Monitoring fungal burden and viability of Sporothrix spp. in skin lesions of cats for predicting antifungal treatment response

Skin lesions in feline sporotrichosis usually present a high fungal burden, making cats an important source of infection. This study evaluated the fungal burden and isolation in skin lesions of feline sporotrichosis during treatment with itraconazole (ITZ), combined with or without potassium iodide (KI). Treatment-naïve cats with culture-confirmed sporotrichosis and presenting skin ulcers were treated for up to 40 weeks with oral ITZ alone (n = 74) or combined with KI (n = 56). These cats were submitted to monthly sampling of the same lesion for mycological culture and cytopathology until healing of lesion or up to twelve weeks. The fungal burden was expressed as the mean yeast cell count in three microscopic fields from imprint smears. The fungal burden before treatment was significantly higher in cats in which the lesion persisted and in cases of treatment failure when using ITZ alone. After twelve weeks, the median fungal burden decreased to zero in both treatment protocols, suggesting a potential decrease in the risk of transmission of Sporothrix spp. from cats. These findings encourage the early treatment of feline sporotrichosis as a control measure. Moreover, the fungal burden in feline sporotrichosis lesions can be a prognostic indicator and a parameter for choosing appropriate therapeutic regimen

Ensaio clínico comparativo entre Itraconazol e associação de Itraconazol e iodeto de potássio no tratamento da esporotricose felina

Made available in DSpace on 2018-05-21T13:34:26Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) erica_reis_ini_dout_2016.pdf: 7177288 bytes, checksum: 3ad6c2b9b9ad7ba5a23160d2cccdd836 (MD5)Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.A esporotricose felina é uma doença endêmica no Rio de Janeiro, Brasil, onde a transmissão zoonótica de Sporothrix spp tem sido relatada desde 1998. O itraconazol (ITZ) permanece como o fármaco de escolha para o tratamento da doença em gatos. No entanto, casos de falha terapêutica e longo tempo de tratamento têm sido descritos. O iodeto de potássio (KI), considerado no passado como um fármaco de efetividade variável em gatos com esporotricose, surge como uma opção importante no tratamento desses animais provenientes da área endêmica do Rio de Janeiro. A fim de avaliar a efetividade e a segurança de ITZ associado ao KI, foi realizado um ensaio clínico randomizado em 166 gatos com esporotricose que recebera ITZ 100 mg/dia ou ITZ 100 mg/dia + KI 2,5-20mg/kg/dia. O estudo foi conduzido em gatos atendidos no Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos (Lapclin-Dermzoo), Instituto Nacional de Infectologia Evandro Chagas (INI)/Fundação Oswaldo Cruz (Fiocruz), entre 2013 e 2016. Os gatos considerados elegíveis para este estudo foram aqueles com esporotricose confirmada pelo isolamento de Sporothrix spp. em cultura; ausência de terapia antifúngica prévia, e peso >= 3 kg. Os gatos foram submetidos a exame clínico e a exames laboratoriais uma vez por mês de acordo com o protocolo de atendimento. O critério para definir acura clínica foi a cicatrização completa das lesões cutâneas/mucosas e remissão dos sinais clínicos inicialmente apresentados Após a cura clínica, a terapia foi mantida por um período adicional de quatro semanas, o que correspondeu à consulta de alta. Todos os procedimentos e fármacos foram fornecidos gratuitamente. Gatos que apresentaram reações adversas clínicas (hiporexia ou anorexia combinada com a perda de > 10% do peso corporal), associadas ou não a alterações das transaminases, tiveram a terapia suspensa temporariamente por um período mínimo de sete dias (ITZ) e 10 dias (KI). A reintrodução de cada fármaco aconteceu em tempos alternados e diferentes na tentativa de descobrir qual fármaco estava causando a reação adversa. Além disso, gatos que apresentaram alteração leva das transaminases hepáticas receberam silimarina 30 mg/kg por via oral, uma vez ao dia. A cura foi observada em 42 (50,6%) gatos do grupo ITZ e73 (88%) do grupo ITZ+ KI, com tempo de tratamento semelhante (15 semanas cada). O Hazard Ratio ajustado pelo modelo logístico demonstrou que o tratamento com ITZ + KI foi associado a cura clínica (HR 1,77, IC95% 1,2- 2,62), mesmo quando controlado por sinais extracutâneos. Incrementos na dose de KI foram necessários em 28 gatos devido à resposta clínica insatisfatória. As reações adversas foram igualmente frequentes entre os gatos que receberam ITZ (33,7%), e ITZ + KI (39,7%) e foram manejados com a suspensão temporária do(s) fármaco(s), e/ou terapia hepatoprotetora. A associação de ITZ e KI é mais efetiva que a monoterapia com ITZ e emerge como a primeira opção para o tratamento da esporotricose felina.Feline sporotrichosis is an endemic disease in Rio de Janeiro, Brazil, where zoonotic transmission of Sporothrix has been reported since 1998. Itraconazole (ITZ) remains the first choice for treating this disease in cats. However, there have been reports of therapeutic failure and a long-term endeavor. Potassium iodide (KI), considered in the past as a drug with variable effectiveness in cats with sporotrichosis, arises as an important option in the treatment of cats from the endemic area of Rio de Janeiro. In order to evaluate the effectiveness and safety of ITZ associated with KI, a randomized clinical trial was performed on 166 cats receiving ITZ 100 mg/day orITZ 100 mg/day +KI 2.5-20 mg/kg/day. The study was conducted in cats assisted at the Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos (Lapclin-Dermzoo), Instituto Nacional de Infectologia Evandro Chagas (INI)/Fundação Oswaldo Cruz Fiocruz), duringthe period of 2013-2016. The cats considered eligible for this study were those with sporotrichosis confirmed by isolation of Sporothrix spp. in culture, no previous systemic antifungal therapy, and weight > 3 kg. The cats underwent a clinical examination and laboratory tests once a month according to the standard care protocol. The criteria for clinical cure were complete healing of the skin/mucosal lesions and remission of clinical signs initially presented. After clinical cure, the therapy was maintained for an additional period of four weeks, which corresponded to the discharge assessment. All procedures and drugs were supplied free-of-charge for the cats\2019 owners Cats presenting hyporexia or anorexia combined with loss of > 10% of body weight, or the association of clinical adverse reactions and an elevation of transaminases levels had a temporary suspension of the drugs (minimum seven days [ITZ] and ten days [KI]). The reintroduction of each drug happened in alternated and different times in the attempt to discover which drug was causing the unwanted effect. Moreover, cats with a mild elevation in transaminases levels received a hepatoprotective therapy with oral silymarin 30 mg/kg, once a day. Cure was observed in 42 (50.6%) cats of the ITZ group and 73 (88%) of the ITZ+KI group within a similar median period of time (15 weeks each). Furthermore, the HR adjusted by the logistic model showed that the ITZ+KI treatment was associated with clinical cure (HR 1.77, 95 per cent CI 1.2 to 2.62), even when controlled for extracutaneous signs. An increase in the KI dose was necessary in 28 cats due to the slow improvement of the lesions. The adverse reactions were equally frequent among cats receiving ITZ (33.7%), and ITZ+KI (39.7%) and were managed with a temporary drug suspension and/or a hepatoprotective therapy. The association of ITZ and KI ismore effective as ITZ monotherapy and arises as a first option for the treatment of feline sporotrichosis

Avaliação da resposta terapêutica ao iodeto de potássio na esporotricose felina

Made available in DSpace on 2018-08-06T13:15:01Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) erica_reis_ipec_mest_2011.pdf: 1379554 bytes, checksum: 75f84f6f3f8cd7f89dd8310f6431b738 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.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 pa pel importante na transmissão zoonótica, especialmente no Rio de Janeiro, onde oc orre 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 espor otricose confirmada pelo isolamento de S. schenckii em cultura. Os gatos foram acompanhados no Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos, Instituto Nacional de Infectologia 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% dos gatos, em 37,5% ocorreu fal ência terapêutica, 10,4% abandonaram o tratamento e 4,2% foram a óbito. Efeitos adversos c línicos foram observados em 52,1% dos casos. Treze gatos apresentaram leve aumento nos ní veis das transaminases hepáticas durante o tratamento, dos quais, seis apresentavam sinais c línicos sugestivos de hepatotoxicidade. Em comparação com estudos prévios realizados com itrac onazol e solução saturada de iodeto de potássio, o tratamento com KI em cápsulas é uma alt ernativa promissora no tratamento da esporotricose felinaSporotrichosis is a subacute or chronic mycosis caused by the dimorphic fungus Sporothrix schenckii, 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 Nacional de Infectologia 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%, treatment failure 37.5%, treatment abandonment 10.4% and death 4.2%. Clinical adverse effects were observed in 52.1% 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 an alternative for feline sporotrichosis treatmen

Co-infection with feline retrovirus is related to changes in immunological parameters of cats with sporotrichosis.

Feline sporotrichosis due to Sporothrix brasiliensis is frequently severe and often correlated to zoonotic transmission. Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) cause immunodeficiency in cats; no association has been identified with critical cases of sporotrichosis. Moreover, the cytokine profile in Sporothrix-infected cats and a potential impact of retrovirus co-infections on their immunity is unknown. This study assessed immunological parameters in cats with sporotrichosis with and without FIV or FeLV co-infection. FeLV infection was detected by antigen ELISA and by provirus PCR. FIV infection was investigated through ELISA and Western blot. Cytokine transcription (IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α) was quantified using RT-qPCR and lymphocyte subpopulations (CD4, CD8, CD5 and CD21) were assessed by flow cytometry. Thirty cats with sporotrichosis were recruited to the study, including three FIV-positive and five FeLV-positive (progressive infection) cats. One cat with regressive FeLV infection was excluded from statistics. In comparison to retrovirus-negative cats, FIV-positive cats and FeLV-positive cats had higher IL-10 levels, FeLV-positive cats had lower IL-4 levels and FIV-positive cats had lower IL-12 levels and a lower CD4+/CD8+ ratio. Remarkably, all cats with poor general condition were FeLV (progressive infection) or FIV-positive, but the retrovirus status was not associated with the sporotrichosis treatment length or outcome. The immunological changes and the more severe clinical presentation observed in cats with retrovirus co-infections encourage future prospective studies that address the impact of these changes on prognostic determinants of feline sporotrichosis and the development of new therapy strategies that control disease spread

Monitoring fungal burden and viability of Sporothrix spp. in skin lesions of cats for predicting antifungal treatment response

Skin lesions in feline sporotrichosis usually present a high fungal burden, making cats an important source of infection. This study evaluated the fungal burden and isolation in skin lesions of feline sporotrichosis during treatment with itraconazole (ITZ), combined with or without potassium iodide (KI). Treatment-naïve cats with culture-confirmed sporotrichosis and presenting skin ulcers were treated for up to 40 weeks with oral ITZ alone (n = 74) or combined with KI (n = 56). These cats were submitted to monthly sampling of the same lesion for mycological culture and cytopathology until healing of lesion or up to twelve weeks. The fungal burden was expressed as the mean yeast cell count in three microscopic fields from imprint smears. The fungal burden before treatment was significantly higher in cats in which the lesion persisted and in cases of treatment failure when using ITZ alone. After twelve weeks, the median fungal burden decreased to zero in both treatment protocols, suggesting a potential decrease in the risk of transmission of Sporothrix spp. from cats. These findings encourage the early treatment of feline sporotrichosis as a control measure. Moreover, the fungal burden in feline sporotrichosis lesions can be a prognostic indicator and a parameter for choosing appropriate therapeutic regimen

Monitoring Fungal Burden and Viability of Sporothrix spp. in Skin Lesions of Cats for Predicting Antifungal Treatment Response

Skin lesions in feline sporotrichosis usually present a high fungal burden, making cats an important source of infection. This study evaluated the fungal burden and isolation in skin lesions of feline sporotrichosis during treatment with itraconazole (ITZ), combined with or without potassium iodide (KI). Treatment-naïve cats with culture-confirmed sporotrichosis and presenting skin ulcers were treated for up to 40 weeks with oral ITZ alone (n = 74) or combined with KI (n = 56). These cats were submitted to monthly sampling of the same lesion for mycological culture and cytopathology until healing of lesion or up to twelve weeks. The fungal burden was expressed as the mean yeast cell count in three microscopic fields from imprint smears. The fungal burden before treatment was significantly higher in cats in which the lesion persisted and in cases of treatment failure when using ITZ alone. After twelve weeks, the median fungal burden decreased to zero in both treatment protocols, suggesting a potential decrease in the risk of transmission of Sporothrix spp. from cats. These findings encourage the early treatment of feline sporotrichosis as a control measure. Moreover, the fungal burden in feline sporotrichosis lesions can be a prognostic indicator and a parameter for choosing appropriate therapeutic regimen