Cytomegalovirus

CMV is a DNA herpesvirus that is:

Epidemiology and Risk Factors

Prevalence rises with age, and reaches 30-70% of the total population. Transmission via:

  • Saliva
  • Sexual contact
  • Breastfeeding
  • Placental transfer
    40% risk of congenital infection in a seronegative mother, leading to severe neurological disease of the child.
  • Tissue transfer
    • Transfusion
    • Solid organ transplant
    • Bone marrow transplant

Risk factors:

  • Seronegative organ recipient
  • Seropositive organ donor
  • Solid organ transplant

Pathophysiology

  • Largest known β human herpesvirus
  • Double-stranded DNA
  • Lifelong persistent (generally latent) presence following infection
    • Persists in bone marrow

Aetiology

Clinical Manifestations

Primary infection of the immunocompetent adult:

  • Rarely serious
  • May present similarly to EBV
    • Persistent fever
    • Myalgia
    • Cervical adenopathy
    • Deranged LFTs
  • Rarer presentations include:
    • Myocarditis
    • Meningitis
    • GBS
    • Colitis

Infection or reactivation in the immunocompromised adult varies with the setting:

  • Solid organ transplants:
    • Disease generally localised to transplanted organ
    • Organ-specific manifestations
      • Kidney transplant
        Renal artery stenosis.
      • Heart transplant
        Coronary artery disease.
      • Lung transplant
        Bronchiolitis obliterans.
      • Liver transplant
        Vanishing bile duct syndrome.
  • Stem cell transplants:
    • Pneumonitis
    • Graft versus host disease
      Positive association.
  • HIV
    • Retinitis

Diagnostic Approach and DDx

CMV is commonly detected and so may be an innocent bystander in another disease process. CMV-associated disease should be diagnosed on a combination of:

  • Clinical findings
    CMV syndrome; 2 or more of:
    • 48 hours of fever ≥38°C
    • Fatigue
    • Leukopenia or neutropenia
    • >5% atypical lymphocytes
    • Thrombocytopenia
    • ↑ Transaminases
  • Evidence of viral detection

Investigations

Laboratory:

  • Antibodies
    Inaccurate if recent plasma administration.
  • Qualitative DNA PCR
    Dies not distinguish between active and latent infection.
  • Antigenaemia essay
    Reliable indirect measure of CMV infection.
  • Viral cultures
    May take up to 21 days to demonstrate positivity.

Imaging:

Other:

Management

Specific therapy:

Curiously, aciclovir and valaciclovir both ↓ mortality of CMV despite both inhibiting thymidine kinase, which is not expressed in CMV. Irrespectively, they have fallen out of favour as they are less effective than ganciclovir.

  • Pharmacological
    • Antivirals
      • 1st line:
        • Ganciclovir
        • Valganciclovir
      • 2nd line:
        • Foscarnet
        • Cidofovir
    • Immunoglobulin
      • CMV-specific
      • Non-specific
  • Physical

Supportive care:

Disposition:

Preventative:

  • Prophylactic therapy in organ recipients prior to symptomatic disease
    • Ganciclovir

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

Immunocompetent:

  • I
    • Superinfection

Transplant:

  • I
    • Chronic rejection

Prognosis

Key Studies

References

  1. Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. The Lancet Infectious Diseases. 2004 Dec;4(12):725–38.