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Indian Journal of Pathology &... 2024
Topics: Humans; Antifungal Agents; Bone Marrow; Histoplasma; Histoplasmosis
PubMed: 38358230
DOI: 10.4103/ijpm.ijpm_200_22 -
Journal of the American Veterinary... May 2024This is the first reported use of posaconazole for the treatment of feline disseminated histoplasmosis.
OBJECTIVE
This is the first reported use of posaconazole for the treatment of feline disseminated histoplasmosis.
ANIMALS
Approximately 1-year-old female spayed domestic longhair cat.
CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES
The cat presented to our institution with weight loss, lymphadenomegaly, hepatosplenomegaly, limb edema, abdominal fluid distension and ulcerated cutaneous nodules. The cat had been previously diagnosed with disseminated histoplasmosis at another institution approximately 6 months prior. Clinical signs had been refractory to treatment with fluconazole. Itraconazole had next been tried, and the cat's weight continued to decline, lesions failed to regress, and the cat formed abdominal fluid distension and marked pelvic limb edema.
TREATMENT AND OUTCOME
The cat was prescribed posaconazole along with prednisolone. The cat's demeanor, body weight, and lesions all markedly improved. Histoplasma antigen was undetectable in urine samples while the cat was receiving posaconazole. However, posaconazole blood levels paired with markedly elevated ALT suggested potential toxicity and the drug was discontinued. Upon cessation of posaconazole, the cat's lesions returned with cytologic evidence of intralesional Histoplasma yeast. Itraconazole combine with terbinafine was prescribed. At last follow-up, the cat was clinically well, off all anti-fungal medication, and without detectable Histoplasma antigen in the urine.
CLINICAL RELEVANCE
Posaconazole therapy showed promise in this case. Had a safe and therapeutic dose been arrived at, we suspect that posaconazole would have cleared or maintained clinical remission of this cat's disease. This is the first report using posaconazole and the first successful report using combination itraconazole and terbinafine for the treatment of feline disseminated histoplasmosis. Generic drugs were used throughout this case report; the drug manufacturers are unknown to the authors.
PubMed: 38324995
DOI: 10.2460/javma.23.12.0677 -
Journal of Equine Veterinary Science Mar 2024In Sub-Saharan Africa (SSA), particularly in Ethiopia, Epizootic Lymphangitis (EL) is the most prevalent fungal disease of equids, which causes significant economic... (Meta-Analysis)
Meta-Analysis Review
In Sub-Saharan Africa (SSA), particularly in Ethiopia, Epizootic Lymphangitis (EL) is the most prevalent fungal disease of equids, which causes significant economic losses as well as a decrease in equid populations. Therefore, this systematic review and meta-analysis were designed to pool the results of individual studies and estimate the prevalence of EL among equids in Ethiopia. A systematic search of research articles on the prevalence and risk factors of EL among equids in Ethiopia was conducted in registers, databases, and other sources. Cochrane's Q, inverse variance (I), sensitivity analysis, funnel plot, Begg's, and Egger's regression tests were used to check heterogeneity and publication bias. A random-effects model was used to calculate the pooled burden of EL among equids. For this meta-analysis, a total of 7217 equids were included in the 14 eligible studies. The overall pooled prevalence of EL among equids in Ethiopia was 20.24% (95% CI: 16.27, 24.21). According to the subgroup analysis, the highest prevalence was observed in cart horses (20.98%), the Amhara region (21.46%), and studies conducted using sample sizes of 384 equids or greater (24.67%) and from 2002 to 2018 (25.52%) study periods. Harness-inflicted wounds, sharing stables or yards with harnesses, and the presence of preexisting wounds were identified as factors significantly associated with EL magnitude. Early diagnosis and proper medication, as well as implementing appropriate prevention and control measures, are necessary for the management of EL in equids.
Topics: Horses; Animals; Ethiopia; Lymphangitis; Prevalence; Histoplasmosis; Risk Factors; Horse Diseases
PubMed: 38320735
DOI: 10.1016/j.jevs.2024.105012 -
Cureus Dec 2023Histoplasmosis is a systemic fungal infection caused by , known for its protean clinical manifestations that often pose diagnostic challenges. Immunocompromised...
Histoplasmosis is a systemic fungal infection caused by , known for its protean clinical manifestations that often pose diagnostic challenges. Immunocompromised patients, such as those on immunosuppressive therapies or with HIV/AIDS, are particularly susceptible to severe forms of the disease. We present a case of a 55-year-old female with a complex medical history, including a renal transplant, who developed fever, malaise, nausea, and vomiting after a month-long stay in Panama. The patient's history included exposure to a bird with apparent infection and mold in her home. Her clinical presentation featured acute kidney injury, elevated liver enzymes, acalculous cholecystitis, and lung nodules. This intricate constellation of symptoms underscores the diverse nature of histoplasmosis presentations and its potential to mimic other diseases. The patient underwent a stepwise diagnostic approach involving imaging, microbiological tests, and multidisciplinary consultations. The positive Fungitell assay, detection in urine, and identification of scattered subcentimeter lung nodules confirmed the diagnosis. This case underscores the significance of considering endemic areas, environmental exposures, and atypical clinical features in immunocompromised patients. The multidisciplinary approach facilitated appropriate management and treatment initiation with liposomal amphotericin B, highlighting the importance of collaboration among various medical specialties in complex cases. As such, this case report emphasizes the complexity of diagnosing and managing histoplasmosis in immunocompromised individuals and highlights the need for a comprehensive evaluation of atypical presentations.
PubMed: 38283423
DOI: 10.7759/cureus.51276 -
JGH Open : An Open Access Journal of... Jan 2024Disseminated histoplasmosis is a rare complication of infection due to . Typically, histoplasmosis is self-limiting and asymptomatic in infected individuals with...
Disseminated histoplasmosis is a rare complication of infection due to . Typically, histoplasmosis is self-limiting and asymptomatic in infected individuals with immunocompetence. Disseminated disease, however, can arise in high-risk populations with primary or acquired cellular immunodeficiency including HIV/AIDS, transplant recipients, and those undergoing immunosuppressive therapy. Here we describe a unique case of extrapulmonary gastrointestinal histoplasmosis by infiltrative Peyer's patch disease with bone marrow involvement in a transgender HIV-infected woman.
PubMed: 38268953
DOI: 10.1002/jgh3.13011 -
Annals of Diagnostic Pathology Apr 2024Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental...
Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.
Topics: Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Liver Transplantation; Incidental Findings; Living Donors; Liver; Fatty Liver
PubMed: 38266545
DOI: 10.1016/j.anndiagpath.2024.152266 -
BioRxiv : the Preprint Server For... Jan 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 transitions into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. We have previously described that is composed of at least five cryptic species that differ genetically, and assigned new names to the lineages. Here we evaluated multiple phenotypic characteristics of 12 strains from five phylogenetic species of to identify phenotypic traits that differentiate between these species: , and an African lineage. We report diagnostic traits for two species. The other three species can be identified by a combination of traits. Our results suggest that 1) there are significant phenotypic differences among the cryptic species of , and 2) that 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.
PubMed: 38260643
DOI: 10.1101/2024.01.08.574719 -
Applied and Environmental Microbiology Feb 2024In this study, we conducted an in-depth analysis to characterize potential () proteins capable of recognizing fungal β-1,3-glucans. specifically anchors curdlan or...
In this study, we conducted an in-depth analysis to characterize potential () proteins capable of recognizing fungal β-1,3-glucans. specifically anchors curdlan or laminarin, indicating the presence of surface β-1,3-glucan-binding molecules. Using optical tweezers, strong adhesion of laminarin- or curdlan-coated beads to was observed, highlighting their adhesive properties compared to controls (characteristic time τ of 46.9 and 43.9 s, respectively). Furthermore, () G217B, possessing a β-1,3-glucan outer layer, showed significant adhesion to compared to a G186 strain with an α-1,3-glucan outer layer (τ of 5.3 s vs τ 83.6 s). The addition of soluble β-1,3-glucan substantially inhibited this adhesion, indicating the involvement of β-1,3-glucan recognition. Biotinylated β-1,3-glucan-binding proteins from exhibited higher binding to G217B, suggesting distinct recognition mechanisms for laminarin and curdlan, akin to macrophages. These observations hinted at the β-1,3-glucan recognition pathway's role in fungal entrance and survival within phagocytes, supported by decreased fungal viability upon laminarin or curdlan addition in both phagocytes. Proteomic analysis identified several proteins capable of binding β-1,3-glucans, including those with lectin/glucanase superfamily domains, carbohydrate-binding domains, and glycosyl transferase and glycosyl hydrolase domains. Notably, some identified proteins were overexpressed upon curdlan/laminarin challenge and also demonstrated high affinity to β-1,3-glucans. These findings underscore the complexity of binding via β-1,3-glucan and suggest the existence of alternative fungal recognition pathways in .IMPORTANCE () and macrophages both exhibit the remarkable ability to phagocytose various extracellular microorganisms in their respective environments. While substantial knowledge exists on this phenomenon for macrophages, the understanding of 's phagocytic mechanisms remains elusive. Recently, our group identified mannose-binding receptors on the surface of that exhibit the capacity to bind/recognize fungi. However, the process was not entirely inhibited by soluble mannose, suggesting the possibility of other interactions. Herein, we describe the mechanism of β-1,3-glucan binding by and its role in fungal phagocytosis and survival within trophozoites, also using macrophages as a model for comparison, as they possess a well-established mechanism involving the Dectin-1 receptor for β-1,3-glucan recognition. These shed light on a potential parallel evolution of pathways involved in the recognition of fungal surface polysaccharides.
Topics: Acanthamoeba castellanii; Amoeba; Mannose; Proteomics; beta-Glucans; Glucans; Histoplasma
PubMed: 38259076
DOI: 10.1128/aem.01736-23 -
MSphere Feb 2024is a dimorphic fungal pathogen acquired via inhalation of soil-resident spores. Upon exposure to mammalian body temperatures, these fungal elements transform into...
is a dimorphic fungal pathogen acquired via inhalation of soil-resident spores. Upon exposure to mammalian body temperatures, these fungal elements transform into yeasts that reside primarily within phagocytes. Macrophages (MΦ) provide a permissive environment for fungal replication until T cell-dependent immunity is engaged. MΦ activated by granulocyte macrophage colony stimulating factor (GM-CSF) induces metallothioneins (MTs) that bind zinc (Zn) and deprive yeast cells of labile Zn, thereby disabling fungal growth. Prior work demonstrated that the zinc transporter, , was important for fungal survival . Hence, we constructed a yeast cell reporter strain that expresses green fluorescent protein (GFP) under control of the zinc-regulated promoter. This reporter accurately responds to a medium devoid of Zn. expression increased in GM-CSF, but not interferon-γ, stimulated MΦ. To examine the response, we infected mice with a reporter yeast strain and assessed expression at 0, 3, 7, and 14 days post-infection (dpi). expression minimally increased at 3 dpi and peaked at 7 dpi, corresponding with the onset of adaptive immunity. We discovered that the major MΦ populations that restrict Zn from the fungus are interstitial MΦ and exudate MΦ. Neutralizing GM-CSF blunted the control of infection but unexpectedly increased expression. This increase was dependent on another cytokine that activates MΦ to control replication, M-CSF. These findings illustrate the reporter's ability to sense Zn and and correlate expression with GM-CSF and M-CSF activation of MΦ.IMPORTANCEPhagocytes use an arsenal of defenses to control the replication of yeasts, one of which is the limitation of trace metals. On the other hand, combats metal restriction by upregulating metal importers such as the Zn importer . This transporter contributes to pathogenesis upon activation of adaptive immunity. We constructed a fluorescent transcriptional reporter to probe Zn sensing during infection and exposed the role for M-CSF activation of macrophages when GM-CSF is absent. These data highlight the ways in which fungal pathogens sense metal deprivation and reveal the potential of metal-sensing reporters. The work adds a new dimension to study how intracellular pathogens sense and respond to the changing environments of the host.
Topics: Mice; Animals; Histoplasma; Granulocyte-Macrophage Colony-Stimulating Factor; Macrophage Colony-Stimulating Factor; Histoplasmosis; Zinc; Saccharomyces cerevisiae; Mammals
PubMed: 38259064
DOI: 10.1128/msphere.00704-23 -
Cureus Dec 2023Histoplasmosis is a systemic mycosis caused by (). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those...
BACKGROUND
Histoplasmosis is a systemic mycosis caused by (). Systemic involvement of histoplasmosis usually occurs in immune-compromised patients, patients with AIDS, or those taking immunosuppressive therapy. The present study aims to describe the clinical and laboratory characteristics and treatment outcome of histoplasmosis as the diagnosis is challenging and management protocol differs.
METHOD
This retrospective study was done using a data registry at the medicine department of Dhaka Medical College Hospital. Here, patients received the standard treatment of histoplasmosis. Here, patients received the standard treatment of histoplasmosis, and clinical outcome was assessed at 3 months following starting standard treatment.
RESULT
A total of nine patients were enrolled, six (66.7%) had systemic histoplasmosis. Three were poultry workers, and the most common comorbidity was diabetes 3 (33.3%). Fever 7 (77.7%), weight loss 6 (66.7%), hyperpigmentation 5 (55.5%), cough 4 (44.4%), oral ulceration 4 (44.4%), lymphadenopathy 4 (44.4%), and hypotension 3 (33.3%) were the most common clinical presentations. Seven (77.7%) out of nine patients were cured of histoplasmosis; however, one died before initiating antifungal medications and another one died due to a hypersensitivity reaction to liposomal amphotericin B. Conclusion: For local histoplasmosis, oral itraconazole is an effective antifungal medication. However, in disseminated Histoplasmosis, liposomal amphotericin B followed by oral itraconazole is still one of the preferable and effective treatment options. Clinicians should be aware of hypersensitivity reactions of liposomal amphotericin B and its management before giving an infusion.
PubMed: 38249268
DOI: 10.7759/cureus.50813