Area under the viraemia curve versus absolute viral load: Utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients

Schäfer, Peter; Tenschert, W; Cremaschi, Liana; Schröter, Matthias; Zöllner, Bernhard; Laufs, Rainer

doi:10.1002/jmv.2005

Cited by 34 publications

(34 citation statements)

References 16 publications

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“…The severity of an episode of CMV viremia is determined not only by its level but also by its duration (25,26). Both quantities can be combined by calculation of the area under the curve of viral load over time (25), a universal means of assessing the interrelationship among peak viral load, initial viral load, and rate of increase of viral load, parameters that have been described as independent risk factors for CMV disease (26).…”

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confidence: 99%

“…Both quantities can be combined by calculation of the area under the curve of viral load over time (25), a universal means of assessing the interrelationship among peak viral load, initial viral load, and rate of increase of viral load, parameters that have been described as independent risk factors for CMV disease (26). In this retrospective study, (re)activation of CMV, as measured by DNA load in plasma, was used as a safety parameter to evaluate the efficacy of ATG versus daclizumab in SPK transplant recipients.…”

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Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients

et al. 2006

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OBJECTIVE -Simultaneous pancreas-kidney (SPK) transplantation in type 1 diabetic patients requires immunotherapy against allo-and autoreactive T-cells. Cytomegalovirus (CMV) infection is a major cause for morbidity after transplantation and is possibly related to recurrent autoimmunity. In this study, we assessed the pattern of CMV viremia in SPK transplant recipients receiving either antithymocyte globulin (ATG) or anti-CD25 (daclizumab) immunosuppressive induction therapy.RESEARCH DESIGN AND METHODS -We evaluated 36 SPK transplant recipients from a randomized cohort that received either ATG or daclizumab as induction therapy. Patients at risk for CMV infection received oral prophylactic ganciclovir therapy. The CMV DNA level in plasma was measured for at least 180 days using a quantitative real-time PCR. Recipient peripheral blood mononuclear cells were cross-sectionally HLA tetramer-stained for CMV-specific CD8 ϩ T-cells.RESULTS -Positive CMV serostatus in donors was correlated with a higher incidence of CMV viremia than negative serostatus. In patients at risk, daclizumab induction therapy significantly prolonged CMV-free survival. CMV viremia occurred earlier and was more severe in patients with rejection episodes than in patients without rejection episodes. CMV-specific CD8 ϩ T-cell counts were significantly lower in patients developing CMV viremia than in those who did not.CONCLUSIONS -Despite their comparable immunosuppressive potential, daclizumab is safer than ATG regarding CMV infection risk in SPK transplantation. ATG-treated rejection episodes are associated with earlier and more severe infection. Furthermore, high CMV-specific tetramer counts reflect antiviral immunity rather than concurrent viremia because they imply low viremic activity. These findings may prove valuable in the discussion on both safety of induction therapy and recurrent autoimmunity in SPK and islet transplantation. Diabetes Care 29:842-847, 2006

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Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients

et al. 2006

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“…Moreover, determination of the CMV viral loads in blood (6,13,(16)(17)(18) and urine (8) has shown its utility in designating patients who at risk for * Corresponding author. Mailing address: Clinical Microbiology/ L40, The Cleveland Clinic Foundation,…”

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“…Moreover, determination of the CMV viral loads in blood (6,13,(16)(17)(18) and urine (8) has shown its utility in designating patients who at risk for disease (12). The clinical utility of the CMV viral load in BAL fluid has not been determined, however (1,15 Therefore, in the present study, we investigated the utility of the CMV Hybrid Capture assay (Digene Corporation, Gaithersburg, Md.)…”

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Correlation between Viral Loads of Cytomegalovirus in Blood and Bronchoalveolar Lavage Specimens from Lung Transplant Recipients Determined by Histology and Immunohistochemistry

Chemaly¹,

et al. 2004

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Cytomegalovirus (CMV) is an important pathogen in lung transplant recipients. Early detection of CMV end-organ disease should help with treatment management. We determined the CMV viral load by hybrid capture in bronchoalveolar lavage (BAL) fluid samples from patients who had undergone lung transplantation. For 39 of these samples (from 25 patients), corresponding transbronchial biopsy samples were available for CMV immunohistochemistry (IHC). The CMV IHC results were interpreted and categorized as positive or negative, and the positive results were subcategorized as typical if cells with both significant nuclear enlargement or Cowdry A-type inclusions and positive staining were present or as atypical if definitive nuclear staining was seen but significant nuclear enlargement was not. Diagnostic CMV viral inclusions were reported in the anatomic diagnosis, based on hematoxylin-eosin staining alone, for three (8%) of the biopsy samples. CMV was detected by IHC in 13 (33%) samples (5 typical, 8 atypical). The median CMV viral load in BAL samples was 0 copies/ml for BAL samples from patients with IHC-negative biopsy samples; 47,678 copies/ml for BAL samples from patients with biopsy samples with positive, atypical staining; and 1,548,827 copies/ml for BAL samples from patients with biopsy samples with positive, typical staining (P < 0.001). Compared to routine pathology of biopsy samples, the use of IHC increased the diagnostic yield of CMV. Also, the CMV viral load in BAL fluid samples increased along with immunoreactivity from negative to positive, atypical staining to positive, typical staining. The CMV viral load determined with the end-organ sample, the BAL fluid sample, was higher than the corresponding viral load determined with blood. Both IHC and determination of the CMV viral load in BAL samples may be useful for the detection of individuals at risk for the development of fulminant invasive CMV disease.Cytomegalovirus (CMV) pneumonitis is associated with high rates of morbidity and mortality rate in solid-organ, blood, and bone marrow transplant recipients (5,7,10,19,20). CMV pneumonitis is quite common in lung transplant recipients in particular, as it develops in more than half of all lung transplant recipients over the first 3 years after transplantation (4, 14, 21). The diagnosis of CMV pneumonitis is based on the presence of signs and/or symptoms of lower respiratory tract infection and diffuse infiltrates on a chest radiograph, in combination with a CMV-positive culture of bronchoalveolar lavage (BAL) fluid, CMV-positive immunohistochemistry (IHC), positivity by in situ hybridization for CMV, or the presence of typical viral inclusions in routine hematoxylin and eosin (H&E)-stained sections (11). A diagnosis of CMV infection may be made in the absence of a positive culture, when definitive CMV viral inclusions are seen upon histopathologic evaluation of lung biopsy samples, sometimes aided by the use of an IHC stain or in situ hybridization for CMV (2,22,23). In the past, we noted definitive CMV-pos...

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“…These studies have shown that viral load is a dominant risk factor for HCMV disease (Cope et al 1997;Gor et al 1998;Spector et al 1998;Emery et al 1999a,b;Hassan-Walker et al 1999;Limaye et al 2001). In addition, kinetics of replication during the early phases of active replication have been defined and used to estimate the basic reproductive number of HCMV (Emery et al 2002) and to provide prognostic information in the immunocompromised host (Emery et al 2000;Schafer et al 2001). Since the virologic parameters, such as initial viral load, peak viral load, rate of increase in viral load prior to disease onset, are highly correlated it has been difficult, using conventional multivariable models, to ascertain the relative contributions of viral load thresholds and continuous presence of virus to the pathogenesis of different HCMV diseases and to produce estimates of the likely time of onset of disease.…”

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Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

et al. 2006

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Human cytomegalovirus can cause a diverse range of diseases in different immunocompromised hosts. The pathogenic mechanisms underlying these diseases have not been fully elucidated, though the maximal viral load during infection is strongly correlated with the disease. However, concentrating on single viral load measures during infection ignores valuable information contained during the entire replication history up to the onset of disease. We use a statistical model that allows all viral load data sampled during infection to be analysed, and have applied it to four immunocompromised groups exhibiting five distinct cytomegalovirus-related diseases. The results show that for all diseases, peaks in viral load contribute less to disease progression than phases of low virus load with equal amount of viral turnover. The model accurately predicted the time of disease onset for fever, gastrointestinal disease and pneumonitis but not for hepatitis and retinitis, implying that other factors may be involved in the pathology of these diseases.

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Area under the viraemia curve versus absolute viral load: Utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients

Cited by 34 publications

References 16 publications

Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients

Choice of Antibody Immunotherapy Influences Cytomegalovirus Viremia in Simultaneous Pancreas-Kidney Transplant Recipients

Correlation between Viral Loads of Cytomegalovirus in Blood and Bronchoalveolar Lavage Specimens from Lung Transplant Recipients Determined by Histology and Immunohistochemistry

Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

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