False positive congenital cytomegalovirus saliva screening results with an FDA-approved assay at two institutions
Copyright © 2023 Elsevier B.V. All rights reserved..
BACKGROUND: Congenital cytomegalovirus (CMV) infection is a significant cause of childhood hearing loss and developmental delay. Congenital CMV screening was implemented at two large hospital-affiliated laboratories using the FDA-approved Alethia CMV Assay Test System. In July 2022, an increase in suspected false-positive results was noted, leading to implementation of prospective quality management strategies.
METHODS: The Alethia assay was performed per manufacturer-provided instructions on saliva swab specimens. After discovery of possible elevated false-positive rates, all positive results were confirmed by repeat Alethia testing on the same specimen, orthogonal polymerase chain reaction (PCR) on the same specimen, and/or clinical adjudication. Additionally, root cause analyses were conducted to pinpoint the source of false-positive results.
RESULTS: At Cleveland Clinic (CCF), 696 saliva specimens were tested after initiation of the prospective quality management strategy, of which 36 (5.2%) were positive for CMV. Five of 36 (13.9%) were confirmed CMV positive by repeat Alethia testing and orthogonal PCR. Vanderbilt Medical Center (VUMC) tested 145 specimens, of which 11 (7.6%) were positive. Two of 11 (18.2%) confirmed as positive by orthogonal PCR or clinical adjudication. The remaining specimens (31 from CCF and 9 from VUMC) were negative for CMV by repeat Alethia and/or orthogonal PCR testing.
DISCUSSION: These findings suggest a false positive rate of 4.5-6.2%, higher than the 0.2% reported for this assay in FDA claims. Laboratories using Alethia CMV may consider prospective quality management to evaluate all positive results. False-positive results can lead to unnecessary follow-up care and testing, and decreased confidence in laboratory testing.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:166 |
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| Enthalten in: |
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology - 166(2023) vom: 15. Sept., Seite 105527 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Atwood, Emily N [VerfasserIn] |
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| Links: |
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| Themen: |
Alethia CMV Assay Test System |
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| Anmerkungen: |
Date Completed 16.08.2023 Date Revised 16.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jcv.2023.105527 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Congenital cytomegalovirus (CMV) infection is a significant cause of childhood hearing loss and developmental delay. Congenital CMV screening was implemented at two large hospital-affiliated laboratories using the FDA-approved Alethia CMV Assay Test System. In July 2022, an increase in suspected false-positive results was noted, leading to implementation of prospective quality management strategies | ||
| 520 | |a METHODS: The Alethia assay was performed per manufacturer-provided instructions on saliva swab specimens. After discovery of possible elevated false-positive rates, all positive results were confirmed by repeat Alethia testing on the same specimen, orthogonal polymerase chain reaction (PCR) on the same specimen, and/or clinical adjudication. Additionally, root cause analyses were conducted to pinpoint the source of false-positive results | ||
| 520 | |a RESULTS: At Cleveland Clinic (CCF), 696 saliva specimens were tested after initiation of the prospective quality management strategy, of which 36 (5.2%) were positive for CMV. Five of 36 (13.9%) were confirmed CMV positive by repeat Alethia testing and orthogonal PCR. Vanderbilt Medical Center (VUMC) tested 145 specimens, of which 11 (7.6%) were positive. Two of 11 (18.2%) confirmed as positive by orthogonal PCR or clinical adjudication. The remaining specimens (31 from CCF and 9 from VUMC) were negative for CMV by repeat Alethia and/or orthogonal PCR testing | ||
| 520 | |a DISCUSSION: These findings suggest a false positive rate of 4.5-6.2%, higher than the 0.2% reported for this assay in FDA claims. Laboratories using Alethia CMV may consider prospective quality management to evaluate all positive results. False-positive results can lead to unnecessary follow-up care and testing, and decreased confidence in laboratory testing | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alethia CMV Assay Test System | |
| 650 | 4 | |a Congenital cytomegalovirus (cCMV) | |
| 650 | 4 | |a Cytomegalovirus (CMV) | |
| 650 | 4 | |a Loop-mediated amplification (LAMP) | |
| 650 | 4 | |a Quality management | |
| 650 | 4 | |a Saliva screening | |
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| 700 | 1 | |a Doud, Mary Kathryn |e verfasserin |4 aut | |
| 700 | 1 | |a Benton, Alison M |e verfasserin |4 aut | |
| 700 | 1 | |a Friesen, Jeremy |e verfasserin |4 aut | |
| 700 | 1 | |a Rodgers, Matthew J |e verfasserin |4 aut | |
| 700 | 1 | |a Humphries, Romney M |e verfasserin |4 aut | |
| 700 | 1 | |a Rhoads, Daniel D |e verfasserin |4 aut | |
| 700 | 1 | |a Gaston, David C |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hannah |e verfasserin |4 aut | |
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