– National Institutes of Health (NIH), 2002
– National Institutes of Health (NIH), 2002
CYTOMEGALOVIRUS: Human cytomegalovirus (CMV) is a common virus related to the viruses that cause chickenpox, herpes simplex, and mononucleosis (mono). It is transmitted via bodily fluids and nearly half of all Americans are infected by the age of 6. In people over age 80, prevalence reaches 90%. The virus typically causes no symptoms and remains latent in the body following infection, but may “reactivate” many years later, leading to serious health issues.
DISEASE: While CMV is usually harmless, it can be serious or even fatal in certain populations. In particular, CMV is a threat to people with weakened immune systems, such as transplant recipients who take immunosuppressive drugs, AIDS patients, people in intensive care units, and individuals with severe intestinal bowel disease (IBD). CMV reactivation is common following either a solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT, sometimes called a bone marrow transplant). Prevalence varies by type of transplant, but in lung transplants, 50-75% of patients develop CMV infection, while in allogenic HSCT, 30% of patients may be affected. Recipients are at highest risk if the transplant donor (D) is CMV positive and the transplant recipient (R) is CMV negative (D+/R-). CMV infection typically occurs 30 to 90 days after transplantation and symptoms include digestive inflammation, pneumonia, brain inflammation, and vision loss. With disease progression, organ failure and death can occur. If patients develop pneumonia or systemic disease, mortality can approach 90%.
CHILDREN: Infants may get the disease from their mothers, a condition known as congenital CMV. About 1 in 200 infants are born with CMV, making it the most common congenital infection. Approximately 10% of infected infants are symptomatic at birth, reflected in low birth weight, jaundice, skin rashes, enlarged spleen, or other abnormalities. Symptomatic babies are at risk of permanent disability, including hearing loss, vision loss, learning disability, and impaired motor functions. Notably, congenital CMV is the leading infectious cause of deafness, learning disabilities, and mental retardation in children. Sadly, there currently are no FDA-approved drugs to treat or prevent congenital CMV.
TREATMENT: There are two main approaches to treating CMV in transplant patients; prophylactic and preemptive. Prophylactic treatment typically involves use of an antiviral, most often ganciclovir, given prior to transplantation to prevent CMV from replicating in the recipient’s body. While prophylaxis is often recommended in high-risk patients, it also involves side effects and the risk of developing resistance. The alternate approach, preemptive treatment, involves administering ganciclovir after the first detection of viral replication, to prevent a symptomatic infection from developing. Preemptive treatment can avoid the worst symptoms of CMV, but cannot fully prevent the indirect effects of viral replication and it requires regular lab tests that may not be feasible for some patients or institutions. Other options include valganciclovir or letermovir, and less frequently, foscarnet or cidofovir, which are usually reserved for severe or resistant cases due to their significant side effects. In general, there are concerns regarding toxicity and resistance for all FDA-approved drugs which target CMV.
AWARENESS: Despite its frequency, CMV reactivation and in particular, congenital CMV, suffer from poor public awareness.
Sources:
National CMV Foundation
https://www.mayoclinic.org/diseases-conditions/cmv/symptoms-causes/syc-20355358
https://www.ncbi.nlm.nih.gov/pubmed/17029132
https://www.ncbi.nlm.nih.gov/pubmed/11843023
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496754/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4883584/