What is Cytomegalovirus (CMV)?

Cytomegalovirus (CMV)

Cytomegalovirus (CMV) is a double-stranded DNA virus in the Herpesvirus family that can cause disseminated or localized end-organ disease in immunocompromised individuals, and is the most common cause of viral infection in newborns. 1, 2

Epidemiology

• CMV is ubiquitous, with prevalence rates of 50-80% in the general population and up to 90% in HIV-infected pregnant women 1
• CMV is the most common perinatally transmitted infection, occurring in 0.2-2.2% of live-born infants in the United States 1
• In high-income countries, CMV affects approximately 1 in 200 of all live-born infants, while in low- and middle-income countries, the rate is higher at 1 in 71 2
• Transmission can occur through:
  • Vertical transmission (mother to child) during pregnancy, birth, or breastfeeding 1
  • Horizontal transmission through contact with virus-containing saliva, urine, or sexual fluids 1
  • Blood transfusions or organ transplantation 3

Clinical Manifestations

In Immunocompetent Individuals

• Most infections are asymptomatic or present with mild symptoms 4, 5
• Up to 7% of cases present as mononucleosis syndrome with symptoms similar to Epstein-Barr virus infection 5
• Primary infection during pregnancy carries the highest risk for fetal transmission, especially in the first trimester 2

In Immunocompromised Individuals

• CMV disease typically occurs in patients with advanced immunosuppression, particularly those with CD4+ T lymphocyte counts <50 cells/µL 1
• Common manifestations include:
  • Retinitis - the most common manifestation, presenting with decreased visual acuity, floaters, or visual field defects 1
  • Colitis - presenting with abdominal pain, diarrhea, and weight loss 1
  • Pneumonitis - presenting with respiratory symptoms 1
  • CMV syndrome - characterized by fever, malaise, leukopenia, atypical lymphocytosis, thrombocytopenia, and elevated liver enzymes 1, 6

In Congenitally Infected Newborns

• Approximately 1 in 8 babies born with CMV infection will have clinically detectable signs at birth 2
• Manifestations may include jaundice, rash, hepatosplenomegaly, microcephaly, or intrauterine growth restriction 2
• CMV is a major cause of hearing loss and brain damage in infants 2

Diagnosis

• In adults, CMV infection can be diagnosed by:
  • Serology (IgM antibodies for acute infection) 5
  • Viral culture of blood, urine, or affected tissues 1
  • Antigenemia assays 1
  • Nucleic acid-based assays (PCR) 1
• In newborns, testing should be done with urine or saliva samples within the first 21 days of life 2
• CMV disease is defined by evidence of CMV infection with attributable symptoms 1

Treatment

In Immunocompromised Patients

• For CMV retinitis or other end-organ disease:
  • Valganciclovir (oral) or ganciclovir (IV) are first-line agents 1
  • Foscarnet is used for patients who cannot tolerate ganciclovir or for second-line therapy 1
• For recurrent or resistant infections:
  • Foscarnet is the treatment of choice for ganciclovir-resistant CMV infection 7
  • When administering foscarnet, strict monitoring of renal function and electrolytes is required 7

In Congenitally Infected Newborns

• Symptomatic newborns should receive treatment with valganciclovir or ganciclovir 2
• Treatment can reduce hearing loss in 5 out of 6 babies and improve long-term neurodevelopmental outcomes 2

Prevention

In Pregnant Women

• Hygiene-based measures are recommended, especially for women in regular contact with young children:
  • Handwashing after contact with young children's saliva or urine 2
  • Avoiding sharing food, drinks, or utensils with young children 1
• Valacyclovir started after primary CMV infection in early pregnancy may reduce the risk of fetal infection 2

In Transplant Recipients

• Strategies include:
  • Use of CMV-seronegative blood products or organs when possible 3
  • Prophylaxis with valganciclovir in high-risk patients (e.g., D+/R- kidney transplants) 6
  • Extending prophylaxis from 100 to 200 days post-transplant has shown superiority in preventing CMV disease 6
  • Pre-emptive therapy guided by regular monitoring 1

Monitoring and Follow-up

• All infants with congenital CMV infection should be followed up for at least 2 years to monitor hearing and neurodevelopment 2
• In transplant recipients, monitoring should consider the time period when CMV viremia is most likely to occur 1
• For HIV patients with CMV retinitis, regular ophthalmologic follow-up is needed even after immune reconstitution 1

Common Pitfalls and Caveats

• CMV can remain latent after primary infection, with potential for reactivation during periods of immunosuppression 3
• Ganciclovir and valganciclovir can cause neutropenia and thrombocytopenia, which can be confused with manifestations of systemic CMV infection 7
• Immune reconstitution inflammatory syndrome (IRIS) can occur in HIV patients after starting antiretroviral therapy, worsening the inflammatory response to CMV 5
• There is currently no licensed vaccine for CMV prevention 2