Rabies Clinical Trial
Official title:
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.
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