TY - JOUR
T1 - Multi-center evaluation of the adenovirus R-gene US assay for the detection of adenovirus in respiratory samples
AU - Manji, Ryhana
AU - Zheng, Xiaotian
AU - Patel, Anami
AU - Kowerska, Malgorzata
AU - Vossinas, Margaret
AU - Drain, Angela
AU - Todd, Kathleen M.
AU - Lenny, Noel
AU - DeVincenzo, John P.
AU - Ginocchio, Christine C.
N1 - Funding Information:
This study was funded by bioMérieux as part of their US FDA submission for approval as an in vitro diagnostic device.
PY - 2014/6
Y1 - 2014/6
N2 - Background: Adenoviruses (AdV) cause a variety of upper and lower respiratory tract infections, with the potential for severe outcomes, especially in persons with immune suppression or other underlying diseases. The ADENOVIRUS US R-gene (AdV R-gene, Argene/bioMérieux) is a FDA cleared real-time PCR assay that utilizes primers and fluorescent probes that target a conserved region of the hexon gene and an internal control DNA. Objectives: This prospective multi-center study evaluated the clinical performance of AdV R-gene for AdV detection in respiratory specimens from symptomatic patients of all ages. Study design: Nucleic acids from nasopharyngeal washes/aspirates (NPW/A; n= 393) and NP flocked swabs (NPS, Copan) (n= 1183) were extracted using NucliSENS easyMAG (bioMérieux) and AdV R-gene PCR was performed using the SmartCycler (Cepheid). AdV R-gene results were compared to R-Mix culture (Quidel/Diagnostic Hybrids). For a subset of samples (n= 946) AdV R-gene and R-Mix results were also compared to A549 cell culture. Results: In first intention analysis for NPS the AdV R-gene positive percent agreement (PPA), and negative percent agreement (NPA) were 91.7% and 96.2%, respectively, and for NPW/A were 100% and 94.4%, respectively, compared to R-Mix culture. In second intention analysis, discordant samples only were tested with an AdV real-time PCR assay (Viracor-IBT Labs) and amplicon sequencing. For NPS, the sensitivity, specificity, PPV and NPV for AdV R-gene were 98.9%, 100%, 100%, and 99.9%, respectively and for R-Mix culture were 51.7%, 99.7%, 93.8%, and 96.3%, respectively. For NPW/A, the sensitivity, specificity, PPV and NPV for AdV R-gene were 100%, 99.7%, 97.6%, and 100%, respectively, and for R-Mix culture were 52.5%, 100%, 100%, and 94.9%, respectively. Overall, AdV was detected by AdV R-gene and R-Mix in 7.4% and 4.1% NPS, respectively, and in 10.7% and 5.3% NPW/A, respectively. Children 5. yr and younger had the highest rates of AdV infections. In a subset of specimens (n= 946) the sensitivity of AdV R-gene, R-Mix, and A549 cell culture were 95.0%, 55.4% and 66.3%. Conclusions: AdV R-gene is sensitive and specific for the detection of AdV in NPW/A and NPS samples. AdV R-gene is simple to use and provides a rapid time to results (within 2.5-3 h).
AB - Background: Adenoviruses (AdV) cause a variety of upper and lower respiratory tract infections, with the potential for severe outcomes, especially in persons with immune suppression or other underlying diseases. The ADENOVIRUS US R-gene (AdV R-gene, Argene/bioMérieux) is a FDA cleared real-time PCR assay that utilizes primers and fluorescent probes that target a conserved region of the hexon gene and an internal control DNA. Objectives: This prospective multi-center study evaluated the clinical performance of AdV R-gene for AdV detection in respiratory specimens from symptomatic patients of all ages. Study design: Nucleic acids from nasopharyngeal washes/aspirates (NPW/A; n= 393) and NP flocked swabs (NPS, Copan) (n= 1183) were extracted using NucliSENS easyMAG (bioMérieux) and AdV R-gene PCR was performed using the SmartCycler (Cepheid). AdV R-gene results were compared to R-Mix culture (Quidel/Diagnostic Hybrids). For a subset of samples (n= 946) AdV R-gene and R-Mix results were also compared to A549 cell culture. Results: In first intention analysis for NPS the AdV R-gene positive percent agreement (PPA), and negative percent agreement (NPA) were 91.7% and 96.2%, respectively, and for NPW/A were 100% and 94.4%, respectively, compared to R-Mix culture. In second intention analysis, discordant samples only were tested with an AdV real-time PCR assay (Viracor-IBT Labs) and amplicon sequencing. For NPS, the sensitivity, specificity, PPV and NPV for AdV R-gene were 98.9%, 100%, 100%, and 99.9%, respectively and for R-Mix culture were 51.7%, 99.7%, 93.8%, and 96.3%, respectively. For NPW/A, the sensitivity, specificity, PPV and NPV for AdV R-gene were 100%, 99.7%, 97.6%, and 100%, respectively, and for R-Mix culture were 52.5%, 100%, 100%, and 94.9%, respectively. Overall, AdV was detected by AdV R-gene and R-Mix in 7.4% and 4.1% NPS, respectively, and in 10.7% and 5.3% NPW/A, respectively. Children 5. yr and younger had the highest rates of AdV infections. In a subset of specimens (n= 946) the sensitivity of AdV R-gene, R-Mix, and A549 cell culture were 95.0%, 55.4% and 66.3%. Conclusions: AdV R-gene is sensitive and specific for the detection of AdV in NPW/A and NPS samples. AdV R-gene is simple to use and provides a rapid time to results (within 2.5-3 h).
KW - Adenovirus
KW - PCR
KW - R-gene
KW - Respiratory samples
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U2 - 10.1016/j.jcv.2014.03.014
DO - 10.1016/j.jcv.2014.03.014
M3 - Article
C2 - 24768208
AN - SCOPUS:84900317304
VL - 60
SP - 90
EP - 95
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
SN - 1386-6532
IS - 2
ER -
