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Infection Aug 2018Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences.
METHODS
One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS.
RESULTS
The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS.
CONCLUSION
Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
Topics: Blood-Brain Barrier; Central Nervous System Fungal Infections; Disease Management; Fungi; Host-Pathogen Interactions; Humans; Risk Factors; Virulence
PubMed: 29785613
DOI: 10.1007/s15010-018-1152-2 -
Expert Review of Respiratory Medicine Jul 2020Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised... (Review)
Review
INTRODUCTION
Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised individuals. The diagnostic approach for many fungal pathogens continues to evolve. Herein, we outline available diagnostic tests for the most common fungal infections with a focus on recent advances and future directions.
AREAS COVERED
We discuss the diagnostic testing methods for angioinvasive molds ( spp. and spp.), invasive yeast ( spp. and ssp.), Pneumocystis, and endemic fungi ( sp., Coccidioides sp., and Hitoplasma sp.). The PubMed-NCBI database was searched within the past 5 years to identify the most recent available literature with dates extended in cases where literature was sparse. Diagnostic guidelines were utilized when available with references reviewed.
EXPERT OPINION
Historically, culture and/or direct visualization of fungal organisms were required for diagnosis of infection. Significant limitations included ability to collect specimens and delayed diagnosis associated with waiting for culture results. Antigen and antibody testing have made great strides in allowing quicker diagnosis of fungal infections but can be limited by low sensitivity/specificity, cross-reactivity with other fungi, and test availability. Molecular methods have a rich history in some fungal diseases, while others continue to be developed.
Topics: Aspergillus; Blastomyces; Candida; Coccidioides; Cryptococcus; Histoplasma; Humans; Lung Diseases, Fungal; Mucor; Pneumocystis; Pneumonia
PubMed: 32290725
DOI: 10.1080/17476348.2020.1753506 -
Cell Sep 2022Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers....
Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 10 tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.
Topics: Biomarkers; Candida; DNA, Fungal; Fungi; Humans; Lung Neoplasms; Mycobiome
PubMed: 36179671
DOI: 10.1016/j.cell.2022.09.015 -
Journal of Fungi (Basel, Switzerland) Jul 2019The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses.... (Review)
Review
The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans spp., including , a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus species, Mucorales, and spp The agricultural application of triazole pesticides has driven an emergence of azole-resistant in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including , which cause disseminated mycoses globally, primarily in HIV infected patients, and and , causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by has emerged as an important disease of felines and people.
PubMed: 31330862
DOI: 10.3390/jof5030067 -
IDCases 2020Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a dimorphic fungus endemic in the soils of the Ohio and Mississippi River Vallys, Great Lakes...
Blastomycosis is a fungal infection caused by Blastomyces dermatitidis, a dimorphic fungus endemic in the soils of the Ohio and Mississippi River Vallys, Great Lakes region, and southeastern United States. It most commonly manifests as a pulmonary infection following inhalation of spores, which causes a broad array of clinical manifestations ranging from asymptomatic infection to fulminant sepsis with acute respiratory distress syndrome and death. Extrapulmonary disease occurs in approximately 25-30% of patients following hematogenous spread from the lungs, with skin being the most common site of exytrapulmonary disease. Here we present a case of disseminated blastomycosis in a healthy 48 year old female.
PubMed: 32489864
DOI: 10.1016/j.idcr.2020.e00786 -
Journal of Fungi (Basel, Switzerland) Aug 2022Blastomycosis, caused by spp., is an endemic mycosis capable of causing significant disease throughout the body. Higher rates of infection are seen in the Mississippi... (Review)
Review
Blastomycosis, caused by spp., is an endemic mycosis capable of causing significant disease throughout the body. Higher rates of infection are seen in the Mississippi and Ohio River valleys, the Great Lakes region of the United States and Canada, much of Africa, and, to a lesser extent, in India and the Middle East. Limited reporting inhibits our true understanding of the geographic distribution of blastomycosis. An estimated 50% of those infected remain asymptomatic. Of those who present with symptomatic disease, pulmonary involvement is most common, while the most common extrapulmonary sites are the skin, bones, genitourinary system, and central nervous system. Itraconazole is the standard therapy for mild-moderate disease. Data for other azoles are limited. Amphotericin is used for severe disease, and corticosteroids are occasionally used in severe disease, but evidence for this practice is limited. Despite increasing incidence and geographic reach in recent years, there are still significant knowledge gaps in our understanding of blastomycosis. Here, we provide an updated review of the epidemiology, clinical presentations, and diagnostic and therapeutic approaches for this infection. We also discuss areas needing further research.
PubMed: 36012812
DOI: 10.3390/jof8080824 -
Cureus Aug 2023Blastomycosis is an endemic mycosis in certain parts of North America. The dimorphic fungus can manifest with both pulmonary and extrapulmonary features. We present...
Blastomycosis is an endemic mycosis in certain parts of North America. The dimorphic fungus can manifest with both pulmonary and extrapulmonary features. We present the case of a 24-year-old African American male with a history of vaping and daily marijuana who presented with hemoptysis and a cough of one-week duration. He was initially treated as community-acquired pneumonia (CAP). The patient had a bronchoscopy with bronchoalveolar lavage (BAL) done in the posterior segment of the right upper lobe. Cultures grew methicillin-resistant (MRSA), followed by in the histopathologic examination. Chronic pulmonary blastomycosis may present with hemoptysis, weight loss, chronic cough, and night sweats, along with upper lobe predominant cavitation. We have to exclude tuberculosis (TB), lung cancer, and chronic pulmonary histoplasmosis. This case epitomizes many classic perils in the identification of pulmonary blastomycosis. The patient was being treated with itraconazole 200 mg BID for 12 months as per infectious disease suggestion. The patient is nine months into treatment. At six months, his chest computed tomography (CT) revealed a reduction in size from 5.0 × 5.3 cm to 4.2 × 4.0 cm. Although there are no articles supporting increased secondary bacterial infections with underlying fungal infections, more research needs to be done to find any associated features.
PubMed: 37779779
DOI: 10.7759/cureus.44288 -
Journal of Fungi (Basel, Switzerland) Jan 2023Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. is the species responsible for most infections in North America and is... (Review)
Review
Blastomycosis is caused by a thermally dimorphic fungus that thrives in moist acidic soil. is the species responsible for most infections in North America and is especially common in areas around the Great Lakes, the St. Lawrence Seaway, and in several south-central and southeastern United States. Other species have more recently been discovered to cause disease in distinct geographic regions around the world. Infection almost always occurs following inhalation of conidia produced in the mold phase. Acute pulmonary infection ranges from asymptomatic to typical community-acquired pneumonia; more chronic forms of pulmonary infection can present as mass-like lesions or cavitary pneumonia. Infrequently, pulmonary infection can progress to acute respiratory distress syndrome that is associated with a high mortality rate. After initial pulmonary infection, hematogenous dissemination of the yeast form of is common. Most often this is manifested by cutaneous lesions, but osteoarticular, genitourinary, and central nervous system (CNS) involvement also occurs. The diagnosis of blastomycosis can be made by growth of the mold phase of spp. in culture or by histopathological identification of the distinctive features of the yeast form in tissues. Detection of cell wall antigens of in urine or serum provides a rapid method for a probable diagnosis of blastomycosis, but cross-reactivity with other endemic mycoses commonly occurs. Treatment of severe pulmonary or disseminated blastomycosis and CNS blastomycosis initially is with a lipid formulation of amphotericin B. After improvement, therapy can be changed to an oral azole, almost always itraconazole. With mild to moderate pulmonary or disseminated blastomycosis, oral itraconazole treatment is recommended.
PubMed: 36675937
DOI: 10.3390/jof9010117 -
Clinics in Chest Medicine Sep 2017The causal agents of blastomycosis, Blastomyces dermatitidis and Blastomyces gilchristii, belong to a group of thermally dimorphic fungi that can infect healthy and... (Review)
Review
The causal agents of blastomycosis, Blastomyces dermatitidis and Blastomyces gilchristii, belong to a group of thermally dimorphic fungi that can infect healthy and immunocompromised individuals. Following inhalation of mycelial fragments and spores into the lungs, Blastomyces spp convert into pathogenic yeast and evade host immune defenses to cause pneumonia and disseminated disease. The clinical spectrum of pulmonary blastomycosis is diverse. The diagnosis of blastomycosis requires a high degree of clinical suspicion and involves culture-based and non-culture-based fungal diagnostic tests. The site and severity of infection, and the presence of underlying immunosuppression or pregnancy, influence the selection of antifungal therapy.
Topics: Antifungal Agents; Blastomycosis; Humans
PubMed: 28797487
DOI: 10.1016/j.ccm.2017.04.006