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Revista Da Sociedade Brasileira de... 2024Accurate diagnosis of paracoccidioidomycosis is crucial for improving patient outcomes. Paracoccidioides antibody detection by double immunodiffusion (DID) is a...
BACKGROUND
Accurate diagnosis of paracoccidioidomycosis is crucial for improving patient outcomes. Paracoccidioides antibody detection by double immunodiffusion (DID) is a convenient diagnostic tool, but testing performance can vary based on certain factors.
METHODS
We assessed DID performance using a commercially prepared Paracoccidioides reagents (IMMY, USA), involving 40 serum specimens, including 20 from patients with proven paracoccidioidomycosis and 20 from patients without the disease. The DID test demonstrated a sensitivity of 90% (95% CI=68%-99%) and a specificity of 100% (95% CI=83%-100%).
CONCLUSIONS
Our findings suggest that DID using commercial reagents may provide a feasible tool with satisfactory testing performance for anti-Paracoccidioides antibody detection.
Topics: Humans; Sensitivity and Specificity; Antibodies, Fungal; Immunodiffusion; Paracoccidioidomycosis; Paracoccidioides; Reagent Kits, Diagnostic; Female; Male
PubMed: 38808801
DOI: 10.1590/0037-8682-0094-2024 -
Journal of Fungi (Basel, Switzerland) Apr 2024Blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses....
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.
PubMed: 38786672
DOI: 10.3390/jof10050317 -
Medicina Oral, Patologia Oral Y Cirugia... Apr 2024Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent...
BACKGROUND
Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC.
MATERIAL AND METHODS
A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated.
RESULTS
A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis.
CONCLUSIONS
Although uncommon, PCM and OSCC should be considered as a diferential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Iincisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.
PubMed: 38615259
DOI: 10.4317/medoral.26518 -
Revista Da Sociedade Brasileira de... 2024Cutaneous involvement in paracoccidioidomycosis (PCM) can exhibit a highly polymorphic spectrum. The infiltrative pattern corresponds to up to 26.6% of observed skin...
Cutaneous involvement in paracoccidioidomycosis (PCM) can exhibit a highly polymorphic spectrum. The infiltrative pattern corresponds to up to 26.6% of observed skin lesions, including sarcoid-like plaques, a rare presentation of cutaneous lesions in PCM. This clinical expression is almost exclusively cutaneous, and its histology reveals a tuberculoid granuloma with a scarcity of fungi, leading to misdiagnosis as other granulomatous diseases. Here, we report a rare form of chronic multifocal paracoccidioidomycosis manifesting as sarcoid-like skin lesions misdiagnosed as granulomatous rosacea in a patient with severe systemic disease.
Topics: Humans; Paracoccidioidomycosis; Sarcoidosis; Skin; Diagnosis, Differential; Diagnostic Errors
PubMed: 38537002
DOI: 10.1590/0037-8682-0605-2023 -
Journal of Fungi (Basel, Switzerland) Feb 2024Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological...
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 and one case of 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.
PubMed: 38535177
DOI: 10.3390/jof10030168 -
Journal of Fungi (Basel, Switzerland) Feb 2024The incidence of paracoccidioidomycosis (PCM) varies in Latin America, and it is influenced by environmental factors. This study evaluated the distribution of PCM...
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/km) 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.
PubMed: 38535174
DOI: 10.3390/jof10030165 -
Medical Mycology Case Reports Jun 2024We report a case of unusual paracoccidioidomycosis reactivation after eyebrow micropigmentation in a Brazilian patient. The cutaneous lesion was the only clinical...
We report a case of unusual paracoccidioidomycosis reactivation after eyebrow micropigmentation in a Brazilian patient. The cutaneous lesion was the only clinical manifestation. Direct cutaneous inoculation in dermal tissues with sp. is extremely rare, explaining why paracoccidioidomycosis is not classically considered a cutaneous implantation mycosis.
PubMed: 38516608
DOI: 10.1016/j.mmcr.2024.100639 -
PloS One 2024Paracoccidioides fungi are thermodimorphic microorganisms that cause paracoccidioidomycosis (PCM), an autochthonous disease from Latin America, with most cases in...
Recombinant 60-kDa heat shock protein from Paracoccidioides brasiliensis induces the death of mouse lymphocytes in a mechanism dependent on Toll-like receptor 4 and tumor necrosis factor.
Paracoccidioides fungi are thermodimorphic microorganisms that cause paracoccidioidomycosis (PCM), an autochthonous disease from Latin America, with most cases in Brazil. Humans become infected by inhaling conidia or mycelial fragments that transform into yeast at body temperature. These fungi cause chronic-granulomatous inflammation, which may promote fibrosis and parenchyma destruction in the lungs. In response to stress imposed by the host, fungi Paracoccidioides spp. increase the expression of heat shock proteins (HSP), which protect them by sustaining cellular proteostasis. Our group has studied the role of HSP60 in PCM, and previous data show that the recombinant HSP60 (rHSP60) has a deleterious effect when used in a single dose as therapy for experimental PCM. Here, we investigated the mechanism by which rHSP60 could worsen the disease. We found that rHSP60 caused the viability loss of splenic or lymph node cells from both immunized and non-immunized mice, including in splenic T lymphocytes under polyclonal stimulation with concanavalin A, probably by undergoing apoptosis. Among analyzed splenic cells, lymphocytes were indeed the main cells to die. When we investigated the death mechanisms, remarkably, we found that there was no viability loss in rHSP60-stimulated splenic cells from mice deficient in Toll-like receptor 4, TRIF adapter protein, and TNF receptor 1(TNFR1), as well as rHSP60-stimulated WT cells incubated with anti-TNF antibody. Besides, caspase-8 inhibitor IETD-CHO blocked the rHSP60 effect on splenic cells, suggesting that rHSP60 induces the extrinsic apoptosis pathway dependent on signaling via TLR4/TRIF and TNFR1.
Topics: Humans; Mice; Animals; Paracoccidioides; Toll-Like Receptor 4; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor Inhibitors; Paracoccidioidomycosis; Tumor Necrosis Factor-alpha; Inflammation; Lymphocytes; Adaptor Proteins, Vesicular Transport
PubMed: 38512915
DOI: 10.1371/journal.pone.0300364 -
Virulence Dec 2024Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that transport several biomolecules and are involved in important mechanisms and functions related to...
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that transport several biomolecules and are involved in important mechanisms and functions related to the pathophysiology of fungal diseases. EVs from , the main causative agent of Paracoccidioidomycosis (PCM), modulate the immune response of macrophages. In this study, we assessed the EVs proteome from a virulent isolated from granulomatous lesions and compared their immunomodulatory ability with EVs isolated from the fungus before the animal passage (control EVs) when challenging macrophages and dendritic cells (DCs). Proteome showed that virulent EVs have a higher abundance of virulence factors such as GP43, protein 14-3-3, GAPDH, as well as virulence factors never described in PCM, such as aspartyl aminopeptidase and a SidJ analogue compared with control EVs. Virulent extracellular vesicles induced higher expression of TLR4 and Dectin-1 than control EVs in macrophages and dendritic cells (DCs). In opposition, a lower TLR2 expression was induced by virulent EVs. Additionally, virulent EVs induced lower expression of CD80, CD86 and TNF-α, but promoted a higher expression of IL-6 and IL-10, suggesting that EVs isolated from virulent -yeast promote a milder DCs and macrophage maturation. Herein, we showed that EVs from virulent fungi stimulated a higher frequency of Th1/Tc1, Th17, and Treg cells, which gives new insights into fungal extracellular vesicles. Taken together, our results suggest that utilizes its EVs as virulence bags that manipulate the immune system in its favour, creating a milder immune response and helping with fungal evasion from the immune system.
Topics: Animals; Toll-Like Receptor 4; Proteome; Paracoccidioidomycosis; Extracellular Vesicles; Virulence Factors; Paracoccidioides; Lectins, C-Type
PubMed: 38511558
DOI: 10.1080/21505594.2024.2329573 -
Frontiers in Immunology 2024Immune checkpoint pathways, i.e., coinhibitory pathways expressed as feedback following immune activation, are crucial for controlling an excessive immune response....
Immune checkpoint pathways, i.e., coinhibitory pathways expressed as feedback following immune activation, are crucial for controlling an excessive immune response. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) are the central classical checkpoint inhibitory (CPI) molecules used for the control of neoplasms and some infectious diseases, including some fungal infections. As the immunosuppression of severe paracoccidioidomycosis (PCM), a chronic granulomatous fungal disease, was shown to be associated with the expression of coinhibitory molecules, we hypothesized that the inhibition of CTLA-4 and PD-1 could have a beneficial effect on pulmonary PCM. To this end, C57BL/6 mice were infected with yeasts and treated with monoclonal antibodies (mAbs) α-CTLA-4, α-PD-1, control IgG, or PBS. We verified that blockade of CTLA-4 and PD-1 reduced the fungal load in the lungs and fungal dissemination to the liver and spleen and decreased the size of pulmonary lesions, resulting in increased survival of mice. Compared with PBS-treated infected mice, significantly increased levels of many pro- and anti-inflammatory cytokines were observed in the lungs of α-CTLA-4-treated mice, but a drastic reduction in the liver was observed following PD-1 blockade. In the lungs of α-CPI and IgG-treated mice, there were no changes in the frequency of inflammatory leukocytes, but a significant reduction in the total number of these cells was observed. Compared with PBS-treated controls, α-CPI- and IgG-treated mice exhibited reduced pulmonary infiltration of several myeloid cell subpopulations and decreased expression of costimulatory molecules. In addition, a decreased number of CD4+ and CD8+ T cells but sustained numbers of Th1, Th2, and Th17 T cells were detected. An expressive reduction in several Treg subpopulations and their maturation and suppressive molecules, in addition to reduced numbers of Treg, TCD4+, and TCD8+ cells expressing costimulatory and coinhibitory molecules of immunity, were also detected. The novel cellular and humoral profiles established in the lungs of α-CTLA-4 and α-PD-1-treated mice but not in control IgG-treated mice were more efficient at controlling fungal growth and dissemination without causing increased tissue pathology due to excessive inflammation. This is the first study demonstrating the efficacy of CPI blockade in the treatment of pulmonary PCM, and further studies combining the use of immunotherapy with antifungal drugs are encouraged.
Topics: Mice; Animals; Paracoccidioidomycosis; CTLA-4 Antigen; Programmed Cell Death 1 Receptor; Mice, Inbred C57BL; Patient Acuity; Immunoglobulin G
PubMed: 38500881
DOI: 10.3389/fimmu.2024.1347318