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Journal of Fungi (Basel, Switzerland) Jul 2023Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal... (Review)
Review
Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed.
PubMed: 37623553
DOI: 10.3390/jof9080782 -
Pathogens (Basel, Switzerland) Jan 2024Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of and species complexes (SC), mostly in developing countries.... (Review)
Review
Antifungal therapy, especially with the azoles, could promote the incidence of less susceptible isolates of and species complexes (SC), mostly in developing countries. Given that these species affect mostly the immunocompromised host, the infections are severe and difficult to treat. This review encompasses the following topics: 1. infecting species and their virulence, 2. treatment, 3. antifungal susceptibility methods and available categorical endpoints, 4. genetic mechanisms of resistance, 5. clinical resistance, 6. fluconazole minimal inhibitory concentrations (MICs), clinical outcome, 7. environmental influences, and 8. the relevance of host factors, including pharmacokinetic/pharmacodynamic (PK/PD) parameters, in predicting the clinical outcome to therapy. As of now, epidemiologic cutoff endpoints (ECVs/ECOFFs) are the most reliable antifungal resistance detectors for these species, as only one clinical breakpoint (amphotericin B and VNI) is available.
PubMed: 38392866
DOI: 10.3390/pathogens13020128 -
Journal of Clinical Immunology Jul 2023Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal... (Review)
Review
BACKGROUND
Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF.
METHODS
We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis.
RESULTS
Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients.
CONCLUSIONS
We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.
Topics: Adult; Humans; Granulocyte-Macrophage Colony-Stimulating Factor; Meningitis, Cryptococcal; Autoantibodies; Colombia; Cryptococcosis; Cryptococcus neoformans
PubMed: 36821021
DOI: 10.1007/s10875-023-01451-5 -
Scientific Reports Sep 2023The Cryptococcus genus comprises more than 100 species, of which C. neoformans and C. gattii are the leading cause of cryptococcosis. The distribution of C. gattii and...
The Cryptococcus genus comprises more than 100 species, of which C. neoformans and C. gattii are the leading cause of cryptococcosis. The distribution of C. gattii and C. neoformans species complexes has been extensively studied and widely reported globally. Other species such as Naganishia albida, Papiliotrema laurentii, and Papiliotrema flavescens have been reported as pathogenic yeasts. Since there are no reports of environmental isolation in the Boyacá region (Colombia), this study aimed to isolate and characterize Cryptococcus and Cryptococcus-like yeasts from pigeon feces, Eucalyptus, and olive trees distributed in the municipalities of Tunja and Ricaute Alto. The environmental data was recovered, and the isolations obtained were identified by microscopy, biochemical test, MALDI-TOF MS, URA5-RFLP, and sequencing of the ITS and LSU loci. For the 93 pigeon dropping samples collected in Tunja, 23 yielded to C. neoformans, 3 to N. globosa, 2 N. albida and 1 to P. laurentii. Of the 1188 samples collected from olive trees, 17 (1.43%) positive samples were identified as C. gattii species complex (4), C. neoformans species complex (2), P. laurentii (3), N. albida (2), N. globosa (5) and P. flavescens (1). Likewise, specimens of C. neoformans presented molecular type VNI and molecular type VNII; for C. gattii the molecular types found were VGIII and one VGIV by URA5-RFLP but VGIII by MALDI-TOF and sequencing of the ITS and LSU. Therefore, it can be concluded that the species of Cryptococcus, Naganishia and Papiliotrema genera, are present in the environment of Boyacá, and show a predilection for climate conditions that are typical of this region.
Topics: Animals; Colombia; Cryptococcus neoformans; Cryptococcus gattii; Cryptococcosis; Climate; Columbidae; Olea
PubMed: 37735454
DOI: 10.1038/s41598-023-41994-6 -
Journal of Fungi (Basel, Switzerland) Nov 2023Invasive fungal diseases are a public health problem. They affect a constantly increasing number of at-risk patients, and their incidence has risen in recent years.... (Review)
Review
Invasive fungal diseases are a public health problem. They affect a constantly increasing number of at-risk patients, and their incidence has risen in recent years. These opportunistic infections are mainly due to sp. but less common or rare yeast infections should not be underestimated. These so-called "less common" yeasts include Ascomycota of the genera (excluding the five major species), , , and , and Basidiomycota of the genera (excluding the / complex members), , and . The aim of this review is to (i) inventory the less common yeasts isolated in humans, (ii) provide details regarding the specific anatomical locations where they have been detected and the clinical characteristics of the resulting infections, and (iii) provide an update on yeast taxonomy. Of the total of 239,890 fungal taxa and their associated synonyms sourced from the MycoBank and NCBI Taxonomy databases, we successfully identified 192 yeasts, including 127 Ascomycota and 65 Basidiomycota. This repertoire allows us to highlight rare yeasts and their tropism for certain anatomical sites and will provide an additional tool for diagnostic management.
PubMed: 37998905
DOI: 10.3390/jof9111099 -
Journal of Fungi (Basel, Switzerland) Oct 2023Fungal infections are an increasingly growing public health concern, and is one of the most problematic fungal organisms causing substantial mortality and morbidity... (Review)
Review
Fungal infections are an increasingly growing public health concern, and is one of the most problematic fungal organisms causing substantial mortality and morbidity worldwide. Clinically, this high incidence of cryptococcosis is most commonly seen in immunocompromised patients, especially those who lack an adaptive T cell response, such as HIV/AIDS patients. However, patients with other underlying immunodeficiencies are also at an increased risk for cryptococcosis. The adaptive immune response, in particular the Th1/Th17 T-cell-mediated responses, to pulmonary infections are required for host protection. Dendritic cells (DCs), encompassing multiple subsets identified to date, are recognized as the major professional antigen-presenting cell (APC) subset essential for the initiation and execution of T-cell immunity. Apart from their prominent role in orchestration of the adaptive arm of the immune defenses, DCs are fully armed cells from the innate immune system capable of the recognition, uptake, and killing of the fungal cells. Thus, DCs serve as a critical point for the endpoint outcomes of either fungal control or unrestrained fungal infection. Multiple studies have shown that DCs are required for anti-cryptococcal defense in the lungs. In addition, the role of DCs in infections is just starting to be elucidated. has recently risen to prominence with multiple outbreaks in the US and Canada, demonstrating increased virulence in non-immunocompromised individuals. infection fails to generate an inflammatory immune response or a protective Th1/Th17 T cell response, at least in part, through a lack of proper DC function. Here we summarize the multiple roles of DCs, including subsets of DCs in both mouse and human models, the roles of DCs during cryptococcal infection, and mechanisms by cryptococcal cells to attempt to undermine these host defenses.
PubMed: 37998856
DOI: 10.3390/jof9111050 -
Journal of Clinical Microbiology Oct 2023Rapid identification of the causative pathogens of central nervous system infections is essential for providing appropriate management and improving patient outcomes....
Rapid identification of the causative pathogens of central nervous system infections is essential for providing appropriate management and improving patient outcomes. The performance of QIAstat-Dx Meningitis/Encephalitis (ME) Panel-a multiplex PCR testing platform-in detecting pathogens implicated in meningitis and/or encephalitis was evaluated using BioFire FilmArray ME Panel as a comparator method. This multicenter study analyzed 585 retrospective residual cerebrospinal fluid specimens and 367 contrived specimens. The QIAstat-Dx ME Panel showed positive percent agreement (PPA) values of 100% for , , K1, , and / on clinical samples compared to the BioFire FilmArray ME Panel. The PPA values observed for and were 80% and 88.24%, respectively. Negative percent agreement (NPA) values were >99.0% for each of the six bacterial targets and one fungal target tested with clinical samples. One viral target, herpes simplex virus 1, exhibited a PPA value of 100.0%, while the remaining viral targets-human parechovirus, herpes simplex virus 2, human herpes virus 6, and varicella zoster virus-were >90.0%, with the exception of enterovirus, which had a PPA value of 77.8%. The QIAstat-Dx ME Panel detected five true-positive and four true-negative cases compared to BioFire FilmArray ME Panel. The NPA values for all viral pathogens were >99.0%. Overall, the QIAstat-Dx ME Panel showed comparable performance to the BioFire FilmArray ME Panel as a rapid diagnostic tool for community-acquired meningitis and encephalitis.
Topics: Humans; Multiplex Polymerase Chain Reaction; Retrospective Studies; Meningitis; Encephalitis; Meningoencephalitis
PubMed: 37702495
DOI: 10.1128/jcm.00426-23 -
World Journal of Nephrology Dec 2023Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus... (Review)
Review
Cryptococcosis is the third most commonly occurring invasive fungal disease in solid organ transplant recipients (SOT). It is caused by encapsulated yeast, Cryptococcus species, predominantly Cryptococcus neoformans and Cryptococcus gattii. Though kidney transplant recipients are at the lowest risk of cryptococcosis when compared to other solid organ transplant recipients such as lung, liver or heart, still this opportunistic infection causes significant morbidity and mortality in this subset of patients. Mortality rates with cryptococcosis range from 10%-25%, while it can be as high as 50% in SOT recipients with central nervous system involvement. The main aim of diagnosis is to find out if there is any involvement of the central nervous system in disseminated disease or whether there is only localized pulmonary involvement as it has implications for both prognostication and treatment. Detection of cryptococcal antigen (CrAg) in cerebrospinal fluid or plasma is a highly recommended test as it is more sensitive and specific than India ink and fungal cultures. The CrAg lateral flow assay is the single point of care test that can rapidly detect cryptococcal polysaccharide capsule. Treatment of cryptococcosis is challenging in kidney transplant recipients. Apart from the reduction or optimization of immunosuppression, lipid formulations of amphotericin B are preferred as induction antifungal agents. Consolidation and maintenance are done with fluconazole; carefully monitoring its interactions with calcineurin inhibitors. This review further discusses in depth the evolving developments in the epidemiology, pathogenesis, diagnostic assays, and management approach of cryptococcosis in kidney transplant recipients.
PubMed: 38230297
DOI: 10.5527/wjn.v12.i5.120 -
Allergology International : Official... Oct 2023Cryptococcus neoformans and Cryptococcus gattii are pathogenic fungi that infect the human respiratory system and cause life-threatening pulmonary cryptococcosis. The... (Review)
Review
Cryptococcus neoformans and Cryptococcus gattii are pathogenic fungi that infect the human respiratory system and cause life-threatening pulmonary cryptococcosis. The immunopathology of cryptococcosis is completely different from that of other fungal allergies. In murine cryptococcal infection models, cryptococcal cells are usually injected via nasal or intratracheal routes. After the infection, the alveolar epithelial cells are impaired and release IL-33, an IL-1 family cytokine that functions as an alarmin. This cytokine detrimentally amplifies allergic responses, and also induces a protective immune response against parasitic infection. In the pulmonary cryptococcosis model, type-II alveolar epithelial cells are the major source of IL-33, and the alveolar epithelial cells, ILC2, and Th2 cells express the IL-33 receptor (ST2). In IL-33- or ST2-deficient mice, allergy-like immune responses are attenuated after the C. neoformans infection. The numbers of ILC2 and Th2 cells and the levels of type 2 cytokines, including IL-4, IL-5, and IL-13, are decreased in the mouse lungs in both models. In association with these changes, total blood IgE, bronchus mucus production, and the number of eosinophils are decreased. Conversely, lung neutrophils and M1-type macrophages are increased. These are protective immune subsets suppressing cryptococcal growth. As a result, the lung fungal burden of IL-33- and ST2-deficient mice is decreased post-infection, and both deficient mice show significantly improved mortality. This pathogenesis varies depending on the cryptococcal and murine strains used in the animal experiments. Here, we overview and discuss the itmmunopathology of the IL-33/ST2 axis in a murine lethal cryptococcal infection model.
Topics: Animals; Humans; Mice; Cryptococcosis; Cryptococcus neoformans; Cytokines; Disease Models, Animal; Immunity, Innate; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Lung; Lymphocytes
PubMed: 37482531
DOI: 10.1016/j.alit.2023.07.002 -
Mycobiology 2023Opportunistic infections due to and species complexes continue to rise unabated among HIV/AIDS patients, despite improved antifungal therapies. Here, we collected a...
Opportunistic infections due to and species complexes continue to rise unabated among HIV/AIDS patients, despite improved antifungal therapies. Here, we collected a total of 20 environmental and 25 presumptive clinical cryptococcal isolates from cerebrospinal fluid (CSF) samples of 175 patients enrolled in an ongoing clinical trial Ambition 1 Project (Botswana-Harvard Partnership). Identity confirmation of the isolates was done using MALDI-TOF MS and PCR. We describe the diversity of the isolates by PCR fingerprinting and sequencing (Oxford Nanopore Technology) of the intergenic spacer region. Mating types of the isolates were determined by amplification of the locus. We report an unusual prevalence of 42.1% of x hybrids Serotype AD ( = 16), followed by 39.5% of Serotype A ( = 15), 5.3% of , D ( 2), 7.9% of ( 3), and 5.3% of 2) in 38 representative isolates that have been characterized. Mating type-specific PCR performed on 38 representative environmental and clinical isolates revealed that 16 (42.1%) were hybrids, 17 (44.7%) were , and five (13.2%) possessed mating type. We used conventional and NGS platforms to demonstrate a potential link between environmental and clinical isolates and lay a foundation to further describe mating patterns/history in Botswana.
PubMed: 38179115
DOI: 10.1080/12298093.2023.2272380