High genetic variability of norovirus leads to diagnostic test challenges

on behalf of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE)

doi:10.1016/j.jcv.2017.10.003

High genetic variability of norovirus leads to diagnostic test challenges

on behalf of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE)

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

11 Citas (Scopus)

Resumen

Background It is important to understand the diagnostic accuracy of multiplex panels such as the Luminex xTAG^® Gastrointestinal Pathogen Panel (GPP) as they are increasingly employed for routine diagnostics worldwide. Recent evaluations in our laboratory identified lower detection rates of norovirus genogroup II (NoV GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis Virus Panel (GVP). Objectives To characterize the cases of discordant NoV GII results between GPP and GVP and determine the sensitivity of the two assays for specific NoV GII genotypes. Study design We genotyped discordant NoV GII strains identified in stool samples or rectal swabs collected prospectively from a cohort of children with acute gastroenteritis between December 2014 and July 2016. The sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various NoV GII genotypes. Results All discordant samples (63/607) were NoV GII positive by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of which were NoV GII genotype 2 (GII.2). The median Ct value of concordant positives was lower than that of discordant results (19.8 vs. 33.7; P < 0.0001). GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4. Discordant GII.2 variant differed genetically from concordant GII.2 variants. Conclusions GPP has lower sensitivity to detect NoV GII.2 than GVP and its use may lead to undetected cases clinically, and an underestimation of NoV disease burden at the population level.

Idioma original	English
Páginas (desde-hasta)	94-98
Número de páginas	5
Publicación	Journal of Clinical Virology
Volumen	96
DOI	https://doi.org/10.1016/j.jcv.2017.10.003
Estado	Published - nov. 2017
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
This research is supported by the Alberta Provincial Pediatric Enteric Infection TEam (APPETITE) , which is funded by a grant from the Alberta Innovates Collaborative Research and Innovation Opportunity (grant number: 20140161 ). APPETITE is also supported by the Alberta Children’s Hospital Research Institute (Calgary, Alberta) and the Women and Children’s Health Research Institute (Edmonton, Alberta). The Pediatric Emergency Medicine Research Associate Program (PEMRAP) is supported by a grant from the Alberta Children’s Hospital Foundation . In-kind support to enable the conduct of this study is provided by Calgary Laboratory Services, ProvLab Alberta, Luminex Corporation, and Copan Italia. Dr. Stephen Freedman is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness . None of the funders had any input into the design or conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Publisher Copyright:
© 2017 Elsevier B.V.

ASJC Scopus Subject Areas

Virology
Infectious Diseases

PubMed: MeSH publication types

Comparative Study
Evaluation Study
Journal Article

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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10.1016/j.jcv.2017.10.003

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@article{4048ff6073964eabb36dd3d52d4cdd06,

title = "High genetic variability of norovirus leads to diagnostic test challenges",

abstract = "Background It is important to understand the diagnostic accuracy of multiplex panels such as the Luminex xTAG{\textregistered} Gastrointestinal Pathogen Panel (GPP) as they are increasingly employed for routine diagnostics worldwide. Recent evaluations in our laboratory identified lower detection rates of norovirus genogroup II (NoV GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis Virus Panel (GVP). Objectives To characterize the cases of discordant NoV GII results between GPP and GVP and determine the sensitivity of the two assays for specific NoV GII genotypes. Study design We genotyped discordant NoV GII strains identified in stool samples or rectal swabs collected prospectively from a cohort of children with acute gastroenteritis between December 2014 and July 2016. The sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various NoV GII genotypes. Results All discordant samples (63/607) were NoV GII positive by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of which were NoV GII genotype 2 (GII.2). The median Ct value of concordant positives was lower than that of discordant results (19.8 vs. 33.7; P < 0.0001). GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4. Discordant GII.2 variant differed genetically from concordant GII.2 variants. Conclusions GPP has lower sensitivity to detect NoV GII.2 than GVP and its use may lead to undetected cases clinically, and an underestimation of NoV disease burden at the population level.",

author = "{on behalf of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE)} and Ran Zhuo and Joanne Cho and Qiu, {Yuan Yuan} and Parsons, {Brendon D.} and Lee, {Bonita E.} and Linda Chui and Freedman, {Stephen B.} and Xiaoli Pang",

note = "Funding Information: This research is supported by the Alberta Provincial Pediatric Enteric Infection TEam (APPETITE) , which is funded by a grant from the Alberta Innovates Collaborative Research and Innovation Opportunity (grant number: 20140161 ). APPETITE is also supported by the Alberta Children{\textquoteright}s Hospital Research Institute (Calgary, Alberta) and the Women and Children{\textquoteright}s Health Research Institute (Edmonton, Alberta). The Pediatric Emergency Medicine Research Associate Program (PEMRAP) is supported by a grant from the Alberta Children{\textquoteright}s Hospital Foundation . In-kind support to enable the conduct of this study is provided by Calgary Laboratory Services, ProvLab Alberta, Luminex Corporation, and Copan Italia. Dr. Stephen Freedman is supported by the Alberta Children{\textquoteright}s Hospital Foundation Professorship in Child Health and Wellness . None of the funders had any input into the design or conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2017 Elsevier B.V.",

year = "2017",

month = nov,

doi = "10.1016/j.jcv.2017.10.003",

language = "English",

volume = "96",

pages = "94--98",

journal = "Journal of Clinical Virology",

issn = "1386-6532",

publisher = "Elsevier",

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TY - JOUR

T1 - High genetic variability of norovirus leads to diagnostic test challenges

AU - on behalf of the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE)

AU - Zhuo, Ran

AU - Cho, Joanne

AU - Qiu, Yuan Yuan

AU - Parsons, Brendon D.

AU - Lee, Bonita E.

AU - Chui, Linda

AU - Freedman, Stephen B.

AU - Pang, Xiaoli

N1 - Funding Information: This research is supported by the Alberta Provincial Pediatric Enteric Infection TEam (APPETITE) , which is funded by a grant from the Alberta Innovates Collaborative Research and Innovation Opportunity (grant number: 20140161 ). APPETITE is also supported by the Alberta Children’s Hospital Research Institute (Calgary, Alberta) and the Women and Children’s Health Research Institute (Edmonton, Alberta). The Pediatric Emergency Medicine Research Associate Program (PEMRAP) is supported by a grant from the Alberta Children’s Hospital Foundation . In-kind support to enable the conduct of this study is provided by Calgary Laboratory Services, ProvLab Alberta, Luminex Corporation, and Copan Italia. Dr. Stephen Freedman is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness . None of the funders had any input into the design or conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Publisher Copyright: © 2017 Elsevier B.V.

PY - 2017/11

Y1 - 2017/11

N2 - Background It is important to understand the diagnostic accuracy of multiplex panels such as the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) as they are increasingly employed for routine diagnostics worldwide. Recent evaluations in our laboratory identified lower detection rates of norovirus genogroup II (NoV GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis Virus Panel (GVP). Objectives To characterize the cases of discordant NoV GII results between GPP and GVP and determine the sensitivity of the two assays for specific NoV GII genotypes. Study design We genotyped discordant NoV GII strains identified in stool samples or rectal swabs collected prospectively from a cohort of children with acute gastroenteritis between December 2014 and July 2016. The sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various NoV GII genotypes. Results All discordant samples (63/607) were NoV GII positive by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of which were NoV GII genotype 2 (GII.2). The median Ct value of concordant positives was lower than that of discordant results (19.8 vs. 33.7; P < 0.0001). GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4. Discordant GII.2 variant differed genetically from concordant GII.2 variants. Conclusions GPP has lower sensitivity to detect NoV GII.2 than GVP and its use may lead to undetected cases clinically, and an underestimation of NoV disease burden at the population level.

AB - Background It is important to understand the diagnostic accuracy of multiplex panels such as the Luminex xTAG® Gastrointestinal Pathogen Panel (GPP) as they are increasingly employed for routine diagnostics worldwide. Recent evaluations in our laboratory identified lower detection rates of norovirus genogroup II (NoV GII) using GPP compared to our laboratory-developed RT-qPCR, Gastroenteritis Virus Panel (GVP). Objectives To characterize the cases of discordant NoV GII results between GPP and GVP and determine the sensitivity of the two assays for specific NoV GII genotypes. Study design We genotyped discordant NoV GII strains identified in stool samples or rectal swabs collected prospectively from a cohort of children with acute gastroenteritis between December 2014 and July 2016. The sensitivities of GVP and GPP for NoV GII were compared by analyses of GVP threshold cycle (Ct) and ten-fold serial dilutions of positive samples of various NoV GII genotypes. Results All discordant samples (63/607) were NoV GII positive by GVP but negative by GPP. Twenty-two were successfully genotyped, fourteen of which were NoV GII genotype 2 (GII.2). The median Ct value of concordant positives was lower than that of discordant results (19.8 vs. 33.7; P < 0.0001). GVP was 10 and at least 10,000-fold more sensitive than GPP in detecting NoV GII.3 and GII.2, respectively, but has similar sensitivity for NoV GII.4. Discordant GII.2 variant differed genetically from concordant GII.2 variants. Conclusions GPP has lower sensitivity to detect NoV GII.2 than GVP and its use may lead to undetected cases clinically, and an underestimation of NoV disease burden at the population level.

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ER -

High genetic variability of norovirus leads to diagnostic test challenges

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODS de las Naciones Unidas

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