Date Published: April 23, 2008
Publisher: Public Library of Science
Author(s): Mary J. Warrell, Anna Riddell, Ly-Mee Yu, Judith Phipps, Linda Diggle, Hervé Bourhy, Jonathan J. Deeks, Anthony R. Fooks, Laurent Audry, Sharon M. Brookes, François-Xavier Meslin, Richard Moxon, Andrew J. Pollard, David A. Warrell, Peter J. Hotez
Abstract: BackgroundThe 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.MethodsTwo 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.FindingsAll 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.ConclusionsThis 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.Trial RegistrationControlled-Trials.com ISRCTN 30087513
Partial Text: Rabies is a neglected disease affecting particularly tropical developing countries . Estimates of the Global use of rabies post-exposure prophylaxis (PEP) are rising. In China, it was 8 million in 2005 , yet rabies currently kills more people than any other infectious disease there. Rabies deaths are underreported and misdiagnosed, for example as cerebral malaria . As the obsolete nervous tissue-based rabies vaccines are replaced by expensive tissue culture vaccines, there is increasing need to reduce the cost of post-exposure prophylaxis. In Africa, the average cost of a standard intramuscular (IM) course of vaccine is $39.6, equivalent to 50 days wages . There is a shortage of affordable rabies vaccines of reliable quality in the developing world .
The CONSORT checklist for this study is available in Supporting Information as Checklist S1.