Efficacy of Selected Drugs against Trichinella spiralis

Abstract

Seven drugs have been tested for efficacy against Trichinella spiralis, namely: thiabendazole, dithiazanine iodide, trichlorphon, hygromycin B, dimethoate, Ruelene, and American Cyanamid CL 38,023 (formerly known as Famophos). Thiabendazole, trichlorphon, and dithiazanine iodide were found to have a high degree of prophylactic activity against T. spiralis. All reduced trichinae yields in swine by more than 99.0%. Thiabendazole apparently prevented infection in four of five pigs. Hygromycin B was ineffective as a prophylactic for swine. Ruelene and CL 38,023 possessed moderate and slight prophylactic activity, respectively, against trichiniasis in rats. In the therapeutic phase of the studies, intraperitoneal injections of trichlorphon proved completely effective against the intestinal phase of the disease in swine while treatment of the migratory phase gave a moderate reduction. A series of intraperitoneal injections against both the migratory and muscular phases gave more than 99.0% reduction in the yields. Dithiazanine iodide demonstrated marked therapeutic efficacy against the intestinal phase with moderate effectiveness against the muscular phase. Therapeutic trials against trichiniasis in rats utilizing dimethoate, Ruelene, and CL 38,023 indicated these drugs were effective only at toxic levels. The drugs were active only against the intestinal phase of the disease. Although Trichinella spiralis was recognized as a human disease entity by Paget in 1835, it is only during the past decade that significant progress has been made toward the development of specific chemotherapeutic agents effective against this parasite. These drugs include piperazine hydrochloride (Chan and Brown, 1954), dithiazanine iodide (McCowen et al., 1958; Kuzmicki, 1962), cadmium oxide (Larsh and Goulson, 1959), thiabendazole (Campbell and Cuckler, 1962), and trichlorphon (Schoop and Lamina, 1959, 1962a, b). Campbell and Cuckler found that thiabendazole, when fed to swine at the 0.1% level, possessed a high degree of prophylactic activity. Moderate therapeutic efficacy was obtained when the drug was fed at 0.3% level beginning on the 14th and 28th days, respectively. Schoop and Lamina found that trichlorphon (Neguvon) possessed marked activity against the intestinal phase of the disease in mice, with slightly less activity against the migratory and muscular phases. Both enteral and parenteral administration of the Received for publication 8 January 1964. drug were effective. The prior administration of an antidote consisting of atropine sulfate and pyridine-2-aldoxin-N-methyl-iodide (PAM) increased the usable dosage threefold with a marked increase in effectiveness of the drug. This report deals with studies to determine the efficacy of selected drugs against T. spiral;s infections in swine or rats. MATERIALS AND METHODS The following drugs were utilized in these studies: hygromycin B; dithiazanine iodide, 3,3' diethylthiadicarbocyanine iodide; thiabendazole, 2, (4'-thiazolyl )-benzimidazole; trichlorphon (Neguvon), 0,0-dimethyl 2,2,2-trichloro-l-hydroxethyl phosphonate with atropine added; Ruelene, 4tert-butyl-2-chlorophenyl methyl methylphosphoramidate; dimethoate, 0,0-dimethyl S(N-methylcarbamoylmethyl) phosphorodithioate; American Cyanamid CL 38,023 (formerly known as Famophos), 0,0-dimethyl 0-p-(dimethylsulfamoyl)-phenyl ester. All rats used in these trials were infected by stomach tube administration of trichinae digested free of meat. Infections were induced in swine by feeding ground carcasses of rats which had been infected with 5,000 excysted T. spiralis larvae 8 weeks or more previously. The sacrificed rats were skinned, eviscerated, and ground through a mechanical food chopper. The ground tissue was then pooled and mixed thoroughly. The trichinae concentration was determined by digestion of four