Search Results (80)

C-type lectin receptors (CLRs) play central roles in sensing fungal pathogens and coordinating Syk-CARD9-dependent inflammatory responses. While Dectin-3 contributes to antifungal immunity against several clinically relevant fungi, its role in host defense against Paracoccidioides brasiliensis remains unknown. Here, we investigated the impact of Dectin-3 deficiency using Clec4d⁻/⁻ mice and primary phagocytes during experimental Paracoccidioidomycosis. Dectin-3-deficient macrophages and dendritic cells displayed unaltered cytokine production, phagocytic capacity, fungicidal activity, and maturation following P. brasiliensis challenge. Consistently, the absence of Dectin-3 did not impact survival or pulmonary fungal burden during long-term systemic infection. These findings are consistent with functional redundancy among CLRs, potentially involving Dectin-1, Dectin-2, or other Syk-coupled receptors rendering Dectin 3 dispensable for immunity to systemic experimental P. brasiliensis infection. Full article

Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Its diagnosis is often delayed due to the limited availability of accessible and rapid molecular tools in endemic settings. In this study, we developed and conducted a preliminary evaluation of a recombinase polymerase amplification assay coupled with a lateral flow readout (RPA-LFA) for genus-level detection of Paracoccidioides spp. using reference strains and DNA extracted from clinical specimens. The assay targets the ITS1–5.8S–ITS2 ribosomal region using dual-labeled primers, which enable visual detection on LFA strips. Analytical specificity, analytical sensitivity, and clinical concordance were evaluated using reference strains, non-target microorganisms, and an exploratory set of clinical samples. No cross-reactivity was observed with Coccidioides posadasii, Emmonsia crescens, Histoplasma capsulatum, or Leishmania braziliensis. The preliminary analytical limit of detection (LOD) was 100 copies/µL. Visual results were obtained within 35 min, including 20 min of amplification at 39 °C and 15 min for LFA readout. In the clinical sample set analyzed, the assay showed complete concordance with direct microscopy. The RPA-LFA approach addresses several operational limitations of conventional molecular methods by combining isothermal amplification, a short turnaround time, visual interpretation, and low equipment requirements. This work provides a proof of concept for a point-of-care-oriented molecular approach for Paracoccidioides detection in clinical specimens. Further validation in larger and more diverse clinical cohorts is required to establish its diagnostic performance and potential implementation in endemic settings. Full article

Background: Histoplasmosis is a major opportunistic fungal infection in immunocompromised individuals, particularly people living with HIV in Latin America. Early diagnosis is essential to reduce morbidity and mortality, but commercial urinary Histoplasma antigen assays are not consistently accessible in many endemic settings. Methods: We developed a locally produced enzyme-linked immunosorbent assay (ELISA) to detect urinary Histoplasma antigen in urine and performed a preliminary clinical evaluation. The assay is based on a sandwich ELISA format using rabbit polyclonal antibodies raised against whole-killed yeast cells of Histoplasma capsulatum. Receiver operating characteristic (ROC) analysis was performed with urine samples from patients with progressive disseminated histoplasmosis (PDH) (n = 37) and healthy controls (n = 20). An exploratory disease-control panel (n = 11) was also tested to assess cross-reactivity. Preliminary analytical characterization included blank-based estimation of the limit of detection (LOD) and limit of quantification (LOQ). Results: Using a Youden-derived cutoff of OD₄₉₂ = 0.243, the in-house ELISA showed a sensitivity of 73.0% (27/37; 95% CI: 55.9–86.2%) and a specificity of 100.0% (20/20; 95% CI: 83.2–100.0%) in the main ROC dataset, with an area under the curve of 0.856. In the exploratory disease-control panel, 2 of 11 specimens were reactive (one paracoccidioidomycosis and one cryptococcosis sample). Preliminary LOD and LOQ estimates were 4.46 ng/mL and 8.15 ng/mL, respectively. Conclusions: This locally developed ELISA represents a feasible and cost-effective alternative for urinary antigen detection of Histoplasma, with potential to improve access to early diagnosis in resource-limited settings. However, its current performance should be considered preliminary. Additional optimization and broader validation, including direct comparison with commercial assays, inter-assay precision, reagent stability, and larger multicenter control panels, are required before routine clinical implementation. Full article

American tegumentary leishmaniasis (ATL) and other infectious granulomatous diseases (IGDs) may present with oral/oropharyngeal mucosal lesions (OOPML). IGD-OOPML can result from fungal, parasitic, or bacterial infections, and squamous cell carcinoma (SCC) represents the main differential diagnosis. ATL, other IGD, and SCC share overlapping clinical and epidemiological features, making diagnostic suspicion challenging. This study compared sociodemographic and clinical characteristics among ATL, other IGD, and SCC. Descriptive, comparative, and multivariable logistic regression analyses were performed. Among 7551 patients, 213 met inclusion criteria (83-SCC and 130-IGD). Except for smoking, which differed only between ATL and SCC, most IGD parameters were similar. Male patients predominated in all groups. SCC patients were significantly older (p < 0.001) and had a shorter median disease duration (p = 0.007). The presence of pain increased the odds of SCC-OOPML by 3.96 times (95% CI 1.97–12.51). SCC patients were more likely to present lesions in a single subsite, either the oral cavity or oropharynx. Painful, ulcerated, or exophytic lesions favored SCC diagnosis, whereas infiltrative, granular, or mulberry-like lesions, involvement of multiple subsites, or associated nasal and laryngeal lesions suggested IGDs. Although clinical differentiation remains difficult, these findings may support early diagnostic suspicion, prompt treatment, and reduced sequelae. Full article

Background/Objective: Pulmonary fungal infections are a significant diagnostic challenge, primarily affecting immunocompromised individuals, such as those with HIV, cancer, or organ transplants, and they often lead to substantial morbidity and mortality if untreated. These infections trigger acute inflammatory and immune responses, which may progress to chronic inflammation. This process involves myofibroblast recruitment, the deposition of extracellular matrix, and vascular remodeling, ultimately contributing to pulmonary hypertension. Despite its clinical relevance, pulmonary hypertension secondary to fungal infections remains under-recognized in practice and poorly studied in research. Results/Conclusion: This narrative mini-review explores three key mechanisms underlying vascular remodeling in this context: (1) endothelial injury caused by fungal emboli or autoimmune reactions, (2) direct vascular remodeling during chronic infection driven by inflammation and fibrosis, and (3) distant vascular remodeling post-infection, as seen in granulomatous diseases like paracoccidioidomycosis. Further research and clinical screening for pulmonary hypertension in fungal infections are crucial to improving patient outcomes. Full article

Paracoccidioides brasiliensis is a thermally dimorphic fungal pathogen and the main etiological agent of paracoccidioidomycosis (PCM), a neglected systemic mycosis endemic in Latin America. The virulence of P. brasiliensis is closely associated with its capacity to survive under hostile host conditions, including acidic environments. In this study, we demonstrate that acidic pH induces melanization in P. brasiliensis, modulates its cell wall composition, and alters the interaction with macrophages. Cultivation at acidic pH resulted in reduced fungal growth without compromising viability and triggered increased production of melanin-like pigments, as confirmed by enhanced laccase activity and upregulation of genes in the DHN-melanin biosynthetic pathway. Additionally, growth under acidic pH induced significant remodeling of the fungal cell wall, leading to increased chitin on the cell wall surface and reduced mannan content, while β-glucan levels remained unchanged. These modifications correlated with decreased viability to Congo Red, suggesting altered cell wall stability. Importantly, P. brasiliensis grown under acidic conditions exhibited reduced phagocytosis by RAW 264.7 macrophages, along with changes in nitric oxide and cytokine production, indicating potential mechanisms of immune evasion. Collectively, our findings suggest that environmental acidification promotes fungal adaptations that enhance survival and modulate host–pathogen interactions, contributing to P. brasiliensis virulence. Understanding how acidic pH regulates these processes provides new insights into the pathobiology of PCM and may contribute to understanding the mechanisms of fungal immune evasion. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Paracoccidiodomycosis (PCM) is the most important systemic mycosis in Brazil, and is usually associated with rural work. PCM is caused by inhalation of infective propagules of thermodimorphic fungi from the genus Paracoccidioides. In the past, it was believed that Paracoccidioides brasiliensis was the single species responsible for PCM cases. However, recent advances in molecular methods allowed the description of several new species, using phylogenetic concordance as the gold standard. Aside from P. brasiliensis sensu stricto, Paracoccidioides americana is also endemic in Rio de Janeiro state, Brazil. This study aimed to evaluate intraspecific genetic variability of Paracoccidioides isolates from patients diagnosed with PCM at a reference center for endemic mycoses in Rio de Janeiro state, from 2015 to 2021. Among the sixteen retrieved isolates, three (18.75%) were identified as P. americana and thirteen (81.25%) as P. brasiliensis sensu stricto. No intraspecific genetic variation was observed by the M-13 primer in P. americana isolates from this geographic region. However, P. brasiliensis sensu stricto isolates were clustered into two distinct molecular profiles, despite being grouped in a single clade in the phylogenetic tree after partial sequencing of arf and gp43 genes. The results suggest a single P. americana lineage and two P. brasiliensis populations causing PCM in Rio de Janeiro, Brazil. Full article

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungal EVs, their cargo, how they are obtained, and their role during the infectious process, which is extremely important for understanding this neglected mycosis. Full article

Human endemic mycoses are potentially fatal diseases caused by a diverse group of fungi that can alter their morphology in response to an increase in temperature. These thermally dimorphic fungi affect both healthy and immunocompromised hosts, causing a substantial health and economic burden. Despite this, the diagnosis of endemic mycoses is still a formidable challenge for several reasons, including similar symptomatology, limited utility of classical diagnostic methods, inaccessibility to reliable molecular approaches in most endemic areas, and a lack of clinical suspicion out of these regions. This review summarizes essential knowledge on thermally dimorphic fungi and the life-threatening diseases they cause. The principle, advantages and limitations of the methods traditionally used for their diagnosis are also described, along with the application status and future directions for the development of alternative diagnostic strategies, which could help to reduce the disease burden in endemic areas. Full article

Deforestation is a common occurrence driven by agricultural expansion, urbanization, and infrastructure development. These activities often lead to increased human interaction with ecosystems, potentially exposing individuals to Paracoccidioides spores (P. brasiliensis and P. lutzii) found in the soil, resulting in Paracoccidioidomycosis (PCM). This fungal infection is endemic to specific regions in Latin America, such as Brazil, Colombia, Venezuela, and Argentina. Diagnosis typically involves a combination of clinical assessment, imaging techniques, and laboratory examinations. P. lutzii lacks the glycoprotein Gp43, a key antigenic protein utilized in serological tests for PCM diagnosis. In this study, a colorimetric test employing gold nanoparticles (AuNPs) and label-free methodology was employed for P. lutzii detection. The effectiveness of the label-free colorimetric test was assessed using a total of 100 samples. This detection was achieved through the amplification of the gp43 gene and the use of a specific probe (5′CAGGGGTGCG3′) in conjunction with AuNPs. The receiver operating characteristic curve was employed to assess the test, revealing that the method can accurately detect P. lutzii with a sensitivity of 100% and a specificity of 100%. The findings indicate a substantial impact on remote endemic regions attributable to the implementation of cost-effective diagnostic methodologies. Full article

Blood count is crucial for assessing bone marrow’s cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic forms of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (standard deviation SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%), which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes’ role in PCM’s immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters. Full article

Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological data. This retrospective study concerned all patients with CBM proven by at least one paraclinical examination and diagnosed in French Guiana between 1950 and 2023. In total, 23 patients were included, mostly males (87%) of Creole origin, living in the coastal region (87%) and involved in outdoor occupations (74%). Lesions were mostly observed on the lower limbs (78.3%), with a median time to diagnosis of four years. Laboratory tests included positive direct microscopic examinations (78.3%) and mycological cultures (69.6%), identifying 14 cases of Fonsecaea pedrosoi and one case of Exophiala janselmei. Various treatments were employed, including antifungals, surgery and combinations of both. In conclusion, CBM in French Guiana involves a different population than other subcutaneous mycoses such as Lobomycosis or Paracoccidioidomycosis, mostly found in the forest hinterland. Surgery should be recommended for recent and limited lesions. Itraconazole and terbinafine should systematically be proposed, either in monotherapy or in combination with surgery or cryotherapy. Full article

The incidence of paracoccidioidomycosis (PCM) varies in Latin America, and it is influenced by environmental factors. This study evaluated the distribution of PCM acute/subacute form (AF) cases and their correlation with geoclimatic factors in the Mato Grosso do Sul (MS) state. The study included 81 patients diagnosed with the PCM/AF at the University Hospital of the Federal University of Mato Grosso do Sul between January 1980 and February 2022. Geographic coordinates, health microregion of patient’s residence, compensated average temperature, relative air humidity (RH), El Niño Southern Oscillation (ENSO), and average global temperature were analyzed. The highest incidence was observed in the Aquidauana (7/100,000 inhabitants), while Campo Grande, the state’s capital, had the highest number (n = 34; 42.4%) and density (4.4 cases/km²) of cases. The number of cases increased during extended periods of the El Niño phenomenon. A positive correlation was found between higher RH and PCM/AF cases. Most PCM/AF cases were found in areas with loamy soils and RH ranging from 60.8 to 73.6%. In MS, the health microregions of PCM/AF patients are characterized by deforestation for agricultural and pasture use, coupled with loamy soils and specific climatic phenomena leading to higher soil humidity. Full article

Paracoccidioidomycosis (PCM) is a systemic mycosis that is diagnosed by visualizing the fungus in clinical samples or by other methods, like serological techniques. However, all PCM diagnostic methods have limitations. The aim of this study was to develop a diagnostic tool for PCM based on Fourier transform infrared (FTIR) spectroscopy. A total of 224 serum samples were included: 132 from PCM patients and 92 constituting the control group (50 from healthy blood donors and 42 from patients with other systemic mycoses). Samples were analyzed by attenuated total reflection (ATR) and a t-test was performed to find differences in the spectra of the two groups. The wavenumbers that had p < 0.05 had their diagnostic potential evaluated using receiver operating characteristic (ROC) curves. The spectral region with the lowest p value was used for variable selection through principal component analysis (PCA). The selected variables were used in a linear discriminant analysis (LDA). In univariate analysis, the ROC curves with the best performance were obtained in the region 1551–1095 cm⁻¹. The wavenumber that had the highest AUC value was 1264 cm⁻¹, achieving a sensitivity of 97.73%, specificity of 76.01%, and accuracy of 94.22%. The total separation of groups was obtained in the PCA performed with a spectral range of 1551–1095 cm⁻¹. LDA performed with the eight wavenumbers with the greatest weight from the group discrimination in the PCA obtained 100% accuracy. The methodology proposed here is simple, fast, and highly accurate, proving its potential to be applied in the diagnosis of PCM. The proposed method is more accurate than the currently known diagnostic methods, which is particularly relevant for a neglected tropical mycosis such as paracoccidioidomycosis. Full article