The reference methodology for evaluating antifungal susceptibility is based on determining the minimum inhibitory concentration (MIC), which is the lowest drug concentration capable of inhibiting fungal growth. However, such MIC data are insufficient to measure antifungal susceptibility if a strain is heteroresistant to the tested drug. In such cases, a minority subpopulation of fungal cells, originating from an initially susceptible lineage, can grow at antifungal drug concentrations above the MIC. In studies on fluconazole heteroresistance in Cryptococcus spp., chromosomal disomy has been shown to result in the overexpression of two genes located on chromosome 1 (Chr1) linked to antifungal resistance: ERG11 and AFR1. This review addresses the underlying mechanisms of antifungal resistance, the evolution of methods for determining antifungal susceptibility, and the clinical implications of Cryptococcus heteroresistance to fluconazole. The analysis of the findings indicated a correlation between heteroresistance and adverse clinical outcomes, although this observation still lacks definite confirmation in the literature. This highlights the need to implement more efficient therapeutic strategies and improve antifungal susceptibility and heteroresistance testing.
Sporotrichosis is an emerging fungal infection that has been causing concern in Brazil since the late 1990s and is the most prevalent and globally distributed among implantation mycoses. In Brazil, the increase in sporotrichosis cases is strongly associated with infections in cats. This study aimed to identify the epidemiological profile and expansion of sporotrichosis in the city of Manaus, Amazonas State, Brazil, based on cases reported from 2020 to 2023. Secondary data from confirmed sporotrichosis cases during this period in Manaus were employed. Human data were extracted from the Brazilian Information System for Notificable Diseases, the Manaus Municipal Health Department, and the RedCap database of the Amazonas Health Surveillance Foundation - Registry of Positive Cases. The animal data were extracted from the spreadsheet of the Dr. Carlos Durand Zoonoses Control Center in Manaus. Data analysis was performed using the RStudio software for the spatial distribution of cases in the QGIS program, which was used to define the areas with the highest absolute number of cases. From August 2020 to December 2023, 4,301 sporotrichosis cases were confirmed, including 3,403 animal cases (of which 99.6% involved cats) and 898 human cases. From 2022 to 2023, the number of human cases doubled and animal cases quadrupled, with cases reported across all areas of Manaus. The expansion of sporotrichosis was observed over a two-year period for nearly the entire area of Manaus, with a significant increase in cases and an association between animal and human cases.
17 February 2022 in Tropical Medicine & International Health
Amazon River dolphins are an important flagship species in the Anavilhanas National Park, Brazil, where they interact with visitors. This study aimed to quantify and identify fungi isolated from dolphin skin and oral samples and their surrounding environment in this unique ecosystem. Samples were collected from three dolphins and water samples from Flutuante dos Botos and the Novo Airão city harbor. Fungi were isolated using culture media and identified through micromorphology assays and ITS region sequencing. Oral swab samples resulted in culture of Trichosporon montevideense and Exophiala dermatitidis. Skin samples from one dolphin revealed Toxicocladosporium irritans and Diaporthe lithocarpus. Water samples exhibited higher fungal counts and diversity, with Rhodotorula mucilaginosa, Exophiala dermatitidis, Penicillium citrinum, Fomitopsis meliae, and Nectria pseudotrichia identified at the collection site and Candida spencermartinsiae and Penicillium chermesinum at the city harbor. This study provides important insights into the fungal diversity associated with Amazon River dolphins and their environment, enhancing our understanding of the public health and ecological dynamics in the Anavilhanas National Park.
Sporotrichosis is a zoonotic fungal infection with increasing incidence in the Brazilian Amazon, primarily affecting domestic cats and posing risks to human health. This study characterized the clinical and epidemiological profiles of 29 feline sporotrichosis cases in Manaus and optimized molecular diagnostic methods for Sporothrix species identification. Most affected cats were young (86.2% aged 1–3 years), male (82.7%), and free-roaming or semi-indoor (44.8% each), frequently presenting cutaneous lesions localized at the nasal planum (23.3%), ears (7%), eyes (2.3%) and other facial areas (18.6%). Three DNA extraction methods were compared; the phenol–chloroform protocol yielded the highest DNA concentration and purity, and ITS1–ITS4 primers showed an adequate sensibility for PCR detection. In silico RFLP profiles using common restriction enzymes showed limited discriminatory power among Sporothrix species. ITS sequencing of four high-quality amplicons confirmed all isolates as Sporothrix brasiliensis. Antifungal susceptibility testing of all isolates revealed geometric mean MICs of 0.25 µg/mL for ketoconazole, 0.57 µg/mL for itraconazole, 7.27 µg/mL for amphotericin B, and 64 µg/mL for fluconazole, respectively. These findings provide clinical, molecular, and therapeutic information supporting the diagnosis and surveillance of feline sporotrichosis in the Amazon, reinforcing the need for ongoing veterinary and public health monitoring.