Low-Cost Intradermal Rabies Vaccination Is Indeed Very Promising

TO THE EDITOR—We read with great interest the recent article by Wieten et al in Clinical Infectious Diseases [1] and, being involved in ongoing research strictly related to this topic, we wish to bring our contribution to their reflections. First, we fully agree that a lower-dose, abbreviated intradermal preand postexposure vaccination schedule may constitute a valid, shorter, and cheaper alternative to the current intramuscular or intradermal 3to 4-week schedules. If proven to be effective, such a schedule would be highly advantageous both for prevention in international travelers and for expanding vaccination in resourcepoor endemic countries. We also agree that further studies are needed to determine precisely which intradermal preexposure regimen is ideal for life-long boostability and which intradermal postexposure regimen gives high effective serology titers at day 7 after exposure. In their literature review, Wieten et al selected 9 studies and described the effects of the different schedules [1]. They stated that direct comparisons of various studies was not possible because of the different timing, dosing, routes of administration, and, in our opinion, also because of the small sample size and of the differences in serologic testing. The 2 most promising intradermal studies were designed by Khawplod [2, 3]: In 5 of the 10 study arms, exclusively intradermal regimens (0.1 mL) were used, with a total dose between 0.4 mL and 0.8 mL. In 2 other studies, authors declared that a total dose of 0.4 mL or 0.6 mL, respectively, of preexposure rabies vaccine administered over a minimum of 2 visits gives an adequate antibody response, irrespective of the time interval since the last dose [4, 5]. Concerning serology, in fact, the World Health Organization guidelines recommend the use of either the rapid fluorescent focus inhibition test (RFFIT) or the fluorescent antibody virus neutralization test. In particular, an RFFIT titer of > 0.5 IU/mL after booster vaccination is considered to be the best surrogate marker to determine protection from rabies infection after an animal bite in endemic zones [6]. Thus, we suggest that studies using only the enzyme-linked immunosorbent assay (ELISA), although reliable as an alternative, should be excluded in future analyses assessing or comparing the boostability of preexposure and postexposure rabies vaccination schedules. For instance, a recent case