Epidemiology and transmission
Varizella-Zoster Virus (VZV) or human herpesvirus 3 (HHV3) is a highly contagious virus that affects people worldwide. VZV is transmitted through airborne respiratory droplets and smear infection of the virus filled lesions of infected people to susceptible contacts. Primary infections normally occur during childhood with moderate symptoms in immunocompetent patients. In immunosuppressed patients the infection may lead to serious complications, such as CNS pathology, pneumonia, and secondary bacterial infections.

Prevalence
The seroprevalence of antibodies to VZV increases from 30% in children by the age of 1 year to about 95% towards the age of 10 years and remains then lifelong at the same level.

Incidence
In the USA the cumulative incidence is 20%, or an annual rate of 3-5 cases/1000 persons. Internationally no accurate data is available, but the incidence seems to be similar to that in the USA. The incidence increases with age and impaired immune status. Immunosuppressed adults (HIV, malignancy) show an increased risk of 30% to 40%, the infection can be life-threatening.

Primary VZV infections and clinical pictures
Primary infections result in varizella (chickenpox), a common disease which affects most of the pediatric population; in immunocompetent children the infection is usually self-limited. The infection affects mucosa and skin (scalp, face, trunk, proximal limbs). The symptoms include malaise, fever, pharyngitis, pruritis, nausea, headaches, and rash. The lesions are characterised by erythematous macules > papules (12-14 h) > vesicles > pustules > crust > scarring (sometimes). The recovery takes about 2-3 weeks.

Latency
After primary infection VZV spreads from mucosa/skin to local sensory nerves where it stays latent for a variable period of time at the dorsal spinal ganglia or trigeminal ganglia.

Reactivation of primary VZV infections and clinical pictures
Reactivation of a latent VZV infection results in Herpes Zoster (shingles). It mainly affects elderly adults with a frequency of 70% and immunosuppressed patients, and the involvement is unilateral. Herpes Zoster presents as a vesicular rash in a dermatome distribution that usually is associated with pain which can be very extreme and incapacitating. The dermatomes include thoracic (56%), cervical (17%), trigeminal nerve (12%), lumbar (10%), and sacral (5%). The inflammation of the peripheral nerves accompanied by pain can persist for months and lead to demyelinisation and sclerosis.

Diagnosis
The clinical presentations of varizella or zoster are so characteristic that laboratory confirmation is rarely required.
However, specific laboratory diagnosis is required for atypical presentations, as found in immunocompromised patients, infections during pregnancy, diseases of the CNS, and pneumonia, taking account of VZV serology. Additionally, for distinguishing between HSV infections and Herpes Zoster.

Direct detection methods from the lesions, such as cytology and electron microscopy (EM), cannot distinguish between VZV and HSV. Immunofluorescence cytology is more sensitive than EM but is more labour intensive and requires greater technical expertise. PCR assays for VZV are available and have been reported to be of use in the diagnosis of VZV meningoenzephalitis from CSF specimens.

The isolation of VZV from fibroblast culture is considered the definitive method for diagnosing VZV infections. However, virus isolation is rarely carried out because of the long length of time required for a result to be available (up to 15 days) and the low sensitivity of 40% to 50%.

If laboratory diagnosis of VZV infections is required, serology has been considered method of choice. The most important use for VZV serology is the determination of the immune status before the administration of prophylactic therapy or vaccines as well as atypical clinical pictures.

For information on indications for the diagnosis with the medac VZV serology please refer to VZV serology in this section.