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Current Topics in Microbiology and... 2019Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts... (Review)
Review
Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts can be clinically silent or it can lead to life-threatening systemic disease, which can occur in immunologically intact or deficient hosts, albeit severe disease is more likely in the setting of compromised cellular immunity. H. capsulatum yeast cells are highly adapted to the mammalian host as they can effectively survive within intracellular niches in select phagocytic cells. Understanding the biological response by both the host and H. capsulatum will facilitate improved approaches to prevent and/or modify disease. This review presents our current understanding of the major pathogenic mechanisms involved in histoplasmosis.
Topics: Animals; Histoplasma; Histoplasmosis; Humans; Virulence
PubMed: 30043340
DOI: 10.1007/82_2018_114 -
Microbiology Spectrum Jun 2016Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in... (Review)
Review
Filamentous mycoses are often associated with significant morbidity and mortality. Prompt diagnosis and aggressive treatment are essential for good clinical outcomes in immunocompromised patients. The host immune response plays an essential role in determining the course of exposure to potential fungal pathogens. Depending on the effectiveness of immune response and the burden of organism exposure, fungi can either be cleared or infection can occur and progress to a potentially fatal invasive disease. Nonspecific cellular immunity (i.e., neutrophils, natural killer [NK] cells, and macrophages) combined with T-cell responses are the main immunologic mechanisms of protection. The most common potential mold pathogens include certain hyaline hyphomycetes, endemic fungi, the Mucorales, and some dematiaceous fungi. Laboratory diagnostics aimed at detecting and differentiating these organisms are crucial to helping clinicians make informed decisions about treatment. The purpose of this chapter is to provide an overview of the medically important fungal pathogens, as well as to discuss the patient characteristics, antifungal-therapy considerations, and laboratory tests used in current clinical practice for the immunocompromised host.
Topics: Antibodies, Fungal; Antifungal Agents; Aspergillus fumigatus; CD4-Positive T-Lymphocytes; Histoplasma; Humans; Immunocompromised Host; Mucorales; Mycoses
PubMed: 27337469
DOI: 10.1128/microbiolspec.DMIH2-0002-2015 -
The New England Journal of Medicine Mar 2019
Topics: AIDS-Related Opportunistic Infections; Adult; CD4 Lymphocyte Count; Fatal Outcome; HIV Infections; Histoplasma; Histoplasmosis; Humans; Male
PubMed: 30865801
DOI: 10.1056/NEJMicm1809792 -
Medical Mycology Aug 2023Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and... (Review)
Review
Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.
Topics: Humans; Animals; Histoplasma; Chiroptera; Histoplasmosis; Saccharomyces cerevisiae; Environment
PubMed: 37553137
DOI: 10.1093/mmy/myad080 -
Open Biology Mar 2022Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on... (Review)
Review
Exposure to fungal pathogens from the environment is inevitable and with the number of at-risk populations increasing, the prevalence of invasive fungal infection is on the rise. An interesting group of fungal organisms known as thermally dimorphic fungi predominantly infects immunocompromised individuals. These potential pathogens are intriguing in that they survive in the environment in one form, mycelial phase, but when entering the host, they are triggered by the change in temperature to switch to a new pathogenic form. Considering the growing prevalence of infection and the need for improved diagnostic and treatment approaches, studies identifying key components of fungal recognition and the innate immune response to these pathogens will significantly contribute to our understanding of disease progression. This review focuses on key endemic dimorphic fungal pathogens that significantly contribute to disease, including , and species. We briefly describe their prevalence, route of infection and clinical presentation. Importantly, we have reviewed the major fungal cell wall components of these dimorphic fungi, the host pattern recognition receptors responsible for recognition and important innate immune responses supporting adaptive immunity and fungal clearance or the failure thereof.
Topics: Fungi; Histoplasma; Humans; Immunity, Innate
PubMed: 35259948
DOI: 10.1098/rsob.210219 -
Applied and Environmental Microbiology Apr 2022Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves... (Review)
Review
Histoplasmosis is a mycotic infection principally affecting pulmonary tissue; sometimes, histoplasmosis can progress into a systemic disease. This infection involves immunocompetent and immunosuppressed human and other mammalian hosts, depending on particular circumstances. Histoplasmosis infection has been documented worldwide. The infection is acquired by inhaling infective mycelial propagules of the dimorphic fungus Histoplasma capsulatum. New reports of clinical cases of histoplasmosis in extreme latitudes could be related to human social adaptations and climate changes in the world, which are creating new favorable environments for this fungus and for bats, its major natural reservoirs and dispersers. has been isolated from most continents, and it is considered a complex of cryptic species, consisting of various groups of isolates that differ genetically and correlate with a particular geographic distribution. Based on updated studies, taxonomy is adjusting to new genetic data. Here, we have suggested that has at least 14 phylogenetic species distributed worldwide and new genotypes that could be under deliberation. 's geographic radiation began in South America millions of years ago when the continents were joined and the climate was favorable. For fungal spreading, the role of bats and some birds is crucial, although other natural factors could also participate.
Topics: Animals; Chiroptera; Histoplasma; Histoplasmosis; Humans; Lung; Phylogeny
PubMed: 35262368
DOI: 10.1128/aem.02010-21 -
PLoS Neglected Tropical Diseases Feb 2022Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum... (Review)
Review
BACKGROUND
Histoplasmosis is a chronic granulomatous disease caused by the thermally dimorphic fungus Histoplasma capsulatum. The 2 variants Histoplasma capsulatum var. capsulatum (Hcc) and Histoplasma capsulatum var. duboisii (Hcd) causes infection in humans and commonly termed classical or American histoplasmosis and African histoplasmosis, respectively. Histoplasma capsulatum var. farciminosum (Hcf) affects equines. In recent times, there have been heightened sensitization on fungal infections such as histoplasmosis in Africa, aimed at improving awareness among relevant stakeholders, particularly healthcare workers. This effort is expected to be paralleled with increased detection of both classical and African histoplasmosis, which has remained underdiagnosed over the years. In this narrative review, we describe the current perspectives of histoplasmosis in Africa, identify knowledge gaps, and suggest research priorities.
METHODS
A PubMed, Google Scholar, and Africa Journal Online (AJOL) literature search was conducted for studies on histoplasmosis in Africa between 2000 and 2020. Histoplasmosis essays in medical mycology textbooks were also consulted. This narrative review was prepared from the data gathered.
FINDINGS
In the past 2 decades, histoplasmosis in general has seen a relative increase in case detection in some Africa countries, probably attributable to the gradually increasing medical mycology advocacy efforts in Africa. Histoplasmosis cases are dominated by African histoplasmosis mostly in Western and Central Africa, while classical histoplasmosis is more common in Southern and Northern Africa. Although both classical and African histoplasmosis are common in Africa, the latter is more restricted to Africa, and cases outside the continent usually have a travel history to the continent. Despite the clinical and laboratory difference between African histoplasmosis and classical histoplasmosis, it is not straightforward to distinguish them. The typical manifestation of African histoplasmosis is the appearance of lesions affecting the skin, bones, and lymph nodes and unusually linked to human immunodeficiency virus (HIV)/AIDS. By contrast, classical histoplasmosis mostly affects the lungs and is often associated with immunosuppression, mainly HIV/AIDS. The present perspectives of histoplasmosis in Africa highlight unclear details on the true burden, strain diversity, infection route and genetic basis of African histoplasmosis, availability of specie-specific diagnostic tools, and compliance with recommended antifungal therapy. These knowledge gaps represent research questions that require scientific exploration.
CONCLUSIONS
Despite a subtle increase in identifying histoplasmosis cases in Africa, it remains underdiagnosed and neglected in some parts of the continent. Increasing awareness and training among healthcare workers, bridging diagnostic and therapeutic gaps, and encouraging more research in Africa are crucial to improve the current perspectives of histoplasmosis in Africa.
Topics: Africa; Animals; Awareness; Health Knowledge, Attitudes, Practice; Histoplasma; Histoplasmosis; Humans; Research
PubMed: 35202403
DOI: 10.1371/journal.pntd.0010111 -
Current Opinion in Microbiology Dec 2019Temperature serves as a fundamental signal in biological systems. In some microbial pathogens of humans, mammalian body temperature triggers establishment and... (Review)
Review
Temperature serves as a fundamental signal in biological systems. In some microbial pathogens of humans, mammalian body temperature triggers establishment and maintenance of a developmental program that allows the microbe to survive and thrive in the host. Histoplasma capsulatum is one of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold form that inhabits the soil into a parasitic form that causes disease in the host. It has been known for decades that temperature is a key signal that is sufficient to trigger the switch from the soil to host form (and vice versa) in the laboratory. Recent molecular studies have identified a number of key regulators that are required to specify each of the developmental forms in response to temperature. Here we review the regulatory circuits that govern temperature-dependent dimorphism in Histoplasma.
Topics: Adaptation, Physiological; Fungal Proteins; Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Humans; Respiratory Tract Infections; Soil Microbiology; Temperature; Virulence
PubMed: 31739263
DOI: 10.1016/j.mib.2019.10.011 -
Balkan Medical Journal Oct 2019
Topics: Adrenal Glands; Aged, 80 and over; Anorexia; Histoplasma; Histoplasmosis; Humans; Male; Tomography, X-Ray Computed
PubMed: 31397142
DOI: 10.4274/balkanmedj.galenos.2019.2019.4.104 -
The FEBS Journal Feb 2016The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are... (Review)
Review
The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are readily controlled by phagocytic cells, H. capsulatum yeasts are able to infect macrophages, survive antimicrobial defenses, and proliferate as an intracellular pathogen. In this review, we discuss some of the molecular mechanisms that enable H. capsulatum yeasts to overcome obstacles to intracellular pathogenesis. H. capsulatum yeasts gain refuge from extracellular obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid triggering signaling receptors such as the β-glucan receptor Dectin-1. H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense enzymes including an extracellular superoxide dismutase and an extracellular catalase. Within the phagosome, H. capsulatum yeasts block phagosome acidification, acquire essential metals such as iron and zinc, and utilize de novo biosynthesis pathways to overcome nutritional limitations. These mechanisms explain how H. capsulatum yeasts avoid and negate macrophage defense strategies and establish a hospitable intracellular niche, making H. capsulatum a successful intracellular pathogen of macrophages.
Topics: Catalase; Histoplasma; Humans; Macrophages; Reactive Oxygen Species; Superoxide Dismutase
PubMed: 26235362
DOI: 10.1111/febs.13389