Simplifying the Rabies Pre-exposure Vaccination

Summary

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.

Timeline

Start

2011-10

Primary completion

2016-01

Completion

2016-01

Outcome

Met primary endpoint

paper All subjects in both study groups possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose. PMID 29939243 ↗

Publications

• Results Soentjens P, Andries P, Aerssens A, Tsoumanis A, Ravinetto R, Heuninckx W, van Loen H, Brochier B, Van Gucht S, Van Damme P, Van Herrewege Y, Bottieau E. Preexposure Intradermal Rabies Vaccination: A Noninferiority Trial in Healthy Adults on Shortening the Vaccination Schedule From 28 to 7 Days. Clin Infect Dis. 2019 Feb 1;68(4):607-614. doi: 10.1093/cid/ciy513.

Drugs

Indications