@article{72dd08bda9734132857e9486eff75eac,
title = "Molecular detection of filamentous fungi in formalin-fixed paraffin-embedded specimens in invasive fungal wound infections is feasible with high specificity",
abstract = "Trauma-related invasive fungal wound infections (IFIs) are associated with significant morbidity and mortality. Early identification and treatment are critical. Traditional identification methods (e.g., fungal cultures and histopathology) can be delayed and insensitive. We assessed a PCR-based sequencing assay for rapid identification of filamentous fungi in formalin-fixed paraffin-embedded (FFPE) specimens obtained from combat casualties injured in Afghanistan. Blinded FFPE specimens from cases (specimens positive on histopathology) and controls (specimens negative on histopathology) were submitted for evaluation with a panfungal PCR. The internal transcribed spacer 2 (ITS2) region of the fungal ribosomal repeat was amplified and sequenced. The PCR results were compared with findings from histopathology and/or culture. If injury sites contributed multiple specimens, findings for the site were collapsed to the site level. We included 64 case subjects (contributing 95 sites) and 102 controls (contributing 118 sites). Compared to histopathology, panfungal PCR was specific (99%), but not as sensitive (63%); however, sensitivity improved to 83% in specimens from sites with angioinvasion. Panfungal PCR identified fungi of the order Mucorales in 33 of 44 sites with angioinvasion (75%), whereas fungal culture was positive in 20 of 44 sites (45%). Saksenaea spp. were the dominant fungi identified by PCR in specimens from angioinvasion sites (57%). Panfungal PCR is specific, albeit with lower sensitivity, and performs better at identifying fungi of the order Mucorales than culture. DNA sequencing offers significant promise for the rapid identification of fungal infection in trauma-related injuries, leading to more timely and accurate diagnoses.",
keywords = "Combat, Invasive fungal infection, Invasive fungal wound infection, Mucormycosis, PCR, PCR-based assay, Trauma",
author = "Anuradha Ganesan and Justin Wells and Faraz Shaikh and Philip Peterson and William Bradley and Carson, {M. Leigh} and Petfield, {Joseph L.} and Mary Klassen-Fischer and Akers, {Kevin S.} and Kevin Downing and Ralf Bialek and Tribble, {David R.} and Wickes, {Brian L.}",
note = "Funding Information: The views expressed are ours and do not reflect the official views of the Uniformed Services University of the Health Sciences; the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; the National Institutes of Health or the Department of Health and Human Services; Brooke Army Medical Center; Walter Reed National Military Medical Center; Landstuhl Regional Medical Center; the U.S. Army Institute of Surgical Research; the U.S. Army Medical Department; the U.S. Army Office of the Surgeon General; the Department of Defense; or the Departments of the Army, Navy, and Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Funding Information: We are indebted to the Infectious Disease Clinical Research Program (IDCRP) TIDOS team of clinical coordinators, microbiology technicians, data managers, clinical site managers, and administrative support personnel for their tireless efforts to ensure the success of this project. We thank Brian Johnson, Denise Bennett, and Teresa Merritt of the IDCRP, as well as Jianmin Fu of the University of Texas Health Sciences Center at San Antonio, for their invaluable contributions to this project. This work (IDCRP-077) was conducted by the Infectious Disease Clinical Research Program, a Department of Defense program executed through the Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics, through a cooperative agreement with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Inter-Agency Agreement Y1-AI-5072); the Department of the Navy under the Wounded, Ill, and Injured Program (HU0001-10-1-0014); and the Defense Medical Research and Development Program (HT9404-12-1-0014). No competing financial interests exist. The views expressed are ours and do not reflect the official views of the Uniformed Services University of the Health Sciences; the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; the National Institutes of Health or the Department of Health and Human Services; Brooke Army Medical Center; Walter Reed National Military Medical Center; Landstuhl Regional Medical Center; the U.S. Army Institute of Surgical Research; the U.S. Army Medical Department; the U.S. Army Office of the Surgeon General; the Department of Defense; or the Departments of the Army, Navy, and Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Funding Information: This project has been funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (Inter-Agency Agreement Y1-AI-5072); the Department of the Navy under the Wounded, Ill, and Injured Program (HU0001-10-1-0014); and the Defense Medical Research and Development Program (HT9404-12-1-0014). Funding Information: This work (IDCRP-077) was conducted by the Infectious Disease Clinical Research Program, a Department of Defense program executed through the Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics, through a cooperative agreement with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). Publisher Copyright: Copyright {\textcopyright} 2019 American Society for Microbiology. All Rights Reserved.",
year = "2020",
month = jan,
doi = "10.1128/JCM.01259-19",
language = "English",
volume = "58",
journal = "Journal of Clinical Microbiology",
issn = "0095-1137",
number = "1",
}