Hepatitis A vaccine in the last-minute traveler

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Current recommendations state that travelers should receive hepatitis A vaccine 2 to 4 weeks before departure. Such recommendations, however, may dissuade last-minute travelers from receiving the vaccine. A preponderance of evidence exists to support hepatitis A vaccination of the imminent-departure traveler and therefore suggests that these guidelines merit reconsideration. In examining this issue, one of the most important elements to determine is the amount of time required for seroconversion following vaccination. Clinical trials of hepatitis A vaccines measured antibody response at 2 and 4 weeks after vaccination. However, studies investigating early seroconversion found that the vast majority of vaccinees develop antibodies within 2 weeks of vaccination, some as early as 12 days after vaccination. This is relevant information, given that the hepatitis A virus has an average incubation period of 28 days. Seroconversion is predicated on achieving a “protective” antibody level. However, levels of antibody considered protective remain debatable. Evidence suggests that clinical disease does not occur at antibody levels lower than those currently accepted as protective. Furthermore, hepatitis A vaccine has been proved effective in controlling outbreaks worldwide. Research data show that a single dose of vaccine can halt outbreaks if an adequate number of susceptible individuals are vaccinated. Information from rapid-outbreak control studies and those assessing postexposure administration of hepatitis A vaccine suggest that late vaccination provides a significant degree of protection. For these reasons, hepatitis A vaccine may be administered at any time before departure because it will still provide travelers with protection.

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Early seroconversion rates after vaccination

Hepatitis A vaccines provide high immunogenicity. Antibodies to HAV (anti-HAV), including neutralizing antibody, rapidly develop within 2 weeks after 1 dose of vaccine. Protection due to vaccination relates to the presence of antibody; postvaccination protection has been associated with the onset of seroconversion and an anamnestic antibody response after a booster dose.8, 9, 10

The 2-week pretravel vaccination recommendation advocated by authorities is based on results of clinical trials that

“Protective” antibody levels reexamined

Natural immunity to HAV is a complex process; several distinct arms of the immune system are operative, including natural killer cells, human leukocyte antigen-restricted cytotoxic T cells, and B-cell antibody.16 On the basis of vast experience with immunoglobulin in protecting against HAV infection, antibody alone is known to provide high-level protection against clinical disease. However, the precise levels of antibody considered protective remain debatable.

Seroconversion is predicated on

Postexposure protection in outbreak studies and controlled trials

Although clinical disease with HAV has been seen as early as 15 days and as late as 50 days after exposure, the average incubation period for natural or experimental infection is 28 days.17, 18 An efficacy trial of a hepatitis A vaccine (Vaqta 25 U) was conducted in a high-risk closed religious community in upstate New York that had experienced annual outbreaks of hepatitis A.19 At the beginning of an outbreak, 519 children received the vaccine and 518 received placebo. Before day 21, 3 cases

Summary

On the basis of current knowledge of hepatitis A antibody kinetics in response to vaccine, the natural incubation period of HAV infection, and postexposure prophylaxis data from outbreak control and animal studies, the current recommendations on timing of hepatitis A vaccine administration clearly require reconsideration.

Theoretically, if an individual were immunized on the way to the airport, arrived at the destination, and were then exposed to HAV during the first meal of the ensuing trip,

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