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Archives of Microbiology Jun 2024Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to... (Review)
Review
Fungal infections are incurring high risks in a range from superficial mucosal discomforts (such as oropharyngeal candidiasis and vulvovaginal candidiasis) to disseminated life-threatening diseases (such as invasive pulmonary aspergillosis and cryptococcal meningitis) and becoming a global health problem in especially immunodeficient population. The major obstacle to conquer fungal harassment lies in the presence of increasing resistance to conventional antifungal agents used in newly clinically isolated strains. Although recombinant cytokines and mono-/poly-clonal antibodies are added into antifungal armamentarium, more effective antimycotic drugs are exceedingly demanded. It is comforting that the development of fungal vaccines and adjuvants opens up a window to brighten the prospective way in the diagnosis, prevention and treatment of fungal assaults. In this review, we focus on the progression of several major fungal vaccines devised for the control of Candida spp., Aspergillus spp., Cryptococcus spp., Coccidioides spp., Paracoccidioides spp., Blastomyces spp., Histoplasma spp., Pneumocystis spp. as well as the adjuvants adopted. We then expound the interaction between fungal vaccines/adjuvants and host innate (macrophages, dendritic cells, neutrophils), humoral (IgG, IgM and IgA) and cellular (Th1, Th2, Th17 and Tc17) immune responses which generally experience immune recognition of pattern recognition receptors, activation of immune cells, and clearance of invaded fungi. Furthermore, we anticipate an in-depth understanding of immunomodulatory properties of univalent and multivalent vaccines against diverse opportunistic fungi, providing helpful information in the design of novel fungal vaccines and adjuvants.
Topics: Fungal Vaccines; Humans; Adjuvants, Immunologic; Mycoses; Animals; Fungi
PubMed: 38850421
DOI: 10.1007/s00203-024-04010-7 -
Journal of the American Veterinary... Jun 2024To determine the sensitivity and specificity of a commercial whole blood real-time PCR assay (RT-PCR) for the diagnosis of histoplasmosis when compared to direct...
OBJECTIVE
To determine the sensitivity and specificity of a commercial whole blood real-time PCR assay (RT-PCR) for the diagnosis of histoplasmosis when compared to direct organism identification and/or urine antigen quantification by enzyme immunoassay (UA-EIA). A secondary objective was to compare the sensitivity and specificity of RT-PCR to anti-Histoplasma immunoglobulin G antibody detection by enzyme immunoassay (IgG-EIA) and IgG-EIA to UA-EIA.
ANIMALS
Cats presented to the Kansas State University Veterinary Health Center from February through September of 2023 in which histoplasmosis was diagnosed or suspected.
METHODS
From February through September of 2023, cats were tested by RT-PCR, IgG-EIA, and UA-EIA if histoplasmosis was diagnosed cytologically or was a differential diagnosis for the presenting clinical signs. Cats were excluded if all 3 tests were not submitted or if the diagnosis of histoplasmosis could not be excluded despite a negative UA-EIA result. Cats with cytologically or histologically confirmed histoplasmosis were designated as proven histoplasmosis cases, and cats with a positive UA-EIA result without cytological or histological confirmation were designated as probable histoplasmosis cases.
RESULTS
10 cats were diagnosed with either proven (n = 6) or probable (4) histoplasmosis, and 10 cats were considered true negatives. Whole blood RT-PCR results were negative in all 20 cats (sensitivity, 0%; 95% CI, 0% to 30.85%). The IgG-EIA was 90% sensitive (95% CI, 55.50% to 99.75%) and 70% specific (95% CI, 34.75% to 93.33%). The UA-EIA results were positive in all cats with proven histoplasmosis.
CLINICAL RELEVANCE
This commercial RT-PCR is insensitive when used on whole blood collected in EDTA and should not be used to diagnose feline histoplasmosis. Further studies are required to determine whether alternate RT-PCR protocols for EDTA-collected whole blood could be useful for diagnosing histoplasmosis in cats.
PubMed: 38848745
DOI: 10.2460/javma.24.03.0220 -
Surgical Case Reports Jun 2024A splenic artery pseudoaneurysm is a rare pathology that occurs mainly secondary to pancreatitis, abdominal trauma, peptic ulcers, pancreatic and gastric cancers, and...
BACKGROUND
A splenic artery pseudoaneurysm is a rare pathology that occurs mainly secondary to pancreatitis, abdominal trauma, peptic ulcers, pancreatic and gastric cancers, and infections. It is best diagnosed using computed tomography angiography and typically treated using endovascular embolization and, in some cases, open or laparoscopic surgery. In this report, we present a case of a ruptured mycotic splenic artery pseudoaneurysm containing Histoplasma capsulatum, which to our knowledge is the first case to report a mycotic splenic artery pseudoaneurysm of this nature.
CASE PRESENTATION
We report a case of a 42-year-old white male with past medical history of Hepatitis C and IV drug abuse who presented to the Emergency Department with a 24-h history of severe diffuse abdominal pain. He was tachycardic and peritonitic on exam. Work-up demonstrated leukocytosis and lactic acidosis. Computed tomography of the abdomen and pelvis with intravenous contrast showed hemoperitoneum and active extravasation of contrast from the splenic artery into the splenic hilum, associated with a surrounding hematoma measuring 5.3 × 5.0 cm, concerning for ruptured splenic artery pseudoaneurysm. The patient was taken emergently for exploratory laparotomy, where a large intraperitoneal hematoma was evacuated. A ruptured splenic artery pseudoaneurysm was identified, isolated, and controlled, followed by completion splenectomy. Final pathology demonstrated a 3.0 × 1.3 × 0.3 cm pseudoaneurysm wall and a 14 × 9.5 × 5.5 cm spleen containing multiple necrotizing granulomata positive for the presence of Histoplasmosis species. The patient recovered appropriately and was discharged on post-operative day five.
CONCLUSIONS
This case demonstrates a successful approach to a ruptured mycotic splenic artery pseudoaneurysm resulting in a positive outcome. It is a unique case as it highlights, to our knowledge, the first report of splenic artery aneurysm secondary to Histoplasma capsulatum infection. This report helps further the understanding of the pathophysiology as well as the natural history of mycotic splenic pseudoaneurysms.
PubMed: 38829447
DOI: 10.1186/s40792-024-01920-y -
Cureus May 2024is a well-known cause of pulmonary infections, but in the right patient population or host environment, it can cause a vast array of symptoms. The fungus possesses a...
is a well-known cause of pulmonary infections, but in the right patient population or host environment, it can cause a vast array of symptoms. The fungus possesses a special set of virulence factors that allows it to evade host immunity and cause infection, particularly in immunosuppressed hosts. Pericarditis is a known presentation of histoplasmosis, but it can be difficult to diagnose and is often treated based on suspicion. We present a case of a healthy young male who mounted a robust inflammatory response to histoplasmosis resulting in pericarditis.
PubMed: 38826985
DOI: 10.7759/cureus.59512 -
Microbiology and Molecular Biology... Jun 2024Histoplasmosis is arguably the most common fungal respiratory infection worldwide, with hundreds of thousands of new infections occurring annually in the United States... (Review)
Review
Histoplasmosis is arguably the most common fungal respiratory infection worldwide, with hundreds of thousands of new infections occurring annually in the United States alone. The infection can progress in the lung or disseminate to visceral organs and can be difficult to treat with antifungal drugs. , the causative agent of the disease, is a pathogenic fungus that causes life-threatening lung infections and is globally distributed. The fungus has the ability to germinate from conidia into either hyphal (mold) or yeast form, depending on the environmental temperature. This transition also regulates virulence. and histoplasmosis have been classified as being of emergent importance, and in 2022, the World Health Organization included as 1 of the 19 most concerning human fungal pathogens. In this review, we synthesize the current understanding of the ecological niche, evolutionary history, and virulence strategies of . We also describe general patterns of the symptomatology and epidemiology of histoplasmosis. We underscore areas where research is sorely needed and highlight research avenues that have been productive.
Topics: Histoplasma; Histoplasmosis; Humans; Virulence; Genetic Variation; Animals; Genotype
PubMed: 38819148
DOI: 10.1128/mmbr.00076-23 -
Journal of Investigative Medicine High... 2024Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) secondary to is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to , affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Histoplasmosis; Female; Middle Aged; Antifungal Agents; Histoplasma; Amphotericin B
PubMed: 38813977
DOI: 10.1177/23247096241258074 -
Journal of Fungi (Basel, Switzerland) May 2024causes a fungal respiratory disease. Some studies suggest that the fungus requires zinc to consolidate the infection. This study aimed to investigate the influence of...
causes a fungal respiratory disease. Some studies suggest that the fungus requires zinc to consolidate the infection. This study aimed to investigate the influence of zinc and the metal chelator TPEN on the growth of in planktonic and biofilm forms. The results showed that zinc increased the metabolic activity, cell density, and cell viability of planktonic growth. Similarly, there was an increase in biofilm metabolic activity but no increase in biomass or extracellular matrix production. N'-N,N,N,N-tetrakis-2-pyridylmethylethane-1,2 diamine (TPEN) dramatically reduced the same parameters in the planktonic form and resulted in a decrease in metabolic activity, biomass, and extracellular matrix production for the biofilm form. Therefore, the unprecedented observations in this study highlight the importance of zinc ions for the growth, development, and proliferation of cells and provide new insights into the role of metal ions for biofilm formation in the dimorphic fungus , which could be a potential therapeutic strategy.
PubMed: 38786716
DOI: 10.3390/jof10050361 -
MSphere Jun 2024Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported...
Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of to identify phenotypic traits that differentiate between these species: , , , , and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including , and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus (), , , and and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of but also for clinicians, as the species could determine the outcome of disease and treatment needed.
Topics: Histoplasma; Phenotype; Phylogeny; Histoplasmosis; Humans; Genome, Fungal
PubMed: 38771035
DOI: 10.1128/msphere.00009-24 -
Cureus May 2024We describe a recent case of bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of...
We describe a recent case of bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of endemic fungal infective endocarditis in the United States caused by , , and . Symptoms preceded infective endocarditis diagnosis by several months. Patients with and infective endocarditis were younger with fewer comorbid conditions. Valvular involvement was relatively uncommon in infective endocarditis (27%). Fungemia was noted in patients with infective endocarditis due to (30%) and (18%). Mortality rates for infective endocarditis were high (, 46%; , 58%; , 80%); infective endocarditis was commonly diagnosed post-mortem ( 58%; 89%). Most surviving patients with infective endocarditis ( 79%; 80%) underwent valve surgery along with prolonged antifungal therapy. The two surviving patients with infective endocarditis received antifungal therapy without surgery.
PubMed: 38746483
DOI: 10.7759/cureus.60285 -
Cureus Apr 2024A 79-year-old man with type II diabetes mellitus and recently diagnosed idiopathic thrombocytopenic purpura presented to the Emergency Department with progressive...
A 79-year-old man with type II diabetes mellitus and recently diagnosed idiopathic thrombocytopenic purpura presented to the Emergency Department with progressive dyspnea over the course of two weeks. He was found to have diffuse miliary nodules, dense cavitary consolidation, and widespread cystic changes on chest imaging and died within 48 hours of admission to the hospital. His serum Coccidioides antibody and urine Histoplasma antigen were both positive. He later grew from the blood, supporting the theory that Histoplasma positivity was likely the result of antigen test cross-reactivity. Coccidioidomycosis typically presents with mild, self-limited symptoms, but may also disseminate rapidly, causing fulminant, life-threatening disease. Prompt recognition of risk factors for fulminant coccidioidomycosis and understanding flaws in serologic testing are essential to the appropriate diagnosis and management of this disease.
PubMed: 38738009
DOI: 10.7759/cureus.58129