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Endemic systemic mycoses such as blastomycosis, coccidioidomycosis, histoplasmosis, talaromycosis, paracoccidioidomycosis are emerging as an important cause of morbidity and mortality worldwide. We conducted a systematic review on endemic systemic mycoses reported in Italy from 1914 to nowadays. We found out: 105 cases of histoplasmosis, 15 of paracoccidioidomycosis, 10 of coccidioidomycosis, 10 of blastomycosis and 3 of talaromycosis. Most cases have been reported in returning travelers and expatriates or immigrants. Thirtytwo patients did not have a story of traveling to an endemic area. Fortysix subjects had HIV/AIDS. Immunosuppression was the major risk factor for getting these infections and for severe outcomes. We provided an overview on microbiological characteristics and clinical management principles of systemic endemic mycoses with a focus on the cases reported in Italy. [ABSTRACT FROM AUTHOR]

Human cysticercosis is caused by the ingestion of eggs of the pork tapeworm (Taenia solium) (1). The ingested eggs evolve into onconspheres that cross the intestinal mucous membrane, distributing themselves to the muscles, making man their intermediate host (3). The condition of rare systemic infestation is known as disseminated cysticercosis. [ABSTRACT FROM AUTHOR]

Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. However, the diagnosis of fungal infections represents a great challenge because of the decline in the expertise needed for identifying fungi, and a reduced number of instruments and assays specific to fungal identification. Unfortunately, time of diagnosis is one of the most important risk factors for mortality rates from many of the systemic mycoses. In addition, phenotypic and biochemical identification methods are often time-consuming, which has created an increasing demand for new methods of fungal identification. In this review, we discuss the current context of the diagnosis of the main systemic mycoses and propose alternative approaches for the identification of new targets for fungal pathogens, which can help in the development of new diagnostic tests. [ABSTRACT FROM AUTHOR]

In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality., (Copyright © 2024. Published by Elsevier Inc.)

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes., (Copyright © 2024. Published by Elsevier Inc.)

The physiopathologic characteristics of COVID-19 (high levels of inflammatory cytokines and T-cell reduction) promote fungal colonization and infection, which can go unnoticed because the symptoms in both diseases are very similar. The objective of this work was to study the current epidemiology of systemic mycosis in COVID-19 times. A literature search on the subject (January 2020–February 2021) was performed in PubMed, Embase, Cochrane Library, and LILACS without language restrictions. Demographic data, etiological agent, risk factors, diagnostic methods, antifungal treatment, and fatality rate were considered. Eighty nine publications were found on co-infection by COVID-19 and pneumocystosis, candidiasis, aspergillosis, mucormycosis, coccidioidomycosis, or histoplasmosis. In general, the co-infections occurred in males over the age of 40 with immunosuppression caused by various conditions. Several species were identified in candidiasis and aspergillosis co-infections. For diagnosis, diverse methods were used, from microbiological to molecular. Most patients received antifungals; however, the fatality rates were 11–100%. The latter may result because the clinical picture is usually attributed exclusively to SARS-CoV-2, preventing a clinical suspicion for mycosis. Diagnostic tests also have limitations beginning with sampling. Therefore, in the remainder of the pandemic, these diagnostic limitations must be overcome to achieve a better patient prognosis. [ABSTRACT FROM AUTHOR]

Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. However, the diagnosis of fungal infections represents a great challenge because of the decline in the expertise needed for identifying fungi, and a reduced number of instruments and assays specific to fungal identification. Unfortunately, time of diagnosis is one of the most important risk factors for mortality rates from many of the systemic mycoses. In addition, phenotypic and biochemical identification methods are often time-consuming, which has created an increasing demand for new methods of fungal identification. In this review, we discuss the current context of the diagnosis of the main systemic mycoses and propose alternative approaches for the identification of new targets for fungal pathogens, which can help in the development of new diagnostic tests.

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions. [ABSTRACT FROM AUTHOR]

Blastomycosis is a systemic fungal infection that most commonly affects dogs and humans. The disease is thought to be endemic in southern regions of Michigan, USA, but epidemiologic investigations have not been reported in detail for this state. The primary aims of this study were to investigate the prevalence and distribution of canine blastomycosis cases in Michigan and to identify risk factors for infection. Over 200 primary care veterinary clinics throughout the state were surveyed regarding blastomycosis prevalence, and demographic information was obtained from medical records of affected dogs that were evaluated at these clinics. A retrospective case control study was conducted for an additional 49 dogs with blastomycosis that were evaluated at specialty referral centers located in the southern mid-Michigan region. Prevalence rates were calculated for each county, and cases were mapped using geocoding software. Univariable and multivariable analyses were used to identify risk factors for infection. Prevalence rates were ≥100 cases per 100,000 dogs in five counties. Most blastomycosis cases originated from the Upper Peninsula or from a high-density area in the northern Lower Peninsula. Multivariable regression analysis identified travel or residence north of the 45th parallel as a strong risk factor for infection (P  < .001). Blastomycosis was uncommon in southern counties. These results refute previous speculations and should be of value to both human and animal health. Given that many heightened risk areas are popular tourist destinations, practitioners across the USA should be mindful of the spatial distribution of blastomycosis in Michigan. [ABSTRACT FROM AUTHOR]

Disease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti–granulocyte macrophage colony-stimulating factor autoantibodies. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis is a systemic mycosis caused in most cases by Paracoccidioides brasiliensis with a high prevalence in South America, especially in Brazil. Studies show an increasing incidence of this infection in different states, as well as a significant mortality rate that represents 50% of the total deaths from fungal diseases in the country. OBJECTIVES: To conduct a case study of a patient diagnosed with Paracoccidioidomycosis, to analyze the instituted therapies and their respective results. METHODOLOGY: This is a descriptive case report research. The patient data will be collected and correlated with the existing literature, in order to obtain a comparative analysis with the other cases already described. [ABSTRACT FROM AUTHOR]

The physiopathologic characteristics of COVID-19 (high levels of inflammatory cytokines and T-cell reduction) promote fungal colonization and infection, which can go unnoticed because the symptoms in both diseases are very similar. The objective of this work was to study the current epidemiology of systemic mycosis in COVID-19 times. A literature search on the subject (January 2020–February 2021) was performed in PubMed, Embase, Cochrane Library, and LILACS without language restrictions. Demographic data, etiological agent, risk factors, diagnostic methods, antifungal treatment, and fatality rate were considered. Eighty nine publications were found on co-infection by COVID-19 and pneumocystosis, candidiasis, aspergillosis, mucormycosis, coccidioidomycosis, or histoplasmosis. In general, the co-infections occurred in males over the age of 40 with immunosuppression caused by various conditions. Several species were identified in candidiasis and aspergillosis co-infections. For diagnosis, diverse methods were used, from microbiological to molecular. Most patients received antifungals; however, the fatality rates were 11–100%. The latter may result because the clinical picture is usually attributed exclusively to SARS-CoV-2, preventing a clinical suspicion for mycosis. Diagnostic tests also have limitations beginning with sampling. Therefore, in the remainder of the pandemic, these diagnostic limitations must be overcome to achieve a better patient prognosis.

Abstract The need for better antifungal therapy is commonly accepted in view of the high mortality rates associated with systemic infections, the low number of available antifungal classes, their associated toxicity and the increasing number of infections caused by strains with natural or acquired resistance. The urgency to expand the range of therapeutic options for the treatment of fungal infections has led researchers in recent decades to seek alternative antifungal targets when compared to the conventional ones currently used. Although new potential targets are reported, translating the discoveries from bench to bedside is a long process and most of these drugs fail to reach the patients. In this review, we discuss the development of antifungal drugs focusing on the approach of drug repurposing and the search for novel drugs for classical targets, the most recently described gene targets for drug development, the possibilities of immunotherapy using antibodies, cytokines, therapeutic vaccines and antimicrobial peptides. [ABSTRACT FROM AUTHOR]

Summary: Epidemiological studies on endemic mycosis can be improved using molecular biology techniques to elucidate the role of bats as reservoirs and vectors of pathogenic fungi for infection of other animals and humans. The objective of this study was to explore the presence of Histoplasma capsulatum, Cryptococcus spp. and Paracoccidioides brasiliensis in insectivorous, frugivorous and nectarivorous bats collected in urban areas. We analysed 172 bats collected by the Epidemiological Surveillance Agency in 12 municipalities of the Midwest region of the state of São Paulo, Brazil. Spleen, liver, intestine and lung samples were subjected to microbiological culture and nested PCR analyses. Prevalence of H. capsulatum infection was 8.1% (14/172), with one bat found to be positive by fungal culturing, 12 positive by nested PCR and one positive by both methods. Two insectivorous bats were found positive by nested PCR for Cryptococcus spp., one in the spleen and the other in the spleen and lung. Two insectivorous bats showed natural infection by P. brasiliensis, in the spleen of one bat and the spleen and liver of the other. Our results reinforce the importance of bats as fungal dispersers in urban environments and the importance of constant epidemiologic surveillance because these synanthropic animals are in close contact with humans and animals. [ABSTRACT FROM AUTHOR]

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

It has been shown that some of the mycotic infections especially systemic mycoses show increased male susceptibility and some steroids have been known to influence the immune response. Researchers found that some fungi including yeasts use "message molecules" including hormones to elicit certain responses, especially in the sexual cycle, but until recently no evidence was available to link specific hormonal evidence to this pronounced sex ratio. More evidence needed to demonstrate that a steroid (s) might in some manner influence the pathogenicity of the fungus in vivo. Therefore, the aim of this review paper is to shed some light on this subject along with effort to make mycologists more aware of this research as a stimulus for the explore of new ideas and design further research in this area of medical mycology.

Paracoccidioidomycosis (PCM) is the most prevalent deep mycosis in Latin America and is caused by fungi from the Paracoccidioides genus. Virulence factors are important fungal characteristics that support the development of disease. Aspartyl proteases (Saps) are virulence factors in many human fungal pathogens that play an important role in the host invasion process. We report here that immunization with recombinant Sap from Paracoccidioides brasiliensis (rPbSap) imparted a protective effect in an experimental PCM model. The rPbSap-immunized mice had decreased fungal loads, and their lung parenchyma were notably preserved. An aspartyl protease inhibitor (pepstatin A) significantly decreased pulmonary injury and reduced fungal loads in the lung. Additionally, we observed that pepstatin A enhanced the fungicidal and phagocytic profile of macrophages against P. brasiliensis. Furthermore, PbSAP expression was highly altered by environmental conditions, including thermal stress, dimorphism switching and low pH. Hence, our data suggest that PbSap is an important virulence regulator in P. brasiliensis. [ABSTRACT FROM AUTHOR]

Paracoccidioides is a thermodimorphic fungus that causes Paracoccidioidomycosis (PCM) – an endemic systemic mycosis in Latin America. The genus comprises several phylogenetic species which present some genetic and serological differences. The diversity presented among isolates of the same genus has been explored in several microorganisms. There have also been attempts to clarify differences that might be related to virulence existing in isolates that cause the same disease. In this work, we analyzed the secretome of two isolates in the Paracoccidioides genus, isolates Pb 01 and Pb Epm83, and performed infection assays in macrophages to evaluate the influence of the secretomes of those isolates upon an in vitro model of infection. The use of a label-free proteomics approach (LC-MS E ) allowed us to identify 92 proteins that are secreted by those strains. Of those proteins, 35 were differentially secreted in Pb 01, and 36 in Pb Epm83. According to the functional annotation, most of the identified proteins are related to adhesion and virulence processes. These results provide evidence that different members of the Paracoccidioides complex can quantitatively secrete different proteins, which may influence the characteristics of virulence, as well as host-related processes. [ABSTRACT FROM AUTHOR]

We report 4 patients in North America with disease caused by Emergomyces canadensis, a newly proposed species of pathogenic dimorphic fungus. Affected persons were immunocompromised; lived in Saskatchewan, Colorado, and New Mexico; and had systemic disease involving blood, skin, cervix, lung, and lymph node. Two cases were fatal. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis causes substantial illness and death in the United States each year. Although most cases are sporadic, outbreaks provide insight into the clinical and environmental features of coccidioidomycosis, high-risk activities, and the geographic range of Coccidioides fungi. We identified reports published in English of 47 coccidioidomycosis outbreaks worldwide that resulted in 1,464 cases during 1940-2015. Most (85%) outbreaks were associated with environmental exposures; the 2 largest outbreaks resulted from an earthquake and a large dust storm. More than one third of outbreaks occurred in areas where the fungus was not previously known to be endemic, and more than half of outbreaks involved occupational exposures. Coccidioidomycosis outbreaks can be difficult to detect and challenging to prevent given the unknown effectiveness of environmental control methods and personal protective equipment; therefore, increased awareness of coccidioidomycosis outbreaks is needed among public health professionals, healthcare providers, and the public. [ABSTRACT FROM AUTHOR]

Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States. [ABSTRACT FROM AUTHOR]

Background: Histoplasma capsulatum is a dimorphic fungus predominately found in soils enriched with bird and bat excreta. Although several cases of histoplasmosis have been reported in India, diagnosis using cytology has been done in very few cases.Case Presentation: We report here a case of disseminated histoplasmosis in a 46-year-old Indian man.Conclusion: Skin scrape cytology is a simple, safe, and rapid technique to establish the initial diagnosis, thus promoting early treatment and favorable outcome, in cutaneous fungal infections. [ABSTRACT FROM AUTHOR]

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Coccidioidomycosis is usually acquired by inhalation of spores of Coccidioides immitis and C. posadasii . The disease ranges from a self-limited acute pneumonia (Valley Fever) to a disseminated disease. We present a 44-year-old healthy male who had patchy hair loss of several months duration resembling discoid lupus. He developed a firm non-scaly red plaque on the right forehead. Initial biopsy showed spongiotic dermatitis, and he was treated with systemic steroids. He then developed forehead and periorbital cellulitis and was treated with systemic antibiotics. A second biopsy showed fungal hyphae, and he was treated with itraconazole 200 mg bid for 4 months beyond clinical resolution. A year later, he presented with intermittent swelling of the right forehead lesion and worsening of the scalp lesions. A forehead biopsy showed interface dermatitis and negative PAS stain for fungi. Scalp biopsy was highly suggestive of discoid lupus and he was started on plaquenil. Many months later, a third biopsy showed fungal infection, and the culture grew C. immitis . He was treated with itraconazole. Retrospectively, the patient gave a history of Valley fever 6 years back when he was in Arizona, USA. [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background Disseminated cutaneous histoplasmosis ( DCH) is one of the manifestations of systemic histoplasmosis infection in HIV-positive patients. Interaction between host immune status and histoplasmosis infection is still poorly understood. It is thought that immune status, represented by CD4 counts, may be correlated with clinical and histopathological findings. Objective To correlate the CD4 counts with the different clinical and histopathological findings in cutaneous histoplasmosis. Methods This was a serial case report of seven HAART-treated HIV positive patients with disseminated histoplasmosis observed within the period of January 2004 through December 2014 from the Dermatology and Venereology Department, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients came with different complaints and clinical findings. CD4 counts were recorded prior to lesion biopsy. Results The CD4 counts were independent from clinical morphology and distribution of lesions. Lower CD4 counts were associated with the presence of intraepidermal yeast-like cells, whereas there is the ability of forming granulomas at higher CD4 counts. Conclusion CD4 count correlates to histopathological findings of cutaneous histoplasmosis. [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Micologia is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Paracoccidioidomycosis ( PCM) is a systemic mycosis that occurs in several Latin American countries, especially in Brazil. It is caused by the thermo-dimorphic fungus Paracoccidioides spp. Serological studies to detect animal infection represent an excellent strategy for data on the agent's ecology. Although the state of Rio Grande do Sul ( RS) is an endemic area for PCM in humans, there is scarce information available on the ecology of the agent in the region. This study aimed to investigate the infection by Paracoccidioides lutzii in animals living in RS, Brazil. A total of 85 wild mammals, 200 horses and 196 domestic dogs, previously tested for infection by P. brasiliensis, were included in this study. Serum samples from the animals were tested by ELISA to detect anti- P. lutzii antibodies. From the 481 animals tested, 105 (21.8%) were seropositive for IgG anti- P. lutzii. Of these, 54 were also positive for P. brasiliensis. A total of 11 horses (10.5%), 30 dogs (28.8%) and 10 wild mammals (9.5%) were positive only for P. lutzii (n=51). The detection of anti- P. lutzii antibodies in animals of RS suggests that the fungus can be found in southern Brazil, despite being described mainly in the midwest and southeast of the country. [ABSTRACT FROM AUTHOR]

Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South America; Histoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp., which are also fungal agents of deadly infections. Nowadays, the actual tendency of therapy is the development of a pan-fungal vaccine. This is, however, not easy because of the complexity of eukaryotic cells and the particularities of different species and isolates. Albeit there are several experimental vaccines being studied, we will focus mainly on peptide vaccines or epitopes of T-cell receptors inducing protective fungal responses. These peptides can be carried by antibody inducing β-(1,3)-glucan oligo or polysaccharides, or be mixed with them for administration. The present review discusses the efficacy of linear peptide epitopes in the context of antifungal immunization and vaccine proposition. [ABSTRACT FROM AUTHOR]

Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo. In this review, we provide a discussion about conventional antifungal and nanoantifungal therapies for systemic mycosis. [ABSTRACT FROM AUTHOR]

A case of disseminated histoplasmosis (DH) in a 60-year-old female patient is reported from Jaipur, Rajasthan, India.he patient presented with multiple papules on the skin surrounding the lips, face, torso, trunk, and back. She also complained of growth in the palate. Histoplasmosis was conirmed by biopsy and histopathology of skin and palatal lesions. This case report highlights the presenting features and occurrence of histoplasmosis in nonendemic region in India. [ABSTRACT FROM AUTHOR]

Background: Coccidioidomycosis, a potentially fatal fungal infection, is considered an emergent mycotic disease because of the increased incidence of fungal infections registered over recent years. Infection occurs through the inhalation of arthroconidia from two main species of Coccidioides: Coccidioides immitis and C. posadasii, which are both endemic to arid and semi-arid regions of North America. Coccidioides species not only infect humans but can also infect other mammals (land, aquatic, wild or domestic), reptiles and birds. Objective: To obtain information regarding the habitat of Coccidioides spp. and the animals infected by this fungus and to identify the role that infected animals play as reservoirs and disseminators of this fungus in nature. Materials: A literature review was conducted to identify the habitat of Coccidioides spp. and the infected non-human animal species targeted by this fungus. Results and conclusions: This review allows us to suggest that Coccidioides spp. may be classified as halotolerant organisms; nevertheless, to perpetuate their life cycle, these organisms depend on different animal species (reservoirs) that serve as a link with the environment, by acting as disseminators of the fungi in nature. [ABSTRACT FROM AUTHOR]

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure. [ABSTRACT FROM AUTHOR]

The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin ( AMB), 5-flucytosine (5 FC), fluconazole ( FCZ), voriconazole ( VRZ), itraconazole ( ITZ) and terbinafine ( TRB). Drug interaction chequerboard assay evaluated: AMB + 5 FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii ( VGII) and C. neoformans isolates were found to belong to genotype VNI ( n = 62) and VNII ( n = 4). C. neoformans VNII was significantly less susceptible than VNI ( P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ ( P < 0.0001). C. deuterogattii was less susceptible than C. neoformans VNI for FCZ ( P = 0.0170), ITZ ( P < 0.0001) and TRB ( P = 0.0090). The combination FCZ + TRB showed 95.16% of synergistic effect against C. neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5 FC. [ABSTRACT FROM AUTHOR]

Paracoccidioides brasiliensis and P. lutzii belong to a group of thermodimorphic fungi and cause paracoccidioidomycosis (PCM), which is a human systemic mycosis endemic in South and Central America. Patients with this mycosis are commonly treated with amphotericin B (AmB) and azoles. The study of fungal virulence and the efficacy and toxicity of antifungal drugs has been successfully performed in a Galleria mellonella infection model. In this work, G. mellonella larvae were infected with two Paracoccidioides spp. and the efficacy and toxicity of AmB and itraconazole were evaluated in this model for the first time. AmB and itraconazole treatments were effective in increasing larval survival and reducing the fungal burden. The fungicidal and fungistatic effects of AmB and itraconazole, respectively, were observed in the model. Furthermore, these effects were independent of changes in haemocyte number. G. mellonella can serve as a rapid model for the screening of new antifungal compounds against Paracoccidioides and can contribute to a reduction in experimental animal numbers in the study of PCM. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies with small sample sizes have shown a wide range of complication rates and no study has investigated the yield of computed tomography-guided transthoracic core needle biopsies (CTTCB) for coccidioidomycosis. To better assess the safety, accuracy, and risk factors for complications of CTTCB of pulmonary nodules, we conducted a retrospective study at a high-volume academic center in an endemic coccidioidomycosis area. Methods: We conducted a retrospective study of 203 patients who underwent CTTCB of pulmonary nodules between December 2010 and May 2013. We collected demographics, clinical, and radiographic data. Each case was reviewed for complications. Diagnostic accuracy was assessed by comparing CTTCB with final diagnoses. Results: The overall complication rate was 25 %. Pneumothorax accounted for 24 % of complications with 7 % of pneumothoraces requiring chest tube. 1.5 % were complicated by hemoptysis but none required blood transfusions. There was an association between complications and age, presence of emphysema on CT, traversed lung length, and lesion depth. The overall sensitivity of the CTTCB for all types of lung cancer was 93 %, and specificity of 100 %. The positive predictive value of CTTCB for lung cancer was 100 %. The sensitivity and specificity of CTTCB for a coccidiomycosis lung nodule was 83 % with a specificity of 100 % with a PPV of 100 %. Conclusion: Our study demonstrates that CTTCB is a relatively safe method for evaluating lung nodules and highly accurate in evaluating lung nodules due to coccidioidomycosis in an endemic area. The primary risk factors for complications from CTTCB are the presence of emphysema on CT scan, lesion depth, and traversed lung length. [ABSTRACT FROM AUTHOR]

Background: Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-γ-producing Th1 cells. It has been proposed that Paracoccidioides brasiliensis is able to modulate the immune response towards a permissive state and that the thymus plays a major role in it.Methods: In this paper, we show that acute infection of BALB/c mice with P. brasiliensis virulent isolate (Pb18) might cause alterations in the thymic environment as well as the prohibitive TCR-expressing T cells in the spleens.Results: After seven days of infection, we found yeast cells on the thymic stroma, the thymic epithelial cells (TEC) were altered regarding their spatial-orientation and inflammatory mediators gene expression was increased. Likewise, thymocytes (differentiating T cells) presented higher migratory ability in ex vivo experiments. Notwithstanding, P. brasiliensis-infected mice showed an increased frequency of prohibitive TCR-expressing T cells in the spleens, suggesting that the selection processes that occur in the thymus may be compromised during the acute infection.Conclusion: In this paper, for the first time, we show that acute infection with Paracoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by which P. brasiliensis subverts the immune response towards the chronic infection observed in humans. [ABSTRACT FROM AUTHOR]

Coccidioides species are soil-dwelling fungi endemic to the Southwest U.S.A., especially Arizona and California and Northern Mexico. The cutaneous findings of coccidioidomycosis have a wide range of pathology, which includes organism-specific and reactive processes. Interstitial granulomatous dermatitis (IGD), a granuloma annulare-like reaction, has been described, in a limited form, in association with acute pulmonary coccidioidomycosis. We present a case of chronic, widespread IGD spanning over 9 years in association with an active coccidioidomycosis infection. Similar clinical and histopathological features have been described in association with drug reactions, connective tissue diseases, systemic vasculitis, lymphomas, other infectious diseases and inflammatory bowel disease. Our patient's dramatic presentation and chronic course expands upon the clinical spectrum of IGD occurring in association with pulmonary coccidioidomycosis. While IGD in association with coccidioidomycosis is rare, both dermatologists and general practitioners see IGD reactions, and our case highlights the importance of identifying the underlying driver. [ABSTRACT FROM AUTHOR]

This article explores an alternative conception held by high school and first-year university biology students regarding the structure of the left and right ventricles of the heart and the significance of the left ventricular wall being thicker than the right. The left ventricular wall of the heart is thicker than the right ventricular wall due to greater back pressure from the aorta during systole, and not because of the differences in the length of the pulmonary and systemic circuits, which is the current understanding. We discuss reasons this alternative conception has arisen and present an explanation to address the current understanding. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is worldwide systemic mycoses caused by the dimorphic fungus Histoplasma capsulatum. The isolation and identification of H. capsulatum in culture is the reference test for histoplasmosis diagnosis confirmation. However, in the absence of it, serology has been used as a presumptive diagnosis through antibody and antigen detection. The purpose of the present study was to validate an immunoassay method (western blot) for antibodies detection in the diagnosis of histoplasmosis.Methods: To validate the western blot (WB) a study was conducted using 118 serum samples from patients with histoplasmosis and 118 serum controls collected from January 2000 to December 2013 in residents of the Rio de Janeiro State, Brazil. Diagnostic validation parameters were calculated based on the categorization of results obtained in a 2 × 2 table and subjected to statistical analysis. In addition, the viability of deglycosylated histoplasmin antigen (ptHMIN) onto nitrocellulose membranes previously sensitized was evaluated during the same period.Results: The WB test showed sensitivity of 94.9 %, specificity of 94.1 %, positive predictive value of 94.1 %, negative predictive value of 94.9 %, accuracy of 94.5 %, and almost perfect precision. Besides, the strips have proved to be viable for using at least 5 years after ptHMIN antigen sensitization.Conclusion: Western blot test using ptHMIN provides sensitive, specific, and faster results. Therefore, could be considered a useful tool in the diagnosis of histoplasmosis being used by public health system, even in situations where laboratory facilities are relatively limited. [ABSTRACT FROM AUTHOR]

Key Clinical Message A 39-year-old female patient was presented with acute abdominal pain. Diagnostic laparoscopy revealed extensive granulomas throughout the abdomen. Disseminated TB was suspected, but the biopsies were negative. Due to a high degree of suspicion, a urine antigen test was performed and was strongly positive for histoplasmosis. [ABSTRACT FROM AUTHOR]

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Paracoccidioidomycosis (PCM), is a pulmonary fungal disease whose severity depends on the adequate development of T cell immunity. Although regulatory T (Treg) cells were shown to control immunity against PCM, deleterious or protective effects were described in different experimental settings. To clarify the function of Treg cells in pulmonary PCM, loss-and gain-of-function approaches were performed with Foxp3GFP knock-in mice and immunodeficient Rag1-/- mice, respectively, which were intratracheally infected with 106 yeast cells. The activity of Foxp3-expressing Treg cells in pulmonary PCM was determined in Foxp3GFP transgenic mice. First, it was verified that natural Treg cells migrate to the lungs of infected mice, where they become activated. Depletion of Treg cells led to reduced fungal load, diminished pathogen dissemination and increased Th1/Th2/Th17 immunity. Further, adoptive transfer of diverse T cell subsets to Rag1-/- mice subsequently infected by the pulmonary route demonstrated that isolated CD4+Foxp3+ Treg cells were able to confer some degree of immunoprotection and that CD4+Foxp3- T cells alone reduced fungal growth and enhanced T cell immunity, but induced vigorous inflammatory reactions in the lungs. Nevertheless, transfer of Treg cells combined with CD4+Foxp3- T cells generated more efficient and balanced immune Th1/Th2/Th17 responses able to limit pathogen growth and excessive tissue inflammation, leading to regressive disease and increased survival rates. Altogether, these loss- and gain-of-function approaches allow us to clearly demonstrate the dual role of Treg cells in pulmonary PCM, their deleterious effects by impairing T cell immunity and pathogen eradication, and their protective role by suppressing exacerbated tissue inflammation. [ABSTRACT FROM AUTHOR]