Definition cmv virus

Antiviral drugs might have some effect against these viruses, making interpretation of causality difficult.

In solid-organ transplant recipients, CMV syndrome is better defined. It is important that cases of CMV syndrome be differentiated from cases of end-organ disease when studies are reported. CMV-associated graft failure. Several publications have suggested that CMV can induce graft failure after stem cell transplantation. It is difficult to define CMV-associated graft failure, because several other possible causes of graft failure exist, including graft rejection, relapse of hematologic disease, drug toxicity, and infection with other viruses e.

Several new diagnostic techniques are in development, the most important of which are techniques for assessment of virus load. These techniques could be used to define end-organ disease as well, but they cannot be introduced into a document on definitions until carefully performed prospective clinical trials have been performed to compare the results of virus load measurements in patients with CMV disease according to current definitions with those in patients without CMV disease.

CMV infection should have been documented earlier than the indirect effect assumed to be associated with CMV.

The evidence for association of CMV with these conditions is based on epidemiologic findings that show an increased risk for indirect effects caused by CMV among patients already infected with CMV. Other evidence is based on findings of reduced incidence of indirect effects during trials of antiviral therapy. This evidence will be reviewed briefly, together with postulated mechanisms.

Evidence from several cohort studies shows that CMV infection is associated with an increased risk of acute graft rejection. This has been shown for recipients of heart [ 4 , 5 ], lung [ 6 ], kidney [ 7—9 ], and liver [ 8 ] transplants. The Kaplan-Meier curves presented in the study by Lowance et al. After heart transplantation, CMV infection was associated with greater incidence and greater severity of coronary atherosclerosis and a higher rate of graft loss in CMV-seropositive heart transplant recipients [ 4 ].

In a rat model, CMV infection accelerated cardiac allograft atherosclerosis [ 11 ]. This effect could be prevented by administration of prophylactic ganciclovir [ 12 ].

A post hoc analysis of a trial, which showed that prophylactic administration of ganciclovir after heart transplantation inhibited CMV disease, reported that this drug also reduced the incidence of atherosclerosis [ 13 ].

Because the risk of developing posttransplantation atherosclerosis is decreased by the use of calcium-channel blockers, patients were stratified according to their use of such drugs. In a comparison of the ganciclovir and placebo groups, a significant difference was seen in the incidence of atherosclerosis among patients who were not taking calcium-channel blockers, but no difference was apparent among patients who were taking calcium-channel blockers.

CMV infects and alters vascular smooth muscle cell growth through inhibition of the tumor suppressor p53 [ 14 ]. Loss of p53 activity may facilitate smooth muscle proliferation and, thus, increased intimal thickness. CMV gene US 28 is a chemokine receptor that causes chemotaxis toward a site of inflammation when it is transfected into smooth muscle cells [ 15 ]. CMV may exert a procoagulant effect by expressing glycoproteins at the surface of infected endothelial cells, thereby increasing the adherence of polymorphonuclear leukocytes [ 4 , 16 ].

CMV seropositivity is a risk factor for invasive fungal infection in recipients of bone marrow transplants [ 17 ] and liver transplants [ 18 ].

For heart transplant recipients, administration of prophylactic ganciclovir can reduce the incidence of fungal infection [ 19 ]. Secondary infections might develop through different mechanisms; for example, CMV could disrupt mucosal surfaces, predisposing the patient to superinfection, or it could cause alterations in humoral and cell-mediated immunity. The data presented in all studies cited in the Indirect Effects section strongly imply that the indirect effects of CMV in transplant recipients are real and important, and they also suggest that future trials of antiviral drugs should be designed to include large-enough study populations and well-defined end points so that these effects can be properly assessed.

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Volume Article Contents Abstract. Direct Effects. Indirect Effects. Per Ljungman , Per Ljungman. Reprints or correspondence: Dr. Per Ljungman, Dept. Ljungman medhs. Oxford Academic. Self-care, such as getting plenty of rest, should be enough for your body to control the infection. If you know you were infected with CMV during your pregnancy, tell your baby's doctor. The doctor will likely assess your baby for hearing or vision problems.

CMV is related to the viruses that cause chickenpox, herpes simplex and mononucleosis. CMV may cycle through periods when it lies dormant and then reactivates. If you're healthy, CMV mainly stays dormant. When the virus is active in your body, you can pass the virus to other people.

The virus is spread through body fluids — including blood, urine, saliva, breast milk, tears, semen and vaginal fluids. Casual contact doesn't transmit CMV. CMV is a widespread and common virus that can infect almost anyone. Complications of CMV infection vary, depending on your overall health and when you were infected. Rarely, CMV causes a healthy adult to develop mononucleosis. Other rare complications for healthy adults include problems with the digestive system, liver, brain and nervous system.

An infant whose mother first became infected with CMV during pregnancy is more likely to experience complications. Complications for the baby can include:.

Careful hygiene is the best prevention against CMV. You can take these precautions:. If you have weakened immunity, you may benefit from taking antiviral medication to prevent CMV disease. Experimental vaccines are being tested for women of childbearing age. These vaccines may be useful in preventing CMV infection in mothers and infants, and reducing the chance that babies born to women who are infected while pregnant will develop disabilities.

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Probable disease is not a recommended category for CMV hepatitis. Due to the risk for other confounders such as acute and chronic allograft rejection in liver transplant recipients or GVHD in HSCT recipients, as well as the common occurrence of drug-associated liver dysfunction, a probable CMV hepatitis category is not defined.

Proven disease requires typical ophthalmological signs judged by an ophthalmologist experienced with the diagnosis of CMV retinitis. If the presentation is atypical or an experienced ophthalmologist is not available, it is recommended that the diagnosis be supported by CMV documented in vitreous fluid by NAT such as PCR. A probable disease category should not be used. Proven disease is defined by the detection of CMV by virus isolation, rapid culture, immunohistochemical analysis, or in situ hybridization in a kidney allograft biopsy specimen obtained from a patient with renal dysfunction together with the identification of histologic features of CMV infection.

Proven disease is defined by the detection of CMV by virus isolation, rapid culture, immunohistochemical analysis, or in situ hybridization in a bladder biopsy specimen obtained from a patient with cystitis together with the identification of conventional histologic features of CMV infection.

Proven disease is defined by the detection of CMV by virus isolation, rapid culture, immunohistochemical analysis, or in situ hybridization in a heart biopsy specimen obtained from a patient with myocarditis together with the identification of conventional histologic features of CMV infection.

Proven disease is defined as the detection of CMV by virus isolation, rapid culture, immunohistochemical analysis, or in situ hybridization in a pancreatic biopsy specimen obtained from a patient with pancreatitis together with the identification of conventional histologic features of CMV infection. CMV can also cause disease in other organs, and the definitions of these additional disease categories include the presence of compatible symptoms and signs and documentation of CMV by biopsy by virus isolation, rapid culture, immunhistochemistry, or DNA hybridization in biopsy material.

New or increased malaise toxicity grade 2 or new or increased fatigue toxicity grade 3 National Cancer Institute: Common Terminology Criteria for Adverse Events, version 4.

Elevation of hepatic aminotransferases alanine aminotransferase or aspartate aminotransferase to 2 times the upper limit of normal applicable to non—liver transplant recipients.

To achieve meaningful comparison of clinical outcomes, it is important that clinical studies of new agents use common standardized definitions regarding trial endpoints. Updating the previous definitions of CMV infection and disease is warranted, as transplant practices and diagnostic techniques have advanced and continue to evolve. It is likely that future studies will include both proven and probable CMV disease definitions in their design, but the classification will allow the possibility to find differences in outcome between patients having developed these different disease categories.

At this time, however, we do not recommend to include these in clinical trial design until more data are available. The gold standard of CMV end-organ disease for documenting the effects of new agents is difficult to incorporate in current clinical trial designs as it has become increasingly rare [ 12 , 13 ]. Use of surrogate outcomes, such as viremia, DNAemia, and antigenemia has been suggested by others.

However, there is variability between different assays used for detection of CMV. Most current assays detect nucleic acids in a quantitative manner. A major advance during the last decade has been the introduction of an international standard for CMV DNA quantitation allowing comparison of results from different techniques [ 6 ], although a recent report indicates that, although the standard is an improvement, variability between assays remains high [ 14 , 15 ].

It is therefore strongly encouraged to use assays that have been calibrated to a standard in the clinical trial setting and preferably to use a central laboratory. Another need for future research is to define thresholds for quantitation of CMV from tissue material, and this is an area of active investigation.

Additional developments are in the field of detecting specific immune responses to CMV, but these techniques are not ready at this time for widespread use and incorporation in clinical trial design.

However, the different clinical symptoms and signs included in the definition are very common in immunocompromised patients. CMV syndrome is not a precisely defined entity; therefore, future research should focus on a scoring system that ultimately establishes a threshold score for this entity. Consisting of data provided by the author to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the author, so questions or comments should be addressed to the author.

The views expressed in this article are those of the authors and do not necessarily reflect the official position of the Swedish Medical Products Agency or the US Food and Drug Administration. Financial support.

Potential conflicts of interest. All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Ljungman P , Griffiths P. Definitions of cytomegalovirus infection and disease. In: Multidisciplinary approach to understanding cytomegalovirus disease. Google Scholar. Google Preview. Ljungman P. Cytomegalovirus infections in transplant patients. Scand J Infect Dis ; Supplementum : 59 — Definitions of cytomegalovirus infection and disease in transplant recipients.

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