CMV Disease Overview
Cytomegalovirus, or CMV, is a member of the herpesvirus family. Infection is common- depending on socioeconomic conditions, prevalence of CMV antibodies in a population ranges from 40 to 100 percent - but serious illness usually occurs only in patients with suppressed immune systems. CMV is found in body fluids, including urine, saliva, breast milk, blood, tears, semen, and vaginal fluids; and once CMV is in a person's body, it stays there for life. In most healthy adults, infection becomes latent, meaning the virus remains in the body and there is potential for reactivation and recurrent illness – such as in the case of an immunosuppressed patient.
CMV is the most frequent viral illness post transplant; it is the most common cause of viral illness-related death in transplant patient. Prophylaxis (preventative treatment) against CMV disease is currently underutilized due to toxicity of current treatments.
The extent and severity of CMV disease depends on the patient population. In “normal” subjects, it is a viral cause of mononucleosis with few long term sequelae. In newborns, transmission of CMV can cause congenital/perinatal disease that can be fatal. In patients with suppressed immune systems, the ramifications of CMV disease are very significant.
In HIV/AIDS, the risk of CMV disease is directly related to severity of HIV disease (i.e., degree of immunosuppression); disease in these patients often is an ocular form of CMV, called CMV retinitis. In recipients of transplants, CMV is the main infection compromising a successful outcome to stem cell transplant (SCT), and occurs after most solid organ transplant (SOT) procedures. Infection can be “new” or due to reactivation, and severe and/or fatal organ involvement can occur.
There is an increased risk of CMV infection across all transplant types:
Possible clinical manifestations of CMV in transplant patients include: Pneumonia (lung), which is particularly severe and often fatal in SCT; hepatitis (liver), which can be mild or severe, and can be confused with rejection in liver transplant recipients; gastroenteritis (stomach, intestines), which can cause ulcers or bleeding; also can be confused with other infections in the GI tract; retinitis (eye); or meningoencephalitis (brain / spinal cord).
Risk of CMV infection (and subsequent morbidity) may be related to the serostatus of donor and recipient. For solid organ transplant patients (SOT), ‘donor-positive/recipient negative’ transplant represents the highest risk, due to the new primary infection in the recipient. For stem cell transplant patients (SCT), all CMV-positive recipients, regardless of donor status, are at highest risk, presumably due to CMV reactivation in the setting of the intense immunosuppression of SCT.
There are approximately 100,000 transplants performed worldwide each year; over 46,000 of these are performed in the US, where the overall number of transplants increases by 3 percent on average each year.
| |
Estimated USA Transplants (2006) |
Estimated USA Transplants (2005) |
Growth |
|
SCT/BMT |
17,356 |
17,100 |
1.1 |
|
SOT LIVER |
6,650 |
6,445 |
3.0 |
|
SOT KIDNEY |
17,090 |
16,477 |
4.0 |
|
SOT HEART |
2,192 |
2,127 |
3.0 |
|
SOT OTHER |
3,223 |
2,848 |
13.2 |
Other patient populations are also at high risk of CMV disease:
HIV/AIDS patients are at high risk of CMV retinitis:
There are 36.3 million adults and 2.3 million children that are HIV positive; of them, approximately 30 percent have AIDS. In the US, according to the US Centers for Control and Prevention (CDC), there are 415,000 patients in the US with AIDS, growing at 4 percent/years. Each of these patients is at risk of CMV disease if CD4 count below 50 cells/mm3, representing between approximately 85,000 patients. Up to 30,000 HIV/AIDS patients develop CMV retinitis each year.
CMV disease occurs in cancer patients:
There are approximately 3,000 patients at increased risk of CMV disease due to chemotherapeutic treatment; both incidence and prevalence during chemotherapy depend on the type of cancer and type of treatment. For example, in patients with Lymphomas, 9 to 22 percent get CMV infections, 3 percent get CMV disease. Reactivation of CMV during chemotherapy occurs, and generally ranges from 0.02 percent to 10 percent in clinical trials in Europe and U.S.
CMV disease in neonates:
In the United States, about 1 to 4 percent of uninfected mothers have primary (or first) CMV infection during a pregnancy. 33 percent of women who become infected with CMV for the first time during pregnancy pass the virus to their unborn babies. Because of this, approximately 8,000 neonates are born each year with permanent disabilities caused by symptomatic CMV disease. Congenital CMV is a common cause of serious disabilities, including mental retardation, microcephaly, seizure disorders, deafness, etc. and comes at a cost of $1.9B to the U.S. healthcare system.
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Learn more about CMV disease on the CDC website at: http://www.cdc.gov/cmv/