Hepatitis A primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [3], Seyedmahdi Pahlavani, M.D. [4]

Overview

Two products are available for the prevention of HAV infection: hepatitis A vaccine and immune globulin (IG) for intramuscular (IM) administration. Administered IM in a 2-dose series at 0 and 6--12 months, these vaccines induce protective antibody levels in virtually all adults. By 1 month after the first dose, 94%--100% of adults have protective antibody levels; 100% of adults develop protective antibody after a second dose. IG is a sterile solution of concentrated immunoglobulins which, when administered IM before or within 2 weeks after exposure to HAV, is >85% effective in preventing HAV infections. Vaccination is the most effective means of preventing HAV transmission among persons at risk for infection (e.g., MSM, illegal drug users, and persons with chronic liver disease). Because transmission of HAV during sexual activity probably results from fecal-oral contact, measures typically used to prevent the transmission of other sexually transmitted disease (e.g., use of condoms) do not prevent HAV transmission.

Primary Prevention

Hepatitis A Vaccine

Inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials and in nonhuman primate models of HAV infection; however, only vaccines made from inactivated HAV have been evaluated for efficacy in controlled clinical trials. The vaccines containing HAV antigen that are currently licensed in the United States are the single-antigen vaccines HAVRIX® (manufactured by GlaxoSmithKline, Rixensart, Belgium) and VAQTA® (manufactured by Merck & Co., Inc., Whitehouse Station, New Jersey) and the combination vaccine TWINRIX® (containing both HAV and HBV antigens; manufactured by GlaxoSmithKline). All are inactivated vaccines.

The Hepatitis A vaccine, Avaxim, protects against the virus in more than 95% of cases and provides protection from the virus for ten years. The vaccine contains inactivated Hepatitis A virus providing active immunity against a future infection.

A recent review by an expert panel, which evaluated the projected duration of immunity from vaccination, concluded that protective levels of antibody to HAV could be present for at least 25 years in adults and at least 14–20 years in children.

Other vaccines such as Hepatitis B, diphtheria, poliovirus (oral and inactivated), tetanus, oral typhoid, cholera, Japanese encephalitis, rabies, and yellow fever vaccines and immune globulin can be given at the same time that Hepatitis A vaccine is given, but at a different injection site.

If the second dose of Hepatitis A vaccine is delayed, it should be administered as soon as possible. The first dose does not need to be readministered.

The safety of Hepatitis A vaccination during pregnancy has not been determined; however, because the vaccine is produced from inactivated HAV, the theoretical risk to the developing fetus is expected to be low. The risk associated with vaccination, however, should be weighed against the risk for Hepatitis A in women who might be at high risk for exposure to HAV.

These vaccines should not be administered to travelers with a history of hypersensitivity to any vaccine component. TWINRIX® should not be administered to people with a history of hypersensitivity to yeast. Because hepatitis A vaccine consists of inactivated virus, and hepatitis B vaccine consists of a recombinant protein, no special precautions are needed for vaccination of immunocompromised travelers.

Dosages and Schedules for Hepatitis A Vaccines

Licensed Dosages and Schedules for HAVRIX®

Age	Dose (ELISA units)	Volume (mL)	No. of doses	Schedule (months)
12 months–18 yrs	720	0.5	2	0,6-12
≥19 years	1,440	1.0	2	0,6-12

Licensed Dosages and Schedules for VAQTA

Age	Dose (U.)	Volume (mL)	No. of doses	Schedule (months)
12 months–18 yrs	25	0.5	2	0,6-18
≥19 years	50	1.0	2	0,6-18

Licensed Dosages and Schedules for TWINRIX®

Age	Dose (ELISA units)	Volume (mL)	No. of doses	Schedule
≥ 18 yrs	720	1.0	3	0, 1, 6 months
≥ 18 yrs	720	1.0	4	0, 7, 21–30 days + 12 months

Immune Globulin (IG)

IG is a sterile solution of concentrated immunoglobulins prepared from pooled human plasma processed by cold ethanol fractionation. In the United States, IG is produced only from plasma that has tested negative for hepatitis B surface antigen, antibodies to HIV and HCV, and HCV RNA. In addition, the process used to manufacture IG inactivates viruses (e.g., HBV, HCV, and HIV). When administered IM before or within 2 weeks after exposure to HAV, IG is >85% effective in preventing HAV infections.

Pre-Exposure Vaccination

Hepatitis A vaccination is recommended for all children at age 1 year, for persons who are at increased risk for infection, for persons who are at increased risk for complications from Hepatitis A, and for any person wishing to obtain immunity.

Groups who Need Hepatitis A Vaccination

• All Children at Age 1 year (i.e., 12–23 months). Children who have not been vaccinated by age 2 can be vaccinated at subsequent visits.

• Children and Adolescents Ages 2–18 Who Live in States or Communities where Routine Hepatitis A Vaccination has been Implemented because of High Disease Incidence. Before 2006, when Hepatitis A vaccination was first recommended for all children at age 1 year, vaccination had been targeted to children living in states or communities that had historically high rates of Hepatitis A. States, counties, and communities with existing Hepatitis A vaccination programs for children aged 2–18 years are encouraged to maintain these programs. In those communities, new efforts focused on routine vaccination of children at age 1 year should enhance, not replace, ongoing programs directed at a broader population of children.

• Persons Traveling to or Working in Countries that have High or Intermediate Rates of Hepatitis A. Persons from developed countries who travel to developing countries are at high risk for Hepatitis A. The risk for Hepatitis A exists even for travelers to urban areas, those who stay in luxury hotels, and those who report that they have good hygiene and that they are careful about what they drink and eat (see Hepatitis A and International Travel for more information).

• Men who have Sex with Men. Sexually active men (both adolescents and adults) who have sex with men should be vaccinated. Hepatitis A outbreaks among men who have sex with men have been reported frequently. Recent outbreaks have occurred in urban areas in the United States, Canada, and Australia.

• Users of Illegal Injection and Noninjection Drugs. During the past two decades, outbreaks of Hepatitis A have been reported with increasing frequency among users of both injection and noninjection drugs (e.g., methamphetamine) in North America, Europe, and Australia.

• Persons who have Occupational Risk for Infection. Persons who work with HAV-infected primates or with HAV in a research laboratory setting should be vaccinated. No other groups have been shown to be at increased risk for HAV infection because of occupational exposure.

• Persons who have Chronic Liver Disease. Persons with chronic liver disease who have never had Hepatitis A should be vaccinated, as they have a higher rate of fulminant Hepatitis A (i.e., rapid onset of liver failure, often leading to death). Persons who are either awaiting or have received liver transplants also should be vaccinated.

• Persons who have Clotting-Factor Disorders. Persons who have never had Hepatitis A and who are administered clotting-factor concentrates, especially solvent detergent-treated preparations, should be vaccinated.

Groups that do NOT Need Routine Vaccination Against Hepatitis A

• Food Service Workers. Foodborne Hepatitis A outbreaks are relatively uncommon in the United States; however, when they occur, intensive public health efforts are required for their control.

Although persons who work as food handlers have a critical role in common-source foodborne outbreaks, they are not at increased risk for Hepatitis A because of their occupation. Consideration may be given to vaccination of employees who work in areas where community-wide outbreaks are occurring and where state and local health authorities or private employers determine that such vaccination is cost-effective.

• Sewage Workers. In the United States, no work-related outbreaks of Hepatitis A have been reported among workers exposed to sewage.

• Health Care Workers. Health care workers are not at increased risk for Hepatitis A. If a patient with Hepatitis A is admitted to the hospital, routine infection-control precautions will prevent transmission to hospital staff.

• Children Under 12 Months of Age. Because of the limited experience with Hepatitis A vaccination among children in this age group, the vaccine is not currently licensed for children age <12 months.

• Child Care Center Attendees. The frequency of outbreaks of Hepatitis A is not high enough in this setting to warrant routine Hepatitis A vaccination. In some communities, however, child care centers play a role in sustaining community-wide outbreaks. In this situation, consideration should be given to adding Hepatitis A vaccine to the prevention plan for unvaccinated children and staff in the involved center(s).

• Residents of Institutions for Developmentally Disabled Persons. Historically, Hepatitis A virus infections were common among persons with developmental disabilities living in institutions. The occurrence of HAV infection has diminished, and routine vaccination against Hepatitis A is no longer recommended for this population.

Hepatitis A and International Travel

All susceptible persons traveling to or working in countries that have high or intermediate rates of Hepatitis A should be vaccinated or receive immune globulin (IG) before traveling. Persons from developed countries who travel to developing countries are at high risk for Hepatitis A. The risk for Hepatitis A exists even for travelers to urban areas, those who stay in luxury hotels, and those who report that they have good hygiene and that they are careful about what they drink and eat.

The first dose of Hepatitis A vaccine should be administered as soon as travel is considered.

• Previously, Hepatitis A vaccination was recommended to be administered at least 2–4 weeks before departure to an area with intermediate or high rates of Hepatitis A. Travelers who were departing in less than 2 weeks were recommended to receive IG for short-term protection.

• However, on the basis of data indicating that immune globulin and vaccine have equivalent postexposure efficacy among healthy persons aged 1–40 years, the Advisory Committee on Immunization Practices (ACIP) has amended its guidelines for Hepatitis A vaccination for travelers. ACIP now recommends that one dose of single-antigen Hepatitis A vaccine administered at any time before departure may provide adequate protection for most healthy persons.

• For optimal protection, older adults, immunocompromised persons, and persons with chronic liver disease or other chronic medical conditions who are planning to depart in <2 weeks should receive the initial dose of vaccine and also can simultaneously be administered IG (0.02 mL/kg) at a separate anatomic injection site.

Travelers who are allergic to a vaccine component or who elect not to receive vaccine should receive a single dose of immune globulin (0.02 mL/kg), which provides effective protection against Hepatitis A virus infection for up to 3 months. Travelers whose travel period exceeds 2 months should be administered immune globulin at 0.06 mL/kg; administration must be repeated if the travel period exceeds 5 months.

For travelers less than 12 months of age, immune globulin is recommended because Hepatitis A vaccine is currently not licensed for use in this age group.

Pre-Vaccination Serologic Testing

• Approximately one third of the U.S. population has serologic evidence of previous HAV infection, which increases with age and reaches 75% among persons aged more than 70 years. Screening for HAV infection might be cost-effective in populations where the prevalence of infection is likely to be high (e.g., persons aged more than 40 years and persons born in areas of high HAV endemicity).
• The potential cost-savings of testing should be weighed against the cost and the likelihood that testing will interfere with initiating vaccination.
• Vaccination of a person who is already immune is not harmful.

Prevaccination testing is recommended only in specific circumstances to reduce the costs of vaccinating people who are already immune to Hepatitis A, including:

• Persons who were born in geographic areas with high or intermediate prevalence of HAV infection
• Older adolescents and adults in certain population groups (i.e., American Indians, Alaska Natives, and Hispanics)
• Adults in groups that have a high prevalence of infection (e.g., injection drug users)

Prevaccination testing might also be warranted for all older adults. The decision to test should be based on:

• The expected prevalence of immunity
• The cost of vaccination compared with the cost of serologic testing
• The likelihood that testing will not interfere with initiation of vaccination

Post-Vaccination Serologic Testing

Postvaccination serologic testing is not indicated because most persons respond to the vaccine. In addition, the commercially available serologic test is not sensitive enough to detect the low, but protective, levels of antibody produced by vaccination.

Hygiene and Sanitation

Hepatitis A might be prevented by good hygiene and sanitation; however, it was reported that efforts to promote good personal hygiene have not been successful in interrupting outbreaks of hepatitis A.

Suggested measures that might prevent hepatitis A include using your own towels and toothbrushes, eating utensils, and other personal products, always washing your hands after and before eating and more importantly after using the toilet.

Risk for travellers

Non-immune travellers to developing countries are at significant risk of infection, particularly in settings with poor food and drinking-water control and poor sanitation People born and raised in developing countries, and those born before 1945 in industrialized countries, have usually been infected with HAV in childhood and are likely to be immune.

Precautions

Avoid or boil potentially contaminated food and water. Short-term protection through injection of human immune globulin is gradually being replaced by hepatitis A vaccination.

Vaccine

Two types of hepatitis A vaccines are currently used worldwide, namely formaldehyde-inactivated vaccines and live attenuated vaccines. Both types are safe and highly immunogenic and provide long-lasting, possibly life-long, protection against hepatitis A in both children and adults.

• Formaldehyde-inactivated vaccines: Inactivated hepatitis A virus vaccines are used in most countries. Monovalent inactivated vaccines are available in both paediatric dose (0.5 ml) for children aged 1 year to 15 years and adult dose (1 ml). Traditionally, a two-dose schedule is recommended, particularly for immunocompromised individuals. However, in healthy individuals, comparable effectiveness has been achieved with a single dose. A combined hepatitis A/typhoid (ViCPS) vaccine, administered as a single dose, confers high levels of protection against both these waterborne diseases. A combination vaccine that provides protection against both hepatitis A and hepatitis B should be considered for travellers who may be exposed to both organisms.
• Live attenuated vaccines (based on the H2 or LA-1 strain of HAV): These vaccines are manufactured in China and available in several other countries. Presence of anti-HAV (IgG) antibodies was documented after 15 years in 72% to 88% of the vaccinees, implying that, in most cases, long-term protection against hepatitis A is achieved with live attenuated vaccines.

Summary of vaccine data

	Considerations
Type of vaccine	Inactivated hepatitis A virus vaccines are licensed for intramuscular administration in a two-dose series.
	The live attenuated vaccine is administered as a single subcutaneous dose.
Number of doses	Minimum age is 1 year for both inactivated and live attenuated hepatitis A virus vaccines. Inactivated vaccine: a complete vaccination schedule as recommended by the manufacturer consists of 2 doses. The interval between the first (primary) dose and the second (booster) dose is flexible (from 6 months up to 4–5 years), but is usually 6–18 months. In healthy individuals, a single dose seems to be similarly efficacious and only one dose is recommended for long-term protection. Live vaccine: one dose.
Boosters	Not necessary.
Contraindications	Severe allergic reaction to previous dose.
Adverse reactions	Inactivated vaccine: mild local reaction of short duration, mild systemic reaction. Live vaccine: few reported.
Before departure	Inactivated and live vaccines: protection is achieved within 2–4 weeks after first dose. Given the long incubation period of hepatitis A (average 2–4 weeks), the vaccine can be administered up to the day of departure and still protect travellers.
Indication	Hepatitis A vaccination should be considered for individuals aged ≥1 year who are travelling to countries or areas of intermediate or high endemicity. Those at high risk of acquiring severe disease, such as immunosuppressed patients and patients with chronic liver disease, should be strongly encouraged to be vaccinated regardless of where they travel. In addition, people at increased risk of hepatitis A including men who have sex with men, those requiring life-long treatment with blood products, and people who inject drugs should be vaccinated.
Special precautions	None.