A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.
BACKGROUND
The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.


METHODS
Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.


RESULTS
All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.


CONCLUSIONS
This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies.


BACKGROUND
Controlled-Trials.com ISRCTN 30087513.
Warrell
Mary J
MJ
The Oxford Vaccine Group, Centre for Clinical Vaccinology & Tropical Medicine University of Oxford, Churchill Hospital, Oxford, United Kingdom. mary.warrell@ndm.ox.ac.uk
Riddell
Anna
A
Yu
Ly-Mee
LM
Phipps
Judith
J
Diggle
Linda
L
Bourhy
Hervé
H
Deeks
Jonathan J
JJ
Fooks
Anthony R
AR
Audry
Laurent
L
Brookes
Sharon M
SM
Meslin
François-Xavier
FX
Moxon
Richard
R
Pollard
Andrew J
AJ
Warrell
David A
DA
D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D011818:Rabies / Q000276:immunology / Q000517:prevention & control; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D011819:Rabies Vaccines