oxantel and Trichuriasis

In the absence of efficient alternative strategies, the control of parasitic nematodes, impacting human and animal health, mainly relies on the use of broad-spectrum anthelmintic compounds. Unfortunately, most of these drugs have a limited single-dose efficacy against infections caused by the whipworm, Trichuris. These infections are of both human and veterinary importance. However, in contrast to a wide range of parasitic nematode species, the narrow-spectrum anthelmintic oxantel has a high efficacy on Trichuris spp. Despite this knowledge, the molecular target(s) of oxantel within Trichuris is still unknown. In the distantly related pig roundworm, Ascaris suum, oxantel has a small, but significant effect on the recombinant homomeric Nicotine-sensitive ionotropic acetylcholine receptor (N-AChR) made up of five ACR-16 subunits. Therefore, we hypothesized that in whipworms, a putative homolog of an ACR-16 subunit, can form a functional oxantel-sensitive receptor. Using the pig whipworm T. suis as a model, we identified and cloned a novel ACR-16-like subunit and successfully expressed the corresponding homomeric channel in Xenopus laevis oocytes. Electrophysiological experiments revealed this receptor to have distinctive pharmacological properties with oxantel acting as a full agonist, hence we refer to the receptor as an O-AChR subtype. Pyrantel activated this novel O-AChR subtype moderately, whereas classic nicotinic agonists surprisingly resulted in only minor responses. We observed that the expression of the ACR-16-like subunit in the free-living nematode Caenorhabditis elegans conferred an increased sensitivity to oxantel of recombinant worms. We demonstrated that the novel Tsu-ACR-16-like receptor is indeed a target for oxantel, although other receptors may be involved. These finding brings new insight into the understanding of the high sensitivity of whipworms to oxantel, and highlights the importance of the discovery of additional distinct receptor subunit types within Trichuris that can be used as screening tools to evaluate the effect of new synthetic or natural anthelmintic compounds.

Topics: Animals; Antinematodal Agents; Caenorhabditis elegans; Female; Helminth Proteins; Male; Pyrantel; Receptors, Cholinergic; Swine; Trichuriasis; Trichuris; Xenopus laevis

Topics: Adolescent; Adult; Aged; Anthelmintics; Child; Electrocardiography; Female; Humans; Male; Middle Aged; Pyrantel; Trichuriasis

Topics: Adolescent; Adult; Aged; Antinematodal Agents; Benzimidazoles; Child; Drug Therapy, Combination; Female; Humans; Male; Mebendazole; Middle Aged; Pyrantel; Pyrantel Pamoate; Trichuriasis

A mixture of oxantel-pyrantel pamoate was given to 147 primary school children. A single daily dose of 15 mg per kg body weight was administered to cases with Ascaris lumbricoides and Trichuris trichiura infections. The same single daily dose was given for three consecutive days to 10 cases with hookworm infections. The cure rate was 93.7% for ascariasis and the egg reduction rate was 98.2%. A cure rate and an egg reduction rate for trichuriasis was 70.2% and 86.5% respectively. All cases with hookworm infection were cured. Side effects were light and did not cause any anxiety.

Topics: Adolescent; Ascariasis; Child; Drug Therapy, Combination; Humans; Indonesia; Necatoriasis; Parasite Egg Count; Pyrantel; Pyrantel Pamoate; Trichuriasis

Topics: Adolescent; Adult; Antinematodal Agents; Ascariasis; Benzimidazoles; Child; Child, Preschool; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Humans; Intestinal Diseases, Parasitic; Male; Mebendazole; Necatoriasis; Nematode Infections; Pyrantel; Pyrantel Pamoate; Trichuriasis

Single doses of oxantel given to 24 children and 37 adults with light to moderate infections of Trichuris trichiura effected cures in 20 of 26 (77%) trials with 10 mg/kg body weight, in 23 of 25 (92%) with 15 mg/kg, and in 10 of 10 trials with 20 mg/kg. In cases not cured, the egg-counts were reduced 50% to 91%. Side effects were not observed, and no drug-associated changes were detected by biochemical, hematologic, and urine examinations before and after treatment.

Topics: Adolescent; Adult; Anthelmintics; Child; Feces; Humans; Pyrantel; Pyrimidines; Styrenes; Trichuriasis; Trichuris