-
Journal of Clinical Microbiology Mar 2020Developing any diagnostic assay that receives United States Food and Drug Administration (FDA) approval can be a slow and difficult process. FDA-approved assays for... (Review)
Review
Developing any diagnostic assay that receives United States Food and Drug Administration (FDA) approval can be a slow and difficult process. FDA-approved assays for fungal diagnosis are generally few in number and are focused mainly on diagnosing candidiasis, which is caused by several species of , in addition to a limited number of systemic mycotic agents. While all microbial diagnostic assays face challenges before they are FDA approved and reach the market, there are a number of challenges to fungal diagnostic assay development that have been difficult hurdles to overcome. These hurdles include template preparation, fungal morphology, how many fungi should be identified in a single assay (scope), taxonomy and nomenclature, discriminating colonizers from invasive infection, combining identification with antifungal susceptibility, and navigating the administrative hurdles required to integrate an assay into a clinical laboratory. Some of these challenges are easier to overcome than others, but all seem to be particularly difficult for fungal diagnostic assays.
Topics: Antifungal Agents; Candida; Drug Resistance, Fungal; Humans; Mycology; Mycoses
PubMed: 31996441
DOI: 10.1128/JCM.01345-19 -
Current Opinion in Microbiology Dec 2023Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised.... (Review)
Review
Fungal infections of the central nervous system (FI-CNS) are a problematic and important medical challenge considering that those most affected are immunocompromised. Individuals with systemic cryptococcosis (67-84%), candidiasis (3-64%), blastomycosis (40%), coccidioidomycosis (25%), histoplasmosis (5-20%), mucormycosis (12%), and aspergillosis (4-6%) are highly susceptible to develop CNS involvement, which often results in high mortality (15-100%) depending on the mycosis and the affected immunosuppressed population. Current antifungal drugs are limited, prone to resistance, present host toxicity, and show reduced brain penetration, making FI-CNS very difficult to treat. Given these limitations and the rise in FI-CNS, there is a need for innovative strategies for therapeutic development and treatments to manage FI-CNS in at-risk populations. Here, we discuss standards of care, antifungal drug candidates, and novel molecular targets in the blood-brain barrier, which is a protective structure that regulates movement of particles in and out of the brain, to prevent and combat FI-CNS.
Topics: Humans; Antifungal Agents; Mycoses; Histoplasmosis; Coccidioidomycosis; Cryptococcosis; Central Nervous System Infections
PubMed: 37898052
DOI: 10.1016/j.mib.2023.102397 -
Infectious Disease Clinics of North... Sep 2023Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular... (Review)
Review
Recently, there have been significant advances in the diagnosis and management of invasive fungal infections. Compared with traditional fungal diagnostics, molecular assays promise improved sensitivity and specificity, the ability to test a range of samples (including noninvasive samples, ie, blood), the detection of genetic mutations associated with antifungal resistance, and the potential for a faster turnaround time. Antifungals in late-stage clinical development include agents with novel mechanisms of action (olorofim and fosmanogepix) and new members of existing classes with distinct advantages over existing antifungals in toxicity, drug-drug interactions, and dosing convenience (oteseconazole, opelconazole, rezafungin, ibrexafungerp, encochleated amphotericin B).
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections; Drug Resistance, Fungal
PubMed: 37532392
DOI: 10.1016/j.idc.2023.05.001 -
Gastroenterology Clinics of North... Jun 2021The thinking about fungi has evolved from unusual agents considered contaminants and colonizers to actual pathogens. Fungi are ubiquitous in nature and are found... (Review)
Review
The thinking about fungi has evolved from unusual agents considered contaminants and colonizers to actual pathogens. Fungi are ubiquitous in nature and are found throughout in association with food, soil, mammals, and insects. Fungi have become important pathogens in animals and humans causing infections extending from superficial disease to disseminated infection. Because the gastrointestinal tract is continually exposed to fungi, it is frequently colonized and infected by numerous yeast and other fungi. It is also the origin of many disseminated fungal infections. The increased incidence of fungal infections has led to the approval and use of novel antifungals.
Topics: Animals; Fungi; Gastrointestinal Tract; Humans; Mycoses
PubMed: 34024440
DOI: 10.1016/j.gtc.2021.02.009 -
The Lancet. Global Health Dec 2022
Topics: Humans; Mycoses; Global Health
PubMed: 36400070
DOI: 10.1016/S2214-109X(22)00478-8 -
Clinical Medicine (London, England) Jan 2024While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to... (Review)
Review
While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to considerable delay to appropriate treatment. Clinical suspicion must be present for respiratory disease, particularly in the immunocompromised or in those not responding to empiric treatment approaches, and an extended travel history should be obtained. This article summarises the epidemiology of PEM, key clinical features, diagnostic strategies and management.
Topics: Humans; Immunocompromised Host; Mycoses; Lung Diseases, Fungal
PubMed: 38382182
DOI: 10.1016/j.clinme.2024.100014 -
Mycopathologia Apr 2023Paracoccidioidomycosis (PCM) defines a broad spectrum of human and animal diseases caused by Paracoccidioides species (Onygenales). In the twenty-first century,... (Review)
Review
Paracoccidioidomycosis (PCM) defines a broad spectrum of human and animal diseases caused by Paracoccidioides species (Onygenales). In the twenty-first century, Paracoccidioides advanced from a monotypic taxon to a genus that harbors seven species, including P. brasiliensis sensu stricto, P. americana, P. restrepiensis, P. venezuelensis, P. lutzii, P. loboi, and P. cetii. Classic PCM, acquired upon inhalation of propagules from P. brasiliensis sensu stricto, P. americana, P. restrepiensis, P. venezuelensis, and P. lutzii, affects the human lungs and may progress to systemic granulomatous disease with tegumentary and visceral involvement. On the other hand, PCM loboi and PCM ceti caused by the unculturable P. loboi and P. cetii are subcutaneous mycoses, typically observed as keloid lesions in humans and dolphins. Such heterogeneity highlights the importance of recognizing species boundaries in Paracoccidioides to gain insights into the ecology, evolution, clinical features, and mitigation strategies to tackle the advance of PCM.
Topics: Animals; Humans; Dolphins; Genomics; Paracoccidioides; Paracoccidioidomycosis; Phylogeny
PubMed: 36633737
DOI: 10.1007/s11046-022-00704-y -
Future Microbiology Nov 2023Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive... (Review)
Review
Fungal infections are a serious problem affecting many people worldwide, creating critical economic and medical consequences. Fungi are ubiquitous and can cause invasive diseases in individuals mostly living in developing countries or with weakened immune systems, and antifungal drugs currently available have important limitations in tolerability and efficacy. In an effort to counteract the high morbidity and mortality rates associated with invasive fungal infections, various approaches are being utilized to discover and develop new antifungal agents. This review discusses the challenges posed by fungal infections, outlines different methods for developing antifungal drugs and reports on the status of drugs currently in clinical trials, which offer hope for combating this serious global problem.
Topics: Humans; Antifungal Agents; Mycoses; Invasive Fungal Infections; Fungi
PubMed: 37750748
DOI: 10.2217/fmb-2022-0269 -
Expert Review of Anti-infective Therapy Nov 2020The global frequency of endemic mycoses has considerably increased, mainly due to environmental changes, population growth in endemic areas, and the increase in... (Review)
Review
INTRODUCTION
The global frequency of endemic mycoses has considerably increased, mainly due to environmental changes, population growth in endemic areas, and the increase in HIV-related immunosuppressed status. Among the most frequent endemic mycoses are coccidioidomycosis in semi-desert climates, and paracoccidioidomycosis, and histoplasmosis in tropical climates. The inoculum can enter the host through the airway or directly through the skin. Lymphatic and hematogenous spread may involve the skin.
AREAS COVERED
In this article, we provide up-to-date epidemiological and diagnostic data on major (histoplasmosis, paracoccidioidomycosis, coccidioidomycosis, blastomycosis) and minor (talaromycosis, adiaspiromycosis, emergomycosis) endemic mycoses.
EXPERT OPINION
Endemic mycoses include diseases with a localized endemic area, and a few of them converge. These mycoses all have in common the airway involvement and can cause pulmonary symptoms following initial asymptomatic infection. Among the risk groups to acquire these mycoses are travelers from endemic areas, archeologists, speleologists, and immigrants. Promising and useful diagnostic tools have been developed in endemic mycoses; however, most of them are not standardized or available in low-income countries.
Topics: Animals; Endemic Diseases; Fungi; Global Health; Humans; Immunocompromised Host; Mycoses; Risk Factors
PubMed: 32620065
DOI: 10.1080/14787210.2020.1792774 -
Parasite Immunology Feb 2023The emergence of deadly fungal infections in Africa is primarily driven by a disproportionately high burden of human immunodeficiency virus (HIV) infections, lack of... (Review)
Review
The emergence of deadly fungal infections in Africa is primarily driven by a disproportionately high burden of human immunodeficiency virus (HIV) infections, lack of access to quality health care, and the unavailability of effective antifungal drugs. Immunocompromised people in Africa are therefore at high risk of infection from opportunistic fungal pathogens such as Cryptococcus neoformans and Pneumocystis jirovecii, which are associated with high morbidity, mortality, and related socioeconomic impacts. Other emerging fungal threats include Emergomyces spp., Histoplasma spp., Blastomyces spp., and healthcare-associated multi-drug resistant Candida auris. Socioeconomic development and the Covid-19 pandemic may influence shifts in epidemiology of invasive fungal diseases on the continent. This review discusses the epidemiology, clinical manifestations, and current management strategies available for these emerging fungal diseases in Africa. We also discuss gaps in knowledge, policy, and research to inform future efforts at managing these fungal threats.
Topics: Humans; Pandemics; COVID-19; Mycoses; Antifungal Agents; HIV Infections
PubMed: 36175380
DOI: 10.1111/pim.12953