Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.

Diagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet th...

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Main Authors: Sunil Pokharel, Lisa J White, Jilian A Sacks, Camille Escadafal, Amy Toporowski, Sahra Isse Mohammed, Solomon Chane Abera, Kekeletso Kao, Marcela De Melo Freitas, Sabine Dittrich
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLOS Global Public Health
Online Access:https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000293&type=printable
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author Sunil Pokharel
Lisa J White
Jilian A Sacks
Camille Escadafal
Amy Toporowski
Sahra Isse Mohammed
Solomon Chane Abera
Kekeletso Kao
Marcela De Melo Freitas
Sabine Dittrich
author_facet Sunil Pokharel
Lisa J White
Jilian A Sacks
Camille Escadafal
Amy Toporowski
Sahra Isse Mohammed
Solomon Chane Abera
Kekeletso Kao
Marcela De Melo Freitas
Sabine Dittrich
author_sort Sunil Pokharel
collection DOAJ
description Diagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet the needs of users. We used a simulation approach to estimate diagnostic outcomes, number of tests required and average turnaround time of using two-test algorithms compared with singular testing; the two tests were reverse transcription polymerase chain reaction (RT-PCR) and an antigen-based rapid diagnostic test (Ag-RDT). A web-based application of the model was developed to visualise and compare diagnostic outcomes for different disease prevalence and test performance characteristics (sensitivity and specificity). We tested the model using hypothetical prevalence data for COVID-19, representing low- and high-prevalence contexts and performance characteristics of RT-PCR and Ag-RDTs. The two-test algorithm when RT-PCR was applied to samples negative by Ag-RDT predicted gains in sensitivity of 27% and 7%, respectively, compared with Ag-RDT and RT-PCR alone. Similarly, when RT-PCR was applied to samples positive by Ag-RDT, specificity gains of 2.9% and 1.9%, respectively, were predicted. The algorithm using Ag-RDT followed by RT-PCR as a confirmatory test for positive patients limited the requirement of RT-PCR testing resources to 16,400 and 3,034 tests when testing a population of 100,000 with an infection prevalence of 20% and 0.05%, respectively. A two-test algorithm comprising a rapid screening test followed by confirmatory laboratory testing can reduce false positive rate, produce rapid results and conserve laboratory resources, but can lead to large number of missed cases in high prevalence setting. The web application of the model can identify the best testing strategies, tailored to specific use cases and we also present some examples how it was used as part of the Access to Covid-19 Tools (ACT) Accelerator Diagnostics Pillar.
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spelling doaj-art-83cc5c28d98945e6bc14da1d594c2d082025-08-20T02:33:20ZengPublic Library of Science (PLoS)PLOS Global Public Health2767-33752022-01-0123e000029310.1371/journal.pgph.0000293Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.Sunil PokharelLisa J WhiteJilian A SacksCamille EscadafalAmy ToporowskiSahra Isse MohammedSolomon Chane AberaKekeletso KaoMarcela De Melo FreitasSabine DittrichDiagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet the needs of users. We used a simulation approach to estimate diagnostic outcomes, number of tests required and average turnaround time of using two-test algorithms compared with singular testing; the two tests were reverse transcription polymerase chain reaction (RT-PCR) and an antigen-based rapid diagnostic test (Ag-RDT). A web-based application of the model was developed to visualise and compare diagnostic outcomes for different disease prevalence and test performance characteristics (sensitivity and specificity). We tested the model using hypothetical prevalence data for COVID-19, representing low- and high-prevalence contexts and performance characteristics of RT-PCR and Ag-RDTs. The two-test algorithm when RT-PCR was applied to samples negative by Ag-RDT predicted gains in sensitivity of 27% and 7%, respectively, compared with Ag-RDT and RT-PCR alone. Similarly, when RT-PCR was applied to samples positive by Ag-RDT, specificity gains of 2.9% and 1.9%, respectively, were predicted. The algorithm using Ag-RDT followed by RT-PCR as a confirmatory test for positive patients limited the requirement of RT-PCR testing resources to 16,400 and 3,034 tests when testing a population of 100,000 with an infection prevalence of 20% and 0.05%, respectively. A two-test algorithm comprising a rapid screening test followed by confirmatory laboratory testing can reduce false positive rate, produce rapid results and conserve laboratory resources, but can lead to large number of missed cases in high prevalence setting. The web application of the model can identify the best testing strategies, tailored to specific use cases and we also present some examples how it was used as part of the Access to Covid-19 Tools (ACT) Accelerator Diagnostics Pillar.https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000293&type=printable
spellingShingle Sunil Pokharel
Lisa J White
Jilian A Sacks
Camille Escadafal
Amy Toporowski
Sahra Isse Mohammed
Solomon Chane Abera
Kekeletso Kao
Marcela De Melo Freitas
Sabine Dittrich
Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
PLOS Global Public Health
title Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
title_full Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
title_fullStr Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
title_full_unstemmed Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
title_short Two-test algorithms for infectious disease diagnosis: Implications for COVID-19.
title_sort two test algorithms for infectious disease diagnosis implications for covid 19
url https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0000293&type=printable
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