Virologic Suppression Measured by a Cytomegalovirus (CMV) DNA Test Calibrated to the World Health Organization International Standard Is Predictive of CMV Disease Resolution in Transplant Recipients

Razonable, Raymund R.; Åsberg, Anders; Rollag, Halvor; Duncan, J.R.; Boisvert, Denis; Yao, Joseph D.; Caliendo, Angela M.; Humar, Atul; D., Tri

doi:10.1093/cid/cit096

Cited by 86 publications

(56 citation statements)

References 14 publications

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“…The growth rate has been calculated at 1.82 units/day (95% confidence interval [CI], 1.44 to 2.56 units/day) (36), which is commensurate to a doubling time of Ͻ2 days (Table 1) (3,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43). Clinically, this translates to a higher incidence and greater severity of CMV disease, characterized by high viral loads, among CMV Dϩ/RϪ SOT recipients (3,5,36,(41)(42)(43)(44)(45).…”

Section: Viral Epidemiology and Mechanisms Of Infectionmentioning

confidence: 99%

“…CMV-seropositive SOT recipients who possess preexisting CMV-specific immunity have a relatively lower risk of CMV disease, and the occurrence of CMV disease in these patients is likely the result of the use of intense immunosuppression that severely impairs T cell function (17,52). In all these cases, the risk of CMV disease and its severity can be correlated directly to viral load-in general, a higher viral load corresponds to a greater risk and severity of CMV disease (3,5,36,(41)(42)(43)(44)(45). CMV infection in SOT recipients starts as local replication at sites that harbor latent virus.…”

Section: Clinical Diseasementioning

confidence: 99%

“…If the virus is uncontrolled, local reactivation is followed by hematogenous dissemination (viremic phase). The vast majority of cases of CMV infection are diagnosed during this viremic phase, through viral load or antigen testing (3,5,36,(41)(42)(43)(44)(45).…”

Section: Clinical Diseasementioning

confidence: 99%

“…However, there remain important limitations to such testing, including the lack (until recently) of widely adopted quantitative standards (4,5). Several platforms and methodologies are used for CMV NAT (2,6), and in the absence of calibration to a common international reference standard, their performance could not be compared directly and accurately.…”

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Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

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Section: Viral Epidemiology and Mechanisms Of Infectionmentioning

confidence: 99%

Section: Clinical Diseasementioning

confidence: 99%

Section: Clinical Diseasementioning

confidence: 99%

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confidence: 99%

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Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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“…Higher-order reference materials carrying values traceable to the SI or another internationally accepted reference (IU) are key to improving the comparability and reducing the variability of quantitative viral load testing (12) by underpinning reproducible characterization of manufacturer's calibrators and assessment of the performance limits of microbiological tests with semiquantitative or qualitative outputs. The recent release of the 1st WHO IS for CMV and EBV will hopefully lead to better definition of viral load values with respect to clinical outcomes (42), as has been observed following the implementation of international standards for HIV and HCV (3). However, the recent adoption of the standards has not yet led to significant improvements in the comparability of results gathered through EQA schemes (V. James; presented at the 24th SoGAT meeting, Ljubljana, Slovenia, 8 to 9 May 2013).…”

Section: Development Of Reference Measurement Systems For Pathogen Naatsmentioning

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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Viral Infections in Transplant Recipients

Razonable

Eid

2016

Molecular Pathology in Clinical Practice

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Virologic Suppression Measured by a Cytomegalovirus (CMV) DNA Test Calibrated to the World Health Organization International Standard Is Predictive of CMV Disease Resolution in Transplant Recipients

Abstract: NCT00431353.

Cited by 86 publications

References 14 publications

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

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

Viral Infections in Transplant Recipients

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