Physicians focused in transplant medicine must contend with the repercussions of the suppressed immune systems of patients undergoing stem cell (bone marrow) or solid organ transplant, including organ failure and rejection, a variety of opportunistic infections, and other transplant complications. In the U.S. alone, there are approximately 46,000 transplants on an annual basis. One of the most significant pathogens contributing to morbidity and mortality in patients undergoing stem cell or solid organ transplant is cytomegalovirus.
Our clinical focus is in developing drugs to prevent and treat cytomegalovirus infections.
Cytomegalovirus
Cytomegalovirus (CMV) is a member of the herpes virus group, which includes the viruses that causes chicken pox, mononucleosis, herpes labialis (cold sores), and herpes genitalis (genital herpes). CMV can cause serious complications in persons with weakened immune systems. Like other herpesviruses, CMV has the ability to remain dormant in the body for long periods of time. Human CMV infection rates average between 50 percent and 85 percent of adults in the U.S. by 40 years of age. In most individuals with intact immune systems, CMV infection causes little to no apparent illness, or mild symptoms such as enlarged lymph nodes, low fever, and fatigue that may or may not be noticed. However, in immunocompromised individuals, CMV can lead to serious disease or death.
After an initial infection, CMV usually remains dormant in the body, but it can reactivate and cause serious symptoms in immunologically suppressed patients, such as those undergoing transplant, patients with HIV/AIDS, or in infants whose immune systems are not yet fully developed.
Risk of Significant CMV Disease to Transplant patients
Patients who are immunosuppressed following hematopoietic stem cell (SCT) or solid organ transplantation (SOT) remain at high risk of CMV infection. In these patients, direct clinical manifestations of CMV disease typically occur within the first ~100 days post-transplant. The most common manifestations of CMV disease in transplant recipients are pneumonia and gastrointestinal disease, although manifestations in a variety of other organ systems can occur. The outcome following established CMV disease in certain settings remains poor:
- CMV disease tends to be more severe in the setting of allogeneic SCT (stem cell from a donor) in which patients receive relatively more potent immunosuppressive therapy than following SOT
- CMV pneumonia among SCT recipients is associated with mortality rates of 50%, despite the availability of currently available anti-CMV drugs
- Indirect effects associated with CMV can include graft rejection and accelerated atherosclerosis (in SOT recipients), as well as secondary bacterial or fungal infections
Before the availability of potent anti-HIV therapy, CMV-associated retinitis was commonly seen in patients with HIV/AIDS. In addition, infants can become infected with CMV before or immediately following birth when the mother becomes infected during pregnancy. In a newborn, CMV can be life threatening, and it can lead to complications such as blindness, hearing problems, mental retardation, and learning disabilities.
Transmission
Cytomegalovirus is present in body fluids (saliva, semen, cervical secretions, and urine) and can be spread from person to person, including transmission from mother to fetus.
Currently available therapies
Currently available systemic anti-CMV therapies are effective against the virus, but their use is limited by their respective toxicities. These toxicities may be of particular concern in transplant patients, particularly in patients whom the bone marrow has been ablated or significantly suppressed, who receive ongoing immunosuppression to prevent organ rejection or graft-versus-host-disease (GvHD), and who may require the use of therapies that are potentially toxic to the kidneys or other organs.
Please see your doctor for additional information on the virus and treatment options.
For additional information on cytomegalovirus, please visit:
The Centers for Disease Control and Prevention: http://www.cdc.gov/cmv/
The National Congenital CMV Disease Registry:
http://www.bcm.edu/pedi/infect/cmv/