The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
David S. Perlin - One of the best experts on this subject based on the ideXlab platform.
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methylprednisolone enhances the growth of Exserohilum rostratum in vitro attenuates spontaneous apoptosis and increases mortality rates in immunocompetent drosophila flies
The Journal of Infectious Diseases, 2014Co-Authors: Dimitrios Farmakiotis, Thomas J. Walsh, David S. Perlin, Emmanuel Roilides, Yanan Zhao, Fazal Shirazi, Peguy J Saad, Nathaniel D Albert, Dimitrios P. KontoyiannisAbstract:High concentrations of methylprednisolone (0.32 mg/mL) accelerated growth and attenuated spontaneous apoptosis of Exserohilum rostratum in vitro. Injection of E. rostratum conidia preexposed to 0.32 mg/mL of methylprednisolone for 7 days in immunocompetent flies led to increased mortality and a higher fungal burden. Exposure to methylprednisolone could enhance the virulence of E. rostratum.
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Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum.
Medical mycology, 2014Co-Authors: Maria Simitsopoulou, Thomas J. Walsh, Daniela Kyrpitzi, Vidmantas Petraitis, Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel RoilidesAbstract:Exserohilum rostratum caused a multistate fungal meningitis outbreak following iatrogenic inoculation of contaminated methylprednisolone in the United States. To gain insight into the immunopathogenesis of this infection, we studied the innate host responses of human neutrophils against E. rostratum conidia and hyphae with or without methylprednisolone. The neutrophil-induced percentage fungal damage against conidia and hyphae was effector-to-target ratio dependent (≤55%). While methylprednisolone did not affect neutrophil-induced fungal damage by treatment of Exserohilum or neutrophils, it compromised phagocytosis of conidia (P < 0.05). These findings suggest that methylprednisolone-treated neutrophils may have altered phagocytic clearance of Exserohilum conidia, reducing host capacity to contain the invasive process.
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Exserohilum infections: Review of 48 cases before the 2012 United States outbreak
Medical mycology, 2014Co-Authors: Aspasia Katragkou, Thomas J. Walsh, Dimitrios P. Kontoyiannis, David S. Perlin, Zoi Dorothea Pana, Emmanuel RoilidesAbstract:Exserohilum species are soilborne fungi that have been uncommon causes of human disease. The ongoing outbreak in the United States warrants improved understanding of this pathogen. We systematically reviewed all cases of Exserohilum spp. infections published before the outbreak in 2012 in order to provide a better understanding of the organism and its wider spectrum of human disease. Cases of Exserohilum infections were retrieved by searching PubMed. Demographic data, underlying conditions, microbiology, clinical manifestations, therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were identified from 1975 to 2012. The number of reported cases increased more than twofold during the study period (P < 0.01). Most cases occurred in the southern United States, India, and Israel. Median age of patients was 25 years, with a male predominance. Most infections were due to E. rostratum (60.4%), followed by E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified species. The most frequent underlying conditions were immunosuppression (27.2%), trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection. Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined with a triazole. Surgery was used in 48% of cases and was combined with antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95% confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases highlights several aspects of epidemiology, clinical presentation, risk factors, and management of this unusual pathogen.
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what can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis
Clinical Infectious Diseases, 2013Co-Authors: Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel Roilides, Thomas J. WalshAbstract:The tragedy of the ongoing epidemic of meningitis caused by Exserohilum rostratum brings into focus the epidemiology, risk factors, pathogenesis, diagnosis, and treatment of a multitude of opportunistic mold infections of the central nervous system. Herein we provide our perspective regarding the translational research objectives of this infection that are needed to make an impact on this important healthcare crisis.
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a real time pcr assay for rapid detection and quantification of Exserohilum rostratum a causative pathogen of fungal meningitis associated with injection of contaminated methylprednisolone
Journal of Clinical Microbiology, 2013Co-Authors: Yanan Zhao, Thomas J. Walsh, Ruta Petraitiene, David S. PerlinAbstract:A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of Exserohilum rostratum infection. As low as 100 fg of E. rostratum DNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg.
Yanan Zhao - One of the best experts on this subject based on the ideXlab platform.
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A Real-Time PCR Assay for Rapid Detection and Quantification of Exserohilum rostratum, a Causative Pathogen of Fungal Meningitis Associated with Injection of Contaminated Methylprednisolone
2016Co-Authors: Yanan Zhao, Ruta Petraitiene, Thomas B J. Walsh, David B S. PerlinaAbstract:A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of Exserohilum rostratum infection. As low as 100 fg of E. rostratumDNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg. Adeadly outbreak of fungal meningitis associated with injec-tions of contaminated methylprednisolone is ongoing in the United States (1). The major cause of this iatrogenic meningitis is Exserohilum rostratum, a plant pathogen that rarely causes human disease. This fungus has been identified from patient tissue and cerebrospinal fluid (CSF) samples, as well as unopened vials of the implicated lots of methylprednisolone, by culture or DNA se-quencing, followed by a PCR assay (1–4). However, cultures from clinical samples, especially CSF, often appear negative due to the paucity of free-floating organisms. There is a need to develop a highly sensitive rapid nucleic acid-based test that can be used to reliably and quantitatively identify Exserohilum rostratum from a variety of patient specimens. Moreover, there is no reliable quan-titative biomarker in CSF by which one can measure a reduc-tion of tissue burden of E. rostratum in response to antifungal therapy. Here, we describe a specific, sensitive, and quantitative real-time PCR assay using molecular beacon (MB) technology to detect and quantify E. rostratum that facilitates primary di-agnosis in the ongoing outbreak investigation, that may be used for monitoring of therapeutic response in infected pa-tients, and that can aid in in-depth animal model studies of this poorly studied fungal pathogen. Seven clinical isolates of E. rostratum (Table 1) were grown on potato dextrose agar (PDA) slants and incubated at 37°C for 5 days. A small piece (1 cm2) ofmyceliummat was scraped off the slant and subjected to DNA extraction using theMasterPure yeas
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methylprednisolone enhances the growth of Exserohilum rostratum in vitro attenuates spontaneous apoptosis and increases mortality rates in immunocompetent drosophila flies
The Journal of Infectious Diseases, 2014Co-Authors: Dimitrios Farmakiotis, Thomas J. Walsh, David S. Perlin, Emmanuel Roilides, Yanan Zhao, Fazal Shirazi, Peguy J Saad, Nathaniel D Albert, Dimitrios P. KontoyiannisAbstract:High concentrations of methylprednisolone (0.32 mg/mL) accelerated growth and attenuated spontaneous apoptosis of Exserohilum rostratum in vitro. Injection of E. rostratum conidia preexposed to 0.32 mg/mL of methylprednisolone for 7 days in immunocompetent flies led to increased mortality and a higher fungal burden. Exposure to methylprednisolone could enhance the virulence of E. rostratum.
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a real time pcr assay for rapid detection and quantification of Exserohilum rostratum a causative pathogen of fungal meningitis associated with injection of contaminated methylprednisolone
Journal of Clinical Microbiology, 2013Co-Authors: Yanan Zhao, Thomas J. Walsh, Ruta Petraitiene, David S. PerlinAbstract:A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of Exserohilum rostratum infection. As low as 100 fg of E. rostratum DNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg.
Thomas J. Walsh - One of the best experts on this subject based on the ideXlab platform.
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The fungal meningitis outbreak five years later: what have we learned about Exserohilum rostratum?
Expert Review of Precision Medicine and Drug Development, 2017Co-Authors: Matthew W. Mccarthy, Thomas J. WalshAbstract:ABSTRACTIntroduction: On 18 September 2012, United States health officials began to react to a large outbreak of fungal meningitis traceable to methylprednisolone from a compounding pharmacy in Framingham, Massachusetts. Although the index case was attributed to the opportunistic mold Aspergillus fumigatus, all subsequent cases were due to the dematiaceous mold Exserohilum rostratum, which had previously been an uncommon cause of disease in humans.Areas covered: In this paper, the authors examine recent advances in the diagnosis and treatment of Exserohilum infection and provide updates on how the innate and acquire immune responses enable clearance of human fungal pathogens.Expert commentary: The fungal meningitis outbreak of 2012 stretched across 20 states and resulted in 753 cases of central nervous system infection and 64 deaths. In this paper, the authors examine how the outbreak prompted investigators to develop novel diagnostic and therapeutic options that have advanced the study of human fungal pa...
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methylprednisolone enhances the growth of Exserohilum rostratum in vitro attenuates spontaneous apoptosis and increases mortality rates in immunocompetent drosophila flies
The Journal of Infectious Diseases, 2014Co-Authors: Dimitrios Farmakiotis, Thomas J. Walsh, David S. Perlin, Emmanuel Roilides, Yanan Zhao, Fazal Shirazi, Peguy J Saad, Nathaniel D Albert, Dimitrios P. KontoyiannisAbstract:High concentrations of methylprednisolone (0.32 mg/mL) accelerated growth and attenuated spontaneous apoptosis of Exserohilum rostratum in vitro. Injection of E. rostratum conidia preexposed to 0.32 mg/mL of methylprednisolone for 7 days in immunocompetent flies led to increased mortality and a higher fungal burden. Exposure to methylprednisolone could enhance the virulence of E. rostratum.
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Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum.
Medical mycology, 2014Co-Authors: Maria Simitsopoulou, Thomas J. Walsh, Daniela Kyrpitzi, Vidmantas Petraitis, Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel RoilidesAbstract:Exserohilum rostratum caused a multistate fungal meningitis outbreak following iatrogenic inoculation of contaminated methylprednisolone in the United States. To gain insight into the immunopathogenesis of this infection, we studied the innate host responses of human neutrophils against E. rostratum conidia and hyphae with or without methylprednisolone. The neutrophil-induced percentage fungal damage against conidia and hyphae was effector-to-target ratio dependent (≤55%). While methylprednisolone did not affect neutrophil-induced fungal damage by treatment of Exserohilum or neutrophils, it compromised phagocytosis of conidia (P < 0.05). These findings suggest that methylprednisolone-treated neutrophils may have altered phagocytic clearance of Exserohilum conidia, reducing host capacity to contain the invasive process.
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Exserohilum infections: Review of 48 cases before the 2012 United States outbreak
Medical mycology, 2014Co-Authors: Aspasia Katragkou, Thomas J. Walsh, Dimitrios P. Kontoyiannis, David S. Perlin, Zoi Dorothea Pana, Emmanuel RoilidesAbstract:Exserohilum species are soilborne fungi that have been uncommon causes of human disease. The ongoing outbreak in the United States warrants improved understanding of this pathogen. We systematically reviewed all cases of Exserohilum spp. infections published before the outbreak in 2012 in order to provide a better understanding of the organism and its wider spectrum of human disease. Cases of Exserohilum infections were retrieved by searching PubMed. Demographic data, underlying conditions, microbiology, clinical manifestations, therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were identified from 1975 to 2012. The number of reported cases increased more than twofold during the study period (P < 0.01). Most cases occurred in the southern United States, India, and Israel. Median age of patients was 25 years, with a male predominance. Most infections were due to E. rostratum (60.4%), followed by E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified species. The most frequent underlying conditions were immunosuppression (27.2%), trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection. Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined with a triazole. Surgery was used in 48% of cases and was combined with antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95% confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases highlights several aspects of epidemiology, clinical presentation, risk factors, and management of this unusual pathogen.
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what can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis
Clinical Infectious Diseases, 2013Co-Authors: Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel Roilides, Thomas J. WalshAbstract:The tragedy of the ongoing epidemic of meningitis caused by Exserohilum rostratum brings into focus the epidemiology, risk factors, pathogenesis, diagnosis, and treatment of a multitude of opportunistic mold infections of the central nervous system. Herein we provide our perspective regarding the translational research objectives of this infection that are needed to make an impact on this important healthcare crisis.
Ruta Petraitiene - One of the best experts on this subject based on the ideXlab platform.
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A Real-Time PCR Assay for Rapid Detection and Quantification of Exserohilum rostratum, a Causative Pathogen of Fungal Meningitis Associated with Injection of Contaminated Methylprednisolone
2016Co-Authors: Yanan Zhao, Ruta Petraitiene, Thomas B J. Walsh, David B S. PerlinaAbstract:A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of Exserohilum rostratum infection. As low as 100 fg of E. rostratumDNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg. Adeadly outbreak of fungal meningitis associated with injec-tions of contaminated methylprednisolone is ongoing in the United States (1). The major cause of this iatrogenic meningitis is Exserohilum rostratum, a plant pathogen that rarely causes human disease. This fungus has been identified from patient tissue and cerebrospinal fluid (CSF) samples, as well as unopened vials of the implicated lots of methylprednisolone, by culture or DNA se-quencing, followed by a PCR assay (1–4). However, cultures from clinical samples, especially CSF, often appear negative due to the paucity of free-floating organisms. There is a need to develop a highly sensitive rapid nucleic acid-based test that can be used to reliably and quantitatively identify Exserohilum rostratum from a variety of patient specimens. Moreover, there is no reliable quan-titative biomarker in CSF by which one can measure a reduc-tion of tissue burden of E. rostratum in response to antifungal therapy. Here, we describe a specific, sensitive, and quantitative real-time PCR assay using molecular beacon (MB) technology to detect and quantify E. rostratum that facilitates primary di-agnosis in the ongoing outbreak investigation, that may be used for monitoring of therapeutic response in infected pa-tients, and that can aid in in-depth animal model studies of this poorly studied fungal pathogen. Seven clinical isolates of E. rostratum (Table 1) were grown on potato dextrose agar (PDA) slants and incubated at 37°C for 5 days. A small piece (1 cm2) ofmyceliummat was scraped off the slant and subjected to DNA extraction using theMasterPure yeas
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a real time pcr assay for rapid detection and quantification of Exserohilum rostratum a causative pathogen of fungal meningitis associated with injection of contaminated methylprednisolone
Journal of Clinical Microbiology, 2013Co-Authors: Yanan Zhao, Thomas J. Walsh, Ruta Petraitiene, David S. PerlinAbstract:A species-specific molecular beacon real-time PCR assay was developed for rapid diagnosis of Exserohilum rostratum infection. As low as 100 fg of E. rostratum DNA can be reliably detected in the presence of 50 ng of human DNA, with a dynamic linear quantification range from 20 ng to 200 fg.
Emmanuel Roilides - One of the best experts on this subject based on the ideXlab platform.
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methylprednisolone enhances the growth of Exserohilum rostratum in vitro attenuates spontaneous apoptosis and increases mortality rates in immunocompetent drosophila flies
The Journal of Infectious Diseases, 2014Co-Authors: Dimitrios Farmakiotis, Thomas J. Walsh, David S. Perlin, Emmanuel Roilides, Yanan Zhao, Fazal Shirazi, Peguy J Saad, Nathaniel D Albert, Dimitrios P. KontoyiannisAbstract:High concentrations of methylprednisolone (0.32 mg/mL) accelerated growth and attenuated spontaneous apoptosis of Exserohilum rostratum in vitro. Injection of E. rostratum conidia preexposed to 0.32 mg/mL of methylprednisolone for 7 days in immunocompetent flies led to increased mortality and a higher fungal burden. Exposure to methylprednisolone could enhance the virulence of E. rostratum.
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Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum.
Medical mycology, 2014Co-Authors: Maria Simitsopoulou, Thomas J. Walsh, Daniela Kyrpitzi, Vidmantas Petraitis, Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel RoilidesAbstract:Exserohilum rostratum caused a multistate fungal meningitis outbreak following iatrogenic inoculation of contaminated methylprednisolone in the United States. To gain insight into the immunopathogenesis of this infection, we studied the innate host responses of human neutrophils against E. rostratum conidia and hyphae with or without methylprednisolone. The neutrophil-induced percentage fungal damage against conidia and hyphae was effector-to-target ratio dependent (≤55%). While methylprednisolone did not affect neutrophil-induced fungal damage by treatment of Exserohilum or neutrophils, it compromised phagocytosis of conidia (P < 0.05). These findings suggest that methylprednisolone-treated neutrophils may have altered phagocytic clearance of Exserohilum conidia, reducing host capacity to contain the invasive process.
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Exserohilum infections: Review of 48 cases before the 2012 United States outbreak
Medical mycology, 2014Co-Authors: Aspasia Katragkou, Thomas J. Walsh, Dimitrios P. Kontoyiannis, David S. Perlin, Zoi Dorothea Pana, Emmanuel RoilidesAbstract:Exserohilum species are soilborne fungi that have been uncommon causes of human disease. The ongoing outbreak in the United States warrants improved understanding of this pathogen. We systematically reviewed all cases of Exserohilum spp. infections published before the outbreak in 2012 in order to provide a better understanding of the organism and its wider spectrum of human disease. Cases of Exserohilum infections were retrieved by searching PubMed. Demographic data, underlying conditions, microbiology, clinical manifestations, therapy, and outcome were recorded and analyzed. Forty-eight evaluable cases were identified from 1975 to 2012. The number of reported cases increased more than twofold during the study period (P < 0.01). Most cases occurred in the southern United States, India, and Israel. Median age of patients was 25 years, with a male predominance. Most infections were due to E. rostratum (60.4%), followed by E. longirostratum (6.3%) and E. mcginnisii (2%), while 31.3% were unidentified species. The most frequent underlying conditions were immunosuppression (27.2%), trauma (16.6%), and atopy (12.5%). Exserohilum disease manifested as systemic (73%), cutaneous (25%), corneal (16.7%), and subcutaneous (10.4%) infection. Antifungal therapy consisted mainly of amphotericin B (44%) alone or combined with a triazole. Surgery was used in 48% of cases and was combined with antifungal therapy in 31%. The all-cause mortality was 23%, which was higher in patients with preexisting immunosuppression (56.2%; odds ratio 15.4; 95% confidence interval, 2.7-88.6). This review of the pre-outbreak reported cases highlights several aspects of epidemiology, clinical presentation, risk factors, and management of this unusual pathogen.
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what can we learn and what do we need to know amidst the iatrogenic outbreak of Exserohilum rostratum meningitis
Clinical Infectious Diseases, 2013Co-Authors: Dimitrios P. Kontoyiannis, David S. Perlin, Emmanuel Roilides, Thomas J. WalshAbstract:The tragedy of the ongoing epidemic of meningitis caused by Exserohilum rostratum brings into focus the epidemiology, risk factors, pathogenesis, diagnosis, and treatment of a multitude of opportunistic mold infections of the central nervous system. Herein we provide our perspective regarding the translational research objectives of this infection that are needed to make an impact on this important healthcare crisis.
