Varicella Zoster Virus (VZV): Biology, Pathogenesis, Clinical Features, and Prevention

Varicella Zoster Virus (VZV)

Basic Biology

The Varicella Zoster Virus (VZV) is a member of the Herpesviridae family and is known as Human herpesvirus 3 (HHV-3). It is a large, linear, double-stranded DNA virus with an envelope. Humans are the only natural host for VZV.

• Family: Herpesviridae

• Genome: Linear dsDNA

• Envelope: Present

• Host: Humans only

Transmission

VZV is highly contagious and spreads primarily through respiratory secretions and direct contact with fluid from skin lesions.

• Respiratory route: Inhalation of droplets from mucus and saliva

• Direct contact: Exposure to fluid from vesicular lesions

Groups at Increased Risk

Severe Primary Varicella (Chickenpox)

Certain populations are at higher risk for severe disease:

• Infants under 1 year old

• Pregnant women (especially early pregnancy; risk of congenital varicella syndrome)

• Adults (more severe than in children)

• Immunocompromised individuals (e.g., cancer, HIV, organ transplantation)

Risk Factors for Reactivation (Herpes Zoster/Shingles)

• Older age (especially over 50)

• Immunosuppression (HIV, malignancy, immunosuppressive drugs)

• Stress, illness, physical trauma

• Chronic medical conditions (diabetes, renal disease, lung disease)

Epidemiology

Chickenpox

Chickenpox is highly contagious and most common in children aged 5–10 years. Vaccination has significantly reduced incidence in the U.S.

• Incidence: Most common in children

• Vaccine impact: Decreased cases post-vaccine introduction

Shingles

• Occurs in about 5/1000 population

• Immunosuppression increases risk

Clinical Presentation

Primary Infection: Chickenpox (Varicella)

Chickenpox typically presents after an incubation period of 10–21 days. Adults may experience a prodrome of fever, malaise, and headache. The hallmark is a vesicular rash appearing in crops, with lesions at different stages simultaneously.

• Prodrome: Fever, malaise, loss of appetite, headache, fatigue

• Rash: Begins on chest, back, and face, then spreads; lesions appear in crops and are at different stages

• Other symptoms: Itching, low-grade fever

• Complications: Secondary bacterial infections, pneumonia, encephalitis, congenital varicella syndrome

Reactivation: Shingles (Herpes Zoster)

Shingles presents with pain, burning, or tingling in a dermatomal distribution, followed by a unilateral vesicular rash. Pain can persist after rash resolution (postherpetic neuralgia).

• Prodrome: Pain, burning, tingling, hypersensitivity

• Rash: Red maculopapular rash evolving into vesicles and pustules; typically unilateral and restricted to one dermatome

• Pain: Moderate to severe nerve pain, may persist as postherpetic neuralgia

• Complications: Postherpetic neuralgia, ophthalmic zoster, secondary bacterial infections, disseminated zoster

Pathogenesis

Chickenpox (Primary Varicella Infection)

VZV enters via the respiratory tract, replicates in mucosa and lymph nodes, then spreads via viremia to the reticuloendothelial system and skin. The virus establishes latency in sensory ganglia after resolution.

• Entry: Respiratory tract

• Replication: Nasopharyngeal mucosa, lymph nodes

• Primary viremia: Spread to liver, spleen, lymph nodes

• Secondary viremia: Spread to skin and mucous membranes

• Rash formation: Infection of epidermal cells, vesicular rash

• Latency: Virus travels to dorsal root/cranial nerve ganglia

Shingles (Herpes Zoster Reactivation)

Years after primary infection, latent VZV reactivates in sensory ganglia due to weakened immunity. The virus travels down sensory nerves, causing localized inflammation and a dermatomal rash.

• Reactivation: Latent virus reactivates in ganglia

• Spread: Virus travels down sensory axons to skin

• Rash: Dermatomal vesicular rash

• Pain: Neuropathic pain from nerve inflammation

Diagnosis

Diagnostic Tests

Diagnosis is usually clinical, but laboratory tests can confirm VZV infection.

• Rash examination

• Blood test

• Viral culture

• Direct fluorescent antibody test

Treatment

Chickenpox

• Usually no treatment required

• Antihistamines for itching

Shingles

• Antiviral medications: Acyclovir, Famciclovir

• NSAIDs for pain

• Capsaicin topical cream for postherpetic neuralgia

Prevention

Varicella (Chickenpox) Vaccine

The live attenuated vaccine (Varivax) is highly effective, preventing about 98% of moderate to severe disease.

Herpes Zoster (Shingles) Vaccine

• Recombinant zoster vaccine (RZV, Shingrix) is preferred in the U.S.

• Reduces risk of shingles and postherpetic neuralgia by >90%

Quiz Questions

Hallmark Sign of Chickenpox

• Correct answer: Vesicular lesions appearing in crops at different stages

Pathogenesis of Shingles in Immunocompromised Patient

• Correct answer: Latent VZV reactivated in sensory ganglia and spread down nerve axons

Prevention Plan for Nursing Home

• Correct answer: Provide recombinant zoster vaccine to residents ≥50 years and varicella vaccine to non-immune staff