Histoplasmosis is a systemic disease caused by the dimorphic fungus Histoplasma capsulatum. Diagnosis is often delayed, or it is misdiagnosed as tuberculosis. In Brazil, the infection is common and cases of histoplasmosis have been described in all regions of the country; however, the real problem is underestimated since notification of histoplasmosis is not mandatory. Human histoplasmosis cases diagnosed in Brazil and published up to December 2018 were identified through a search conducted in the PubMed/MEDLINE, SciELO, and Web of Science databases. Moreover, the isolation of H. capsulatum from animals or environmental sources in Brazil was also evaluated. A total of 207 articles fulfilled the inclusion criteria and were evaluated, involving a total of 3530 patients with a diagnosis of histoplasmosis during the period studied. Of these patients, 78.3% were male, giving a male-to-female ratio of approximately 4:1. Histoplasmosis presented a higher frequency in individuals between the fourth and fifth decades of life. Disseminated disease was the most common form of histoplasmosis. Isolation of H. capsulatum on culture media and histopathology using staining methods were the diagnostic methods with the best efficiency. The best results in the identification of the H. capsulatum were achieved for samples from mononuclear phagocyte system components, skin and mucosa, and hematological samples. Regarding predisposing factors for histoplasmosis, HIV infection was the most common underlying condition. The overall mortality rate was 33.1%. This study represents the first available systematic review demonstrating Brazilian cases of histoplasmosis in the literature and highlights that the disease is more widespread in the Brazilian territory than has previously been thought.

Although considered rare, the emergent Candida haemulonii species complex, formed by C. haemulonii sensu stricto (Ch), C. duobushaemulonii (Cd) and C. haemulonii var. vulnera (Chv), is highlighted due to its profile of increased resistance to the available antifungal drugs. In the present work, 25 clinical isolates, recovered from human infections during 2011–2020 and biochemically identified by automated system as C. haemulonii, were initially assessed by molecular methods (amplification and sequencing of ITS1-5.8S-ITS2 gene) for precise species identification. Subsequently, the antifungal susceptibility of planktonic cells, biofilm formation and susceptibility of biofilms to antifungal drugs and the secretion of key molecules, such as hydrolytic enzymes, hemolysins and siderophores, were evaluated by classical methodologies. Our results revealed that 7 (28%) isolates were molecularly identified as Ch, 7 (28%) as Chv and 11 (44%) as Cd. Sixteen (64%) fungal isolates were recovered from blood. Regarding the antifungal susceptibility test, the planktonic cells were resistant to (i) fluconazole (100% of Ch and Chv, and 72.7% of Cd isolates), itraconazole and voriconazole (85.7% of Ch and Chv, and 72.7% of Cd isolates); (ii) no breakpoints were defined for posaconazole, but high MICs were observed for 85.7% of Ch and Chv, and 72.7% of Cd isolates; (iii) all isolates were resistant to amphotericin B; and (iv) all isolates were susceptible to echinocandins (except for one isolate of Cd) and to flucytosine (except for two isolates of Cd). Biofilm is a well-known virulence and resistant structure in Candida species, including the C. haemulonii complex. Herein, we showed that all isolates were able to form viable biofilms over a polystyrene surface. Moreover, the mature biofilms formed by the C. haemulonii species complex presented a higher antifungal-resistant profile than their planktonic counterparts. Secreted molecules associated with virulence were also detected in our fungal collection: 100% of the isolates yielded aspartic proteases, hemolysins and siderophores as well as phospholipase (92%), esterase (80%), phytase (80%), and caseinase (76%) activities. Our results reinforce the multidrug resistance profile of the C. haemulonii species complex, including Brazilian clinical isolates, as well as their ability to produce important virulence attributes such as biofilms and different classes of hydrolytic enzymes, hemolysins and siderophores, which typically present a strain-dependent profile.

Zoonotic sporotrichosis, a subcutaneous mycosis caused by Sporothrix brasiliensis, has become hyperendemic and a serious public health issue in Brazil and an emerging disease throughout the world. Typical sporotrichosis is defined as fixed or lymphocutaneous lesion development, however, reports of atypical presentations have been described in hyperendemic areas, which may result in a worse prognosis. Thus, considering an increase in atypical cases and in more severe extracutaneous cases and hospitalizations reported in Brazil, we aimed to perform a systematic review to search for hypersensitivity reactions (HRs) and extracutaneous presentations associated with zoonotic sporotrichosis. A systematic review was performed, following the PRISMA guidelines to search for atypical/extracutaneous cases (mucosal, osteoarthritis, HRs, pulmonary, meningeal) of zoonotic sporotrichosis. A total of 791 published cases over 26 years (1998–2023) in eleven Brazilian states were reviewed. Most cases corresponded to a HR (47%; n = 370), followed by mucosal (32%; n = 256), multifocal (8%; n = 60), osteoarthritis (7%; n = 59), meningeal (4%; n = 32), and pulmonary (2%; n = 14) infections. When available (n = 607), the outcome was death in 7% (n = 43) of cases. Here, we show a frequent and worrisome scenario of zoonotic sporotrichosis in Brazil, with a high and dispersed incidence of atypical/extracutaneous cases throughout the Brazilian territory. Therefore, educational measures are necessary to make health professionals and the overall population aware of this fungal pathogen in Brazil as well as in other countries in the Americas.

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan–Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.

Histoplasmosis is a severe mycotic disease affecting thousands of immunocompetent and immunocompromised individuals with high incidence in Latin America, where the disease agents are Histoplasma capsulatum and Histoplasma suramericanum. In this work, we used whole-genome sequencing to infer the species diversity and the population structure of H. suramericanum in South America. We find evidence for strong population structure and little admixture within the species. Genome-level phylogenetic trees indicate the existence of at least three different discrete populations. We recovered the existence of a previously identified population, LAmB, and confirm that it is highly differentiated along the whole genome. We also find that H. suramericanum is composed of two populations, one in Northern South America, and another in the southern portion of the continent. Moreover, one of the lineages from the southern population is endemic to Rio de Janeiro and there was no association with clinical data and species isolated from patients with histoplasmosis. Our results point out the need to characterize the symptomatology of histoplasmosis caused by different species and lineages of Histoplasma spp.