Producing sufficient quantities of the vaccine to immunize all children against chickenpox has proven to be a major obstacle. Weakened viruses for vaccines are grown in cell cultures. However unlike other weakened viruses, varicella zoster remains in the cell rather than being secreted from the cell and collected from the culture medium. Thus the infected cells must be collected and broken open by ultrasound. The released virus is extremely sensitive to heat caused by ultrasound, and Merck scientists had to determine the precise conditions for opening the cells and releasing the virus unharmed. The company built a new production facility for Varivax that uses robots to strictly control the ultrasound procedure.

In addition to the live attenuated varicella virus, Varivax contains:

• bovine (cow) albumin or serum
• sodium ethylenediamine tetraacidic acid (EDTA)
• gelatin
• monosodium glutamate
• protein from the human cell line MRC-5
• neomycin, an antibiotic
• phosphate buffers
• sodium chloride
• sucrose

Effectiveness

VZV is considered to be safe and 70 to 90 percent effective. Vaccinated children who do contract chickenpox usually have milder symptoms. The vaccine also prevents chickenpox in children exposed to the virus three to five days prior to vaccination .

The Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics, and the American Academy of Family Physicians all recommend that healthy children be vaccinated against chickenpox. In 2001 child-care facilities and public schools began phasing in a varicella vaccination requirement for enrollment. By 2002, some 81 percent of American children had been vaccinated with VZV, and the CDC determined that the number of chickenpox cases had declined substantially. The CDC expects that widespread childhood vaccination against chickenpox will further reduce the incidence of the virus in the general population. This, in turn, will reduce the incidence of chickenpox among those who cannot receive VZV, including children who are most at risk for serious complications from the disease.

Breakthrough infections

As of 2004 it was unclear whether VZV provided life-long immunity to chickenpox. The U.S. Food and Drug Administration (FDA) required Merck to follow several thousand children for 15 years, to determine the long-term effects of the vaccine and whether additional booster shots of VZV would be necessary. It is possible that vaccinated children obtain booster immune effects through repeated contact with the virus from infected children.

Early evidence suggested that the rate of breakthrough chickenpox infections (infections in previously vaccinated children) was about 2 percent annually and that the likelihood of such infections did not increase with time after vaccination. Breakthrough infections in vaccinated children usually are very mild. They last only a few days and there are fewer than 50 lesions on the child's body and little or no fever . It is not clear whether breakthrough chickenpox infections are less contagious than infections in unvaccinated children.

Some physicians remain reluctant to vaccinate against an usually mild childhood disease such as chickenpox. Some also are concerned that vaccinated children may contract chickenpox as adults when it can be a much more serious disease with a 20 percent higher risk of death.

Shingles

Although children who have had chickenpox are immune to the disease and cannot contract it a second time, the varicella zoster virus can remain inactive in the human body. These dormant viruses are concentrated in nerve cells near the spinal cord and may reactivate in adults, causing the disease herpes zoster or shingles. The reactivated virus further infects nerve cells, causing severe pain , burning, or itching . Shingles usually occurs in people over the age of 50 and may be associated with a weakening immune system.

It is not known whether the weakened virus used for VZV can remain dormant in the body, eventually causing shingles in the same way that the naturally occurring varicella virus can. In 1998 the CDC found 2.6 cases of post-vaccination herpes zoster for every 100,000 distributed doses of VZV. In contrast there were 68 cases of herpes zoster in healthy children under age 20, following natural infection with varicella. However, as of 2004, it is too early to determine whether vaccinated children are more or less likely to develop shingles in adulthood as compared with adults who were naturally infected with chickenpox as children.

A 2002 study indicated that exposure to varicella is much higher in adults living with children and that such exposure substantially boosts immunity against shingles. The authors of the study predicted that mass vaccination against varicella will create an epidemic of herpes zoster, affecting as many as 50 percent of those who were between the ages of ten and 44 at the time that the vaccine was introduced.

General use

Consequences of chickenpox

Chickenpox is highly contagious and easily transmitted among children through personal contact, coughing, or sneezing. The disease is characterized by red spots on the face, chest, back, and other body parts. These spots fill with fluid, rupture, and crust over. Symptoms of chickenpox may not appear for as long as two to three weeks following infection. The virus is contagious from one or two days before the first rash appears until the blisters have formed complete scabs and no new rash has appeared for 24 hours. This may take from five days to two weeks. Thus the varicella virus can spread very rapidly within families and among groups of children in school and daycare.

In most instances chickenpox is not a serious disease, although the itchy lesions and fever and other mild flu-like symptoms may cause a week or two of discomfort. However the disease can have serious complications. Scratching the pox can cause bacterial infection that can lead to permanent scars. In rare cases chickenpox can lead to the following:

• muscle aches
• sore throat
• ear infections
• pneumonia
• arthritis
• neurological symptoms, including shakiness
• encephalitis , an inflammation of the brain

In the United States more children die of chickenpox than of any other disease that can be prevented by a vaccine. Prior to the introduction of VZV, there were about 100 deaths and 12,000 hospitalizations annually as a result of chickenpox infections. Approximately 40 percent of the deaths and 60 percent of the hospitalizations occurred in children under age ten. Teenagers and adults, as well as children with leukemia or other cancers or with impaired immune systems, are at particular risk for severe chickenpox and its complications. Babies whose mothers contracted chickenpox during pregnancy are at risk for multiple birth defects. Babies whose mothers contract chickenpox shortly before or after giving birth are at risk of developing a severe form of the disease. As many as 5 percent of these babies die. Most high-risk children and non-immune adults contract chickenpox from unvaccinated children.

Children with chickenpox miss an average of five to six days of school and their parents miss an average of three to four days of work while caring for them. The CDC estimates that, including direct medical costs and indirect societal costs, $5.40 is saved for every $1.00 spent on childhood VZV immunization.

Vaccine administration

It is recommended that babies receive a single-dose injection of Varivax between the ages of 12 and 18 months, usually at the same time that they receive their first measles, mumps , and rubella (MMR) vaccine. Children and adolescents who have not already had chickenpox can be vaccinated at any time. However, adolescents aged 13 or older, as well as adults, require two doses of Varivax, four to eight weeks apart, to obtain the same level of immunity as children under 13. The reason for this is not known.

VZV usually is covered by health insurance. In the United States the Vaccines for Children program covers the cost of chickenpox vaccination for children without health insurance and for specific other groups of children, including Native Americans.

Precautions

In rare instances it is possible to contract the weakened vaccine strain of varicella from a recently vaccinated child.

Healthy children

Children on long-term steroids for any reason, including asthma , should consult their physician about the timing of the vaccination. Children should not receive VZV if the following applies:

• They are allergic to gelatin or the antibiotic neomycin.
• They have had a serious reaction to a previous varicella vaccination.
• They are taking aspirin or other salicylates that have the remote possibility of causing Reye's syndrome.

In addition, infants under one year and pregnant teenagers should not receive VZV. Females should not become pregnant within one month of receiving VZV.

Children at high risk for severe chickenpox or its complications, including newborns and premature infants exposed to chickenpox after birth, often are given varicella-zoster immune globulin (VZIG). VZIG is made from the blood serum of people with high antibody levels against the varicella virus. It must be administered within 96 hours of exposure to chickenpox, and it results in a passive immunity against the disease for about three months.

Additional CDC precautions for administrating VZV pertain to the following groups of children:

• those with a family history of immunodeficiency
• those who have had a blood transfusion or received other blood or serum products within the past five months
• those who have received antibody-containing products, including VZIG or other immune globulin, within the past 11 months

Children with medical conditions

Medical conditions that preclude vaccination against chickenpox include active, untreated tuberculosis and any other moderate or serious illness. Moreover, children with weakened immune systems should not receive a live virus vaccine such as VZV. This restriction applies to children who have the following situations:

• They have leukemia or other cancers.
• They have had cancer treatments, including radiation or drugs.
• They have received organ transplants or hematopoietic stem cell transplants.
• They have a weakened immune system due to HIV/AIDS.

Children with leukemia in remission or HIV-infected children with normal immune function may be eligible for VZV. However, chickenpox can cause serious complications in HIV-infected children with compromised immune systems. Therefore, the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD) are as of 2004 sponsoring a clinical study of the safety and effectiveness of Varivax in HIV-infected children. In the initial phase of the study, HIV-infected children who were without symptoms tolerated Varivax well. Since shingles is very common in HIV-infected children, the NIAID and NICHD also launched a clinical study to determine whether Varivax can prevent shingles in HIV-infected children who have had chickenpox.

Side effects

Reactions to VZV are usually mild and may include:

• pain, rash, hardness, and/or swelling at the injection site in about 20 percent of children and about one in three adolescents
• small chickenpox lesions one to two weeks after vaccination
• generalized mild rashes or small bumps up to a month after vaccination in 1–4 percent of VZV recipients

Moderate or severe reactions to VSV have been reported very rarely. These reactions include: high fever or seizures one to six weeks after vaccination in fewer than one out of 1,000 children; pneumonia; and anaphylaxis , an allergic reaction that may include weakness, wheezing, breathing difficulties, hives , a fast heart rate, dizziness , or behavior changes, within a few minutes to a few hours after the injection. Other reactions, such as a low blood count or brain involvement, including encephalitis, occur so rarely that they may not be associated with VZV.

Following the distribution of the first 10 million doses of VZV, it was determined that severe reactions occurred with a frequency of approximately one in 50,000. This is far lower than the risks associated with chickenpox. There is no evidence that healthy children who have had chickenpox or who received VZV previously are at a greater for adverse effects from an additional dose of Varivax.

The National Vaccine Injury Compensation Program helps pay for medical expenses resulting from vaccine reactions. In case of a serious reaction to VZV, parents should do the following:

• A doctor should be consulted immediately.
• The date, time, and type of reaction should be recorded.
• Medical personnel or the local health department should file a Vaccine Adverse Event Report.

Interactions

VZV is not known to interact with any foods or drugs. However, antiviral drugs for treating herpes viruses, including acyclovir or valacyclovir, should not be administered within 24 hours of Varivax, because these drugs can reduce the effectiveness of the vaccine.

Parental concerns

Most children are afraid of injections; however, there are simple methods for easing a child's fear . Prior to the vaccination, parents should do the following:

• Tell children that they will be getting a shot and that it will feel like a prick; however, it will only sting for a few seconds.
• Explain to children that the shot will prevent them from becoming sick.
• Have older siblings comfort and reassure a younger child.
• Bring along the child's favorite toy or blanket.
• Never threaten children by telling them they will get a shot.
• Read the vaccination information statement (VIS) and ask the medical practitioner questions.

During the vaccination, parents should follow these steps:

• Hold the child.
• Make eye contact with the child and smile.
• Talk softly and comfort the child.
• Distract the child by pointing out pictures or objects or by using a hand puppet.
• Sing or tell the child a story.
• Have the child tell a story.
• Teach the child how to focus on something other than the shot.
• Help the child to take deep breaths.
• Allow the child to cry.
• Stay calm.

Parents may choose to use a comforting restraint method while the child is receiving the injection. These methods enable the parent to control and steady the child's arm while not holding the child down. With toddlers, the positions are as follows:

• The child is held on the parent's lap.
• The child's arm is behind the parent's back, held under the parent's arm.
• The parent's arm and hand control the child's other arm.
• The child's feet are held between the parent's thighs and steadied with the parent's other arm.

With older children, the parent and child can assume the following positions:

• The child is held on the parent's lap or stands in front of the seated parent.
• he parent's arms embrace the child.
• The child's legs are between the parent's legs.

Following the vaccination, parents should do the following:

• Hold and caress or breastfeed the child.
• Talk soothingly and reassuringly.
• Hug and praise the child for doing well.
• Review the VIS for possible side effects.
• Use a cool, wet cloth to reduce soreness or swelling at the injection site.
• Check the child for rashes over the next few days.

In addition, parents should anticipate that their children may eat less during the first 24 hours after the injection, and they should receive plenty of fluids. The medical practitioner may suggest a non-aspirin-containing pain reliever.

KEY TERMS

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Booster shot —An additional dose of a vaccine to maintain immunity to the disease.

Breakthrough infection —A disease that is contracted despite a successful vaccination against it.

Herpes zoster virus —Acute inflammatory virus that attacks the nerve cells on the root of each spinal nerve with skin eruptions along a sensory nerve ending. It causes chickenpox and shingles. Also called varicella zoster virus.

Immunity —Ability to resist the effects of agents, such as bacteria and viruses, that cause disease.

Varicella zoster —The virus that causes chickenpox (varicella).

Varicella-zoster immune globulin —A substance that can reduce the severity of chickenpox symptoms.

Resources

BOOKS

Atkinson, William, and Charles (Skip) Wolfe, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases, 7th ed. Atlanta, GA: National Immunization Program, Centers for Disease Control and Prevention, 2003.

PERIODICALS

Brisson, M., et al. "Exposure to Varicella Boosts Immunity to Herpes-Zoster: Implications for Mass Vaccination Against Chickenpox." Vaccine 20 (June 7, 2002): 2500–07.

ORGANIZATIONS

National Immunization Program. NIP Public Inquiries, Mailstop E-05, 1600 Clifton Rd. NE, Atlanta, GA 30333. Web site: <www.cdc.gov/nip>.

National Vaccine Information Center. 421-E Church St., Vienna, VA 22180. Web site: <www.909shot.com>.

WEB SITES

"Guide to Contraindications to Vaccinations." National Immunization Program, May 18, 2004. Available online at <www.cdc.gov/nip/recs/contraindications.htm> (accessed December 20, 2004).

"Varicella Vaccine (Chickenpox)." National Immunization Program, December 20, 2001. Available online at <www.cdc.gov/nip/vaccine/varicella/faqs-genvaccine.htm> (accessed December 20, 2004).

Margaret Alic, Ph.D.