Chicken Pox - Varicella Zoster Virus

 VARICELLA-ZOSTER VIRUS

·       VZV causes chickenpox (varicella) upon recurrence, and causes herpes zoster, or shingles.

·       As an alphaherpesvirus, VZV shares many characteristics with HSV.

·       Causes Clinical chicken pox (primary infection).

·       90% of cases before age 10, peak incidence 2-8 years.

·       Recurrent infection - shingles (herpes zoster) in adults.

·       VZV is seen worldwide and is highly infectious,

·       Human is the only natural host of the virus.

1. Virus transmission and Structure

·       Virus entry through inhalation – airborne transmission.

·       Direct contact.

·       Vesicle fluids.

·       Viral particle size: 180-200nm in diameter.

·       Lipid envelope encloses the icosahedral form of the nucleocapsid.

·       DNA is linear, Smallest genome.

·       Replicates slower.

(Image source: https://www.creative-diagnostics.com/tag-varicella-zoster-virus-antigens-39.htm)

2. Replication

·       Replicates in the respiratory tract (mucosal epithelial) and invades lymph nodes.

·       Local replication is followed by spread to tonsils and other regional lymphoid tissues, where VZV gains access to T cells.

·       Virus envelope glycoprotein binds to mannose-6-phosphate receptor8 or myelin-associated glycoprotein9.

·       Infected T cells then deliver the virus to cutaneous sites of replication.

·       Viremia: spreads the virus to target organs.

·       Incubation period 14-18 days.

·       Belong to the alpha herpesvirus subfamily of herpesviruses.

·       Double stranded DNA enveloped virus.

·       Genome size 125 kbp, long icosahedral capsid (shaped like spheres),

·       Transmission mainly occurs via droplets or particles in the air.

4. Pathogenesis

·       VZV is generally acquired by inhalation, and primary infection begins in the tonsils and mucosa of the respiratory tract.

·       The virus then progresses via the bloodstream and lymphatic system to the cells of the reticuloendothelial system.

·       Reticuloendothelial system –Phagocytic Cells in fixed tissues (Liver, Heart gall bladder).

·       A secondary viremia occurs after 11 to 13 days and spreads the virus throughout the body and to the skin.

·       The virus infects T cells, and these cells can home to the skin and transfer virus to skin epithelial cells.

·       The virus overcomes inhibition by interferon-α, and vesicles are produced in the skin and cause lesions in successive crops.

·       Fever and systemic symptoms occur with the rash.

·       The lesions are superficial and all the stages

      -Macule, Papule, Vesicle and scab.

·       The virus becomes latent in the dorsal root or cranial nerve ganglia after the primary infection.

·       The virus can be reactivated in older adults when immunity wanes or in patients with impaired cellular immunity.

·       On reactivation, the virus replicates and is released along the entire neural pathway to infect the skin, causing a vesicular rash along the entire dermatome, known as herpes zoster, or shingles.

·       This damages the neuron and may result in post herpetic neuralgia.

Mechanism of spread of varicella-zoster virus (VZV) within the body

5. Clinical Symptoms of Chickenpox

·       Rash appears first on the head, neck, and trunk.

·       Vesicles contain clear fluid (itch).

·       New vesicles appear during the first week.

·       Mild fever, malaise, headache.

·       Recovery in 2 weeks.

·       Adult infections are more severe (pneumonia).

·       Neonatal infection (encephalitis).

6. Laboratory diagnosis

o   Specimen collection - skin lesions, respiratory specimens, or organ biopsy specimens.

o   Immunofluorescent antibody staining

o   Polymerase Chain Reaction (PCR) - vesicles, scabs, maculopapular lesions.

o   ELISA.

o   In-vitro cultivation - Human Diploid Fibroblasts (MRC-5 cells), melanoma (MeWo) cells, or retinal pigmented epithelial (ARPE-19) cells.

o   These cells are also used to isolate VZV, research, and vaccine preparation.

7. Treatment

·       ACV, famciclovir, and valacyclovir

·       Live attenuated vaccine Oka (VARIVAX) – 2 doses, Intramuscular or Subcutaneous administration, VARIVAX approximately 0.5 mL.

·       First dose is administered at 12 to 15 months of age.

Second dose is administered at 4 to 6 years of age.

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