Submitted to: Journal of Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 24, 1997
Publication Date: N/A
Interpretive Summary: The whipworm, Trichuris suis, is a serious nematode pathogen of swine which causes diarrhea, severe anemia, growth retardation, and is a major cause of economic loss in the production of feeder pigs. Eradication of whipworm infection in a herd is difficult due to the presence of resistant, infective eggs released by adult worms into the environment. Previous studies have demonstrated the presence of an oxidative enzyme from adult female T. suis worms which strengthens and imparts resistance to the parasite egg shell. In a mouse model of trichuriasis, disulfiram, a potent inhibitor of oxidative enzymes, was used to disrupt egg shell formation in T. muris. T. muris from mice given low, medium and high doses of disulfiram by mouth released malformed eggs into the environment. Many of these malformed egg shells were perforated, and the eggs did not contain embryonic material. Treatment with disulfiram disrupts normal egg shell formation in this nematode, and suggests a target enzyme which may be exploited for control of this and other nematode parasites which utilize this enzyme for egg shell strengthening.
The effect of disulfiram on eggshell morphology in the parasitic nematode Trichuris muris was studied in vitro and in vivo assays. Treatment of mice infected with T. muris daily for 26 days beginning 25 days after infection resulted in the production of malformed eggs by the adult female worms in all treated groups. In addition, fewer adult worms were found at necropsy in mice treated with 5.0 or 7.5 mg/kg/day of disulfiram than in mice treated with 2.5 mg/kg/day or in control mice. Adult worms collected from infected, untreated mice and placed in aerobic culture for 5 days in media containing 4 or 8 æg/ml of disulfiram released malformed eggs into the culture medium after 30 hours in culture. The results of these studies indicate that inhibition of the phenol oxidase enzyme results in disruption of normal egg production by T. muris females and might be a useful target in the development of control strategies aimed at nematode parasites that rely on the phenol oxidase enzyme for normal egg shell hardening.