Description
Hepatitis A is a viral infection of the liver caused by hepatitis A virus (HAV).
HAV infection may be asymptomatic or its clinical manifestations may range in
severity from a mild illness lasting 1-2 weeks to a severely disabling disease
lasting several months. Clinical manifestations of hepatitis A often include fever,
malaise, anorexia, nausea, and abdominal discomfort, followed within a few days by jaundice (1).
Occurrence
HAV is shed in the feces of persons with HAV infection. Transmission can occur
through direct person-to-person contact; through exposure to contaminated water,
ice, or shellfish harvested from sewage-contaminated water; or from fruits,
vegetables, or other foods that are eaten uncooked and that were contaminated
during harvesting or subsequent handling.
HAV infection is common (high or intermediate endemicity) throughout the developing
world, where infections most frequently are acquired during early childhood and
usually are asymptomatic or mild. In developed countries, HAV infection is less
common (low endemicity), but communitywide outbreaks still occur in some areas of
the United States. Map 4-3 indicates the seroprevalence of antibody to HAV
(total anti-HAV) as measured in selected cross-sectional studies among each
country's residents. The seroprevalence of anti-HAV provides an estimate of
the endemicity of HAV infections, including asymptomatic infections, within
a population (2).
MAP 4-03 Prevalence of antibody to hepatitis A virus, by country, 2006.
Risk for Travelers
Hepatitis A is one of the most common vaccine-preventable infections acquired
during travel (3,4). The number of cases associated with travel, as well as the
overall incidence, has decreased in recent years, according to notifiable disease
data in the United States and Europe (3,5). However, the proportion of overall
cases attributed to travel has increased in the United States. Among reported
cases in persons younger than 15 years old, 40% were associated with travel (5).
The risk for acquiring HAV infection for U.S. residents traveling abroad varies
with living conditions, length of stay, and the incidence of HAV infection in the
area visited. Travelers to North America (except Mexico), Japan, Australia,
New Zealand, and developed countries in Europe are at no greater risk for infection
than in the United States. For travelers to other countries, risk for infection
increases with duration of travel and is highest for those who live in or visit
rural areas, trek in back-country areas, or frequently eat or drink in settings
of poor sanitation. Nevertheless, many cases of travel-related hepatitis A occur
in travelers to developing countries with "tourist" itineraries,
accommodations, and food consumption behaviors (2).
Clinical Presentation
The incubation period for hepatitis A averages 28 days (range 15-50 days).
Hepatitis A typically has an abrupt onset of symptoms that can include fever,
malaise, anorexia, nausea, abdominal discomfort, dark urine, and jaundice.
The likelihood of having symptoms with HAV infection is related to the infected
person's age. In children younger than 6 years old, most (70%) infections are
asymptomatic; if illness does occur, its duration is usually less than 2 months.
No chronic or long-term infection is associated with hepatitis A, but 10% of
infected persons will have prolonged or relapsing symptoms over a 6- to 9-month
period. The overall case-fatality rate among cases reported to CDC is 0.3%;
however, the rate is 1.8% among adults older than 50 years of age (1).
Prevention
Hepatitis A vaccine, immune globulin (IG), or both, are recommended for all
susceptible persons traveling to or working in countries with an intermediate
or high endemicity of HAV infection. Health-care providers should administer
hepatitis A vaccination for persons traveling for any purpose, frequency or
duration to countries that have high or intermediate endemicity of HAV infection
(1). In addition, health-care providers should be alert to opportunities to provide
vaccination for all travelers whose plans might include travel at some time in the
future to an area of high or intermediate endemicity, including those whose current
medical evaluation is for travel to an area where hepatitis A vaccination is not
currently recommended.
VACCINE AND IMMUNE GLOBULIN
Two monovalent hepatitis A vaccines are currently licensed in the United States
for persons at least 12 months of age: HAVRIX, manufactured by GlaxoSmithKline
(Table 4-3), and VAQTA (manufactured by Merck & Co., Inc.) (Table 4-4).
Both vaccines are made of inactivated hepatitis A virus adsorbed to aluminum
hydroxide as an adjuvant. HAVRIX is prepared with 2-phenoxyethanol as a preservative,
while VAQTA is formulated without a preservative. All hepatitis A vaccines should be
administered intramuscularly in the deltoid muscle (1).
TWINRIX, manufactured by GlaxoSmithKline, is a combined hepatitis A and hepatitis B
vaccine licensed for persons >18 years of age, containing 720 EL.U. of hepatitis A
antigen (50% of the HAVRIX adult dose) and 20 µg of recombinant hepatitis B surface
antigen protein (the same as the ENGERIX-B adult dose) (Table 4-5). Primary immunization
consists of three doses, given on a 0-, 1-, and 6-month schedule, the same schedule as
that commonly used for monovalent hepatitis B vaccine. TWINRIX contains aluminum phosphate
and aluminum hydroxide as adjuvants and 2-phenoxyethanol as a preservative. An accelerated
schedule of Twinrix (i.e., doses at days 0, 7, and 21) for travelers has been approved by
the FDA. A booster dose should be given at 1 year.
The first dose of hepatitis A vaccine should be administered as soon as travel to countries
with high or intermediate endemicity is considered. One month after receiving the first dose
of monovalent hepatitis A vaccine, 94%-100% of adults and children will have protective concentrations
of antibody. The final dose in the hepatitis A vaccine series is necessary to promote
long-term protection. The immunogenicity of TWINRIX is equivalent to that of the monovalent
hepatitis vaccines when tested after completion of the licensed schedule.
Many persons will have detectable antibody to hepatitis A virus (anti-HAV) response
to the monovalent vaccine by 2 weeks after the first vaccine dose. The proportion
of persons who develop a detectable antibody response at 2 weeks may be lower when
smaller vaccine dosages are used, such as with the use of TWINRIX. Travelers who
receive hepatitis A vaccine less than 2 weeks before traveling to an endemic area
and who do not receive immune globulin (either by choice or because of lack of
availability) likely will be at lower risk of infection than those who do not
receive hepatitis A vaccine or IG. In the case of travel within 4 weeks of vaccine
administration, a dose of immune globulin (0.02 mL/kg) may be given alone or in
addition to hepatitis A vaccine, at a different site, for optimal protection.
In the case of unavailability or refusal of immune globulin, administration of
hepatitis A vaccine alone for this group is recommended, but they should be informed
that they are not optimally protected from acquiring hepatitis A in the immediate
future (i.e., the subsequent 2-4 weeks) (1,2).
Although vaccination of an immune traveler is not contraindicated and does not
increase the risk of adverse effects, screening for total anti-HAV before travel
can be useful in some circumstances to determine susceptibility and eliminate
unnecessary vaccination or IG prophylaxis of immune travelers. Such serologic
screening for susceptibility might be indicated for adult travelers who are
likely to have had prior HAV infection if the cost of screening (laboratory and office visit)
is less than the cost of vaccination or IG prophylaxis and if testing will not
delay vaccination and interfere with timely receipt of vaccine or IG before travel.
Such travelers may include those older than 40 years of age and those born in areas
of the world with intermediate or high endemicity. Postvaccination testing for
serologic response is not indicated (1).
Using the vaccines according to the licensed schedules is preferable. However,
an interrupted series does not need to be restarted. Given their similar immunogenicity,
a series that has been started with one brand of monovalent vaccine (i.e., HAVRIX or VAQTA)
may be completed with the other brand. Hepatitis A vaccine may be administered at
the same time as IG or other commonly used vaccines for travelers, at different
injection sites (1,2).
In adults and children who have completed the vaccine series, anti-HAV has been shown
to persist for at least 5-12 years after vaccination. Results of mathematical models
indicate that after completion of the vaccination series, anti-HAV will likely persist
for 20 years or more. For children and adults who complete the primary series, booster
doses of vaccine are not recommended (6). Serologic testing to assess antibody
levels after vaccination is not indicated.
Travelers who are younger than 12 months of age, are allergic to a vaccine component,
or otherwise elect not to receive vaccine should receive a single dose of IG (0.02 mL/kg),
which provides effective protection against HAV infection for up to 3 months (Table 4-6).
Those who do not receive vaccination and plan to travel for longer than 3 months should
receive an IG dose of 0.06 mL/kg, which must be repeated if the duration of travel is
longer than 5 months (1,7).
Adverse Reactions
Among adults, the most frequently reported side effects occurring 3-5 days after
a vaccine dose are tenderness or pain at the injection site (53%-56%) or headache
(14%-16%). Among children, the most common side effects reported are pain or
tenderness at the injection site (15%-19%), feeding problems (8% in one study),
or headache (4% in one study). No serious adverse events in children or adults
that could be definitively attributed to the vaccine or increases in serious
adverse events among vaccinated persons compared with baseline rates have been identified (1).
Immune globulin for intramuscular administration prepared in the United States
has few side effects (primarily soreness at the injection site) and has never
been shown to transmit infectious agents (hepatitis B virus, hepatitis C virus
[HCV], or HIV). Since December 1994, all IG products commercially available in
the United States have had to undergo a viral inactivation procedure or be
negative for HCV RNA before release (1).
Precautions and Contraindications
These vaccines should not be administered to travelers with a history of
hypersensitivity to any vaccine component. HAVRIX or TWINRIX should not be
administered to travelers with a history of hypersensitivity reactions to the
preservative 2-phenoxyethanol. TWINRIX should not be administered to persons
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 need to be taken for vaccination of immunocompromised travelers (1).
Pregnancy
The safety of hepatitis A vaccine for pregnant women has not been determined.
However, because hepatitis A vaccine is produced from inactivated HAV, the
theoretical risk to either the pregnant woman or the developing fetus is thought
to be very low. The risk of vaccination should be weighed against the risk of
hepatitis A in women travelers who might be at high risk for exposure to HAV.
Pregnancy is not a contraindication to using IG.>
OTHER PREVENTION TIPS
Boiling or cooking food and beverage items for at least 1 minute to 185°F (85°C)
inactivates HAV. Foods and beverages heated to this temperature and for this
length of time cannot serve as vehicles for HAV infection unless they become
contaminated after heating. Adequate chlorination of water as recommended in
the United States will inactivate HAV. Travelers should be advised that,
to minimize their risk of hepatitis A and other enteric diseases in developing countries,
they should avoid potentially contaminated water or food. Travelers should also be
advised to avoid drinking beverages (with or without ice) of unknown purity,
eating uncooked shellfish, and eating uncooked fruits or vegetables that are
not peeled or prepared by the traveler personally (see Chapter 2) (8).
TABLE 4-03. Licensed schedule for HAVRIX1
AGE GROUP
(YRS) DOSE
(EL.U.)2 VOLUME NO. OF
DOSES SCHEDULE
(MONTHS)
1-18 720 0.5 mL 2 0, 6 to 12
=19 1,440 1.0 mL 2 0, 6 to 12
1Hepatitis A vaccine, inactivated, GlaxoSmithKline
2EL.U. = enzyme-linked immunosorbent assay (ELISA) units
TABLE 4-04. Licensed schedule for VAQTA1
AGE GROUP
(YRS) DOSE
(EL.U.)2 VOLUME NO. OF
DOSES SCHEDULE
(MONTHS)
1-18 25 units 0.5 mL 2 0, 6 to 18
=19 50 units 1.0 mL 2 0, 6 to 18
1Hepatitis A vaccine, inactivated, Merck & Co., Inc.
TABLE 4-05. Licensed schedule for TWINRIX1
AGE GROUP
(YRS) DOSE
(EL.U.)2 VOLUME NO. OF
DOSES SCHEDULE
(MONTHS)
=18 720 EL.U2 / 20 µg 1.0 mL 3 0, 1, 6 months
=18 720 EL.U2 / 20 µg 1.0 mL 4 0, 7, 21 days
+ 1 year
1Combined hepatitis A and hepatitis B vaccine, GlaxoSmithKline
2 EL.U. = enzyme-linked immunosorbent assay (ELISA) units
TABLE 4-06. Recommended doses of immune globulin (IG) for protection against Hepatitis A
SETTING DURATION OF
COVERAGE DOSE (mL/kg)*
Pre - exposure Short-term (1-2 mos)
Long-term (3-5 mos) 0.02
0.06
Postexposure --- 0.02
*IG should be administered by intramuscular injection into either the deltoid or
gluteal muscle. For children aged (12 months, IG can be administered in the anterolateral thigh muscle.
Repeat every 5 months if continued exposure to hepatitis A virus occurs.)
Treatment
No specific treatment is available for persons with hepatitis A. Treatment is supportive.
References
CDC. Prevention of hepatitis A through active or passive immunization:
recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR Morbid Mortal Wkly Rep. 2006; RR 55:1-23.
Bell BP, Feinstone SM. Hepatitis A vaccine. In: Plotkin SA, Orenstein WA, editors.
Vaccines. 4th edition. Philadelphia: W.B. Saunders, 2004.
Mutsch M, Spicher VM, Gut C, Steffen R. Hepatitis A virus infections in travelers, 1988-2004.
Clin Infect Dis. 2006;42:490-7.Bacaner N, Stauffer B, Boulware DR, Walker PF, Keystone JS.
Travel medicine considerations for North American immigrants visiting friends and relatives.
JAMA. 2004;291:2856-64.
CDC. Hepatitis Surveillance Report No. 61. 2005.
Atlanta: U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. 2006.
van Damme P, Banatvala J, Fay O, Iwarson S, McMahon B, Van Herck K, et al.
Hepatitis A booster vaccination: is there a need? Lancet. 2003;362:1065-71.
Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin Infect Dis. 1992;14:580-6.
Fiore AE. Hepatitis A transmitted by food. Clin Infect Dis. 2004;38:705-15.
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