Histologic Features of Zygomycosis

2001 ◽  
Vol 125 (3) ◽  
pp. 375-378 ◽  
Author(s):  
John L. Frater ◽  
Gerri S. Hall ◽  
Gary W. Procop
Keyword(s):  
Perineural Invasion ◽  
Inflammatory Responses ◽  
Fungal Growth ◽  
Positive Culture ◽  
Clinical History ◽  
Invasive Disease ◽  
Medical Intervention ◽  
Common Finding ◽  
Fungus Ball ◽  
Fungal Morphology

Abstract Objective.—Invasive zygomycosis is rapidly progressive and is associated with angioinvasion and infarction. Invasive disease requires emergent surgical and medical intervention. Because it is important for surgical pathologists to recognize these fungi and their preferential sites of growth, the objective of this article is to describe the fungal morphology and histopathologic findings in biopsies from patients with zygomycotic disease, with emphasis on preferential sites of fungal growth. Design.—Medical record and histologic review identified 20 patients with zygomycosis. Inclusion criteria included the presence of typical ribbonlike hyphae and positive culture, a clinical history of invasive zygomycosis, or both. The histologic features of disease and the fungal morphology were assessed. Results.—Fungus ball (15%), rhinocerebral (55%), and pulmonary (30%) disease were the types of disease represented. The inflammatory responses were predominantly neutrophilic (50%), predominantly granulomatous (5%), pyogranulomatous (25%), or absent (20%). Invasive disease was characterized by prominent infarcts (94%), angioinvasion (100%), and, surprisingly, prominent perineural invasion (90%) in biopsies that contained nerves for evaluation. At least rare hyphal septa were always seen (100%), and most branches (95%) varied from 45° to 90°. Conclusions.—As known to mycologists, zygomycetes are pauciseptate, rather than aseptate, molds. Therefore, the presence of an occasional septum is expected. Perineural invasion is a common finding in invasive zygomycosis, as are angioinvasion and infarcts. Therefore, prior to excluding the presence of these fungi in biopsies suspected to contain zygomycetes, the perineural space should be carefully examined.

Mixed mould species in laboratory cultures of respiratory specimens: how should they be reported, and what are the indications for susceptibility testing?: Table 1

2011 ◽  
Vol 64 (6) ◽  
pp. 543-545 ◽  
Author(s):  
J Purcell ◽  
J McKenna ◽  
P Critten ◽  
D W Denning ◽  
I A Hassan
Keyword(s):  
Clinical Microbiology ◽  
Susceptibility Testing ◽  
Positive Culture ◽  
Invasive Disease ◽  
Clinical Samples ◽  
Transplant Recipients ◽  
Patient Case ◽  
Tertiary Centre ◽  
Risk Patients ◽  
Respiratory Specimens

AimsTo investigate how clinical microbiology laboratories should report and interpret mixed mould isolates including Aspergillus species from clinical samples and the criteria for susceptibility testing of the isolates.MethodsRetrospectively collected data from our laboratory information system of moulds isolated between January 2005 and December 2007. Patient case notes were also reviewed.ResultsA total of 502 isolates (from 273 patients) were found. 20 patients with clinical diagnosis of a probable fungal infection had mixed Aspergillus species.ConclusionsIn most instances, the isolation of Aspergillus species from non-sterile sites does not represent clinical disease, but only colonisation/contamination. However, for high-risk patients including transplant recipients, a positive culture is associated with invasive disease. Our tertiary centre routinely reports single fungal isolates and mixed cultures with appropriate comments, and those considered significant will also have susceptibility testing carried out. The correlation of culture results with clinical features can differentiate between invasive disease and contamination.

scholarly journals Toll-Like Receptor 9 Modulates Immune Responses to Aspergillus fumigatus Conidia in Immunodeficient and Allergic Mice

2008 ◽  
Vol 77 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Hemanth Ramaprakash ◽  
Toshihiro Ito ◽  
Theodore J. Standiford ◽  
Steven L. Kunkel ◽  
Cory M. Hogaboam
Keyword(s):  
Immune Responses ◽  
Aspergillus Fumigatus ◽  
Inflammatory Responses ◽  
Fungal Growth ◽  
Lower Airway ◽  
Interleukin 17 ◽  
Toll Like Receptor ◽  
Wild Type ◽  
Immunodeficient Mice

ABSTRACT The role of Toll-like receptor 9 (TLR9) in antifungal responses in the immunodeficient and allergic host is unclear. We investigated the role of TLR9 in murine models of invasive aspergillosis and fungal asthma. Neutrophil-depleted TLR9 wild-type (TLR9+/+) and TLR9-deficient (TLR9−/−) mice were challenged with resting or swollen Aspergillus fumigatus conidia and monitored for survival and lung inflammatory responses. The absence of TLR9 delayed, but did not prevent, mortality in immunodeficient mice challenged with resting or swollen conidia compared to TLR9+/+ mice. In a fungal asthma model, TLR9+/+ and TLR9−/− mice were sensitized to soluble A. fumigatus antigens and challenged with resting or swollen A. fumigatus conidia, and both groups of mice were analyzed prior to and at days 7, 14, and 28 after the conidium challenge. When challenged with resting conidia, TLR9−/− mice exhibited significantly lower airway hyper-responsiveness compared to the TLR9+/+ groups. In contrast, A. fumigatus-sensitized TLR9−/− mice exhibited pulmonary fungal growth at days 14 and 28 after challenge with swollen conidia, a finding never observed in their allergic wild-type counterparts. Increased fungal growth in allergic TLR9−/− mice correlated with markedly decreased dectin-1 expression in whole lung samples and isolated dendritic cell populations. Further, whole lung levels of interleukin-17 were lower in allergic TLR9−/− mice compared to similar TLR9+/+ mice. Together, these data suggest that TLR9 modulates pulmonary antifungal immune responses to swollen conidia, possibly through the regulation of dectin-1 expression.

scholarly journals Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Jiansheng Li ◽  
Peng Zhao ◽  
Liping Yang ◽  
Ya Li ◽  
Yange Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Arachidonic Acid ◽  
Energy Metabolism ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Medical Intervention ◽  
Arachidonic Acid Metabolism ◽  
Chronic Obstructive ◽  
Therapeutic Effects

Chronic obstructive pulmonary disease (COPD) is a serious health problem. However, the molecular pathogenesis of COPD remains unknown. Here, we explored the molecular effects of cigarette smoke and bacterial infection in lung tissues of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on the COPD rats and integrated transcriptome, proteome, and metabolome data for a global view of molecular mechanisms of COPD progression. Using molecular function and pathway analyses, the genes and proteins regulated in COPD and APL-treated rats were mainly attributed to oxidoreductase, antioxidant activity, energy and fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2), and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative stress. Then, we identified the significantly regulated metabolic pathways in lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic acid, and α-linolenic acid metabolism, which belong to the lipid metabolism. In particular, we picked the arachidonic acid metabolism for a more detailed pathway analysis of transcripts, proteins, and metabolites. We could observe an increase in metabolites and genes involved in arachidonic acid metabolism in COPD rats and the decrease in these in APL-treated rats, suggesting that inflammatory responses were up-regulated in COPD rats and down-regulated in APL-treated rats. In conclusion, these system-wide results suggested that COPD progression and its treatment might be associated with oxidative stress, lipid and energy metabolism disturbance. Additionally, we demonstrated the power of integrated omics for the elucidation of genes, proteins, and metabolites’ changes and disorders that were associated with COPD.

scholarly journals Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease

2013 ◽  
Vol 8 ◽  
Author(s):  
Nuri Tutar ◽  
Gokhan Metan ◽  
Ayşe Nedret Koç ◽  
Insu Yilmaz ◽  
Ilkay Bozkurt ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Amphotericin B ◽  
Clinical Status ◽  
Invasive Pulmonary Aspergillosis ◽  
Positive Culture ◽  
Common Finding ◽  
Chronic Obstructive ◽  
Pulmonary Aspergillosis ◽  
Obstructive Pulmonary Disease

Background: Invasive pulmonary aspergillosis (IPA) is an infection often occurring in neutropenic patients and has high mortality rates. In recent years, it has been reported that the incidence of IPA has also increased in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study is to investigate the clinical and demographic characteristics and treatment responses of IPA in patients with COPD. Methods: Seventy-one patients with a positive culture of Aspergillus from lower respiratory tract samples were examined retrospectively. Eleven (15.4%) of these patients, affected with grade 3 or 4 COPD, had IPA. Results: Aspergillus hyphae were detected in lung biopsy in three (27.3%) out of 11 patients and defined as proven IPA; a pathological sample was not taken in the other eight (72.7%) patients, and these were defined as probable IPA. Aspergillus isolates were identified as six cases of Aspergillusfumigatus and three of Aspergillusniger in nine patients, while two isolates were not identified at species level. While five patients required intensive care unit admission, four of them received mechanical ventilation. The most common finding on chest X-ray and computed tomography (CT) (respectively 63.6%, 72.7%) was infiltration. Amphotericin B was the initial drug of choice in all patients and five patients were discharged with oral voriconazole after amphotericin B therapy. Six patients (54.5%) died before treatment was completed. Conclusions: IPA should be taken into account in the differential diagnosis particularly in patients with severe and very severe COPD presenting with dyspnea exacerbation, poor clinical status, and a new pulmonary infiltrate under treatment with broad-spectrum antibiotics and steroids.

scholarly journals Macrophage LC3-associated phagocytosis is an immune defense against Streptococcus pneumoniae that diminishes with host aging

2020 ◽  
Vol 117 (52) ◽  
pp. 33561-33569
Author(s):  
Megumi Inomata ◽  
Shuying Xu ◽  
Pallavi Chandra ◽  
Simin N. Meydani ◽  
Genzou Takemura ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Inflammatory Responses ◽  
The Elderly ◽  
Invasive Disease ◽  
Immune Defense ◽  
Bacterial Killing ◽  
Murine Bone Marrow ◽  
Aged Mice ◽  
Age Related ◽  
Old Mice

Streptococcus pneumoniae is a leading cause of pneumonia and invasive disease, particularly, in the elderly. S. pneumoniae lung infection of aged mice is associated with high bacterial burdens and detrimental inflammatory responses. Macrophages can clear microorganisms and modulate inflammation through two distinct lysosomal trafficking pathways that involve 1A/1B-light chain 3 (LC3)-marked organelles, canonical autophagy, and LC3-associated phagocytosis (LAP). The S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers an autophagic response in nonphagocytic cells, but the role of LAP in macrophage defense against S. pneumoniae or in age-related susceptibility to infection is unexplored. We found that infection of murine bone-marrow-derived macrophages (BMDMs) by PLY-producing S. pneumoniae triggered Atg5- and Atg7-dependent recruitment of LC3 to S. pneumoniae-containing vesicles. The association of LC3 with S. pneumoniae-containing phagosomes required components specific for LAP, such as Rubicon and the NADPH oxidase, but not factors, such as Ulk1, FIP200, or Atg14, required specifically for canonical autophagy. In addition, S. pneumoniae was sequestered within single-membrane compartments indicative of LAP. Importantly, compared to BMDMs from young (2-mo-old) mice, BMDMs from aged (20- to 22-mo-old) mice infected with S. pneumoniae were not only deficient in LAP and bacterial killing, but also produced higher levels of proinflammatory cytokines. Inhibition of LAP enhanced S. pneumoniae survival and cytokine responses in BMDMs from young but not aged mice. Thus, LAP is an important innate immune defense employed by BMDMs to control S. pneumoniae infection and concomitant inflammation, one that diminishes with age and may contribute to age-related susceptibility to this important pathogen.

scholarly journals Perineural invasion, Gleason score and prostate specific antigen; is there any association?

2019 ◽  
Vol 8 (4) ◽  
pp. 37-37
Author(s):  
Mohammad Yazdani ◽  
Ali Karami ◽  
Emadeddin Yazdani-Kachouei ◽  
Farhad Tadayon
Keyword(s):  
Prostate Specific Antigen ◽  
Gleason Score ◽  
Prostatic Cancer ◽  
Perineural Invasion ◽  
Specific Antigen ◽  
Cross Sectional Study ◽  
Common Finding ◽  
Sectional Study ◽  
Cross Sectional ◽  
Prostate Biopsies

Introduction: Prostatic cancer is one of the most common malignancies among males. Perineural invasion (PNI) is a common finding of prostate cancer associated with more aggressive malignancies. Objectives: The current study was conducted to assess the association of PNI with serum prostate specific antigen (PSA) and Gleason score. Patients and Methods: This analytical cross-sectional study conducted on 354 known cases of prostatic cancer (2015 until 2017). Patients’ last PSA and Gleason score wit h presence/lack of PNI in their prostate biopsies were recorded. The association of PNI with PSA and Gleason score was assessed. Results: Serum level of PSA and Gleason core were significantly higher in patients with PNI (P< 0.001 for both). Gleason score was independently a predictor of PNI (odds ratio [OR]: 3.05, 95% CI:2.32- 4.001; P=0.001). Serum PSA level of 17 ng/mL had specificity of 90.3% and sensitivity of 42.7% for prediction of PNI. Conclusion: In this study we found, Gleason score is independently a prognostic factor of PNI among cases undergone prostate biopsy. In addition, serum PSA level of 17 ng/mL was 90.3% specific and 42.7% sensitive for PNI occurrence. However, our findings require further evaluations by larger studies.

Fungal Sinusitis: Progression of Disease in Immunosuppression — A Case Report

1998 ◽  
Vol 77 (3) ◽  
pp. 207-215 ◽  
Author(s):  
Anil Gungor ◽  
Vijay Adusumilli ◽  
Jacquelynne P. Corey
Keyword(s):  
Kidney Transplantation ◽  
Case Report ◽  
Invasive Disease ◽  
Fungus Ball ◽  
Fungal Sinusitis ◽  
Donor Kidney ◽  
Progression Of Disease ◽  
Disseminated Disease ◽  
Cadaver Donor ◽  
Donor Kidney Transplantation

Fungal sinusitis is a disease which can be grouped into invasive and noninvasive forms. The invasive entities include the acute/fulminant and chronic/indolent forms. The noninvasive entities include the fungus ball and allergic forms. The noninvasive forms, however, can develop into invasive disease under certain immunosuppressive states. The patient in this case report had the fungus ball form of fungal sinusitis which evolved into chronic, and then the acute/fulminant form approximately two weeks after undergoing cadaver-donor kidney transplantation. Due to the patient's immunosuppressed state, the fungus spread beyond the sinus region and eventually lead to fulminant disseminated disease. The severity of the fungal disease corresponded directly to the severity of the patient's immunosuppression.

Treatment for Early, Uncomplicated Coccidioidomycosis: What Is Success?

2019 ◽  
Vol 70 (9) ◽  
pp. 2008-2012 ◽  
Author(s):  
John N Galgiani ◽  
Janis E Blair ◽  
Neil M Ampel ◽  
George R Thompson
Keyword(s):  
Clinical Improvement ◽  
Antifungal Therapy ◽  
Tissue Damage ◽  
Management Strategy ◽  
Inflammatory Responses ◽  
Fungal Growth ◽  
Clinical Indicators ◽  
Is Success ◽  
Rational Management ◽  
Immunologic Reactions

Abstract The care of primary pulmonary coccidioidomycosis remains challenging. Such infections produce a variety of signs, symptoms, and serologic responses that cause morbidity in patients and concern in treating clinicians for the possibility of extrapulmonary dissemination. Illness may be due to ongoing fungal growth that produces acute inflammatory responses, resulting in tissue damage and necrosis, and for this, administering an antifungal drug may be of benefit. In contrast, convalescence may be prolonged by other immunologic reactions to infection, even after fungal replication has been arrested, and in those situations, antifungal therapy is unlikely to yield clinical improvement. In this presentation, we discuss what findings are clinical indicators of fungal growth and what other sequelae are not. Understanding these differences provides a rational management strategy for deciding when to continue, discontinue, or reinstitute antifungal treatments.

scholarly journals Clinical Specificity of the Enzyme Immunoassay Test for Coccidioidomycosis Varies According to the Reason for Its Performance

2012 ◽  
Vol 20 (1) ◽  
pp. 95-98 ◽  
Author(s):  
Janis E. Blair ◽  
Neil Mendoza ◽  
Shannon Force ◽  
Yu-Hui H. Chang ◽  
Thomas E. Grys
Keyword(s):  
Enzyme Immunoassay ◽  
Positive Culture ◽  
Clinical History ◽  
Immunoglobulin M ◽  
Reference Laboratory ◽  
Test Results ◽  
Radiographic Findings ◽  
Asymptomatic Patients ◽  
Record Review

ABSTRACTThe diagnosis of coccidioidomycosis relies heavily on serologic test results in addition to clinical history, physical examination, and radiographic findings. Use of the enzyme immunoassay (EIA) has increased because it is rapidly performed and does not require referral to a reference laboratory, as do complement fixation and immunodiffusion tests. However, interpretation of immunoglobulin M (IgM) reactivity by EIA in the absence of immunoglobulin G (IgG) reactivity has been problematic. We conducted a retrospective medical record review of all patients with such IgM reactivity at our institution to identify situations where the finding was more likely to be clinically specific for coccidioidal infection. From 1 January 2004 through 31 December 2008, a total of 1,117 patients had positive EIA coccidioidal serology or EIA IgM-only reactivity; of these, 102 patients (9%) had EIA IgM-only reactivity. Among the 102 patients with EIA IgM-only reactivity, 60 were tested to evaluate symptomatic illness, 13 for follow-up of previously abnormal serology, and 29 for screening purposes. Of the 102 patients, 80 (78%) had positive serologic findings by other methods or had positive culture or histology. Fifty-four (90%) of the 60 patients whose serology was performed to evaluate symptomatic illness had coccidioidal infection, whereas 13 (45%) of 29 patients whose serology was performed for screening purposes had coccidioidal infection. Of the 102 patients with isolated IgM reactivity by EIA, 12 later seroconverted to IgG and IgM reactivity. The use of EIA for screening in 29 asymptomatic persons was associated with unconfirmable results in 13 (45%). Although the majority of patients in our study with isolated IgM reactivity by EIA had probable or confirmed coccidioidomycosis, this result must be interpreted with caution for asymptomatic patients.

Visual micromethod for assay of fungal growth

1978 ◽  
Vol 24 (5) ◽  
pp. 574-578 ◽  
Author(s):  
Sharon Kerbs ◽  
Robert D. Hutton ◽  
James W. Hollister
Keyword(s):  
Inhibitory Concentration ◽  
Fungal Growth ◽  
Trichophyton Mentagrophytes ◽  
Weight Basis ◽  
Fungal Morphology ◽  
Standard Assay ◽  
Antifungal Effects ◽  
Weight Method ◽  
Germination And Growth ◽  
Germ Tubes

A visual micromethod for measuring antifungal effects on germination and growth is described. The antifungal agent griseofulvin and the fungus Trichophyton mentagrophytes were used as materials to compare the micromethod with a standard assay based on dry mycelial weight. The micromethod was more sensitive than the weight method in detecting the minimum inhibitory concentration of griseofulvin (0.18 and 0.35 μg/ml, respectively). At higher concentrations of griseofulvin (22.5 μg/ml), the micromethod measured minimal fungal growth that was undetectable on a weight basis. The micromethod showed that griseofulvin does not change the number of spores forming germ tubes. Progressively severe alterations in fungal morphology occured as the concentration of griseofulvin was increased from 0.09 to 22.5 μg/ml.

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