Varicella vaccine

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

progression.

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 rash.

 

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

these vaccines.

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.

2. Varillex

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

infection.

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).

Vaccination schedule:

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

 Pregnancy

 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.

Focused discussion

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

http://www.who.int/immunization/sage/meetings/2014/april/1_SAGE_varicella_background_paper_FINAL.pdf