Enzyme-morphological criteria for diagnosing the stages of hepatorenal syndrome development in canine babesiosis
Abstract
The study presents the characterization of the stag es of babesiosis manifestations depending on the sex of dogs, as well as enzymatic diagnostics of liver pathology and the determination of urea and creatinine concentrations in the blood serum of dogs with acute babesiosis. Additionally, we investigated the macro- and microscopic structure of the organs in dogs affected by acute babesiosis . Based on the observational data, specific features of the course of babesiosis in dogs were identified, indicating a stage-by-stage progression of the disease with a sequential transition from the incubation period to the period of clinical manife s tation. According to the anamne sis data, the incubation period ( from pathogen entry into the body to the appearance of the first clinica l signs ) lasted 5–8 days. This duration showed seasonal variation: 6–8 days in spring and 5–6 days in autumn. Clinical signs of acute babesiosis were identified in 45 spontaneously infected dogs of different breeds (German s hepherd, Central Asian s hepherd, and Rottweiler), aged 1.5–8 . 0 years, of both sexes, kept in individual households and some kennels in Zhytomyr. The intensity of Babesia canis invasion was reflected in the severity of clinical signs and depended on the duration of disease progre s sion: T he longer the pathological process persisted, the greater the intensity of invasion, which proportionally increased the seve r ity of the disease. Based on the analysis of the obtained data, three stages of acute babesiosis were identified. Among the total group of spontaneously infected dogs (n = 45), 16 animals were assigned to stage I, 13 to stage II, and 16 to stage III. The degree of hepatic parenchymal damage depended on the nature of the injurious factor, duration of exposure, and individual susceptibi l ity. Histological examination of the liver revealed disorganization of hepatic cords in certain lobular areas, focal hemorrhages, and conge s tion of capillaries. The interlobular connective tissue exhibited serous edema . Interlobular bile ducts were dilated and filled with bile. Most hepatocytes were in a state of granular (protein) dystrophy , with accumulation of brown pigment (hemofuscin) in the cytoplasm. These cells also showed signs of atrophy and severe destructive changes, leading to intrahepatic cholestasis. This was confirmed by a significant increase in the activity of the cholestatic enzyme gamma-glutamyl transpeptidase, which in the dogs at stage III of the disease exceeded normal values fourfold. Histological examination of the kidneys revealed granular dystrophy and necrosis of the epithelial cells of the convoluted renal tubules, as well as hemorrhages in both cortical and medullary regions. These changes led to impaired renal circulation and decreased filtration, excretory, and reabsorptive functions. The results of this study, along with the data from other researchers, allow us to identif y the patterns in morphological changes in the organs and tissues during the acute course of the disease and contribute to the understanding of the functional significance of their structural components.References
Baneth, G., Cardoso, L., Brilhante-Simões, P., & Schnittger, L. (2019). Establishment of Babesia vulpes n. sp. (Apicomplexa: Babesiidae), a piroplasmid species pathogenic for domestic dogs. Parasites and Vectors, 12(1), 129.
Bartnicki, M., Łyp, P., Dębiak, P., Staniec, M., Winiarczyk, S., Buczek, K., & Adaszek, Ł. (2017). Cardiac disorders in dogs infected with Babesia canis. Polish Journal of Veterinary Sciences, 20(3), 573–581.
Beri, D., Singh, M., Rodriguez, M., Yazdanbakhsh, K., & Lobo, C. A. (2021). Sickle cell anemia and Babesia infection. Pathogens, 10(11), 1435.
Beugnet, F., & Moreau, Y. (2015). Babesiosis. Revue Scientifique et Technique, 34(2), 627–639.
Beugnet, F., Lebon, W., & de Vos, C. (2019). Prévention de la transmission de Babesia rossi par Haemaphysalis elliptica chez les chiens traités avec Nexgard® [Prevention of the transmission of Babesia rossi by Haemaphysalis elliptica in dogs treated with Nexgard®]. Parasite, 26, 49.
Bloch, E. M., Kasubi, M., Levin, A., Mrango, Z., Weaver, J., Munoz, B., & West, S. K. (2018). Babesia microti and malaria infection in Africa: A pilot serosurvey in Kilosa District, Tanzania. The American Journal of Tropical Medicine and Hygiene, 99(1), 51–56.
Ćoralić, A., Gabrielli, S., Zahirović, A., Stojanović, N. M., Milardi, G. L., Jažić, A., Zuko, A., Čamo, D., & Otašević, S. (2018). First molecular detection of Babesia canis in dogs from Bosnia and Herzegovina. Ticks and Tick-borne Diseases, 9(2), 363–368.
Dubova, O. A. (2017). Sezonna dynamika klinichnykh pokaznykiv krovi khvorykh na babezioz sobak m. Zhytomyr [The seasonal dynamics of clinical blood indicators of dogs with babesiosis in Zhytomyr]. Problemy zooinzheneriyi ta Veterynarnoyi Medytsyny, 35(2), 38–42 (in Ukrainian).
Dubova, O. A., & Duboviy, A. A. (2018). Hepatopathy and nephropathy in canine babesiosis: Pseudo hepatorenal syndrome. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies, Series: Veterinary Sciences, 20(83), 102–107.
Dubova, O. A., & Soroka, N. M. (2005). Epizootychni osoblyvosti babeziozu sobak u Zhytomyri za period 2003–2004 rokiv [Epizootic features of canine babesiosis in Zhytomyr for the period 2003–2004]. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies Named after S. Z. Gzhytskyj, 7(2), 20–24 (in Ukrainian).
Dubova, O. A., Zgozinska, O. A., Kovalova, L. O., & Kovalev, P. V. (2019). Splenomegaly as a complication of babesiosis in dogs. Bulletin of the Poltava State Agrarian Academy, 2, 126–132.
Dunaievska, O., Horalskyi, L., Kolesnik, N., Sokulskyi, I., & Horalska, I. (2020). Comparative morphology of the spleen of birds of the families phasianidae and columbidae. Scientific Horizons, 23(8), 164–170.
Dunaievska, O., Sokulskyi, I., Radzykhovskii, M., Gutyj, B., Dyshkant, O., Khomenko, Z., & Brygadyrenko, V. (2024). Immunophysiological state of dogs according to the immunoregulatory index of their blood and spleens. Animals, 14(5), 706.
El Haj, N., Kachani, M., & Bouslikhane, M. (2002). Seroepidemiologied el a theileriosea Theileria annulata et de la babesiosea Babesia bigemina au Maroco. Revue de Medecine Veterinaire, 153(3), 189–196.
Fasolya, V. P., & Goralska, I. Y. (2010). Ratsional’na terapiya polimorbidnoyi vnutrishn’oyi patolohiyi pry babeziozi u sobak [Rational therapy of polymorbid internal pathology for babesiosis in dogs]. Scientific Messenger of Lviv National University of Veterinary Medicine and Biotechnologies Named after S. Z. Gzhytskyj, 12(3), 281–287 (in Ukrainian).
Goralska, I. Y., & Shpanarska, I. I. (2013). Hemopoez u sobak z babeziozom [Hematopoiesis in dogs with babesiosis]. Visnyk Zhytomyrskoho Natsional’noho Ahroekolohichnoho Universytetu, 36, 256–261 (in Ukrainian).
Goralska, I. Y., Rusak, V. S., & Pinskyi, O. V. (2017). Efektyvnist’ likuvannia hepatorenal’noho syndromu u sobak z babeziozom [Effectiveness of treatment of hepatorenal syndrome in dogs with babesiosis]. Visnyk Zhytomyrs’koho Natsional’noho Ahroekolohichnoho Universytetu, 63, 25–32 (in Ukrainian).
Goralska, I., & Pinsky, О. (2016). Indicators hematopoiesis dog for babesiosis. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies, Series: Veterinary Sciences, 18(66), 40–43.
Goralskyi, L. P., Goralska, I. Y., & Shpanarska, I. I. (2012). Rozvytok hemosyderozu vnaslidok babeziozu u sobak [Development of hemosiderosis due to babesiosis in dogs]. Visnyk Zhytomyrs’koho Natsional’noho Ahroekolohichnoho Universytetu, 33, 178–181 (in Ukrainian).
Gryshchenko, V., Semenko, O., & Bilokur, D. (2023). Dogs’ general response to babesiosis infection of various severities. Ukrainian Journal of Veterinary Sciences, 14(4), 59–73.
Hoenig, M., & Ferguson, D. C. (2002). Effects of neutering on hormonal concentrations and energy requirements in male and female cats. American Journal of Veterinary Research, 63(5), 634–639.
Holovakha, V. I., Piddubnуak, О. V., Bakhur, T. I., Vovkotrub, N. V., Antipov, A. A., Anfiorova, M. V., Gutyj, B. V., Slivinska, L. G., Kurdeko, O. P., & Macynovich, A. O. (2018). Changes in erythrocytopoesis indices in dogs with babesiosis. Regulatory Mechanisms in Biosystems, 9(3), 379–383.
Homer, M. J., Aguilar-Delfin, I., Telford, S. R., Krause, P. J., & Persing, D. H. (2000). Babesiosis. Clinical Microbiology Reviews, 13(3), 451–469.
Horalskyi, L. P., Khomych, V. T., & Kononskyi, O. I. (2019). Osnovy histolohichnoyi tekhniky ta morfofunktsional’nykh metodiv doslidzhennia v normi ta patolohiyi [Fundamentals of histological technique and morphofunctional research methods during normal state and pathology]. Polissia, Zhytomyr (in Ukrainian).
Karasová, M., Blaňarová, L., Tóthová, C., Hrčková, G., Kisková, T., Ševčíková, Z., Revajová, V., Nagy, O., & Víchová, B. (2024). Successful transmammary treatment of Babesia gibsoni infection in newborn puppies after the administration of Malarone®, Azithromycin, and Artesunate to a lactating dam. Pathogens, 13(7), 562.
Karasová, M., Tóthová, C., Grelová, S., & Fialkovičová, M. (2022). The etiology, incidence, pathogenesis, diagnostics, and treatment of canine babesiosis caused by Babesia gibsoni infection. Animals, 12(6), 739.
Kondrakhin, I. (2006). Etiolohichnyi ta patohenetychnyi zviazok mnozhynnoyi patolohiyi, osoblyvosti likuvannia ta profilaktyky [Etiological and pathogenetic relationship of multiple pathologies, features of treatment and prevention]. Naukovyi Visnyk Veterynarnoyi Medytsyny, 2, 9–10 (in Ukrainian).
Köster, L. S., Lobetti, R. G., & Kelly, P. (2015). Canine babesiosis: A perspective on clinical complications, biomarkers, and treatment. Veterinary Medicine, 6, 119–128.
Köster, L. S., Steiner, J. M., Suchodolski, J. S., & Schoeman, J. P. (2015). Serum canine pancreatic-specific lipase concentrations in dogs with naturally occurring Babesia rossi infection. Journal of the South African Veterinary Association, 86(1), E1–E7.
Kovalchuk, I. I. (2013). Patomorfolohichni zminy v leheniakh sobak za babeziozu [The pathomorphological changes in the lungs of dogs under babesiosis]. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies, Series: Veterinary Sciences, 57, 124–129 (in Ukrainian).
Kovalchuk, I. I. (2014). Morfolohichna kharakterystyka nyrok sobak za hostroho perebihu babeziozu [Morphological characteristics of the kidneys of dogs during the acute course of babesiosis]. Visnyk Zhytomyrs’koho Natsional’noho Ahroekolohichnoho Universytetu, 46, 221–225 (in Ukrainian).
Kovalchuk, I. I. (2014). Morfolohichna kharakterystyka nyrok sobak pid chas hostroho perebihu babeziozu [Morphological characteristics of the kidneys of dogs during the acute course of babesiosis]. Visnyk Zhytomyrs’koho Natsional’noho Ahroekolohichnoho Universytetu, 46, 221–225 (in Ukrainian).
Kurman, A. F., Hrubich, P. Y., Mokryi, Y. O., & Lepeta, L. V. (2011). Novi aspekty laboratornoyi diahnostyky babeziozu u sobak [New aspects of laboratory diagnosis of babesiosis in dogs]. Bulletin of the Poltava State Agrarian Academy, 3, 115–116 (in Ukrainian).
Levchenko, V. I., Holovakha, V. I., Kondrakhin, I. P. (2010). Metody laboratornoyi klinichnoyi diahnostyky khvorob tvaryn [Methods of laboratory clinical diagnosis of animal diseases]. Urozhay, Kyiv (in Ukrainian).
Levytska, V. A., Berezovskyi, A. V., & Mushynskyi, A. B. (2020). Diahnostyka i likuvannia babeziozu sobak, osoblyvosti vykorystannia ukrayinskykh terapevtychnykh [Diagnosis and treatment of babesiosis in dogs, features of the use of Ukrainian therapeutic drugs]. Ahrarnyi Visnyk Prychornomoria, 97, 24–32 (in Ukrainian).
Matjila, P. T., Penzhorn, B. L., Bekker, C. P., Nijhof, A. M., & Jongejan, F. (2004). Confirmation of occurrence of Babesia canis vogeli in domestic dogs in South Africa. Veterinary Parasitology, 122(2), 119–125.
Mazannyі, O., Prykhodko, Y., Nikiforova, O., Fedorova, H., & Lyulin, P. (2020). Clinical and diagnostic studies babesiosis of dogs. Veterinary Biotechnology, 37, 51–62.
Mishalov, V. D., Chaikovskyi, Y. B., & Tverdokhlib, I. V. (2007). Pro pravovi, zakonodavchi ta etychni normy i vymohy pry vykonanni naukovykh morfolohichnykh doslidzhen’ [On legal, legislative and ethical norms and requirements when conducting scientific morphological research]. Morfolohiia, 1(2), 108–115 (in Ukrainian).
Onishi, T., Ueda, K., Horie, M., Kajikawa, T., & Ohishi, I. (1990). Serum hemolytic activity in dogs infected with Babesia gibsoni. The Journal of Parasitology, 76(4), 564–567.
Otranto, D., Dantas-Torres, F., & Breitschwerdt, E. B. (2009). Managing canine vector-borne diseases of zoonotic concern: Part one. Trends in Parasitology, 25(4), 157–163.
Prus, M. P. (2001). Klinichnyi proiav ta deiaki pytannia patohenezu babeziozu u sobak [Clinical manifestation and some aspects of the pathogenesis of babesiosis in dogs]. Naukovyi Visnyk Natsional’noho Ahrarnoho Universytetu, 42, 193–198 (in Ukrainian).
Prus, M. P., Galat, V. F., & Paskhalova, L. V. (2000). Klinichni oznaky ta rezul’taty doslidzhen’ krovi sobak, khvorykh na babezioz [Clinical signs and results of blood tests of dogs with babesiosis]. Veterynarna Medytsyna Ukrayiny, 6, 28–29 (in Ukrainian).
Prus, M. P., Semenko, O. V., & Galat, M. V. (2017). Babezioz u sobak [Babesiosis in dogs]. Comprint, Kyiv (in Ukrainian).
Radzikhovsky, N., Sokulskiy, I., & Dyshkant, O. (2020). Pathomorphology of certain organs of immunogenesis by experimental reproduction of coronavirus infection in dogs. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies, Series: Veterinary Sciences, 22(99), 75–79.
Rajapakse, P., & Bakirhan, K. (2021). Autoimmune hemolytic anemia associated with human babesiosis. Journal of Hematology, 10(2), 41–45.
Semenko, O. V., Galat, M. V., Shcherbak, O. V., Galat, V. F., & Shulga, I. V. (2017). Peculiarities of dog babesiosis distribution in Kyiv City. Vestnik Zoologii, 51(6), 493–498.
Ubah, A. S., Abalaka, S. E., Idoko, I. S., Obeta, S. S., Ejiofor, C. E., Mshelbwala, P. P., Omeje, J. N., & Ajayi, I. E. (2019). Canine babesiosis in a male Boerboel: Hematobiochemical and anatomic pathological changes in the cardiorespiratory and reproductive organs. Veterinary and Animal Science, 7, 100049.
Wężyk, D., Romanczuk, K., Rodo, A., Kavalevich, D., & Bajer, A. (2023). Haematological indices and immune response profiles in dogs naturally infected and co-infected with Dirofilaria repens and Babesia canis. Scientific Reports, 13, 2028.
Winiarczyk, D., Adaszek, Ł., Bartnicki, M., Abramowicz, B., Łyp, P., Madany, J., & Winiarczyk, S. (2017). Utility of urinary markers in the assessment of renal dysfunction in canine babesiosis. Tierarztliche Praxis. Ausgabe K, Kleintiere/Heimtiere, 45(2), 84–88.
Zygner, W., Gójska-Zygner, O., & Norbury, L. J. (2023). Pathogenesis of anemia in canine babesiosis: Possible contribution of pro-inflammatory cytokines and chemokines – a review. Pathogens, 12(2), 166.
Zygner, W., Gójska-Zygner, O., Bartosik, J., Górski, P., Karabowicz, J., Kotomski, G., & Norbury, L. J. (2023). Canine babesiosis caused by large Babesia species: Global prevalence and risk factors – a review. Animals, 13(16), 2612.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.


