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Transplant Infectious Disease : An... Aug 2019Histoplasma capsulatum is an endemic fungus that most oftenly causes a self-limiting illness but can result in severe infections in immunocompromised patients including... (Review)
Review
Histoplasma capsulatum is an endemic fungus that most oftenly causes a self-limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra-pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper-erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.
Topics: Aged; Antifungal Agents; Histoplasma; Histoplasmosis; Humans; Immunocompromised Host; Itraconazole; Kidney; Kidney Transplantation; Larynx; Male; Transplant Recipients
PubMed: 31063620
DOI: 10.1111/tid.13102 -
Frontiers in Immunology 2021As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among...
As there are more than 6 million human deaths due to mycoses each year, there is an urgent need to develop fungal vaccines. Moreover, given the similarities among pathogenic fungi, it may be possible to create a multi-fungi vaccine. In this study, we combined immunoproteomic and immunopeptidomic methods, for which we have adapted a technique based on co-immunoprecipitation (Co-IP) that made it possible to map epitopes for the first time in a natural context using murine dendritic cells (DCs) and macrophages (Mφ). Although polysaccharide epitopes exist, this research focused on mapping protein epitopes as these are more immunogenic. We used different algorithms to screen proteins and peptides identified by two-dimensional electrophoresis (2-D) and Co-IP. Seventeen proteins were revealed by 2-D gels, and 45 and 24 peptides from distinct proteins were presented by DCs and Mφ, respectively. We then determined which epitopes were restricted to MHC-I and II from humans and mice and showed high promiscuity, but lacked identity with human proteins. The 4 most promising peptides were synthesized, and the peptides with and without incorporation into glucan particles induced CD4+ and CD8+ T cell proliferation and produced a Th1 and Th17 response marked by the secretion of high levels of IFN-γ, IL-17 and IL-2. These epitopes were from heat shock protein 60, enolase, and the ATP-dependent molecular chaperone HSC82, and they each have a high degree of identity with proteins expressed by other medically important pathogenic fungi. Thus, the epitopes described in this study have the potential for use in the development of vaccines that could result in cross-protection among fungal species.
Topics: Animals; Epitope Mapping; Fungal Vaccines; Histoplasma; Male; Mice; Mice, Inbred C57BL; Peptidomimetics; Proteomics
PubMed: 34880863
DOI: 10.3389/fimmu.2021.764501 -
Emerging Infectious Diseases Mar 2021In Europe, pulmonary histoplasmosis is rarely diagnosed except in travelers. We report a probable autochthonous case of severe chronic pulmonary histoplasmosis in an...
In Europe, pulmonary histoplasmosis is rarely diagnosed except in travelers. We report a probable autochthonous case of severe chronic pulmonary histoplasmosis in an immunocompetent man in Switzerland without travel history outside of Europe. Diagnosis was achieved by histopathology, fungal culture, and serology, but the source of the infection remains speculative.
Topics: Europe; Histoplasma; Histoplasmosis; Humans; Lung Diseases, Fungal; Male; Switzerland
PubMed: 33622462
DOI: 10.3201/eid2703.191831 -
Open Forum Infectious Diseases Jul 2021We report 2 cases of severe coronavirus disease 2019 requiring prolonged hospitalization complicated by the late onset of opportunistic fungal infections,...
We report 2 cases of severe coronavirus disease 2019 requiring prolonged hospitalization complicated by the late onset of opportunistic fungal infections, histoplasmosis, and cryptococcosis.
PubMed: 34621913
DOI: 10.1093/ofid/ofab016 -
North American Spine Society Journal Dec 2023Atypical spinal infections (ASIs) of the spine are a challenging pathology to management with potentially devastating morbidity and mortality. To identify patients with...
Atypical spinal infections (ASIs) of the spine are a challenging pathology to management with potentially devastating morbidity and mortality. To identify patients with atypical spinal infections, it is important to recognize the often insidious clinical and radiographic presentations, in the setting of indolent and smoldering organism growth. Trending of inflammatory markers, and culturing of organisms, is essential. Once identified, the spinal infection should be treated with antibiotics and possibly various surgical interventions including decompression and possible fusion depending on spine structural integrity and stability. Early diagnosis of ASIs and immediate treatment of debilitating conditions, such as epidural abscess, correlate with fewer neurological deficits and a shorter duration of medical treatment. There have been great advances in surgical interventions and spinal fusion techniques for patients with spinal infection. Overall, ASIs remain a perplexing pathology that could be successfully treated with early diagnosis and immediate, appropriate medical, and surgical management.
PubMed: 37915965
DOI: 10.1016/j.xnsj.2023.100282 -
The Journal of Molecular Diagnostics :... Jun 2021Laboratory diagnosis of histoplasmosis is based on various methods, including microscopy, culture, antigen, and DNA detection of Histoplasma capsulatum var. capsulatum...
Laboratory diagnosis of histoplasmosis is based on various methods, including microscopy, culture, antigen, and DNA detection of Histoplasma capsulatum var. capsulatum or Histoplasma capsulatum var. duboisii. To improve sensitivity of existing real-time quantitative PCR (qPCR) assays, we developed a new RT-qPCR assay that allows amplification of whole nucleic acids of Histoplasma spp. validated on suspected cases. The limit of detection was 20 copies, and the specificity against 114 fungal isolates/species was restricted to Histoplasma spp. Whole nucleic acids of 1319 prospectively collected consecutive samples from 907 patients suspected of having histoplasmosis were tested routinely between May 2015 and May 2019 in parallel with standard diagnostic procedures performed in parallel. Forty-four had proven histoplasmosis attributable to H. capsulatum var. capsulatum (n = 40) or H. capsulatum var. duboisii (n = 4) infections. The results of RT-qPCR were positive in 43 of 44 patients (97.7% sensitivity) in at least one specimen. Nine of 863 cases (99% specificity) were RT-qPCR positive and therefore classified as possible cases. RT-qPCR was positive in 13 of 30 (43.3%) blood samples tested in proven cases. A positive RT-qPCR result in blood was significantly associated with H. capsulatum var. capsulatum progressively disseminated histoplasmosis with a positive RT-qPCR result in 92.3% of the immunocompromised patients with disseminated disease. This new Histoplasma RT-qPCR assay enabling amplification of H. capsulatum var. capsulatum and H. capsulatum var. duboisii is highly sensitive and allows the diagnosis of histoplasmosis advantageously from blood and bronchoalveolar lavage fluid.
Topics: DNA, Fungal; Genes, Fungal; Histoplasma; Humans; Limit of Detection; Prospective Studies; Real-Time Polymerase Chain Reaction; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 33706012
DOI: 10.1016/j.jmoldx.2021.02.007 -
Pharmaceutics Sep 2022Infectious diseases caused by intracellular microorganisms such as represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles...
Infectious diseases caused by intracellular microorganisms such as represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles (NPs) is a valuable alternative to improving drug solubility and bioavailability, preventing undesirable interactions and drug degradation, and reaching the specific therapeutic target with lower doses. This work reports on Itraconazole (ITZ) encapsulated into core-shell-like polymeric NPs and functionalized with anti-F4/80 antibodies for their targeted and controlled release into macrophages. Uptake assay on co-culture showed significant differences between the uptake of functionalized and bare NPs, higher with functionalized NPs. In vitro assays showed that F4/80-NPs with 0.007 µg/mL of encapsulated ITZ eliminated the fungus in co-culture with macrophages effectively compared to the bare NPs, without any cytotoxic effect on macrophages after 24 h interaction. Furthermore, encapsulated ITZ modulated the gene expression of anti and pro-inflammatory cytokines (IL-1, INF-Y, IL-6 and IL-10) on macrophages. Additionally, the anti-F4/80 antibody-coating enhanced natural and adequate antifungal response in the cells, exerting a synergistic effect that prevented the growth of the fungus at the intracellular level. Functionalized NPs can potentially improve macrophage-targeted therapy, increasing NPs endocytosis and intracellular drug concentration.
PubMed: 36145686
DOI: 10.3390/pharmaceutics14091932 -
Frontiers in Cellular and Infection... 2020is a thermodimorphic fungus that causes histoplasmosis, a mycosis of global incidence. The disease is prevalent in temperate and tropical regions such as North America,...
is a thermodimorphic fungus that causes histoplasmosis, a mycosis of global incidence. The disease is prevalent in temperate and tropical regions such as North America, South America, Europe, and Asia. It is known that during infection macrophages restrict Zn availability to as a microbicidal mechanism. In this way the present work aimed to study the response of to zinc deprivation. analyses showed that has eight genes related to zinc homeostasis ranging from transcription factors to CDF and ZIP family transporters. The transcriptional levels of , , and were induced under zinc-limiting conditions. The decrease in Zn availability increases fungicidal macrophage activity. Proteomics analysis during zinc deprivation at 24 and 48 h showed 265 proteins differentially expressed at 24 h and 68 at 48 h. Proteins related to energy production pathways, oxidative stress, and cell wall remodeling were regulated. The data also suggested that low metal availability increases the chitin and glycan content in fungal cell wall that results in smoother cell surface. Metal restriction also induces oxidative stress triggered, at least in part, by reduction in pyridoxin synthesis.
Topics: Asia; Europe; Histoplasma; North America; Zinc
PubMed: 33330123
DOI: 10.3389/fcimb.2020.573097 -
The American Journal of Dermatopathology Aug 2020Disseminated histoplasmosis is a rare but serious complication of infection with the dimorphic fungus Histoplasma capsulatum. We report a case of disseminated...
Disseminated histoplasmosis is a rare but serious complication of infection with the dimorphic fungus Histoplasma capsulatum. We report a case of disseminated histoplasmosis with cutaneous involvement diagnosed by touch wet preparation and confirmed with histopathology and culture. "Touch prep" performed from a lesional punch biopsy, prepared with Wright-Giemsa followed by chlorazol black containing KOH, revealed abundant yeast organisms localized within multinucleated giant cells, and a rapid diagnosis of disseminated histoplasmosis with cutaneous involvement was achieved. This report demonstrates the utility of wet prep techniques as an invaluable and rapid beside diagnostic tool in the setting of cutaneous histoplasmosis. In addition, we compare the distinguishing histopathologic features of the infectious organisms within the differential diagnosis of parasitized histiocytes.
Topics: Biopsy; Cytodiagnosis; Dermatomycoses; Histoplasmosis; Humans; Male; Middle Aged; Staining and Labeling
PubMed: 32701694
DOI: 10.1097/DAD.0000000000001578 -
Journal de Mycologie Medicale Jun 2024Histoplasmosis is a mycosis due to a dimorphic fungus Histoplasma capsulatum. This study aimed at providing an overview of histoplasmosis epidemiological, clinical,... (Review)
Review
Histoplasmosis is a mycosis due to a dimorphic fungus Histoplasma capsulatum. This study aimed at providing an overview of histoplasmosis epidemiological, clinical, diagnostic, and therapeutic aspects from the last 30 years. This review was carried out using a systematic literature search on histoplasmosis from 1992 to 2021. We describe the clinical features, diagnostic methods and treatment. Empirical searches were conducted via the databases PubMed, Google Scholar and Science Direct. Between 1992 and 2021, 190 manuscripts were published and reported 212 cases of histoplasmosis. These publications included 115 and 97 cases of American and African histoplasmosis respectively. The number of publications increased over the last ten years with a maximum in 2020 (12.34 % of the cases reported). The disseminated forms of histoplasmosis were the most frequently reported cases as compared to the localized forms. This was the case with the American histoplasmosis (75.65 %) as well as with the African histoplasmosis (55.67 %). Itraconazole (31.17 %) and Amphotericin B (26.62 %) were the most used drugs in the management of these cases. American histoplasmosis is distributed worldwide whereas African histoplasmosis is mainly present in intertropical Africa. There is a critical need for setting up a global surveillance system, towards a better understanding of the disease.
Topics: Histoplasmosis; Humans; Histoplasma; Antifungal Agents; Itraconazole; Amphotericin B; Africa
PubMed: 38484562
DOI: 10.1016/j.mycmed.2024.101474