Experimental studies on Obeliscoides cuniculi, a trichostrongylid stomach worm of rabbits. II. Anthelmintic studies in the dutch rabbit.

Phenothiazine, tetrachlorethylene, hexylresorcinol, CI-416 (a 2,4,5-trichlorophenolpiperazine salt), CI-474 (a cyanine compound), pyrvinium pamoate, and methyridine were effective against Obeliscoides cuniculi in single oral doses, as measured by reduction in worm burden and/or the percentage of rabbits cleared of worms. CI-474 and CI-416 showed the greatest potency of the ten compounds tested. The therapeutic failure of bephenium pamoate, thiabendazole, or Ruelene indicates an absence of direct correlation of effect of these drugs in rabbits with their action against trichostrongylid stomach worms of ruminants. The availability of nematode strains adapted to laboratory animals has assumed increasing importance as the search for new anthelmintics has intensified. Despite taxonomic dissimilarities between many laboratory host-parasite systems and the ultimate parasite problems of human or veterinary importance, the success of such laboratory screening is a matter of record. The development of bephenium as an anthelmintic for hookworms, Ascaris, and Nematodirus was based upon the initial discovery of its effect on Nematospiroides dubius and Nippostrongylus muris in rodents (Copp et al., 1958). Likewise, the oxyuricidal effect of pyrvinium pamoate was first detected against oxyurids in mice (Thompson et al., 1962). The present study was undertaken to evaluate the response of Obeliscoides cuniculi in the Dutch rabbit to a series of standard anthelmintics. A primary objective was to determine to what extent such rabbit bioassay data could be extrapolated to the chemotherapy of ruminant nematodiasis. MATERIALS AND METHODS The nematode strain and methods for its handling have been described (Worley, 1963). Dutch rabbits of either sex were infected with 40 to 150 larvae when 6 to 10 weeks old and were housed in groups of 3 or 4 in wire-bottomed cages. Dosing was deferred for 16 to 20 days postinoculation to permit the worms to mature. Composite fecal samples from each group were examined for worm eggs before treatment was started. Pelleted Rockland rabbit ration was fed ad libitum. Drugs were administered by gavage as a single dose suspended in 0.5% hydroxyethyl cellulose after an 18-hr fast. Dosages were expressed as the active component and were administered in a volume of 10 ml of vehicle per kg of body weight with a flexible plastic catheter. Drug effect was assessed by comparing the number of worms remaining in the stomach 3 to 5 days after treatment with the number in sham-dosed controls. Host tolerance of drugs was evaluated by post-treatment weight changes and by gross indications of intolerance such as diarrhea. The rabbits were fasted for a minimum of 32 hr before necropsy to permit the clearance of excessive ingesta from the stomach. This extended fasting period was necessary because the habitual reingestion of fecal pellets resulted in delayed emptying of the stomach. Post-mortem worm counts were made after removing the excised stomach of each animal to a petri dish containing 0.86% saline solution. The mucosa was scraped and examined for worms under a Dazor 3X magnifying lens, and any remaining ingesta were washed through a 20-mesh screen to remove finer debris. The mucosal scrapings and washed stomach contents were examined with a dissecting microscope, and the number, sex, and condition of the worms recorded. Statistical analysis of the percentage of rabbits cleared of worms was obtained with the fourfold contingency tables of Mainland, Herrera, and Sutcliffe (1956), and worm burden means were compared with Student's t test. Anthelmintics tested, with key references to the newer ones, were: phenothiazine, CI-416 [bis (2,4,5-trichlorophenol)piperazine salt] (Short and Elslager, 1962; Thompson, Worley, and McClay, 1962), hexylresorcinol, tetrachlorethylene, pyrvinReceived for publication 20 August 1962. * Present address: Veterinary Research Laboratory, Montana State College, Bozeman.