Seasonality of sporotrichosis in Brazil: A modelled analysis of the epidemic in São Paulo, 2011-2020.

BACKGROUND: Sporotrichosis is an endemic subcutaneous mycosis classically caused by the Sporothrix schenckii species complex. Recently, sporotrichosis has emerged in Brazil as a cat-transmitted epidemic caused by a new species, Sporothrix brasiliensis. OBJECTIVES: To survey the clinical-epidemiological profile of all sporotrichosis cases diagnosed between 2011 and 2020 at a reference hospital in São Paulo metropolitan area and evaluate the annual distribution of cases in relation to seasonality. METHODS: Patients' demographic and clinical-epidemiological data were surveyed. A generalized linear model was fitted to relate the quarterly number of sporotrichosis cases detected between 2015 and 2019 with precipitation and temperature series. Prediction of the number of cases from 2011 to 2014 was attempted based on the fitted model without the trend component that appears from 2015. RESULTS: Among 271 suspected cases admitted during 2011-2020, 254 were confirmed by fungal isolation and/or clinical-epidemiological criteria. We observed that 2015 onwards the number of cases regularly increased during Autumn and Winter, the driest and coldest stations of the year. We verified that temperature series affected the number of cases (p = .005) because an increase of 1°C in the temperature series was associated with a 14.24% decrease in the average cases number, with the average number of cases increasing by 10.96% (p < .0001) every quarter, corresponding to an annual increase of 52%. Between 2011 and 2014, the predicted number of sporotrichosis cases averaged 10-12 per year, with 33%-38% occurring in the winter. CONCLUSION: We hypothesize that sporotrichosis seasonality is associated with the felines' oestrus cycle, which may provide alternative, cat-directed approaches to the sporotrichosis epidemic control.

Treatment of Human Sporotrichosis Caused by Sporothrix brasiliensis.

We describe the successful treatment of a series of 30 zoonotic sporotrichosis cases from southern Brazil. Sporothrix brasiliensis was the species genotypically identified in all 25 confirmed cases. Five other cases were classified as probable, without laboratory confirmation, but with clinical and epidemiological data of cat-transmitted sporotrichosis. Two isolates were sequenced by translation elongation factor-1 alpha (EF1α) loci in order to compare their sequences, and both of them showed distinct genotypes from S. brasiliensis strains from other Brazilian states. Itraconazole (ITZ) or potassium iodide (KI) were the first choice treatment in 28 and 2 cases, respectively. Microdilution assay showed a wild-type profile of S. brasiliensis isolates to ITZ. However, a lack of clinical response occurred in 42% of cases, especially those treated with ITZ 100 mg/day, and treatment needed modifications, by either increased doses or antifungal combinations. Clinical cure required a mean of 187 days of treatment, which was dependent on the clinical form of the disease and age of patients. Therapy, including dosages and durations, for cutaneous forms of sporotrichosis requires re-evaluation, since cases caused by S. brasiliensis may influence treatment efficacy.

Development and evaluation of a multiplex qPCR assay for rapid diagnostics of emerging sporotrichosis.

Sporothrix schenckii and related species are the agents of human and animal sporotrichosis. Routine diagnoses using classical mycological approaches are unspecific due to overlapping phenotypes. As the frequency and prevalence of sporotrichosis increases worldwide, developing specific, sensitive and cost-effective diagnostic tools is essential to understand the distribution patterns, map-affected areas and promote specific public health strategies to mitigate future outbreaks. Polymorphisms among the ß-tubulin gene were exploited to speciate S. brasiliensis, S. schenckii and S. globosa in a one-tube multiplex probe-based qPCR assay. A panel of 84 Sporothrix revealed 100% specificity (AUC = 1.000, 95% CI = 0.971-1.000, p < .0001) without cross-reacting with other medically relevant fungi, human, feline or murine DNA. Speciation via multiplex qPCR matched phylogenetic identification (Kappa = 1.0; 95% CI = 1.0-1.0; very good agreement), supporting its use as a reliable alternative to DNA sequencing. Remarkably, the lower limit of detection was 3 copies of the target for all species. As a proof of concept, we used swabs of wound exudate of 70 cats suspected of sporotrichosis to reveal an overwhelming occurrence of S. brasiliensis in 69 specimens (sensitivity = 98.57%; 95%CI: 92.3-100.0 and specificity = 100%; 95% CI = 78.2-100). In comparison to culture, qPCR showed a larger area under the curve (AUC = 0.993±0.007; 95% CI = 0.944-1.000; p < .0001; Youden's index = 0.9857), supporting that qPCR is an essential tool for accurately detect Sporothrix DNA directly from clinical samples, thus accelerating the diagnosis of sporotrichosis. Moreover, our multiplex qPCR system has the potential to increase diagnostic capacity in Sporothrix-affected areas, helping the local animal health agent or veterinarian to quickly identify and isolate new cases, which will likely benefit thousands of patients infected every year worldwide.

Associated factors and spatial patterns of the epidemic sporotrichosis in a high density human populated area: A cross-sectional study from 2016 to 2018.

An epidemiological characterization of human and feline sporotrichosis was carried out between 2016 and 2018, in a high density-populated area in Brazil. Professionals were trained to identify suspect cats and notify vets to interview the owners and collect swabs of the wounds from these animals. Mycological cultures were performed, and colonies identified as Sporothrix spp. Subsequently, data regarding the outcome from suspect animals were collected. Confirmed cases of human sporotrichosis (56) were also counted and analyzed for spatial distribution. 118 positive animals were observed. The prevalence of feline sporotrichosis was 8.36 ‰ (CI 95 %, 5.38-9.55 ‰). The odds for being positive in animals that lived only partially at home were 3.02 times greater than for those cats without access to the street (OR 3.02, CI 95 % 1,96-10,43). There was no statistically significant association between environmental variables and positive diagnosis, corroborating the hypothesis that direct transmission by infected cats plays a greater role in the occurrence and continuous outbreaks of sporotrichosis in Brazil. Among the positive animals, 61.90 % (CI 95 % 58.95-64.96) died, and they had an odds to die in the next six months 6.30 times greater than negative animals (p < 0.05, OR 6.30, CI 95 % 2,79-14,42). The case fatality rate was 55.08 % in cats (CI 95 % 49.20-51.15). The cause-specific death rate was 4.6 ‰ in cats (CI 95 % 3.4-6 ‰). Only 7.62 % (CI 95 % 7.12-8.16) positive cats were treated and cured. Among dead positive animals, 29.23 % were inappropriately discarded. In the study period 56 human cases were recorded in the Barreiro region. Regions with highest prevalence of feline sporotrichosis, had greater frequencies of both human and feline cases. This is the first report on the epidemic of sporotrichosis in Minas Gerais, Brazil. The free offer for treatment and veterinary care for these animals should be taken into consideration, as well as the collection and incineration of the dead ones, as measures of public health, followed by the guidance and care for the human patient.

Human sporotrichosis: A zoonotic outbreak in southern Brazil, 2012-2017.

Zoonotic sporotrichosis has undergone a geographical expansion in Brazil in the last decade. Rio Grande do Sul (RS) is the second state of the country in which a number of feline sporotrichosis cases have been described. Since cats are the main zoonotic source of infection, this study aimed to describe 100 cases of human sporotrichosis occurring in the last 5 years in the southern region of RS, Brazil. In addition, we aimed to illustrate the zoonotic importance of the disease, describing four cases in the same family due to transmission by their cat. This great number of human cases in a short period of evaluation highlights the severity of sporotrichosis as a public health problem in the region, suggesting that a possible outbreak is occurring that requires immediate public intervention actions to weaken its impact.