Abstract
Simple SummaryMost parasitic diseases, including Leishmania infection, often show more severe clinical signs in males than females. This is related to a different immune response, presumably related to testosterone activity. The present study aimed to evaluate the efficacy of a gonadotropin-releasing hormone GnRH agonist implant (deslorelin acetate) in association with meglumine antimoniate plus allopurinol in the treatment of dogs affected by Leishmania. Deslorelin acetate is a GnRH agonist, widely used for chemical reversible sterilization in male dogs, inducing testosterone suppression. Dogs treated with deslorelin show a significant decrease of clinical scores and serological test, suggesting a possible employ of GnRH agonist in the treatment of canine leishmaniosis.Sex-associated hormones such as testosterone have been demonstrated to modulate immune responses, which can result in different disease outcomes. The present study was aimed at evaluating the efficacy of a gonadotropin-releasing hormone GnRH agonist implant as deslorelin acetate in association with meglumine antimoniate plus allopurinol in dogs with canine leishmaniosis (CanL). Twenty-two dogs with CanL confirmed by clinical findings and laboratory tests were included in the study. Dogs were randomized into two groups. A control group (CTR, n = 12) was treated with meglumine antimoniate 50 mg/kg SC q 12 h for 28 days plus allopurinol at 10 mg/kg PO q 12 h for the whole study period (six months). An experimental group was treated with allopurinol and meglumine antimoniate, plus an implant of 4.7 mg deslorelin acetate (DES, n = 10). The animals were observed for three months, during which clinical evaluation, indirect fluorescent antibody test (IFAT) titre and testosterone assay were performed on time at day (D)0, 90 and 180. A significantly lower clinical score was recorded in DES than in CTR (p < 0.01) at D90 and D180 (p < 0.01). After 180 days of treatment (D180), a significant reduction of mean levels of IFAT was observed in the DES group (p = 0.03). A highly significant reduction of testosterone (p = 0.01) was observed in the DES group during the study. No statistical correlation between clinical scores, IFAT titres and testosterone within two groups was observed. Data suggested that the agonist of GnRH may be useful in the treatment of CanL.
Highlights
Canine leishmaniosis (CanL) is a zoonosis caused by the protozoan Leishmania infantum currently considered endemic in southern Europe, Africa, Asia and South America [1,2,3,4]
Inclusion criteria were an anti-Leishmania antibody titre higher than 1/320 in indirect fluorescent antibody test (IFAT) [20] and cytological identification of Leishmania amastigotes or detection of parasite DNA using real-time polymerase chain reaction (RTPCR), associated with clinical signs and/or laboratory abnormalities corresponding to LeishVet canine leishmaniosis (CanL) clinical stages [6]
One dog in the deslorelin acetateacetate (DES) group died of a cardiorespiratory arrest related to chronic heart failure; two dogs in the CTR group did not complete the study for a reason unrelated to the progression of the disease
Summary
It has been reported that different factors not related to the immune system may be involved in the effectiveness of immune response and the development of CanL [14]. Sex hormones such as androgens, oestrogens and progestins may have a critical role in defining the intensity of parasite infection by modifying the interplay between the parasite and definitive host. Receptors for sex hormones are present on the surface of macrophages and T cells, the two major cell types involved in the progression of the disease. Sex hormones oestrogen and progesterone promote the Th2 immune response, while testosterone seems to favour type Th1 immune response [16]. Gonadotropin-releasing hormone GnRH agonist slow-release implants are widely considered to be a reversible alternative to surgical neutering on males [17]
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