RESUMEN
Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.
RESUMEN
Feline sporotrichosis is an endemic disease with high occurrence in Brazil. Itraconazole (ITZ) remains the drug of choice for treating this disease in cats, despite the increasing reports of therapeutic failure. A controlled, randomized clinical trial was performed on 166 naive cats with sporotrichosis to assess the effectiveness and safety of the combination therapy with ITZ and potassium iodide (KI) compared with ITZ monotherapy. Cats were randomly allocated into two treatment groups: G1-ITZ 100 mg/cat/day-and G2-ITZ 100 mg/cat/day + KI 2.5-20 mg/kg/day. Cats treated in G2 presented 77% more risk of reaching a clinical cure (a positive effect) than those treated in G1, even when controlled by negative predictors. The survival curves of the two treatment protocols indicate that a clinical cure was achieved faster in G2. An increase in the KI dose was necessary in 28 cats due to the persistence of clinical signs. Adverse reactions were equally frequent in both groups and manageable with a temporary drug suspension and/or a hepatoprotective therapy. The combination therapy was associated with a higher cure rate and a shorter treatment time, suggesting that ITZ+KI arises as a better option for treating feline sporotrichosis and should be considered the first-line treatment, especially in the presence of negative predictors.
RESUMEN
A esporotricose é uma micose subaguda ou crônica ca usada pelo fungo dimórfico Sporothrix schenckii que infecta o ser humano e uma variedade de animais . O felino doméstico é o animal mais susceptível à doença e desempenha um papel importante na transmissão zoonótica, especialmente no Rio de Janeiro, onde ocorre uma epidemia envolvendo os seres humanos, cães e gatos desde 1998. A efetividade do iodeto de potássio foi avaliada em uma coorte longitudinal constituída por gatos com esporotricose confirmada pelo isolamento de S. schenckii em cultura. Os gatos foram acompanhados no Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos, Instituto de Pesquisa Clínica Evandro Chagas, Fiocruz, entre abril de 2010 e julho de 2011 e fora m submetidos à terapia com iodeto de potássio (KI) em cápsulas na dose entre 2,5 mg/kg e 20 mg/kg, a cada 24 horas. A cura clínica foi obtida em 47,9 por cento dos gatos, em 37,5 por cento ocorreu falência terapêutica, 10,4 por cento abandonaram o tratamento e 4,2 por cento foram a óbito. Efeitos adversos clínicos foram observados em 52,1 por cento dos casos. Treze gatos apresentaram leve aumento nos níveis das transaminases hepáticas durante o tratamento, dos quais, seis apresentavam sinais clínicos sugestivos de hepatotoxicidade. Em comparação com estudos prévios realizados com itraconazol e solução saturada de iodeto de potássio, o tratamento com KI em cápsulas é uma alternativa promissora no tratamento da esporotricose felina.
Sporotrichosis is a subacute or chronic mycosis caused by the dimorphic fungus Sporothrixschenckii, which infects man as well as other mammals. The domestic cat is the animal most affected by this mycosis and plays an important role in the zoonotic transmission of this disease especially in Rio de Janeiro, Brazil, with a large number of cases involving man, dogs and cats since 1998. In order to evaluate the effectiveness of potassium iodide treatment, an observational cohort was conducted in 48 cats with sporotrichosis confirmed by isolation of S.schenckii in culture at Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz between April 2010 and July 2011. All cats received potassium iodide capsules,2.5mg/kg to 20mg/kg, once a day. The cure rate was 47.9 percent, treatment failure 37.5 percent,treatment abandonment 10.4 percent and death 4.2 percent. Clinical adverse effects were observed in52.1 percent of the cases. Thirteen cats had a mild increase in hepatic transaminase levels during the treatment, six of them presented clinical signs suggestive of hepatotoxicity. Compared to previous studies with itraconazole and iodide (SSKI), potassium iodide capsules are analternative for feline sporotrichosis treatment.
