Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. The three species of exserohilum that are identified as human pathogens are. Exserohilum rostratum was the major cause of the multistate outbreak of fungal. Wholegenome analysis of exserohilum rostratum from an outbreak of fungal meningitis and other infections article pdf available in journal of clinical microbiology 529 june 2014 with 77 reads. Invasive rhinosinusitis by exserohilum rostratum in an immunocompetent child. Pdf characterization of exserohilum rostratum, a new causal. Realworld experience in the midst of an exserohilum. Depending on the nature of the infection, a topical or systemic agent may be used. Even after 2 weeks, when the conidia developed into the features suggestive of exserohilum spp. Once the primary pathogen in this outbreak was determined to be exserohilum rostratum, cdc developed a realtime pcr assay to detect dna from this organism in cerebrospinal fluid csf and other body fluids from patients in this outbreak.
It is also found in soils and on textiles in subtropical and tropical regions. Fatal disseminated infection due to exserohilum rostratum. Dec 01, 20 shortly thereafter, additional cases of fungal meningitis were reported, and so began a large, unprecedented, multistate fungal meningitis outbreak. Microscopic morphology hyphae are septate and brown. Multistate outbreak of fungal meningitis and other. Utility of realtime pcr for detection of exserohilum. The infections were traced to injections of methylprednisolone manufactured by the new england compounding center necc and contaminated with the fungus exserohilum rostratum.
Wholegenome analysis of exserohilum rostratum from an outbreak. On september 26, 2012, necc voluntarily recalled three lots of preservativefree mpa associated with the multistate outbreak of fungal meningitis and other infections on october 6, necc expanded its recall to include all products in circulation external icon that were distributed from its facility in framingham, massachusetts on october 11, 2012 fda released a. The present study describes a case of cutaneous phaeohyphomycosis caused by exserohilum rostratum in a child undergoing treatment for leukemia. Insights into fungal pathogenesis from the iatrogenic. Exserohilum rostratum is a thermophilic dematiaceous melanized mold that is. Insights into fungal pathogenesis from the iatrogenic epidemic of. Fungal meningitis outbreak what should clinicians do. These recommendations are based upon evidence that exserohilum rostratum a brownblack mold is the predominant pathogen in this outbreak, and expert opinion and published literature indicating that voriconazole may be effective in treating infections due to brownblack molds, as well as infections due to aspergillus species. The inoculation of a fungus into a site with limited immunological responsiveness allowed the organism to produce progressive necrotizing fatal disease in the central nervous system cns, helped by the coadministered steroid. Wikipedia so far in the month of september there have been eight confirmed cases of hantavirus pulmonary syndrome hps and three confirmed deaths due to infections with sin nombre virus, a hantavirus contracted at yosemite national park. The outbreak is presumably the result of direct inoculation of e. Walsh, what can we learn and what do we need to know amidst the iatrogenic outbreak of exserohilum rostratum meningitis. New england compounding center meningitis outbreak wikipedia.
In 2012 the medical community in the united states faced an unprecedented outbreak. Our patient initially presented with signs and symptoms of sinusitis, which. Prevention of future outbreaks such as this one will require an overhaul of the. Wholegenome analysis of exserohilum rostratum from an. The centers for disease control and prevention cdc cannot attest to the accuracy of a nonfederal website. Apart from the outbreak in the usa, this fungus has been implicated in 10 cases of acute invasive rhinosinusitis and 9 cases of allergic fungal sinusitis until now. Exserohilum rostratum, exserohilum is a common mold found in soil and on plants, especially grasses, and it thrives in warm and humid climates.
A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Recently, an outbreak in the united states was identified, linked to contaminated injections of methylprednisolone acetate mpa. Hospitalacquired phaeohyphomycosis due to exserohilum. The illnesses were caused by contamination of a preservativefree corticosteroid used for injection that was prepared by a compounding pharmacy in massachusetts. Multistate fungal meningitis outbreak interim guidance. Last month, 17 states reported cases with fungal meningitis. The outbreak was traced back toexserohilum rostratum contaminated medication for epidural steroid injections, packaged and marketed by the new england compounding center framingham, ma. Cdc image of exserohilum rostratum other pathogenic. Investigation by the centers for disease control and prevention cdc quickly led to the discovery that the causative organism was a rare, usually nonpathogenic brownblack mold, exserohilum rostratum, and that infection was associated with epidural injection of methylprednisolone acetate that had been contaminated at the compounding center at. Realworld experience in the midst of an exserohilum meningitis outbreak. Exserohilum rostratum c is a clinical isolate from a deceased patient obtained during an autopsy in a florida hospital in 2012. Invasive rhinosinusitis by exserohilum rostratum in an. Before the 2012 outbreak from contaminated methylprednisolone in the us, human infections with e rostratum were exceedingly rare.
Antiviral agents and monoclonal antibody treatments for chikungunya are in early stages of testing. Exserohilum rostratum, exserohilum longirostratum and exserohilum mcginnisii. Exserohilum rostratum is a dematiaceous fungus that rarely causes infection in humans. What can we learn and what do we need to know amidst the. It is estimated that more than 14,000 people may have been exposed to the contaminated medication.
Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone. Anatomy of a national outbreak of fungal meningitis, clinical microbiology newsletter on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Contamination of a methylprednisolone injection preparation by this pathogen resulted in more than 284 cases of exserohilum rostratum meningitis. Here, we focus on exserohilum rostratum, a dematiaceous mold that caused 753. For example, an outbreak of fungal meningitis in patients receiving steroid preparations con taminated with the rare pathogen exserohilum rostratum resulted in 750 infected patients and 61 deaths. Secondary epidural abscesses emerge in meningitis outbreak. Most recently, the mycology laboratory assisted with early guidance to clinical laboratories for rapid. 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. Nov 08, 2012 the race to understand a common but deadly. What can we learn and what do we need to know amidst the iatrogenic outbreak of exserohilum rostratum meningitis. Exserohilum definition of exserohilum by medical dictionary. Pdf extensive exserohilum infection in a burn patient. These invasive infections are difficult both to identify and to eradicate given lowsensitivity diagnostics and hightoxicity, lowefficacy antifungal therapies, hence resulting in high rates of morbidity and mortality.
The carbohydrate lectin receptor dectin1 mediates the. Four strains of exserohilum or bipolaris collected from human and plant sources were used in this study. Until this outbreak, very few human cases of exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually. As of october 23, 20, the final case count stood at 751 patients and 64 deaths, and no additional cases are. As of 24 january 2012, there have been 678 cases reported from 19 states and 44 associated deaths. Appendix d biographical sketches of workshop speakers. Yeast infections in the vagina, caused by candida albicans, can be treated with. Previously, we developed a fungal dna extraction procedure and broadrange and e. Little is known about infections caused by exserohilum rostratum, the predominant outbreak associated pathogen. Though the cfr exempts compounding pharmacies from newdrug registration requirements, it does not exempt those acting as manufacturers. Treatment should be undertaken in consultation with an infectious diseases specialist. Gillece,d chandler roe, ddavid smith, paul keim,d shawn r. The predominant etiologic agent was exserohilum rostratum, a black mould that was not known to have previously caused an outbreak of such devastating disease of this magnitude. Contamination of methylprednisolone acetate with the black mold, exserohilum rostratum, was the primary cause of the outbreak, with,000 persons exposed to the potentially contaminated drug, 741 confirmed drugrelated infections, and 55 deaths.
The largest health care associated fungal outbreak in the u. Before it was over, 751 patients were reported with fungal meningitis, stroke, spinal or paraspinal infection, or peripheral osteoarticular infection, and 64 8. The cdc, as of march 20, has found exserohilum rostratum as the primary fungal infection although 22 other species were identified including the aspergillus. Cdc and the food and drug administration fda continue to work closely with state and local public health departments on the multistate meningitis outbreak investigation of fungal infections among patients who received a steroid injection of a potentially contaminated product into the spinal area. Low quality of some generic cardiovascular medicinal products.
Utility of realtime pcr for detection of exserohilum rostratum in. Exserohilum rostratum a brownblack mold is the predominant pathogen in this outbreak, and expert opinion and published literature indicate that voriconazole might be effective in treating infections caused by brownblack molds and infections caused by aspergillus species. Jof free fulltext posaconazole alone and in combination. Although the index case had aspergillus fumigatus meningitis, subsequent reports indicated that the majority of affected patients had meningitis caused by exserohilum rostratum, an extremely rare cause of human fungal disease 1,3,4.
September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intraarticular injections. Exserohilum rostratum keratitis in a patient with human. However, the recent multistate outbreak of meningitis infection linked to steroid formulations contaminated with aspergillus fumigatus and exserohilum rostratum 9 has reignited debate. In october 2012, the cdc reported an outbreak of fungal meningitis associated with methylprednisolone injections. Several chikungunya vaccines are in development weaver et al.
Antifungal susceptibilities of outbreak strains of exserohilum rostratuma. Pathogens free fulltext genetic characterization of. Exserohilum is a very rare cause of infection in people, but it has been known to cause several different types of infections, including infection in the skin or the cornea the clear, front part of the. In midseptember 2012, the largest healthcareassociated outbreak in u. The authors wrote that little is known about infections from exserohilum rostratum, the predominant outbreak associated fungus. Exserohilum rostratum australia pdf ppt case reports. Treatment antifungal drugs are used to treat mycoses. Iatrogenic exserohilum infection of the central nervous. Little is known about its management, especially when the cns is involved. Furthermore, these outbreaks identified new populations under threat in. Exserohilum rostratum fungal meningitis associated with. Multistate fungal meningitis outbreak exserohilum rostratum.
Furthermore, cdc was able to isolate four more fungal species cladosporium cladosporioides, exserohilum rostratum, rhodotorula laryngis and rhizopus stolonifer from some of the unopened vials examined. Wholegenome analysis of exserohilum rostratum from an outbreak of fungal meningitis and other infections anastasia p. Pdf wholegenome analysis of exserohilum rostratum from. The infection was possibly due to contaminated intravenous dressings and was successfully treated with surgical. Kill shot available for download and read online in other formats.
Linking to a nonfederal website does not constitute an endorsement by cdc or any of its employees of the sponsors or the information and products presented on the website. In september 2012, the centers for disease control and prevention, in collaboration with state and local health departments and the food and drug administration fda, began investigating a multistate outbreak of fungal meningitis and. Exserohilum is a common mold found in soil and on plants that only rarely causes infections. The big safety story toward the end of the year involved an outbreak of noninfectious meningitis in 419 people in 19 states that had killed 30 as of november 6. Exserohilum rostratum, the killing fungus danny haelewaters. The pharmacokinetics of amphotericin b vary substantially depending on whether the drug is administered as conventional amphotericin b, amphotericin b lipid complex, or amphotericin b liposomal. Conidia are olivaceous brown, broadest at the basal end. A total of 22 patients had laboratory confirmation of exserohilum rostratum infection 21 patients or aspergillus fumigatus infection 1 patient. The team said that labconfirmed e rostratum was found in 96 of. As in the exserohilum outbreak described, many microorganisms involved with compounding pharmacyrelated infections are uncommon causes of human disease. Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality.
Review of 48 cases before the 2012 united states outbreak aspasia katragkou. The outbreak was deadly and affected a total of 751 individuals resulting in 64 deaths, as of october 23, 20. Volume 20 issue 1 clinical infectious diseases oxford. Fungal infections associated with contaminated steroid injections. Exserohilum rostratum is an example of a rare fungal pathogen with less than 50 reported cases prior to the steroid injection outbreak 27, even though the fungus has been known for 50 years. 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. This fungus is a common plant pathogen, causing leaf spots as well as crown rot and root rot in grasses. Exserohilum rostratum is an environmental fungal phytopathogen that was the major cause of an outbreak of fungal disease including meningitis in the usa in 201220. It is estimated that more than 14,000 people may have been exposed to the contaminated medicationthey are not necessarily infected.
Exserohilum rostratum is an example of a rare fungal pathogen with less than 50 reported cases prior to the steroid injection outbreak 27, even though. The genus is characterized by its conidia, which are ellipsoidal, distoseptate, and have a protruding and truncate hilum. Early in the epidemic, other fungi were implicated as possibly related to this outbreak based on the isolation of aspergillus fumigatus from the index case 2, 3, but all other proven infections have been related to exserohilum rostratum 25. Text is available under the creative commons attributionsharealike license. At least three lots of mpa and one of cardioplegia solution, all manufactured by necc have been found to be contaminated, most by the fungus exserohilum rostratum. Characterization of exserohilum rostratum, a new causal agent of banana leaf spot disease in china article pdf available in australasian plant pathology 403. Exserohilum spores have an inner cuplike structure which is visible in the basal cell. Conidiophores are up to 200 m long, septate, simple, geniculate, and become pale near the apex.
Setosphaeria rostrata an overview sciencedirect topics. To assess the performance of this pcr test, cdc tested 888 samples from 461 casepatients. Oct, 20 mold infections of the central nervous system cns present as abscesses, infarcts, hemorrhages, and, less commonly, meningitis. Also, large nosocomial outbreaks due to uncommon fungal species such as exserohilum rostratum and sarocladium kiliense, were both linked to contamination of medical products, however the source of another outbreak, caused by saprochaete clavata, remains unresolved. We describe a patient with severe aplastic anemia who developed fatal disseminated disease caused by e. 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. Setosphaeria rostrata is a thermophilic fungus with an asexual reproductive form treated in the genus exserohilum as exserohilum rostratum. We previously reported the mycological procedures and histopathological features for the identification of e. A new england compounding center meningitis outbreak that began in september 2012 sickened 798 individuals and resulted in the deaths of more than 100 people. The recommended treatment for exserohilum rostratum infections in this outbreak is voriconazole, according carol kauffman, md, professor of internal medicine at. Although recent molecular studies have demonstrated that the latter two species are probable synonyms of e. Many outbreak fungal infections involved cns cidrap.
Links with this icon indicate that you are leaving the cdc website. 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. Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated. Sep 10, 2019 recall injectable methylprednisolone acetate compounded at new england compounding pharmacys facility in framingham ma contaminated with environmental moulds exserohilum rostratum after an outbreak of fungal infections meningitis included caused 64 deaths 8% 12 december 2012, fda. Colonies are grey to blackishbrown, suedelike to floccose in texture, and have an olivaceous black reverse. Cdc image of exserohilum rostratum other pathogenic fungi. Pdf outbreaks of healthcareassociated fungal infections have repeatedly been. Read insights into fungal pathogenesis from the iatrogenic epidemic of exserohilum rostratum fungal meningitis, fungal genetics and biology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Litvintseva, asteven hurst, lalitha gade,a michael a. Utility of realtime pcr for detection of exserohilum rostratum in body and tissue fluids during the multistate outbreak of fungal meningitis and other infections lalitha gade,a dale e. The first cases of meningitis occurred in early september and the outbreak reached its peak in late october. Multistate fungal meningitis outbreak interim guidance for treatment. Cdc and public health response to the 2012 fungal meningitis. Exserohilum rostratum is a thermophilic dematiaceous mold, which was found to be an aggressive fungal pathogen in causing human disease in the recent multistate outbreak in the us 7,8.
Small molecules targeting fungal polyketide synthase would provide potentially novel therapeutic advances against e. Exserohilum and bipolaris isolates and culture maintenance. Infection cases caused by exposure to exserohilum are rare, but its the most well studied detail of the fungi. Shortly thereafter, additional cases of fungal meningitis were reported, and so began a large, unprecedented, multistate fungal meningitis outbreak. Exserohilum infections associated with contaminated. We report the results of sensitivity and specificity testing of this novel realtime. Fatal disseminated infection due to exserohilum rostratum in a patient with aplastic anemia.
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