Enterovirus D68 outbreak detection through a syndromic disease epidemiology network.
Lindsay Meyers, Jennifer Dien Bard, Ben Galvin, Jeff Nawrocki, Hubert G M Niesters, Kathleen A Stellrecht, Kirsten St George, Judy A Daly, Anne J Blaschke, Christine Robinson, Huanyu Wang, Camille V Cook, Ferdaus Hassan, Sam R Dominguez, Kristin Pretty, Samia Naccache, Katherine E Olin, Benjamin M Althouse, Jay D Jones, Christine C Ginocchio, Mark A Poritz, Amy Leber, Rangaraj Selvarangan
Author Information
Lindsay Meyers: BioFire Diagnostics, Salt Lake City, UT, 84103, United States. Electronic address: lindsay.meyers@biofiredx.com.
Jennifer Dien Bard: Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, CA 90027, United States; Keck School of Medicine, University of Southern California, Los Angeles, CA 90039, United States. Electronic address: jdienbard@chla.usc.edu.
Ben Galvin: BioFire Diagnostics, Salt Lake City, UT, 84103, United States. Electronic address: Ben.Galvin@biofiredx.com.
Jeff Nawrocki: BioFire Diagnostics, Salt Lake City, UT, 84103, United States. Electronic address: Jeff.Nawrocki@biofiredx.com.
Hubert G M Niesters: The University of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Division of Clinical Virology, Groningen, The Netherlands. Electronic address: h.g.m.niesters@umcg.nl.
Kathleen A Stellrecht: Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States. Electronic address: StellrK@amc.edu.
Kirsten St George: New York State Department of Health, Albany, NY, 12202, United States. Electronic address: kirsten.st.george@health.ny.gov.
Judy A Daly: Department of Pathology, University of Utah, Salt Lake City, UT 84132, United States; Division of Inpatient Medicine, Primary Children's Hospital, Salt Lake City, UT 84132, United States. Electronic address: Judy.Daly@imail.org.
Anne J Blaschke: Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT 84132, United States. Electronic address: Anne.Blaschke@hsc.utah.edu.
Christine Robinson: Department of Pathology and Laboratory Medicine, Children's Colorado, Aurora, CO 80045, United States. Electronic address: Christine.Robinson@childrenscolorado.org.
Huanyu Wang: Department of Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, United States. Electronic address: huanyu.wang@nationwidechildrens.org.
Camille V Cook: BioFire Diagnostics, Salt Lake City, UT, 84103, United States. Electronic address: Camille.Cook@biofiredx.com.
Ferdaus Hassan: Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO 64108, United States. Electronic address: mfhassan@cmh.edu.
Sam R Dominguez: Department of Pathology and Laboratory Medicine, Children's Colorado, Aurora, CO 80045, United States. Electronic address: Samuel.Dominguez@childrenscolorado.org.
Kristin Pretty: Department of Pathology and Laboratory Medicine, Children's Colorado, Aurora, CO 80045, United States. Electronic address: Kristin.Pretty@childrenscolorado.org.
Samia Naccache: Department of Pathology and Laboratory Medicine, Children's Hospital of Los Angeles, Los Angeles, CA 90027, United States. Electronic address: snaccache@chla.usc.edu.
Katherine E Olin: BioFire Diagnostics, Salt Lake City, UT, 84103, United States.
Benjamin M Althouse: Information School, University of Washington, Seattle, WA, 98105, United States; Department of Biology, New Mexico State University, Las Cruces, NM, 88003, United States. Electronic address: bma85@uw.edu.
Jay D Jones: BioFire Diagnostics, Salt Lake City, UT, 84103, United States. Electronic address: Jay.Jones@biofiredx.com.
Christine C Ginocchio: BioFire Diagnostics, Salt Lake City, UT, 84103, United States; Global Medical Affairs, bioMérieux, Durham, NC 27712, United States; Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, United States. Electronic address: christine.ginocchio@biomerieux.com.
Mark A Poritz: BioFire Defense, Salt Lake City, UT 84107, United States. Electronic address: mporitz@firebirdbio.com.
Amy Leber: Department of Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, United States. Electronic address: Amy.Leber@nationwidechildrens.org.
Rangaraj Selvarangan: Department of Pathology and Laboratory Medicine, Children's Mercy Hospital, Kansas City, MO 64108, United States. Electronic address: rselvarangan@cmh.edu.
BACKGROUND: In 2014, enterovirus D68 (EV-D68) was responsible for an outbreak of severe respiratory illness in children, with 1,153 EV-D68 cases reported across 49 states. Despite this, there is no commercial assay for its detection in routine clinical care. BioFire® Syndromic Trends (Trend) is an epidemiological network that collects, in near real-time, deidentified. BioFire test results worldwide, including data from the BioFire® Respiratory Panel (RP). OBJECTIVES: Using the RP version 1.7 (which was not explicitly designed to differentiate EV-D68 from other picornaviruses), we formulate a model, Pathogen Extended Resolution (PER), to distinguish EV-D68 from other human rhinoviruses/enteroviruses (RV/EV) tested for in the panel. Using PER in conjunction with Trend, we survey for historical evidence of EVD68 positivity and demonstrate a method for prospective real-time outbreak monitoring within the network. STUDY DESIGN: PER incorporates real-time polymerase chain reaction metrics from the RPRV/EV assays. Six institutions in the United States and Europe contributed to the model creation, providing data from 1,619 samples spanning two years, confirmed by EV-D68 gold-standard molecular methods. We estimate outbreak periods by applying PER to over 600,000 historical Trend RP tests since 2014. Additionally, we used PER as a prospective monitoring tool during the 2018 outbreak. RESULTS: The final PER algorithm demonstrated an overall sensitivity and specificity of 87.1% and 86.1%, respectively, among the gold-standard dataset. During the 2018 outbreak monitoring period, PER alerted the research network of EV-D68 emergence in July. One of the first sites to experience a significant increase, Nationwide Children's Hospital, confirmed the outbreak and implemented EV-D68 testing at the institution in response. Applying PER to the historical Trend dataset to determine rates among RP tests, we find three potential outbreaks with predicted regional EV-D68 rates as high as 37% in 2014, 16% in 2016, and 29% in 2018. CONCLUSIONS: Using PER within the Trend network was shown to both accurately predict outbreaks of EV-D68 and to provide timely notifications of its circulation to participating clinical laboratories.
