Accelerated Vaccination Schedules Provide Protection Against Hepatitis A and B
in Last-Minute Travelers

Posted 11/19/2004
Hans D. Nothdurft; Jane Zuckerman; Michel Stoffel; Ilse Dieussaert; Pierre Van
Damme


Hepatitis A and B are the most common vaccine-preventable diseases for
travelers; nevertheless, up to 50% of confirmed cases of hepatitis A and B in
Europe are still acquired during travel.[1] This reflects an increasing trend in
travel to endemic regions and illustrates that current immunization practices
are suboptimal. The number of last-minute travelers has grown in recent years; a
survey of 609 travelers in Europe found that 20% had planned their trip within
the last 2 weeks and more than one-third had not sought health advice.[2] Of
those who had consulted a travel clinic, over 40% had waited until 4 weeks prior
to departure before doing so.

A single dose of hepatitis A vaccine is sufficient to convey rapid immunity,
with nearly all subjects developing hepatitis A antibodies (anti-HAV) within 2
weeks.[3] However, a second dose of vaccine, given 6 or 12 to 18 months after
the first dose in accordance with the current recommended schedule, is required
for long-term protection. Although HAV vaccine can provide the rapid protection
required by last-minute travelers, this protection is not always provided by all
standard vaccination schedules. This has led to alternative schedules of
immunization being developed for this important group of travelers.

Accelerated vaccination schedules have been described for the monovalent
hepatitis B and combined hepatitis A and B vaccines, Engerix-B and Twinrix
(GlaxoSmithKline Biologicals, Rixensart, Belgium), respectively, offering rapid
and convenient immunization for the last-minute traveler.[4,5] The accelerated
vaccination schedule for monovalent hepatitis B vaccine, administered on days 0,
7 and 21, rapidly induces long-lasting (>12 months) hepatitis B antibodies
(anti-HBs) and high rates of seroprotection.[4]

Combined vaccines offer a number of advantages for last-minute travelers. The
combined hepatitis A and B vaccine is usually administered as three separate
doses over a 6-month period. A large randomized trial, conducted in 479 adults
(aged 18 to 45 years) recruited from travel clinics in the UK and Germany, found
that the combined vaccine can also be effectively administered within 3
weeks.[5] It compared the accelerated schedule of the combined vaccine with the
monovalent hepatitis A and B vaccines. Subjects received either the combined
hepatitis A and B vaccine, administered on days 0, 7 and 21, or the monovalent
hepatitis A vaccine, administered as a single dose on day 0 and the monovalent
hepatitis B vaccine, administered on days 0, 7 and 21. A booster dose of each
vaccine was given at month 12 to provide long-term protection.

Within 1 month of administration of the combined vaccine according to the
accelerated schedule, seroconversion rates of 100% were observed for anti-HAV
and seroprotection rates of 82% for anti-HB (Table 1.).[5] The rates at month 1
compared favorably with those observed in subjects receiving the monovalent
hepatitis A and B vaccines according to the accelerated schedule: 99% and 84%,
respectively (Table 1). At months 3 and 12, anti-HAV and anti-HB titers were
higher in subjects receiving the combined vaccine (Table 1). Following the
fourth dose (i.e., month 13), all subjects were seropositive for anti-HAV and
seroprotected against hepatitis B.

For hepatitis A, the differences between the groups (combined vs. monovalent)
for geometric mean concentrations (GMCs) are significant (Wilcoxon rank sum
test) at all time points, but for seroconversion rates, the groups were judged
to be equivalent. For hepatitis B, no significant differences were noted.

The accelerated schedule was well tolerated by all subjects, and there were no
apparent adverse effects related to receiving three doses in short
succession.[5] It should be noted that, prior to the fourth dose, subjects in
the combined vaccine group received three injections of hepatitis A and B
antigen, whereas those receiving the monovalent vaccines only received one
injection of hepatitis A antigen.

Comparison of these results with historical data from subjects treated with the
monovalent hepatitis A and B vaccines according to standard schedules showed
that, at month 1, seroprotection rates for anti-HBs of greater than 80% were
observed with the accelerated schedules compared with only 33% for the standard
schedule (Figure 1.)[6,7]


Figure 1. (click image to zoom) Anti-HB seroprotection rates among subjects
vaccinated with the combined hepatitis A and B vaccine (accelerated schedule) or
monovalent hepatitis A and hepatitis B vaccines (accelerated schedule), compared
with historical data for monovalent hepatitis A and hepatitis B vaccines
(standard schedule).


Therefore, the accelerated schedule provides earlier protection against
hepatitis B than the standard schedule.

Accelerated schedules of other monovalent hepatitis A and B vaccines have also
been studied. In one study, using GenHevac B from Pasteur, comparing accelerated
(days 0, 10 and 21) and standard (days 0, 28 and 56) schedules, seroprotection
rates of 70% and 92%, respectively, were observed 1 month after the third
dose.[8] Furthermore, seroconversion rates of 78% to 98% were reported 14 days
after a single dose of a different hepatitis A vaccine.[9]

In summary, efficient schedules exist for administration of monovalent and
combined hepatitis A and B vaccines to accommodate and so provide protection for
last-minute travelers visiting endemic areas. Travel health practitioners should
consider using the accelerated vaccination schedule for the combined hepatitis A
and B vaccine in travelers requiring protection against both diseases who
present as late as 3 to 4 weeks before departure. The vaccine manufacturers have
the accelerated schedules included in the package insert in all the member
states of the European Union and in a number of other countries (Canada,
Australia, New Zealand) but not yet in the US.

Travelers at high risk of acquiring hepatitis B who present more than 1 month in
advance of departure may also benefit from this schedule. Those presenting 1 or
2 weeks before departure can be effectively immunized against hepatitis A using
only the monovalent vaccine, but optimum hepatitis B immunity cannot be
provided. However, consideration should be given to starting vaccination to
provide some degree of protection.






Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




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