, Martínez-Orellana P, Baneth G, Nachum-Biala Y, Brooks-Brownlie H, Solano-Gallego L, Tasker S (2017) Follow-up monitoring in a cat with leishmaniosis and coinfections with Hepatozoon felis and 'Candidatus Mycoplasma haemominutum'. JFMS Open Rep 3(2), 2055116917740454 PubMed.
  • Giannelli A, Latrofa M S, Nachum-Biala Y, Hodžić A, Greco G, Attanasi A, Annoscia G, Otranto D, Baneth G (2017) Three different Hepatozoon species in domestic cats from southern Italy. Ticks Tick Borne Dis 8(5), 721-724 PubMed.
  • Hodžić A, Alić A, Prašović S, Otranto D, Baneth G, Duscher G G (2017) Hepatozoon silvestris sp. nov.: morphological and molecular characterization of a new species of Hepatozoon (Adeleorina: Hepatozoidae) from the European wild cat (Felis silvestris silvestris). Parasitology 144(5),650-661 PubMed.
  • Baneth G, Sheiner A, Eyal O, Hahn S, Beaufils J P, Anug Y, Talmi-Frank D (2013) Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission. Parasit Vectors 6, 102 PubMed.
  • Baneth G, Aroch I, Tal N, Harrus S (1998) Hepatozoon species infection in domestic cats: a retrospective study. Vet Parasitol 79(2), 123-133 PubMed.

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