Adrenal response to the low dose ACTH stimulation test and the cortisol-to-adrenocorticotrophic hormone ratio in canine babesiosis

Abstract

This prospective, interventional, case-controlled study sought to determine the association between adrenocortical function and mortality in dogs with naturally occurring Babesia rossi babesiosis. Sixty-eight dogs with canine babesiosis were studied and fifteen normal dogs were used as controls. Blood samples were obtained from the jugular vein in each dog prior to treatment, at admission to hospital, for the measurement of basal plasma ACTH (adrenocorticotrophic hormone) and serum cortisol concentrations. Immediately thereafter, each dog was injected intravenously with 5 g/kg of ACTH (tetracosactrin). A second blood sample was taken 1 h later for serum ACTH-stimulated cortisol measurement and the resultant calculation of delta cortisol by subtracting basal from ACTH-stimulated cortisol. Diagnosis of babesiosis was confirmed by polymerase chain reaction (PCR) and reverse line blot (RLB). Three outcomes were defined: hospitalization with subsequent death (n = 4); hospitalization followed by recovery (n = 48); and treatment as an outpatient (n = 16). Basal cortisol, but not ACTH-stimulated cortisol, was significantly higher in patients compared to control dogs. Basal-and ACTH-stimulated serum cortisol concentrations were significantly higher in the dogs that died, compared to hospitalized dogs that survived and compared to dogs treated as outpatients. There was no significant difference in delta cortisol concentrations or cortisol to ACTH ratios across outcome groups in dogs suffering from B. rossi babesiosis However, dogs with delta cortisol concentrations below 83 nmol/l had significantly higher cortisol to ACTH ratios compared to dogs with delta cortisol concentrations above 83 nmol/l. These findings of increased basal-and ACTH-stimulated cortisol and increased cortisol to ACTH ratios confirm the absence of adrenal insufficiency and concur with those in human malaria.

Prognostic Markers in Acute Babesia canis Infections

“…17,19 A markedly increased serum cortisol concentration was found in dogs with lethal B. rossi infections, indicating a potential immunosuppressed state in these animals, which also is indicated by an unexpected mild to moderate regenerative response of lymphocytes in dogs that survived. 24,38 Furthermore, studies in humans with acute malaria infections with Plasmodium falciparum and P. vivax, which are related to Babesia spp., identified mechanisms that could explain a depletion of lymphocytes from the peripheral blood by acute sequestration of the cells in the lymph nodes or other parts of the body or by immune cell exhaustion and abnormal cell death through parasite-induced apoptosis. 39,40 Similarly, toxic parasitic factors have been shown to be involved in canine B. gibsoni infection.…”

“…19,20 In canine B. rossi infections, poor prognosis and mortality are associated with hyperlactatemia, hypoglycemia, clinically compromised circulation, high parasite load, increased serum cortisol concentrations, and signs of consumptive coagulopathy. [21][22][23][24][25] Accordingly in B. canis infections, an excessive inflammatory response with increased concentrations of fibrinogen, Creactive protein (CRP) and secreted intracellular adhesion molecule-1 (sICAM-1) from erythrocytes, and thrombocytopenia have been associated with poor outcome. 19 Furthermore, an increase in lipid mediators has been shown to be associated with severe complications such as development of SIRS and multiple organ dysfunction.…”

Low T3 syndrome in canine babesiosis associated with increased serum IL-6 concentration and azotaemia

“…Moreover, IL-6 stimulates secretion of cortisol directly, and by stimulation of adrenocorticotropic hormone and corticotropin releasing hormone (Kishimoto, 2003), and the increased concentrations of glucocorticoids may also lead to the suppression of TSH secretion (Torpy et al, 1998;Warner and Beckett, 2010). In previous studies increased cortisol concentrations in dogs infected with B. rossi were observed (Schoeman et al, 2007b;Schoeman and Herrtage, 2008a). Thus, it seems probable that in this study IL-6 might have also influenced the concentration of TSH by stimulation of the hypothalamic-pituitary-adrenal axis.…”

Serum DHEA-S increases in dogs naturally infected with Ehrlichia canis

“…Adrenocortical involvement may be expected in dogs infected with E. canis due to the challenges to the immune system that have previously been observed in both critical human (Leal et al, 2003;Libonati et al, 2006) and canine patients (Schoeman and Herrtage, 2008;Schoeman et al, 2007) with other diseases. Thus, this study was developed to assess the adrenocortical involvement before and after ACTH stimulation in naturally occurring canine monocytic ehrlichiosis by quantifying serum DHEA-S.…”

“…Additionally, the dogs were required to be negative for anti-Babesia canis antibodies (RIFI), PCR for B. canis and antiLeptospira spp. antibodies (microscopic agglutination test), since leptospirosis and babesiosis are frequently diagnosed in the region where the study was developed and also, because adrenocortical hormonal changes have already been described in dogs infected with Babesia canis (Schoeman and Herrtage, 2008;Varshney et al, 2003). Another 10 healthy dogs, with mean body weight of 18.2 kg and mean age of 3 years old (4 males -2 neutered and 2 intact males; and 6 females -one spayed and 5 intact females) were selected from the Veterinary Teaching Hospital kennel; these dogs exhibited no alterations in the physical examinations, screening tests or infectious agent tests that were described for Group 1, and comprised Group 2 (control group).…”