-
Antonie Van Leeuwenhoek May 2020Paracoccidiodomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The disease requires long and... (Review)
Review
Paracoccidiodomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. The disease requires long and complicated treatment. The aim of this review is to address the fungal virulence factors that could be the target of the development of new drugs for PCM treatment. Virulence factors favoring the process of fungal infection and pathogenicity are considered as a microbial attribute associated with host susceptibility. P. brasiliensis has some known virulence factors which are 43 kDa glycoprotein (gp 43) which is an important fungal antigen, 70 kDa glycoprotein (gp 70), the carbohydrates constituting the fungal cell wall α-1,3, glucan and β-1,3-glucan, cell adhesion molecules and the presence of melanin pigments. The discovery and development of drugs that interact with these factors, such as inhibitors of β-1,3-glucan, reduced synthesis of gp 43, inhibitors of melanin production, is of great importance for the treatment of PCM. The study of virulence factors favors the understanding of pathogen-host relationships, aiming to evaluate the possibility of developing new therapeutic targets and mechanisms that these molecules play in the infectious process, favoring the design of a more specific treatment for this disease.
Topics: Animals; Antifungal Agents; Cell Wall; Central America; Fungal Proteins; Glucans; Glycoproteins; Host-Pathogen Interactions; Humans; Melanins; Paracoccidioides; Paracoccidioidomycosis; Prevalence; South America; Virulence Factors
PubMed: 31902009
DOI: 10.1007/s10482-019-01382-5 -
Journal of Fungi (Basel, Switzerland) Feb 2021The dimorphic fungi of the genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in... (Review)
Review
The dimorphic fungi of the genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of spp. This review describes the most relevant biological features of spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.
PubMed: 33557381
DOI: 10.3390/jof7020116 -
Journal of Fungi (Basel, Switzerland) Apr 2022This review discusses the inclusion of sex and gender variables in studies of fungal infections in humans at the pathogen, host, and antifungal trial levels. The mating... (Review)
Review
This review discusses the inclusion of sex and gender variables in studies of fungal infections in humans at the pathogen, host, and antifungal trial levels. The mating type of some fungi, or perhaps more likely the absence of the other, appears to be associated with some infections. Sexual and parasexual reproduction of some fungi is an important mechanism for the development of antifungal drug resistance. Host sex or gender influences the incidence of some infections such as aspergillosis, cryptococcosis, paracoccidioidomycosis, dermatophytosis, and candidiasis due to differences in immune response, behavior, and awareness for early detection and treatment. Participant sex (and age) is relevant not only in clinical antifungal trials but also in preclinical studies. The dimensions of sex and gender are important determinants throughout the fungal infection process and in approaches to prevent or treat these infections, as well as in development of antifungal drugs. Failure to consider sex and gender may be detrimental to the holistic understanding of the processes involved in fungal infection.
PubMed: 35628717
DOI: 10.3390/jof8050461 -
Brazilian Journal of Microbiology :... Sep 2023Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by the thermodimorphic fungi Paracoccidioides spp. Their distribution is highly variable....
BACKGROUND AND OBJECTIVE
Paracoccidioidomycosis (PCM) is a systemic fungal disease caused by the thermodimorphic fungi Paracoccidioides spp. Their distribution is highly variable. Paracoccidioides lutzii is predominantly found in North and Middle-West Brazil and Ecuador. This study evaluated the clinicopathological characteristics of 10 patients diagnosed with PCM caused by P. lutzii in a reference center located in southeastern Brazil.
DESIGN
Double immunodiffusion assay (DID) was used to investigate 35 patients' sera with negative serology for P. brasiliensis against a P. lutzii CFA (cell-free antigen).
RESULTS
Out of the 35 retested patients, 10 (28.6%) were positive for P. lutzii CFA. Four patients did not report any displacement to P. lutzii endemic areas. Our results reinforce the importance of using different antigens when testing patients with clinical manifestations of PCM and negative serological tests for P. brasiliensis, primarily in cases of the report of displacement to or former residence in P. lutzii endemic regions.
CONCLUSIONS
The availability of tests for different Paracoccidioides species antigens is fundamental for reaching an adequate diagnosis, patient follow-up, and definition of prognosis.
Topics: Humans; Paracoccidioidomycosis; Paracoccidioides; Brazil; Antigens, Fungal
PubMed: 37289316
DOI: 10.1007/s42770-023-01019-w -
Cureus Jan 2022Paracoccidioidomycosis is a systemic fungal disease caused by the dimorphic species endemic to South America. Infection classically presents with pulmonary, mucosal,...
Paracoccidioidomycosis is a systemic fungal disease caused by the dimorphic species endemic to South America. Infection classically presents with pulmonary, mucosal, or reticuloendothelial involvement, though other organs can be involved. Central nervous system involvement is rare, and almost universally reported within the endemic area for the fungus. We present a 60-year-old Brazilian male who complained of occipital headache, ataxia, dysmetria, and dysarthria for two months, diagnosed with neuroparacoccidioidomycosis in Houston, Texas. The patient had a cerebellar mass and a left pulmonary spiculated apical mass suspicious for a lung metastatic malignancy and a preliminary histological report consistent with invasive cryptococcosis. The patient's work and travel history were paramount in achieving the final diagnosis.
PubMed: 35165582
DOI: 10.7759/cureus.21129 -
Journal of Fungi (Basel, Switzerland) Aug 2021Clinical observations have long suggested that women are protected against paracoccidioidomycosis. 17β-estradiol, the main female estrogen, inhibits conidia-to-yeast...
Clinical observations have long suggested that women are protected against paracoccidioidomycosis. 17β-estradiol, the main female estrogen, inhibits conidia-to-yeast transformation (C-to-Y), which is required for the infection establishment. However, experiments in murine models have yielded conflicting results, suggesting that C-to-Y inhibition, alone, fails to explain the female-associated protection and that sexual hormones may also act by modulating the host's immune responses. Therefore, this issue remains unsolved. Strikingly, no studies have compared the severity of paracoccidioidomycosis between men and women. This retrospective case-control study compared 36 women with 72 age-matched men for clinical-demographic, laboratory, and chest imaging findings. Overall, paracoccidioidomycosis in women presented the main features described in the acute/subacute and chronic forms seen in men. Women also showed similar demographic features and clinical-laboratory and imaging severity scores as men. We additionally reviewed 58 paracoccidioidin skin test surveys undertaken by volunteers from endemic areas. Data accumulated from 10.873 tests showed that females and males are infected with similar magnitudes (21.9% vs. 25.2%) and that reactivity steadily increased with age, peaking after the age of 60. We discuss the paradox of similar infection rates but much lower disease prevalence in women, considering the current pathogenetic views of paracoccidioidomycosis, and we raise alternative hypotheses to account for this paradox.
PubMed: 34436194
DOI: 10.3390/jof7080655 -
Mycoses Feb 2023Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of... (Review)
Review
BACKGROUND
Advanced neuroimaging demonstrated that neurological involvement occurs in up to 30% of paracoccidioidomycosis (PCM) cases. Current knowledge of neuroparacoccidioidomycosis (NPCM) is based on a 2009 systematic review. However, in the last decade, several new cases have been published, with modern neuroimaging techniques.
OBJECTIVES
We believe a new systematic review is needed to summarise these advances.
METHODS
We searched PubMed/MEDLINE, Embase and LILACS for studies from January 2010 to May 2022. Case series and case reports of NPCM were included. We performed a metaproportion to estimate a summary proportion with 95% confidence intervals (CI).
RESULTS
Thirty-four studies including 104 patients were evaluated. We combined our data with the results from the previous review that included 257 cases, totalling 361 patients. We found no new important demographic, clinical or laboratory characteristics. On magnetic resonance imaging (MRI), we found that 72% (95%CI: 38-91) had hyperintensity on T1-weighted image; 84% (95%CI: 71%-92%) had hypointensity on T2-weighted image; 80% (95%CI: 66-89) had contrast enhancement with the classical ring-enhancing pattern. All 8 patients undergoing spectroscopy presented lipid peaks. We found a 16% mortality, lower than in the previous review (44%).
CONCLUSION
NPCM presents a characteristic pattern on MRI that may help to differentiate it from other causes of single or multiple brain lesions. Albeit there is a frequent pattern, it is not specific, as other granulomatous diseases may show similar findings. Advances in neuroimaging with early diagnosis and appropriate management of the disease may have contributed to reducing its mortality.
Topics: Humans; Brain; Central Nervous System Fungal Infections; Magnetic Resonance Imaging; Neuroimaging; Paracoccidioidomycosis
PubMed: 36062632
DOI: 10.1111/myc.13525 -
Revista Da Sociedade Brasileira de... 2021
Topics: Humans; Paracoccidioidomycosis; Spinal Cord Diseases
PubMed: 33950124
DOI: 10.1590/0037-8682-0115-2021 -
Clinical and Translational Medicine Nov 2020
PubMed: 33252858
DOI: 10.1002/ctm2.213 -
Transboundary and Emerging Diseases May 2021Armadillos are specialist diggers and their burrows are used to find food, seek shelter and protect their pups. These burrows can also be shared with dozens of...
Armadillos are specialist diggers and their burrows are used to find food, seek shelter and protect their pups. These burrows can also be shared with dozens of vertebrate and invertebrate species and; consequently, their parasites including the zoonotics. The aim of this study was to diagnose the presence of zoonotic parasites in four wild-caught armadillo species from two different Brazilian ecosystems, the Cerrado (Brazilian savanna) and the Pantanal (wetland). The investigated parasites and their correspondent diseases were: Toxoplasma gondii (toxoplasmosis), Trypanosoma cruzi (Chagas disease), Leishmania spp., (leishmaniasis), Paracoccidioides brasiliensis (Paracoccidioidomicosis) and Mycobacterium leprae (Hansen's disease). Forty-three free-living armadillos from Pantanal and seven road-killed armadillos from the Cerrado were sampled. Trypanosoma cruzi DTU TcIII were isolated from 2 out of 43 (4.65%) armadillos, including one of them also infected with Trypanosoma rangeli. Antibodies anti-T. gondii were detected in 13 out of 43 (30.2%) armadillos. All seven armadillos from Cerrado tested positive for P. brasiliensis DNA, in the lungs, spleen, liver fragments. Also, by molecular analysis, all 43 individuals were negative for M. leprae and Leishmania spp. Armadillos were infected by T. cruzi, T. rangeli, P. brasiliensis and presented seric antibodies to T. gondii, highlighting the importance of those armadillos could have in the epidemiology of zoonotic parasites.
Topics: Animals; Armadillos; Brazil; Chagas Disease; Female; Leishmania; Leishmaniasis; Leprosy; Male; Mycobacterium leprae; Paracoccidioides; Paracoccidioidomycosis; Species Specificity; Toxoplasma; Toxoplasmosis, Animal; Trypanosoma cruzi; Zoonoses
PubMed: 32964690
DOI: 10.1111/tbed.13839