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

Hans D. Nothdurft; Jane Zuckerman; Michel Stoffel; Ilse Dieussaert; Pierre Van Damme

Disclosures

Introduction

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]

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.


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