Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis

Abstract

Despite antiviral prophylaxis, a high percentage (over 90%) of heart transplant patients experience active cytomegalovirus (CMV) infection, diagnosed by detection of viral DNA in peripheral blood polymorphonuclear leukocytes within the first few months posttransplantation. Viral DNA was detected in mononuclear cells prior to detection in granulocytes from CMV-seropositive recipients (R ؉ ) receiving a heart from a CMV-seropositive donor (D ؉ ). Based on assessment of systemic infection in leukocyte populations, both R ؉ subgroups (R ؉ /D ؊ and R ؉ /D ؉ ) experienced a greater infection burden than the R ؊ /D ؉ subgroup, which was aggressively treated because of a higher risk of acute CMV disease. Despite widespread systemic infection in all at-risk patient subgroups, CMV DNA was rarely (<3% of patients) detected in transplanted heart biopsy specimens. The R ؉ patients more frequently exceeded the 75th percentile of the CMV DNA copy number distribution in leukocytes (110 copies/10 5 polymorphonuclear leukocytes) than the R ؊ /D ؉ subgroup. Therefore, active systemic CMV infection involving leukocytes is common in heart transplant recipients receiving prophylaxis to reduce acute disease. Infection of the transplanted organ is rare, suggesting that chronic vascular disease attributed to CMV may be driven by the consequences of systemic infection.

High Incidence of Cytomegalovirus Disease in D+/R− Heart Transplant Recipients Shortly After Completion of 3 Months of Valganciclovir Prophylaxis

“…10 Despite anti-viral prophylaxis, Ͼ90% of heart transplant recipients may still experience an active CMV infection. 11 In a recent study, KijpittayaritArthurs et al described a 29% incidence of CMV disease in the D ϩ /R Ϫ heart transplant recipients who received 3 months of valganciclovir prophylaxis. The median time to onset of disease was 125 days after the discontinuation of CMV prophylaxis.…”

Human Cytomegalovirus Infection of Langerhans-Type Dendritic Cells Does Not Require the Presence of the gH/gL/UL128-131A Complex and Is Blocked after Nuclear Deposition of Viral Genomes in Immature Cells

“…iLC and mLC populations derived from the progenitor cells of four different donors were exposed to BAC4 at an MOI of 10 PFU/cell for 15 min, 1 h, or 4 h. At each time point, cells were collected, washed, and stored (untreated) or washed and treated with citrate buffer for 1 min at room temperature or with proteinase K for 1 h at 4°C. After additional washes, cells were pelleted and subjected to real-time quantitative PCR with primers hybridizing to the viral UL122/123 ORF (79) or to the cellular albumin gene (63) and the number of viral genomes/cell was calculated.…”

Simultaneous Monitoring of Cytomegalovirus-Specific Antibody and T-cell levels in Seropositive Heart Transplant Recipients

“…However, there is no consensus on the duration of prophylaxis or the ideal antiviral agent for long-term prophylaxis. In any case, the occurrence of subclinical CMV infection [4], late CMV disease after interruption of prophylaxis [5], and ganciclovir-resistant disease [6] highlights the need for new strategies. As CMV disease occurs only when specific immune responses are compromised, early evaluation of an individual's protective capacity could improve the accuracy of current monitoring [7].…”