The study reported herein describes the clinical picture, laboratory findings and diagnostic procedures of a Cytauxzoon sp. clinical infection in a domestic cat from Germany. A previous piroplasmid fatal infection was described in a captive Bengal tiger from a zoo in Germany, when parasitic inclusions resembling Cytauxzoon spp. were visualised in histological sections of various tissues, the largest number being found in blood vessels of lymph nodes and spleen. Even though there was no evidence of tick infestation in the tiger, three bobcats originating from an American zoo were incriminated as a possible source of the infection [26].
The cat patient in the current report was also diagnosed with a FIV infection, being presented in a critical condition a few days following clinical examination due to suspected kidney disease. Since in dogs, clinical cases of babesiosis and theilerioses are known to cause acute or chronic nephropathy or glomerulonephritis [27, 28], the renal disturbances observed in this patient could have been attributed to the piroplasmid infection, to FIV or both. Previous studies have confirmed that FIV infection can induce the accumulation of immune complexes in renal tissue, therefore, a causative relationship between FIV infection and glomerulonephritis has been posited [29–32]. In the light of this information and the laboratory results (hypoalbuminemia pointing toward a renal loss of protein, increased creatinine and phosphate values as well as a very high SDMA value) one could postulate that the patient had glomerular disease due to immune-complex deposition in terms of a membranoproliferative glomerulonephritis. Other potential causes of hypalbuminaemia in this patient would include decreased production, other causes of loss (i.e. blood loss, protein-losing enteropathy) or haemodilution. In cases of renal injury, SDMA serum concentration increases earlier than creatinine, remaining elevated also in cases of chronic kidney disease (on average with 40% reduction of glomerular filtration rate, compared with up to 75% reduction needed to increase the creatinine value) [33].
Regarding the pathogenesis of FIV infection, cats remain asymptomatic for several years until functional immunodeficiency (by increasing the susceptibility to secondary infections and neoplasia) and/or immune-mediated diseases will eventually translate into clinical manifestation around 4 to 6 years of age or older [31]. In the present case, the cat did not display any noticeable symptoms at 5 years of age, approximately 1 year before merozoites resembling Cytauxzoon sp. were detected in high numbers in the blood smear. Therefore, it can be presumed that, as a result of immunosuppression caused by FIV, the piroplasm contributed as an opportunistic factor triggering the clinical picture. Furthermore, several reports have identified a positive relationship between FIV infection or other immune-mediated conditions and cytauxzoonosis in Europe [5, 11]. The clinical role of Cytauxzoon sp. in domestic cats without immunosuppression and coinfections remains debatable, as the information about pathogenesis and clinical involvement is limited. Although some cases of clinical illness and fatal outcome have been described [7, 10, 11], the majority of Cytauxzoon sp. infected cats were apparently healthy, with only few animals showing mild anaemia syndrome [5, 8, 9, 11].
As the molecular confirmation of Cytauxzoon sp. infection was established post-mortem, no specific anti-piroplasm treatment was applied. Although, in C. felis infection, the recommended therapeutic protocol consists of atovaquone and azithromycin [34], the optimal therapy for Cytauxzoon sp. infection remains unknown due to the lack of controlled clinical studies. In a recently published case report, three 2 month old kittens infected with Cytauxzoon sp. were treated with a combination of atovaquone and azithromycin, with a putative success [11]. Also, previously published Cytauxzoon sp. infections in domestic cats have been medicated with various antiprotozoal drugs, including imidocarb dipropionate and doxycycline [7–10]. Clinical studies in Europe reported that a single imidocarb dipropionate administration was not successful in treating cytauxzoonosis, although the addition of doxycycline cleared parasitaemia in one cat [7, 9].
Based on the sequencing results performed on the partial 18S rRNA gene amplification product, Cytauxzoon sp. detected in the present case revealed a high homology (99–100%) with Cytauxzoon sp. reported in European domestic felids [7, 11] and with Cytauxzoon manul (99.80%) described from Pallas’ cats from Mongolia [3]. In addition, the sequence displayed a similarity of 95% to C. felis 18S rRNA partial sequences deposited in GenBank®.
Microscopic examination of the blood smear revealed a degree of parasitaemia of approximately 33%. Other clinical studies showed lower levels of parasitaemia [, 7–9, 15], while similar percentages of piroplasm-infected erythrocytes were observed in the blood smear of three cats with cytauxzoonosis from Switzerland [11].
A significant association between the detection of Cytauxzoon sp. DNA in European domestic cats and outdoor lifestyle has been found, particularly in rural areas [5, 8]. In agreement with previous results, the cat from the present study showed an outdoor lifestyle. This would suggest a higher risk of infection, potentially due to exposure to tick vectors and wildlife reservoirs. For C. felis infections of domestic cats, the American bobcat (Lynx rufus) is assumed to act as the main reservoir [35] and Amblyomma americanum and Dermacentor variabilis are the confirmed tick-vectors [36, 37]. However, for the European isolates of Cytauxzoon sp. little is known about vectors and routes of transmission. In Europe, high prevalences of Cytauxzoon sp. infection were found in Felis silvestris in Romania [19], Italy [20], Bosnia and Herzegovina [21], and Spain [12, 14]. Moreover, Germany has one of the biggest European populations of Felis silvestris, that is concentrated in the low altitude mountain areas [38]. Studies on wild cat distribution suggest that Saarlouis city is surrounded by an abundant population [39]. Consequently, considering that they might live in close proximity to urban and rural areas and crossbreed with domestic cats, it is possible that wild cats play a central role in the transmission of Cytauxzoon sp. in west Germany, as in probably all of Europe. Ixodes ricinus is the most commonly found tick in Germany [40], and it has already been hypothesized to be a possible vector for Cytauxzoon sp. [19].
This study describes, to the best of our knowledge, the first case of molecularly confirmed Cytauxzoon sp. infection in Germany.