ORIGINAL_ARTICLE Effects of doxycycline treatment on hematological and blood biochemical parameters in dogs naturally infected with Ehrlichia canis Ehrlichia canis, the etiologic agent of canine monocytic ehrlichiosis (CME), is mainly transmitted by the brown dog tick Rhipicephalus sanguineus. Clinical signs of the disease can be various, depending on the stage of the disease. Typical changes in hematological and blood biochemical parameters are: severe thrombocytopenia, mild to marked non regenerative anaemia and hypoalbuminemia. In order to present the effects of the treatment protocol on several hematological and biochemistry parameters, 34 Ehrlichia canis positive dogs were compared before and after treatment with doxycycline 10mg/kg/day, in duration of four weeks. Besides the clinical sings and laboratory findings, diagnosis was confirmed by antibody tests (Bionote, Korea, AGROLABO S.p.A., Italy). The most common clinical sings were depression, lethargy, pyrexia, vomiting and anorexia. Hematological analyses were performed on the automatic hematology analyzer Exigo ЕоѕVet (Sweden), while biochemistry analyses (alanine aminotransferase, aspartate aminotransferase, urea, creatinine, albumin, total protein, globulin and alkaline phosphatase) were performed using the automatic analyzer ChemWell 2910 (Awareness Technology, INC, USA). Statistically significant difference (p<0.05) in hematology changes was present regarding the red blood cells count, platelet count, hematocrit and hemoglobin before and after treatment. Hypoalbuminaemia (Mean 19.21 ±4.96 g/l) was the only serum biochemistry parameter with significant change before and after treatment, as well. Treatment with doxycycline in patients with E.canis resulted in significant increase of hematology parameters (red blood cells, hemoglobin, haematocrit and platelets), as well as albumins in serum. https://macvetrev.mk/Files/Article/2020/10.2478/macvetrev-2018-0011/macvetrev-2018-0011.pdf 2018-03-15T09:00:00 99 105 10.2478/macvetrev-2018-0011 Ehrlichia canis doxycycline clinical sings hematology biochemical parameters Elena Atanaskova Petrov eatanaskova@fvm.ukim.edu.mk false 1 University Veterinary Hospital, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia LEAD_AUTHOR Igor Ulcar false 2 Department of Pathophysiology, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Irena Celeska false 3 Department of Pathophysiology, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Ksenija Ilievska false 4 University Veterinary Hospital, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Pandorce Spasovska Trenkovska false 5 Veterinary Clinic D-r Naletoski, 1244 No 36, 1000 Skopje, Macedonia AUTHOR Todor Novakov false 6 University Veterinary Hospital, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Kiril Krstevski false 7 Department of Infectious Diseases, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Toni Dovenski false 8 Department of Reproduction, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Jovana Stefanovska false 9 Department of Parasitology and Parasitic Diseases, Faculty of Veterinary Medicine, University Ss. Cyril and Methodius, Lazar Pop Trajkov 5-7, 1000 Skopje, Macedonia AUTHOR Baneth, G., Harrus, S., Ohnona, F. S., Schlesinger, Y. (2009). Longitudinal quantification of Ehrlichia canis in experimental infection with comparison to natural infection. Vet Microbiol. 136 (3):321-325. PMid:19128893 1 10.1016/j.vetmic.2008.11.022 Donatien, A., Lestoquard, F. (1935). Existence en Algerie d'une rickettsia du chien. Bull Soc Pathol Exot. 28, 418–419. 2 Kontos, V.I., Athanasiou, L.V., Bitschava D. (1998). Serological study of erhlichiosis in dogs with clinical leishmaniasis. J Hellenic Vet Med Soc. 171-174. 3 Hamel, D., Silaghi, C., Knaus, M., Visser, M., Kusi, I., Rapti, D., Pfister, K. (2009). Detection of Babesia canis subspecies and other arthropod-borne diseases in dogs from Tirana, Albania. Wien Klin Wochenschr. 121 (3):42-45. PMid:19915816 4 10.1007/s00508-009-1234-3 Potkonjak, A., Savic, S., Jurisic, A., Petrovic, A., Suvajdzic, L., Lako, B., Novakovic, Z. (2013). Seroepidemiological research of canine monocytic ehrlichiosis in the autonomous province of Vojvodina, Serbia. Acta Sci Vet. 41 (1106):1-8. 5 Tsachev, I., Papadogiannakis, E. I., Kontos, V., Zarkov, I., Petrov, V., Pelagic, V. (2006). Seroprevalence of Ehrlichia canis infection among privately-owned dogs in northern Bulgaria (In Greek and English). J Hellenic Vet Med Soc. 57 (3):212-216. 6 Stefanovska, J., Kochevsk,i Z., Iskra, C., Farkas, R., Naletoski, I., Mrenoshki, S., Mitrov, D., Pendovski, L. (2012). Serological evidence of Ehrlichia canis and Leishmania infantum co-infection in naturally exposed dogs on the territory of Republic of Macedonia. Proceedings of the 3rd International Scientific Meeting Days of Veterinary Medicine, September, 2-4, (pp. 38-39), Ohrid, Macedonia. 7 Waner, T., Keysary, A., Bark, H., Sharabani, E., Harrus, S. (1999). Canine monocytic ehrlichiosis-an overview. Isr J Vet Med. 54 (4):103-107. 8 Mylonakis, M. E., Theodorou, K. N. (2017). Canine monocytic ehrlichiosis:An update on diagnosis and treatment. Acta Vet (Beogr). 67 (3):299-317. 9 10.1515/acve-2017-0025 Waner, T., Harrus, S. (2013). Canine monocytic ehrlichiosis-from pathology to clinical manifestations. Isr J Vet Med. 68 (1):12-18. 10 Neer, T.M., Breitschwerdt, E.B., Greene, R.T., Lappin, M.R. (2002). Consensus statement on ehrlichial disease of small animals from the infectious disease study group of the ACVIM. J Vet Intern Med. 16, 309-315. PMid:12041661 11 Woody, B. J., Hoskins, J. D. (1991). Ehrlichial diseases of dogs. Vet Clin N Am Small Anim Pract. 21, 75–98. 12 10.1016/S0195-5616(91)50009-7 Griffin, M.O., Fricovsky, E., Ceballos, G., Villarreal, F.J. (2010). Tetracyclines:A pleiotropic family of compounds with promising therapeutic properties. Am J Physiol Cell Physiol. 299, 539-548. PMid:20592239 PMCid:PMC2944325 13 10.1152/ajpcell.00047.2010 Bartsch, R.C., Greene, R.T. (1996). Post-therapy antibody titers in dogs with ehrlichiosis:follow-up study on 68 patients treated primarily with tetracycline and/or doxycycline. J Vet Intern Med. 10, 271–274. PMid:8819054 14 10.1111/j.1939-1676.1996.|atb02061.x Wen, B., Rikihisa, Y., Mott, J.M., Greene, R., Kim, H.Y., Zhi, N., Couto, G.C., Unver, A. Bartsch, R. (1997). Comparison of nested PCR with immunofluorescent-antibody assay for detection of Ehrlichia canis infection in dogs treated with doxycycline. J Clin Microbiol. 35 (7):1852-1855. PMid:9196207 PMCid:PMC229855 15 Iqbal, Z., Rikihisa, Y. (1994). Reisolation of Ehrlichia canis from blood and tissues of dogs after doxycycline treatment. J Clin Microbiol. 32, 1644–1649. PMid:7929751 PMCid:PMC263749 16 Harrus, S., Kenny, M., Miara, L., Aizenberg, I., Waner, T. Shaw, S. (2004). Comparison of simultaneous splenic sample PCR with blood sample PCR for diagnosis and treatment of experimental Ehrlichia canis infection. Antimicrob Chemoth. 48, 4488-4490. PMid:15504892 PMCid:PMC525421 17 10.1128/AAC.48.11.4488-4490.2004 Schaefer, J. J., Kahn, J., Needham, G. R., Rikihisa, Y., Ewing, S. A., Stich, R. W. (2008). Antibiotic clearance of Ehrlichia canis from dogs infected by intravenous inoculation of carrier blood. Ann N Y Acad Sci. 1149, 263–269. PMid:19120226 PMCid:PMC3052985 18 10.1196/annals.1428.087 Breitschwerdt, E. B., Hegarty, B. C., Hancock, S. I. (1998). Doxycycline hyclate treatment of experimental canine ehrlichiosis followed by challenge inoculation with two Ehrlichia canis strains. Antimicrob Agents Chemother. 42, 362–368. PMid:9527787 PMCid:PMC105415 19 Troy, G. C., Forrester, S. D. (1990). Ehrlichia canis, E. equi, and E. Risticii infections. In:Greene CE (Ed.), Infectious Diseases of the Dog and Cat (pp. 404–414). Philadelphia, PA:WB Saunders. 20 Sainz, A., Tesouro, M. A., Amusategui, I., Rodriguez, F., Mazzucchelli, F., Rodriguez, M. (2000). Prospective comparative study of 3 treatment protocols using doxycycline or imidocarb dipropionate in dogs with naturally occurring ehrlichiosis. J Vet Intern Med. 14 (2):134-139. PMid:10772483 21 10.1111/j.1939-1676.2000.|atb02226.x Spasojević-Kosić, L., Savić, S., Potkonjak, A., Vračar, V. (2015). Retrospective analysis of clinical and laboratory findings in hunting dogs with serologic reactions to tick-borne pathogens (Anaplasma phagocytophilum, Borrelia burgdorferi, Babesia canis, Ehrlichia canis, Ricketsia conorii). Vet glas. 69 (3-4):219-232. 22 Nakaghi, A. C. H., Machado, R. Z., Costa, M. T., André, M. R., Baldani, C. D. (2008). Canine ehrlichiosis:clinical, hematological, serological and molecular aspects. Ciênc Rural. 38 (3):766-770. 23 10.1590/S0103-84782008000300027 Neer, T.M. (1995). Ehrlichiosis update. Proceedings of the 13th Annual Congress of the American College of Veterinary Internal Medicine. San Diego, California, United States of America. Proceedings. pp. 822-826. 24 Neer, T.M., Harrus, S. (2006). Canine monocytotropic ehrlichiosis and neorickettsiosis (E. canis, E. chaffeensis, E. ruminantium, N. sennetsu, and N. risticii infections). In:Greene, C.E. (Ed.), Infectious diseases of the dog and cat, Third Ed. Saunders Elsevier (pp. 203–216). St. Louis, MO, USA. 25 Villaescusa, A., García-Sancho, M., Rodríguez-Franco, F., Tesouro, M. Á., Sainz, Á. (2015). Effects of doxycycline on haematology, blood chemistry and peripheral blood lymphocyte subsets of healthy dogs and dogs naturally infected with Ehrlichia canis. Vet J. 204 (3):263-268. PMid:25957920 26 10.1016/j.tvjl.2015.03.031 Webb, J. A., Allen, D. G., Abrams-Ogg, A. C., Gentry, P. A. (2006). Effects of doxycycline, amoxicillin, cephalexin, and enrofloxacin on hemostasis in healthy dogs. Am J Vet Res. 67 (4):569-576. PMid:16579747 27 10.2460/ajvr.67.4.569 Abeygunavardena, I., I. Kakoma, Smith, R. D. (1990). Pathophysiology of canine ehrlichiosis, In:J. C. Williams and I. Kakoma (Eds.), Ehrlichiosis, a vector-borne disease of animals and humans (pp. 78-92). Boston:Kluwer Academic Publishers. 28 de Castro, M. B., Machado, R. Z., de Aquino, L. P. C. T., Alessi, A. C., Costa, M. T. (2004). Experimental acute canine monocytic ehrlichiosis:clinicopathological and immunopathological findings. Vet Parasitol. 119 (1):73-86. PMid:15036578 29 10.1016/j.vetpar.2003.10.012 Harrus, S., Kass, P. H., Klement, E., Waner, T. (1997). Canine monocytic ehrlichiosis:a retrospective study of 100 cases, and an epidemiological investigation of prognostic indicators for the disease. Vet Rec. 141 (14):360-363. PMid:9351183 30 10.1136/vr.141.14.360 Frank, J. R., Breitschwerdt, E. B. (1999). A retrospective study of ehrlichiosis in 62 dogs from North Carolina and Virginia. J Vet Intern Med. 13 (3):194-201. PMid:10357108 31 10.1111/j.1939-1676.1999.|atb02178.x Mylonakis, M. E., Kritsepi-Konstantinou, M.. Dumler, J. S., Diniz, P.V.P., Day, M. J., Siarkou, V. I., Breitschwerdt, E. B., Psychas, V., Petanides, T., Koutinas, A. F. (2010). Severe hepatitis associated with acute Ehrlichia canis infection in a dog. J Vet Intern Med. 24 (3):633-638. PMid:20384948 32 10.1111/j.1939-1676.2010.0501.|ax