Varicella and Varicella Vaccines
Najwa Khuri-Bulos MD,FIDSA
Chief Editor, Immunizeme.co
Virology, epidemiology and clinical manifestations
Varicella Zoster Virus (VZV) is a DNA virus that belongs to the herpes
viruses which include Herpes simplex types 1 and 2, CMV, EBV, HHV6,
7 and 8. VZV causes a rash which is characteristically vesicular in nature
and is limited to humans. The infection is worldwide in distribution and
is usually spread from person to person by the respiratory or contact
routes. Patients are contagious one or two days before the onset of rash
by the respiratory route and are contagious to others by contact until the
lesions are crusted. Varicella is a highly contagious disease and
secondary attack rates in non-immune contacts may be as high as 90%.
Asymptomatic infection is uncommon.
Upon entry through the respiratory tract or conjunctiva, primary and
secondary viremia ensues leading to generalized distribution of the virus
and manifests mainly as a generalized vesicular rash. This rash starts in
the head and spreads to the rest of the body. The rash starts as a macule,
which rapidly progresses to become popular and progresses to become
vesicular. These lesions appear in crops and there are usually several
stages of the rash at any part of the body. At a later stage the vesicles
become dry and crust after a few days. Some of these become pruritic.
Dry crusts are not contagious.
Following acute infection, and similar to other herpes viruses varicella
has the capacity to persist in the host. The virus persists in dorsal root
ganglia and reactivation of infection manifests as a localized rash that is
dermatomal in distribution and is usually unilateral (Herpes Zoster).
Herpes Zoster is more common in the elderly and the
immunecompromised. Primary VZV infection (chickenpox) on the other
hand is characterized by a generalized vesicular rash with a distinctive
Photograph of Herpes Zoster. Note the unilateral distribution of the rash
While the disease is usually mild in most children and is typically
accompanied by low-grade fever and malaise, complications may occur
and include secondary bacterial infection of the skin primarily with
streptococci or staph aureus. On rare occasions other complications may
occur including encephalitis, acute cerebella ataxia, aseptic meningitis
and purpura fulminans. Reye’s syndrome was an important complication,
which was associated with the use of aspirin (ASA) during the acute
illness; this however has become distinctly rare after the recommendation
against the use of ASA in children less than 16 years of age. It is
noteworthy that chickenpox infection is more severe in adults some of
whom may also develop pneumonia and hepatitis.
Varicella is a serious disease in the immune compromised individuals
who may develop disseminated infection (generalized varicella). This
complication may occur in up to one third of these cases and is associated
with a high mortality rate. These patients develop disseminated varicella
infection of the lungs, liver and CNS in addition to a dense severe
Varicella is also a serious illness in pregnant women and their offspring.
The risk of varicella infection may occur during pregnancy or during the
perinatal period. Congenital varicella may occur if maternal infection
occurs during pregnancy especially in the first 20 weeks. The congenital
varicella syndrome may manifest by hypoplasia of an extremity, skin
scarring, muscular dystrophy, encephalitis, cortical atrophy and
microcephaly. The risk of such an outcome is about 2%.
In the latter stages of pregnancy and the perinatal period, varicella is also
a serious illness in pregnant women and their offspring. The onset of
varicella from 5 days till 2 days after delivery may lead to overwhelming
neonatal varicella infection with fatality rates, as high as 30%. The
course in newborns whose mothers develop chickenpox 5 days or more
prior to delivery however is characterized by a mild course possibly due
to the passive transfer of maternal antibody to the newborn.
While the importance of varicella infection is well defined in developed
countries, the burden of varicella infection is difficult to determine in
many developing countries since surveillance data is not readily
available. In Jordan, which is one of the countries that has adopted
chickenpox reporting as part of the surveillance system at the ministry of
health, the following chart shows the numbers reported to the MOH since
2004. It is noteworthy that reporting of varicella infection may not be
complete since this reporting is from MOH centers only. In addition since
this depends on passive reporting many cases may be missed. However,
even with this shortcoming this surveillance is needed if countries are to
adopt the use of chickenpox vaccines that have proved effective when
used as per the following recommendations.
Varicella Zoster Vaccines
Varicella vaccines have been introduced in many parts of the
developed world for many years. The first country to introduce the
vaccine was Japan where a live attenuated vaccine was introduced
(Oka strain). This strain is the strain, which is now used in all of
There are two chickenpox vaccines that are licensed for use in children
and young adults. Both of these vaccines are derived from the original
OKA strain and are live attenuated viral vaccines.
1. Varivax (Merck) is a live attenuated viral vaccine derived from the
OKA strain. This was first used in Japan and was introduced in the
US market for children at the age of 12 months in 1995.
This vaccine is manufactured by GSK. It too is a live attenuated
vaccine using the OKA strain.
Varicella vaccine leads to antibody in more than 90% of vaccines that
maintain the antibody level for more than six years. The vaccine was
initially recommended for all children as a single dose starting 12 months
of age. However a recommendation for a second dose was made due to
the fact that some vaccinees developed infection several years after
receiving the first dose. Among adolescents 78% develop antibodies
after one dose and 99% develop antibodies after the second dose.
While immunity appears to be long lasting following vaccination,
breakthrough infection may occur in vaccinees, but is usually milder that
the primary infection. Among the risk factors for this breakthrough
infection is vaccination at <15 months of age, use of steroids and asthma.
Receiving another live vaccine in a period that is less than one month
between the two live vaccines is also associated with breakthrough
Herpes Zoster and Herpes Zoster vaccine
Herpes zoster infection is due to reactivation of varicella virus that is
dormant in dorsal root ganglia. The manifestations of this infection are
limited to the skin in the majority of patients. However this can be a
debilitating infection since it is very painful and may lead to post herpetic
neuralgia in the long run. It can also lead to disseminated varicella
infection in the immune compromised individuals. Herpes Zoster may be
transmitted to other individuals but the route is primarily through contact
and secondary infection is manifested by chickenpox in the infected
individuals. The lifetime risk of herpes zoster in older individuals is 32%
and may be up to 50% of persons living until the age of 85 years. It is due
to this high burden that Herpes Zoster vaccine was introduced.
Zoster vaccine is recommended for individuals who are older than 50
years who have an increased risk to develop zoster. Varicella Zoster
Vaccine is made from the same viral strain as the other vaccines in use
for children, the OKA strain but at a much higher titer (a minimum of
19,400 PFU versus 1,350 PFU in varicella vaccine).
Chickenpox vaccine for children
Routine vaccination of children 12-15 months of age with a second
dose recommended at 4-6 years. The minimum interval between the
two doses is 3 months.
Zoster vaccine for adults older than 50 years of age
Single dose Zoster vaccine is recommended for individuals older than
50 years. However if there is vaccine shortage, preference should be
provided to individuals who are older than 60 years of age since they
have a higher risk of Zoster.
Varicella vaccine precautions and contraindications
Immune suppression affecting T cell mediated immunity such
as high dose steroids, HIV infection.
Patients with hypogammaglobulinemia may be vaccinated with
single antigen varicella vaccine but not MMRV
Recent blood products
Use of varicella vaccine in post exposure prophylaxis
Varicella vaccine is effective in post exposure prophylaxis if provided
within the first 3-5 days post exposure (effectiveness 70-100%)
Vaccine is NOT effective if given after 5 days of exposure. However
if given it will produce immunity if the recipient is not infected and is
not contraindicated in that situation.
Are we ready for adopting chickenpox vaccine in the Jordan EPI??
At the present time, while VZV vaccine should be provided to
individuals who wish to use it in the private market, further evidence
for burden of disease has to be provided in order to help the National
Immunization Program (NIP) to provide funding for the introduction
of this vaccine to all children in the country.
Suggested readings and references
Background Paper on Varicella Vaccine SAGE Working Group on Varicella and
Herpes Zoster Vaccine