Hepatozoonosis

Edited November 2, 2015

 

The Hepatozoonosis guidelines were first published in the Journal of Feline Medicine and Surgery (2015) 17, 642–644 by Albert Lloret et al., and edited by Karin Möstl.

 

 

Synopsis

 

Hepatozoonosis of domestic cats has been reported in several countries, mainly as a subclinical infection. The infection has been described mostly in the same areas where canine infection is present and, in recent years, a different species Hepatozoon felis has been identified by molecular techniques. The vector for feline hepatozoonosis remains unknown and the pathogenesis has not been elucidated. Feline hepatozoonosis is mainly a subclinical infection and few cases have been reported with clinical signs associated with the infection. The diagnosis of hepatozoonosis in cats can be made by observation of parasite gamonts in blood smears, parasite meronts in muscles by histopathology and detection of parasite DNA in blood and tissue by PCR.

 

No treatment of choice is recommended, but single cases have been treated with doxycycline or oxytetracycline and primaquine. Although the mode of transmission and the type of vector is not known, preventive treatment against blood sucking vectors (fleas and ticks) is advised.

 

 

Agent properties

 

Hepatozoon species are apicomplexan parasites (family Hepatozoiae) with a blood-sucking arthropod final host and a vertebrate intermediate host.1 In general, the agent is acquired by ingestion of the infected arthropod (e.g. Rhipicephalus sanguineus in H canis and H americanum infection of dogs), but meat eating and hunting are also routes of infection (H americanum), as well as transplacental transmission (H canis).2

 

More than 340 species of Hepatozoon have been described, not only in mammals but also in amphibians, reptiles, birds and marsupials.

 

The first report in a domestic cat dates from 1908 when the parasite was named Leucocytozoon felis domestici.3 Later it was reclassified in the genus Hepatozoon spp4 as a result of the similarities to the species infecting dogs and wild canids. For some time, reports of the infection in cats referred to Hepatozoon spp or Hepatozoon-like spp.

 

More recently, with the use of molecular techniques, H felis was identified as a distinct and predominant species in cat infections5,6; however, there is also evidence that H canis can infect cats.7,8,9

 

 

Epidemiology

 

Feline hepatozoonosis has been reported in several countries worldwide, including India, South Africa, Nigeria, USA, Brazil, Israel, Spain, France and Portugal.3,6,10,11,12,13,14,15,16 The prevalence of the infection varies depending on the geographical area, cat life style and type of samples tested. Two studies showed a high prevalence of infection in Israel. In one study, meronts were found in the myocardium of 36 % of cats examined post mortem.14 In a more recent study, hepatozoon DNA in blood was found in 36 % of cats tested.9 In Spain, in studies using blood PCR, prevalence values were much lower, but varied depending on the study populations: 0.6 % in domestic cats, 16 % in a colony of feral cats and 4 % in a group of privately owned cats visiting a referral hospital.5,6,17 Two recent studies in Portugal found H felis DNA in blood samples in 15.6 % of randomly sampled cats and 8.6 % of owned and shelter cats.16,18

 

A significant association between infection and outdoor access has been reported, but no association with gender, age or FIV infection has been observed.9 However, other studies found a significant association between FIV and FeLV infection and hepatozoonosis in cats.15,17,19

 

The route of transmission has not been fully elucidated yet, but the association with outdoor access suggests transmission by some ubiquitous vectors such as the common flea, mite or ticks, or predation as in other species. The arthropod vectors of H felis remain unknown, but recently H felis DNA was detected in ticks (Rhipicephalus sanguineus) in Turkey and Portugal.20,21 Transplacental transmission of H felis has been suggested and could be an important route of transmission.9

 

 

Pathogenesis

 

There have been no published studies on the pathogenesis of infection in cats. Two forms of the parasite have been found in the cat, intracellular gamonts in neutrophils and monocytes in blood smears and meronts in several tissues. H felis usually produces an infection of myocardial and skeletal muscles.14,15 The infection does not lead to significant inflammatory reaction around the parasite meronts, so the cat rarely develops clinical signs.9,14,15 The presence of meronts has been observed in many other tissues as well as skeletal muscle and myocardium, for example lungs, liver, pancreas, bone marrow, lymph nodes, placenta and amniotic fluid.9

 

The level of parasitaemia is low, with less than 1 % of the neutrophils and monocytes containing H felis gamonts.19 Some studies have shown that there is no correlation between the presence of gamonts in blood smears and meronts in muscular tissues.7,14,19

 

 

Clinical presentation

 

Feline hepatozoonosis caused by H. felis is mostly sub-clinical; a high proportion of cats appears to be infected with no overt clinical signs.9

 

Scarce clinical information on the disease is based on three clinical case reports describing systemic disease; liver and/or kidney disease were present and hepatozoon like parasites were demonstrated in liver or blood.11,12,22 The remaining reported cases were infected cats with no clinical signs. In a retrospective study of 7 cats with Hepatozoon spp detected in blood smears, diverse clinical signs (lethargy, fever, weakness, lymphadenopathy) and clinicopathological abnormalities (anaemia and thrombocytopenia) were described. However, all 7 cats were suffering from other diseases, which could explain the clinical signs. Four of the cats were co-infected with retrovirus and 2 with haemotropic mycoplasmas, suggesting that the clinicopathological abnormalities were not associated with hepatozoon infection. Interestingly, 5 of the cats had clinicopathological abnormalities suggesting muscular damage (elevated levels of creatinine kinase and lactate dehydrogenase).19

 

Observation of H felis gamonts in a cat blood smear might be a sign of immunosuppression, which is why retrovirus testing and investigations for other co-infections and diseases is indicated. In an epidemiological study in Barcelona, 4 cats which tested positive for H felis were sick (attributed to other diseases) and one had leishmaniosis,6 suggesting that immunosuppression and/or another disease could be risk factors for hepatozoon infection.

 

 

Diagnosis

 

In clinical practice, diagnosis is usually made by the observation of hepatozoon gamonts in the cytoplasm of neutrophils and monocytes in blood smears stained with Diff-Quick or May-Grunwald Giemsa methods. H felis gamonts have an ellipsoidal shape and are 10.5 x 4.7 µm in size (Fig. 1), they are less prominent and so are easily missed compared with the larger H canis gamonts in dogs.

 

Fig. 1. Hepatozoon felis gamont within a neutrophil in a cat blood smear. Courtesy of Prof. Gad Baneth, School of Veterinary Medicine, Hebrew University, Jerusalem, Israel.

Fig. 1. Hepatozoon felis gamont within a neutrophil in a cat blood smear. Courtesy of Prof. Gad Baneth, School of Veterinary Medicine, Hebrew University, Jerusalem, Israel.

 

Several studies have shown that blood smears have low sensitivity for diagnosis of infection compared to PCR detection of DNA. In one study in Thailand, 32 % of 300 cats were PCR positive but only in 0.7 % of cats gamonts were observed in blood smears.7 Similarly, in a study in Israel, none of the cats with meronts in the myocardium tested positive when blood smears were examined.14 Therefore, blood PCR should be considered the diagnostic test of choice for confirming hepatozoon infection when blood smears do not shown parasites and it is the best tool for prevalence and epidemiological studies. However, positive DNA results should be interpreted in the light of the clinical picture, as it is most likely that clinical signs are associated with another infectious agent. A quantitative PCR test has been developed to improve the sensitivity of detection.8

 

Meronts (round to oval parasites surrounded by a thick membrane with a length of 39 x 34,5 µm) in skeletal muscle (Figure 2) might be detected in cats in which muscle biopsies are obtained during investigations of muscle pain or polymyositis, but this scenario has not been reported so far. The detection of meronts in skeletal and myocardial muscle histologically might occur as incidental or unexpected findings in the necropsy of cats in endemic areas.

 

Fig. 2. Hepatozoon felis meront within myocardial muscle in a cat. Courtesy of Prof. Gad Baneth, School of Veterinary Medicine, Hebrew University, Jerusalem, Israel.

Fig. 2. Hepatozoon felis meront within myocardial muscle in a cat. Courtesy of Prof. Gad Baneth, School of Veterinary Medicine, Hebrew University, Jerusalem, Israel.

 

Treatment

 

There have been no prospective controlled studies on the treatment of feline hepatozoonosis and so all information is based on a few case reports published a long time ago. Doxycycline was used in one case with no clear results12 and a combination of oxytetracycline and primaquine in another case led to a successful outcome.11 The use of other drugs frequently used in canine hepatozoonosis has not been reported in cats.

 

 

Prevention

 

No clear guidelines on the prevention of infection can be made, as the routes of transmission in cats remain unknown. It is likely that, as in dogs, transmission is related to blood sucking vectors, as well as the consumption of meat and vertical transmission. Therefore, preventive treatment against external parasites (fleas, ticks, others) is strongly recommended in any cat, not only but especially in cats with outdoor access.

 

 

References

 

1. Smith TG. The genus Hepatozoon. J Parasitol 1996; 82: 565-585.
2. Baneth G. Perspectives on canine and feline hepatozoonosis. Vet Parasitol 2011; 181: 3-11.
3. Patton WS. The haemogregarines of mammals and reptiles. Parasitol 1908; 1: 318-321.
4. Wenyon CM. Protozoology: A Manual for Medical Men, Veterinarians and Zoologists. William Wood, New York, 1926, pp 1085-1095.
5. Criado-Fornelio A, Ruas JL, Casado N, Farias NA, Soares MP, Müller G, et al. New molecular data on mammalian Hepatozoon species (Apicomplexa: Adeleorina) from Brazil and Spain. J Parasitol 2006; 92: 93–99.
6. Tabar MD, Altet L, Francino O, Sánchez A, Ferrer L, Roura X. Vector-borne infections in cats: molecular study in Barcelona area (Spain). Vet Parasitol 2008; 151(2-4): 332-336.
7. Jittapalapong S, Rungphisutthipongse O, Maruyama S, Schaefer JJ, Stich RW. Detection of Hepatozoon canis in stray dogs and cats in Bangkok, Thailand. Ann NY Acad Sci 2006; 1081: 479–488.
8. Criado-Fornelio A, Buling A, Cunha-Filho NA, Ruas JL, Farias NA, Rey-Valeiron C, et al. Development and evaluation of a quantitative PCR assay for detection of Hepatozoon spp. Vet Parasitol 2007; 150(4): 352-356.
9. Baneth G, Sheiner A, Eyal O, Hahn S, Beaufils JP, Anug Y, et al. Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood from morphology, and possibly transplacental transmission. Parasit Vectors 2013; 6: 102.
10. Leeflang P, Ilemobade AA. Tick-borne disease of domestic animals in northern Nigeria. II. Research summary, 1966 to 1976. Trop Anim Health Prod 1977; 9: 211-218.
11. Van Amstel S. Hepatozoonose in ‘n kat. J S Afr Vet Med Assoc 1979; 50: 215-216.
12. Ewing GO. Granulomatous cholangiohepatitis in a cat due to a protozoan parasite resembling Hepatozoon canis. Feline Pract 1977; 7: 37-40.
13. Perez RR, Rubini AS, O’Dwyer LH. The first report of Hepatozoon spp. (Apicomplexa, hepatozoidae) in domestic cats from Säo Paolo state, Brazil. Parasitol Res 2004; 94: 83-85.
14. Klopfer U, Nobel TA, Neumann F. Hepatozoon-like parasite (schizonts) in the myocardium of the domestic cat. Vet Pathol 1973; 10(3): 185-190.
15. Beaufils JP, Martin-Granel J, Jumelle P. Hepatozoon spp. parasitemia and feline leukemia virus infection in two cats. Feline Pract 1998; 26: 10–13.
16. Vilhena H, Martínez-Díaz VL, Cardoso L, Vieira L, Altet L, Francino O, et al. Feline vector-borne pathogens in the north and centre of Portugal. Parasit Vectors 2013; 6: 99.
17. Ortuño A, Castellà J, Criado-Fornelio A, Buling A, Barba-Carretero JC. Molecular detection of a Hepatozoon species in stray cats from a feline colony in North-eastern Spain. Vet J 2008; 177(1): 134-135.
18. Maia C, Ramos C, Coimbra M, Bastos F, Martins A, Pinto P, et al. Bacterial and protozoal agents of feline vector-borne diseases in domestic and stray cats from southern Portugal. Parasit Vectors 2014a; 7: 115.
19. Baneth G, Aroch I, Tal N, Harrus S. Hepatozoon species infection in domestic cats: a retrospective study. Vet Parasitol 1998; 79: 123-133.
20. Aktas M. A survey of ixodid tick species and molecular identification of tick-borne pathogens. Vet Parasitol 2014; 200(3-4): 276-283.
21. Maia C, Ferreira A, Nunes M, Vieira ML, Campino L, Cardoso L. Molecular detection of bacterial and parasitic pathogens in hard ticks from Portugal. Ticks Tick Borne Dis 2014b; 5: 409-414.
22. Baneth G, Lavy E, Presentey BZ. Hepatozoon spp. parasitemia in a domestic cat. Feline Pract 1995; 23: 10-12.

 

 

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