Aspectos clínicos e imunológicos em cães com leishmaniose visceral tratados com miltefosina e/ou alopurinol

Abstract

In Brazil, the treatment of canine visceral leishmaniasis (LVC) with miltefosine (MilteforanTM, Virbac) was authorized in 2016 and the drug launched on the Brazilian market in January 2017. Reports on the clinical, clinical-pathological and immunological conditions of treated dogs in the country are scarce. Thus, this therapeutic clinical trial evaluated and monitored, in the short-term, the efficacy of three pharmacotherapeutic protocols: miltefosine monotherapy (G1), allopurinol-associated miltefosine (G2) and allopurinol (G3) monotherapy in dogs naturally infected with Leishmania infantum. Forty-five dogs with CVL were also assigned to one of the three treatment groups and examined before (D0) and after (D29) the drug intervention. Article 1 was developed with all groups, while Article 2 was written with two groups G1 and G2. The dogs were evaluated for clinical, hematological, biochemical signs, serum concentration of antibodies and cytokines and urinary biomarkers. Significant reduction (p <0.05) in clinical scores was observed in all evaluated protocols, with no difference between groups. The hematological and biochemical parameters improved in D29, with better results observed in G2. The anti-Leishmania antibody titer remained increased in all groups. The quantification of serum cytokines demonstrated a mixed Th1 / Th2 profile in LVC. The levels of IL-2 decreased in all groups after treatment, but there was no statistical difference. The evaluation of IFN-y and IL-10 did not show changes in the groups analyzed and did not contribute to short-term therapeutic followup. Proteinuria and urinary density did not decrease significantly after treatments. Regarding biomarkers, cystatin C and microalbuminuria did not show significant changes. The NGAL presented a significant reduction in the G2 group (p <0.05). All therapeutic protocols promoted, in varying degrees, improvement in the general condition (clinical, hematological and biochemical sign) of dogs. However, the combination of miltefosine and allopurinol (G2) promoted better effects in the shortterm treatment, representing the best option for the treatment of CVL, even when compared to the only therapeutic protocol allowed in Brazil, miltefosine monotherapy (G1). IL-2 showed similar behavior in the groups after treatments, suggesting that the decrease in this cytokine may be associated with the therapeutic control of the infection, in addition to being potential therapeutic markers for the monitoring and follow-up of dogs with CVL. These drugs proved to be safe for kidney function during the follow-up period, promoting improvement in the analyzed urinary biomarkers.