Systematic Review of Mammalian Models for Experimental Sporotrichosis: Pathogenesis, Methodological Variables, and...

In this review, we aimed to condense data on mammalian models of experimental infection with species of the genus Sporothrix, the causal agent of sporotrichosis, using the PRISMA methodology to search in three electronic databases: PubMed, Lilacs, and Web of Science. We analyzed the mammals used and the criteria that determine the course of the infection, including inoculum size and route of inoculation, the host's immune status, and the fungal species employed, as well as information on ethical principles and criteria for determining the pathogenicity/virulence of the fungal species used, and presented a scoring system to be used in experimental infection studies in animal models alongside clinical parameters to assess the humane endpoint and provide reliable results while respecting animal welfare. Our results demonstrated that most articles described mice as mammalian models for experimental sporotrichosis. Over half of the articles cited an intermediate inoculum, ranging from 10⁶ to 10⁷ cells/mL. Subcutaneous is the inoculation route described in 27.71% of the articles, followed by intraperitoneal and intravenous routes, with 25.30% and 21.08%, respectively. Seventy-nine point five-two percent of the studies used immunocompetent models, 9.04% used immunosuppressed animals, and 10.84% included both immunocompetent and immunosuppressed animals. We also observed that Sporothrix schenckii was the most widely used species, considering both the entire period (1900-2024: 77.11%) and the period after the description of new species (2008-2024: 56.47%). Animal welfare conditions were poorly detailed in all articles. Only four studies reported a humane endpoint to terminate the experiment, and one presented consideration of the 3Rs (Replace, Reduce, and Refine). A few articles mentioned the most significant criteria grouped to evaluate the pathogenicity/virulence of the fungal species studied.