M R Lokeshwar
Consultant Pediatrician, B.J.Wadia Hospital for Children, Mumbai, India
First Created: 02/04/2002 


What type of virus is varicella-zoster virus (VZV)?

Varicella-zoster virus is a member of the herpesviral family. The virus has icosahedral symmetry containing centrally located double-stranded DNA with a surrounding envelope. The DNA contains 125,000 base pairs and encodes approximately 75 proteins.

What are the reservoirs of VZV?

Humans are the only reservoir for VZV.

What are the common modes of transmission of VZV infection?

The virus is extremely labile and is unable to survive for a long period in scabs or fomites. Therefore, transmission via inanimate objects is unlikely. The infection is usually transmitted through inhalation of infectious respiratory secretions from an infected person (droplet infection), direct physical contact with a vesicular lesion, and by a vertical transmission during pregnancy.

Is chickenpox a totally benign illness?

In most immunocompetent and healthy children, chickenpox is a self-limited disease. Complications do occur but they are infrequent as can be gauged by the fact that some infected children, who are otherwise healthy do need to be hospitalized. In adults, pregnant women, and immunocompromised individuals, the disease is not so benign. In these persons, complications are more frequent and the risk of mortality is higher.

How long is the child with chickenpox infectious?

A child with chickenpox is infectious from two days prior to the onset of rash till all the lesions are scabbed: which usually occurs 5 days after the appearance of the rash.

What events occur immediately following the infection?

Following the entry of VZV into the body via the respiratory tract and/or the conjunctiva, the virus replicates in the regional lymph nodes for 4-6 days. The virus then disseminates throughout the bloodstream and lymphatic system. Following this phase of primary viremia, VZV is taken up by the cells of the reticuloendothelial system and undergoes another stage of replication in the liver and other organs. This is followed by secondary viremia; whose appearance coincides with the appearance of prodromal symptoms. These events following infection generally take 14-16 days, which is the incubation period of chickenpox (range 10-21 days). This period may be shorter in immunocompromised patients but longer (up to 28 days) in individuals who have received varicella-zoster immunoglobulin (VZIG).

How is herpes zoster related to VZV?

Herpes zoster is secondary to reactivation of VZV that has remained dormant in the dorsal root ganglia following the primary attack of varicella.

How Does Epidemiology of Chickenpox Vary in Different Geographical Areas?

The VZV infections are known to occur at a much earlier age in temperate climate while they are supposed to occur at a later age in individuals staying in warmer tropical areas. Thus in the United States and European Union, as many as 60% of the pre-school children demonstrate antibody to VZV. The proportion of seroprevalence rises to 78% by 11 years of age. In contrast, the mean age of chickenpox sufferer is higher in tropical countries, with many more cases occurring among adolescents and adults. There is a paucity of Indian data. One study showed that only 29.7% of student nurses aged 17-20 years had antibodies against varicella while another study showed that less than 5% of under-five children were seropositive. Studies from Southeast Asia and Latin America also indicate a much lower age-specific seroprevalence rate.

What are the Clinical Manifestations of VZV infection in children?

The primary VZV infection results in chickenpox, which has characteristic clinical manifestation. It presents with a rash, low-grade fever, and malaise. Few patients may have prodromal symptoms for 1-2 days prior to the appearance of the exanthem. The rash usually starts on the face, scalp, or trunk. It is often the first manifestation of illness. Lesions that are hidden by hair can often be detected by running the hands along the scalp, before the appearance of a large number of lesions in other areas. Occasionally a group of two to three lesions appears on the trunk a day or two before the generalized eruption. The skin manifestations, the hallmark of infection, consist of maculopapular, vesicles, and scabs in varying stages of evolution. The lesions initially contain clear vesicular fluid, but over a short period of time, they pustulate and scab. Most lesions are small having an erythematous base with a diameter of 5-12 mm. The lesions can be round or oval. As healing progresses, central umbilication occurs in them. Successive crops of lesions generally appear over a period of 2-4 days as the rash spreads centripetally. These successive crops are responsible for lesions of various stages of evolution. The crusts completely fall off within a week or two after the onset of infection, leaving behind a slightly depressed scar over the skin.

The rash may be accompanied by constitutional symptoms such as malaise, pruritis, anorexia, and listlessness. These symptoms generally resolve as the illness abates. There could be lesions on the mucosa of the oropharynx and the vagina. However, these are relatively uncommon.

What are the Manifestations and Complications of Chickenpox in Adults?

As is true of many viral diseases, chickenpox may be much more severe in adults than in children. The lesions are frequently confluent and systemic symptoms such as myalgia, arthralgia, and malaise are much more common. The complication of chickenpox is usually more severe too and occurs more frequently than in children. Respiratory complications like pneumonitis manifesting with cough, fever, dyspnea, and sometimes, pleuritic pain and hemoptysis within 5 days of the appearance of the rash; are especially common. Varicella infection in adults is associated with a 15-fold rise in mortality than that seen in children.

What are the Effects of Varicella Infection in Immunocompromised Individuals?

Immunocompromised children and adults are prone to severe forms of varicella infection. The constellation of manifestations is referred to as "progressive varicella syndrome". It has a shorter incubation period than usual. The rash is severe, confluent, involves even palms and soles, and is likely to last longer. The fever and constitutional symptoms are more severe and the complication rate is much higher. Almost one-third of these individuals have involvement of multiple organs including the lungs, liver, and central nervous system. The fatality rate is higher (15-18%) and accounts for 70% of deaths due to varicella.

What are the Effects of Varicella Infection during Pregnancy?

A woman who develops varicella during pregnancy is more prone to develop pneumonitis. Some authorities believe that pregnant women usually tend to have more have a more severe form of varicella.

The consequences for the fetus and the newborn baby depend upon the timing of varicella infection. If a woman develops varicella infection during the first trimester, the fetus may have defective organogenesis and the baby may have congenital varicella syndrome. If the infection is developed during the second trimester, the baby is normal but is likely to develop herpes zoster within the first 1-2 years of life. This is an unusual event, given the fact that zoster generally develops in adults above the age of 55 years. If the mother develops varicella infection within 5 days preceding the delivery or within 2 days after the delivery, the neonate receives the virus but does not receive maternal antibodies, given the underdeveloped immune system in neonates, a baby born to such a mother is prone to develop progressive varicella syndrome with severe manifestation, the higher chance of developing serious complications and at an enhanced risk of death from the infection.

What is Congenital Varicella Syndrome?

When a fetus gets infected with varicella due to maternal infection occurring during the first trimester of pregnancy, there is a probability of a virus disrupting organogenesis in the fetus. Such an infected fetus shows multiple abnormalities at birth and the constellation of these manifestations are referred to as congenital varicella syndrome. Such a baby has characteristic abnormalities (chorioretinitis, Horner's syndrome, microphthalmia, cataract, and nystagmus) and abnormalities of the central nervous system (cortical atrophy). Other abnormalities that have been described include equinovarus, abnormal or absent digits, prematurity, and low birth weight. These children have mental retardation, poor sphincteric control, and are at risk to develop clinical zoster in infancy and early childhood.

Herpes Zoster in Immunocompetent Individuals

Herpes zoster occurs frequently in adults but is not uncommon in children. Adults have a painful vesicular eruption. The rash consists of grouped vesicles surrounded by an erythematous base. Vesicles may coalesce to form bullous lesions. The rash is unilateral and limited to the distribution of one of the nerves or dermatomes. It more commonly affects the thoracic and lumbar regions. The next most commonly affected site is the trigeminal nerve affecting the face and possibly the eye. The lesions may continue to form over 3-5 days with the total duration of diseases being 10-15 days. However, it may take up to 1 month before the skin returns to normal. The rash is unaccompanied by systemic symptoms other than mild fever.

Pain within the affected region may precede the appearance of the rash by 48-72 hours and produce a diagnostic problem. Normal children infrequently experience severe pain with their eruption. Although herpes zoster has a self-limited course, it is followed by neuralgia (postherpetic neuralgia), even in immunocompetent individuals. This painful condition may last for several months or even for years. The pain can be excruciating and is notoriously unresponsive to routinely use analgesics. At its worst, neuralgia can be incapacitating.

Herpes zoster ophthalmicus associated with keratitis is a potentially sight-threatening complication. Keratitis may be followed by severe iridocyclitis, secondary glaucoma, or neuroparalytic keratitis. Encephalitis and pneumonia are rare complications of herpes zoster.

Immunocompromised States that Make the Child Prone to Develop Progressive Varicella Syndrome or Severe Complications following Varicella Infection

The following immunodeficiency states predispose a child to develop progressive varicella syndrome or severe complication following varicella infection:

  • Malignancy: Leukemia
  • Therapy-related: Children on corticosteroid therapy, radiotherapy, cancer chemotherapy or immunosuppressive drugs prior to or after organ transplants.
  • Infection: HIV infection.

Clinical Features of Herpes Zoster in Immunocompromised Children

Herpes zoster causes disseminated infection in immunosuppressed children. Usually, two to three days after the appearance of localized lesions, vesicles appear in other areas of the trunk and extremities. The appearance of the remote lesion may continue for up to 2 weeks after that. There may be visceral involvement as well, including varicella pneumonitis, hepatitis, and meningoencephalitis. Certain categories of immunocompromised children may suffer from chronic herpes zoster. Complications such as VZV retinitis, acute retinal necrosis, and chronic progressive encephalitis have been reported.

How Does One Diagnose Chickenpox in a Child?

Chickenpox is usually diagnosed on clinical grounds alone. A history of contact with a case of chickenpox, characteristic pruritic, papulovesicular rash, and the relative absence or mildness of constitutional symptoms make this possible. Laboratory tests are indeed available. The most rapid test used is tzanck cyst diagnosis. Smears of the scraped vesicular base are stained with Giemsa, hematoxylin, and eosin or Papanicolaou and are examined under a microscope for multinucleated giant cells and intranuclear inclusion bodies. However, one cannot differentiate between VZV and herpes simplex virus (HSV) infection on the basis of tzanck smear.

Serological tests have been devised for the diagnosis of VZV infection. These tests detect the presence of antibodies synthesized actively in response to VZV infection. Various techniques such as complement fixation, fluorescent antibody, immune adherence haemagglutination (IAHA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA) have been employed. A four-fold rise in antibody titers between the acute and convalescent sera is considered to be confirmatory of VZV infection. PCR is being evaluated as a diagnostic tool.

Chickenpox Chickenpox 2002-02-04
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