Abstract
BackgroundThe single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known.MethodologyWe studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species.Principal findingsThe motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6–17.2%) as compared to O. dentatum (0.8–0.9%).Conclusion/SignificanceThe general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum.
Highlights
The whipworm Trichuris trichiura has been estimated to infect 600 million people worldwide resulting in an estimated 1.6–6.4 million disability adjusted life-years lost globally [1]
The current global control strategy against these worms is regular administration of anthelmintic drugs, mostly albendazole and mebendazole, both belonging to the drug-class benzimidazoles
We evaluated the in vitro effect of two benzimidazoles; i.e., albendazole, fenbendazole, and another type of anthelmintic, levamisole, on the whipworm (T. suis) and the nodular worm (Oesophagostomum dentatum) of the pig
Summary
The whipworm Trichuris trichiura has been estimated to infect 600 million people worldwide resulting in an estimated 1.6–6.4 million disability adjusted life-years lost globally [1]. The current control strategy against T. trichiura and other soil-transmitted helminths (STHs) is administration of single-dose anthelmintic drugs [1,2]. The efficacy of single-dose BZ against T. trichiura is not satisfactory. A metaanalysis of 20 randomized, placebo-controlled trials reported an average cure rate (CR) of 28% for ALB (400 mg) and 36% for MBD (500 mg) [3]. Other randomized controlled trials have reported similar low CR and egg reduction rates (ERR) ranging from 31.5–40.3% (CR) and 9.8–54.0% (ERR) for ALB and 22.9– 66.7% (CR) and 18.8–81.0% (ERR) for MBD [4,5,6,7]. The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. The benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known
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