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PLoS Neglected Tropical Diseases Feb 2021Paracoccidioidomycosis (PCM) is a neglected mycosis most commonly occurring in Latin America. The etiologic agents are thermo dimorphic fungi of the genus...
Paracoccidioidomycosis (PCM) is a neglected mycosis most commonly occurring in Latin America. The etiologic agents are thermo dimorphic fungi of the genus Paracoccidioides, and cause an important granulomatous response in affected tissues. The Botucatu Medical School, from São Paulo State University (UNESP), is a PCM study pole, located in São Paulo State Midwest region, which is classified as a hyperendemic area in the Southeast region in Brazil. This study aimed to perform a retrospective epidemiological, geographical, and clinical analysis by the information available in medical records. It was listed as socio-demographic data along with clinical characteristics from patients diagnosed and treated during a 10-year period in Botucatu, totaling 177 patients with Paracoccidioidomycosis confirmed by the histopathological test. It was observed that the main clinical presentation was the chronic type (76,3%), most commonly identified in white male individuals over the age of 29 years old, smokers, and alcoholics, providing evidences for the first time that white individuals were more affected by the disease, in comparison to non-white individuals that may be more resistant to infection. This data opens new avenues for study within ancestry, resistance and susceptibility in paracoccidioidomycosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brazil; Disease Susceptibility; Ethnicity; Female; Humans; Male; Middle Aged; Paracoccidioides; Paracoccidioidomycosis; Pregnancy; Retrospective Studies; Young Adult
PubMed: 33561154
DOI: 10.1371/journal.pntd.0009086 -
Revista Da Sociedade Brasileira de... 2009This study is the first systematic review of cases of neuroparacoccidioidomycosis available in the literature. Through searches in the MEDLINE and LILACS databases, 257... (Review)
Review
This study is the first systematic review of cases of neuroparacoccidioidomycosis available in the literature. Through searches in the MEDLINE and LILACS databases, 257 cases were found in 81 published studies, mainly after the 1970s-1980s. Approximately 93% of the patients were men, especially farm laborers, with a mean age of 43 years. The characteristic symptoms were motor deficits or intracranial hypertension. The chronic pseudotumoral form predominated. The mean period of evolution was 4.9 months. The lesions were mainly supratentorial (66.8%), located in the frontal and parietal lobes. The diagnosis was determined by biopsy in 57.2% of the cases and neuroimaging methods were used in 64.6% of them. A large proportion of the cases were associated with the pulmonary form of the disease (59.1%). The mortality rate was 44.1%, and 50.1% of the survivors developed sequelae, especially motor impairment. Thus, neuroparacoccidioidomycosis should be considered in the differential diagnosis for expansive and meningoencephalitic processes in the central nervous system, in order to establish early treatment and to avoid disabling sequelae.
Topics: Adolescent; Adult; Aged; Central Nervous System Fungal Infections; Child; Female; Humans; Male; Middle Aged; Paracoccidioidomycosis; Young Adult
PubMed: 20209357
DOI: 10.1590/s0037-86822009000600016 -
Memorias Do Instituto Oswaldo Cruz 2021Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in Latin America that is caused by thermodimorphic fungal species of the Paracoccidioides genus.
BACKGROUND
Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in Latin America that is caused by thermodimorphic fungal species of the Paracoccidioides genus.
OBJECTIVES
In this study, we used quantitative polymerase chain reaction (qPCR) to investigate the expression of genes related to the virulence of Paracoccidioides brasiliensis (Pb18) and P. lutzii (Pb01) strains in their mycelial (M) and yeast (Y) forms after contact with alveolar macrophages (AMJ2-C11 cell line) and fibroblasts (MRC-5 cell line).
METHODS
The selected genes were those coding for 43 kDa glycoprotein (gp43), enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 14-3-3 protein (30 kDa), phospholipase, and aspartyl protease.
FINDINGS
In the Pb18 M form, the aspartyl protease gene showed the highest expression among all genes tested, both before and after infection of host cells. In the Pb18 Y form after macrophage infection, the 14-3-3 gene showed the highest expression among all genes tested, followed by the phospholipase and gp43 genes, and their expression was 50-fold, 10-fold, and 6-fold higher, respectively, than that in the M form. After fibroblast infection with the Pb18 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 25-fold, 10-fold, and 10-fold higher, respectively, than that in the M form. Enolase and aspartyl protease genes were expressed upon infection of both cell lines. After macrophage infection with the Pb01 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 18-fold, 12.5-fold, and 6-fold higher, respectively, than that in the M form.
MAIN CONCLUSIONS
In conclusion, the data show that the expression of the genes analysed may be upregulated upon fungus-host interaction. Therefore, these genes may be involved in the pathogenesis of paracoccidioidomycosis.
Topics: Fibroblasts; Gene Expression; Humans; Latin America; Macrophages; Paracoccidioides; Paracoccidioidomycosis; Virulence Factors
PubMed: 33787770
DOI: 10.1590/0074-02760200592 -
Clinical Infectious Diseases : An... Aug 2016Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel,...
BACKGROUND
Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV.
METHODS
The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed.
RESULTS
Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events.
CONCLUSIONS
ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents.
CLINICAL TRIALS REGISTRATION
NCT00634049.
Topics: Adult; Aged; Antifungal Agents; Blastomycosis; Coccidioidomycosis; Cryptococcosis; Female; Histoplasmosis; Humans; Male; Middle Aged; Mycoses; Nitriles; Paracoccidioidomycosis; Pyridines; Triazoles; Young Adult
PubMed: 27169478
DOI: 10.1093/cid/ciw305 -
Anais Brasileiros de Dermatologia 2013Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression,...
Paracoccidioidomycosis is an acute - to chronic systemic mycosis caused by fungi of the genus Paracoccidioides. Due to its frequent tegument clinical expression, paracoccidioidomycosis is an important disease for dermatologists, who must be up-to-date about it. This article focuses on recent epidemiological data and discusses the new insights coming from molecular studies, as well as those related to clinical, diagnostic and therapeutic aspects. In the latter section, we give particular attention to the guideline on paracoccidioidomycosis organized by specialists in this subject.
Topics: Age Distribution; Brazil; Female; Humans; Male; Paracoccidioidomycosis; Prevalence; Sex Distribution
PubMed: 24173174
DOI: 10.1590/abd1806-4841.20132463 -
Antimicrobial Agents and Chemotherapy Nov 2018Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the genus, which is restricted to Latin America....
Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the genus, which is restricted to Latin America. The infection is acquired through the inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs and tissues. The treatment for PCM is commonly performed via the administration of antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The antifungal toxicity and side effects, in addition to their long treatment times, have stimulated research for new bioactive compounds. Argentilactone is a compound that was isolated from the Brazilian savanna plant , and it has been suggested to be a potent antifungal, inhibiting the dimorphism of and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach via affinity chromatography was the methodology used to explore the interactions between proteins and argentilactone. A total of 109 proteins were identified and classified functionally. The most representative functional categories were related to amino acid metabolism, energy, and detoxification. Argentilactone inhibited the enzymatic activity of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase. Furthermore, argentilactone induces the production of reactive oxygen species and inhibits the biosynthesis of cell wall polymers.
Topics: A549 Cells; Amphotericin B; Antifungal Agents; Brazil; Cell Line, Tumor; Cell Wall; Humans; Itraconazole; Lactones; Paracoccidioides; Paracoccidioidomycosis
PubMed: 30150478
DOI: 10.1128/AAC.00737-18 -
Memorias Do Instituto Oswaldo Cruz 2021Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Etiological agents are Paracoccidioides species that diverge phylogenetically throughout...
BACKGROUND
Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Etiological agents are Paracoccidioides species that diverge phylogenetically throughout South America.
OBJECTIVES
This study aimed to document the epidemiology of PCM in Venezuela.
METHODS
We have performed a retrospective cross-sectional descriptive study in 31,081 clinical records of patients from two reference centres during 65 years (1954-2019).
FINDINGS
PCM diagnosis was confirmed in 745 patients. Chronic PCM was the most prevalent form (90.06% cases); 80.67% were male and the most affected age range was 41-60. Farming and construction were the most prevalent occupation and Miranda State had a higher prevalence. Lung and skin were the most affected organs, followed by oral manifestations. Direct examination, culture and serology showed a high sensibility, and no statistical difference was observed among the diagnostic tools. Out of 17 Paracoccidioides isolates genotyped from Venezuela, one was typed as Paracoccidioides americana and 16 as Paracoccidioides venezuelensis.
MAIN CONCLUSIONS
Clinical manifestations observed, information about the epidemiology and molecular profile is essential not only for diagnosis but also for understanding therapeutic responses to mycotic drugs and prognosis. Therefore, it is necessary to sequence all positive isolated strains in order to confirm the dominance of P. venezuelensis in Venezuela.
Topics: Cross-Sectional Studies; Humans; Male; Paracoccidioides; Paracoccidioidomycosis; Retrospective Studies; Venezuela
PubMed: 34755819
DOI: 10.1590/0074-02760210203 -
Cells Jul 2021Paracoccidioidomycosis (PCM) is a systemic disease caused by spp. PCM is endemic in Latin America and most cases are registered in Brazil. This mycosis affects mainly...
Paracoccidioidomycosis (PCM) is a systemic disease caused by spp. PCM is endemic in Latin America and most cases are registered in Brazil. This mycosis affects mainly the lungs, but can also spread to other tissues and organs, including the liver. Several approaches have been investigated to improve treatment effectiveness and protection against the disease. Extracellular vesicles (EVs) are good antigen delivery vehicles. The present work aims to investigate the use of EVs derived from as an immunization tool in a murine model of PCM. For this, male C57BL/6 were immunized with two doses of EVs plus adjuvant and then infected with . EV immunization induced IgM and IgG in vivo and cytokine production by splenocytes ex vivo. Further, immunization with EVs had a positive effect on mice infected with , as it induced activated T lymphocytes and NKT cell mobilization to the infected lungs, improved production of proinflammatory cytokines and the histopathological profile, and reduced fungal burden. Therefore, the present study shows a new role for EVs in the presence of adjuvant as modulators of the host immune system, suggesting their utility as immunizing agents.
Topics: Animals; Antibodies, Fungal; Antigens, Fungal; Cell Movement; Cytokines; Extracellular Vesicles; Immunization; Immunologic Memory; Lung; Lymphocyte Activation; Male; Mice, Inbred C57BL; Natural Killer T-Cells; Paracoccidioides; Paracoccidioidomycosis; Protective Agents; Reference Standards; Mice
PubMed: 34359982
DOI: 10.3390/cells10071813 -
Epidemiologia E Servicos de Saude :... Aug 2018
Topics: Brazil; Disease Notification; Humans; Paracoccidioidomycosis; Population Surveillance
PubMed: 30133689
DOI: 10.5123/S1679-49742018000500002 -
Immunobiology Jan 2015Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into...
BACKGROUND
Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into understanding the natural course of the disease and its clinical manifestations, hence contributing to the development of preventive measures and treatment proposals. The aim of this study was to evaluate the histopathological and immunological aspects involved in the role of different effector and regulatory responses, as well as the correlation between the TLRs, Galectins, Matrix Metalloproteinases and cytoplasmic proteases of mast cells in this infection.
METHODS
Sixteen biopsy specimens with oral lesions of chronic PCM, as well as 13 sections of normal oral mucosa were analyzed. Histopathological and immunological aspects involved in the role of different effector and regulatory responses were evaluated. Indirect immunohistochemistry was performed for IL-17, IL-10, IL-4, TGF-β, FoxP3, Gal-1, Gal-3, Gal-9, TLR-2, TLR-4, MMP-3 and MMP-9, as well as for chymase and tryptase for mast cells identification. Fibrosis was quantified using Picrosirius.
RESULTS
There was a significant increase in the area of fibrosis and in the number of cells expressing IL-10, IL-4, IL-17, FoxP3, Gal-3, TLR-2, MMP3 and MMP9 in patients with PCM in comparison with patients in the group control. There was no difference in the expression of TGF-β, TLR-4, Gal-1 or Gal-9. Mast cells number was found to be significantly lower in oral chronic PCM when compared to control samples after quantification of mast cells and expression of chymase and tryptase. PCM granulomas were classified to the morphological aspects in organized ou non-organized. Expression of IL-4 in non-organized granulomas was significantly higher.
CONCLUSION
The proteins studied herein appear to play an important role in the development and maintenance of oral lesions of PCM, as well as in the processes of development and progression of lesions caused by the fungus and by the immune response associated with the infection.
Topics: Biopsy; Cell Count; Cytokines; Galectins; Humans; Immunohistochemistry; Mast Cells; Matrix Metalloproteinases; Mouth Diseases; Paracoccidioidomycosis; Toll-Like Receptors
PubMed: 25204704
DOI: 10.1016/j.imbio.2014.08.006