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.