CMV-1
Cytomegalovirus - (CMV) - CMV disease is an opportunistic infection caused by the cytomegalovirus, which can complicate and interfere with transplants recipients' full recovery. Although the virus is present in about half of the worldwide population, in patients with a suppressed immune system, such as transplant recipients, the virus is able to reactivate. In transplant patients, the most common clinical manifestations of CMV disease are CMV pneumonia, CMV hepatitis, and CMV gastointestinal disease, and frequently involves the transplanted organ.
Valcyte - (valganciclovir) is comparable to Cytovene -(ganciclovir) Capsules in reducing the incidence of cytomegalovirus(CMV) disease in solid organ transplant recipients, after a 12 month study. The study showed that the incidence of CMV disease during the first 12 months post transplant was 17.2% in patients treated with Valcyte compared to 18.4% in Cytovene- treated patients.
Many lung transplant programs employ lengthy regimens of IV ganciclovir therapy to prevent disease due to CMV. A new regimen was introduced of delayed ganciclovir prophylaxis for CMV infection. This consisted of 2 weeks of IV ganciclovir therapy, initiated 3 to 4 weeks after transplant, with subsequent viral monitoring and preemptimve theapy as needed. When not receiving ganciclovir, patients received oral acyclovir, 800mg tid, for 6 months. In the study no, no seropositive patient receiving the delayed regimen developed CMV. (Source: Chest, Feb 2002)
Cytovene ( ganciclovir capsules) - has been demonstrated to significantly reduce the chances of developing CMV disease in solid organ transplant recipients. Studies have shown that using Cytovene capsules for the first 14 weeks after transplnat reduced the risk of CMV. (Source: Roche Laboratories)
Resource : The World of Human Cytomegalovirus
http://ueber25.clanintern.de/php/html/index.php
Current Opinion in Organ Transplantation 2003; 8(4):269-275
Cytomegalovirus and solid organ transplantation: an update
Cytomegalovirus is a major viral pathogen complicating organ transplantation. Recent advantages have been achieved through the development of new diagnostic technologies and use of antivirals. Cytomegalovirus-associated indirect effects, such as risk of rejection, transplant vasculopathy, and other infections, have been Investigated.Recent findings Quantitative molecular methods to monitor viral load, especially the new real-time polymerase chain reaction techniques, are commonly used to guide treatment of cytomegalovirus infections and preemptive therapy. Intravenous ganciclovir is the drug of choice for treatment of symptomatic infections, and its oral form is successfully used in prophylactic and preemptive regimens. High-dose acyclovir or its derivative valacyclovir is useful for prophylaxis of cytomegalovirus disease, and valganciclovir, a derivative of ganciclovir, is under clinical investigation. The criteria for cytomegalovirus infection and disease have been updated. Besides enhanced transplant vasculopathy, the indirect effects of cytomegalovirus-association with acute or chronic rejection-are suggestive but not conclusive. Involvement of cytomegalovirus in coronary artery remodeling is associated with the impaired ability of the vessel wall to enlarge in response to intimal increase. Alloresponse is involved in the pathogenesis of cytomegalovirus-enhanced chronic changes; chemokines play a major role in this process, as shown in animal models. Posttransplant recurrence of hepatitis C virus and concurrent activation of human herpesvirus-6 and human herpesvirus-7 are new associations of cytomegalovirus. Summary Although new diagnostic techniques and prophylactic and preemptive therapies have made it easier to control the virus, cytomegalovirus infection remains a significant problem in transplantation. Further clinical investigation is needed to understand the indirect effects of cytomegalovirus.
Prevention and Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients: The Clinical and Economic Impact of Evolving Strategies
Mark D. Pescovitz Am J Health-Syst Pharm 2003 American Society of Health-System Pharmacists -Cytomegalovirus (CMV) is a ubiquitous herpesvirus that persists indefinitely after primary infection, usually in a latent form in various tissues (e.g., kidney, liver, lung). One percent of newborns are infected with CMV. Transmission of the virus (e.g., in milk or saliva) is common in the perinatal period and early childhood. Transmission also can occur sexually and through blood transfusion and organ transplantation from an infected donor. Approximately 40-90% of adults have antibodies to CMV (i.e., they have been infected with the virus). Primary infection often is asymptomatic in healthy persons, but CMV can cause serious illness in patients who are immunocompromised (e.g., patients with human immunodeficiency virus (HIV) infection or the acquired mmunodeficiency syndrome). CMV is the most common opportunistic infection after solid organ transplantation. The incidence of clinically apparent infection ranges from 20-60%. The mortality rate from CMV infection is as high as 90% if it is left untreated. CMV disease usually manifests 1-4 months after transplantation or after completion of antiviral prophylactic drug therapy, although some patients are asymptomatic.[2] Primary (direct) effects include a CMV syndrome characterized by a prolonged high fever, fatigue, malaise, anorexia, arthralgias or myalgias, leukopenia, thrombocytopenia, and atypical lymphocytosis. CMV disease (i.e., CMV syndrome with CMV viremia) may present as infection with signs and symptoms of fever, malaise, leukopenia, or documented CMV
invasive disease into organs. CMV disease is classified as being both a tissue invasive problem and a syndrome. CMV infection is the presence of virus as determined by DNA techniques or culture or antigen tests. Tissue-invasive disease often affects the allograft (e.g., mild hepatitis and mild respiratory involvement to severe pneumonitis are common in patients with liver and lung transplants, respectively), although various other organs (e.g., the kidneys, intestines, retinas) may be affected. CMV disease can result in gastroenteritis, which may lead to ulcers and bleeding or perforation of the esophagus, stomach, small intestine, or colon. CMV nephritis may resemble graft rejection. In transplant recipients, retinitis is uncommon. CMV syndrome is often mildly asymptomatic or accompanied by a mononucleosis-like syndrome characterized by fever and neutropenia. Central nervous system involvement (e.g., encephalitis) is uncommon and usually is associated with progressive disease.CMV infection also can cause secondary (indirect) effects because it suppresses the immune system, which increases the risk of opportunistic infections. Invasive bacterial and fungal superinfection (e.g., Pneumocystis carinii) and septicemia may result. CMV infection may lead to acute and chronic allograft injury and rejection. The virus appears to play a role in arteriosclerosis and rejection after heart transplantation. Cardiac complications (e.g., arrhythmias) also can occur in patients with CMV infection and other types of solid organ transplants. CMV has mutagenic effects, and concerns have been raised about a possible role for the virus in oncogenesis.The first article describes the impact of CMV prophylactic treatment using oral ganciclovir, an antiviral agent, on the incidence of CMV disease, allograft survival, and costs in solid organ transplant recipients. Factors that influence these outcomes are discussed. The second article addresses the cost savings and other advantages of the oral route of administration for ganciclovir compared with the intravenous route. Data were obtained from patients with HIV infection who were treated for CMV retinitis and a model of hypothetical patients receiving liver transplants and CMV prophylactic drug therapy. The third article explains the limitations of oral ganciclovir for prophylaxis of CMV disease in solid organ transplant recipients and compares the pharmacology, pharmacokinetics, efficacy, and safety of ganciclovir and valganciclovir, an oral prodrug of ganciclovir, in this patient population. The fourth article lists the criteria for evaluating CMV prophylactic drugs for inclusion in a formulary and compares the advantages and disadvantages of various drugs, including ganciclovir and valganciclovir, using these criteria. Mark D. Pescovitz, M.D., is Professor of Surgery, Microbiology, and Immunology and Director of the Organ Transplant Program, Indiana University Medical Center, Indianapolis, IN.
Cytomegaloviral infection and other infections related to lung allograft survival -(Added 10/4/04) - The use of better refined immunosuppression strategies and antimicrobial prophylaxis protocols in at-risk lung transplant recipients (LTR) has significantly reduced the burden of acute infection syndromes in the lung allograft. Human cytomegalovirus (HCMV) as an example of how improved diagnostic tools and therapeutic strategies can help us better understand and manage this problem.Recent findings: Although early ganciclovir prophylaxis has dramatically reduced the occurrence of HCMV pneumonitis as a major infectious cause of early morbidity and mortality in LTR, subclinical HCMV reactivation is often detected in either the blood or bronchoalveolar lavage, and this has been associated with reduced long-term lung allograft survival. Increasingly, ongoing research has identified HCMV reactivation as both a marker of ongoing alloreactivity/inflammation and a significant contributor to these processes as evidenced by epidemiological association data and specific information from therapeutic intervention studies, respectively.The conceptual model of infection in the lung allograft that has evolved from these considerations now also gives us an excellent framework with which to better understand the interaction between the lung allograft and other relevant viral, bacterial, and fungal pathogens that may be both a marker of and a contributor to significant reductions in graft survival after lung transplantation.(Source:Current Opinion in Organ Transplantation September 2004)
