178 results on '"Brandt ME"'
Search Results
2. Three competitors in three dimensions: photogrammetry reveals rapid overgrowth of coral during multispecies competition with sponges and algae
- Author
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Olinger, LK, primary, Chaves-Fonnegra, A, additional, Enochs, IC, additional, and Brandt, ME, additional
- Published
- 2021
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3. Effects of grazing, nutrients, and depth on the ciguatera-causing dinoflagellate Gambierdiscus in the US Virgin Islands
- Author
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Loeffler, CR, primary, Richlen, ML, additional, Brandt, ME, additional, and Smith, TB, additional
- Published
- 2015
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4. Response of forage plants to alteration of temperature and spring thaw date: implications for geese in a warming Arctic
- Author
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Paul L. Flint and Brandt Meixell
- Subjects
Alaska ,biomass ,Carex subspathacea ,climate change ,forage ,geese ,Ecology ,QH540-549.5 - Abstract
Abstract Changes in summer temperatures in Arctic Alaska have led to longer and warmer growing seasons over the last three decades. Corresponding with these changes in climate, the abundance and distributions of geese have increased and expanded over the same period. We used an experimental approach to assess the response of goose forage plants to simulated environmental change. We subjected Carex subspathacea, a preferred goose forage growing on the Arctic Coastal Plain (ACP) of Alaska, to manipulations of temperature and timing of spring thaw to measure potential effects in terms of plant nitrogen concentration, aboveground biomass, and total nitrogen availability. Carex subspathacea responded to warming in a dynamic fashion. Increases in temperature led to decreases in leaf nitrogen concentration but increases in aboveground biomass. The increase in biomass was stronger than the decline in nitrogen concentration such that total nitrogen availability was increased with temperature for the first 35–40 d of the season. Grazing removal accounted for only minimal offtake of biomass, and we found no indication that grazing maintained elevated levels of nitrogen concentration longer in the season as reported in other studies. Based on demonstrated relationships in the literature between forage nitrogen concentrations and gosling growth rates, we conclude that there is currently abundant high‐quality forage available across the ACP. This finding fits with recent evidence of high gosling growth rates and increasing trends in goose abundance on the ACP. Our results suggest that with climate warming of a few degrees, nitrogen concentration of forage may decrease, but forage biomass and total nitrogen availability will increase. Our data suggest that nitrogen concentration will not fall below the minimum threshold required by geese in the near future. As such, we suggest that there is currently no bottom‐up limitation to goose numbers on the ACP.
- Published
- 2021
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5. Dynamics and impact of the coral disease white plague: insights from a simulation model
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Brandt, ME, primary and McManus, JW, additional
- Published
- 2009
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6. Severe hurricanes increase recruitment and gene flow in the clonal sponge Aplysina cauliformis.
- Author
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Segura-García I, Olson JB, Gochfeld DJ, Brandt ME, and Chaves-Fonnegra A
- Subjects
- Animals, Gene Flow, Coral Reefs, Ecosystem, Caribbean Region, Cyclonic Storms, Anthozoa
- Abstract
Upright branching sponges, such as Aplysina cauliformis, provide critical three-dimensional habitat for other organisms and assist in stabilizing coral reef substrata, but are highly susceptible to breakage during storms. Breakage can increase sponge fragmentation, contributing to population clonality and inbreeding. Conversely, storms could provide opportunities for new genotypes to enter populations via larval recruitment, resulting in greater genetic diversity in locations with frequent storms. The unprecedented occurrence of two Category 5 hurricanes in close succession during 2017 in the U.S. Virgin Islands (USVI) provided a unique opportunity to evaluate whether recolonization of newly available substrata on coral reefs was due to local (e.g. re-growth of remnants, fragmentation, larval recruitment) or remote (e.g. larval transport and immigration) sponge genotypes. We sampled A. cauliformis adults and juveniles from four reefs around St. Thomas and two in St. Croix (USVI). Using a 2bRAD protocol, all samples were genotyped for single-nucleotide polymorphisms (SNPs). Results showed that these major storm events favoured sponge larval recruitment but did not increase the genetic diversity of A. cauliformis populations. Recolonization of substratum post-storms via clonality was lower (15%) than expected and instead was mainly due to sexual reproduction (85%) via local larval recruitment. Storms did enhance gene flow among and within reef sites located south of St. Thomas and north of St. Croix. Therefore, populations of clonal marine species with low pelagic dispersion, such as A. cauliformis, may benefit from increased frequency and magnitude of hurricanes for the maintenance of genetic diversity and to combat inbreeding, enhancing the resilience of Caribbean sponge communities to extreme storm events., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
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7. Rapid prototyping for quantifying belief weights of competing hypotheses about emergent diseases.
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Robertson EP, Walsh DP, Martin J, Work TM, Kellogg CA, Evans JS, Barker V, Hawthorn A, Aeby G, Paul VJ, Walker BK, Kiryu Y, Woodley CM, Meyer JL, Rosales SM, Studivan M, Moore JF, Brandt ME, and Bruckner A
- Subjects
- Animals, Bayes Theorem, Uncertainty, Anthozoa
- Abstract
Emerging diseases can have devastating consequences for wildlife and require a rapid response. A critical first step towards developing appropriate management is identifying the etiology of the disease, which can be difficult to determine, particularly early in emergence. Gathering and synthesizing existing information about potential disease causes, by leveraging expert knowledge or relevant existing studies, provides a principled approach to quickly inform decision-making and management efforts. Additionally, updating the current state of knowledge as more information becomes available over time can reduce scientific uncertainty and lead to substantial improvement in the decision-making process and the application of management actions that incorporate and adapt to newly acquired scientific understanding. Here we present a rapid prototyping method for quantifying belief weights for competing hypotheses about the etiology of disease using a combination of formal expert elicitation and Bayesian hierarchical modeling. We illustrate the application of this approach for investigating the etiology of stony coral tissue loss disease (SCTLD) and discuss the opportunities and challenges of this approach for addressing emergent diseases. Lastly, we detail how our work may apply to other pressing management or conservation problems that require quick responses. We found the rapid prototyping methods to be an efficient and rapid means to narrow down the number of potential hypotheses, synthesize current understanding, and help prioritize future studies and experiments. This approach is rapid by providing a snapshot assessment of the current state of knowledge. It can also be updated periodically (e.g., annually) to assess changes in belief weights over time as scientific understanding increases. Synthesis and applications: The rapid prototyping approaches demonstrated here can be used to combine knowledge from multiple experts and/or studies to help with fast decision-making needed for urgent conservation issues including emerging diseases and other management problems that require rapid responses. These approaches can also be used to adjust belief weights over time as studies and expert knowledge accumulate and can be a helpful tool for adapting management decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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8. Stony coral tissue loss disease induces transcriptional signatures of in situ degradation of dysfunctional Symbiodiniaceae.
- Author
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Beavers KM, Van Buren EW, Rossin AM, Emery MA, Veglia AJ, Karrick CE, MacKnight NJ, Dimos BA, Meiling SS, Smith TB, Apprill A, Muller EM, Holstein DM, Correa AMS, Brandt ME, and Mydlarz LD
- Subjects
- Animals, Coral Reefs, Transcriptome, Gene Expression Profiling, Symbiosis genetics, Anthozoa physiology, Dinoflagellida genetics
- Abstract
Stony coral tissue loss disease (SCTLD), one of the most pervasive and virulent coral diseases on record, affects over 22 species of reef-building coral and is decimating reefs throughout the Caribbean. To understand how different coral species and their algal symbionts (family Symbiodiniaceae) respond to this disease, we examine the gene expression profiles of colonies of five species of coral from a SCTLD transmission experiment. The included species vary in their purported susceptibilities to SCTLD, and we use this to inform gene expression analyses of both the coral animal and their Symbiodiniaceae. We identify orthologous coral genes exhibiting lineage-specific differences in expression that correlate to disease susceptibility, as well as genes that are differentially expressed in all coral species in response to SCTLD infection. We find that SCTLD infection induces increased expression of rab7, an established marker of in situ degradation of dysfunctional Symbiodiniaceae, in all coral species accompanied by genus-level shifts in Symbiodiniaceae photosystem and metabolism gene expression. Overall, our results indicate that SCTLD infection induces symbiophagy across coral species and that the severity of disease is influenced by Symbiodiniaceae identity., (© 2023. The Author(s).)
- Published
- 2023
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9. A meta-analysis of the stony coral tissue loss disease microbiome finds key bacteria in unaffected and lesion tissue in diseased colonies.
- Author
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Rosales SM, Huebner LK, Evans JS, Apprill A, Baker AC, Becker CC, Bellantuono AJ, Brandt ME, Clark AS, Del Campo J, Dennison CE, Eaton KR, Huntley NE, Kellogg CA, Medina M, Meyer JL, Muller EM, Rodriguez-Lanetty M, Salerno JL, Schill WB, Shilling EN, Stewart JM, and Voss JD
- Abstract
Stony coral tissue loss disease (SCTLD) has been causing significant whole colony mortality on reefs in Florida and the Caribbean. The cause of SCTLD remains unknown, with the limited concurrence of SCTLD-associated bacteria among studies. We conducted a meta-analysis of 16S ribosomal RNA gene datasets generated by 16 field and laboratory SCTLD studies to find consistent bacteria associated with SCTLD across disease zones (vulnerable, endemic, and epidemic), coral species, coral compartments (mucus, tissue, and skeleton), and colony health states (apparently healthy colony tissue (AH), and unaffected (DU) and lesion (DL) tissue from diseased colonies). We also evaluated bacteria in seawater and sediment, which may be sources of SCTLD transmission. Although AH colonies in endemic and epidemic zones harbor bacteria associated with SCTLD lesions, and aquaria and field samples had distinct microbial compositions, there were still clear differences in the microbial composition among AH, DU, and DL in the combined dataset. Alpha-diversity between AH and DL was not different; however, DU showed increased alpha-diversity compared to AH, indicating that, prior to lesion formation, corals may undergo a disturbance to the microbiome. This disturbance may be driven by Flavobacteriales, which were especially enriched in DU. In DL, Rhodobacterales and Peptostreptococcales-Tissierellales were prominent in structuring microbial interactions. We also predict an enrichment of an alpha-toxin in DL samples which is typically found in Clostridia. We provide a consensus of SCTLD-associated bacteria prior to and during lesion formation and identify how these taxa vary across studies, coral species, coral compartments, seawater, and sediment., (© 2023. The Author(s).)
- Published
- 2023
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10. Disease resistance in coral is mediated by distinct adaptive and plastic gene expression profiles.
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MacKnight NJ, Dimos BA, Beavers KM, Muller EM, Brandt ME, and Mydlarz LD
- Subjects
- Animals, Coral Reefs, Disease Resistance genetics, Plastics, Transcriptome, Anthozoa genetics
- Abstract
Infectious diseases are an increasing threat to coral reefs, resulting in altered community structure and hindering the functional contributions of disease-susceptible species. We exposed seven reef-building coral species from the Caribbean to white plague disease and determined processes involved in (i) lesion progression, (ii) within-species gene expression plasticity, and (iii) expression-level adaptation among species that lead to differences in disease risk. Gene expression networks enriched in immune genes and cytoskeletal arrangement processes were correlated to lesion progression rates. Whether or not a coral developed a lesion was mediated by plasticity in genes involved in extracellular matrix maintenance, autophagy, and apoptosis, while resistant coral species had constitutively higher expression of intracellular protein trafficking. This study offers insight into the process involved in lesion progression and within- and between-species dynamics that lead to differences in disease risk that is evident on current Caribbean reefs.
- Published
- 2022
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11. Experimental transmission of Stony Coral Tissue Loss Disease results in differential microbial responses within coral mucus and tissue.
- Author
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Huntley N, Brandt ME, Becker CC, Miller CA, Meiling SS, Correa AMS, Holstein DM, Muller EM, Mydlarz LD, Smith TB, and Apprill A
- Abstract
Stony coral tissue loss disease (SCTLD) is a widespread and deadly disease that affects nearly half of Caribbean coral species. To understand the microbial community response to this disease, we performed a disease transmission experiment on US Virgin Island (USVI) corals, exposing six species of coral with varying susceptibility to SCTLD. The microbial community of the surface mucus and tissue layers were examined separately using a small subunit ribosomal RNA gene-based sequencing approach, and data were analyzed to identify microbial community shifts following disease acquisition, potential causative pathogens, as well as compare microbiota composition to field-based corals from the USVI and Florida outbreaks. While all species displayed similar microbiome composition with disease acquisition, microbiome similarity patterns differed by both species and mucus or tissue microhabitat. Further, disease exposed but not lesioned corals harbored a mucus microbial community similar to those showing disease signs, suggesting that mucus may serve as an early warning detection for the onset of SCTLD. Like other SCTLD studies in Florida, Rhodobacteraceae, Arcobacteraceae, Desulfovibrionaceae, Peptostreptococcaceae, Fusibacter, Marinifilaceae, and Vibrionaceae dominated diseased corals. This study demonstrates the differential response of the mucus and tissue microorganisms to SCTLD and suggests that mucus microorganisms may be diagnostic for early disease exposure., (© 2022. The Author(s).)
- Published
- 2022
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12. Alphaflexivirus Genomes in Stony Coral Tissue Loss Disease-Affected, Disease-Exposed, and Disease-Unexposed Coral Colonies in the U.S. Virgin Islands.
- Author
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Veglia AJ, Beavers K, Van Buren EW, Meiling SS, Muller EM, Smith TB, Holstein DM, Apprill A, Brandt ME, Mydlarz LD, and Correa AMS
- Abstract
Stony coral tissue loss disease (SCTLD) is decimating Caribbean corals. Here, through the metatranscriptomic assembly and annotation of two alphaflexivirus-like strains, we provide genomic evidence of filamentous viruses in SCTLD-affected, -exposed, and -unexposed coral colonies. These data will assist in clarifying the roles of viruses in SCTLD.
- Published
- 2022
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13. Investigating the roles of transforming growth factor-beta in immune response of Orbicella faveolata, a scleractinian coral.
- Author
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Fuess LE, Butler CC, Brandt ME, and Mydlarz LD
- Subjects
- Animals, Caribbean Region, Cells, Cultured, Coral Reefs, Dinoflagellida, Immunity, Immunomodulation, Signal Transduction, Symbiosis, Transcriptome, Anthozoa immunology, Transforming Growth Factor beta metabolism
- Abstract
Symbiotic relationships range from parasitic to mutualistic, yet all endosymbionts face similar challenges, including evasion of host immunity. Many symbiotic organisms have evolved similar mechanisms to face these challenges, including manipulation of the host's transforming growth factor-beta (TGFβ) pathway. Here we investigate the TGFβ pathway in scelaractinian corals which are dependent on symbioses with dinoflagellates from the family Symbiodiniaceae. Using the Caribbean coral, Orbicella faveolata, we explore the effects of enhancement and inhibition of the TGFβ pathway on host gene expression. Following transcriptomic analyses, we demonstrated limited effects of pathway manipulation in absence of immune stimulation. However, manipulation of the TGFβ pathway significantly affects the subsequent ability of host corals to mount an immune response. Enhancement of the TGFβ pathway eliminates transcriptomic signatures of host coral immune response, while inhibition of the pathway maintains the response. This is, to our knowledge, the first evidence of an immunomodulatory role for TGFβ in a scelaractinian coral. These findings suggest variation in TGFβ signaling may have implications in the face of increasing disease prevelance. Our results suggest that the TGFβ pathway can modulate tradeoffs between symbiosis and immunity. Further study of links between symbiosis, TGFβ, and immunity is needed to better understand the ecological implications of these findings., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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14. Constitutively active MyD88/CD40 costimulation enhances expansion and efficacy of chimeric antigen receptor T cells targeting hematological malignancies.
- Author
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Collinson-Pautz MR, Chang WC, Lu A, Khalil M, Crisostomo JW, Lin PY, Mahendravada A, Shinners NP, Brandt ME, Zhang M, Duong M, Bayle JH, Slawin KM, Spencer DM, and Foster AE
- Subjects
- Animals, Antigens, CD19 immunology, Cell Proliferation drug effects, HEK293 Cells, Humans, Immunotherapy, Adoptive methods, Lymphocyte Activation immunology, Mice, Mice, Inbred NOD, Signal Transduction immunology, THP-1 Cells, CD40 Antigens immunology, CD8-Positive T-Lymphocytes immunology, Hematologic Neoplasms immunology, Hematologic Neoplasms therapy, Myeloid Differentiation Factor 88 immunology, Receptors, Antigen, T-Cell immunology, Receptors, Chimeric Antigen immunology
- Abstract
Successful adoptive chimeric antigen receptor (CAR) T-cell therapies against hematological malignancies require CAR-T expansion and durable persistence following infusion. Balancing increased CAR-T potency with safety, including severe cytokine-release syndrome (sCRS) and neurotoxicity, warrants inclusion of safety mechanisms to control in vivo CAR-T activity. Here, we describe a novel CAR-T cell platform that utilizes expression of the toll-like receptor (TLR) adaptor molecule, MyD88, and tumor-necrosis factor family member, CD40 (MC), tethered to the CAR molecule through an intentionally inefficient 2A linker system, providing a constitutive signal that drives CAR-T survival, proliferation, and antitumor activity against CD19
+ and CD123+ hematological cancers. Robust activity of MC-enhanced CAR-T cells was associated with cachexia in animal models that corresponded with high levels of human cytokine production. However, toxicity could be successfully resolved by using the inducible caspase-9 (iC9) safety switch to reduce serum cytokines, by administration of a neutralizing antibody against TNF-α, or by selecting "low" cytokine-producing CD8+ T cells, without loss of antitumor activity. Interestingly, high basal activity was essential for in vivo CAR-T expansion. This study shows that co-opting novel signaling elements (i.e., MyD88 and CD40) and development of a unique CAR-T architecture can drive T-cell proliferation in vivo to enhance CAR-T therapies.- Published
- 2019
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15. Two-Dimensional Regulation of CAR-T Cell Therapy with Orthogonal Switches.
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Duong MT, Collinson-Pautz MR, Morschl E, Lu A, Szymanski SP, Zhang M, Brandt ME, Chang WC, Sharp KL, Toler SM, Slawin KM, Foster AE, Spencer DM, and Bayle JH
- Abstract
Use of chimeric antigen receptors (CARs) as the basis of targeted adoptive T cell therapies has enabled dramatic efficacy against multiple hematopoietic malignancies, but potency against bulky and solid tumors has lagged, potentially due to insufficient CAR-T cell expansion and persistence. To improve CAR-T cell efficacy, we utilized a potent activation switch based on rimiducid-inducible MyD88 and CD40 (iMC)-signaling elements. To offset potential toxicity risks by this enhanced CAR, an orthogonally regulated, rapamycin-induced, caspase-9-based safety switch (iRC9) was developed to allow in vivo elimination of CAR-T cells. iMC costimulation induced by systemic rimiducid administration enhanced CAR-T cell proliferation, cytokine secretion, and antitumor efficacy in both in vitro assays and xenograft tumor models. Conversely, rapamycin-mediated iRC9 dimerization rapidly induced apoptosis in a dose-dependent fashion as an approach to mitigate therapy-related toxicity. This novel, regulatable dual-switch system may promote greater CAR-T cell expansion and prolonged persistence in a drug-dependent manner while providing a safety switch to mitigate toxicity concerns.
- Published
- 2018
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16. Depth and coral cover drive the distribution of a coral macroborer across two reef systems.
- Author
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Maher RL, Johnston MA, Brandt ME, Smith TB, and Correa AMS
- Subjects
- Animals, Geography, Gulf of Mexico, Image Processing, Computer-Assisted, Regression Analysis, Anthozoa physiology, Coral Reefs, Thoracica physiology
- Abstract
Bioerosion, the removal of calcium carbonate from coral frameworks by living organisms, influences a variety of reef features, from their topographic complexity to the net balance of carbonate budgets. Little is known, however, about how macroborers, which bore into reef substrates leaving traces greater than 0.1 mm diameter, are distributed across coral reefs, particularly reef systems with high (>50%) stony coral cover or at mesophotic depths (≥30 m). Here, we present an accurate and efficient method for quantifying macroborer densities from stony coral hosts via image analysis, using the bioeroding barnacle, Lithotrya dorsalis, and its host coral, Orbicella franksi, as a case study. We found that in 2014, L. dorsalis densities varied consistently with depth and host percent cover in two Atlantic reef systems: the Flower Garden Banks (FGB, northwest Gulf of Mexico) and the U.S. Virgin Islands (USVI). Although average barnacle density was nearly 4.5 times greater overall in the FGB than in the USVI, barnacle density decreased with depth in both reef regions. Barnacle density also scaled negatively with increasing coral cover in the study areas, suggesting that barnacle populations are not strictly space-limited in their distribution and settlement opportunities. Our findings suggest that depth and host coral cover, and potentially, local factors may strongly influence the abundance of macroborers, and thus the rate of CaCO3 loss, in a given reef system. Our image analysis method for quantifying macroborers can be standardized across historical and modern reef records to better understand how borers impact host growth and reef health., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
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17. Coral reef health response to chronic and acute changes in water quality in St. Thomas, United States Virgin Islands.
- Author
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Ennis RS, Brandt ME, Wilson Grimes KR, and Smith TB
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- Animals, Anthozoa physiology, Chlorophyll analysis, Environmental Monitoring methods, Geologic Sediments, Rain, Seawater, Seaweed, United States Virgin Islands, Coral Reefs, Water Quality
- Abstract
It is suspected that land cover alteration on the southern coast of St. Thomas, USVI has increased runoff, degrading nearshore water quality and coral reef health. Chronic and acute changes in water quality, sediment deposition, and coral health metrics were assessed in three zones based upon perceived degree of human influence. Chlorophyll (p<0.0001) and turbidity (p=0.0113) were significantly higher in nearshore zones and in the high impact zone during heavy precipitation. Net sediment deposition and terrigenous content increased in nearshore zones during periods of greater precipitation and port activity. Macroalgae overgrowth significantly increased along a gradient of decreasing water quality (p<0.0001). Coral bleaching in all zones peaked in November with a regional thermal stress event (p<0.0001). However, mean bleaching prevalence was significantly greater in the most impacted zone compared to the offshore zone (p=0.0396), suggesting a link between declining water quality and bleaching severity., (Published by Elsevier Ltd.)
- Published
- 2016
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18. Clinical and Laboratory Profile of Persons Living with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Histoplasmosis from a Colombian Hospital.
- Author
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Caceres DH, Tobón AM, Cleveland AA, Scheel CM, Berbesi DY, Ochoa J, Restrepo A, Brandt ME, Chiller T, and Gómez BL
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- Abdominal Pain etiology, Acquired Immunodeficiency Syndrome blood, Acquired Immunodeficiency Syndrome complications, Adult, Coinfection complications, Coinfection physiopathology, Colombia, Cough etiology, Diarrhea etiology, Dyspnea etiology, Female, HIV Infections complications, HIV Infections physiopathology, Headache etiology, Hepatomegaly etiology, Histoplasmosis complications, Histoplasmosis physiopathology, Humans, Karnofsky Performance Status, Leukopenia etiology, Lymphadenopathy etiology, Male, Nausea etiology, Skin Ulcer etiology, Splenomegaly etiology, Thrombocytopenia etiology, Tuberculosis complications, Tuberculosis physiopathology, Vomiting etiology, Weight Loss, Alanine Transaminase blood, Aspartate Aminotransferases blood, Coinfection blood, HIV Infections blood, Histoplasmosis blood, Tuberculosis blood
- Abstract
Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La María in Medellín, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHA with PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum., (© The American Society of Tropical Medicine and Hygiene.)
- Published
- 2016
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19. Caribbean mesophotic coral ecosystems are unlikely climate change refugia.
- Author
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Smith TB, Gyory J, Brandt ME, Miller WJ, Jossart J, and Nemeth RS
- Subjects
- Animals, Anthozoa, Caribbean Region, Ecosystem, Climate Change, Coral Reefs, Refugium
- Abstract
Deeper coral reefs experience reduced temperatures and light and are often shielded from localized anthropogenic stressors such as pollution and fishing. The deep reef refugia hypothesis posits that light-dependent stony coral species at deeper depths are buffered from thermal stress and will avoid bleaching-related mass mortalities caused by increasing sea surface temperatures under climate change. This hypothesis has not been tested because data collection on deeper coral reefs is difficult. Here we show that deeper (mesophotic) reefs, 30-75 m depth, in the Caribbean are not refugia because they have lower bleaching threshold temperatures than shallow reefs. Over two thermal stress events, mesophotic reef bleaching was driven by a bleaching threshold that declines 0.26 °C every +10 m depth. Thus, the main premise of the deep reef refugia hypothesis that cooler environments are protective is incorrect; any increase in temperatures above the local mean warmest conditions can lead to thermal stress and bleaching. Thus, relatively cooler temperatures can no longer be considered a de facto refugium for corals and it is likely that many deeper coral reefs are as vulnerable to climate change as shallow water reefs., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2016
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20. Notes from the Field: Probable Mucormycosis Among Adult Solid Organ Transplant Recipients at an Acute Care Hospital - Pennsylvania, 2014-2015.
- Author
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Novosad SA, Vasquez AM, Nambiar A, Arduino MJ, Christensen E, Moulton-Meissner H, Keckler MS, Miller J, Perz JF, Lockhart SR, Chiller T, Gould C, Sehulster L, Brandt ME, Weber JT, Halpin AL, and Mody RK
- Subjects
- Adult, Cluster Analysis, Critical Care, Cross Infection diagnosis, Hospitals, Humans, Mucormycosis diagnosis, Pennsylvania epidemiology, Cross Infection epidemiology, Disease Outbreaks, Mucormycosis epidemiology, Organ Transplantation adverse effects, Transplant Recipients
- Abstract
On September 17, 2015, the Pennsylvania Department of Health (PADOH) notified CDC of a cluster of three potentially health care-associated mucormycete infections that occurred among solid organ transplant recipients during a 12-month period at hospital A. On September 18, hospital B reported that it had identified an additional transplant recipient with mucormycosis. Hospitals A and B are part of the same health care system and are connected by a pedestrian bridge. PADOH requested CDC's assistance with an on-site investigation, which started on September 22, to identify possible sources of infection and prevent additional infections.
- Published
- 2016
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21. Seasonal Variability in Calorimetric Energy Content of Two Caribbean Mesophotic Corals.
- Author
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Brandtneris VW, Brandt ME, Glynn PW, Gyory J, and Smith TB
- Subjects
- Animals, Anthozoa metabolism, Caribbean Region, Photosynthesis, Principal Component Analysis, Anthozoa physiology, Energy Metabolism, Seasons
- Abstract
Energetic responses of zooxanthellate reef corals along depth gradients have relevance to the refugia potential of mesophotic coral ecosystems (MCEs). Previous observations suggested that MCEs in the Caribbean are thermally buffered during the warmest parts of the year and occur within or just below the chlorophyll maximum, suggesting abundant trophic resources. However, it is not known if mesophotic corals can maintain constant energy needs throughout the year with changing environmental and biological conditions. The energetic content of tissues from the stony coral species Orbicella faveolata and Agaricia lamarcki was measured on the southern insular shelf of St. Thomas, US Virgin Islands (USVI), using micro-bomb calorimetry. Three sites for each species, at depths of 6m, 25m, 38m and 63m, were selected to capture energetic differences across the major vertical range extent of both species in the USVI-and sampled over five periods from April 2013 to April 2014. Mesophotic colonies of O. faveolata exhibited a significant reduction in energetic content during the month of September 2013 compared to mid-depth and shallow colonies (p = 0.032), whereas A. lamarcki experienced similar energetic variability, but with a significant reduction in energy content that occurred in July 2013 for colonies at sites deeper than 25m (p = 0.014). The results of calorimetric analyses indicate that O. faveolata may be at risk during late summer stress events, possibly due to the timing of reproductive activities. The low-point of A. lamarcki energy content, which may also coincide with reproduction, occurs prior to seasonal stress events, indicating contrasting, species-specific responses to environmental variability on MCEs.
- Published
- 2016
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22. Agreement of Direct Antifungal Susceptibility Testing from Positive Blood Culture Bottles with the Conventional Method for Candida Species.
- Author
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Jabeen K, Kumar H, Farooqi J, Mehboob R, Brandt ME, and Zafar A
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- Candida classification, Disk Diffusion Antimicrobial Tests, Humans, Microbial Sensitivity Tests standards, Prospective Studies, Reproducibility of Results, Antifungal Agents pharmacology, Candida drug effects, Candida isolation & purification, Microbial Sensitivity Tests methods
- Abstract
Early availability of antifungal susceptibilities can ensure timely institution of targeted therapy in candidemia, which can improve patient outcomes. This study prospectively determines the agreement between the results of direct testing of antifungal susceptibilities from blood culture bottles by disk diffusion and Etest and the results of standardized susceptibility testing methods; direct testing would allow susceptibility results to be available 1 to 2 days earlier. A total of 104 blood cultures with different Candida species (28% C. albicans, 27% C. parapsilosis, 26% C. tropicalis, etc.) were evaluated between January 2012 and May 2013 for agreement of fluconazole, voriconazole, and amphotericin B susceptibility results by disk diffusion. Agreement in MICs obtained by Etest was determined for fluconazole (21 isolates), voriconazole (28 isolates), amphotericin (29 isolates), and caspofungin (29 isolates). The kappa scores for categorical agreement were highest for fluconazole by disk diffusion (0.902, standard error [SE] = 0.076) and Etest (1.00, SE = 0.218) and for amphotericin B by disk diffusion (1.00, SE = 0.098). The Pearson correlation (r) of zone diameters was strongest for fluconazole (0.69) and amphotericin (0.70) and moderate for voriconazole (0.60), and the Pearson correlation of MICs was strongest for fluconazole (0.94) and caspofungin (0.88). However, the moderate correlation of amphotericin MICs with zone diameters (-0.42) precludes the use of amphotericin B disk diffusion for susceptibility testing. There were no very major errors; however, there were 1 (1%) major and 5 (4.8%) minor errors with disk diffusion and 4 (13.3%) minor errors with Etest. Thus, antifungal disk diffusion directly from blood culture bottles is a rapid and easy method for fluconazole and voriconazole susceptibility testing for timely tailoring of candidemia therapy., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
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23. Evaluation of the Specificity of Two Enzyme Immunoassays for Coccidioidomycosis by Using Sera from a Region of Endemicity and a Region of Nonendemicity.
- Author
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Lindsley MD, Ahn Y, McCotter O, Gade L, Hurst SF, Brandt ME, Park BJ, and Litvintseva AP
- Subjects
- Arizona, Coccidioidomycosis epidemiology, Endemic Diseases, Healthy Volunteers, Humans, Immunodiffusion, Immunoglobulin G blood, Immunoglobulin M blood, Mexico, Puerto Rico, Reagent Kits, Diagnostic, Sensitivity and Specificity, Antibodies, Fungal blood, Coccidioides immunology, Coccidioidomycosis diagnosis, Immunoenzyme Techniques standards, Serologic Tests methods
- Abstract
Coccidioidomycosis (CM), a serious life-threatening fungal infection endemic to arid regions of the western United States and Mexico, can be challenging to diagnose in a timely manner. Commercially developed enzyme immunoassays (EIAs) (from Meridian Biosciences and Immuno-Mycologics [IMMY]) have provided faster, simpler means for serodiagnosis; however, independent evaluations have questioned EIA specificity, particularly IgM-positive/IgG-negative results. This study was conducted to evaluate EIA specificity among persons residing in Puerto Rico (n = 534), where CM is not endemic (who were not likely to have been exposed to Coccidioides spp.), compared to blood bank donors residing in Arizona (n = 1,218), where CM is endemic. Upon comparing serum reactivity between Puerto Rico and Arizona, the Meridian EIA showed a significant difference in IgG reactivity (0.37% versus 3.6%; P < 0.001) but not IgM reactivity (3.4% versus 2.4%; P = 0.31). No IgM-/IgG-reactive sera were detected among sera from Puerto Rico, compared to 7 (0.57%) sera from Arizona. Similar results were observed using the IMMY EIA, although significantly (P = 0.03) fewer IgM-reactive sera from Arizona were observed, compared to the Meridian EIA. EIA-reactive sera were also evaluated by immunodiffusion before and after 3- to 4-fold concentration of the sera. These results demonstrate that elevated IgG EIA reactivity is present in sera from healthy individuals in regions of endemicity and that IgM EIA reactivity observed in sera from individuals residing outside regions of endemicity is most likely nonspecific. Other criteria, including clinical and microbiological evaluations, should be taken into account when interpreting results from surveillance studies and other reporting measures., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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24. Environmental conditions influence tissue regeneration rates in scleractinian corals.
- Author
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Sabine AM, Smith TB, Williams DE, and Brandt ME
- Subjects
- Animals, Environment, Geologic Sediments, Oxygen analysis, United States Virgin Islands, Anthozoa physiology, Environmental Monitoring, Regeneration physiology, Water Quality
- Abstract
Natural and anthropogenic factors may influence corals' ability to recover from partial mortality. To examine how environmental conditions affect lesion healing, we assessed several water quality parameters and tissue regeneration rates in corals at six reefs around St. Thomas, US Virgin Islands. We hypothesized that sites closer to developed areas would have poor water quality due to proximity to anthropogenic stresses, which would impede tissue regeneration. We found that water flow and turbidity most strongly influenced lesion recovery rates. The most impacted site, with high turbidity and low flow, recovered almost three times slower than the least impacted site, with low turbidity, high flow, and low levels of anthropogenic disturbance. Our results illustrate that in addition to lesion-specific factors known to affect tissue regeneration, environmental conditions can also control corals' healing rates. Resource managers can use this information to protect low-flow, turbid nearshore reefs by minimizing sources of anthropogenic stress., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
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25. Phaeohyphomycosis in transplant recipients: Results from the Transplant Associated Infection Surveillance Network (TRANSNET).
- Author
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McCarty TP, Baddley JW, Walsh TJ, Alexander BD, Kontoyiannis DP, Perl TM, Walker R, Patterson TF, Schuster MG, Lyon GM, Wingard JR, Andes DR, Park BJ, Brandt ME, and Pappas PG
- Subjects
- Adult, Aged, Antifungal Agents therapeutic use, Epidemiological Monitoring, Female, Humans, Male, Middle Aged, Opportunistic Infections drug therapy, Opportunistic Infections mortality, Opportunistic Infections pathology, Phaeohyphomycosis drug therapy, Phaeohyphomycosis mortality, Phaeohyphomycosis pathology, Prospective Studies, Survival Analysis, Opportunistic Infections epidemiology, Phaeohyphomycosis epidemiology, Transplant Recipients
- Abstract
Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P = <.001). The most frequent pathogen was Alternaria species (32%). Disseminated disease was found in 55.4%. Cutaneous infection was more common in SOT (53.3% vs 23.1%; P = .021), while pulmonary disease was more common in SCT (57.7 vs. 26.7; P = .019). Voriconazole (44.6%) and amphotericin B preparations (37.5%) were the most common antifungal therapies. Overall mortality was 25% and was higher in SCT than in SOT (42% vs 10%; P = <.001). A wide variety of organisms encompass phaeohyphomycosis contributing to varying types of infection in transplant recipients. Site of infection, time to disease, and mortality varies significantly between SCT and SOT recipients. Lipid formulations of amphotericin B and voriconazole were the most common antifungals used to treat this disorder., (© The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)
- Published
- 2015
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26. Investigating fungal outbreaks in the 21st century.
- Author
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Litvintseva AP, Brandt ME, Mody RK, and Lockhart SR
- Subjects
- Animals, Fungi metabolism, History, 21st Century, Humans, Disease Outbreaks history, Disease Outbreaks prevention & control, Environmental Exposure, Fungi isolation & purification, Genome, Microbial genetics, Genotype
- Published
- 2015
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27. Notes from the field: Fatal gastrointestinal mucormycosis in a premature infant associated with a contaminated dietary supplement--Connecticut, 2014.
- Author
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Vallabhaneni S, Walker TA, Lockhart SR, Ng D, Chiller T, Melchreit R, Brandt ME, and Smith RM
- Subjects
- Connecticut, Fatal Outcome, Gastroenteritis etiology, Gastrointestinal Tract blood supply, Humans, Infant, Newborn, Infant, Premature, Diseases etiology, Ischemia diagnosis, Ischemia etiology, Male, Mucormycosis etiology, Dietary Supplements adverse effects, Food Contamination, Gastroenteritis diagnosis, Infant Food adverse effects, Infant, Premature, Diseases diagnosis, Mucormycosis diagnosis
- Abstract
In October 2014, a hospital in Connecticut notified CDC and the Connecticut Department of Public Health of a fatal case of gastrointestinal mucormycosis in a preterm infant. The infant, born at 29 weeks' gestation and weighing 1,400 grams (about 3 pounds), had developed signs and symptoms initially consistent with necrotizing enterocolitis approximately 1 week after birth. Exploratory laparotomy revealed complete ischemia of the gastrointestinal tract from the esophagus to the rectum; a portion of necrotic cecum was sent for microscopic examination. Following surgery, the infant developed multiple areas of vascular occlusion, including a large clot in the aorta, findings not usually associated with necrotizing enterocolitis. The infant died soon after. Histopathology results from the resected cecum revealed an angioinvasive fungal infection consistent with mucormycosis. Gastrointestinal mucormycosis is an extremely rare fungal infection caused by mold in the order Mucorales. It occurs predominantly in low birth weight infants, patients with diarrhea and malnutrition, and those receiving peritoneal dialysis; mortality is 85%. Local investigation revealed that the infant had received a dietary supplement, ABC Dophilus Powder, for 7 days, beginning on day 1 of life.
- Published
- 2015
28. 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.
- Author
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Gade L, Grgurich DE, Kerkering TM, Brandt ME, and Litvintseva AP
- Subjects
- Ascomycota genetics, Body Fluids microbiology, Drug Monitoring, Female, Humans, Male, Meningitis, Fungal diagnosis, Meningitis, Fungal drug therapy, Meningitis, Fungal microbiology, Methylprednisolone administration & dosage, Methylprednisolone adverse effects, Methylprednisolone Acetate, Molecular Diagnostic Techniques methods, New England epidemiology, Sensitivity and Specificity, Ascomycota isolation & purification, Disease Outbreaks, Drug Contamination, Iatrogenic Disease epidemiology, Meningitis, Fungal epidemiology, Methylprednisolone analogs & derivatives, Real-Time Polymerase Chain Reaction methods
- Abstract
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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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29. Valley fever: finding new places for an old disease: Coccidioides immitis found in Washington State soil associated with recent human infection.
- Author
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Litvintseva AP, Marsden-Haug N, Hurst S, Hill H, Gade L, Driebe EM, Ralston C, Roe C, Barker BM, Goldoft M, Keim P, Wohrle R, Thompson GR 3rd, Engelthaler DM, Brandt ME, and Chiller T
- Subjects
- Cluster Analysis, Coccidioides classification, Coccidioides genetics, DNA, Fungal chemistry, DNA, Fungal genetics, Genome, Fungal, Humans, Microbiological Techniques, Molecular Sequence Data, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA, Sequence Homology, Washington, Coccidioides isolation & purification, Coccidioidomycosis epidemiology, Coccidioidomycosis microbiology, Endemic Diseases, Soil Microbiology
- Abstract
We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
- Published
- 2015
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30. Whole-genome analysis of Exserohilum rostratum from an outbreak of fungal meningitis and other infections.
- Author
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Litvintseva AP, Hurst S, Gade L, Frace MA, Hilsabeck R, Schupp JM, Gillece JD, Roe C, Smith D, Keim P, Lockhart SR, Changayil S, Weil MR, MacCannell DR, Brandt ME, and Engelthaler DM
- Subjects
- Ascomycota isolation & purification, Cluster Analysis, Humans, Meningitis, Fungal microbiology, Molecular Epidemiology, Molecular Sequence Data, Molecular Typing, Mycological Typing Techniques, Mycoses microbiology, New England, Phylogeny, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Ascomycota classification, Ascomycota genetics, Disease Outbreaks, Genome, Fungal, Meningitis, Fungal epidemiology, Mycoses epidemiology
- Abstract
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., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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31. Validation of an enzyme-linked immunosorbent assay that detects Histoplasma capsulatum antigenuria in Colombian patients with AIDS for diagnosis and follow-up during therapy.
- Author
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Caceres DH, Scheel CM, Tobón AM, Ahlquist Cleveland A, Restrepo A, Brandt ME, Chiller T, and Gómez BL
- Subjects
- AIDS-Related Opportunistic Infections diagnosis, Cohort Studies, Colombia, Enzyme-Linked Immunosorbent Assay methods, Histoplasmosis drug therapy, Humans, Prospective Studies, Sensitivity and Specificity, Antigens, Fungal urine, Clinical Laboratory Techniques methods, Drug Monitoring methods, Histoplasma immunology, Histoplasmosis diagnosis
- Abstract
We validated an antigen capture enzyme-linked immunosorbent assay (ELISA) in Colombian persons with AIDS and proven histoplasmosis and evaluated the correlation between antigenuria and clinical improvement during follow-up. The sensitivity of the Histoplasma capsulatum ELISA was 86%, and the overall specificity was 94%. The antigen test successfully monitored the response to therapy., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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32. Coccidioides immitis identified in soil outside of its known range - Washington, 2013.
- Author
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Marsden-Haug N, Hill H, Litvintseva AP, Engelthaler DM, Driebe EM, Roe CC, Ralston C, Hurst S, Goldoft M, Gade L, Wohrle R, Thompson GR, Brandt ME, and Chiller T
- Subjects
- Coccidioidomycosis epidemiology, Humans, Washington epidemiology, Coccidioides classification, Coccidioides isolation & purification, Soil Microbiology
- Abstract
Coccidioidomycosis ("valley fever") is caused by inhaling spores of the soil-dwelling fungi Coccidioides immitis or Coccidioides posadasii. Most infections are subclinical. When clinical manifestations do occur (typically 1-4 weeks after exposure), they are similar to those associated with influenza or community-acquired pneumonia. Disseminated disease is rare. Residual pulmonary nodules can lead to chronic lung disease. Fluconazole or other triazoles often are used for treatment, but mild cases often resolve without specific therapy. A total of 17,802 cases were reported in the United States in 2012.
- Published
- 2014
33. Real-time PCR assays for genotyping of Cryptococcus gattii in North America.
- Author
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Kelley EJ, Driebe EM, Etienne K, Brandt ME, Schupp JM, Gillece JD, Trujillo JS, Lockhart SR, Deak E, Keim PS, and Engelthaler DM
- Subjects
- Animals, Cryptococcosis microbiology, Cryptococcosis veterinary, Cryptococcus gattii isolation & purification, DNA, Fungal genetics, Environmental Microbiology, Humans, Molecular Epidemiology methods, North America epidemiology, Sensitivity and Specificity, Cryptococcus gattii classification, Cryptococcus gattii genetics, Genotyping Techniques methods, Mycological Typing Techniques methods, Real-Time Polymerase Chain Reaction methods
- Abstract
Background: Cryptococcus gattii has been the cause of an ongoing outbreak starting in 1999 on Vancouver Island, British Columbia and spreading to mainland Canada and the US Pacific Northwest. In the course of the outbreak, C. gattii has been identified outside of its previously documented climate, habitat, and host disease. Genotyping of C. gattii is essential to understand the ecological and geographical expansion of this emerging pathogen., Methods: We developed and validated a mismatch amplification mutation assay (MAMA) real-time PCR panel for genotyping C. gattii molecular types VGI-VGIV and VGII subtypes a,b,c. Subtype assays were designed based on whole-genome sequence of 20 C. gattii strains. Publically available multilocus sequence typing (MLST) data from a study of 202 strains was used for the molecular type (VGI-VGIV) assay design. All assays were validated across DNA from 112 strains of diverse international origin and sample types, including animal, environmental and human., Results: Validation revealed each assay on the panel is 100% sensitive, specific and concordant with MLST. The assay panel can detect down to 0.5 picograms of template DNA., Conclusions: The (MAMA) real-time PCR panel for C. gattii accurately typed a collection of 112 diverse strains and demonstrated high sensitivity. This is a time and cost efficient method of genotyping C. gattii best suited for application in large-scale epidemiological studies.
- Published
- 2014
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34. 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.
- Author
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Litvintseva AP, Lindsley MD, Gade L, Smith R, Chiller T, Lyons JL, Thakur KT, Zhang SX, Grgurich DE, Kerkering TM, Brandt ME, and Park BJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Proteoglycans, Sensitivity and Specificity, Clinical Laboratory Techniques methods, Diagnostic Tests, Routine methods, Disease Outbreaks, Drug Monitoring methods, Meningitis, Fungal diagnosis, Meningitis, Fungal epidemiology, beta-Glucans cerebrospinal fluid
- Abstract
Background: The 2012 outbreak of fungal meningitis associated with contaminated methylprednisolone produced by a compounding pharmacy has resulted in >750 infections. An important question facing patients and clinicians is the duration of antifungal therapy. We evaluated (1-3)-β-d-glucan (BDG) as a marker for monitoring response to treatment., Methods: We determined sensitivity and specificity of BDG testing using the Fungitell assay, by testing 41 cerebrospinal fluid (CSF) specimens from confirmed cases of fungal meningitis and 66 negative control CSF specimens. We also assessed whether BDG levels correlate with clinical status by using incident samples from 108 case patients with meningitis and 20 patients with serially collected CSF., Results: A cutoff value of 138 pg/mL provided 100% sensitivity and 98% specificity for diagnosis of fungal meningitis in this outbreak. Patients with serially collected CSF were divided into 2 groups: those in whom BDG levels declined with treatment and those in whom BDG remained elevated. Whereas most patients with a decline in CSF BDG had clinical improvement, all 3 patients with continually elevated BDG had poor clinical outcomes (stroke, meningitis relapse, or development of new disease)., Conclusions: Our data suggest that measuring BDG in CSF is a highly sensitive test for diagnosis of fungal meningitis in this outbreak. Analysis of BDG levels in serially collected CSF demonstrated that BDG may correlate with clinical response. Routine measurement of BDG in CSF may provide useful adjunctive data for the clinical management of patients with outbreak-associated meningitis.
- Published
- 2014
- Full Text
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35. Potential role of viruses in white plague coral disease.
- Author
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Soffer N, Brandt ME, Correa AM, Smith TB, and Thurber RV
- Subjects
- Animals, Anthozoa microbiology, Anthozoa ultrastructure, Biodiversity, Caribbean Region, DNA Viruses classification, DNA Viruses genetics, DNA Viruses ultrastructure, DNA, Satellite genetics, DNA, Single-Stranded genetics, Genome, Viral genetics, Intracellular Space virology, Microscopy, Electron, Transmission, Seawater virology, Anthozoa virology, Coral Reefs, DNA Viruses physiology
- Abstract
White plague (WP)-like diseases of tropical corals are implicated in reef decline worldwide, although their etiological cause is generally unknown. Studies thus far have focused on bacterial or eukaryotic pathogens as the source of these diseases; no studies have examined the role of viruses. Using a combination of transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24 viral metagenomes generated from Montastraea annularis corals showing signs of WP-like disease and/or bleaching, control conspecific corals, and adjacent seawater. TEM was used for visual inspection of diseased coral tissue. No bacteria were visually identified within diseased coral tissues, but viral particles and sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA viruses and their associated satellites (SCSDVs) were abundant in WP diseased tissues. In contrast, sequence similarities to SCSDVs were not found in any healthy coral tissues, suggesting SCSDVs might have a role in WP disease. Furthermore, Herpesviridae gene signatures dominated healthy tissues, corroborating reports that herpes-like viruses infect all corals. Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently identified in cultures of Symbiodinium (the algal symbionts of corals), were most common in bleached corals. This finding further implicates that these NCLDV viruses may have a role in bleaching, as suggested in previous studies. This study determined that a specific group of viruses is associated with diseased Caribbean corals and highlights the potential for viral disease in regional coral reef decline.
- Published
- 2014
- Full Text
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36. Clinical findings for fungal infections caused by methylprednisolone injections.
- Author
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Chiller TM, Roy M, Nguyen D, Guh A, Malani AN, Latham R, Peglow S, Kerkering T, Kaufman D, McFadden J, Collins J, Kainer M, Duwve J, Trump D, Blackmore C, Tan C, Cleveland AA, MacCannell T, Muehlenbachs A, Zaki SR, Brandt ME, and Jernigan JA
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents adverse effects, Antifungal Agents therapeutic use, Arachnoiditis microbiology, Arachnoiditis mortality, Ascomycota genetics, Ascomycota isolation & purification, Aspergillus fumigatus isolation & purification, Drug Compounding, Female, Humans, Injections, Epidural, Injections, Spinal, Male, Meningitis, Fungal microbiology, Meningitis, Fungal mortality, Meningitis, Fungal pathology, Middle Aged, Polymerase Chain Reaction, Stroke microbiology, Stroke mortality, United States epidemiology, Young Adult, Arachnoiditis epidemiology, Disease Outbreaks, Drug Contamination, Glucocorticoids administration & dosage, Meningitis, Fungal epidemiology, Methylprednisolone administration & dosage, Stroke epidemiology
- Abstract
Background: Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections., Methods: We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification., Results: Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis., Conclusions: The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.).
- Published
- 2013
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37. Fungal infections associated with contaminated methylprednisolone injections.
- Author
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Smith RM, Schaefer MK, Kainer MA, Wise M, Finks J, Duwve J, Fontaine E, Chu A, Carothers B, Reilly A, Fiedler J, Wiese AD, Feaster C, Gibson L, Griese S, Purfield A, Cleveland AA, Benedict K, Harris JR, Brandt ME, Blau D, Jernigan J, Weber JT, and Park BJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents therapeutic use, Ascomycota isolation & purification, Aspergillus fumigatus isolation & purification, Drug Compounding, Female, Humans, Infectious Disease Incubation Period, Injections, Spinal adverse effects, Male, Meningitis, Fungal drug therapy, Middle Aged, Public Health, Stroke epidemiology, Stroke microbiology, United States epidemiology, Young Adult, Disease Outbreaks, Drug Contamination, Glucocorticoids administration & dosage, Meningitis, Fungal epidemiology, Methylprednisolone administration & dosage
- Abstract
Background: Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy., Methods: Three lots of methylprednisolone acetate were recalled by the pharmacy; examination of unopened vials later revealed fungus. Notification of all persons potentially exposed to implicated methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. We collected clinical data on standardized case-report forms, and we tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing., Results: By October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249); 40 patients (5%) had a stroke., Conclusions: Analysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.
- Published
- 2013
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38. Think fungus–prevention and control of fungal infections.
- Author
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Brandt ME and Park BJ
- Subjects
- Communicable Disease Control, Communicable Diseases, Emerging epidemiology, Communicable Diseases, Emerging microbiology, Humans, Mycoses epidemiology, United States epidemiology, Communicable Diseases, Emerging prevention & control, Mycoses prevention & control
- Published
- 2013
- Full Text
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39. Filamentous Basidiomycetes in the Clinical Laboratory.
- Author
-
Brandt ME
- Abstract
Filamentous basidiomycetes are difficult to identify in the clinical laboratory, mostly due to lack of sporulation, and their role as agents of fungal infection can be difficult to assess. More cases of infection with these agents are being reported as more laboratories gain proficiency with the recognition of their subtle morphologic features and the use of DNA-based methods for identification. Most infections occur in the respiratory tract and sinuses, although brain infection has been reported. Susceptibility testing suggests that these agents will respond well to azole drugs other than fluconazole.
- Published
- 2013
- Full Text
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40. Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases.
- Author
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Ritter JM, Muehlenbachs A, Blau DM, Paddock CD, Shieh WJ, Drew CP, Batten BC, Bartlett JH, Metcalfe MG, Pham CD, Lockhart SR, Patel M, Liu L, Jones TL, Greer PW, Montague JL, White E, Rollin DC, Seales C, Stewart D, Deming MV, Brandt ME, and Zaki SR
- Subjects
- Adult, Aged, Aged, 80 and over, Ascomycota cytology, Ascomycota ultrastructure, Female, Humans, Immunohistochemistry, Injections, Epidural, Male, Meningitis microbiology, Meningitis pathology, Methylprednisolone administration & dosage, Methylprednisolone adverse effects, Methylprednisolone Acetate, Middle Aged, Mycoses epidemiology, Mycoses microbiology, Polymerase Chain Reaction, Steroids adverse effects, United States epidemiology, Ascomycota physiology, Drug Contamination, Methylprednisolone analogs & derivatives, Mycoses etiology, Mycoses pathology, Steroids administration & dosage
- Abstract
September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2013
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41. PRP8 intein in cryptic species of Histoplasma capsulatum: evolution and phylogeny.
- Author
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Theodoro RC, Scheel CM, Brandt ME, Kasuga T, and Bagagli E
- Subjects
- Amino Acid Sequence, Evolution, Molecular, Histoplasma classification, Histoplasmosis microbiology, Humans, Molecular Sequence Data, Multilocus Sequence Typing, Phylogeny, Sequence Alignment, Genes, Fungal, Histoplasma genetics, Inteins genetics
- Abstract
The PRP8 intein is the most widespread intein among the Kingdom Fungi. This genetic element occurs within the prp8 gene, and is transcribed and translated simultaneously with the gene. After translation, the intein excises itself from the Prp8 protein by an autocatalytic splicing reaction, subsequently joining the N and C terminals of the host protein, which retains its functional conformation. Besides the splicing domain, some PRP8 inteins also have a homing endonuclease (HE) domain which, if functional, makes the intein a mobile element capable of becoming fixed in a population. This work aimed to study (1) The occurrence of this intein in Histoplasma capsulatum isolates (n=99) belonging to different cryptic species collected in diverse geographical locations, and (2) The functionality of the endonuclease domains of H. capsulatum PRP8 inteins and their phylogenetic relationship among the cryptic species. Our results suggest that the PRP8 intein is fixed in H. capsulatum populations and that an admixture or a probable ancestral polymorphism of the PRP8 intein sequences is responsible for the apparent paraphyletic pattern of the LAmA clade which, in the intein phylogeny, also encompasses sequences from LAmB isolates. The PRP8 intein sequences clearly separate the different cryptic species, and may serve as an additional molecular typing tool, as previously proposed for other fungi genus, such as Cryptococcus and Paracoccidioides., (Copyright © 2013 Elsevier B.V. All rights reserved.)
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- 2013
- Full Text
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42. Preliminary laboratory report of fungal infections associated with contaminated methylprednisolone injections.
- Author
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Lockhart SR, Pham CD, Gade L, Iqbal N, Scheel CM, Cleveland AA, Whitney AM, Noble-Wang J, Chiller TM, Park BJ, Litvintseva AP, and Brandt ME
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents pharmacology, Ascomycota drug effects, Female, Humans, Injections, Male, Methylprednisolone adverse effects, Microbial Sensitivity Tests, Middle Aged, United States epidemiology, Young Adult, Ascomycota isolation & purification, Disease Outbreaks, Drug Contamination, Methylprednisolone administration & dosage, Mycoses chemically induced, Mycoses epidemiology
- Abstract
In September 2012, the Centers for Disease Control and Prevention (CDC) initiated an outbreak investigation of fungal infections linked to injection of contaminated methylprednisolone acetate (MPA). Between 2 October 2012 and 14 February 2013, the CDC laboratory received 799 fungal isolates or human specimens, including cerebrospinal fluid (CSF), synovial fluid, and abscess tissue, from 469 case patients in 19 states. A novel broad-range PCR assay and DNA sequencing were used to evaluate these specimens. Although Aspergillus fumigatus was recovered from the index case, Exserohilum rostratum was the primary pathogen in this outbreak and was also confirmed from unopened MPA vials. Exserohilum rostratum was detected or confirmed in 191 specimens or isolates from 150 case patients, primarily from Michigan (n=67 patients), Tennessee (n=26), Virginia (n=20), and Indiana (n=16). Positive specimens from Michigan were primarily abscess tissues, while positive specimens from Tennessee, Virginia, and Indiana were primarily CSF. E. rostratum antifungal susceptibility MIC50 and MIC90 values were determined for voriconazole (1 and 2 μg/ml, respectively), itraconazole (0.5 and 1 μg/ml), posaconazole (0.5 and 1 μg/ml), isavuconazole (4 and 4 μg/ml), and amphotericin B (0.25 and 0.5 μg/ml). Thirteen other mold species were identified among case patients, and four other fungal genera were isolated from the implicated MPA vials. The clinical significance of these other fungal species remains under investigation. The laboratory response provided significant support to case confirmation, enabled linkage between clinical isolates and injected vials of MPA, and described significant features of the fungal agents involved in this large multistate outbreak.
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- 2013
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43. Trichosporon asahii among intensive care unit patients at a medical center in Jamaica.
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Fanfair RN, Heslop O, Etienne K, Rainford L, Roy M, Gade L, Peterson J, O'Connell H, Noble-Wang J, Balajee SA, Brandt ME, Lindo JF, and Park BJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cross Infection diagnosis, Cross Infection prevention & control, Equipment Contamination, Female, Fomites microbiology, Guideline Adherence, Guidelines as Topic, Humans, Jamaica, Male, Middle Aged, Trichosporon genetics, Trichosporonosis diagnosis, Trichosporonosis prevention & control, Young Adult, Cross Infection microbiology, Disinfection standards, Intensive Care Units standards, Trichosporon isolation & purification, Trichosporonosis microbiology
- Abstract
We investigated an increase in Trichosporon asahii isolates among inpatients. We identified 63 cases; 4 involved disseminated disease. Trichosporon species was recovered from equipment cleaning rooms, washbasins, and fomites, which suggests transmission through washbasins. Patient washbasins should be single-patient use only; adherence to appropriate hospital disinfection guidelines was recommended.
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- 2013
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44. One fungus, one name: defining the genus Fusarium in a scientifically robust way that preserves longstanding use.
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Geiser DM, Aoki T, Bacon CW, Baker SE, Bhattacharyya MK, Brandt ME, Brown DW, Burgess LW, Chulze S, Coleman JJ, Correll JC, Covert SF, Crous PW, Cuomo CA, De Hoog GS, Di Pietro A, Elmer WH, Epstein L, Frandsen RJ, Freeman S, Gagkaeva T, Glenn AE, Gordon TR, Gregory NF, Hammond-Kosack KE, Hanson LE, Jímenez-Gasco Mdel M, Kang S, Kistler HC, Kuldau GA, Leslie JF, Logrieco A, Lu G, Lysøe E, Ma LJ, McCormick SP, Migheli Q, Moretti A, Munaut F, O'Donnell K, Pfenning L, Ploetz RC, Proctor RH, Rehner SA, Robert VA, Rooney AP, Bin Salleh B, Scandiani MM, Scauflaire J, Short DP, Steenkamp E, Suga H, Summerell BA, Sutton DA, Thrane U, Trail F, Van Diepeningen A, Vanetten HD, Viljoen A, Waalwijk C, Ward TJ, Wingfield MJ, Xu JR, Yang XB, Yli-Mattila T, and Zhang N
- Subjects
- Fusarium genetics, Phylogeny, Plant Diseases microbiology, Fusarium classification, Plants microbiology
- Abstract
In this letter, we advocate recognizing the genus Fusarium as the sole name for a group that includes virtually all Fusarium species of importance in plant pathology, mycotoxicology, medicine, and basic research. This phylogenetically guided circumscription will free scientists from any obligation to use other genus names, including teleomorphs, for species nested within this clade, and preserve the application of the name Fusarium in the way it has been used for almost a century. Due to recent changes in the International Code of Nomenclature for algae, fungi, and plants, this is an urgent matter that requires community attention. The alternative is to break the longstanding concept of Fusarium into nine or more genera, and remove important taxa such as those in the F. solani species complex from the genus, a move we believe is unnecessary. Here we present taxonomic and nomenclatural proposals that will preserve established research connections and facilitate communication within and between research communities, and at the same time support strong scientific principles and good taxonomic practice.
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- 2013
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45. Detection of fungal DNA in human body fluids and tissues during a multistate outbreak of fungal meningitis and other infections.
- Author
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Gade L, Scheel CM, Pham CD, Lindsley MD, Iqbal N, Cleveland AA, Whitney AM, Lockhart SR, Brandt ME, and Litvintseva AP
- Subjects
- DNA, Fungal genetics, DNA, Ribosomal Spacer genetics, Drug Contamination, Humans, Limit of Detection, Meningitis, Fungal cerebrospinal fluid, Meningitis, Fungal epidemiology, Molecular Diagnostic Techniques, Molecular Typing, Mycological Typing Techniques, Polymerase Chain Reaction, United States epidemiology, Ascomycota genetics, DNA, Fungal cerebrospinal fluid, Disease Outbreaks, Meningitis, Fungal diagnosis
- 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.
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- 2013
- Full Text
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46. Invasive candidiasis in Pakistan: clinical characteristics, species distribution and antifungal susceptibility.
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Farooqi JQ, Jabeen K, Saeed N, Iqbal N, Malik B, Lockhart SR, Zafar A, Brandt ME, and Hasan R
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Candidiasis, Invasive drug therapy, Child, Child, Preschool, Drug Resistance, Fungal, Female, Humans, Infant, Infant, Newborn, Male, Microbial Sensitivity Tests, Middle Aged, Pakistan epidemiology, Young Adult, Antifungal Agents pharmacology, Candida classification, Candida drug effects, Candida genetics, Candida isolation & purification, Candidiasis, Invasive epidemiology, Candidiasis, Invasive microbiology
- Abstract
This study reports for the first time, to our knowledge, descriptive epidemiological data for 188 invasive Candida isolates from Pakistan, including species identification and antifungal susceptibility against fluconazole, itraconazole, voriconazole, caspofungin, micafungin, anidulafungin and amphotericin. Risk factors for invasive candidiasis (IC) were determined for 96 patients from Karachi, Pakistan. In adults and neonates, Candida tropicalis (38 and 36 %, respectively) was the most common species, followed in adults by Candida parapsilosis (17.8 %), Candida glabrata (15.9 %) and Candida albicans (12.3 %). C. albicans (21 %) was the second most common in neonates. In children, C. albicans (31.9 %), C. tropicalis (26.4 %) and C. parapsilosis (19.4 %) were the most common. C. albicans IC was significantly associated with paediatric age [crude odds ratio (COR) 3.46, 95 % confidence interval (CI) 1.63-7.32]. Rare species made up 17.5 % of the total isolates studied. Resistance to fluconazole was seen in C. glabrata (15 .0%) and Candida krusei (100 .0%). Only one isolate (C. glabrata) was resistant to all three echinocandins. Low MICs of fluconazole for 98 % (184/188) of isolates tested support its continued use as an empiric therapy for IC. Non-C. albicans IC was associated with the use of β-lactam inhibitor combinations (COR 3.16, 95 % CI 1.05-9.57). Use of healthcare devices was documented in 85.4 % of IC patients, whilst 75 .0% had been admitted to special care units. Surprisingly, 66.7 % of patients with IC were not obviously immunosuppressed. The high frequency of modifiable risk factors in this population indicates that candidaemia can be reduced with stringent antibiotic and infection control measures. These data will be useful for empiric selection of antifungals in Karachi, and contribute to global assessments of antifungal resistance.
- Published
- 2013
- Full Text
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47. Disturbance driven colony fragmentation as a driver of a coral disease outbreak.
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Brandt ME, Smith TB, Correa AM, and Vega-Thurber R
- Subjects
- Animals, Cluster Analysis, Cyclonic Storms, Environmental Monitoring, Geologic Sediments microbiology, Hot Temperature, United States Virgin Islands, Anthozoa microbiology, Coral Reefs
- Abstract
In September of 2010, Brewer's Bay reef, located in St. Thomas (U.S. Virgin Islands), was simultaneously affected by abnormally high temperatures and the passage of a hurricane that resulted in the mass bleaching and fragmentation of its coral community. An outbreak of a rapid tissue loss disease among coral colonies was associated with these two disturbances. Gross lesion signs and lesion progression rates indicated that the disease was most similar to the Caribbean coral disease white plague type 1. Experiments indicated that the disease was transmissible through direct contact between colonies, and five-meter radial transects showed a clustered spatial distribution of disease, with diseased colonies being concentrated within the first meter of other diseased colonies. Disease prevalence and the extent to which colonies were bleached were both significantly higher on unattached colony fragments than on attached colonies, and disease occurred primarily on fragments found in direct contact with sediment. In contrast to other recent studies, disease presence was not related to the extent of bleaching on colonies. The results of this study suggest that colony fragmentation and contact with sediment played primary roles in the initial appearance of disease, but that the disease was capable of spreading among colonies, which suggests secondary transmission is possible through some other, unidentified mechanism.
- Published
- 2013
- Full Text
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48. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011.
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Neblett Fanfair R, Benedict K, Bos J, Bennett SD, Lo YC, Adebanjo T, Etienne K, Deak E, Derado G, Shieh WJ, Drew C, Zaki S, Sugerman D, Gade L, Thompson EH, Sutton DA, Engelthaler DM, Schupp JM, Brandt ME, Harris JR, Lockhart SR, Turabelidze G, and Park BJ
- Subjects
- Adolescent, Adult, Aged, Case-Control Studies, DNA, Fungal analysis, DNA, Ribosomal, Dermatomycoses epidemiology, Dermatomycoses mortality, Disasters, Fasciitis, Necrotizing epidemiology, Fasciitis, Necrotizing mortality, Female, Humans, Male, Middle Aged, Missouri epidemiology, Mucorales classification, Mucorales genetics, Mucormycosis epidemiology, Mucormycosis mortality, Risk Factors, Skin injuries, Soft Tissue Infections epidemiology, Soft Tissue Infections mortality, Young Adult, Dermatomycoses etiology, Fasciitis, Necrotizing etiology, Mucorales isolation & purification, Mucormycosis etiology, Soft Tissue Infections etiology, Tornadoes, Wounds and Injuries complications
- Abstract
Background: Mucormycosis is a fungal infection caused by environmentally acquired molds. We investigated a cluster of cases of cutaneous mucormycosis among persons injured during the May 22, 2011, tornado in Joplin, Missouri., Methods: We defined a case as a soft-tissue infection in a person injured during the tornado, with evidence of a mucormycete on culture or immunohistochemical testing plus DNA sequencing. We conducted a case-control study by reviewing medical records and conducting interviews with case patients and hospitalized controls. DNA sequencing and whole-genome sequencing were performed on clinical specimens to identify species and assess strain-level differences, respectively., Results: A total of 13 case patients were identified, 5 of whom (38%) died. The patients had a median of 5 wounds (range, 1 to 7); 11 patients (85%) had at least one fracture, 9 (69%) had blunt trauma, and 5 (38%) had penetrating trauma. All case patients had been located in the zone that sustained the most severe damage during the tornado. On multivariate analysis, infection was associated with penetrating trauma (adjusted odds ratio for case patients vs. controls, 8.8; 95% confidence interval [CI], 1.1 to 69.2) and an increased number of wounds (adjusted odds ratio, 2.0 for each additional wound; 95% CI, 1.2 to 3.2). Sequencing of the D1-D2 region of the 28S ribosomal DNA yielded Apophysomyces trapeziformis in all 13 case patients. Whole-genome sequencing showed that the apophysomyces isolates were four separate strains., Conclusions: We report a cluster of cases of cutaneous mucormycosis among Joplin tornado survivors that were associated with substantial morbidity and mortality. Increased awareness of fungi as a cause of necrotizing soft-tissue infections after a natural disaster is warranted.
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- 2012
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49. Pseudo-outbreak of Lecanicillium and Acremonium species in orthopedic surgery patients.
- Author
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Neal CO, Deak E, Chang LS, Gilmartin H, Gade L, Imanishi M, Price C, Brandt ME, Chiller T, and Balajee SA
- Subjects
- Environmental Microbiology, Humans, Molecular Diagnostic Techniques methods, Mycoses microbiology, Postoperative Complications microbiology, Acremonium isolation & purification, Disease Outbreaks, Hypocreales isolation & purification, Mycoses epidemiology, Orthopedics, Postoperative Complications epidemiology
- Abstract
Acremonium species cause a variety of human infections, while Lecanicillium species have not been reported as human pathogens. We describe a pseudo-outbreak involving both organisms, highlighting the role and limitations of molecular methods in the characterization of rare fungal isolates. Repeated isolation of these fungi from patient tissue samples raises concerns about exogenous contamination in the hospital environment.
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- 2012
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50. Investigating the behavioural responses of trapped fishes using underwater video surveillance.
- Author
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Renchen GF, Pittman SJ, and Brandt ME
- Subjects
- Animals, Coral Reefs, Fisheries instrumentation, Species Specificity, Behavior, Animal physiology, Fishes physiology, Video Recording
- Abstract
An underwater video surveillance system known as TrapCam was used to continuously record (15 ×c. 24 h periods) fish behaviour within and immediately surrounding an experimental fish trap situated in a coral reef ecosystem in the United States Virgin Islands. Of the 100 fishes (18 species, 12 families) trapped, surgeonfishes (Acanthuridae) and snappers (Lutjanidae) were most common. Thirteen distinctively identifiable behaviours were observed for trapped fishes. Species did not differ significantly in the proportion of time allocated to different behaviours (ANOSIM, R = 0·142). Doctorfish Acanthurus chirurgus and grey angelfish Pomacanthus arcuatus allocated the largest proportion of their recorded time to enter and exit the trap. Fishes spent an average of 15 min in the trap before escaping. Sixty-seven per cent of trap approaches consisted of an individual of the same species as one already trapped suggesting that conspecific attraction may have occurred. Fifteen per cent of trapped species were observed with abrasions to the head and 70% were observed approaching the trap corners. The results of this study provide a greater understanding of the behavioural interactions between fishes and traps that can help explain patterns of catch composition, the physical condition of fishes in traps and inform design of gear modifications to optimize by-catch reduction in the trap fishery., (© 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.)
- Published
- 2012
- Full Text
- View/download PDF
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