Cytomegalovirus (CMV) Infection 

1️⃣ Introduction

Cytomegalovirus (CMV) is a double-stranded DNA virus belonging to the Herpesviridae family (Human herpesvirus-5). It is characterized by:

  • Major opportunistic pathogen in ICU, transplant, HIV, and neonatal settings

2️⃣  Virological Features

  • Causes cytomegaly (enlarged cells)
  • Produces “owl’s eye” intranuclear inclusion bodies
  • Establishes lifelong latency
  • Reactivates during immunosuppression

3️⃣ Epidemiology

  • Worldwide prevalence: 60–95% adults seropositive
  • Transmission common in:
    • Developing countries
    • Lower socioeconomic settings
    • Healthcare and transplant populations

High-Risk Groups

  • Immunocompromised patients
  • Solid organ transplant recipients
  • Hematopoietic stem cell transplant
  • HIV/AIDS
  • Neonates (congenital infection)
  • ICU patients (reactivation)

4️⃣ Modes of Transmission

Horizontal Transmission

  • Saliva
  • Sexual contact
  • Blood transfusion
  • Organ transplantation
  • Breast milk

Vertical Transmission

  • Transplacental (congenital CMV)
  • Perinatal exposure
  • Breastfeeding

5️⃣ Pathogenesis

Stepwise Pathogenesis

  1. Primary mucosal infection
  2. Viremia
  3. Dissemination to organs
  4. Latency establishment
  5. Reactivation with immune suppression

Target Organs

  • Retina
  • Gastrointestinal tract
  • Lungs
  • Liver
  • CNS
  • Bone marrow

6️⃣ Clinical Manifestations

A. CMV in Immunocompetent Individuals

Usually asymptomatic or mild illness resembling Infectious mononucleosis

Features

  • Fever
  • Malaise
  • Lymphocytosis
  • Hepatitis
  • Mild splenomegaly

Differentiating from EBV

Feature

CMV

EBV

Pharyngitis

Rare

Common

Lymphadenopathy

Mild

Prominent

Heterophile antibody

Negative

Positive

B. CMV in Immunocompromised Patients

Severe, invasive disease common.

1. CMV Retinitis (Most Common AIDS Manifestation)

Features

  • Painless progressive vision loss
  • Floaters
  • Visual field defects
  • “Pizza pie” / “Cottage cheese and ketchup” retina appearance

Risk

Usually occurs when:

  • CD4 count < 50 cells/mm³

2. CMV Pneumonitis

Common in:

  • Bone marrow transplant
  • ICU immunosuppressed patients

Features

  • Dyspnea
  • Hypoxemia
  • Diffuse interstitial infiltrates
  • High mortality

3. CMV Colitis

Symptoms

  • Bloody diarrhea
  • Abdominal pain
  • Fever
  • Bowel perforation (severe)

4. CMV Esophagitis

Features

  • Odynophagia
  • Dysphagia
  • Large linear ulcers

5. CMV Hepatitis

  • Mild transaminitis
  • Severe disease in transplant recipients

6. CMV Encephalitis / Myelitis

  • Confusion
  • Seizures
  • Radiculopathy
  • Polyradiculomyelitis in AIDS

7. Bone Marrow Suppression

  • Leukopenia
  • Thrombocytopenia

C. Congenital CMV Infection

Most common congenital viral infection worldwide.

Classic Triad

  • Sensorineural hearing loss
  • Periventricular calcification
  • Developmental delay

Additional Features

  • Microcephaly
  • Chorioretinitis
  • Hepatosplenomegaly
  • Thrombocytopenia
  • “Blueberry muffin rash”

7️⃣ Histopathology

Characteristic Finding

✅ Enlarged cells with:

  • Basophilic intranuclear inclusion
  • Perinuclear halo
  • “Owl’s eye appearance”

8️⃣ Diagnosis

A. Laboratory Tests

1. PCR (Gold Standard)

  • Detects CMV DNA
  • Quantitative viral load monitoring
  • Used in transplant patients

2. CMV Antigenemia Assay

  • pp65 antigen detection
  • Useful in early infection

3. Serology

Antibody

Significance

IgM

Acute infection

IgG

Past exposure

(Not reliable in immunocompromised)

4. Tissue Diagnosis

  • Biopsy showing inclusion bodies
  • Immunohistochemistry

5. Culture

  • Rarely used (slow)

B. Organ-Specific Diagnosis

Organ

Test

Retinitis

Fundoscopy

Pneumonitis

BAL PCR

Colitis

Colon biopsy

CNS

CSF PCR

Congenital

Urine/saliva PCR

9️⃣ Treatment

Indications for Treatment

  • Symptomatic CMV disease
  • High viral load in transplant
  • Congenital symptomatic infection
  • End-organ disease

First-Line Antiviral Drugs

1. Ganciclovir

2. Valganciclovir

  • Oral prodrug of ganciclovir
  • Used for maintenance and mild disease

3. Foscarnet

Indications:

  • Ganciclovir resistance
  • Severe neutropenia

4. Cidofovir

  • Reserved for resistant CMV
  • Nephrotoxic → Give with probenecid

Drug Toxicities 

Drug

Major Toxicity

Ganciclovir

Bone marrow suppression

Foscarnet

Nephrotoxicity, electrolyte imbalance

Cidofovir

Severe nephrotoxicity

🔟 CMV in Transplant Medicine

Types of Disease

  1. Primary infection
  2. Reactivation
  3. Superinfection

Prevention Strategies

1. Universal Prophylaxis

  • Valganciclovir post transplant

2. Pre-emptive Therapy

  • Treat when viral load rises

CMV in ICU 

Reactivation occurs in:

  • Sepsis
  • ARDS
  • Prolonged ventilation
  • Steroid therapy

Clinical Impact

  • Increased ventilator days
  • Increased mortality
  • Secondary bacterial infection risk

 CMV in HIV

Occurs when:

  • CD4 < 50 cells/mm³

Common Manifestations

  • Retinitis
  • Colitis
  • Esophagitis
  • Encephalitis

 Prognosis

Depends on:

  • Immune status
  • Organ involvement
  • Timing of therapy
  • Viral load

Worst outcomes:

  • Pneumonitis
  • CNS disease
  • Congenital CMV

 Prevention

General Measures

  • Safe transfusion screening
  • Hand hygiene
  • Transplant donor-recipient matching

Vaccination

🚫 No approved CMV vaccine yet (under research)