Cytomegalovirus DNAemia Research Articles

Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy

Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy

Quantitative changes in cytomegalovirus DNAemia and genetic analysis of the UL97 and UL54 genes in AIDS patients receiving cidofovir following ganciclovir therapy

Five AIDS patients with cytomegalovirus (CMV) retinitis who had received ganciclovir (GCV) therapy were followed with serial blood sampling to detectchanges both in CMV load and in the genetic composition of genes UL97 and UL54 whilst receiving cidofovir (CDV) therapy. CDV neither reduced CMV load in blood nor prevented its quantitative resurgence during therapy. These effects were not explained by the initial presence or development of CDV-associated drug resistance mutations in UL54. In two patients, UL97 genotypic resistance to GCV involving either a L595S mutation or a deletion of amino acids 590-603 were present at the initiation of CDV and, in both patients, repopulation of CMV strains with wild-type UL97 sequences occurred during CDV therapy. These data are consistent with GCV-resistant strains containing UL97 mutations being less fit than their wild-type counterparts and so being able to persist only with the selective pressure of GCV.

Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence, risk factors, clinical features, complications, and outcome of cytomegalovirus (CMV) infection. A total of 26 patients (13%) developed CMV viremia (n = 5), DNAemia (n = 3), viruria (n = 18) and/or disease (n = 3) at a median of 45 days following stem cell infusion. None of the patients underwent surveillance testing for CMV. A diagnosis was established by culture and polymerase chain reaction of blood, urine or other tissue samples submitted when patients exhibited clinical features suggestive of CMV infection. Cytomegalovirus seropositivity prior to transplantation was the only statistically significant risk factor predicting subsequent identification of CMV (P < 0.001). The symptoms were severe enough in 23 patients to warrant treatment with intravenous ganciclovir. Three patients developed CMV disease; two developed fatal CMV pneumonia and one developed CMV gastritis which responded to antiviral treatment. Clinical signs and symptoms as well as viremia and viruria resolved with (20 patients) and without (three patients) treatment in the remaining individuals. All instances of CMV viremia, DNAemia, viruria and disease occurred within 3 months of stem cell infusion. These results demonstrate that CMV is a common pathogen after autologous PBSCT and may result in fatality in rare instances. Surveillance programs appear to be neither useful nor cost-effective. Diagnostic evaluation should be performed only in patients exhibiting suspicious clinical features and antiviral chemotherapy should be administered for persistent and severe signs and symptoms.

Quantity of human cytomegalovirus (CMV) DNAemia as a risk factor for CMV disease in renal allograft recipients: Relationship with donor/recipient CMV serostatus, receipt of augmented methylprednisolone and antithymocyte globulin (ATG)

A prospective longitudinal study of 87 renal allograft recipients identified 31 patients with cytomegalovirus (CMV) viraemia. Previous studies have identified CMV viraemia, donor positivity, and CMV load in urine as independent risk factors for disease following renal transpl antation. We used quantitative-competitive polymerase chain reaction (QC-PCR) to quantify the CMV DNA load in blood from these patients, and report that it is a significant and independent risk factor for CMV disease. Patients with symptomatic CMV infection had significantly higher maximum CMV loads than those with no disease (P = .0003). We also found that peak loads were significantly higher in individuals experiencing primary CMV infection (P < .01), and CMV re-infection (P < .05) compared with recipients reactivating endogenous CMV. Univariate analysis revealed that CMV DNA load in blood, donor seropositivity, and receipt of antithymocyte globulin (ATG) were all significantly associated with disease (P = .005, .04, and .05, respectively). However, the association of donor/recipient serostatus, and receipt of ATG became nonsignificant in multivariate analyses whereas the significance of the quantity of CMV DNAemia was maintained, illustrating that CMV load plays a central role in the pathogenesis of CMV disease.

Quantity of human cytomegalovirus (CMV) DNAemia as a risk factor for CMV disease in renal allograft recipients: Relationship with donor/recipient CMV serostatus, receipt of augmented methylprednisolone and antithymocyte globulin (ATG)

Quantity of human cytomegalovirus (CMV) DNAemia as a risk factor for CMV disease in renal allograft recipients: Relationship with donor/recipient CMV serostatus, receipt of augmented methylprednisolone and antithymocyte globulin (ATG)

Assessing the time of first onset of viremia, antigenemia, and dnaemia and the time to clearing during ganciclovir therapy fascilitates prediction of cytomegalovirus (CMV) disease vs. CMV syndrome in renal allograft recipients

The risk factors associated with CMV DNAemia are not well known after haploidentical stem cell transplantation (SCT).This study investigated the risk factors and prognosis for CMV DNAemia among CMV seromatched donors and recipients (D+/R+).A retrospective study of patients undergoing haploidentical stem cell transplantation (SCT) between January 2010 and January 2012 was conducted. Cox regression analysis was performed to identify the risk factors for CMV DNAemia. These possible factors included recipient/donor age, recipient/donor gender, gender disparity, recipient HBsAg serostatus, diagnosis, risk stratification, anti-thymocyte globulin (ATG) dose (6 mg/kg,10 mg/kg), early neutrophil engraftment (≤12 days, >12 days), absolute lymphocyte count on day 30 (ALC30) and the occurrence of acute GVHD before CMV DNAemia.The total number of patients was 248 with median age of 31 years (range, 14–56). The cumulative incidence of CMV DNAemia (146/248) was 59.5%. CMV DNAemia was first detected after a median of +35 days (range,12–82). Seventeen patients (17/146, 11.6%) developed CMV disease. Multivariate analysis identified HBsAg seropositivity (P = 0.002, hazard ratio (HR) = 1.833; 95%CI = 1.257–2.673) and the occurrence of acute GVHD before CMV DNAemia (P = 0.014; HR = 1.520; 95%CI = 1.088–2.124) as risk factors for CMV DNAemia. CMV DNAemia was associated with subsequent II-IV acute graft-versus-host disease (GVHD) (P = 0.014), III-IV aGVHD (P = 0.013) and chronic GVHD (P = 0.008). Totally, CMV DNAemia was found to be a poor prognostic factor in terms of non-relapse mortality (NRM) (P = 0.003, HR = 2.730; 95%CI = 1.406–5.197), and overall survival (OS) (P = 0.045, HR = 1.654; 95%CI = 1.012–2.701).Our data showed HBsAg seropositivity was associated with an increased risk of cytomegalovirus DNAemia. Detection of CMV DNAemia proved to be a poor prognostic factor for haploidentical patients.

Diagnosis of cytomegalovirus (CMV) disease in renal allograft recipients: the role of semiquantitative polymerase chain reaction (PCR)

Cytomegalovirus disease remains a significant cause of morbidity and mortality in the renal allograft recipient. There is a need for rapid and sensitive techniques predictive of CMV disease to allow initiation of early antiviral therapy. Seventy-seven renal allograft recipients were enrolled in a prospective study where CMV viruria (shell vial culture/DEAFF test), viraemia (shell vial culture), serology and detection of virus DNA in peripheral blood leukocytes by PCR (CMV DNAemia) were correlated with clinical evidence of CMV disease. Serology and shell vial culture had poor sensitivity for the early diagnosis of CMV disease. CMV DNAemia appeared to correlate with active virus replication. CMV DNAemia had a sensitivity and negative predictive value of 100% and a positive predictive value of 27% for CMV disease. Patients with symptomatic CMV disease were shown to have higher levels of CMV DNAemia than those with asymptomatic infection. A negative CMV DNAemia result excluded CMV disease with confidence, but a positive result (given the low positive predictive value) did not by itself provide a reliable guide for the initiation of pre-emptive antiviral therapy. However, the semiquantitative CMV DNAemia result taken together with the clinical findings provided useful information for patient management.