Varicella-Zoster Virus (VZV)

Varicella-Zoster Virus (VZV)

• VZV transmits through respiratory droplets and direct contact with lesions.
• It is a highly contagious childhood disease that occurs worldwide.
• Over 90% of people in the U.S. have antibodies by age 10.
• VZV infects the mucosa of the upper respiratory tract.
• It spreads via the blood to the skin, causing a papulovesicular rash.
• The virus infects sensory neurons and travels via retrograde axonal flow into the dorsal root ganglia.
• In the dorsal root ganglia VZV becomes latent and can be reactivated by reduced cell-mediated immunity or local trauma.
• Activation results in vesicular skin lesions and nerve pain (Zoster).

Varicella

• Incubation period is 14-21 days.
• Prodromal symptoms include fever and malaise.
• The papulovesicular rash appears in crops on the trunk, spreading to the head and extremities.
• The rash evolves from papules to vesicles, pustules, and crusts.
• Itching is a prominent symptom, especially when vesicles are present.
• Varicella is generally mild in children but more severe in adults.
• Rare complications include varicella pneumonia and encephalitis (often in adults).
• Reye’s syndrome, causing encephalopathy and liver degeneration, is associated with VZV and influenza B virus infection, especially in children given aspirin.

Zoster

• Clinical symptoms include painful vesicles along a sensory nerve of the head or trunk.
• Pain can last for weeks, and post-zoster neuralgia can be debilitating.
• In immunocompromised patients, it can cause life-threatening disseminated infection such as pneumonia.

Diagnosis of VZV

• Diagnosis is based on clinical presentation.
• A Tzanck smear can identify multinucleated giant cells.
• PCR to detect VZV in skin lesions is most sensitive.
• Direct fluorescent antibody to membrane antigen (FAMA) can examine skin lesion scrapings or biopsy specimens.
• IgM serologic testing is less sensitive than PCR of skin lesions.
• A four-fold increase in IgG antibodies indicates varicella.

Treatment and Prevention of VZV

• Treatment is not always necessary for children.
• Adults or immunocompromised individuals get acyclovir, famciclovir, and valacyclovir for shingles.
• VZV infection in children induces lifelong immunity.
• Varicella-Zoster immune globulin (VZIG) is for immunocompromised individuals.
• A live attenuated vaccine is available after two years of age, similar to the MMR vaccine.
• VZV is a neurotropic, double-stranded, enveloped DNA virus.
• It is structurally and morphologically similar to other herpesviruses but antigenically different.
• There is a single serotype.
• Multinucleated giant cells with intranuclear inclusions are found in the base of the lesions.

Herpes Simplex Virus (HSV) 1 & 2

• HSV-1 and HSV-2 are double-stranded, enveloped DNA viruses.
• They are human herpes viruses with 50% nucleotide sequence identity, sharing common features in replication, disease production, and latency.
• Key features include skin and mucous membrane lesions, clusters of small, painful, fluid-filled blisters, herpetic whitlow, herpes gladiatorum, and keratoconjunctivitis.
• Both HSV-1 and HSV-2 belong to the Herpesviridae family and Alphaherpesvirinae subfamily.
• They contain linear, double-stranded DNA.

Diseases Caused by HSV-1 and HSV-2

• HSV-1 is mostly common in adults, causing gingivostomatitis, recurrent herpes labialis, keratoconjunctivitis, and encephalitis.
• HSV-2 causes genital herpes, neonatal encephalitis, other forms of neonatal herpes, and aseptic meningitis.
• Both HSV-1 and HSV-2 can cause erythema multiforme.

Epidemiology of HSV-1 and HSV-2

• HSV-1 transmits primarily in saliva.
• HSV-2 transmits by sexual contact.
• HSV-1 infections mainly occur on the face, while HSV-2 lesions occur in the genital area.
• Asymptomatic shedding of both HSV-1 and HSV-2 is common.
• Roughly 80% of people in the United States are infected with HSV-1, and 40% of those have recurrent herpes labialis.
• Most primary infections by HSV-1 occur in childhood.

Pathogenesis of HSV-1 and HSV-2

• The virus replicates in the skin or mucous membranes at the initial site of infection.
• It migrates up the neuron by retrograde axonal flow and becomes latent in the sensory ganglion cells.
• HSV-1 generally becomes latent in the trigeminal ganglia.
• HSV-2 generally becomes latent in the lumbar and sacral ganglia.
• Reactivation from the latent state can be triggered by sunlight, hormonal changes, trauma, stress, and fever.
• The virus migrates down the neuron and replicates in the skin, causing recurrent lesions.

Clinical Symptoms Caused by HSV-1

• Gingivostomatitis occurs primarily in children, characterized by fever, irritability, and vesicular lesions in the mouth, healing spontaneously in 2-3 weeks.
• Herpes labialis is a milder recurrent form, characterized by crops of vesicles at the mucocutaneous junction of the lips or nose.
• Keratoconjunctivitis is characterized by corneal ulcers and lesions of the conjunctival epithelium; recurrences can lead to scarring and blindness.
• Encephalitis is characterized by a necrotic lesion in one temporal lobe with fever, headache, vomiting, seizures, and altered mental status; it has a high mortality rate and causes severe neurological sequelae in survivors.
• Herpetic whitlow is a pustular lesion of the skin of the finger or hand, occurring in medical personnel due to contact with patients' lesions.
• Herpes gladiatorum occurs in wrestlers and others with close body contact, characterized by vesicular lesions on the head, neck, and trunk.
• Eczema herpeticum is an infection of the skin of a patient with atopic dermatitis or eczema, with vesicular lesions at the site of the atopic dermatitis or eczema, mostly in children.
• Disseminated infections such as esophagitis and pneumonia occur in immunocompromised patients with depressed T cell function.

Diseases Caused by HSV-2

• Many infections are asymptomatic.
• Genital herpes is characterized by painful vesicular lesions of the male and female genitals and anal area; lesions are more severe and protracted in primary disease than in recurrences.
• Primary infections are associated with fever and inguinal adenopathy.
• HSV-2 causes 80-90% of genital herpes.
• Neonatal herpes results from contact with vesicular lesions or asymptomatic shedding in the birth canal, varying from asymptomatic to milder lesions to disseminated lesions and encephalitis.
• Both HSV-1 and HSV-2 cause erythema multiforme, target symbol or bull's eye lesion.
• Lesions are papular and occur symmetrically on the trunk, hands, and feet.
• It is due to an immune-mediated reaction to the presence of HSV antigens.

Diagnosis of HSV-1 and HSV-2 Infections

• An important feature is isolation of the virus from the lesion by growth in cell culture, with a cytopathic effect in 1-3 days with multinuclear cells and ground glass chromatin.
• A rapid diagnosis can be made from skin lesions by using the Tzanck smear, staining cells from the base of vesicles with Giemsa stain to show multinucleated giant cells.
• If herpes encephalitis is suspected, a rapid diagnosis can be made by detecting HSV DNA in the spinal fluid using PCR.
• Serological tests, such as neutralization tests, can be used in the serodiagnosis of primary infection.
• HSV-1 can be distinguished from HSV-2 in ELISA by using monoclonal antibody against glycoprotein G.

Treatment of HSV-1 and HSV-2 Infections

• Acyclovir can be used for treating encephalitis and systemic diseases, primary and recurrent genital herpes, and neonatal infections.
• Foscarnet can be used for treating acyclovir-resistant HSV-1.
• Trifluridine topically can be used for treating HSV-1 eye infections.
• Oral acyclovir can be used for treating HSV keratitis.
• Valacyclovir or famciclovir can be used for treating genital herpes.