Alterations of cardiac and renal biomarkers in horses naturally infected with theileria equi
Introduction
Equine piroplasmosis is an infectious and tick‐borne disease caused by the hemoprotozoan parasites Theileria equi and Babesia caballi, which affects all equid species, including horses, donkeys, mules, and zebras. Infection with either or both of these obligate, intraerythrocytic organisms can cause varying degrees of hemolytic anemia and associated systemic illness [1]. Equine theileriosis due to T. equi is probably the most widespread and pathogenic disease of equines, as it can impose heavy economic losses on the horse-racing industry [2,3]. The clinical disease can manifest in different forms and with acute T. equi infection, clinical signs are usually related to marked hemolysis and resultant anemia [1].
It has been claimed anemia is closely associated with cardiac and renal complications [4]. Acute renal failure in equine piroplasmosis can occur because of hemolysis and subsequent pigment nephropathy induced by hemoglobin, as well as due to renal hypotension resulted from systemic inflammatory reaction to the infection [1]. With this aspect, a highly decreased glomerular filtration rate and an increased gamma-glutamyltransferase: creatinine ratio indicating acute renal failure have previously been reported in the horse with B. caballi [5].
Considering that theileriosis usually comes with various degrees of hemolytic anemia in all species of animals, it is of significant importance to evaluate both cardiac and renal complications. Cardio-renal biofunctions can easily be accesses by measuring a variety of biomarkers in serum or plasma samples. Urea and creatinine are conventional biomarkers of kidney function, which are commonly measured in the both medicine and veterinary medicine. However, cystatin-C as an efficient biomarker for early diagnosis of renal malfunction has been introduced, within the past 2 decades [6]. A number of biomarkers have been defined to assess cardiovascular integrity in horses, of which cardiac troponin I (cTn-I) is probably the most important one because it is uniquely expressed in the myocardium [7]. The troponin complex is composed of 3 polypeptide subunits: troponin I, T, and C that regulates the calcium-dependent actin–myosin interaction necessary for muscle contraction. Troponins I and T have cardiac-specific isoforms that are distinguishable from those of skeletal muscle, allowing differentiation between myocardial and skeletal muscle damages [8]. Another important biomarker of cardiovascular system is homocysteine (Hcy), an amino acid produced from cellular metabolism of methionine. Despite its importance, there is limited knowledge of Hcy in horses and only recently it was measured in plasma samples of healthy horses and those of with atrial fibrillation [9]. Creatine kinase-myocardial band (CKMB) is a form of an enzyme found primarily in heart muscle cells. It is usually measured together with cTn-I or where cTn-I is not available. With this aspect, increased levels of both cTn-I and CKMB have been reported in horses after a long-distance endurance ride [10]. d-dimer is a fibrin degradation product, a small protein fragment found in the blood after a blood clot is degraded by fibrinolysis. Therefore, d-dimer is a specific indicator of fibrinolysis. Plasma d-dimer has been very useful in assessing blood hypercoagulation and hyperfibrinolysis in horses suffering from colitis and laminitis. It is also very helpful in diagnosis of thrombosis. Thus, it can be considered as a sensitive marker in evaluating fibrinolytic activity and consequently coagulation activity [11].
Previously, effects of piroplasmosis on cardiovascular system of sheep, cattle and buffaloes were studied by measuring the aforementioned biomarkers and electrocardiography [7,[12], [13], [14]]. Despite the intensive research done on equine theileriosis, such determinations have not yet been undertaken or at least is very limited in horses. Therefore, the current study aimed at the aforementioned shortcomings and designed to evaluate alterations of cardio-renal biomarkers in horses naturally infected with T. equi. Additionally, the association between these parameters and the level of parasitemia was determined. To the authors' knowledge, this is the first study in the literature which evaluates the effects of theileriosis on cardio-renal axis in equines.
Section snippets
Source of animals and sampling
This study was conducted in rural areas of five different provinces including West Azerbaijan, Kurdistan, Kermanshah, Ilam and Khuzestan located in the western border of Iran where equine piroplasmosis is prevalent during the seasons, early May - late September 2016−2019. A total of 300 male horses (60 from each province) with the age of 3–4 years old, were examined and 28 male horses were diagnosed to be infected with T. equi. The diagnosis was established on history, clinical signs and blood
Results
Both routine thin blood films and molecular assays were employed to identify the parasitic infection. The maximum parasitemia was found to be 5%. All of the 28 positive cases were confirmed by PCR, to be infected with T. equi. Of the 28 animals, 9 (32.14 %), 13 (46.43 %) and 6 (21.42 %) horses suffered from low, moderate and high parasitemia, respectively. All of the infected animals were identified to be positive using T. equi-specific primers (an expected 392 bp fragment), meanwhile, no PCR
Discussion
Equine theileriosis is prevalent worldwide and can lead to serious health and economic impacts. Several aspects of the infection including epidemiology, identification, immune responses and oxidative stress have previously been studied [20,[22], [23], [24]]. However, none of these studies has focused on assessing cardio-renal biomarkers. Acute renal failure, nephropathy and cardiac lesions are among the fatal consequences of infection with T. equi. Therefore, early diagnosis or prediction of
Declaration of Competing Interest
The authors disclose no conflict of interest.
Acknowledgement
This paper is part of DVM thesis of Saman Ahmadpour, numbered 1681, under supervision of Esmaeilnejad, B and Dalir-Naghade, B.
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