LETTER TO THE EDITOR
Comparison of the IMDx Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus A/B Assay on the m2000 Platform with Real-Time Reverse Transcriptase PCR Assays Dena Adachi,a Julian W. Tang,a,b,c Roberta Lundeberg,a Graham Tipples,a,b Carmen L. Charlton,a,d Steven J. Drewsa,e Alberta Provincial Laboratory for Public Health, Alberta, Canadaa; Departments of Medical Microbiology and Immunology,b Medical Genetics,c and Laboratory Medicine and Pathology,d University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Calgary, Calgary, Alberta, Canadae
he increasing demand for timely respiratory virus testing for both diagnostic and surveillance purposes emphasizes the need to strike a sustainable approach for testing clinical specimens. Streamlined automated approaches allow clinically relevant diagnosis while avoiding pitfalls (e.g., subjective interpretation and retest algorithms) that impact laboratory workflow and test turnaround times. The IMDx influenza A/B virus and respiratory syncytial virus (RSV) assay (Abbott Molecular, Abbott Park, IL, USA) is an FDA-approved molecular assay for influenza A virus, influenza B virus, and combined RSV A/B testing on the Abbott m2000 platform. The assay requires minimal operator manipulation; total nucleic acid extraction and molecular detection are performed on the same platform. A MaxRatio algorithm, an automated approach utilizing several variables, including cycle number, curve shapes, and relative measures of amplification efficiency, is used to determine test positivity to avoid subjective interpretations. The assay also contains an internal MS2 control to monitor for inhibition (1). This evaluation study compared detection of influenza A/B viruses and RSV by the IMDx assay against our modified influenza A virus (CDC-M) and influenza B virus (NS1) singleplex real-time reverse transcriptase PCR (rRT-PCR) assays and laboratory-developed tests (LDTs) (2, 3), an RSV A/B rRT-PCR LDT (4), and the Luminex respiratory virus panel (RVP) classic assay (3). The MagMax total-nucleic-acid extraction system (Life Technologies Corp., Burlington, Ontario, Canada) was used for all the assays except the IMDx. Our analysis utilized nasopharyngeal swab specimens of convenience collected in Alberta, Canada, in the 2013-2014 respiratory illness season. Selected specimens (n ⫽ 371) were blinded and evaluated. To assess accuracy, specimens were run in parallel by the aforementioned assays, with commercial tests run as per the package inserts. Specimens positive for other respiratory virus targets (Luminex RVP classic) were run in parallel for each assay to determine specificity. No cross-reactivity was observed for specimens positive for adenovirus (n ⫽ 8), human coronavirus 229E (n ⫽ 4), HKU1 (n ⫽ 1), OC43 (n ⫽ 5), parainfluenza (PIV) 1 (n ⫽ 6), PIV2 (n ⫽ 5), PIV3 (n ⫽ 5), PIV4 (n ⫽ 3), rhino/enterovirus (n ⫽ 10), and human metapneumovirus (n ⫽ 14). Relative limits of detection (LOD), determined as levels at which 50% of replicates were positive (5), were calculated. LOD panels used influenza A virus pdm09 and seasonal influenza virus H3 collected in 2014, one specimen each of influenza A virus, influenza B virus, RSV A, and RSV B diluted in viral transport medium in serial dilutions from 10⫺1 to 10⫺9. The vast majority of these H3 isolates in Canada in the 2013-2014 respiratory illness season belonged to the A/Texas/50/2012 strain (http://www.phac-aspc.gc.ca/fluwatch /13-14/w34_14/pdf/fw2014-34-eng.pdf). The relative LODs are
December 2014 Volume 52 Number 12
TABLE 1 Comparable relative limits of detection for lab-developed real-time PCRs (LDT) and IMDx IMDx
Influenza A virus H3 Influenza A virus Pdm09 Influenza B virus RSV A/B
10⫺4–10⫺5 10⫺5–10⫺6 10⫺5; 10⫺4–10⫺5 10⫺5–10⫺6 10⫺6 10⫺5–10⫺6; 10⫺5
a
LDT
Luminex (GZ positive; GZ negative)a
Virus
10⫺5 10⫺5–10⫺6 10⫺4–10⫺5; 10⫺4 10⫺5–10⫺6 10⫺5–10⫺6 10⫺4; 10⫺3–10⫺4 (RSV A); 10⫺5–10⫺6; 10⫺4–10⫺5 (RSV B)
GZ, grey zone.
identified in Table 1. For Luminex RVP assays, values obtained when grey zones were reported as positive and as negative are given. Two approaches were used to calculate sensitivity and specificity: comparison of IMDx and the Luminex RVP classic assay against rRT-PCR and comparison of each result against an aggregate gold standard (Aggstd: each specimen was defined as positive if ⬎2 independent tests scored the result as positive) (Table 2) (6). Sensitivities, specificities, and 95% confidence intervals were determined (Vassarstats Clinical Calculator 1). When an LDT rRTPCR was used as the gold standard, the results were as follows: for influenza A virus, 94 positive and 129 negative; for influenza B virus, 69 positive and 99 negative; and for RSV A/B, 76 positive and 94 negative. When the Aggstd was used as the gold standard, the results were as follows: for influenza A virus, 92 positive and 131 negative; for influenza B virus, 66 positive and 102 negative; and for RSV A/B, 76 positive and 94 negative. Similarly, typespecific influenza A virus analyses for pdm09 and H3 subtypes were compared using rRT-PCR as a gold standard: for pdm09, 77 positive and 96 negative; for H3, 16 positive and 94 negative. A similar analysis used Aggstd as the gold standard: for pdm09, 76 positive and 97 negative; for H3, 16 positive and 94 negative. The proportion of positives detected was not significantly different between the LDT and the IMDx for overall influenza A virus detection and detection of influenza A virus subtype pdm09 (Fisher’s exact test; GraphPad QuickCalcs, 2014).
Published ahead of print 1 October 2014 Editor: Y.-W. Tang Address correspondence to Steven J. Drews, [email protected]. Copyright © 2014, American Society for Microbiology. All Rights Reserved. doi:10.1128/JCM.02565-14
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TABLE 2 Relative test characteristics of the IMDx influenza A/B virus and RSV assays Percentage (95% CI) for targeta Influenza A virus Subtype pdm09
Subtype H3
Subtype not resolved
All subtypes
Influenza B virus
RSV A and B
94.8 (86.5–98.3) 99.0 (93.5–99.9)
100 (75.9–100) 100 (95.1–100)
0 (0–94.5) 100 (96.3–100)
94.7 (87.5–98.0) 99.2 (95.1–100)
95.7 (87.0–98.9) 100 (95.3–100)
100 (94.0–100) 100 (95.1–100)
xTAG RVP vs. LDT Sensitivity Specificity
97.4 (90.1–99.5) 100 (95.2–100)
93.8 (67.7–99.7) 100 (95.1–100)
0 (0–94.5) 100 (96.3–100)
96.8 (90.3–99.2) 100 (96.4–100)
89.9 (79.6–95.5) 100 (95.3–100)
98.7 (91.9–99.9) 100 (95.1–100)
IMDx vs. Aggstd Sensitivity Specificity
96.1 (88.1–99.0) 99.0 (93.6–99.9)
100 (75.9–100) 100 (95.1–100)
NAN 100 (96.4–100)
96.7 (90.1–99.2) 99.2 (95.2–100)
100 (93.1–100) 100 (95.5–100)
100 (94.0–100) 100 (95.1–100)
LDT vs. Aggstd Sensitivity Specificity
100 (94.0–100) 99.0 (93.6–99.9)
100 (75.9–100) 100 (95.1–100)
NAN 99.2 (95.1–100)
100 (95.0–100) 98.5 (94.0–99.7)
100 (93.1–100) 97.1 (91.0–99.2)
100 (94.0–100) 100 (95.1–100)
xTAG RVP vs. Aggstd Sensitivity Specificity
98.7 (91.9–99.9) 100 (95.3–100)
93.8 (67.7–99.7) 100 (95.1–100)
NAN 100 (96.4–100)
98.9 (93.2–99.9) 100 (96.4–100)
93.9 (84.4–98.0) 100 (95.5–100)
98.7 (91.9–99.9) 100 (95.1–100)
a
NAN, not able to numerate. Boldface indicates key test characteristics for the IMDx assay.
With clinical specimens, the IMDx assay showed equivalent sensitivity and specificity for influenza A virus, influenza B virus, and RSV compared to both LDTs and Aggstds. Wide ranges in some 95% confidence interval (CI) values in Table 2 (e.g., H3 xTAG and IMDx) were likely due to small numbers of specimens tested. The clinical significance of low positive results and how they impact clinical management is largely unknown, and the decision to implement an assay should rest on the ability to detect a target at clinically relevant levels (7, 8). Overall, the IMDx assay was easier to use than the existing LDT due to its automated platform and the MaxRatio-calculated interpretations, which do not require operator intervention (1). This evaluation study provides the preliminary data to support the use of the IMDx assay as an automated front-end screening assay for seasonal influenza virus and RSV. At our institution, clinical samples are first tested by our LDT for influenza A/B viruses, and negative samples are reflexed to a comprehensive viral panel. Replacement of our LDT with the IMDx assay to include RSV in the front-line screening assay is estimated to remove approximately one-fifth of specimens from further testing, which represents a significant cost savings to the laboratory (data not shown). This analysis indicates that the IMDx assay has molecular test characteristics similar to those of other molecular detection approaches for the detection of seasonal influenza A virus, influenza B virus, and RSV. ACKNOWLEDGMENT IMDx kits for evaluation were provided by Abbott Molecular, Abbott Park, IL, USA.
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REFERENCES 1. Shain EB, Clemens JM. 2008. A new method for robust quantitative and qualitative analysis of real-time PCR. Nucleic Acids Res. 36:e91. http://dx .doi.org/10.1093/nar/gkn408. 2. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. 2009. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N. Engl. J. Med. 360: 2605–2615. http://dx.doi.org/10.1056/NEJMoa0903810. 3. Pabbaraju K, Wong S, Tokaryk KL, Fonseca K, Drews SJ. 2011. Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections. J. Clin. Microbiol. 49:1738 –1744. http://dx.doi.org/10.1128/JCM.02090-10. 4. van Elden LJ, van Loon AM, van der Beek A, Hendriksen KA, Hoepelman AI, van Kraaij MG, Schipper P, Nijhuis M. 2003. Applicability of a real-time quantitative PCR assay for diagnosis of respiratory syncytial virus infection in immunocompromised adults. J. Clin. Microbiol. 41:4378 – 4381. http://dx.doi.org/10.1128/JCM.41.9.4378-4381.2003. 5. Caraguel CG, Stryhn H, Gagne N, Dohoo IR, Hammell KL. 2011. Selection of a cutoff value for real-time polymerase chain reaction results to fit a diagnostic purpose: analytical and epidemiologic approaches. J. Vet. Diagn. Invest. 23:2–15. http://dx.doi.org/10.1177/104063871102300102. 6. Bolotin S, De LC, Choi KW, Lombos E, Burton L, Mazzulli T, Drews SJ. 2009. Validation of the TaqMan influenza A detection kit and a rapid automated total nucleic acid extraction method to detect influenza A virus in nasopharyngeal specimens. Ann. Clin. Lab Sci. 39:155–159. 7. Esbenshade JC, Edwards KM, Esbenshade AJ, Rodriguez VE, Talbot HK, Joseph MF, Nwosu SK, Chappell JD, Gern JE, Williams JV, Talbot TR. 2013. Respiratory virus shedding in a cohort of on-duty healthcare workers undergoing prospective surveillance. Infect. Control Hosp. Epidemiol. 34: 373–378. http://dx.doi.org/10.1086/669857. 8. Lau LL, Cowling BJ, Fang VJ, Chan KH, Lau EH, Lipsitch M, Cheng CK, Houck PM, Uyeki TM, Peiris JS, Leung GM. 2010. Viral shedding and clinical illness in naturally acquired influenza virus infections. J. Infect. Dis. 201:1509 –1516. http://dx.doi.org/10.1086/652241.
Journal of Clinical Microbiology
Downloaded from http://jcm.asm.org/ on May 24, 2015 by PURDUE UNIV LIB TSS
Comparison IMDx vs. LDT Sensitivity Specificity
Comparison of the IMDx Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus A/B Assay on the m2000 Platform with Real-Time Reverse Transcriptase PCR Assays Dena Adachi,a Julian W. Tang,a,b,c Roberta Lundeberg,a Graham Tipples,a,b Carmen L. Charlton,a,d Steven J. Drewsa,e Alberta Provincial Laboratory for Public Health, Alberta, Canadaa; Departments of Medical Microbiology and Immunology,b Medical Genetics,c and Laboratory Medicine and Pathology,d University of Alberta, Edmonton, Alberta, Canada; Department of Medical Microbiology and Immunology, University of Calgary, Calgary, Alberta, Canadae
he increasing demand for timely respiratory virus testing for both diagnostic and surveillance purposes emphasizes the need to strike a sustainable approach for testing clinical specimens. Streamlined automated approaches allow clinically relevant diagnosis while avoiding pitfalls (e.g., subjective interpretation and retest algorithms) that impact laboratory workflow and test turnaround times. The IMDx influenza A/B virus and respiratory syncytial virus (RSV) assay (Abbott Molecular, Abbott Park, IL, USA) is an FDA-approved molecular assay for influenza A virus, influenza B virus, and combined RSV A/B testing on the Abbott m2000 platform. The assay requires minimal operator manipulation; total nucleic acid extraction and molecular detection are performed on the same platform. A MaxRatio algorithm, an automated approach utilizing several variables, including cycle number, curve shapes, and relative measures of amplification efficiency, is used to determine test positivity to avoid subjective interpretations. The assay also contains an internal MS2 control to monitor for inhibition (1). This evaluation study compared detection of influenza A/B viruses and RSV by the IMDx assay against our modified influenza A virus (CDC-M) and influenza B virus (NS1) singleplex real-time reverse transcriptase PCR (rRT-PCR) assays and laboratory-developed tests (LDTs) (2, 3), an RSV A/B rRT-PCR LDT (4), and the Luminex respiratory virus panel (RVP) classic assay (3). The MagMax total-nucleic-acid extraction system (Life Technologies Corp., Burlington, Ontario, Canada) was used for all the assays except the IMDx. Our analysis utilized nasopharyngeal swab specimens of convenience collected in Alberta, Canada, in the 2013-2014 respiratory illness season. Selected specimens (n ⫽ 371) were blinded and evaluated. To assess accuracy, specimens were run in parallel by the aforementioned assays, with commercial tests run as per the package inserts. Specimens positive for other respiratory virus targets (Luminex RVP classic) were run in parallel for each assay to determine specificity. No cross-reactivity was observed for specimens positive for adenovirus (n ⫽ 8), human coronavirus 229E (n ⫽ 4), HKU1 (n ⫽ 1), OC43 (n ⫽ 5), parainfluenza (PIV) 1 (n ⫽ 6), PIV2 (n ⫽ 5), PIV3 (n ⫽ 5), PIV4 (n ⫽ 3), rhino/enterovirus (n ⫽ 10), and human metapneumovirus (n ⫽ 14). Relative limits of detection (LOD), determined as levels at which 50% of replicates were positive (5), were calculated. LOD panels used influenza A virus pdm09 and seasonal influenza virus H3 collected in 2014, one specimen each of influenza A virus, influenza B virus, RSV A, and RSV B diluted in viral transport medium in serial dilutions from 10⫺1 to 10⫺9. The vast majority of these H3 isolates in Canada in the 2013-2014 respiratory illness season belonged to the A/Texas/50/2012 strain (http://www.phac-aspc.gc.ca/fluwatch /13-14/w34_14/pdf/fw2014-34-eng.pdf). The relative LODs are
December 2014 Volume 52 Number 12
TABLE 1 Comparable relative limits of detection for lab-developed real-time PCRs (LDT) and IMDx IMDx
Influenza A virus H3 Influenza A virus Pdm09 Influenza B virus RSV A/B
10⫺4–10⫺5 10⫺5–10⫺6 10⫺5; 10⫺4–10⫺5 10⫺5–10⫺6 10⫺6 10⫺5–10⫺6; 10⫺5
a
LDT
Luminex (GZ positive; GZ negative)a
Virus
10⫺5 10⫺5–10⫺6 10⫺4–10⫺5; 10⫺4 10⫺5–10⫺6 10⫺5–10⫺6 10⫺4; 10⫺3–10⫺4 (RSV A); 10⫺5–10⫺6; 10⫺4–10⫺5 (RSV B)
GZ, grey zone.
identified in Table 1. For Luminex RVP assays, values obtained when grey zones were reported as positive and as negative are given. Two approaches were used to calculate sensitivity and specificity: comparison of IMDx and the Luminex RVP classic assay against rRT-PCR and comparison of each result against an aggregate gold standard (Aggstd: each specimen was defined as positive if ⬎2 independent tests scored the result as positive) (Table 2) (6). Sensitivities, specificities, and 95% confidence intervals were determined (Vassarstats Clinical Calculator 1). When an LDT rRTPCR was used as the gold standard, the results were as follows: for influenza A virus, 94 positive and 129 negative; for influenza B virus, 69 positive and 99 negative; and for RSV A/B, 76 positive and 94 negative. When the Aggstd was used as the gold standard, the results were as follows: for influenza A virus, 92 positive and 131 negative; for influenza B virus, 66 positive and 102 negative; and for RSV A/B, 76 positive and 94 negative. Similarly, typespecific influenza A virus analyses for pdm09 and H3 subtypes were compared using rRT-PCR as a gold standard: for pdm09, 77 positive and 96 negative; for H3, 16 positive and 94 negative. A similar analysis used Aggstd as the gold standard: for pdm09, 76 positive and 97 negative; for H3, 16 positive and 94 negative. The proportion of positives detected was not significantly different between the LDT and the IMDx for overall influenza A virus detection and detection of influenza A virus subtype pdm09 (Fisher’s exact test; GraphPad QuickCalcs, 2014).
Published ahead of print 1 October 2014 Editor: Y.-W. Tang Address correspondence to Steven J. Drews, [email protected]. Copyright © 2014, American Society for Microbiology. All Rights Reserved. doi:10.1128/JCM.02565-14
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p. 4441– 4442
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TABLE 2 Relative test characteristics of the IMDx influenza A/B virus and RSV assays Percentage (95% CI) for targeta Influenza A virus Subtype pdm09
Subtype H3
Subtype not resolved
All subtypes
Influenza B virus
RSV A and B
94.8 (86.5–98.3) 99.0 (93.5–99.9)
100 (75.9–100) 100 (95.1–100)
0 (0–94.5) 100 (96.3–100)
94.7 (87.5–98.0) 99.2 (95.1–100)
95.7 (87.0–98.9) 100 (95.3–100)
100 (94.0–100) 100 (95.1–100)
xTAG RVP vs. LDT Sensitivity Specificity
97.4 (90.1–99.5) 100 (95.2–100)
93.8 (67.7–99.7) 100 (95.1–100)
0 (0–94.5) 100 (96.3–100)
96.8 (90.3–99.2) 100 (96.4–100)
89.9 (79.6–95.5) 100 (95.3–100)
98.7 (91.9–99.9) 100 (95.1–100)
IMDx vs. Aggstd Sensitivity Specificity
96.1 (88.1–99.0) 99.0 (93.6–99.9)
100 (75.9–100) 100 (95.1–100)
NAN 100 (96.4–100)
96.7 (90.1–99.2) 99.2 (95.2–100)
100 (93.1–100) 100 (95.5–100)
100 (94.0–100) 100 (95.1–100)
LDT vs. Aggstd Sensitivity Specificity
100 (94.0–100) 99.0 (93.6–99.9)
100 (75.9–100) 100 (95.1–100)
NAN 99.2 (95.1–100)
100 (95.0–100) 98.5 (94.0–99.7)
100 (93.1–100) 97.1 (91.0–99.2)
100 (94.0–100) 100 (95.1–100)
xTAG RVP vs. Aggstd Sensitivity Specificity
98.7 (91.9–99.9) 100 (95.3–100)
93.8 (67.7–99.7) 100 (95.1–100)
NAN 100 (96.4–100)
98.9 (93.2–99.9) 100 (96.4–100)
93.9 (84.4–98.0) 100 (95.5–100)
98.7 (91.9–99.9) 100 (95.1–100)
a
NAN, not able to numerate. Boldface indicates key test characteristics for the IMDx assay.
With clinical specimens, the IMDx assay showed equivalent sensitivity and specificity for influenza A virus, influenza B virus, and RSV compared to both LDTs and Aggstds. Wide ranges in some 95% confidence interval (CI) values in Table 2 (e.g., H3 xTAG and IMDx) were likely due to small numbers of specimens tested. The clinical significance of low positive results and how they impact clinical management is largely unknown, and the decision to implement an assay should rest on the ability to detect a target at clinically relevant levels (7, 8). Overall, the IMDx assay was easier to use than the existing LDT due to its automated platform and the MaxRatio-calculated interpretations, which do not require operator intervention (1). This evaluation study provides the preliminary data to support the use of the IMDx assay as an automated front-end screening assay for seasonal influenza virus and RSV. At our institution, clinical samples are first tested by our LDT for influenza A/B viruses, and negative samples are reflexed to a comprehensive viral panel. Replacement of our LDT with the IMDx assay to include RSV in the front-line screening assay is estimated to remove approximately one-fifth of specimens from further testing, which represents a significant cost savings to the laboratory (data not shown). This analysis indicates that the IMDx assay has molecular test characteristics similar to those of other molecular detection approaches for the detection of seasonal influenza A virus, influenza B virus, and RSV. ACKNOWLEDGMENT IMDx kits for evaluation were provided by Abbott Molecular, Abbott Park, IL, USA.
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REFERENCES 1. Shain EB, Clemens JM. 2008. A new method for robust quantitative and qualitative analysis of real-time PCR. Nucleic Acids Res. 36:e91. http://dx .doi.org/10.1093/nar/gkn408. 2. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. 2009. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N. Engl. J. Med. 360: 2605–2615. http://dx.doi.org/10.1056/NEJMoa0903810. 3. Pabbaraju K, Wong S, Tokaryk KL, Fonseca K, Drews SJ. 2011. Comparison of the Luminex xTAG respiratory viral panel with xTAG respiratory viral panel fast for diagnosis of respiratory virus infections. J. Clin. Microbiol. 49:1738 –1744. http://dx.doi.org/10.1128/JCM.02090-10. 4. van Elden LJ, van Loon AM, van der Beek A, Hendriksen KA, Hoepelman AI, van Kraaij MG, Schipper P, Nijhuis M. 2003. Applicability of a real-time quantitative PCR assay for diagnosis of respiratory syncytial virus infection in immunocompromised adults. J. Clin. Microbiol. 41:4378 – 4381. http://dx.doi.org/10.1128/JCM.41.9.4378-4381.2003. 5. Caraguel CG, Stryhn H, Gagne N, Dohoo IR, Hammell KL. 2011. Selection of a cutoff value for real-time polymerase chain reaction results to fit a diagnostic purpose: analytical and epidemiologic approaches. J. Vet. Diagn. Invest. 23:2–15. http://dx.doi.org/10.1177/104063871102300102. 6. Bolotin S, De LC, Choi KW, Lombos E, Burton L, Mazzulli T, Drews SJ. 2009. Validation of the TaqMan influenza A detection kit and a rapid automated total nucleic acid extraction method to detect influenza A virus in nasopharyngeal specimens. Ann. Clin. Lab Sci. 39:155–159. 7. Esbenshade JC, Edwards KM, Esbenshade AJ, Rodriguez VE, Talbot HK, Joseph MF, Nwosu SK, Chappell JD, Gern JE, Williams JV, Talbot TR. 2013. Respiratory virus shedding in a cohort of on-duty healthcare workers undergoing prospective surveillance. Infect. Control Hosp. Epidemiol. 34: 373–378. http://dx.doi.org/10.1086/669857. 8. Lau LL, Cowling BJ, Fang VJ, Chan KH, Lau EH, Lipsitch M, Cheng CK, Houck PM, Uyeki TM, Peiris JS, Leung GM. 2010. Viral shedding and clinical illness in naturally acquired influenza virus infections. J. Infect. Dis. 201:1509 –1516. http://dx.doi.org/10.1086/652241.
Journal of Clinical Microbiology
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Comparison IMDx vs. LDT Sensitivity Specificity
