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Diagnostic Cytopathology Mar 2010
Topics: Adrenal Gland Diseases; Histoplasma; Histoplasmosis; Humans; Silver Staining
PubMed: 19373915
DOI: 10.1002/dc.21080 -
Seminars in Respiratory Infections Jun 2001Histoplasma capsulatum is well adapted to be infectious and pathogenic for humans. As a soil fungus with no known requirement for interacting with a mammalian host as... (Review)
Review
Histoplasma capsulatum is well adapted to be infectious and pathogenic for humans. As a soil fungus with no known requirement for interacting with a mammalian host as part of an obligate lifecycle, its plethora of strategies for successful pathogenesis is particularly remarkable. These features include the dimorphic mold-yeast transition, entry into host macrophages, subcellular localization, intracellular survival and proliferation during active infection, and persistence during clinically inapparent infection with the capacity for reactivation. To thrive within the harsh environment of a professionally phagocytic and antimicrobial host cell, H. capsulatum displays mechanisms for modulating its microenvironmental pH level, resisting host reactive oxygen and nitrogen intermediates and degradative enzymes, and withstanding nutrient starvation conditions, including acquisition of iron and calcium and biosynthesis of nucleic acid precursors. Attention has been focused on identifying virulence-associated phenotypic traits and genes that are differentially expressed under relevant conditions, such as yeast morphotype-specific genes and genes that are up-regulated during infection. These studies, together with the increasing ability to perform molecular genetic manipulations in this fungus, may yield novel antifungal drug or vaccine targets as well as elucidating pathogenic mechanisms.
Topics: Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Humans
PubMed: 11521241
DOI: 10.1053/srin.2001.24239 -
Trends in Microbiology Oct 2003Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although... (Review)
Review
Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose histoplasmosis. Research is needed to reduce false-negative and false-positive results, and to improve the identification of the organism in tissues. Approaches to the diagnosis of histoplasmosis and areas that require further research will be reviewed.
Topics: Antigens, Fungal; Cross Reactions; Histoplasma; Histoplasmosis; Humans
PubMed: 14557032
DOI: 10.1016/j.tim.2003.08.007 -
Seminars in Respiratory Infections Jun 2001Histoplasma capsulatum is a facultative intracellular pathogen, and the causative agent of the most common systemic fungal infection. Over the past several years, many... (Review)
Review
Histoplasma capsulatum is a facultative intracellular pathogen, and the causative agent of the most common systemic fungal infection. Over the past several years, many new insights have been learned concerning the biology, biochemistry, and molecular genetics of this microorganism. This review focuses on the immunology of host defense against H. capsulatum yeasts with emphasis on the development of cell-mediated immunity, and the strategies used by the fungus to survive and multiply within macrophages.
Topics: Histoplasma; Histoplasmosis; Humans; Immunity, Cellular
PubMed: 11521242
DOI: 10.1053/srin.2001.24240 -
Microbes and Infection Jul 2008Histoplasma capsulatum is the most common cause of invasive fungal pulmonary disease worldwide. The interaction of H. capsulatum with a host is a complex, dynamic... (Review)
Review
Histoplasma capsulatum is the most common cause of invasive fungal pulmonary disease worldwide. The interaction of H. capsulatum with a host is a complex, dynamic process. Severe disease most commonly occurs in individuals with compromised immunity, and the increasing utilization of immunomodulators in medicine has revealed significant risks for reactivation disease in patients with latent histoplasmosis. Fortunately, there are well developed molecular tools and excellent animal models for studying H. capsulatum virulence and numerous recent advances have been made regarding the pathogenesis of this fungus that will improve our capacity to combat disease.
Topics: Antibodies, Monoclonal; Databases, Genetic; Fungal Vaccines; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans
PubMed: 18672088
DOI: 10.1016/j.micinf.2008.07.011 -
Current Opinion in Microbiology Dec 2013Histoplasma capsulatum (Hc) is the causative organism of a spectrum of disease affecting both the immunocompetent and the immunocompromised host. Hc is a dimporhic... (Review)
Review
Histoplasma capsulatum (Hc) is the causative organism of a spectrum of disease affecting both the immunocompetent and the immunocompromised host. Hc is a dimporhic fungus that converts from conidia to the pathogenic yeast phase after entry into the mammalian host. Despite rapid ingestion by macrophages, it survives intracellularly within the macrophage. The intracellular survival strategy of Hc yeasts focuses on regulating the phagosomal compartment by modulating the intraphagosomal pH to 6.5. As an intracellular pathogen of MΦ, Hc obtains iron from Fe-transferrin, ferritin, or both, via the production of hydroxamate siderophores, and the production of ferric reductases. A better understanding of the mechanisms by which Hc yeasts acquire iron from the host may lead to novel therapeutics for histoplasmosis.
Topics: Histoplasma; Iron; Macrophages; Phagosomes; Virulence
PubMed: 24094809
DOI: 10.1016/j.mib.2013.09.001 -
Journal of Microbiology (Seoul, Korea) Mar 2016Histoplasma capsulatum is a dimorphic pathogenic fungus and causative agent of histoplasmosis, which is a respiratory and systemic infection that is particularly severe... (Review)
Review
Histoplasma capsulatum is a dimorphic pathogenic fungus and causative agent of histoplasmosis, which is a respiratory and systemic infection that is particularly severe in immunocompromised hosts and represents the fungal homolog of tuberculosis. In highly endemic regions, the majority of individuals have been infected and carry the organism in a persistent latent form that is a danger for reactivation if host defenses are suppressed. H. capsulatum has been a model organism for intracellular pathogenesis and fungal morphogenesis for decades. New genomic information and application of approaches for molecular genetic manipulation are shedding new light on virulence mechanisms.
Topics: Animals; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans; Immunocompromised Host; Virulence
PubMed: 26920886
DOI: 10.1007/s12275-016-6044-5 -
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 -
Virulence Dec 2019is a member of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold... (Review)
Review
is a member 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 into a parasitic host form that causes disease. is a primary fungal pathogen, meaning it is able to cause disease in healthy individuals. We are beginning to understand how host temperature is utilized as a key signal to facilitate growth in the parasitic yeast form and promote production of virulence factors. In recent years, multiple regulators of morphology and virulence have been identified in . Mutations in these regulators render the pathogen unable to convert to the parasitic yeast form. Additionally, several virulence factors have been characterized for their importance in survival and pathogenesis. These virulence factors and regulators can serve as molecular handles for the development of effective drugs and therapeutics to counter infection.
Topics: Animals; Body Temperature; Gene Expression Regulation, Fungal; Histoplasma; Histoplasmosis; Host-Pathogen Interactions; Humans; Mice; Mutation; Virulence; Virulence Factors
PubMed: 31560240
DOI: 10.1080/21505594.2019.1663596 -
Current Opinion in Microbiology Dec 2017Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent... (Review)
Review
Mammalian body temperature triggers differentiation of the fungal pathogen Histoplasma capsulatum into yeast cells. The Drk1 regulatory kinase and an interdependent network of Ryp transcription factors establish the yeast state. Beyond morphology, the differentiation-dependent expression program equips yeasts for invasion and survival within phagosomes. Yeast cells produce α-glucan and the Eng1 endoglucanase which hide yeasts from immune detection. Secretion of yeast phase-specific Sod3 and CatB detoxify phagocyte-derived reactive oxygen molecules. Histoplasma cells adapt to iron and zinc limitation in activated macrophages by production of siderophores and the Zrt2 transporter, respectively. Yeasts also respond to inflammation-associated hypoxia. Histoplasma pathogenicity thus relies on factors controlled by yeast differentiation as well as environment-dependent responses.
Topics: Animals; Fungal Proteins; Histoplasma; Histoplasmosis; Humans; Phagocytes
PubMed: 29096192
DOI: 10.1016/j.mib.2017.10.003