Risk Of Cytomegalovirus Disease Research Articles

Detection of CMV DNA in peripheral blood leukocytes as a long-range harbinger of CMV disease in HIV-infected patients

The incidence of cytomegalovirus (CMV) end-organ disease can be reduced in AIDS patients by oral ganciclovir. However, the cost effectiveness of this prophylaxis is low. Targeting prophylaxis to patients with the highest risk of developing CMV disease might be useful. Several studies have shown the potential of various polymerase chain reaction (PCR) assays and of the antigenemia assay to identify the subset of patients with a definitely higher risk of developing CMV disease. We studied the CMV viral load using quantitative PCR in the leukocytes and plasma (or serum) of 28 patients in the four years before they experienced a CMV event. We observed rising CMV DNA copy numbers in the patients' leukocytes a year before the event. In contrast, plasma or serum copy numbers rose later and in fewer patients. In a control population of 21 profoundly immunodeficient patients (median CD4+ T cell count: 31/mm 3 ) without history of CMV disease, only five had detectable CMV DNA in the leukocytes, three of whom had barely above-threshold levels. We suggest that, at the present time, leukocyte CMV DNA PCR might represent a sensitive test providing an early warning signal of increased risk of CMV disease. Performing it twice a year might identify patients at risk so that closer monitoring and targeted prophylaxis can be conducted.

A prospective study of the predictive value of polymerase chain reaction assay for cytomegalovirus in asymptomatic kidney transplant recipients

Cytomegalovirus (CMV) infection carries the potential for high morbidity in transplant recipients. The institution of pre‐emptive therapy prior to the onset of clinical disease on the basis of CMV‐polymerase chain reaction (PCR) is very attractive. We prospectively studied 52 asymptomatic kidney transplant recipients to test the hypothesis that serial CMV‐PCR assays during the first 3 months post‐transplant would identify patients at risk for CMV disease. Twenty‐three patients (44.2%) had positive CMV‐PCR tests at least once; 2 (8.6%) developed CMV. None of the 29 patients continuously negative for CMV‐PCR developed CMV disease. CMV‐PCR status did not influence patient and graft survival or the incidence of acute rejection. We conclude that while a substantial number of kidney transplant recipients become positive for CMV‐PCR in the early post‐transplant period, only a minority will develop CMV disease. Negative CMV‐PCR assay is an accurate negative predictor for CMV disease but the value of CMV‐PCR as a guide for pre‐emptive anti‐CMV therapy in kidney transplant recipients appears limited.

Cytomegalovirus Viremia in Lung Transplant Recipients Receiving Ganciclovir and Immune Globulin

Cytomegalovirus (CMV) disease is an important cause of organ transplant-related morbidity and mortality. During the last 5 years at our institution, prophylactic ganciclovir and hyperimmune globulin have been routinely administered to lung transplant recipients whenever the donor or the recipient was CMV antibody-positive. We sought to assess the efficacy of prophylaxis on viremia, CMV disease, and bronchiolitis obliterans syndrome (BOS). A retrospective chart review of 61 consecutive lung transplants performed between recipients between January 1993 and August 1995 was performed. Fifty-six patients who survived at least 1 month were analyzed. Patients were considered at risk for CMV disease whenever pretransplant donor or recipient serology was positive. Fourteen of the 39 patients at risk (36%) had viremia while on prophylaxis. The rate of CMV disease was 13% during the first 6 months following transplantation. A donor whose CMV serology was positive appeared to increase the risk of BOS in a Cox regression model (relative risk=2.4; 95% confidence interval=0.86-6.74; p=0.0957). Neither age, CMV infection (viremia or a positive specimen from BAL), recipient's serology at the time of transplantation, or CMV disease was associated with BOS. None of these variables was associated with mortality on Cox regression analysis or univariate analysis. Administration of combination ganciclovir and hyperimmune globulin prophylactic therapy to lung transplant recipients at risk for CMV infection and disease is associated with a relatively low incidence of disease, which appears only after prophylaxis treatment with ganciclovir is completed. Ganciclovir prophylaxis does not prevent CMV viremia; however, viremia while on prophylaxis is not predictive of disease.

Use of a quantitative cytomegalovirus (CMV) antigenemia test in evaluating HIV+ patients with and without CMV disease.

Cytomegalovirus (CMV) infection remains a life-threatening infection in patients with HIV disease. A rapid, quantitative diagnostic technique is needed to adi in the diagnosis of CMV disease. This study was undertaken to evaluate the CMV antigenemia test in patients with HIV disease who are at risk for CMV disease. The study included 22 patients who underwent ophthalmologic exams or selected diagnostic techniques in whom CMV cultures and CMV antigenemia tests were performed. All of 11 patients with CMV disease had positive CMV antigenemia assays [range, 48-1,000 positive cells/2 x 10(5) peripheral blood leukocytes (PBL)], and 10 were also CMV viremic. There was no clinical evidence of CMV disease in 11 patients, including seven in whom the CMV antigenemia assay was negative and who remained without evidence of CMV disease after a median follow-up of 159 days. Four patients had low antigenemia levels. Of these four, two subsequently developed CMV retinitis. In conclusion, a positive CMV antigenemia result with > or = 48 positive cells/2 x 10(5) PBL correlated with concurrent CMV disease. The CMV antigenemia test appears to be a valuable tool for the rapid diagnosis of CMV disease in HIV-infected individuals.

Cytomegalovirus prophylaxis in renal transplantation

With the tremendous growth of solid organ transplantation over the past 30 years, a great deal has been learned about the significance of cytomegalovirus. Much knowledge regarding the epidemiology, pathogenesis, and diagnosis of cytomegalovirus infection has come from experience with renal transplants, which account for the largest number of solid organ transplantation procedures performed. Cytomegalovirus disease is clearly one of the most important infectious causes of morbidity and mortality in this population. The devastating effects of established cytomegalovirus disease have been ameliorated by effective antiviral treatment with ganciclovir therapy. The continued high incidence of cytomegalovirus infection, combined with the cost of treating cytomegalovirus disease, both in terms of patient well-being and financial issues, has stimulated great interest in the development of effective prophylactic and preemptive regimens. Philosophy regarding the best means of prevention varies. Prophylactic strategies provide therapy for all patients who are designated to be at risk for cytomegalovirus disease. These patients are usually stratified according to cytomegalovirus serologic status. Preemptive strategies provide preventative therapy selectively. Preemptive therapy is administered only when there is evidence for asymptomatic infection by established surveillance criteria (ie, positive cytomegalovirus cultures, positive antigenemia assays, or recent seroconversion). Unfortunately, the terms prophylaxis and preemptive are used loosely, which can lead to confusion when reviewing the literature. This overview focuses on pertinent issues regarding cytomegalovirus in renal transplantation and the various strategies for prophylaxis and preemptive therapy. The approach to cytomegalovirus prophylaxis among renal transplant centers varies widely. Often a specific approach within a given center is inconsistent, poorly documented, and based on anecdotal experience. Although the literature is replete with studies using single-agent or combination therapy, they are usually single-center studies of a relatively small number of patients. Large randomized prospective studies are unfortunately few in number. Hopefully, after reviewing the available data, it will be possible to propose an ideal strategy that is both cost-effective and maximally therapeutic.

Nonpulmonary manifestations of cytomegalovirus infection in immunocompromised patients.

Nonpulmonary manifestations of cytomegalovirus (CMV) infection in immunocompromised patients include chorioretinitis, gastrointestinal infection, and central nervous system disease. Diagnosis of end organ disease, especially in the gastrointestinal tract, is best substantiated by histologic evidence of CMV inclusions. Positive cultures of CMV provide evidence for supporting infection but do not define actual end organ disease. Satisfactory treatment of the disease can be accomplished with ganciclovir or foscarnet, although these agents only suppress virus replication. In many instances, severe CMV-induced end organ disease in immunocompromised patients will progress despite treatment. In some instances, resistance to the antiviral agent is the basis for drug failure. Patients at high risk for CMV disease can be identified, and studies of prophylaxis are in progress.

Cytomegalovirus infection.

Cytomegalovirus infection was for many years one of the major complications of allogeneic bone marrow transplantation. During the past few years there have been major advances in the management of patients at risk for cytomegalovirus disease, and there are now several strategies that can be used. Antiviral prophylaxis has improved considerably and there are now three antiviral agents that can be used. Immunoprophylaxis by infusion of specific cytotoxic T cells is now feasible. The development of techniques for rapid diagnosis of cytomegalovirus infection including the antigenemia assay and the polymerase chain reaction for detection of cytomegalovirus DNA have made the use of preemptive therapy an attractive strategy. The outcome of therapy of cytomegalovirus pneumonia is still poor, with a survival of only approximately 50%, despite use of the combination of ganciclovir and high-dose immunoglobulin.