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Joseph Beyene - One of the best experts on this subject based on the ideXlab platform.
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galactomannan β d glucan and polymerase chain reaction based assays for the diagnosis of invasive Fungal Disease in pediatric cancer and hematopoietic stem cell transplantation a systematic review and meta analysis
Clinical Infectious Diseases, 2016Co-Authors: Thomas Lehrnbecher, Brian T Fisher, Theoklis E Zaoutis, Andreas H Groll, Paula D Robinson, William J Steinbach, Elio Castagnola, Zelalem Negeri, Joseph BeyeneAbstract:We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive Fungal Disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All Fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of Fungal biomarkers in pediatric cancer and HSCT.
Matthew C Allender - One of the best experts on this subject based on the ideXlab platform.
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Snake Fungal Disease alters skin bacterial and Fungal diversity in an endangered rattlesnake
Scientific Reports, 2018Co-Authors: Matthew C Allender, Sarah Baker, Megan Britton, Angela D. KentAbstract:Snake Fungal Disease (SFD), caused by Ophidiomyces ophiodiicola , is the most recently described Fungal Disease afflicting wildlife populations across North America and Europe. It has been proposed as a significant conservation threat yielding high mortality and yet much its ecology is unknown. We collected 144 skin swabs from Eastern Massasaugas ( Sistrurus catenatus ) in 2015 and 2016 to determine document ongoing prevalence and assess differences in microbial assemblages between positive and negative individuals. Alpha diversity of fungi was reduced in SFD positive animals, while beta diversity identified distinct assemblages of microbes between SFD–positive and –negative samples. Ophidiomyces was present on the skin of affected animals, even on body sites distant to lesions indicating that the microbiome on entire surface of the skin is altered. Ophidiomyces was not detected in any non-SFD snake. There were smaller, but significant, influences of year sampled. Bacterial genera Janthinobacterium and Serratia were significantly increased in SFD snakes, while Xylanimicrobium , Cellulosimicrobium , and Rhodococcus were the only bacterial taxa significantly reduced. The relative abundance of fungi within the orders Pleosporales and Canopdiales was reduced in SFD-positive samples, though Pyrenochaetopsis pratorum was the only species found to differ significantly. This is the first study to determine the impact that this Fungal pathogen has on the skin microbiome.
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pharmacokinetics efficacy and safety of voriconazole and itraconazole in healthy cottonmouths agkistrodon piscivorus and massasauga rattlesnakes sistrurus catenatus with snake Fungal Disease
Journal of Zoo and Wildlife Medicine, 2017Co-Authors: Dana M. Lindemann, Marta Rzadkowska, Grace Archer, Elizabeth Ann Driskell, Shihhsuan Hsiao, Eric Baitchman, Lauren P. Kane, Matthew C Allender, Kuldeep Singh, John M. SykesAbstract:Abstract Snake Fungal Disease (SFD; Ophidiomyces ophiodiicola) is posing a significant threat to several free-ranging populations of pitvipers. Triazole antiFungals have been proposed for the treatment of mycoses in reptiles; however, data are lacking about their safety and efficacy in snakes with SFD. Study 1 investigated in vitro susceptibility, and identified that plasma concentrations >250 ng/ml (voriconazole) and >1,000 ng/ml (itraconazole) may be effective in vivo for SFD. In Study 2, the pharmacokinetics after a single subcutaneous voriconazole injection were assessed in apparently healthy free-ranging cottonmouths (Agkistrodon piscivorus). Based on pilot-study results, four snakes were administered a single injection of voriconazole (5 mg/kg). One pilot snake and three full-study snakes died within 12 hr of voriconazole administration. All surviving snakes maintained plasma concentrations >250 ng/ml for 12–24 hr. In Study 3, two Eastern massasaugas (Sistrurus catenatus) and a timber rattlesnake (C...
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detection of ophidiomyces the causative agent of snake Fungal Disease in the eastern massasauga sistrurus catenatus in michigan usa 2014
Journal of Wildlife Diseases, 2016Co-Authors: Matthew C Allender, Jennifer A Moore, Eric T Hileman, Sasha J TetzlaffAbstract:Abstract Snake Fungal Disease (SFD), caused by Ophidiomyces ophiodiicola, threatens free-ranging snake populations across the US. We assayed 112 swabs from 102 individual eastern massasaugas (Sistrurus catenatus) at three locations in Michigan in 2014 for Ophidiomyces using quantitative PCR (qPCR). We observed a 12.7% qPCR prevalence of skin lesions. Individuals at each site had lesions, and occurrence of skin lesions was not significantly different between sites. We detected Ophidiomyces DNA at each of the three sites in five individuals (4.9%). We found no difference in detection probabilities between sites; however, snakes with dermatitis had higher Ophidiomyces DNA detection probabilities (P=0.15±0.08 SE) than snakes without dermatitis (P=0.02±0.01 SE, P=0.026). The emergence of SFD mortalities has potentially serious consequences for the viability of the eastern massasauga in Michigan. Future work should track temporal patterns in vital rates and health parameters, link health data to body condition ...
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plasma electrophoretic profiles in the eastern massasauga sistrurus catenatus and influences of age sex year location and snake Fungal Disease
Journal of Zoo and Wildlife Medicine, 2015Co-Authors: Matthew C Allender, Sarah Bakerwylie, Eric T Hileman, Lisa J Faust, Randall E. Junge, Carolyn CrayAbstract:Abstract: The purpose of this study was to establish reference intervals of the protein electrophoretic fractions and the acute-phase proteins hemoglobin binding protein (as determined by the haptoglobin assay) and C-reactive protein (CRP) and assess any possible correlations between varying age class, sex, location (Illinois or Michigan), year, or presence of snake Fungal Disease (SFD). Banked plasma samples were assayed from 130 eastern massasaugas from 2009 to 2014 in Illinois and Michigan. Snakes from Michigan had higher total protein (mean: 5.50 g/dl), albumin/globulin ratio (0.42), albumin (1.59 g/dl), and gamma globulins (0.55 g/dl) than from snakes in Illinois (4.72 g/dl, 0.29, 1.03 g/dl, 0.38 g/dl, respectively). Snakes in Illinois (22.19 g/ml) had higher CRP than snakes in Michigan (10.89 mg/ml). Adults had higher gamma globulins (0.47 g/dl) than juveniles (0.28 g/dl). Males had higher alpha-2 globulins (0.98 g/dl) and CRP (21.4 mg/ml) than females (0.85, 11.6, respectively). There were no sign...
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development of snake Fungal Disease after experimental challenge with ophidiomyces ophiodiicola in cottonmouths agkistrodon piscivorous
PLOS ONE, 2015Co-Authors: Matthew C Allender, Sarah J Baker, Daniel B Wylie, Daniel Loper, Michael J Dreslik, Christopher A Phillips, Carol W Maddox, Elizabeth Ann DriskellAbstract:Snake Fungal Disease (SFD) is a clinical syndrome associated with dermatitis, myositis, osteomyelitis, and pneumonia in several species of free-ranging snakes in the US. The causative agent has been suggested as Ophidiomyces ophiodiicola, but other agents may contribute to the syndrome and the pathogenesis is not understood. To understand the role of O. ophiodiicola in SFD, a cottonmouth snake model of SFD was designed. Five cottonmouths (Agkistrodon piscivorous) were experimentally challenged by nasolabial pit inoculation with a pure culture of O. ophiodiicola. Development of skin lesions or facial swelling at the site of inoculation was observed in all snakes. Twice weekly swabs of the inoculation site revealed variable presence of O. ophiodiicola DNA by qPCR in all five inoculated snakes for 3 to 58 days post-inoculation; nasolabial flushes were not a useful sampling method for detection. Inoculated snakes had a 40% mortality rate. All inoculated snakes had microscopic lesions unilaterally on the side of the swabbed nasolabial pit, including erosions to ulcerations and heterophilic dermatitis. All signs were consistent with SFD; however, the severity of lesions varied in individual snakes, and Fungal hyphae were only observed in 3 of 5 inoculated snakes. These three snakes correlated with post-mortem tissue qPCR evidence of O. ophiodiicola. The findings of this study conclude that O. ophiodiicola inoculation in a cottonmouth snake model leads to Disease similar to SFD, although lesion severity and the Fungal load are quite variable within the model. Future studies may utilize this model to further understand the pathogenesis of this Disease and develop management strategies that mitigate Disease effects, but investigation of other models with less variability may be warranted.
Thomas Lehrnbecher - One of the best experts on this subject based on the ideXlab platform.
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risk factors for invasive Fungal Disease in pediatric cancer and hematopoietic stem cell transplantation a systematic review
Journal of the Pediatric Infectious Diseases Society, 2018Co-Authors: Brian T Fisher, Theoklis E Zaoutis, Thomas Lehrnbecher, Paula D Robinson, William J Steinbach, Bob Phillips, Lillian SungAbstract:Background.: Although a number of risk factors have been associated with invasive Fungal Disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. Methods.: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. Results.: Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host Disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. Conclusions.: With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.
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Progress in the Diagnosis of Invasive Fungal Disease in Children
Current Fungal Infection Reports, 2017Co-Authors: Adilia Warris, Thomas LehrnbecherAbstract:Purpose of Review This review summarizes the Fungal diagnostic measures currently available for use in paediatric patients at high risk for developing invasive Fungal Disease (IFD) and those suspected of having an IFD. The clinical utility of each test is described based on reported performances of individual tests in specific paediatric populations. Recent Findings Available studies in the paediatric population are scarce and are characterized by a huge heterogeneity in underlying Diseases (e.g. different risk for IFD), different study objectives and management strategies (screening versus diagnostic) used. Summary A final valuation of paediatric studies on Fungal diagnostic tools is limited. While the galactomannan and Fungal PCR assays are useful to exclude the presence of IFD, it is unclear if mannan, mannan antibodies and β-D-glucan are of benefit due to a lack of studies or validation of the cut-off, respectively. Well-designed multicentre paediatric studies are urgently needed to improve the outcome of IFD.
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Immunotherapy of Invasive Fungal Disease
Immunogenetics of Fungal Diseases, 2017Co-Authors: Thomas Lehrnbecher, Darius Armstrong-jamesAbstract:Despite the availability of new antiFungal compounds, morbidity and mortality of invasive Fungal Disease are still unacceptably high, in particular in immunocompromised patients such as patients with hematological malignancies, allogeneic hematopoietic stem cell, solid organ transplant recipients, or advanced HIV infection. However, our knowledge of the immunopathogenesis of invasive Fungal Disease has greatly expanded over the last decades, which, in turn, provides critical information to augment host immunity against Fungal pathogens. Potential approaches for enhancing the host immune system in the combat against invasive Fungal Disease include the administration of effector and regulatory cells (e.g., granulocytes, antiFungal T cells, natural killer cells, dendritic cells) and the administration of recombinant cytokines, antibodies, interferons, and growth factors (e.g., interferon-γ, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor). Although promising results are reported on in vitro data and animal studies, the real challenge in the future is to perform appropriately designed and powered clinical trials.
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galactomannan β d glucan and polymerase chain reaction based assays for the diagnosis of invasive Fungal Disease in pediatric cancer and hematopoietic stem cell transplantation a systematic review and meta analysis
Clinical Infectious Diseases, 2016Co-Authors: Thomas Lehrnbecher, Brian T Fisher, Theoklis E Zaoutis, Andreas H Groll, Paula D Robinson, William J Steinbach, Elio Castagnola, Zelalem Negeri, Joseph BeyeneAbstract:We systematically reviewed and analyzed the available data for galactomannan (GM), β-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive Fungal Disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All Fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of Fungal biomarkers in pediatric cancer and HSCT.
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β-d-Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Journal of Clinical Microbiology, 2015Co-Authors: Antonia Koltze, Peter Micheal Rath, Stefan Schöning, Joerg Steinmann, Thomas A. Wichelhaus, Peter Bader, Konrad Bochennek, Thomas LehrnbecherAbstract:While the assessment of β-d-glucan (BDG) levels in adults improves the early diagnosis of invasive Fungal Disease (IFD), data on BDG levels in children are limited. We therefore assessed in a prospective cohort study the value of serial BDG screening for early detection of IFD in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT). IFD was defined according to the revised European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, with the necessary modification that BDG was not included as a microbiological criterion. For the analysis, a total of 702 serum samples were obtained in 34 pediatric HSCT recipients. Proven IFD occurred in two patients (fusariosis and Candida sepsis, respectively), and probable invasive aspergillosis was diagnosed in four patients. Analyses including different cutoff values for BDG levels and different definitions of the onset of IFD demonstrated that the BDG assay has a relatively high sensitivity and good negative predictive value, whereas the positive predictive value has major limitations (
Terence M Farrell - One of the best experts on this subject based on the ideXlab platform.
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tracking outcomes of snake Fungal Disease in free ranging pygmy rattlesnakes sistrurus miliarius
Journal of Wildlife Diseases, 2018Co-Authors: Craig M Lind, Ciera M Mccoy, Terence M FarrellAbstract:Abstract: Snake Fungal Disease (SFD) is caused by the fungus Ophidiomyces ophiodiicola and its documentation in wild snake populations has risen sharply in the past decade. Little is known regarding the fate of individual, free-ranging snakes afflicted with SFD. We monitored an afflicted population of pygmy rattlesnakes (Sistrurus miliarius) at Lake Woodruff National Wildlife Refuge in Central Florida, US for 2 yr. The severity of SFD in individual snakes was unrelated to the probability of their recapture later in the study, and half of the snakes diagnosed as severely infected at the onset of the study were recaptured later with no clinical signs of SFD. The clinical progress of 12 serially recaptured individuals also showed that individuals cleared the infection and fluctuated between no or low and severe clinical signs over the 2-yr study.
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environmental and physiological correlates of the severity of clinical signs of snake Fungal Disease in a population of pigmy rattlesnakes sistrurus miliarius
Conservation Physiology, 2017Co-Authors: Ciera M Mccoy, Craig M Lind, Terence M FarrellAbstract:In the past decade, snake Fungal Disease (SFD) has been identified as an emerging threat to snake populations throughout the eastern USA. Snake Fungal Disease is caused by the fungus Ophidiomyces ophiodiicola. Little is known regarding the environmental or physiological variables that affect host vulnerability and O. ophiodiicola virulence in wild snake populations. Understanding the intrinsic and extrinsic factors that correlate with infection severity is a key first step in understanding host–pathogen dynamics. Host vulnerability may vary seasonally as a result of thermal conditions or energetic trade-offs, and pathogen growth rates or dispersal may be tied to seasonal trends in climate. To determine whether season, environmental temperature or energetic trade-offs associated with life-history stage influence an individual's susceptibility to infection, we monitored the severity of clinical signs of SFD, surface air temperature, reproductive status, body condition and serum complement activity (plasma bactericidal ability) in free-ranging pigmy rattlesnakes, Sistrurus miliarius, over the course of 18 months. Seasonal increases in the severity of clinical signs of SFD were correlated negatively with monthly air surface temperature and the mean body condition of the population. Bactericidal ability varied seasonally, but pigmy rattlesnakes suffering from active SFD infections did not exhibit deficits in innate immune function. Infected snakes were in significantly lower body condition when compared with the general population, but seasonal patterns in the mean body condition of the population were not driven by seasonal patterns of infection severity. Our results highlight the potential importance of the thermal environment and energetic status in determining infection severity and outcomes and the need for managers and researchers to consider seasonality of symptom presentation when the goal is to identify the prevalence or incidence of SFD in populations.
David S Blehert - One of the best experts on this subject based on the ideXlab platform.
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experimental infection of snakes with ophidiomyces ophiodiicola causes pathological changes that typify snake Fungal Disease
Mbio, 2015Co-Authors: Jeffrey M Lorch, Julia S Lankton, Katrien Werner, Elizabeth A Falendysz, Kevin Mccurley, David S BlehertAbstract:ABSTRACT Snake Fungal Disease (SFD) is an emerging skin infection of wild snakes in eastern North America. The fungus Ophidiomyces ophiodiicola is frequently associated with the skin lesions that are characteristic of SFD, but a causal relationship between the fungus and the Disease has not been established. We experimentally infected captive-bred corn snakes (Pantherophis guttatus) in the laboratory with pure cultures of O. ophiodiicola. All snakes in the infected group (n = 8) developed gross and microscopic lesions identical to those observed in wild snakes with SFD; snakes in the control group (n = 7) did not develop skin infections. Furthermore, the same strain of O. ophiodiicola used to inoculate snakes was recovered from lesions of all animals in the infected group, but no fungi were isolated from individuals in the control group. Monitoring progression of lesions throughout the experiment captured a range of presentations of SFD that have been described in wild snakes. The host response to the infection included marked recruitment of granulocytes to sites of Fungal invasion, increased frequency of molting, and abnormal behaviors, such as anorexia and resting in conspicuous areas of enclosures. While these responses may help snakes to fight infection, they could also impact host fitness and may contribute to mortality in wild snakes with chronic O. ophiodiicola infection. This work provides a basis for understanding the pathogenicity of O. ophiodiicola and the ecology of SFD by using a model system that incorporates a host species that is easy to procure and maintain in the laboratory. IMPORTANCE Skin infections in snakes, referred to as snake Fungal Disease (SFD), have been reported with increasing frequency in wild snakes in the eastern United States. While most of these infections are associated with the fungus Ophidiomyces ophiodiicola, there has been no conclusive evidence to implicate this fungus as a primary pathogen. Furthermore, it is not understood why the infections affect different host populations differently. Our experiment demonstrates that O. ophiodiicola is the causative agent of SFD and can elicit pathological changes that likely impact fitness of wild snakes. This information, and the laboratory model we describe, will be essential in addressing unresolved questions regarding Disease ecology and outcomes of O. ophiodiicola infection and helping to conserve snake populations threatened by the Disease. The SFD model of infection also offers utility for exploring larger concepts related to comparative Fungal virulence, host response, and host-pathogen evolution.
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taqman real time polymerase chain reaction for detection of ophidiomyces ophiodiicola the fungus associated with snake Fungal Disease
BMC Veterinary Research, 2015Co-Authors: Elizabeth A Bohuski, Jeffrey M Lorch, Kathryn M Griffin, David S BlehertAbstract:Background Fungal skin infections associated with Ophidiomyces ophiodiicola, a member of the Chrysosporium anamorph of Nannizziopsis vriesii (CANV) complex, have been linked to an increasing number of cases of snake Fungal Disease (SFD) in captive snakes around the world and in wild snake populations in eastern North America. The emergence of SFD in both captive and wild situations has led to an increased need for tools to better diagnose and study the Disease.
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Fungal Disease and the developing story of bat white nose syndrome
PLOS Pathogens, 2012Co-Authors: David S BlehertAbstract:Two recently emerged cutaneous Fungal Diseases of wildlife, bat white-nose syndrome (WNS) [1] and amphibian chytridiomycosis [2], have devastated affected populations. Fungal Diseases are gaining recognition as significant causes of morbidity and mortality to plants, animals, and humans [3], yet fewer than 10% of Fungal species are known [4]. Furthermore, limited antiFungal therapeutic drugs are available, antiFungal therapeutics often have associated toxicity, and there are no approved antiFungal vaccines. The unexpected emergence of WNS, the rapidity with which it has spread, and its unprecedented severity demonstrate both the impacts of novel Fungal Disease upon naive host populations and challenges to effective management of such Diseases.
