Nathaniel Hupert, MD, MPH; Marissa Person, MSPH; Dan Hanfling, MD; Rita M. Traxler, MHS; William A. Bower, MD; Katherine Hendricks, MD, MPH&TM
Note: The authors dedicate this work to the memory of Dr. Toby Merlin, who as Director of the Division of Preparedness and Emerging Infections at the Centers for Disease Control and Prevention championed science, mentored with grace and great leadership, and inspired countless collaborations both in the United States and abroad to advance the public's health.
Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Acknowledgment: The authors thank Stefan Katharios-Lanwermeyer for extracting data for the original systematic review; Rosa Borensztein for assisting with primary data collection at NewYork–Presbyterian Hospital; our Epidemic Intelligence Service officer at the time; Tom Doker for asking more than once, “What if people present earlier during an event?” during the design phase of our data extraction tool; and Thitipong Mongkolrattanothai for reformatting references, tables, graphics, and appendixes.
Financial Support: Dr. Hupert was funded under U.S. Department of Health and Human Services Assignment Agreement IPA 1608836 to work on this project.
Disclosures: Dr. Hupert reports personal fees and nonfinancial support from the U.S. Defense Threat Reduction Agency's Proliferation Security Initiative outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1817.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: Available in the main article and the Supplement and from Dr. Hendricks (e-mail, email@example.com). Statistical code: Available from Ms. Person (e-mail, firstname.lastname@example.org). Data set: The case data set is available in the Supplement. The control data set is unavailable because of institutional review board restrictions.
Corresponding Author: Kate Hendricks, MD, MPH&TM, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS H24-12, Atlanta, GA 30329-4027; e-mail, email@example.com.
Current Author Addresses: Dr. Hupert: Department of Healthcare Policy and Research and Department of Medicine, Weill Cornell Medicine, 402 East 67th Street, LA-219, New York, NY 10065; Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30329-4027.
Ms. Person, Ms. Traxler, and Drs. Bower and Hendricks: Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS H24-12, Atlanta, GA 30329-4027.
Dr. Hanfling: Department of Emergency Medicine, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042.
Author Contributions: Conception and design: N. Hupert, M. Person, D. Hanfling, W.A. Bower, K. Hendricks.
Analysis and interpretation of the data: N. Hupert, M. Person, D. Hanfling, R.M. Traxler, W.A. Bower, K. Hendricks.
Drafting of the article: N. Hupert, M. Person, R.M. Traxler, K. Hendricks.
Critical revision of the article for important intellectual content: N. Hupert, M. Person, D. Hanfling, R.M. Traxler, W.A. Bower, K. Hendricks.
Final approval of the article: N. Hupert, M. Person, D. Hanfling, R.M. Traxler, W.A. Bower, K. Hendricks.
Provision of study materials or patients: N. Hupert, D. Hanfling, R.M. Traxler, K. Hendricks.
Statistical expertise: N. Hupert, M. Person.
Obtaining of funding: N. Hupert.
Administrative, technical, or logistic support: R.M. Traxler, W.A. Bower, K. Hendricks.
Collection and assembly of data: N. Hupert, M. Person, D. Hanfling, R.M. Traxler, W.A. Bower, K. Hendricks.
Population exposure to Bacillus anthracis spores could cause mass casualties requiring complex medical care. Rapid identification of patients needing anthrax-specific therapies will improve patient outcomes and resource use.
To develop a checklist that rapidly distinguishes most anthrax from nonanthrax illnesses on the basis of clinical presentation and identifies patients requiring diagnostic testing after a population exposure.
Comparison of published anthrax case reports from 1880 through 2013 that included patients seeking anthrax-related care at 2 epicenters of the 2001 U.S. anthrax attacks.
Outpatient and inpatient.
408 case patients with inhalation, ingestion, and cutaneous anthrax and primary anthrax meningitis, and 657 control patients.
Diagnostic test characteristics, including positive and negative likelihood ratios (LRs) and patient triage assignation.
Checklist-directed triage without diagnostic testing correctly classified 95% (95% CI, 93% to 97%) of 353 adult anthrax case patients and 76% (CI, 73% to 79%) of 647 control patients (positive LR, 3.96 [CI, 3.45 to 4.55]; negative LR, 0.07 [CI, 0.04 to 0.11]; false-negative rate, 5%; false-positive rate, 24%). Diagnostic testing was needed for triage in up to 5% of case patients and 15% of control patients and improved overall test characteristics (positive LR, 8.90 [CI, 7.05 to 11.24]; negative LR, 0.06 [CI, 0.04 to 0.09]; false-negative rate, 5%; false-positive rate, 11%). Checklist sensitivity and specificity were minimally affected by inclusion of pediatric patients. Sensitivity increased to 97% (CI, 94% to 100%) and 98% (CI, 96% to 100%), respectively, when only inhalation anthrax cases or higher-quality case reports were investigated.
Data on case patients were limited to nonstandardized, published observational reports, many of which lacked complete data on symptoms and signs of interest. Reporting bias favoring more severe cases and lack of intercurrent outbreaks (such as influenza) in the control populations may have improved test characteristics.
A brief checklist covering symptoms and signs can distinguish anthrax from other conditions with minimal need for diagnostic testing after known or suspected population exposure.
U.S. Department of Health and Human Services.
Hupert N, Person M, Hanfling D, et al. Development and Performance of a Checklist for Initial Triage After an Anthrax Mass Exposure Event. Ann Intern Med. 2019;170:521–530. [Epub ahead of print 19 March 2019]. doi: https://doi.org/10.7326/M18-1817
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Published: Ann Intern Med. 2019;170(8):521-530.
Published at www.annals.org on 19 March 2019
Bioterrorism Infectious Agents, Emergency Medicine, Hospital Medicine, Infectious Disease, Pulmonary/Critical Care.
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