A surprising finding: The curious case of a tongue lesion misdiagnosed as paracoccidioidomycosis / Un hallazgo inesperado: el curioso caso de una lesión en la lengua diagnosticada erróneamente como paracoccidioidomicosis

Background: Paracoccidioidomycosis is an endemic mycosis caused by members of the Paracoccidioides genus. Brazil remains the focus area and, to a lesser extent, the disease has been reported from Argentina, Colombia and Venezuela. Aims: A Venezuelan Paracoccidioides brasiliensis strain, isolated from a patient diagnosed with chronic multifocal paracoccidioidomycosis, was subjected to whole genome sequencing to provide more insight about Paracoccidioides outside the endemic focus area. Methods: P. brasiliensis strain CBS 118890 was whole genome sequenced using nanopore; library preparation with the ‘native barcoding genomic DNA kit’ was followed by sequencing on Flongle and MinION flowcells. Batches of strain CBS 118890 were re-identified by sequencing the internal transcribed spacer (ITS) region, and final identification was made based on phylogenetic analysis. Results: Surprisingly, the Venezuelan P. brasiliensis strain CBS 118890 turned out to be a Nannizziopsis species. The batches of this strain were ITS sequenced followed by phylogenetic analysis and resulted in the final identification of Nannizziopsis arthrosporioides. Conclusions: Nannizziopsis infections are commonly seen in a wide variety of reptiles, but are particularly rare in human infections. This case underlines the need for molecular characterization of cases that clinically mimic paracoccidioidomycosis but that are serologically negative for Paracoccidioides.(AU)

Antecedentes: La paracoccidioidomicosis es una micosis endémica causada por especies del género Paracoccidioides. Brasil sigue siendo el área con la mayor incidencia y, en menor medida, se ha informado de casos en Argentina, Colombia y Venezuela. Objetivos: Una cepa venezolana de Paracoccidioidesbrasiliensis, obtenida de un paciente diagnosticado con paracoccidioidomicosis multifocal crónica, se sometió a secuenciación completa del genoma para obtener más información sobre Paracoccidioides fuera del área de foco endémico. Métodos: Se secuenció el genoma completo de la cepa CBS 118890 de P. brasiliensis mediante la técnica de secuenciación de nanoporos; tras la preparación de la librería con el «native barcoding genomic DNA kit» se procedió a la secuenciación con el Flongle y MinION flowcells. Los lotes de la cepa CBS 118890 se volvieron a identificar mediante la secuenciación de la región del espaciador transcrito interno (ITS), y la identificación final se realizó en función del análisis filogenético. Resultados: Sorprendentemente, la cepa venezolana P. brasiliensis CBS 118890 resultó ser una especie de Nannizziopsis. Los lotes de esta cepa se secuenciaron mediante ITS seguido de un análisis filogenético y dieron como resultado la identificación de la especie Nannizziopsis arthrosporioides. Conclusiones: Las infecciones por Nannizziopsis se observan comúnmente en una amplia variedad de reptiles, pero son particularmente raras en infecciones humanas. Este caso subraya la necesidad de la caracterización molecular de los casos que clínicamente reflejan paracoccidioidomicosis, pero que son serológicamente negativos para Paracoccidioides.(AU)

Sporotrichosis in dogs: epidemiological and clinical-therapeutic profile and the emergence of itraconazole-resistant isolates.

Sporotrichosis is a neglected and emerging mycosis caused by the traumatic implantation of Sporothrix propagules into the (sub)cutaneous tissues of humans and animals. We evaluated canine sporotrichosis's clinical-therapeutic, epidemiological profile, and in vitro susceptibility of isolates to itraconazole. The variables were evaluated by a chi-square test. A total of 69 dogs were infected with Sporothrix spp., and the molecular identification revealed an overwhelming occurrence of S. brasiliensis as the etiological agent. The epidemiological profile was male (56.5%), adults (4.9 ± 1.92 years old; 69.6%), and mongrels (53.6%). The clinical signs were 76.8%, ulcers, draining tracts, and nodules were predominant, mainly in the nasal region (82.2%). Dogs were diagnosed late with an evolution time of up to 3 months (34.8%). According to the prior therapeutic information, 52.2% received empirical therapy, 79.2% antibiotics, and had a 0.29 significantly greater chance of presenting lesion evolution time ˃ 3 months (P < .05; Odds Ratio [OR] 1/0.29). Additionally, 25 S. brasiliensis isolates recovered between 2006-2012 (n = 15; Minimal inhibitory concentration (MIC): 0.06-2 µg/ml) and 2013-2018 (n = 10; MIC: 2→16 µg/ml) were tested against itraconazole (ITZ). These findings highlighted the resistance to ITZ in clinical cases due to S. brasiliensis occurring after 2013, showing the temporal evolution of ITZ-resistance. We warn of the importance of accurate and early diagnosis in Sporothrix-affected areas, and we report the emergence of ITZ-resistant isolates in Southern Brazil.

Sporotrichosis is a fungal zoonosis. We investigated the clinical-therapeutic, epidemiological profile, and in vitro susceptibility of isolates to itraconazole (ITZ) in canine cases in Southern Brazil. Our study highlighted the emergence of ITZ-resistant Sporothrix brasiliensis and the main challenges for clinical control of this neglected disease.

Advances and challenges in the management of feline sporotrichosis / Avances y desafíos en el manejo de la esporotricosis felina

The domestic cat is the most susceptible host to Sporothrix infection, developing severe clinical forms. Few effective antifungal agents are available for treating feline sporotrichosis, and cases of treatment failure are common. Treatment success depends on cat health status, therapy-related factors, as well as social/economic issues, but it is mainly contingent upon the host–fungus interaction. The owner's adherence is critical and should be reinforced throughout the treatment to increase the chances of a successful outcome. The antifungal agents described for feline sporotrichosis are most often used in monotherapy regimens. Due to cases in which the treatment with itraconazole failed, the use of antifungal agents in combination should be considered to achieve synergy. The combination of itraconazole and potassium iodide represents an important option for the treatment of naïve cats presenting multiple cutaneous lesions, nasal mucosal lesions and/or respiratory signs, as well as for refractory cases. However, the therapeutic options for unsuccessfully treated cases are scarce. Therefore new options are needed, even more taking into account that there are many in vitro potential molecules not available for use in cats yet. More studies are necessary to correlate in vitro antifungal susceptibility tests results and the outcome of cats treated due to sporotrichosis. This review will briefly discuss both the antifungal drugs and treatment protocols used in cats with sporotrichosis, as well as the determinants of treatment failure. (AU)

El gato doméstico es el huésped más susceptible a la infección por Sporothrix, llegando a desarrollar formas clínicas graves. Hay pocos agentes antimicóticos efectivos disponibles para tratar la esporotricosis felina, y los casos de fracaso terapéutico son habituales. El éxito del tratamiento depende del estado de salud del gato, los factores relacionados con la terapia y los problemas sociales/económicos, pero se asocia principalmente con la interacción huésped-hongo. El cumplimiento del tratamiento por parte del propietario es fundamental y debe reforzarse durante todo el proceso para aumentar las posibilidades de éxito. Los agentes antimicóticos descritos para la esporotricosis felina se usan con mayor frecuencia en monoterapia. Debido a los casos de fallo terapéutico en el tratamiento con itraconazol se debe considerar el uso combinado de agentes antifúngicos en sinergia. La combinación de itraconazol y yoduro de potasio es una buena opción en el caso de gatos no tratados previamente y con múltiples lesiones cutáneas, en la mucosa nasal y/o con signos respiratorios, así como para casos refractarios. Sin embargo, las opciones terapéuticas para la mayoría de los casos que fracasan son escasas. Por tanto, son necesarias nuevas opciones terapéuticas, más aún cuando existen muchas moléculas potenciales in vitro, no disponibles de momento para su uso en gatos. Son necesarios más estudios que correlacionen los resultados de las pruebas de sensibilidad in vitro a los antifúngicos con aquellos del tratamiento de gatos con esporotricosis. Esta revisión discutirá brevemente los fármacos antimicóticos y los protocolos terapéuticos utilizados para tratar gatos con esporotricosis, así como los factores determinantes del fracaso del tratamiento. (AU)

Fatal pulmonary sporotrichosis caused by Sporothrix brasiliensis in Northeast Brazil.

BACKGROUND: A relevant case of pulmonary sporotrichosis due to Sporothrix brasiliensis is reported in a 50-year-old immunocompetent woman who had no history of skin trauma, but was in close contact with several stray cats at her nap time. The patient was hospitalized after 7 months of illness. The survey was conducted for pulmonary tuberculosis, an endemic disease in Brazil. She presented multiple central pulmonary nodules images, with central cavitation. METHODOLOGY/PRINCIPAL FINDINGS: The patient bronchoalveolar lavage was cultured and Sporothrix sp. growth was obtained. Then, the isolate (LMMM1097) was accurately identified to the species level by using species-specific polymerase chain reaction (PCR). Molecular diagnosis revealed that the emerging species Sporothrix brasiliensis was the agent of primary pulmonary sporotrichosis and the patient was treated with Amphotericin B lipid complex, but presented severe clinical symptoms and the fatal outcome was observed at day 25 after hospitalization. CONCLUSIONS/SIGNIFICANCE: Our report adds important contributions to the clinical-epidemiological features of sporotrichosis, showing the geographic expansion of the agent within different regions of Brazil and a rare clinical manifestation (primary pulmonary sporotrichosis) caused by the emerging agent S. brasiliensis in an immunocompetent female patient.

A case of paracoccidioidomycosis due to Paracoccidioides lutzii presenting sarcoid-like form.

Paracoccidioidomycosis (PCM) is a fungal disease caused by Paracoccidioides spp., which can cause a systemic granulomatous infection with tegumentary and visceral involvement. Sarcoid-like skin lesions are uncommon and can be misdiagnosed due to similarities with other granulomatous diseases. We report a case of a women presenting with erythematous infiltrated plaques on her face that was treated for leprosy and rosacea with no response and was later diagnosed with PCM, presenting positive serology for Paracoccidioides lutzii.

Clotrimazole is highly effective in vitro against feline Sporothrix brasiliensis isolates.

PURPOSE: Sporothrix brasiliensis, the most virulent species in the Sporothrix schenckii complex, is responsible for the ongoing epidemics of human and animal sporotrichosis in Brazil. Feline outbreaks are usually driven by S. brasiliensis and followed by extensive transmission to humans. Itraconazole is the first-line treatment for both feline and human sporotrichosis; however, reduced sensitivity is an emerging issue. Thus, we investigated the effect of the widely used antifungal clotrimazole - alone or in combination with itraconazole - against the pathogenic (yeast) form of feline and human S. brasiliensis isolates, in vitro. METHODOLOGY: Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were determined for treatment with clotrimazole and itraconazole, as monotherapy or in combination. In addition, the effect of the drugs on neutral lipid levels and the yeast ultrastructure were evaluated by flow cytometry and transmission electron microscopy (TEM), respectively. RESULTS: The MIC and MFC values show that clotrimazole was more effective than itraconazole against feline S. brasiliensis isolates, while human isolates were more sensitive to itraconazole. Similarly to itraconazole, treatment with clotrimazole induced statistically significant neutral lipid accumulation in S. brasiliensis yeasts, and treated yeasts displayed irregularities in the cell membrane and a thicker cell wall when observed by TEM. Clotrimazole increased the antifungal activity of itraconazole in combination assays, with a synergistic effect for two feline isolates. CONCLUSION: The strong activity of clotrimazole against feline S. brasiliensis isolates suggests that this drug is potentially a new alternative for the treatment of feline sporotrichosis, alone or in combination with itraconazole.