Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi
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            e CMV Assay in the Era of the CMV International Standard

Schnepf, Nathalie; Scieux, Catherine; Resche-Riggon, Matthieu; Feghoul, Linda; Xhaard, Aliénor; Gallien, Sébastien; Molina, Jean‐Michel; Socié, Gèrard; Viglietti, Denis; Simon, François; Mazeron, Marie‐Christine; Goff, Jérôme Le

doi:10.1128/jcm.00067-13

Cited by 42 publications

(33 citation statements)

References 25 publications

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“…16,17 CMV reactivation was defined as a CMV viral load of over 1000 copies/mL. Pre-emptive antiviral therapy was given when the viral load reached this threshold on two successive determinations.…”

Section: Virological Monitoringmentioning

confidence: 99%

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

et al. 2014

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Acute GVHD grades 0-1 (n=219) Acute GVHD grades 2-4 (n=202)Bone marrow transplantation (n=99) Peripheral blood stem cell transplantation (n=323) AcuteGVHD 0-1, NK ≤ 111.7 (n=60) AcuteGVHD 2-4, NK ≤ 111.7 (n=80) AcuteGVHD 0-1, NK > 111.7 (n=84) AcuteGVHD 2-4, NK > 111.7 (n=48) AcuteGVHD 0-1, NK ≤ 111.7 (n=19) AcuteGVHD 2-4, NK ≤ 111.7 (n=23) AcuteGVHD 0-1, NK > 111.7 (n=25) AcuteGVHD 2-4, NK > 111.7 (n=23)

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Section: Virological Monitoringmentioning

confidence: 99%

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

et al. 2014

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“…The availability of fully automated tests for CMV quantification that employ DNA extraction followed by qPCR has enabled an improvement in measurements for both approaches, possibly as a result of reducing the bias during manual sample transfer between steps. The Cobas AmpliPrep/Cobas TaqMan CMV Test (15). However, differences in the sensitivity of the two tests have been observed (15), which warrants traceable measurement results with respect to the LOD with welldefined reference materials in the long term.…”

Section: Quantitative Methodsmentioning

confidence: 99%

“…The Cobas AmpliPrep/Cobas TaqMan CMV Test (15). However, differences in the sensitivity of the two tests have been observed (15), which warrants traceable measurement results with respect to the LOD with welldefined reference materials in the long term. Factors contributing to interlaboratory variability in viral load quantification of EBV and BK virus.…”

Section: Quantitative Methodsmentioning

confidence: 99%

Standardization of Nucleic Acid Tests for Clinical Measurements of Bacteria and Viruses

Pavšič

Devonshire²,

Parkes³

et al. 2015

J Clin Microbiol

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f Nucleic acid-based tests for infectious diseases currently used in the clinical laboratory and in point-of-care devices are diverse. Measurement challenges associated with standardization of quantitative viral load testing are discussed in relation to human cytomegalovirus, BK virus, and Epstein-Barr virus, while the importance of defining the performance of qualitative methods is illustrated with Mycobacterium tuberculosis and influenza virus. The development of certified reference materials whose values are traceable to higher-order standards and reference measurement procedures, using, for instance, digital PCR, will further contribute to the understanding of analytical performance characteristics and promote clinical data comparability. Molecular approaches, such as nucleic acid (NA) amplification-based tests (NAATs) and sequence analysis, are increasingly replacing conventional microbiological methods, such as pathogen propagation in culture and techniques for the detection of antigens, for (i) viral load quantification, (ii) the detection of pathogenic viruses and bacteria, (iii) monitoring viral and bacterial resistance to therapeutic agents, and (iv) monitoring transmission across communities, as they often enable faster, more accurate, or more sensitive measurements (1, 2). However, commercial and in-house NAATs for infectious diseases utilize different technologies, reaction chemistries, and calibration materials, leading to demonstrable variability in the test results in terms of (i) numerical values (e.g., numbers of genome copies) for quantitative methods or (ii) presence or absence of the pathogen for qualitative methods (3-5).The In Vitro Diagnostics Directive (IVDD) in Europe has promoted assay standardization in the clinical laboratory community, through requiring manufacturers to provide information about the traceability of their calibrators (for definitions of terms in italics, see Table 1), in compliance with ISO 17511 (6). The concept of metrological traceability in clinical chemistry and laboratory medicine has been comprehensively discussed in several articles (7-9). For small-molecule measurements in clinical chemistry, such as those of blood glucose, creatinine, cortisol, and electrolytes, reference measurement procedures of high metrological quality are available which relate the quantity value of the calibrators and reference materials used in a calibration hierarchy traceable to the International System of Units (SI) as described in ISO 17511 (6, 8). However, for the majority of the more complex biomeasurements, including those based on NA testing and infectious pathogen detection, reference materials whose values are traceable to the SI and reference measurement procedures (with well-understood uncertainty) are not yet available. ISO 17511 indicates recognition of the fact that, for measurements of, for example, viral NAs (for human cytomegalovirus [CMV], human immunodeficiency virus [HIV], and hepatitis B virus [HBV]), typically WHO international standards (IS) are available, w...

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“…This is likely to have contributed to the differing results observed for the patient samples and the IS when diluted in each matrix. If the calibration for the whole-blood process been performed against the IS in whole blood, then the stated conversion factor would have been lower, but comparable with those of other studies (4,5).…”

mentioning

confidence: 76%

Commutability of the World Health Organization International Standard for Human Cytomegalovirus: Standard or Assay

et al. 2016

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T he development and widespread use of calibrants that are traceable to a higher-order standard enable the results of diagnostic tests performed by different laboratories or at different times to be compared effectively. However, for this to be the case, then it is essential that all reference materials are calibrated appropriately and perform in a similar manner to a patient sample. In 2010, the first WHO international standard (IS) for human cytomegalovirus (CMV) was established as a high-order reference material. Its intended use is to calibrate secondary reference materials used in CMV nucleic acid amplification techniques (NAT) in international units (IU) (1). The CMV IS comprises laboratorygrown virus formulated in a Tris-HCl buffer to enable dilution in the matrix appropriate to the assay (1, 2). This was designed to control for matrix effects and ensure that the standard would be commutable, although at the time of establishment, this was not assessed formally. In their recent study, Jones et al. report on their studies of the commutability of the CMV IS with plasma and whole-blood specimens using the Abbott RealTime CMV assay (3). The authors report that the CMV IS behaves differently when diluted in plasma and whole-blood matrices and extracted using the respective protocols for these matrices, whereas patient samples do not. This matrix effect appeared to reduce the signal for the IS when diluted in whole blood by 0.4 log IU/ml compared with the plasma extraction procedure in this assay platform. The authors conclude that the IS is not commutable.Commutability of a reference standard is dependent not only on the material itself but also on the assay in which it is applied. In particular, in quantitative assays where internal calibrators are included, the nature of these calibrators and the way that they are processed will impact the outcome of the assay (1). In the reported assay, the plasmid-based calibrator used in both plasma and whole-blood processes was calibrated against the IS in plasma alone, rather than in both matrices as recommended (2). This is likely to have contributed to the differing results observed for the patient samples and the IS when diluted in each matrix. If the calibration for the whole-blood process been performed against the IS in whole blood, then the stated conversion factor would have been lower, but comparable with those of other studies (4, 5).In order to fully establish the commutability of reference materials, large-scale studies using multiple assay platforms in many laboratories are required (6, 7). We are undertaking studies to investigate the commutability of the IS for CMV NAT and are collaborating in studies organized by others. The results will contribute to this active debate and clarify the benefit and limitations of specific reference materials in the standardization of assays and data that are designed to assist the clinical management of CMV. Until that time, it will not be possible to fully establish whether the different results observed in the article a...

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Fully Automated Quantification of Cytomegalovirus (CMV) in Whole Blood with the New Sensitive Abbott RealTi m e CMV Assay in the Era of the CMV International Standard

Cited by 42 publications

References 25 publications

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Standardization of Nucleic Acid Tests for Clinical Measurements of Bacteria and Viruses

Commutability of the World Health Organization International Standard for Human Cytomegalovirus: Standard or Assay

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