Hepatitis B vaccine

Definition

The hepatitis B vaccine (HBV or HepB) is an injection that protects children from contracting hepatitis B, a serious disease caused by the hepatitis B virus.

Description

The hepatitis B vaccine consists of a small protein from the surface of the hepatitis B virus called the hepatitis B surface antigen (HBsAg). After vaccination with HBV, the child's immune system recognizes HBsAg as foreign and produces antibodies that attach to the protein (anti-HBs). These specific antibodies remain in the blood. Later, if the child becomes infected with the hepatitis B virus, the antibodies recognize the protein and stimulate the immune system to produce large quantities of specific antibodies that attach to and destroy the virus and prevent the disease.

HBV is usually the first vaccine a child receives, most often before leaving the hospital after birth. The second and third HBV immunizations are administered by the age of 18 months, in conjunction with other routine childhood vaccinations.

Vaccine formulations

The HBsAg in HBVs is referred to as recombinant because it is genetically engineered. The gene encoding the DNA for HBsAg is introduced into common baker's yeast. The yeast is grown in vats in which large amounts of HBsAg are produced. The yeast cells are broken, and the HBsAg is isolated and purified. It is adsorbed into aluminum hydroxide.

Packaged hepatitis B vaccine contains the following:

• up to 95 percent HBsAg, with 10 to 40 micrograms of HBsAg per milliliter of vaccine
• no more than 5 percent yeast protein
• a small amount of aluminum hydroxide (0.5 mg/ml)
• very small amounts of other additives to stabilize and preserve the vaccine

Two HBVs are approved for use in the United States. Recombivax HB, manufactured by Merck & Company, is as of 2004 available as a pediatric/adolescent formulation (orange cap) and as an adult formulation (green cap). Engerix-B, made by SmithKline Beecham Biologicals, is as of 2004 available as a pediatric formulation (blue cap) and as an adult formulation (orange cap). In general these HBVs are interchangeable and either or both can be used in an individual immunization series. An HBV derived from the blood serum of people with hepatitis B was as of 2004 no longer produced in the United States.

Dosages

The immune response to HBV varies among individual children. Therefore, the HBV dose should be determined by a medical professional. In general, the recommended doses are as follows:

• Newborns: 2.5 to 20 micrograms injected into the anterolateral thigh muscle within seven days of birth or at the first visit to the physician's office, and one month and six months after the first dose, for a total of three doses.
• Newborns: 10 to 20 micrograms injected into the thigh muscle within seven days of birth and one month, two months, and 12 months after the first dose, for a total of four doses.
• Older child or adolescent: 2.5 to 20 micrograms injected into the deltoid arm muscle, with additional doses one month and six months after the first injection, for a total of three doses.

Safety

Although the vast majority of parents believe that vaccinations are important for their children, the majority of parents are also concerned about the safety of vaccines including HBV. Although controversy over the safety of HBV resulted in congressional hearings in 1999, the National Academy of Science's Institute of Medicine, as well as other authorities, considers HBV to be safe. Repeated studies have found no association between HBV and sudden infant death syndrome (SIDS) or other medical conditions, including neurological or immune system disorders.

Effectiveness

HBV usually is effective in protecting against hepatitis B. (HBV also protects against the related hepatitis D virus, which occurs as a co-infection with hepatitis B and usually results in more severe disease symptoms.) However, the immune response to HBV varies among children, apparently due to genetic variations in individual immune systems. In addition, the following medical conditions may cause children to benefit less from HBV:

• stomach pain
• cirrhosis (scarring) of the liver
• immune system impairment
• medical conditions requiring kidney dialysis

The duration of hepatitis B immunity following infant vaccination is not known. A 2004 study found that most low-risk children vaccinated at birth did not have antibodies against hepatitis B in their blood by the time they reached the age of five. Although the majority of these children responded positively to a booster HBV immunization, one-third of them did not respond. Likewise, a 2003 Israeli study found a steady decline in anti-hepatitis-B antibodies over time in children vaccinated as infants. The steepest decline in the antibodies occurred between five and eight years after vaccination.

General use

Hepatitis B in children

The U.S. Centers for Disease Control and Prevention (CDC) estimates that, prior to the launch of the infant HBV immunization program, about 33,000 American children of non-infected mothers acquired hepatitis B by the age of ten. Hepatitis B is a potentially serious disease caused by the hepatitis B virus. It may result in inflammation and damage to the liver. Hepatitis B infection may be without symptoms or with acute or short-lived symptoms that can include:

• jaundice (a yellowing of the skin and whites of the eyes)
• joint pain
• stomach pain
• itchy red hives on the skin

The hepatitis B virus is eventually cleared from the bodies of most infected adolescents and adults. Only about 2–6 percent of infected older children and adults develop chronic hepatitis B and can continue to transmit the virus to other people. By contrast 90 percent of infants and 30 percent of young children infected with hepatitis B develop chronic disease: the younger the child, the more likely that a hepatitis B infection will become chronic. The consequences of chronic hepatitis B infection may include:

• chronic liver disease
• cirrhosis
• liver cancer
• liver failure

There is no cure for hepatitis B and approximately one-fourth of chronic hepatitis B victims die of cirrhosis or liver cancer, including children who do not survive to young adulthood. Of the approximately 1.25 million Americans with chronic hepatitis B, 20–30 percent were infected as infants or children.

Risk of childhood infection

Those with the highest risk for infection are older adolescents and adults engaging in high-risk behaviors such as drug use and unprotected sex with multiple partners.

Far less common sources of childhood hepatitis B infection include:

• breast milk from an infected mother
• contact with blood, saliva, tears, or urine from an infected household member
• cuts
• blood transfusions

However, the following children are at particular risk for hepatitis B infection:

• children of immigrants and refugees or children adopted from regions where hepatitis B is endemic, including Asia, Sub-Saharan Africa, the Amazon Basin, Eastern Europe, and the Middle East
• Alaskan natives and Pacific Islanders
• children living in households with a chronically hepatitis-B-infected person
• children living in institutions
• children receiving hemodialysis
• children receiving certain blood products

Children born to infected mothers

Children of hepatitis B-infected mothers are at a 10–85 percent risk of becoming infected during birth. The CDC estimates that, prior to the infant HBV immunization program, about 12,000 American infants per year were infected by their mothers at birth. In addition, children of hepatitis B-infected mothers are at high risk of becoming infected before the age of five.

Children under the age of five who become infected with hepatitis B are at high risk for chronic infection and severe liver damage and disease later in life, even though initially they may have no symptoms. These infected children have a 90 percent risk of chronic hepatitis B infection and as many as 25 percent of them will die of chronic liver disease as adults. Mothers who have emigrated from countries with high rates of endemic hepatitis B are more likely to be infected.

Mothers with acute or chronic infectious hepatitis B can be identified by a blood test for HBsAg. Children born to mothers who have hepatitis B or whose hepatitis B status is unknown should receive their first HBV dose within 12 hours of birth. The second and third doses are given at two and six months of age. In many parts of the world, vaccine intervention before birth is required to prevent hepatitis B infection and its consequences in newborns.

It is recommended that newborns whose mothers are HBsAg-positive receive hepatitis B immune globulin (HBIG)—a preparation of serum containing high levels of antibodies to hepatitis B—as well as HBV within 12 hours of birth. About 70 percent of these newborns will be protected from chronic hepatitis B. A child's immune response to either hepatitis B infection or to HBV can be measured by a blood test for antibodies to HBsAg (anti-HBs). If a vaccinated child is exposed to hepatitis B, a measure of the anti-HBs in the blood will indicate whether another dose of HBV is required. Infants born to mothers who are HBsAg-positive should be tested for anti-HBs three to nine months following their last dose of vaccine. Their anti-HB levels should be at least 10 milli-international units per milliliter (mIU/ml), indicating that they are immune due to vaccination.

Mass immunization

HBV first became available in the United States in 1982. Between 1979 and 1989, the incidence of acute hepatitis B increased in the United States by 37 percent. There were 200,000–300,000 new infections annually between 1980 and 1991. In 1991 the CDC developed a strategy for eliminating the transmission of hepatitis B via universal childhood vaccination. The World Health Organization also declared the goal of immunizing all infants worldwide.

Nearly all states enacted laws requiring hepatitis B vaccination for enrollment in daycare, schools, and colleges. All these laws include exemptions for medical reasons and most include exemptions for religious reasons; however, only a few states allow exemptions from vaccination on philosophical grounds. Most states do not have laws mandating the screening of pregnant women for HBsAg.

By 2002, 90 percent of American children had been vaccinated against hepatitis B. The number of children carrying the virus was subsequently reduced substantially. Infant death from hepatitis B and the incidence of liver disease in children also decreased significantly. The CDC estimates that in 1998 the vaccine prevented 6,800 infections during birth and 18,700 infections in infants and children up to the age of nine. About 12,900 of these children would have developed chronic hepatitis and 3,000 of them eventually would have died of cirrhosis or liver cancer. The CDC expects the overall incidence of hepatitis B in the American population to fall throughout the early 2000s as a result of mass childhood vaccination. However, as of 2004, infants receiving HBV since 1991 had not yet reached the age when high-risk behaviors increase the likelihood of hepatitis B infection. In Pacific Island nations—where rates of hepatitis B infection are among the highest in the world—a regionally coordinated immunization program has significantly reduced the incidence of chronic infection.

Costs

HBV usually is covered by health insurance. In the United States the Vaccines for Children program covers the cost of hepatitis B vaccination for those without health insurance and for other specific groups of children, including Native Americans. The CDC estimates that infant hepatitis B vaccination saves fifty cents in direct medical costs for every dollar spent on HBV.

Precautions

Because most children are not at high risk for hepatitis B infection, and because the duration of immunity provided by HBV is not known, some parents and medical professionals question the need for and the effectiveness of childhood vaccination against hepatitis B. Some also continue to question the safety of the vaccine.

Children should not receive HBV if they are allergic to baker's yeast or thimerosal, are allergic to any other components in a combination vaccine, or have had a previous allergic reaction to HBV. A 2003 study found that HBV was safe and effective in children with asthma , even those on inhaled steroid therapy.

Side effects

Although most children experience no side effects from HBV, the most common side effects are as follows:

• fatigue or irritability in up to 20 percent of children
• soreness at the point of the injection, lasting one to two days, in about one out of eleven children and adolescents
• a mild to moderate fever in one out of 14 children and adolescents

Other less common side effects of HBV include:

• a purple spot, hard lump, redness, swelling, pain, or itching at the point of injection
• unusual tiredness or weakness
• dizziness
• fever of 100°F (37.7 °C) or higher
• headache

Other rare reactions to HBV include:

• general feeling of discomfort or illness
• aches or pain in joints or muscles
• skin rash or welts that may occur days or weeks after receiving the vaccine
• blurred vision or other vision changes
• muscle weakness or numbness or tingling in the arms and legs
• back pain or stiffness or pain in the neck or shoulder
• chills
• diarrhea or stomach cramps
• nausea or vomiting
• increased sweating
• sore throat or runny nose
• itching
• decreased or lost appetite
• sudden redness of the skin
• swelling of glands in the armpit or neck
• difficulty sleeping

Although allergic reactions to HBV are rare, if they occur emergency medical help should be sought immediately. Symptoms of an allergic reaction include:

• reddening of the skin, especially around the ears
• swelling of the eyes, face, or inside of the nose
• hives
• itching, especially of the feet or hands
• sudden and severe tiredness or weakness
• difficulty breathing or swallowing

Parental concerns

Preparing a child for an injection

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

• 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 and ask questions of the medical practitioner.

During the vaccination parents should take the following 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 using a hand puppet.
• Sing or tell the child a story.
• Have the child tell a story.
• Teach the child to focus on something other than the shot.
• Help the child take deep breaths.
• Allow the child to cry.
• Stay calm.

Comforting restraint

Parents may choose to use a comforting restraint method while their child is receiving an injection. These methods enable the parent to control and steady the child's arm while not holding the child down. With infants and toddlers, the following holds may be effective:

• 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 following positions may be effective:

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

After the injection

Following an injection parents should help in the following ways:

• Hold and caress a child or breastfeed an infant.
• Talk soothingly and reassuringly.
• Hug and praise the child for doing well.
• Review the information 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 following few days.
• In addition, parents should remember the following:
• The child may eat less during the first 24 hours following a vaccination.
• The child should drink plenty of fluids.
• The medical practitioner may suggest a non-aspirin pain reliever for the child.

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.

Blumberg, Baruch S. Hepatitis B: The Hunt for a Killer Virus. Princeton, NJ: Princeton University Press 2003.

Converse, Judy. When Your Doctor Is Wrong: Hepatitis B and Autism. Philadelphia, PA: Xlibris Corp., 2002.

Hepatitis B Vaccine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: Icon Group International, 2004.

PERIODICALS

Petersen, K. M., et al. "Duration of Hepatitis B Immunity in Low Risk Children Receiving Hepatitis B Vaccinations from Birth." The Pediatric Infectious Disease Journal 23 (July 2004): 650–5.

Shouval, D. "Hepatitis B Vaccines." Journal of Hepatology 39 Suppl. 1 (2003): S70–6.

ORGANIZATIONS

Immunization Action Coalition. 1573 Selby Ave., St. Paul, MN 55104. Web site: http://www.immunize.org.

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

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

WEB SITES

"Hepatitis B Facts: Testing and Vaccination." Immunization Action Coalition. Available online at http://www.immunize.org/catg.d/p2110.htm (accessed December 22, 2004).

Margaret Alic, Ph.D.