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Modern Pathology : An Official Journal... Jun 2023Invasive fungal infections are an increasingly important cause of morbidity and mortality. We provide a summary of important changes in the epidemiology of invasive... (Review)
Review
Invasive fungal infections are an increasingly important cause of morbidity and mortality. We provide a summary of important changes in the epidemiology of invasive fungal infections, citing examples of new emerging pathogens, expanding populations who are at-risk, and increasing antifungal resistance. We review how human activity and climate change may play a role in some of these changes. Finally, we discuss how these changes create the need for advances in fungal diagnostics. The limitations of existing fungal diagnostic testing emphasize the critically important role of histopathology in the early recognition of fungal disease.
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections
PubMed: 37059227
DOI: 10.1016/j.modpat.2023.100187 -
Journal of Experimental Zoology. Part... Dec 2020Understanding host immune function and ecoimmunology is increasingly important at a time when emerging infectious diseases (EIDs) threaten wildlife. One EID that has... (Review)
Review
Understanding host immune function and ecoimmunology is increasingly important at a time when emerging infectious diseases (EIDs) threaten wildlife. One EID that has emerged and spread widely in recent years is chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), which is implicated unprecedented amphibian declines around the world. The impacts of Bd have been severe for many amphibian species, but some populations have exhibited signs of persistence, and even recovery, in some regions. Many mechanisms may underpin this pattern and amphibian immune responses are likely one key component. Although we have made great strides in understanding amphibian immunity, the complement system remains poorly understood. The complement system is a nonspecific, innate immune defense that is known to enhance other immune responses. Complement activation can occur by three different biochemical pathways and result in protective mechanisms, such as inflammation, opsonization, and pathogen lysis, thereby providing protection to the host. We currently lack an understanding of complement pathway activation for chytridiomycosis, but several studies have suggested that it may be a key part of an early and robust immune response that confers host resistance. Here, we review the available research on the complement system in general as well as amphibian complement responses to Bd infection. Additionally, we propose future research directions that will increase our understanding of the amphibian complement system and other immune responses to Bd. Finally, we suggest how a deeper understanding of amphibian immunity could enhance the conservation and management of amphibian species that are threatened by chytridiomycosis.
Topics: Amphibians; Animals; Batrachochytrium; Complement System Proteins; Mycoses
PubMed: 33052039
DOI: 10.1002/jez.2419 -
Current Opinion in Microbiology Dec 2020Despite the availability of antifungal treatments, fungal infections are still causing morbidity all around the globe with unacceptably high mortality rates. A major... (Review)
Review
Despite the availability of antifungal treatments, fungal infections are still causing morbidity all around the globe with unacceptably high mortality rates. A major driver for the rising incidence of serious fungal infections is due to a substantial increase in immunocompromised individuals with autoimmune diseases, cancers and transplants. Because of growing resistance in fungus to frontline triazole antifungals and the association of fungal disease with the immunocompromised host, adjunctive host-directed therapy is seen as a promising choice to improve patient outcomes. Immunotherapeutic treatments being explored as adjunct therapies to existing antifungal treatments include cytokine therapy, monoclonal antibodies and cellular immunotherapy. In this review, we give a brief overview of potential immunotherapies and recent developments in the field, which are needed to tackle the growing problem of fungal diseases.
Topics: Animals; Antibodies, Monoclonal; Fungi; Humans; Immunotherapy; Mycoses
PubMed: 33147544
DOI: 10.1016/j.mib.2020.09.007 -
Clinical Microbiology Reviews Mar 2024Over recent decades, the global burden of fungal disease has expanded dramatically. It is estimated that fungal disease kills approximately 1.5 million individuals... (Review)
Review
Over recent decades, the global burden of fungal disease has expanded dramatically. It is estimated that fungal disease kills approximately 1.5 million individuals annually; however, the true worldwide burden of fungal infection is thought to be higher due to existing gaps in diagnostics and clinical understanding of mycotic disease. The development of resistance to antifungals across diverse pathogenic fungal genera is an increasingly common and devastating phenomenon due to the dearth of available antifungal classes. These factors necessitate a coordinated response by researchers, clinicians, public health agencies, and the pharmaceutical industry to develop new antifungal strategies, as the burden of fungal disease continues to grow. This review provides a comprehensive overview of the new antifungal therapeutics currently in clinical trials, highlighting their spectra of activity and progress toward clinical implementation. We also profile up-and-coming intracellular proteins and pathways primed for the development of novel antifungals targeting their activity. Ultimately, we aim to emphasize the importance of increased investment into antifungal therapeutics in the current continually evolving landscape of infectious disease.
Topics: Humans; Antifungal Agents; Mycoses; Drug Resistance, Fungal
PubMed: 38294218
DOI: 10.1128/cmr.00142-23 -
Molecules (Basel, Switzerland) Jun 2022Respiratory mycosis is a major health concern, due to the expanding population of immunosuppressed and immunocompromised patients and the increasing resistance to... (Review)
Review
Respiratory mycosis is a major health concern, due to the expanding population of immunosuppressed and immunocompromised patients and the increasing resistance to conventional antifungals and their undesired side-effects, thus justifying the development of new therapeutic strategies. Plant metabolites, namely essential oils, represent promising preventive/therapeutic strategies due to their widely reported antifungal potential. However, regarding fungal infections of the respiratory tract, information is disperse and no updated compilation on current knowledge is available. Therefore, the present review aims to gather and systematize relevant information on the antifungal effects of several essential oils and volatile compounds against the main type of respiratory mycosis that impact health care systems. Particular attention is paid to , the main pathogen involved in aspergillosis, , currently emerging as a major pathogen in certain parts of the world, and , one of the main pathogens involved in pulmonary cryptococcosis. Furthermore, the main mechanisms of action underlying essential oils' antifungal effects and current limitations in clinical translation are presented. Overall, essential oils rich in phenolic compounds seem to be very effective but clinical translation requires more comprehensive in vivo studies and human trials to assess the efficacy and tolerability of these compounds in respiratory mycosis.
Topics: Animals; Antifungal Agents; Humans; Mycoses; Oils, Volatile; Plant Oils; Respiration Disorders
PubMed: 35807386
DOI: 10.3390/molecules27134140 -
Frontiers in Immunology 2021Fungi are an integral part of the mammalian microbiota colonizing most if not all mucosal surfaces and the skin. Maintaining stable colonization on these surfaces is... (Review)
Review
Fungi are an integral part of the mammalian microbiota colonizing most if not all mucosal surfaces and the skin. Maintaining stable colonization on these surfaces is critical for preventing fungal dysbiosis and infection, which in some cases can lead to life threatening consequences. The epithelial barriers are protected by T cells and additional controlling immune mechanisms. Noncirculating memory T cells that reside stably in barrier tissues play an important role for host protection from commensals and recurrent pathogens due to their fast response and local activity, which provides them a strategic advantage. So far, only a few specific examples of tissue resident memory T cells (TRMs) that act against fungi have been reported. This review provides an overview of the characteristics and functional attributes of TRMs that have been established based on human and mouse studies with various microbes. It highlights what is currently known about fungi specific TRMs mediating immunosurveillance, how they have been targeted in preclinical vaccination approaches and how they can promote immunopathology, if not controlled. A better appreciation of the host protective and damaging roles of TRMs might accelerate the development of novel tissue specific preventive strategies against fungal infections and fungi-driven immunopathologies.
Topics: Animals; Fungal Vaccines; Fungi; Host-Pathogen Interactions; Humans; Immunologic Memory; Memory T Cells; Mycoses; Phenotype
PubMed: 34113356
DOI: 10.3389/fimmu.2021.693055 -
The Journal of Antimicrobial... Nov 2022Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In...
Advances in medicine have led to a growing number of people with compromised or suppressed immune systems who are susceptible to invasive fungal infections. In particular, severe fungal infections are becoming increasingly common in ICUs, affecting people within and outside of traditional risk groups alike. This is exemplified by the emergence of severe viral pneumonia as a significant risk factor for invasive pulmonary aspergillosis, and the recognition of influenza-associated pulmonary aspergillosis and, more recently, COVID-19-associated pulmonary aspergillosis. The treatment landscape for haematological malignancies has changed considerably in recent years, and some recently introduced targeted agents, such as ibrutinib, are increasing the risk of invasive fungal infections. Consideration must also be given to the risk of drug-drug interactions between mould-active azoles and small-molecule kinase inhibitors. At the same time, infections caused by rare moulds and yeasts are increasing, and diagnosis continues to be challenging. There is growing concern about azole resistance among both moulds and yeasts, mandating continuous surveillance and personalized treatment strategies. It is anticipated that the epidemiology of fungal infections will continue to change and that new populations will be at risk. Early diagnosis and appropriate treatment remain the most important predictors of survival, and broad-spectrum antifungal agents will become increasingly important. Liposomal amphotericin B will remain an essential therapeutic agent in the armamentarium needed to manage future challenges, given its broad antifungal spectrum, low level of acquired resistance and limited potential for drug-drug interactions.
Topics: Humans; Mycoses; Antifungal Agents; Invasive Fungal Infections; Azoles; Fungi; Pulmonary Aspergillosis; COVID-19 Drug Treatment
PubMed: 36426674
DOI: 10.1093/jac/dkac353 -
Expert Review of Molecular Diagnostics 2023Invasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly... (Review)
Review
BACKGROUND
Invasive fungal infections cause millions of infections annually, but diagnosis remains challenging. There is an increased need for low-cost, easy to use, highly sensitive and specific molecular assays that can differentiate between colonized and pathogenic organisms from different clinical specimens.
AREAS COVERED
We reviewed the literature evaluating the current state of molecular diagnostics for invasive fungal infections, focusing on current and novel molecular tests such as polymerase chain reaction (PCR), digital PCR, high-resolution melt (HRM), and metagenomics/next generation sequencing (mNGS).
EXPERT OPINION
PCR is highly sensitive and specific, although performance can be impacted by prior/concurrent antifungal use. PCR assays can identify mutations associated with antifungal resistance, non-Aspergillus mold infections, and infections from endemic fungi. HRM is a rapid and highly sensitive diagnostic modality that can identify a wide range of fungal pathogens, including down to the species level, but multiplex assays are limited and HRM is currently unavailable in most healthcare settings, although universal HRM is working to overcome this limitation. mNGS offers a promising approach for rapid and hypothesis-free diagnosis of a wide range of fungal pathogens, although some drawbacks include limited access, variable performance across platforms, the expertise and costs associated with this method, and long turnaround times in real-world settings.
Topics: Humans; Antifungal Agents; Mycoses; Pathology, Molecular; Fungi; Invasive Fungal Infections; Sensitivity and Specificity
PubMed: 37801397
DOI: 10.1080/14737159.2023.2267977 -
Advanced Drug Delivery Reviews Jul 2024
Topics: Humans; Fungi; Antifungal Agents; Theranostic Nanomedicine; Mycoses; Drug Delivery Systems
PubMed: 38782093
DOI: 10.1016/j.addr.2024.115343 -
Vestnik Otorinolaringologii 2023In the structure of morbidity and mortality has significantly increased the role of mycoses. The increase in their spread is due not only to the improvement of the... (Review)
Review
In the structure of morbidity and mortality has significantly increased the role of mycoses. The increase in their spread is due not only to the improvement of the quality of diagnosis, but also the emergence of new strains resistant to previously used antifungal drugs, a significant change in the immune status of the population. In addition to environmental factors, it is important to introduce modern methods of treatment that increase survival in the whole spectrum of diseases. This situation can't affect the structure of diseases of ENT organs: the number of mycoses has increased significantly in recent decades. The issues of diagnosis and treatment of mycoses of the paranasal sinuses continue to be an urgent problem of otorhinolaryngology. The reason for this is a number of difficulties associated with the diagnosis: the absence of specific symptoms of the disease, the possible secondary nature of the attachment of fungal infection against the background of bacterial lesions, transient carrier of infection, technical difficulties and errors in the study of biomaterial with insufficient standardization of microbiological methods. Our report is devoted to the clinical case of aspergillosis of the maxillary sinus and a review of the literature on this issue, which in our opinion can be very interesting to the medical community.
Topics: Humans; Maxillary Sinus; Mycoses; Antifungal Agents; Otolaryngology; Paranasal Sinus Diseases
PubMed: 37450396
DOI: 10.17116/otorino20228803178