T H E ANTIRICKETTSIAL EFFECT OF THIONINE DYES I. THE USE OF METHYLENE Bntm AND TOLD-DINE BLUE TO COMBAT EXPEILI- MENTAL TSUTSUGAMusm DISEASE (ScRuB TxPmlS) BY OSLER

Since the outbreak of the recent war a number of contributions have been made to the chemotherapy of rickettsial diseases. Forbisen (4-41-bis-antipyrine) and toluidine blue (TB) were shown to be active against routine typhus infections in mice (1). Although found to be effective against pulmonary infections in mice with murine and epidemic rickettsiae, p-sulfamidobenzamidine and p-sulfamidobenzamidoxine proved to be both toxic and ineffective in human cases of epidemic typhus (2). Against murine typhus infections of mice and of chick embryo yolk sacs, penicillin was found effective (3, 4), but when tested against Rocky Mountain spotted fever in guinea pigs, it showed no activity (5). Furthermore, in limited trials against human cases of scrub typhus (Tsutsugamushi disease) (6) and of epidemic typhus (8), penicillin was found to be of uncertain value. A growing body of evidence testifies to the effectiveness against both experimental and naturally occurring infections with various members of the rickettsial group of still another agent, paraaminobenzoic acid (PABA). First shown to be active against murine typhus in mice, PABA has since been found to be active in experimental infections of animals and of embryo yolk sacs with the rickettsiae of epidemic typhus, Rocky Mountain spotted fever, and scrub typhus; furthermore, favorable reports have appeared concerning its activity in human cases of all three of the last named diseases (7-16).