A Simplified 4-Site Economical Intradermal Post-Exposure Rabies Vaccine Regimen: A Randomised Controlled Comparison with Standard Methods

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

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

“…After the third dose, antibody titers were 29.8, 3.2 and 1.59 IU/ml, respectively. These titers are within the limits described in the literature in trials using the VeroRab TM vaccine after administration of three doses (see for example: Warrell et al [18]). …”

“…However, vaccination costs against rabies virus can be highly prohibitive and severely limit the usage of this life-saving vaccine. Intradermal regimes of vaccinations have been developed and used in tropical countries in an effort to reduce vaccination costs [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Even though this new vaccination mode may reduce costs, it requires multiple visits to vaccination facilities and skilled practitioners in order to administer the vaccine.…”

Cost-Safety-Effectiveness Analysis of Different Methods of Rabies Vaccination

“…There are some reports comparing the effectiveness of different techniques. The recent publication by Warrell et al compared several techniques and can be useful for further policy making (2). Nevertheless, the important concern in decision making is "cost" and "effectiveness".…”

“…Data on cost refers to the standard vaccine cost, in US dollar, from the Red Cross Society, Thailand. The effectiveness and safety refer to the published data by Warrell et al (2). The cost-safety-effectiveness analysis can be defined as cost per safe fraction of vaccine effectiveness, which can be calculated using the following equation: The data of analysis is shown in Table 1.…”

“…According to the analysis, in terms of cost, effectiveness and safety, the 2-site ID regimen is the most favorable method with the lowest cost and highest safe effectiveness. (2). b Effectiveness at 1 year period, refers to mean responsive serological activity (IU/ML).…”