Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes.

The control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant parasites. Nicotine has also historically been used as a de-wormer but was removed from the market when modern anthelmintics became available. The pharmacological target of nicotine has been identified in nematodes as acetylcholine-gated ion channels. Nicotinic-sensitive acetylcholine receptors (N-AChRs) therefore represent validated pharmacological targets that remain largely under-exploited. In the present study, using an automated larval migration assay (ALMA), we report that nicotinic derivatives efficiently paralyzed a multiple (benzimidazoles/levamisole/pyrantel/ivermectin) resistant field isolate of H. contortus. Using C. elegans as a model we confirmed that N-AChRs are preferential targets for nornicotine and anabasine. Functional expression of the homomeric N-AChR from C. elegans and the distantly related horse parasite Parascaris equorum in Xenopus oocytes highlighted some striking differences in their respective pharmacological properties towards nicotine derivative sensitivity. This work validates the exploitation of the nicotine receptors of parasitic nematodes as targets for the development of resistance-breaking compounds.

A field study on the anthelmintic resistance of Parascaris spp. in Arab foals in the Riyadh region, Saudi Arabia.

BACKGROUND: In the last decade, Parascaris spp. resistance to anthelmintics has been recorded in many countries. In Saudi Arabia, there are limited data available on Parascaris spp. resistance to anthelmintics. OBJECTIVE: To determine the current status of ivermectin, abamectin and praziquantel combined, and fenbendazole resistance to Parascaris spp. in horses in Saudi Arabia. METHODS: Three hundred and forty-one foals from eleven different farms were examined by faecal egg count (FEC). The foals were all Arab horses aged 17.2 ± 4.5 (SD) months. Ivermectin (n = 46 foals), abamectin and praziquantel combined (n = 46), and fenbendazole (n = 46) were administered on day 0 and faeces were collected on day 14. The study comprised 41 untreated foals as controls. Animals that have FEC of ≥100 eggs per gram (EPG) were used to measure anthelmintic efficacy. Parascaris spp. populations were considered susceptible when faecal egg count reduction (FECR) was ≥95% associated with a lower 95% confidence limit (LCL) >90%, suspected resistant when FECR ≤90% or LCL <90% and resistant when FECR <90% and LCL <90%. RESULTS: Prevalence of Parascaris spp. infection was 53% (179/341 horses). Anthelmintic resistance to Parascaris spp. were highest following fenbendazole (55% of farms and 65% of foals) and to a lower extent following ivermectin or the combination of abamectin and praziquantel which comprised 27% of farms (and 46% of foals) and 18% of farms (and 10% of foals), respectively. CONCLUSION: These data indicate that anthelmintics-resistant Parascaris spp. populations are present on horse farms in Saudi Arabia.

Baylisascaris procyonis larva migrans in two white-headed lemurs (Eulemur albifrons) in Spain and response to treatment derived from a human pediatric protocol.

Baylisascaris procyonis is a well-known ascaridoid nematode that causes larva migrans in humans and many other animal species. The North American raccoon (Procyon lotor) is the definitive host, which has been successfully introduced in the past decades to other geographical regions around the world. Two white-headed lemurs (Eulemuralbifrons) from a Zoological Park in Lugo, Spain, developed severe neurological signs within a brief period after being transferred from exhibit and placed in close contact with three captive raccoons from the same zoo. One lemur was euthanized due to the severity of disease progression and histopathology revealed granulomatous inflammation and ascaridoid larvae in kidneys, lung, spleen and brain. Larvae were identified as B. procyonis larvae by real time PCR. In light of the results, the cage mate with similar neurological signs was put on an albendazole treatment regimen adapted from a human pediatric protocol. The aggressive anthelmintic treatment likely contributed to the arrest of clinical signs and recovery of some motor skills. Importantly, Baylisascaris procyonis infection might occur in wild raccoon populations in Spain.

Comparative efficacy of ivermectin and levamisole for reduction of migrating and encapsulated larvae of Baylisascaris transfuga in mice.

The comparative efficacy of 2 anthelmintics (ivermectin and levamisole) against Baylisascaris transfuga migrating and encapsulated larvae was studied in mice. A total of 60 BALB/c mice inoculated each with about 1,000 embryonated B. transfuga eggs were equally divided into 6 groups (A-F) randomly. Mice of groups A and B were treated with ivermectin and levamisole, respectively, on day 3 post-infection (PI). Mice of groups A-C were killed on day 13 PI. Similarly, groups D and E were treated with ivermectin and levamisole, respectively, on day 14 PI, and all mice of groups D-F were treated on day 24 PI. The groups C and F were controls. Microexamination was conducted to count the larvae recovering from each mouse. The percentages of reduction in the number of migrating larvae recovered from group A (ivermectin) and B (levamisole) were 88.3% and 81.1%, respectively. In addition, the reduction in encapsulated larvae counts achieved by ivermectin (group D) and levamisole (group E) was 75.0% and 49.2%, respectively. The results suggested that, to a certain extent, both anthelmintics appeared to be more effective against migrating larvae than encapsulated larvae. However, in the incipient stage of infection, ivermectin may be more competent than levamisole as a larvicidal drug for B. transfuga.

Efficacy of ivermectin in the oral paste formulation against naturally acquired adult and larval stages of Parascaris equorum in pony foals.

The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective against adult P equorum. At 2 WAT, ivermectin was 100% effective against lung larval stages and 91% effective against intestinal larvae of P equorum. Efficacy of ivermectin against all intestinal stages was 93%. Intestinal and lung larval populations were similar in ivermectin-treated and nontreated foals at 5 WAT, indicating that the foals had become reinfected from the contaminated drylots, with larvae repopulating in the tissues 2 to 5 WAT. Apparent increases in severity of lymphoproliferative and inflammatory tissue reactions were observed histologically in lung and liver tissues of treated foals. Clear differences in clinical conditions between foals in treated and nontreated groups were not observed. However, weight gains in foals were greatest after treatment.