Monitoring antigenemia is useful in guiding treatment of severe cytomegalovirus disease after organ transplantation

Berg, Amy; Tegzess, A. M.; Scholten-Sampson, A.; Schirm, J; Giessen, M. ptvan der; The, T. H.; Son, Willem J. van

doi:10.1111/j.1432-2277.1992.tb01763.x

Cited by 22 publications

(1 citation statement)

References 32 publications

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“…Although CMV-PCR is a useful test for the diagnosis of CMV infection [13, 14, 15], many authors consider CMV-AG to be the best method for monitoring CMV infection and disease [16, 17, 18]. Tanabe et al [19]observed a good correlation between the results of CMV-AG and the clinical course of the disease in renal transplant recipients who where recovering from CMV disease after ganciclovir therapy.…”

Section: Discussionmentioning

confidence: 91%

Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Gómez

Oña

Melón

et al. 1999

Nephron

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Background: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. Methods: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 10⁵ PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. Results: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 ± 31 (25–175) mg, a mean percentage decrease of 76 ± 27% (25–100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 ± 66, 196 ± 54 and 164 ± 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. Conclusion: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.

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Section: Discussionmentioning

confidence: 91%

Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Gómez

Oña

Melón

et al. 1999

Nephron

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Quantitation of human cytomegalovirus in recipients of solid organ transplants by real‐time quantitative PCR and pp65 antigenemia

Mengelle

Pasquier

Rostaing

et al. 2002

Journal of Medical Virology

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Human cytomegalovirus (HCMV) infections and anti-HCMV treatment are usually monitored by measuring pp65 antigenemia. This method is time-consuming, labour-intensive and requires skilled operators. We have compared results obtained using real-time Light Cycler quantitative PCR (QPCR) and the pp65 antigen assay on serial samples collected from recipients of solid organ transplants. We collected 198 blood samples from 14 solid organ transplant recipients and assayed them for pp65 antigen and with Light Cycler PCR. HCMV DNA was extracted from leukocytes and measured using primers and probe located in the UL83 region. The quantity of HCMV DNA was calculated using a standard curve prepared from a plasmid containing the target sequence. There was a good correlation between the number of pp65-positive cells and the DNA copy number (r = 0.57, P < 0.0001). A clinical threshold of 50 positive polymorphonuclear leukocytes/200,000 cells was equivalent to two log10 genome copies per capillary by Light Cycler PCR. HCMV DNA was detected before pp65 antigen in three patients at a mean time of 10 days, whereas the two tests were positive simultaneously for eight patients. Both the pp65 antigen data and DNA copy number decreased over time during antiviral treatment, although the QPCR was positive 28.2 days after the pp65 antigen assay had become negative. The real-time Light Cycler quantitative PCR assay is a rapid and labour-saving technique. This molecular method could be useful for monitoring infections and antiviral treatment in recipients of solid organ transplants.

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Quantitation of cytomegalovirus in the blood of liver transplant recipients

et al. 1995

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An assay for quantitation of cytomegalovirus (CMV) has been developed. The assay combines DNA amplification and enzyme-linked immunosorbent assay (ELISA) detection. In this study, the assay has been used to examine sequential buffycoats from 32 consecutive liver transplant recipients. In a febrile patient, CMV titres in excess of lo4 copies per 150,000 cells strongly suggest a diagnosis of symptomatic CMV infection. Antiviral therapy causes a rapid decline in viral titre. Viral titres are seen to rise presymptomatically in nfection with cytomegalovims (CMV) remains an I important cause of morbidity in immunosuppressed transplant recipients. The association of symptomatic infection with virus isolation from buQ-coat is well e~tab1ished.l.~ Recently, the polymerase chain reaction (PCR) has been proposed as a potentially useful test for the detection of CMV in this ~e t t i n g .~. '~ Assay sensitivity depends on (1) method of substrate preparation, (2) primer design, (33 thermal cycling conditions, and (4) post-PCR detection method. When performance of the assay is optimized, CMV can be detected in blood of immunocompetent blood donor^.'^,'^ Such a sensitive assay would not provide useful information for the management of immunosuppressed patients. Most investigators agree that PCR has excellent sensitivity and negative predictive value (for the diagnosis of symptomatic infection), but that specificity and positive predictive value are poor. Discordant conclusions concerning the clinical utility of PCR detection may result from differences in assay DNA detection sensitivity, which in turn result from interlaboratory methodological differences.For any given substrate and conditions, the efficiency of the PCR reaction varies. Problems of interpretation arising from interassay and interlaboratory variation in PCR efficiency might be overcome by the inclusion of an internal standard DNA sequence in each r e a c t i~n . '~.~~ We have developed a quantitative assay for CMV detection that combines a single PCR reaction with enzyme-linked immunosorbent assay (ELISA) detection.Sequential bu&-coats Materials and MethodsThirtytwo consecutive liver transplant recipients were studied for 3 months after transplantation. Prospective virologcal surveillance was not performed. Sera were examined retrospectively for CMV immunoglobulin (19, M, and for the purposes of this report CMV infection is defined by the presence of CMV IgM. Symptomatic CMV infection ("CMV disease") is defined by the following criteria. Fever (>38"C on at least 2 consecutive days) and serum IgM positivity, with either leukopenia (count < 3 x 10y/l), and/or histological evidence of invasive infection.Patients did not receive antiviral prophylaxis. When symptomatic CMV infection was diagnosed, treatment included reduction of immunosuppression and administration of ganciclovir ( I 0 mg/kg/d adjusted for renal dysfunction).Blood was sampled weekly during the inpatient stay, and then at each outpatient attendance for 3 months. Serum was separated from clotted bloo...

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Monitoring antigenemia is useful in guiding treatment of severe cytomegalovirus disease after organ transplantation

Cited by 22 publications

References 32 publications

Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Quantitation of human cytomegalovirus in recipients of solid organ transplants by real‐time quantitative PCR and pp65 antigenemia

Quantitation of cytomegalovirus in the blood of liver transplant recipients

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