Sporotrichosis

BackgroundSporotrichosis is a chronic (sub)cutaneous infection caused by thermodimorphic fungi in the order, Ophiostomatales. These fungi are characterized by major differences in routes of transmission, host predilections, species virulence, and susceptibilities to antifungals. Sporothrix species emerge in the form of outbreaks. Large zoonoses and sapronoses are ongoing in Brazil and China, respectively. Current diagnostic methods based on morphology and physiology are inaccurate due to closely related phenotypes with overlapping components between pathogenic and non-pathogenic Sporothrix. There is a critical need for new diagnostic tools that are specific, sensitive, and cost-effective.MethodologyWe developed a panel of novel markers, based on calmodulin (CAL) gene sequences, for the large-scale diagnosis and epidemiology of clinically relevant members of the Sporothrix genus, and its relative, Ophiostoma. We identified specific PCR-based markers for S. brasiliensis, S. schenckii, S. globosa, S. mexicana, S. pallida, and O. stenoceras. We employed a murine model of disseminated sporotrichosis to optimize a PCR assay for detecting Sporothrix in clinical specimens.ResultsPrimer-BLAST searches revealed candidate sequences that were conserved within a single species. Species-specific primers showed no significant homology with human, mouse, or microorganisms outside the Sporothrix genus. The detection limit was 10-100 fg of DNA in a single round of PCR for identifying S. brasiliensis, S. schenckii, S. globosa, S. mexicana, and S. pallida. A simple, direct PCR assay, with conidia as a source of DNA, was effective for rapid, low-cost genotyping. Samples from a murine model of disseminated sporotrichosis confirmed the feasibility of detecting S. brasiliensis and S. schenckii DNA in spleen, liver, lungs, heart, brain, kidney, tail, and feces of infected animals.ConclusionsThis PCR-based method could successfully detect and identify a single species in samples from cultures and from clinical specimens. The method proved to be simple, high throughput, sensitive, and accurate for diagnosing sporotrichosis.

BackgroundThe fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes.ResultsThe genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE's) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style.ConclusionsComparative genomic data suggest a unique ecological shift in the Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis.

BackgroundSporotrichosis is a mycotic infectious disease that is generally acquired by traumatic inoculation of contaminated materials especially from plant debris or through bites and scratches from diseased animals, such as domestic cats. It affects the skin, lymphatic system, and other organs in the warm-blooded host. Etiological agents are embedded in the plant-associated order Ophiostomatales. With essential differences between possible outbreak sources and ecological niche, host-environment interactions are classic determinants of risk factors for disease acquisition. Sporotrichosis outbreaks with zoonotic transmission, such as those that are ongoing in southern and southeastern Brazil, have highlighted the threat of cross-species pathogen transmission. Sporothrix brasiliensis has emerged as a human threat owing to the intimate contact pattern between diseased cats and humans in endemic areas.ResultsWe describe the recent emergence of feline sporotrichosis in the metropolitan region of São Paulo, Brazil, with an overwhelming occurrence of S. brasiliensis as the etiological agent. A phylogenetic and a haplotype approach were used to investigate the origin of this epidemic and the impact of feline transmission on genetic diversity. During the last 3-year period, 163 cases of feline sporotrichosis were reported in São Paulo with proven S. brasiliensis culture. The haplotype diversity of feline S. brasiliensis isolates revealed the expansion of a clonal population with low genetic diversity. Haplotype analysis confirmed that isolates from São Paulo shared the haplotype originated in the long-lasting outbreak of cat-transmitted sporotrichosis in Rio de Janeiro, which differed from the haplotype circulating in the Rio Grande do Sul epidemic.ConclusionsThe fast spread of sporotrichosis in a short period of time highlights the potential for outbreaks and suggests that the mycosis may affect an urban population with a high concentration of susceptible felines. The feline sporotrichosis epidemic shows no signs of slowing, and this epidemiological pattern may require specific public health strategies to control future outbreaks.

BackgroundSporotrichosis is a dimorphic fungal infection of increasing global relevance. Although usually cutaneous or lymphocutaneous, disseminated disease occurs in immunocompromised hosts. Large-scale data on its epidemiology, treatment and outcomes remain limited.ObjectivesTo characterise the clinical features, comorbidities, antifungal prescribing patterns and one-year mortality associated with sporotrichosis, with emphasis on patients with HIV and other forms of immunosuppression.Patients/methodsWe performed a retrospective global cohort study using the TriNetX Research Network. Adults (≥ 18 years) diagnosed with sporotrichosis were identified using ICD-9/10 codes (1995-2024). Demographics, comorbidities, laboratory parameters and antifungal prescriptions were analysed. The primary outcome was all-cause mortality at 1 year. Secondary outcomes included hospitalisation and admission to the intensive care unit (ICU).ResultsAmong 2124 adults, the mean age was 52 years, and 56.5% were female. Nearly half of the cases originated internationally, with the southeastern United States accounting for the majority of domestic cases. Neoplasms (25%) and diabetes (11%) were the most common comorbidities. Lymphocutaneous disease was uncommon (9%), and disseminated infection occurred in 1% of cases. One-year mortality was 17%, with a higher risk among older adults and those with neoplasms, lymphocutaneous or disseminated infection or hyperferritinemia. Seventeen patients (0.8%) had HIV and were more likely to have pulmonary or disseminated disease. Itraconazole was the most commonly prescribed antifungal (52%), while the use of amphotericin B remained low (ConclusionsSporotrichosis causes substantial global mortality. Outcomes appear driven by host factors and gaps in guideline-based management. Earlier recognition, optimised antifungal therapy, and use of inflammatory markers to guide risk stratification may improve outcomes and inform prevention strategies.