title: A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.
abstract: 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.
authors.affiliation: The Oxford Vaccine Group, Centre for Clinical Vaccinology & Tropical Medicine University of Oxford, Churchill Hospital, Oxford, United Kingdom. mary.warrell@ndm.ox.ac.uk
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Warrell
authors.forename: Anna
authors.initials: A
authors.lastname: Riddell
authors.forename: Ly-Mee
authors.initials: LM
authors.lastname: Yu
authors.forename: Judith
authors.initials: J
authors.lastname: Phipps
authors.forename: Linda
authors.initials: L
authors.lastname: Diggle
authors.forename: Hervé
authors.initials: H
authors.lastname: Bourhy
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Deeks
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fooks
authors.forename: Laurent
authors.initials: L
authors.lastname: Audry
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Brookes
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Meslin
authors.forename: Richard
authors.initials: R
authors.lastname: Moxon
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: David A
authors.initials: DA
authors.lastname: Warrell
mesh_terms: 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
chemical_list: D011819:Rabies Vaccines