Simplifying the Rabies Pre-exposure Vaccination
Simplifying the Rabies Pre-exposure Vaccination
Rabies is a viral zoonosis that causes an encephalitis, almost invariably fatal. It is widely
 distributed across the globe: the World Health Organization (WHO) estimates that about 2,4
 billion people live in endemic areas for canine rabies. Vaccination of domestic animals is
 limited to industrialized and middle-income countries.

 The development of clinical rabies can be prevented through timely immunization after
 exposure: however, preventive vaccination simplifies the post-exposure procedure
 considerably, as immunoglobulins are no longer needed and less vaccine administrations are
 scheduled. Pre-exposure prophylaxis consists of an intramuscular (IM)of intradermal (ID) dose
 given on days 0, 7 and 21 or 28. The development of immunological memory after this
 vaccination is critical for the establishment of long lasting immunity. Subjects receiving a
 booster dose 1 year after pre-exposure prophylaxis segregate themselves into 'good' and
 'poor' responders; the former may not need further boosters for 10 years, whereas the latter
 may need more frequent boosters.

 Until recently, guidelines in travel medicine recommended pre-exposure vaccination only for
 some risk groups. Since recent studies have shown the effectiveness of the ID vaccination,
 the policies are changing towards pre-exposure vaccination for a larger population, including
 travelers to endemic regions, where immunoglobulins and vaccine are often not readily
 available.

 Based on the above, the investigators must stress the concept of "boostability" after a risk
 exposure. However, the current pre-exposure vaccination scheme could be improved: a schedule
 of 1 week would be less time consuming, would improve compliance and give less interference
 with other prophylaxis measures, e.g. mefloquine. Two small studies suggest that a schedule
 of 1 week interval is as effective and immunogenic as the standard one.

 The investigators will investigate whether the accelerated schedule is as effective as the
 classical schedule, by carrying out a randomized, non-inferiority study.
Rabies is a viral infection that affects the central nervous system and causes an
 encephalitis which is almost invariably fatal. Being a zoonosis, the infection usually occurs
 following a transdermal bite or scratch by an infected animal, but contamination may also
 occur when infectious material, usually saliva, comes into direct contact with the victim's
 mucosa or with fresh skin wounds. Human-to-human transmission is extremely uncommon.

 Rabies is widely distributed across the globe: the World Health Organization (WHO) estimates
 that 87 countries with a total population of about 2,4 billion people are afflicted with
 endemic canine rabies, and the inclusion of all species poses a potential threat to >3.3
 billion people. The number of rabid wild animals that die without being detected is however
 estimated to be more than 90% of the total, so identified infections represent only a small
 fraction of wild animal rabies cases. Vaccination of domestic animals is limited to
 industrialized nations, the most urbanized areas of Latin America and some Asian countries
 such as Thailand.

 The development of clinical rabies can be prevented through timely immunization after
 exposure to the infecting agent: preventive vaccination alone implies no complete protection,
 but it simplifies the post-exposure procedure considerably, as immunoglobulins are no longer
 needed and less vaccine administrations are scheduled. Pre-exposure prophylaxis consists of
 an intramuscular (IM)of intradermal (ID) dose given on days 0, 7 and 21 or 28. The
 development of immunological memory after this vaccination is therefore critical for the
 establishment of long lasting immunity against rabies in humans. If a booster dose is given 1
 year after pre-exposure prophylaxis, subjects segregate themselves into 'good' and 'poor'
 responders; the former group, who represent 75% of subjects, may not need further booster
 vaccination for 10 years, whereas the latter may need more frequent boosters.

 Until recently, guidelines in travel medicine recommended the pre-exposure vaccination only
 to the classic risk groups. Since recent studies have shown the effectiveness of the ID
 vaccination, the policies are changing towards the recommendation of pre-exposure vaccination
 for a larger population, including all travelers to endemic regions, where rabies
 immunoglobulins and vaccine are often not readily available. The ID pre-exposure vaccination,
 which is more cost-effective, could also become an affordable alternative to protect the
 local population in high endemic regions.

 Based on all the above, the investigators must stress the concept of "boostability" after a
 risk exposure: the main target of travel medicine today is to get a sufficient serological
 response on day 7 after a risk in prevaccinated persons (accelerated immune response through
 memory cells) and after two post-exposure vaccinations (day 0 and 3). It should also be noted
 that a schedule of 1 week would be preferable to the current schedule, because it would be
 less time consuming, would improve compliance and gives less interference with the intake of
 other prophylaxis measures, e.g. mefloquine. Two recent but small studies from Thailand
 suggest that an accelerated schedule of three intradermal injections within 1 week interval
 is as effective and immunogenic as administered within 4 weeks.

 Therefore, this randomized, non-inferiority study will investigate whether the accelerated
 schedule is as effective as the classical schedule. The investigators will also increase the
 number of sites of injection, from one to two, to stimulate several different groups of lymph
 nodes on the same time to initiate more antibody production.
Inclusion Criteria:

 -  Willingness to provide written consent

 -  Seronegative for rabies

 -  Belgian soldiers who are deployable and visit the Travel clinic in Brussels during
 their preparation phase before deployment OR military students at the schools of
 Belgian Defense are eligible in preparation of an overseas exercise or during the
 scheduled vaccination program at the end of their studies

 -  Prepared to follow the study schedule

 Exclusion Criteria:

 -  Subjects who have had rabies vaccination (complete or incomplete) in the past due to
 post-exposure prophylaxis.

 -  Subjects with a known allergy to one of the components of the vaccine.

 -  Immune depressed persons or intake of immunodepressant medication.

 -  Subjects who take mefloquine

 -  Planned deployment to overseas areas within 35 days.