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Thomas M Kerkering - One of the best experts on this subject based on the ideXlab platform.
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epidemiological effectiveness and cost of a Fungal Meningitis outbreak response in new river valley virginia local health department and clinical perspectives
Disaster Medicine and Public Health Preparedness, 2018Co-Authors: Nargesalsadat Dorratoltaj, Thomas M Kerkering, Margaret Odell, Paige Bordwine, Kerry J Redican, Kaja AbbasAbstract:Objective We evaluated the effectiveness and cost of a Fungal Meningitis outbreak response in the New River Valley of Virginia during 2012-2013 from the perspective of the local public health department and clinical facilities. The Fungal Meningitis outbreak affected 23 states in the United States with 751 cases and 64 deaths in 20 states; there were 56 cases and 5 deaths in Virginia. Methods We conducted a partial economic evaluation of the Fungal Meningitis outbreak response in New River Valley. We collected costs associated with the local health department and clinical facilities in the outbreak response and estimated the epidemiological effectiveness by using disability-adjusted life years (DALYs) averted. Results We estimated the epidemiological effectiveness of this outbreak response to be 153 DALYs averted among the patients, and the costs incurred by the local health department and clinical facilities to be $30,413 and $39,580, respectively. Conclusions We estimated the incremental cost-effectiveness ratio of $198 per DALY averted and $258 per DALY averted from the local health department and clinical perspectives, respectively, thereby assisting in impact evaluation of the outbreak response by the local health department and clinical facilities. ( Disaster Med Public Health Preparedness . 2018;12:38–46)
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clinical response outbreak investigation and epidemiology of the Fungal Meningitis epidemic in the united states systematic review
Disaster Medicine and Public Health Preparedness, 2016Co-Authors: Kaja Abbas, Thomas M Kerkering, Nargesalsadat Dorratoltaj, Margaret Odell, Paige Bordwine, Kerry J RedicanAbstract:We conducted a systematic review of the 2012-2013 multistate Fungal Meningitis epidemic in the United States from the perspectives of clinical response, outbreak investigation, and epidemiology. Articles focused on clinical response, outbreak investigation, and epidemiology were included, whereas articles focused on compounding pharmacies, legislation and litigation, diagnostics, microbiology, and pathogenesis were excluded. We reviewed 19 articles by use of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. The source of the Fungal Meningitis outbreak was traced to the New England Compounding Center in Massachusetts, where injectable methylprednisolone acetate products were contaminated with the predominant pathogen, Exserohilum rostratum. As of October 23, 2013, the final case count stood at 751 patients and 64 deaths, and no additional cases are anticipated. The multisectoral public health response to the Fungal Meningitis epidemic from the hospitals, clinics, pharmacies, and the public health system at the local, state, and federal levels led to an efficient epidemiological investigation to trace the outbreak source and rapid implementation of multiple response plans. This systematic review reaffirms the effective execution of a multisectoral public health response and efficient delivery of the core functions of public health assessment, policy development, and service assurances to improve population health.
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economic evaluation of Fungal Meningitis outbreak response in new river valley local health department perspective
Frontiers in Public Health, 2015Co-Authors: Kaja Abbas, Thomas M Kerkering, Nargesalsadat Dorratoltaj, Margaret Odell, Paige Bordwine, Kerry J RedicanAbstract:The multi-state Fungal Meningitis outbreak started in September 2012 in Tennessee. The cause of the outbreak was injection of contaminated lots of methylprednisolone acetate used in epidural spinal injections. Roanoke and New River Valley were the epicenter of this outbreak in Virginia, with two clinical centers having administered the contaminated injections to their patients. New River Health District, in coordination with hospitals, and state and federal agencies, deployed its resources to control the local impact of the outbreak.The objective of this study was to conduct an economic evaluation of the Fungal Meningitis outbreak response in New River Valley of Virginia, from the local public health department perspective.The health department conducted the outbreak investigation from October 2012 until March 2013 to ascertain that all possible cases were identified and treated. Data were collected on the costs associated with the local health department in the outbreak response, and the epidemiologic effectiveness estimated, using the metric of disability adjusted life years (DALYs).The cost incurred by the local health department was estimated to be $30,493; the epidemiologic effectiveness was estimated to be 138 DALYs averted among the patients, for an incremental cost-effectiveness ratio of $221 per DALY averted.The incremental cost effectiveness ratio of the Fungal Meningitis outbreak response in New River Valley assists the local health department to analyze the costs and epidemiologic effectiveness of the outbreak response.
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utility of real time pcr for detection of exserohilum rostratum in body and tissue fluids during the multistate outbreak of Fungal Meningitis and other infections
Journal of Clinical Microbiology, 2015Co-Authors: Lalitha Gade, Dale E Grgurich, Thomas M Kerkering, Mary E Brandt, Anastasia P. LitvintsevaAbstract:Exserohilum rostratum was the major cause of the multistate outbreak of Fungal Meningitis linked to contaminated injections of methylprednisolone acetate produced by the New England Compounding Center. Previously, we developed a Fungal DNA extraction procedure and broad-range and E. rostratum-specific PCR assays and confirmed the presence of Fungal DNA in 28% of the case patients. Here, we report the development and validation of a TaqMan real-time PCR assay for the detection of E. rostratum in body fluids, which we used to confirm infections in 57 additional case patients, bringing the total number of case patients with PCR results positive for E. rostratum to 171 (37% of the 461 case patients with available specimens). Compared to Fungal culture and the previous PCR assays, this real-time PCR assay was more sensitive. Of the 139 identical specimens from case patients tested by all three methods, 19 (14%) were positive by culture, 41 (29%) were positive by the conventional PCR assay, and 65 (47%) were positive by the real-time PCR assay. We also compared the utility of the real-time PCR assay with that of the previously described beta-d-glucan (BDG) detection assay for monitoring response to treatment in case patients with serially collected CSF. Only the incident CSF specimens from most of the case patients were positive by real-time PCR, while most of the subsequently collected specimens were negative, confirming our previous observations that the BDG assay was more appropriate than the real-time PCR assay for monitoring the response to treatment. Our results also demonstrate that the real-time PCR assay is extremely susceptible to contamination and its results should be used only in conjunction with clinical and epidemiological data.
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utility of 1 3 β d glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of Fungal Meningitis and other infections
Clinical Infectious Diseases, 2014Co-Authors: Anastasia P. Litvintseva, Rachel M Smith, Lalitha Gade, Mark D Lindsley, Tom Chiller, Jennifer L Lyons, Kiran T Thakur, Sean X Zhang, Dale E Grgurich, Thomas M KerkeringAbstract:Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of Fungal Meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of Meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of Fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the Fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of Fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among Fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with Fungal Meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for Fungal Meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.
Anastasia P. Litvintseva - One of the best experts on this subject based on the ideXlab platform.
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utility of real time pcr for detection of exserohilum rostratum in body and tissue fluids during the multistate outbreak of Fungal Meningitis and other infections
Journal of Clinical Microbiology, 2015Co-Authors: Lalitha Gade, Dale E Grgurich, Thomas M Kerkering, Mary E Brandt, Anastasia P. LitvintsevaAbstract:Exserohilum rostratum was the major cause of the multistate outbreak of Fungal Meningitis linked to contaminated injections of methylprednisolone acetate produced by the New England Compounding Center. Previously, we developed a Fungal DNA extraction procedure and broad-range and E. rostratum-specific PCR assays and confirmed the presence of Fungal DNA in 28% of the case patients. Here, we report the development and validation of a TaqMan real-time PCR assay for the detection of E. rostratum in body fluids, which we used to confirm infections in 57 additional case patients, bringing the total number of case patients with PCR results positive for E. rostratum to 171 (37% of the 461 case patients with available specimens). Compared to Fungal culture and the previous PCR assays, this real-time PCR assay was more sensitive. Of the 139 identical specimens from case patients tested by all three methods, 19 (14%) were positive by culture, 41 (29%) were positive by the conventional PCR assay, and 65 (47%) were positive by the real-time PCR assay. We also compared the utility of the real-time PCR assay with that of the previously described beta-d-glucan (BDG) detection assay for monitoring response to treatment in case patients with serially collected CSF. Only the incident CSF specimens from most of the case patients were positive by real-time PCR, while most of the subsequently collected specimens were negative, confirming our previous observations that the BDG assay was more appropriate than the real-time PCR assay for monitoring the response to treatment. Our results also demonstrate that the real-time PCR assay is extremely susceptible to contamination and its results should be used only in conjunction with clinical and epidemiological data.
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Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections
Journal of clinical microbiology, 2014Co-Authors: Anastasia P. Litvintseva, Steven F. Hurst, Lalitha Gade, Michael Frace, Remy Hilsabeck, James M. Schupp, John D. Gillece, Chandler C. Roe, David Smith, Paul KeimAbstract:Exserohilum rostratum was the cause of most cases of Fungal Meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with Meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum.
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utility of 1 3 β d glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of Fungal Meningitis and other infections
Clinical Infectious Diseases, 2014Co-Authors: Anastasia P. Litvintseva, Rachel M Smith, Lalitha Gade, Mark D Lindsley, Tom Chiller, Jennifer L Lyons, Kiran T Thakur, Sean X Zhang, Dale E Grgurich, Thomas M KerkeringAbstract:Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of Fungal Meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of Meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of Fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the Fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of Fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among Fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with Fungal Meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for Fungal Meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.
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detection of Fungal dna in human body fluids and tissues during a multistate outbreak of Fungal Meningitis and other infections
Eukaryotic Cell, 2013Co-Authors: Lalitha Gade, Mark D Lindsley, Mary E Brandt, Christina M Scheel, Cau D Pham, Naureen Iqbal, Angela A Cleveland, Anne M Whitney, Shawn R Lockhart, Anastasia P. LitvintsevaAbstract:ABSTRACT Exserohilum rostratum was the major cause of an outbreak of Fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple Fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of Fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of Fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating Fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to Fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.
Lalitha Gade - One of the best experts on this subject based on the ideXlab platform.
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utility of real time pcr for detection of exserohilum rostratum in body and tissue fluids during the multistate outbreak of Fungal Meningitis and other infections
Journal of Clinical Microbiology, 2015Co-Authors: Lalitha Gade, Dale E Grgurich, Thomas M Kerkering, Mary E Brandt, Anastasia P. LitvintsevaAbstract:Exserohilum rostratum was the major cause of the multistate outbreak of Fungal Meningitis linked to contaminated injections of methylprednisolone acetate produced by the New England Compounding Center. Previously, we developed a Fungal DNA extraction procedure and broad-range and E. rostratum-specific PCR assays and confirmed the presence of Fungal DNA in 28% of the case patients. Here, we report the development and validation of a TaqMan real-time PCR assay for the detection of E. rostratum in body fluids, which we used to confirm infections in 57 additional case patients, bringing the total number of case patients with PCR results positive for E. rostratum to 171 (37% of the 461 case patients with available specimens). Compared to Fungal culture and the previous PCR assays, this real-time PCR assay was more sensitive. Of the 139 identical specimens from case patients tested by all three methods, 19 (14%) were positive by culture, 41 (29%) were positive by the conventional PCR assay, and 65 (47%) were positive by the real-time PCR assay. We also compared the utility of the real-time PCR assay with that of the previously described beta-d-glucan (BDG) detection assay for monitoring response to treatment in case patients with serially collected CSF. Only the incident CSF specimens from most of the case patients were positive by real-time PCR, while most of the subsequently collected specimens were negative, confirming our previous observations that the BDG assay was more appropriate than the real-time PCR assay for monitoring the response to treatment. Our results also demonstrate that the real-time PCR assay is extremely susceptible to contamination and its results should be used only in conjunction with clinical and epidemiological data.
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Whole-Genome Analysis of Exserohilum rostratum from an Outbreak of Fungal Meningitis and Other Infections
Journal of clinical microbiology, 2014Co-Authors: Anastasia P. Litvintseva, Steven F. Hurst, Lalitha Gade, Michael Frace, Remy Hilsabeck, James M. Schupp, John D. Gillece, Chandler C. Roe, David Smith, Paul KeimAbstract:Exserohilum rostratum was the cause of most cases of Fungal Meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with Meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum.
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utility of 1 3 β d glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of Fungal Meningitis and other infections
Clinical Infectious Diseases, 2014Co-Authors: Anastasia P. Litvintseva, Rachel M Smith, Lalitha Gade, Mark D Lindsley, Tom Chiller, Jennifer L Lyons, Kiran T Thakur, Sean X Zhang, Dale E Grgurich, Thomas M KerkeringAbstract:Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of Fungal Meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of Meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of Fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the Fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of Fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among Fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with Fungal Meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for Fungal Meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.
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detection of Fungal dna in human body fluids and tissues during a multistate outbreak of Fungal Meningitis and other infections
Eukaryotic Cell, 2013Co-Authors: Lalitha Gade, Mark D Lindsley, Mary E Brandt, Christina M Scheel, Cau D Pham, Naureen Iqbal, Angela A Cleveland, Anne M Whitney, Shawn R Lockhart, Anastasia P. LitvintsevaAbstract:ABSTRACT Exserohilum rostratum was the major cause of an outbreak of Fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple Fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of Fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of Fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating Fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to Fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak.
Karen Roos - One of the best experts on this subject based on the ideXlab platform.
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cerebrospinal fluid 1 3 β d glucan detection as an aid for diagnosis of iatrogenic Fungal Meningitis
Journal of Clinical Microbiology, 2013Co-Authors: Jennifer L Lyons, Kiran T Thakur, Karen Roos, Kieren A Marr, Henry Neumann, Julie B Trivedi, Dorlan J Kimbrough, Lisa Steiner, Daniel M Harrison, Sean X ZhangAbstract:ABSTRACT This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-β-d-glucan in cerebrospinal fluid during the current U.S. outbreak of Fungal Meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.
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Fungal Meningitis due to contaminated epidural steroid injections
CONTINUUM Lifelong Learning in Neurology, 2012Co-Authors: Karen RoosAbstract:In the fall of 2012, as we finalized this issue of , an unprecedented outbreak of Fungal Meningitis occurred that was caused by contaminated preservative-free methylprednisolone acetate solution from the New England Compounding Center used in epidural steroid injections in thousands of patients. The predominant pathogen was found to be Exserohilum rostratum (a black mold). Aspergillus fumigatus and Cladosporium were identified, as well. At the time of writing, all of the patients who have become sick received epidural steroid injections with methylprednisolone from one of three contaminated methylprednisolone lots. Seventeen thousand five hundred vials of methylprednisolone from these contaminated lots were distributed to 75 facilities in 23 states. Neurologists are knowledgeable about the treatment and complications of Fungal Meningitis. In this issue of , Drs Zunt and Baldwin review the diagnosis and treatment of Meningitis due to Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, and Aspergillus fumigatus in the article ‘‘Chronic and Subacute Meningitis.’’ The complications of Fungal MeningitisVmost notably hydrocephalus, increased intracranial pressure, and strokeVare difficult to manage. Shunt obstructions in CNS mold infections are common, requiring multiple shunt revisions and associated morbidity. Fungal Meningitis causes ‘‘subacute Meningitis,’’ which by definition is headache and low-grade fever of 4 weeks’ or greater duration caused by inflammation that evolves over weeks tomonths. As of November 5, 2012, the US Centers for Disease Control and Prevention (CDC) has not recommended antiFungal prophylaxis or lumbar puncture for asymptomatic patients who received epidural steroid injections. The CDC has recommended the initiation of IV voriconazole, 6 mg/kg every 12 hours, for symptomatic patients with Meningitis or parameningeal infections who received contaminated epidural steroid injections until the etiology of the Meningitis or parameningeal infection can be determined. In addition, the CDC has recommended consideration of IV liposomal amphotericin B, 7.5 mg/kg/day, in addition to voriconazole, in patients with severe disease and in those who do not improve or have progressive disease with voriconazole monotherapy. As the number of deaths continues to rise, both neurologists and their patients hope for the ability to identify CNS infection or parameningeal infection prior to the onset of symptoms. The index case of Exserohilum rostratum, reported by Lyons and colleagues, had abnormal enhancement on MRI in cervical paraspinal muscles at the epidural steroid injection site suggestive of possible infected fluid collection. Two serologic tests are * 2012, American Academy of Neurology.
Kiran T Thakur - One of the best experts on this subject based on the ideXlab platform.
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resolution of a Fungal mycotic aneurysm after a contaminated steroid injection a case report
BMC Research Notes, 2014Co-Authors: George Nelson, Kiran T Thakur, Olga Fermo, Elizabeth Felton, Jee Bang, Lucy Wilson, Susan Rhee, Rafael H Llinas, Kristine E Johnson, David J SullivanAbstract:In the past ten years there have been three separate outbreaks of Fungal contaminated steroid injections from compounding pharmacies. The 2012 outbreak of central nervous system Fungal infections associated with contaminated methylprednisolone produced by a United States compounding pharmacy has led to 750 infections (151 with Meningitis and paraspinal infections and 325 cases with paraspinal infections without Meningitis) and 64 deaths as of October 23, 2013. Exserohilum rostratum has been the predominant pathogen identified by culture, polymerase chain reaction or antibody tests. According to previous reports, cerebral involvement with phaeohyphomycosis has a high risk of morbidity and mortality. We report a 41 year-old Caucasian woman who received a lumbar methylprednisolone injection from a contaminated lot in August 2012. She was diagnosed with Fungal Meningitis by cerebrospinal fluid pleocytosis and positive (1, 3) beta-D-glucan after cultures and polymerase chain reaction were negative. Two weeks after onset of therapy, she developed a 4.1 mm superior cerebellar artery mycotic aneurysm associated with new stroke symptoms, which resolved with thirty-two weeks of antiFungal treatment. This is the rare case report of successful medical management of a cerebral mycotic aneurysm with stroke symptoms related to a presumed phaeohyphomycosis in an immunocompetent individual. Further studies are needed to determine the utility of cerebrospinal fluid (1, 3) beta-D-glucan in diagnosing and monitoring patients with Meningitis thought to be related to Fungal infection.
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utility of 1 3 β d glucan testing for diagnostics and monitoring response to treatment during the multistate outbreak of Fungal Meningitis and other infections
Clinical Infectious Diseases, 2014Co-Authors: Anastasia P. Litvintseva, Rachel M Smith, Lalitha Gade, Mark D Lindsley, Tom Chiller, Jennifer L Lyons, Kiran T Thakur, Sean X Zhang, Dale E Grgurich, Thomas M KerkeringAbstract:Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of Fungal Meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of Meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of Fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the Fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of Fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among Fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with Fungal Meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for Fungal Meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.
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cerebrospinal fluid 1 3 β d glucan detection as an aid for diagnosis of iatrogenic Fungal Meningitis
Journal of Clinical Microbiology, 2013Co-Authors: Jennifer L Lyons, Kiran T Thakur, Karen Roos, Kieren A Marr, Henry Neumann, Julie B Trivedi, Dorlan J Kimbrough, Lisa Steiner, Daniel M Harrison, Sean X ZhangAbstract:ABSTRACT This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-β-d-glucan in cerebrospinal fluid during the current U.S. outbreak of Fungal Meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.
