Intradermal pre-exposure rabies immunisation
in New Zealand
Marc M. Shawa,b,*, Peter A. Leggatb, Megan L. Williamsa
aWorldwise Travellers Health Centres of New Zealand, 72 Remuera Road, Newmarket,
Auckland, New Zealand
bSchool of Public Health and Tropical Medicine, James Cook University, Townsville 4811, Australia
Received 27 September 2004; received in revised form 4 November 2004; accepted 8 November 2004
Available online 7 January 2005
to consider in those travellers going to rabies endemic areas. In those at high risk,
a course of three immunisations may be given by the intramuscular (IM) or
intradermal (ID) route, both of which are approved by the World Health
Organization (WHO) and the Centers for Disease Control (CDC). Little is known
in the New Zealand context regarding the effectiveness of pre-exposure ID rabies
Methods. The data was collected prospectively on all travellers requiring the
immunisation from July 2001 to September 2003 in Auckland. The standard WHO
rabies immunisation protocol was used with three ID injections of 0.1 ml, given on
days 0, 7, and 21 or 28 with a booster after 12 months. The vaccine used was the
Pasteur Merieux human diploid cell vaccine (HDCV) or the Rabipur Purified chick
embryo cell (PCEC) vaccine. Both vaccines are approved by the WHO and the CDC,
and are interchangeable. Serology was performed approximately 2 weeks after
completion of the primary immunisation course or after a booster, wherever
possible. Antibody levels were measured using EIA, and levels of O0.5 IU/ml were
Results. Of the 263 travellers assessed in this study, 125 were males and 138 were
females. The mean age of the cohort was 34.8 years (SDZ11.7). There were not
found to be any statistically significant correlations between age and antibody levels
neither was there any significant association between gender and antibody levels. In
addition to the sample group, a further 12 travellers had rabies serology performed
but were excluded from the study because they had IM vaccines as part of their
primary course. Whilst rabies serology ranged from 0.2 to 27.9 IU/ml in the study
cohort, the mean antibody level for the group was 4.7 IU/ml (SDZ4.1 IU/ml). The
mean antibody level for males was 4.3 IU/ml (SDZ3.3), and for females, 5.2 IU/ml
(SDZ4.6). Of the 263 travellers, all had some level of detectable antibodies. The
overall seroconversion rate was 95.1%.
Background. Rabies is a fatal infection and immunisation is important
Travel Medicine and Infectious Disease (2006) 4, 29–33
1477-8939/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
* Corresponding author. Address: Worldwise Travellers Health Centres of New Zealand, 72 Remuera Road, Newmarket,
Auckland, New Zealand.
E-mail address: email@example.com (M.M. Shaw).
Conclusions. ID rabies immunisation appears effective, when given according to
the standard WHO protocol, in New Zealand. ID rabies immunisation is also more
affordable for travellers, especially those on a restrictive budget. ID rabies
immunisation can continue to be recommended, particularly where follow-up
serology can be done before travel and where there are staff who are experienced in
q 2004 Elsevier Ltd. All rights reserved.
Between 40,000 and 70,000 people die each year
from rabies1and about 90% of these deaths are
reported in Asia.2Rabies is an acute fatal encepha-
litis caused by neurotropic viruses in the genus
Lyssavirus, family Rhabdoviridae.3It can be trans-
mitted to humans by the saliva of infected wild and
domestic animals, usually dogs.1,3An effective
vaccine is available and, if administered before
the onset of symptoms following a bite or lick of an
open wound or mucous membrane from an infected
animal, it normally prevents the infection develop-
ing.2Because rabies is invariably a fatal disease
once symptoms develop, an estimated 10 million
people each year receive post-exposure immunis-
ation after being exposed to rabies suspect animals.
Such immunisations have traditionally been admi-
nistered intramuscularly, which represents a huge
cost on the economies of both developing countries
and of intending travellers. To minimalise costs in
the most efficient and effective manner, by admin-
istering vaccine by the intradermal route, would be
an advantage to target populations.
Rabies is found in most countries of the world,
especially in Africa and Asia, where the disease is
endemic and account for more than 50% of the
deaths due to rabies each year.2In the Pacific Rim
area, New Zealand, Australia, Papua New Guinea,
the Pacific Islands and Japan are rabies free.4
Travellers from these countries may, however, be
exposed to rabies when they travel to rabies
endemic countries. Both the WHO5and CDC6
recommend that those who are likely to be exposed
to rabies travelling to endemic areas should be
offered pre-exposure immunisation. This applies
particularly to children who are regarded conserva-
tively as being four times more likely to be bitten
than adults in both developed and developing
countries,7and travellers who will be either
engaged in remote regions in endemic areas or
put themselves through high-risk activities, such as
bicycling, caving, or working or living with warm
Pre-exposure immunisation may be given either
by the intra-muscular or intra-dermal route.
Normally, the WHO recommends 1.0 ml IM or
0.1 ml ID doses which are administered into the
deltoid region on days 0, 7 and 21 or 28.4Serology is
recommended 1–3 weeks following the course of
vaccines.4The ID route is preferable to many
travellers as it reduces cost and discomfort,
however, in Australia there is a requirement for
serology to be undertaken following ID immunis-
ation, which can result in delays and inconveni-
ence.8Whilst this is not yet so in New Zealand, it is
increasingly considered an expected part of any
consultation on rabies pre-exposure management.
At present, ID immunisation is largely restricted
to dedicated travel clinics in New Zealand and
Australia, even though current guidelines give ID
immunisation as an option in the presence of post-
immunisation serology. The restriction largely
comes about partly because the immunisation is
not presently licensed for ID use in these countries
and dedicated travel health clinics have staff
trained in giving ID immunisations, and partly
because it needs to be administered according to
the strict criteria that the WHO outline.5
Although some concerns exist concerning the
effectiveness of ID rabies immunisation, a recent
Australian study suggested that ID rabies immunis-
ation is effective in the travel clinic setting, when
given by trained nurses.9Little is known in the New
Zealand context regarding the effectiveness of pre-
exposure ID rabies immunisation. This study was
designed to investigate serological response to the
standard course of three intradermal rabies vacci-
nations for pre-exposure immunisation for travel-
lers from New Zealand.
The data was collected prospectively from July
2001 to September 2003 at a dedicated travel
medicine clinic in Auckland, New Zealand. People
presenting at the clinic included package tourists,
backpackers, expeditioners, those going to work
abroad, volunteer aid workers and humanitarian
groups. Those going into risk areas, as previously
noted, were offered rabies an ID immunisation.
M.M. Shaw et al.30
Two hundred and seventy five consultations
involved consultation and pre-travel management
of rabies pre-exposure immunisation. Included in
the cost of immunisation was the cost of having a
rabies serological test to confirm WHO acceptable
levels for immune status. All medical and nursing
staff at the clinic are experienced in the ID rabies
The standard clinic protocol for ID rabies
immunisation is a course of three injections given
on days 0, 7, and either on day 21 or 28. A booster is
given after 12 months, with a recommended follow
up serology 2 weeks later to confirm accepted
serological protection. Future boosting is then
dependant on monitoring further serology before
travel abroad. The vaccines used for the immunis-
ations were either the Pasteur Merieux human
diploid cell vaccine (HDCV) or the Chiron Rabipur
Purified chick embryo cell vaccine (PCECV).
Serology was offered to all travellers who had
any ID vaccines as part of their primary course. It
was also offered pre-booster at 12 months. Serology
was normally recommended about 2 weeks after
the primary course or after a booster to confirm
immunity, which we have included as part of this
The blood samples were sent via courier on the
day of collection to Lab Plus, the Auckland Hospital
Laboratory doing the centralised testing. Antibody
levels were measured using Enzyme Immuno-Assay
(EIA) and levels of 0.5 IU/ml are considered
protective.5–7,9,10Results were generally available
within 1 week, and all travellers were informed, by
either phone or email, of their immune status at the
earliest availability of serological results. For some,
however, this meant part way through their travel.
Whenever this occurred, travellers were advised to
have a booster dose of cell-derived vaccine. Non-
immune travellers, who had results to hand before
they travelled, were asked to return for a further
dose of ID vaccine, and any non-immune traveller
overseas was advised that a full post-exposure
series would be required for any adverse event.
Those that were initially non-immune, and who had
a further dose, were offered repeat serology 2
weeks later. Variations in the standard protocol for
immunisation and time lag to serology were due to
patient non-compliance or difficulty in returning to
the clinic (e.g. patients living in remote areas or
overseas). Travellers were excluded from the study
if they had any IM injections as part of their primary
course or as the booster.
Data was entered using the Statistical Package
for the Social Sciences.11Missing data has been
excluded from analysis.
A total of 263 travellers were included in this study.
A further 12 had rabies serology performed but
were excluded because they had IM vaccines as part
of their primary course. The demographic charac-
teristics of the travellers are given in Fig. 1. The
mean age was 34.8 years (SDZ11.7). There were
125 males and 138 females.
An antibody levels in this study ranged from 0.2
to 27.9 IU/ml with a mean of 4.7 IU/ml (SDZ4.1).
Some results were reported by the laboratory as
‘O9’ or ‘O8.8’ rather than as a specific titre. These
were recorded as 9 or 8.8, respectively, rather than
the true values. The mean antibody level for males
was 4.3 IU/ml (SDZ3.3), and for females, 5.2 IU/ml
(SDZ4.6) (Fig. 2). The overall mean antibody level
after a primary course was 7.28 IU/ml and after a
booster, 15.30 IU/ml. Of the 263 travellers, all had
some level of detectable antibodies. The overall
seroconversion rate (i.e. those that showed a level
of 0.5 IU/ml or over, as per WHO criteria) was
95.1%. There were no statistically significant
correlations shown to exist between age and
antibody levels, neither was there any significant
association found between gender and antibody
levels (Fig. 2).
Demographics of travellers.
Intradermal pre-exposure rabies immunisation 31
This is the first New Zealand data to report on
seroconversion rates after ID rabies immunisation.
It has shown that ID rabies vaccine with either of
the interchangeable WHO approved vaccines was
very effective and had a seroconversion rate of
95.1%. This is consistent with other studies in
Australia8and the USA.12,13
Whilst the mean rabies serology level is accep-
table, it may in fact have been underestimated for
two principle reasons:
† A significant delay in obtaining serological
confirmation in a subset of the sample cohort,
† The laboratory reporting of mean antibody levels
as O9 or O8.8, rather than the true values.
As expected, in confirmation of other studies,
there was neither an association between gender
and serological titre nor was there any between age
It is well establised that IM immunisation will
give higher antibody titres than ID immunisation,
using a similar schedule of 0, 7, 28 days.6,14
Nevertheless, this study has used the recommended
WHO/CDC ID schedule,5,6on an intending travelling
population from New Zealand.
Reported effectiveness of ID rabies immunisation
is variable.7,8Vaccinator’s skill in ID administration
is a major factor in this. Another is the interval
between the completion of the immunisation series
and serological testing. A Thai study showed that
the response to standard post-exposure treatment
in previously vaccinated individuals was insufficient
during the first 5 days, but that all had adequate
levels by day 14.15The same study also suggested
that patients with high risk and severe exposure to
rabies, and who have had prior pre-exposure ID
immunisations, be treated for exposure to the
disease as if they had not previously been
Mean serology levels by age and sex.
Advantages and disadvantages of pre-exposure rabies immunisation.
Provides psychological security for travel to endemic regions16
Delays in post-exposure treatment are less crucial8
Avoids the need for human or equine immunoglobulin6–8,16
Protects against anticipated exposure16
Enables medical facilties to be reached before infection16
Simplifies post-exposure treatment16
Cost a factor in compliance, especially with IM immunisation, although reduced with ID immunisation6–8
Multiple doses are required, which travellers may not have time to complete prior to travel
No licensed ‘rapid series’ available for early departing travellers
Disadvantages specifically for ID rabies immunisation
Serology requires an extra visit to the clinic at 2 weeks and a further delay of a week for the results to be available
Limited availability of rabies serology
Further immunisation may be needed if antibody levels are low8
Local reactions may be higher with ID compared with IM immunisation12,17
Antibody level is reduced if ID rabies immunisation is given concurrently with antimalarials such as chloroquine7,18
Immunosuppression with concurrent steroids will effect immunity of ID rabies immunisation6
M.M. Shaw et al.32
immunised. It would be useful in future studies to Download full-text
examine any differences in serology between
primary vaccinations and with that after boosting.
The advantages and disadvantages of pre-
exposure rabies immunisation have been summar-
ised in the Table 1
ID rabies immunisation appears very effective when
given according to the standard WHO protocol in a
cohort of intending New Zealand travellers. As ID
rabies immunisation is more affordable for the
majority of travellers, especially those on a tight
budget, this result is very acceptable in considering
rabies as a highly vaccine preventable disease. ID
rabies immunisation is highly recommended for
those at risk of exposure, particularly where follow-
up serology can be done before travel and where
there are staff who are experienced in ID
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Intradermal pre-exposure rabies immunisation33