Frequent detection of cytomegalovirus (CMV) DNA in the lower respiratory tract in CMV-seropositive pediatric patients with underlying chronic bronchopulmonary diseases lacking canonical immunosuppression.

Cytomegalovirus (CMV) may be a relevant cause of morbidity in patients displaying various inflammatory diseases. In this study, it was investigated whether CMV DNA is detected in the lower respiratory tract and the systemic compartment in pediatric patients with chronic or recurrent bronchopulmonary diseases. A total of 42 lower respiratory tract specimens and 11 paired plasma samples from 42 patients were analyzed for the presence of CMV DNA by real-time PCR. The respiratory specimens were also screened for the presence of respiratory viruses and human herpesvirus 6 (HHV-6) and 7 (HHV-7) by PCR methods. Quantitative bacterial and fungal cultures were performed. IL-6 levels in the respiratory specimens were quantified using ELISA. CMV DNA was detected either in the lower respiratory airways, in plasma, or both in 54.5% of CMV-seropositive patients. The levels of IL-6 were significantly higher in these patients than in those with no detectable levels of CMV DNA. HHV-6 and HHV-7 DNA were detected in three and one patients, respectively. Respiratory viruses were detected in 13 of the 42 patients. Significant growth of one or more bacterial species was observed in 17 patients. No significant association was found between the presence of CMV DNA and the detection of other microorganisms. The data indicated that the presence of CMV DNA in the lower respiratory tract is a frequent finding in children with chronic or recurrent bronchopulmonary diseases. Further, prospective observational studies are needed to assess the impact of this phenomenon, if any, on the clinical course of these patients.

Immunological insights into the pathogenesis of active CMV infection in non-immunosuppressed critically ill patients.

Dissociation of cytomegalovirus (CMV) DNA loads between the lower respiratory tract and blood, with high levels in the former compartment and low or undetectable levels in the latter, commonly occurs during active CMV infection in critically ill patients despite the presence of high frequencies of CMV-specific IFN-γ-producing CD8(+) and CD4(+) T cells in blood. Data presented in this case report suggest that inter-compartmental differences in interleukin-10 (IL-10) levels may, in part, explain the pathobiology of this phenomenon. In the absence of ganciclovir treatment, a significant correlation was observed between IL-10 levels and CMV DNA loads in lower respiratory tract specimens (P = 0.016), but not in plasma samples (P = 0.46). Comparable data were obtained during the course of active CMV infection episodes that developed in six CMV-seropositive critically ill patients with no canonical immunosuppression. The presence of higher levels of IL-10 in the lower respiratory tract than in plasma may result in increased impairment of CMV-specific T-cell effector responses in the lung compared to the systemic compartment, facilitating local CMV replication.

Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells during episodes of viral DNAemia in allogeneic stem cell transplant recipients: potential implications for the management of active CMV infection.

The dynamics of CMV pp65 and IE-1-specific IFNgamma-producing CD8(+) (IFNgamma CD8(+)) and CD4(+) (IFNgamma CD4(+)) T cells and CMV DNAemia were assessed in 19 pre-emptively treated episodes of active CMV infection. Peripheral counts of IFNgamma CD8(+) and IFNgamma CD4(+) T cells inversely correlated with CMV DNAemia levels (P = <0.001 and P = 0.003, respectively). A threshold value of 1.3 cells/microl predicting CMV DNAemia clearance was established for IFNgamma CD8(+) T cells (PPV, 100%; NPV, 93%) and for IFNgamma CD4(+) T cells (PPV, 100%; NPV, 75%). Undetectable T-cell responses were usually observed at the time of initiation of pre-emptive therapy. Either a rapid (within 7 days) or a delayed (median 31 days) expansion of both T-cell populations concomitant with CMV DNAemia clearance was observed in 5 and 8 episodes, respectively. An inconsistent or a lack of expansion of both T-cell subsets was related to a persistent CMV DNAemia. Robust and maintained CMV-specific T-cell responses after CMV DNAemia clearance and cessation of antiviral therapy were associated with a null incidence of relapsing infections at least during the following month. Data obtained in the present study may be helpful in the design of therapeutic strategies for the management of active CMV infections in the allo-SCT recipient.

Prevalence and prognostic implications of active cytomegalovirus infection in patients with acute heart failure.

AHF (acute heart failure) causes significant morbidity and mortality. Recent studies have postulated that the expression of inflammatory mediators, such as cytokines and chemokines, plays an important role in the development and progression of heart failure. A pro-inflammatory state has been postulated as a key factor in triggering CMV (cytomegalovirus) reactivation. Therefore we sought to determine the prevalence of active CMV infection in immunocompetent patients admitted for AHF and to quantify the association with the risk of the combined end point of death or AHF readmission. A total of 132 consecutive patients admitted for AHF were enrolled in the present study. Plasma CMV DNAaemia was assessed by qRT-PCR (quantitative real-time PCR), and cytokine measurements in plasma were performed by ELISA. Clinical data were evaluated by personnel blinded to CMV results. The independent association between active CMV infection and the end point was determined by Cox regression analysis. During a median follow-up of 120 [IQR (interquartile range), 60-240] days, 23 (17.4%) deaths, 34 (24.2%) readmissions for AHF and 45 (34.1%) deaths/readmissions for AHF were identified. Plasma CMV DNAaemia occurred in 11 (8.3%) patients, albeit at a low level (<100 copies/ml). The cumulative rate of the composite end point was higher in patients with CMV DNAaemia (81.8 compared with 29.8%; P<0.001). After adjusting for established risk factors, the occurrence of CMV DNAaemia was strongly associated with the clinical end point [hazard ratio = 4.39 (95% confidence interval, 2.02-9.52); P<0.001]. In conclusion, active CMV infection occurs, although uncommonly, in patients with AHF, and may be a marker of disease severity.

Virological and immunological features of active cytomegalovirus infection in nonimmunosuppressed patients in a surgical and trauma intensive care unit.

Cytomegalovirus (CMV) reactivation occurs frequently in critically ill patients. The natural course of CMV infection and the interaction between CMV and the adaptive immune system in this setting remain poorly defined. Fifty-three CMV-seropositive patients in a surgical and trauma intensive care unit were included in this study. The CMV DNA load in tracheal aspirates (TA) and plasma (PL) was monitored by qPCR. CMV-specific T-cell immunity was assessed by intracellular cytokine staining. Plasma TNF-alpha levels were determined by ELISA. CMV reactivation occurred in 39.7% of patients (23% had CMV DNA detected only in TA). The analysis of TA allowed an earlier diagnosis in 28% of patients. Clearance of CMV DNAemia preceded that of CMV DNA in TA in some episodes. Peak CMV DNA levels were significantly higher in TA than in PL (P = 0.02). CMV reactivation developed in the presence of CMV-specific T cells. Termination of CMV reactivation was associated with an expansion of functional CMV-specific T cells. Plasma levels of TNF-alpha did not allow for the prediction of the occurrence of CMV reactivation. CMV-specific T-cell immunity is preserved in most critically ill patients experiencing CMV reactivation. Analysis of respiratory specimens is imperative for an optimal monitoring of CMV reactivation in this setting.