New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

Abstract

SUMMARY In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

Pre-emptive treatment with oral valganciclovir in management of CMV infection after cardiac transplantation

“…Cytokines, chemokines, and growth factors elaborated in response to the presence of replicating virus can depress host defenses against opportunistic superinfection. 1,2 It has been proposed that CMV contributes to chronic allograft injury and long-term survival of transplant recipients due to its immunomodulating effect. [2][3][4] Mechanisms by which CMV induces direct effects on vasculature include its ability to enhance vascular smooth muscle cell proliferation and increase the etherified LDL content of these cells.…”

“…1,2 It has been proposed that CMV contributes to chronic allograft injury and long-term survival of transplant recipients due to its immunomodulating effect. [2][3][4] Mechanisms by which CMV induces direct effects on vasculature include its ability to enhance vascular smooth muscle cell proliferation and increase the etherified LDL content of these cells. Indirect vascular effects of CMV include upregulating of pro-inflammatory cytokines; induction of reactive oxygen species that facilitate its own gene expression and replication; activation of leukocytes to express maladaptive functions, such as the production of acute phase reactants, some of which are known to influence arteriosclerosis.…”

“…2,7 Symptomatic infection occur in 9% to 35% of heart recipients not receiving antiviral prophylaxis. 8 -10 Currently, the prevalence of life-threatening CMV complications has been extensively reduced by pharmacologic intervention, resulting in improved patient survival.…”

Diagnostic value of HCMV pp65 antigen detection by FCA for symptomatic and asymptomatic infection: compared to quantification of HCMV DNA and detection of IgM antibody in infants

“…Virological surveillance with highly sensitive techniques is required for the early identiWcation and pre-emptive treatment of the infection before the development of HCMV disease [13,14]. Therefore, at neonatal period, it is essential to use appropriate and sensitive tests for diagnosis of HCMV infection.…”

“…Detectable HCMV DNA in urine samples indicates HCMV exist in body. HCMV pp65 antigenemia is known to be clinically useful for the diagnosis of HCMV infection in neonate and immunocompromised patients [19,20]. Traditional method for detection of HCMV pp65 antigenemia is to count the numbers of peripheral blood cells labeled by Xuorescence-conjugated pp65 antibody under microscopy.…”