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Hepatitis, Viral, Type A
Description
Hepatitis A is a viral infection of the liver caused
by hepatitis A virus (HAV). The clinical manifestations of HAV infection
range in clinical severity from no symptoms to 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.
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.
Risk for Travelers
The risk of 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 low-income 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 “standard” tourist itineraries,
accommodations, and food consumption behaviors.
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 <6 years old,
most (70%) infections are asymptomatic; if illness does occur it
is not usually last <2 months. There is no chronic or long-term
infection 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 >50 years of age.
Prevention
Hepatitis A is one of the most common vaccine-preventable diseases in
travelers. 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.
Vaccine and Immune Globulin
Two monovalent hepatitis A vaccines are currently
licensed in the United States for persons >2 years of age: HAVRIX,
manufactured by GlaxoSmithKline (Table 3–4),
and VAQTA (manufactured by Merck & Co., Inc.) (Table
3–5). 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.
Table 3–4.
Licensed schedule for HAVRIX*
| 2–18 |
720 |
0.5 mL |
2 |
0, 6 to 12TD>
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| 19 or older |
1,440 |
1.0 mL |
2 |
0, 6 to 12 |
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Table 3–5.
Licensed schedule for VAQTA*
| 2–18 |
25 units |
0.5 mL |
2 |
0, 6 to 18 |
| 19 or older |
50 units |
1.0 mL |
2 |
0, 6 to 12 |
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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 3–6). 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 adjuvant and 2-phenoxyethanol as a preservative.
Table 3–6.
Licensed schedule for TWINRIX*
| 18 years or older |
720 EL.U†/
20 µg |
1.0 mL |
3 |
0, 1, 6 months |
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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 a 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 lower
vaccine dosages are used. Travelers who need optimal protection earlier
than 4 weeks after the first dose of vaccine
should also receive immune globulin with the first vaccine dose (0.02
mL/kg), at a different injection site. Travelers who receive their
hepatitis A vaccine <2 weeks before traveling to an endemic area
and who do not receive immune globulin either by choice or because
of lack of availability need to realize that they are still at risk
of infection with Hepatitis A.
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 prior to travel. Such travelers may include those >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.
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 other commonly used vaccines
for travelers or as IG, at different injection sites.
In adults and children who have completed the vaccine
series, anti-HAV has been shown to persist for at least 5–8
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. Serologic testing to assess
antibody levels after vaccination is not indicated.
Travelers who are <2 years of age, 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
3–7). Anyone traveling for >3 months should receive
an IG dose of 0.06 mL/kg, which must be repeated if the duration
of travel is >5 months.
Table 3–7.
Immune globulin for protection
against viral Hepatitis A
| <3
months |
<50 |
<23 |
0.5 |
Dose
volume depends on body weight and length of stay. |
| 50–100 |
23–45 |
1.0 |
| >100 |
>45 |
2.0 |
| 3–5
months |
<22 |
<10 |
0.5 |
| 22–49 |
10–22 |
1.0 |
| 50–100 |
23–45 |
2.5 |
| >100 |
>45 |
5.0 |
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Adverse Reactions
Among adults, the most frequently reported side effects
occurring 3–5 days after a vaccine dose were tenderness or pain
at the injection site (53%–56%) or headache (14%–16%). Among
children, the most common side effects reported were 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.
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.
Precautions and Contraindications
These vaccines should not be administered to travelers
with a history of hypersensitivity to any vaccine component including
alum. 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.
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 resource-poor 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.
Treatment
No specific treatment is available for persons with
hepatitis A. Treatment is supportive.
— Miriam
Alter, Beth Bell, Anthony Fiore, Eric Mast, Linda Moyer
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