Search

Background. Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane. Methods. We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6-12 years before and 25-27 days after treatment with praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds. Results. The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%-93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%-99.08%) or 1 round (95% BCI, 95.51%-98.96%) of MDA.We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8-9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal praziquantel efficacy set by the World Health Organization. Conclusions. The reduced efficacy of praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored. [ABSTRACT FROM AUTHOR]

Utilization of chemical pesticide to control monogenean diseases is often restricted in many countries due to the development of pesticide resistance and concerns of chemical residues and environmental contamination. Thus, the use of antiparasitic agents from plants has been explored as a possible way for controlling monogenean infections. Extracts from Cinnamomum cassia were investigated under in vivo conditions against Dactylogyrus intermedius in goldfish. The two bioactive compounds, cinnamaldehyde and cinnamic acid, were identified using nuclear magnetic resonance and electrospray ionization mass spectrometry. The 48 h median effective concentrations (EC50) for these compounds against D. intermedius were 0·57 and 6·32 mg L−1, respectively. The LD50 of cinnamaldehyde and cinnamic acid were 13·34 and 59·66 mg L−1 to goldfish in 48 h acute toxicity tests, respectively. These data confirm that cinnamaldehyde is effective against D. intermedius, and the cinnamaldehyde exhibits potential for the development of a candidate antiparasitic agent. [ABSTRACT FROM AUTHOR]

Industry guidelines for anthelmintic testing call for postmortem inspection of animals to verify treatment efficacy. A previous study showed that capsule endoscopy (CE) can be performed on dogs in vivo to quantify hookworms in the small intestine. Adoption of a minimally invasive procedure such as this could reduce the need for necropsy in efficacy trials. The present study employed CE to enumerate Toxocara canis in dogs, with two main goals: to determine if multiple capsule examinations improves the accuracy of worm counts compared to a single examination, and to establish if the efficacy of an anthelmintic compound is the same whether calculated using CE or necropsy data. To avoid needless animal sacrifice, the study was carried out on beagle dogs already in a product development trial with a planned terminal endpoint. Dogs were infected by oral inoculation with T. canis eggs. Untreated control dogs ( n = 8) were evaluated by CE three times while dogs treated with test compounds (3 groups of 4) were examined only once. Utilizing either the average count or just the last complete capsule examination, a robust correlation was found between CE and postmortem numbers ( r = 0.94, p < 0.001). Calculated anthelmintic efficacy was essentially identical for the two enumeration methods, ranging from 94% to 100% for the three research compounds. CE may therefore be a viable alternative to necropsy for T. canis parasiticide trials. [ABSTRACT FROM AUTHOR]

Preliminary data suggest that topical eprinomectin in goat shows an individual variation in anthelmintic efficacy when used off-license at a dose rate of 0.5 or 1.0 mg/kg BW. As a result, the use of oral administration of topical formulation of eprinomectin tends to develop in dairy goat farms in France. The plasma levels and milk excretion as well as the anthelmintic efficacy of eprinomectin were determined in goats following oral administration of a topical formulation of the drug at dose rates of 0.5 and 1 mg/kg BW. The area under the concentration–time curve (AUC) values were 17.62 ± 9.68 ng day/ml and 6.56 ± 4.00 ng day/ml for plasma and milk respectively after the administration of 0.5 mg/kg BW and 45.32 ± 13.90 ng day/ml and 13.88 ± 1.77 ng day/ml for plasma and milk, respectively after the administration of 1 mg/kg BW. The milk-to-plasma ratio ranged from 0.33 to 0.36 and the amount of drug recovered in the milk was 0.4% of the total administered dose. The maximum concentrations of eprinomectin residues determined in milk after oral treatment were <20 μg/kg (Maximum Residue Limit in goat milk). The anthelmintic efficacy of the oral administration of topical eprinomectin was 100% through Faecal Egg Count Reduction Test in natural infection and ≥99.8% through Controlled Test in experimental infection ( Haemonchus contortus and Trichostrongylus colubriformis ). Additional information is needed about the fate of the vehicles used for topical formulation when given by oral route concerning food safety. [ABSTRACT FROM AUTHOR]

Objective To describe an ovine parasitological monitoring service delivered by a rural veterinary practice and determine associations between flock, anthelmintic and monitoring factors and worm control. Design Retrospective study of records from a rural veterinary practice in south-eastern Australia over an 8.75-year period. Methods Records of sheep producers using veterinary services for gastrointestinal parasite management from 1 August 2003 to 30 April 2012 were analysed. Results from pre- ( FECt1) and post-treatment faecal egg counts ( FECt2) were used to identify factors influencing anthelmintic effectiveness, calculated as faecal egg count reduction percentage ( FECR%) by linear mixed model analyses. The trends in anthelmintic merchandising and uptake of veterinary services for parasite management were determined by logistic regression analyses. Results FECR% varied according to the treatment group used ( P < 0.001), with an apparent decreasing effectiveness of the macrocylic lactone group over the duration of the study ( P = 0.008). Wether and ram flocks displayed lower FECR% than ewe flocks ( P < 0.05). Time between FECt1 and treatment ( P = 0.031), as well as time between treatment and FECt2 ( P < 0.001), had a significant negative association with FECR%. The proportion of properties purchasing 4-way combination anthelmintics increased significantly over the study period ( P < 0.001), with declines observed in other anthelmintics ( P < 0.05). The proportion of properties performing FECR% monitoring to those that purchased anthelmintics increased significantly over the study period ( P = 0.001). Conclusion Anthelmintic treatment type, sex of the flock and time between drenching and testing had the greatest influence on drench effectiveness ( FECR%). An increasing reliance on 4-way combination drenches to manage gastrointestinal parasitism was demonstrated. Benefits of parasitological monitoring include: appropriate advice on parasitological management; observations on trends in regional anthelmintic usage; estimation of drench effectiveness; early indication of anthelmintic resistance; and improved service provision by the rural veterinary practice. [ABSTRACT FROM AUTHOR]

Background: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was ⩾200 eggs per gram and the interval post-sampling was 10-14 days for BZ products, 4-7 days for LEV products and 14-18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was ⩾95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective. [ABSTRACT FROM AUTHOR]

Current gyrodactylids treatments using chemicals such as rotenone, piperazine and trichlorfon cause environmental and human health issues, especially their toxicity to the host. Therefore, search for alternative anthelmintic agents is urgent and natural compounds from herbs show promising solution to this problem. In our previous study, we screened 33 herbal medicines and found that Angelica dahurica has a good anthelmintic efficacy. In order to identify the active compounds from Angelica dahurica , bioassay-guided isolation was performed using a Carassius auratus - Gyrodactylus kobayashii model in this study. After extraction, purification and characterization step by step, isoimperatorin was eventually separated as the main active ingredient for eradicating G. kobayashii in goldfish. Compared to the control groups, bathing G. kobayashii -infected goldfish in isoimperatorin significantly reduced infection prevalence and intensity, with EC 50 values of 0.63 (24 h) and 0.53 mg/L (48 h), respectively. Acute toxicity assays indicated that the LC 50 (96 h) of isoimperatorin against goldfish was 10.16 mg/L, which was 19.17 times higher than EC 50 (48 h). In addition, scanning electron microscope (SEM) and RT-qPCR were used to explore the anthelminthic mechanism of isoimperatorin. TEM results showed that after exposure to isoimperatorin, morphological alterations in the tegument of G. kobayashii were observed, which disrupted its homeostasis. Besides, isoimperatorin significantly downregulated the expression of ATPase genes (ATP5A1 , ATP5C , ATP5F) and oxidative phosphorylation pathway genes (NDUFS8, NDUFA8, SDH). After treatment with isoimperatorin, the content of ATP in the worms decreased significantly. In summary, isoimperatorin showed promising anti G. kobayashii efficacy via damaging tegument, supplying insufficient energy to the G. kobayashii. • Isoimperatorin was identified from Angelica dahurica by bioassay-guided isolation method. • Results from in vivo experiments showed 48 h EC 50 of isoimperatorin was 0.53 mg/L. • Mechanism of isoimperatorin was related to tegumental structure damages and ATP inhibition. [ABSTRACT FROM AUTHOR]

The present study was carried out to evaluate the efficacy of crude neem (Azadirachta indica) leaf powder in goats naturally infected with strongyle infections. Based on faecal sample examination, 24 adult goats positive for strongyle infection with ≥ 1000 EPG (egg per gram) were selected and grouped as I, II, III and IV with 6 animals in each group. Group I was treated with Closantel @10mg/ kg body weight and Groups II and III were treated with crude neem leaf powder @ 0.5 g and 1.0 g/kg. b.wt. respectively whereas group IV was kept as infected untreated control. Faecal samples from each animal were examined on day 0, 7, 15 and 30 post-treatment and EPG was determined. The result showed significant reduction (p<0.05) in EPG in Group I from day 7 and was maintained till day 30 and in Group III on day 15 post-treatment but there was no significant variation in term of EPG in control group. Thus, it can be concluded that crude neem leaf powder has anthelmintic property. [ABSTRACT FROM AUTHOR]

Abstract: The egg hatch assay (EHA) is one of the main in vitro methods for detection of benzimidazole resistance in nematode parasites of small ruminants. However, although the EHA has been standardised at the laboratory level, the diagnostic performance of this method has not been fully characterised for field screenings. In the present work, monthly variation of benzimidazole resistance estimated by EHA was surveyed over two years in three sheep flocks and in one goat and an additional sheep flock sharing the same pastures. Resistance was measured by calculating both the effective dose of thiabendazole (TBZ) that inhibited hatching of ≥50% of parasite eggs (ED50) and the proportion (P dd) of eggs hatching at a discriminating dose of 0.1μg/ml TBZ. P dd exhibited higher variability than ED50, in agreement with the higher sensitivity of P dd to changes in resistance levels. Both resistance parameters, however, were highly correlated, and their variation was similarly related to the same factors. Resistance levels differed among sheep flocks, and the resistance level of the goat flock was higher than that measured for the sheep flock sharing the same pasture. Moreover, monthly variation of resistance in goats did not mirror that recorded in sheep. Resistance levels varied seasonally, with the highest values recorded in the spring, and they were inversely related to the number of days that samples were stored under anaerobic conditions. In addition, they were directly associated with the relative abundance of Teladorsagia spp. but inversely related to the relative abundance of Haemonchus spp. After controlling for the effects of these identified factors for variation, inter-monthly sampling variation due to unknown factors was the main source of variability, accounting for more than 60–70% of variance for both resistance parameters and yielding absolute estimation errors higher than 0.06 for ED50 or 0.2 for P dd when resistance was estimated from a single sampling. Optimum sample size, estimated from variance components, suggested that at least 4–5 samplings would be needed to halve this absolute error, whereas additional samplings would slightly increase precision but at the cost of substantially increasing sampling effort. More research is needed to identify the main factors involved in this inter-sampling variation to standardise the implementation of EHA under field conditions. [Copyright &y& Elsevier]

Abstract: Disease caused by Dactylogyrus vastator has resulted in considerable economic damage in aquaculture. To control this parasite effectively, the anthelmintic properties of several extracts obtained from Euphorbia fischeriana and four common anthelmintic drugs (trichlorfon, praziquantel, 40% phoxim and mebendazole) against adults and eggs of D. vastator were assessed in vitro and in vivo. Trichlorfon (0.5, 1 and 1.5mg/L), praziquantel (10 and 20mg/L), 40% phoxim (0.1, 0.2 and 0.4mg/L), mebendazole (0.02 and 0.04mg/L) and the ethyl acetate extract of E. fischeriana (10 and 20mg/L) were effective to kill the parasites in vitro, while the other extracts (petroleum ether, n-butanol and distilled water) of E. fischeriana had no significant effects. Praziquantel effectively killed adults with the efficacy of 80.3% at 20mg/L and inhibited egg hatching, while trichlorfon and the ethyl acetate extract of E. fischeriana effectively eliminated adult parasites with the efficacy of 87.3% and 80.1% at 2.5mg/L and 14mg/L, but had no effect on egg viability. 40% phoxim was highly effective in suppressing egg hatching, but mebendazole was not significantly effective on either adults or eggs. Overall, this study found that 40% phoxim and praziquantel could prevent horizontal infection via eggs in aquaculture facilities and that trichlorfon, praziquantel and the ethyl acetate extract of E. fischeriana could be effective against adult parasites. However, the effective dose of the ethyl acetate extract of E. fischeriana was very close to the toxic dose, a factor that likely limits its practical application in aquaculture. [Copyright &y& Elsevier]

Abstract: Cyathostomins are considered to be the most important group of helminths to affect equids due to their high prevalence, potential pathogenicity and ability to develop anthelmintic resistance. Their control relies almost exclusively on frequent anthelmintic use. Currently, fenbendazole (FBZ), pyrantel embonate (PYR), ivermectin (IVM) and moxidectin (MOX) are licensed for use in horses in the UK. With no new anthelmintics likely to be licensed in the near future, it is essential that investigations into the efficacy of current anthelmintics in different locations are performed to help inform control programmes. Here, efficacy of FBZ, PYR, IVM and MOX in horse populations in the South of England was investigated. Horses with a strongyle faecal egg count (FEC) of ≥50eggs per gram (EPG) were enrolled onto a faecal egg count reduction test (FECRT) study. Efficacy was determined by calculating the percentage reduction in FEC between the group mean at Day 0 and 14 days post-treatment. Efficacy was indicated when a group arithmetic faecal egg count reduction (FECR) of ≥90% was recorded for FBZ and PYR, and ≥95% for IVM and MOX. Between March and December 2012, 404 FECRT were performed on 12 yards examining 101, 110, 93 and 100 equids for FBZ, PYR, IVM, and MOX, respectively. FBZ resistance was identified on all yards (mean FECR range 0–65.8%). On 10 of 12 yards, PYR efficacy was >90% (91.0–99.4%) and on two yards, PYR resistance was suspected (86.8–87.2%). IVM (96.4–100%) and MOX (99.9–100%) were >95% efficacious on all yards. As the prevalence of FBZ resistance was 100%, the future use of this anthelmintic for the control of strongyles should be questioned. PYR should be used strategically to reduce reliance on the macrocyclic lactone class products. Over-dispersion of FEC between horses was observed (average k =0.21) with 80% of the strongyle eggs counted measured in 15% of horses tested, strongly supporting the application of targeted helminth control programmes in this host species. [Copyright &y& Elsevier]

Abstract: The faecal egg count reduction test (FECRT) is the main method of detection of anthelmintic resistance (AR) in nematodes of veterinary importance. However, although the FECRT is standardised, the diagnostic performance of this method has not been fully characterised. In this survey Monte Carlo routines were used to simulate the estimation of faecal egg count reduction (FECR) with several FECRT protocols that were performed under different field and laboratory conditions. The goal was to determine, from a practical viewpoint, the most suitable protocols for farm routines and to evaluate the diagnostic performance of FECRTs across different parasitological scenarios with several levels of AR. The simulated field procedures included variations in the sample size and the sampling (or not) of a control group, whereas the simulated laboratory procedures comprised group mean individual-based vs. composite-based FECR estimations and variations in the egg detection threshold of the McMaster technique. For composite procedures, the random weight variations among individual samples and an increased number of McMaster chamber counts were also simulated. The results showed that FECRTs were moderately affected by inaccuracy but crucially affected by imprecision, and both parameters were clearly dependent on the parasitological conditions and the laboratory and field procedures used. An individual-based FECRT method performed without a control group was the most appropriate to quantify the AR, whereas a composite-based method with a control group was the easiest method for discriminating susceptible and resistant parasite populations. More interestingly, the diagnostic performance of the simulated FECRT methods was low for the procedures that are currently recommended by the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) and for many of the typical field and laboratory procedures that are currently implemented. Therefore, the results suggest that the diagnostic performance of the FECRT should be re-evaluated, and the recommendations of the W.A.A.V.P. should be redefined. Finally, theoretic critical conditions for FECRT procedures have been defined to improve future AR surveys and to allow the interpretation of FECRT results with the necessary caution according to the diagnostic performance expected for every FECRT procedure and parasitological scenario. [Copyright &y& Elsevier]

Abstract: A study was conducted between April and July, 2011 to determine and compare the efficacy of albendazole (ABZ), levamisole (LVM) and ivermectin (IVM) against gastrointestinal nematodes in naturally infected Mubende and Boer crossbred goats at the National Semi-arid Resources Research Institute in Serere, Uganda. Forty Mubende goats and 31 Boer crosses were each blocked by age and sex and randomly assigned to four groups. The first group of each breed served as the untreated control, the second was treated with albendazole (5mg/kg BW), the third with levamisole hydrochloride and oxyclozanide (7.5 and 15mg/kg BW) and the fourth with ivermectin (0.2mg/kg BW). Each group included 7–11 animals. Treatments were administered with doses of goats in albendazole and ivermectin, and doses of sheep in levamisole, as recommended by the manufacturers. In the treated groups, goats received anthelmintics basing on individual weights. Fecal egg counts, expressed as eggs per gram and larval cultures were done on day zero before treatment and on day 13 after anthelmintic treatment. Efficacy for each anthelmintic was determined by the Fecal Egg Count Reduction Test (FECRT). In Mubende goats, ABZ, LVM, and IVM reduced FEC by 28.5%, 91%, and 98%, respectively. In Boer crosses, ABZ, LVM, and IVM reduced FEC by 11%, 84.88% and 78.47%, respectively. At a 95% CI, only IVM was more effective in Mubende goats than Boer crosses (t =2.564, p <0.05). This may indicate occurrence of anthelmintic resistance in the goat farming sector in Uganda. Further studies need to be done to clarify the state of efficacy of the commonly used anthelmintics covering different agro ecological zones and species of animals in Uganda. [Copyright &y& Elsevier]

The article discusses research on the impact of anthelmintic drugs moxidectin, ivermectin and albendazole on free-ranging kangaroos at a golf course in Victoria. Particular focus is given to the strongylid fecal egg counts (FECs) over time and anthelmintic efficacy using fecal egg count reduction tests (FECRTs). Findings revealed low efficacy for moxidectin and ivermectin with maximum FEC reductions. Meanwhile, treatment with albendazole reduced FECs by 100% in kangaroos.

Abstract: Parasitic infections constitute an important group of diseases in sheep concerning the health status, welfare and productivity. On a global scale, there are considerable differences concerning the epidemiological situation with respect of the various parasite species. However, there are also numerous species, which occur on all continents and, potentially, in every country. Accordingly, the present review aims to providing an overview about the recent developments in methods and technologies for the laboratory diagnosis of parasite infections in sheep. Following in principle a systematic order the review encompasses publications addressing the diagnosis of helminthes (i.e., trematodes, cestodes and nematodes) and arthropod species. New approaches using conventional (e.g., microscopic), immunological and molecular techniques are being considered. The diagnosis of anthelmintic resistance is highlighted separately, due to its significant importance. The review ends with an outlook into the future by discussing most recent technological advances, which might become of use for the diagnosis of parasite infections in sheep in the future. [Copyright &y& Elsevier]

Abstract: The faecal egg count reduction test (FECRT) is the method of choice to monitor anthelmintic efficacy against gastro-intestinal nematodes in livestock. Guidelines on how to conduct a FECRT are made available by the World Association for the Advancement of Veterinary Parasitology (WAAVP). Since the publication of these guidelines in the early 1990s, some limitations have been noted, including (i) the ignorance of host–parasite interactions that depend on animal and parasite species, (ii) their feasibility under field conditions, (iii) appropriateness of study design, and (iv) the high detection limit of the recommended faecal egg count (FEC) method. Therefore, the objective of the present study was to empirically assess the impact of the level of excretion and aggregation of FEC, sample size and detection limit of the FEC method on the sensitivity and specificity of the FECRT to detect reduced efficacy (<90% or <95%) and to develop recommendations for surveys on anthelmintic resistance. A simulation study was performed in which the FECRT (based on the arithmetic mean of grouped FEC of the same animals before and after drug administration) was conducted under varying conditions of mean FEC, aggregation of FEC (inversely correlated with k), sample size, detection limit and ‘true’ drug efficacies. Classification trees were built to explore the impact of the above factors on the sensitivity and specificity of detecting a truly reduced efficacy. For a reduced-efficacy threshold of 90%, most combinations resulted in a reliable detection of reduced and normal efficacy. For the reduced-efficacy threshold of 95% however, unreliable FECRT results were found when sample sizes <15 were combined with highly aggregated FEC (k =0.25) and detection limits ≥5 EPG or when combined with detection limits ≥15 EPG. Overall, an increase in sample size and mean preDA FEC, and a decrease in detection limit improved the diagnostic accuracy. FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The results highlight that (i) the interpretation of this FECRT is affected by a complex interplay of factors, including the level of excretion and aggregation of FEC and (ii) the diagnostic value of FECRT to detect small reductions in efficacy is limited. This study, therefore, provides a framework allowing researchers to adapt their study design according to a wide range of field conditions, while ensuring a good diagnostic performance of the FECRT. [Copyright &y& Elsevier]

Abstract: There has been an increase in the number of wild ungulates kept in captivity for ecotourism and conservation in Zambia and these animals are susceptible to a number of diseases including gastrointestinal helminth infections. Surveys to determine anthelmintic efficacy to gastrointestinal nematodes in captive-wildlife are not common and there have been no reports of anthelmintic resistance in captive-wildlife in Zambia. This study was carried out to determine the efficacy of the benzimidazole anthelmintic fenbendazole in captive wild impala (Aepyceros melampus) in Zambia. During the month of April 2011, at the end of the rainy season, the faecal egg count reduction test was performed at a private game facility for assessing anthelmintic efficacy of oral fenbendazole and the anthelmintic treatment showed an efficacy of 90%. Haemonchus spp. and Trichostrongylus spp. were the predominant genera present before treatment, but Haemonchus spp. larvae were the only genus recovered from the faecal cultures after anthelmintic treatment. This represents the first documentation of anthelmintic treatment failure in captive wild-antelopes in Zambia. It also demonstrated the ineffectiveness of the common traditional practice of deworming captive-wild antelopes at the end of the rainy season due to the rapid re-infection of impala that occurs due to high pasture infectivity. Suggestions on changes to current anthelmintic use/practices that will make them more efficacious and reduce the possibility of development of anthelmintic resistance in captive wild game in Zambia are also made. [Copyright &y& Elsevier]

Abstract: As it has been 30 years since a new anthelmintic class was released, it is appropriate to review management practices aimed at slowing the development of anthelmintic resistance to all drug classes. Recommendations to delay anthelmintic resistance, provide refugia and the use of a simulation model were reviewed to find optimum treatment strategies that maintain nematode control. Simulated Australian conditions indicated that a common successful low-risk treatment program was a rapid rotation between a “triple-combination” product (benzimidazole+levamisole+abamectin) and a new high-efficacy drug (monepantel). Where Haemonchus contortus was a threat, moxidectin was required at critical times because of its persistent activity against this parasite. Leaving up to 4% of adult sheep untreated provided sufficient “refugia” for non-selected worms to reduce the risk of selecting for anthelmintic resistance without compromising nematode control. For a new anthelmintic, efficacy estimated by faecal egg count reduction (FECR) is likely to be at or close to 100%, however using current methods the 95% confidence limits (CL) for 100% are incorrectly determined as 100%. The fewer eggs counted pre-treatment, the more likely an estimate of 100% will occur, particularly if the true efficacy is >90%. A novel way to determine the lower-CL (LCL) for 100% efficacy is to reframe FECR as a binomial proportion, i.e. define: n and x as the total number of eggs counted (rather than eggs per gram of faeces) for all pre-treatment and post-treatment animals, respectively; p the proportion of resistant eggs is p = x/n and percent efficacy is 100×(1− p) (assuming equal treatment group sizes and detection levels, pre- and post-treatment). The LCL is approximated from the cumulative inverse beta distribution by: 95%LCL=100×(1−(BETAINV(0.975, x +1, n − x +1))). This method is simpler than the current method, independent of the number of animals tested, and demonstrates that for 100% efficacy at least 37 eggs (not eggs per gram) need to be counted pre-treatment before the LCL can exceed 90%. When nematode aggregation is high, this method can be usefully applied to efficacy estimates lower than 100%, and in this case the 95% upper-CL (UCL) can be estimated by: 95%UCL=100×(1((BETAINV(0.025, x +1, n − x +1))), with the LCL approximated as described above. A simulation study to estimate the precision and accuracy of this method found that the more conservative 99%CL was optimum; in this case 0.975 and 0.025 are replaced by 0.995 and 0.005 to estimate the LCL and UCL, respectively. [Copyright &y& Elsevier]

Abstract: The current accepted standard for evaluating the efficacy of gastrointestinal anthelmintic drugs is necropsy of infected animals followed by a comparison of worm counts between treated and non-treated groups. In this study capsule endoscopy, a minimally invasive method of imaging the small intestine of humans, is evaluated as a possible alternative to necropsy for the purposes of worm quantification in dogs. Eighteen Beagle dogs were included in this study. These dogs were part of a separate trial intended to determine the efficacy of various candidate parasiticides against Ancylostoma caninum via the necropsy standard. Dogs were inoculated with A. caninum L3s 4weeks prior to treatment with one of the candidate compounds; a control group (n =8) received no treatment. Capsule endoscopy was performed 6–14days post-treatment, followed by necropsy the following day. Seventeen dogs had complete examinations, i.e. the capsule traversed the small intestine and reached the colon within the battery life of the capsule. A strong correlation (r s =0.87, P <0.0001) was observed between the worm counts acquired by capsule endoscopy and necropsy. There was no clear relationship between the ability of the capsule endoscope to detect hookworms and either visibility of the intestinal lumen or small intestinal transit time. Generation of a virtual spatial record of hookworm location from the capsule endoscopy data revealed a temporal trend, with the majority of worms present in the proximal small intestine in the morning versus the central to distal small intestine in the afternoon. Worm distribution as determined by capsule endoscopy closely resembled post-mortem findings. In conclusion, capsule endoscopy shows promise as an alternative to necropsy for the enumeration of A. caninum in the canine small intestine, although further work is required to improve completion rates and optimise intestinal examination. [Copyright &y& Elsevier]

Abstract: Anthelmintic resistant cattle nematodes have been reported in different regions around the world. However, in Western Europe the assessment of the problem relies largely on case reports and no prevalence data based on wide-scale surveys are available. Therefore, we performed a survey to (1) screen for reduced anthelmintic efficacy in Belgian and German cattle farms; (2) evaluate the usefulness of a simplified faecal egg count reduction test (FECRT), where efficacies are based on the mean FECs of 10 at random collected faecal samples pre- and post-treatment per farm and (3) identify possible risk factors for reduced anthelmintic efficacy. Of 88 farms included in this study, 84 farms used macrocyclic lactones (MLs). A FECR <95% was observed on 39% of these 84 farms. However, using a Markov chain Monte Carlo simulation analysis, to correct for the used McMaster FEC technique with a detection limit of 50epg, reduced efficacy could only be confirmed in 25% of the farms (21/84). Only Cooperia spp. were found in significant numbers in the coprocultures post-treatment. Reduced efficacy was significantly associated with farm type and with a lower efficacy in beef herds compared to dairy herds. Four farms were revisited and a standardized FECRT was performed to confirm anthelmintic resistance (AR). Surprisingly, macrocyclic lactone resistance against Cooperia oncophora was only confirmed in one of four farms. In conclusion, our results show that a reduced efficacy observed in a FECRT are not only caused by AR but that the detection limit of the FEC technique used and the (in)correct administration of the anthelmintic drugs are confounding factors of major importance. [Copyright &y& Elsevier]

Abstract: The Faecal Egg Count Reduction Test (FECRT) is the most widely used method of assessing the efficacy of anthelmintics, and is the only in vivo technique currently approved for use with horses. Equine Faecal Egg Count (FEC) data are frequently characterised by a low mean, high variability, small sample size and frequent zero count observations. Accurate analysis of the data therefore depends on the use of an appropriate statistical technique. Analyses of simulated FECRT data by methods based on calculation of the empirical mean and variance, non-parametric bootstrapping, and Markov chain Monte Carlo (MCMC) are compared. The MCMC method consistently outperformed the other methods, independently of the distribution from which the data were generated. Bootstrapping produced notional 95% confidence intervals containing the true parameter as little as 40% of the time with sample sizes of less than 50. Analysis of equine FECRT data yielded inconclusive results in 53 of 63 (84%) datasets, suggesting that the routine use of prior sample size calculations should be adopted to ensure sufficient data are collected. The authors conclude that computationally intensive parametric methods such as MCMC be used for analysis of FECRT data with sample sizes of less than 50, in order to avoid erroneous inference about the true efficacy of anthelmintics in the field. [Copyright &y& Elsevier]

Abstract: The process of conducting a faecal egg count reduction test was simulated to examine whether arithmetic or geometric means offer the best estimate of efficacy in a situation where the true efficacy is known. Two components of sample variation were simulated: selecting hosts from the general population which was modelled by the negative binomial distribution (NBD), and taking an aliquot of faeces from the selected host to estimate the worm egg count by assuming a Poisson distribution of sample counts. Geometric mean counts were determined by adding a constant (C) to each count prior to log transformation, C was set at 25, 12 or 1. Ten thousand Monte Carlo simulations were run to estimate mean efficacy, the 2.5% (lower) and the 97.5% (upper) percentile based on arithmetic or geometric means. Arithmetic means best estimated efficacy for all different levels of worm aggregation. For moderate levels of aggregation and with C =1 the geometric mean substantially overestimated efficacy. The bias was reduced if C was increased to 25 but the results were no better than those based on arithmetic means. For very high levels of aggregation (over-dispersed populations) the geometric mean underestimated efficacy regardless of the size of C. It is recommended that the guidelines on anthelmintic resistance be revised to advocate the use of arithmetic means to estimate efficacy. [Copyright &y& Elsevier]

Abstract: The rapid development of anthelmintic resistance, associated with the high cost of the available anthelmintic drugs, has limited the success of gastrointestinal nematodiosis control in sheep and goats and thus created interest in studying medicinal plants as an alternative source of anthelmintics. We tested ethyl acetate and ethanol extracts of Azadirachta indica on Haemonchus contortus eggs and larvae. The extracts were evaluated at five concentrations: 0.19, 0.78, 3.12, 12.5 and 50.0mg/ml. At 50mg/ml, the ethyl acetate extract inhibited egg hatching by 51.31% and larval development by 68.10%. The ethanol extract was more effective, inhibiting egg hatching by 99.77% at 3.12mg/ml and larval development by 87.11% at 50mg/ml. These results suggest A. indica extracts may be useful in the control of gastrointestinal nematodes of small ruminants. However, in vivo studies and toxicological evaluation are still necessary. [Copyright &y& Elsevier]

The faecal egg count reduction (FECR) in faeces is the most widely used method to assess the efficacy of anthelmintics against gastrointestinal strongyles. Several methods are used and they yield different efficacy values. They give important weight to those animals which excrete the majority of eggs, before or after treatment. We propose using individual animal FECR tests that give equal weight to every tested host. The first method is based on a before and after treatment without untreated controls, whereas the second one takes into account the use of non-treated control hosts. Confidence interval at P=0.95 were established on bootstrap resamples for both individual-based methods. The individual-based FECR presented lower values than the average-based FECR in most cases. The individual FECR provided reliable evaluation when egg counts were over 300 eggs/g and when at least 10 animals were tested. [Copyright &y& Elsevier]

Albizia anthelmintica Brong., belongs to the plant family Mimosaceae. The plant is widely used in East Africa by poor smallholder farmers and pastoralists to treat their livestock against internal parasites. The anthelmintic effects of water extracts from the bark of A. anthelmintica, obtained from three different geographic areas in Kenya and using different methods of preparation, were tested at different doses in sheep and mice infected with the nematode parasites Haemonchus contortus and Heligmosomoides polygyrus, respectively. Lambs were infected with 3000 infective larvae of H. contortus and treated with the plant preparations 28 days later, while mice were infected with 200 infective larvae of H. polygyrus and treated 18 days later. Proximate analysis established high levels of crude proteins in A. anthelmintica bark. Two sheep out of the 45 treated with the plant preparations suffered from transient bloat, which was relieved by dosing with a surfactant. Significant reductions in faecal egg counts were observed in lambs treated with A. anthelmintica in two of the three experiments undertaken, but the efficacy levels achieved were well below the 70% reduction required. Similar values of packed red cell volume and live weight gain were observed for treated and control lambs. There was no overall significant effect of treatment with A. anthelmintica on faecal egg and total worm counts in mice. A dose rate of 1000 mg/kg bodyweight of A. anthelmintica preparation resulted in death of all mice. The results show that A. anthelmintica at the doses and preparations used is not efficacious against H. contortus in sheep or against H. polygyrus in mice. [Copyright &y& Elsevier]

A total of 80 crossbred, high-risk heifers (initially 250 ± 4.2 kg BW), were transported from an Oklahoma City, Oklahoma sale barn to the Kansas State University Beef Cattle Research Center. Cattle were unloaded and randomly placed into one of four receiving pens and provided ad libitum hay and water. Each pen was randomly assigned to one of the four rest times before processing: (1) immediately upon arrival (0); (2) after a 6-h rest period (6); (3) after a 24-h rest period (24); and (4) after a 48-h rest period (48). After all cattle were processed, heifers were allotted into individual pens with ad libitum access to a receiving ration and water. Heifers were weighed individually on d 0, 7, 14, 21, 28, and 35 to calculate average daily gain (ADG). Feed added and refusals were measured daily to determine dry matter intake (DMI). A fecal egg count reduction test and analysis of blood serum metabolites were also conducted. All data were analyzed using the GLIMMIX procedure of SAS (v. 9.4, Cary, NC) with individual animal as the experimental unit. Processing time did not impact ( P > 0.05) heifer BW or ADG. From d 0 to 35, DMI decreased linearly ( P = 0.027) as rest time increased. The number of days for heifers to reach a DMI of 2.5% BW was linearly increased ( P = 0.023) as rest time increased. There was no evidence of differences ( P ≥ 0.703) among rest times for feed efficiency. While morbidity did not differ between treatments ( P > 0.10), mortality increased linearly ( P = 0.026) as the time of rest increased. A significant processing time × day interaction ( P < 0.0001) was observed for the prevalence of fecal parasites, where the percentage of positive samples was significantly lower 14-d after anthelmintic treatment, regardless of the processing time. Serum IBR titer for heifers processed at either 0 or 6-h upon arrival was significantly higher ( P < 0.01) on d 35 compared to d 0. Heifers processed after a 48-h rest period had significantly higher glucose values ( P < 0.01) on d 0 compared to heifers processed at 0, 6, or 24-h. In summary, rest time prior to processing did not impact receiving calf growth performance. A 6-h rest period upon arrival appeared to be most beneficial to DMI. Anthelmintic treatment at processing reduced the parasitic load in heifers processed at all times. Vaccine titer did not increase after initial processing in heifers processed 24- or 48-h after arrival, indicating the seroconversion of IBR antibodies during the longer rest period., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Anthelmintic resistance (AR) is a growing concern for effective parasite control in farmed ruminants globally. Combatting AR will require intensified and integrated research efforts in the development of innovative diagnostic tests to detect helminth infections and AR, sustainable anthelmintic treatment strategies and the development of complementary control approaches such as vaccination and plant-based control. It will also require a better understanding of socio-economic drivers of anthelmintic treatment decisions, in order to support a behavioural shift and develop targeted communication strategies that promote the uptake of evidence-based sustainable solutions. Here, we review the state-of-the-art in these different fields of research activity related to AR in helminths of livestock ruminants in Europe and beyond. We conclude that in the advent of new challenges and solutions emerging from continuing spread of AR and intensified research efforts, respectively, there is a strong need for transnational multi-actor initiatives. These should involve all key stakeholders to develop indicators of infection and sustainable control, set targets and promote good practices to achieve them., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Quarantine treatments can be used to prevent bringing resistant parasites onto a farm. However, in the face of growing anthelmintic resistance and variations in farm practices, assessing efficacy of such treatments before full implementation is needed. In this case report, a combination treatment of ivermectin (injectable formulation) and fenbendazole (both approximately double doses) administered orally within minutes of each other was assessed in 19 sheep. The mean pretreatment Strongylid eggs per gram of feces, determined using a McMaster, was 2639. The mean post treatment count (at 14 days) was 2663 with 12 animals having a decrease in egg counts. There was an average increase of 0.9% using pre and post treatment egg count means. This combination treatment was not effective as a quarantine treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Noxious pathogens always lead to high rates of mortality, which results in severe economic losses in aquaculture. Currently, gyrodactylosis treatments mainly rely on unapproved chemicals, which are not always satisfactory. According to the previous study, arctigenin is an efficient natural product for controlling gyrodactylosis. For the sake of seeking high-efficiency compounds, a new arctigenin derivative (CCA) was synthesized. Next, we evaluated the anthelmintic activity of CCA in vitro and in vivo , and studied the mechanism of action. The number of Gyrodactylus kobayashii significantly reduced as compared with the control group, the EC 50 value at 24 and 48-h after CCA treatment was 0.616 and 0.451 mg/L, respectively, with EC 100 at CCA concentration of 3 mg/L after 1 h bath treatment. In vitro results showed that CCA can rapidly reduce the amount of G. kobayashii and inhibit its mobility that could normally lead to death. The concentration and duration of CCA were positively correlated with the mortality of G. kobayashii. In addition, CCA displayed 100% efficacy against G. kobayashii at 4.0 mg/L after only 20 min exposure. Acute toxicity assay demonstrated that the LC 50 of CCA against goldfish was 5.012 mg/L, which was 8.13 times higher than that of the EC 50. Furthermore, the results of confocal microscope study revealed that CCA leaded to the epidermal structure and dissolved muscles of worms. Moreover, the ATP level of worms were decreased sharply after both in vitro and in vivo exposures with CCA. The anthelminthic mechanism of CCA against gyrodactylids was related to epidermal structure damages and energy insufficient. From the previous study, the EC 50 of CCA against G. kobayashii (0.616 mg/L) was much lower than the EC 50 (1.85 mg/L) of arctigenin (Tu et al., 2018). In summary, CCA is more effective than arctigenin and has great potential in control of Gyrodactylus infections. • A novel arctigenin derivative, chloro (3-chloropropoxy) methanone-arctigenin (CCA), was designed and synthesised. • CCA displayed a better anti- Gyrodactylus kobayashii activity than the lead compound in in vitro and in vivo. • The mechanism of CCA against gyrodactylids was related to epidermal structure damages and inhibition of ATP production. [ABSTRACT FROM AUTHOR]

Monogenean parasites are responsible for severe economic losses of both freshwater and marine aquaculture industries. Current chemotherapeutic treatments are consuming, expensive, and harmful to water quality and human health. Medicinal plants are a reliable source of alternative anthelmintic agents. In the pursuit of novel anti-monogenean drugs, in vivo anthelminthic efficacy of 26 selected phytochemical compounds was studied, by choosing Gyrodactylus kobayashi infecting goldfish (Carassius auratus) as a model. The screening results showed that four compounds (plumbagin (PLB), thymoquinone, osthole and psoralen) had the highest activity against G. kobayashii with EC 99 value ranging from 0.4 to 4.0 mg/L after 48-h exposure. Among these active compounds, PLB was the most efficacious one and selected for the next study. In vitro trials revealed the clear anti-parasitic effects of PLB, with complete death at 45 min of exposure at a concentration of 2.0 mg/L, withdrawal of PLB afterward did not lead to the recovery of the exposed parasites. Bathing G. kobayashii infected goldfish in PLB also significantly reduced the worm burden, with an extremely low EC 50 value of 0.09 mg/L after 48-h immersion. The results also showed that one short bath using very low concentrations of 0.4–0.7 mg/L for 30–60 min was effective in eliminating G. kobayashii infection with no visible fish toxicity. Acute toxicity assay indicated the 48-h LC 50 of PLB against goldfish was 0.657 mg/L. Furthermore, SEM analysis displayed that PLB-mediated worm killing was associated with the tegumental damages. As seen by TEM, in vivo treatment against G. kobayashii with PLB also caused vacuolization and lysis of parasite's tegument, besides, differing degrees of damage to vitelline cells were observed in treated worms. Collectively, simple chemical structure along with the potent efficacy demonstrated that PLB could serve as an ideal leading compound in the development of a commercial drug to control Gyrodactylus infections in aquaculture • Plumbagin showed potent in vitro and in vivo anthelmintic efficacies against G. kobayashii. • Morphological changes and tegumental alternations of worms treated by plumbagin were observed by SEM and TEM. • Plumbagin is safe for fish at the treatment concentrations. [ABSTRACT FROM AUTHOR]

Efficacy of fenbendazole, levamisole and ivermectin was checked in comparison to untreated controls in twenty Jamunapari goats, naturally infected with gastrointestinal nematode parasites. Faecal examination at day 0 revealed an egg per gram of 930 ± 175.1, 1350 ± 421.1, 1060 ± 224.9 and 800 ± 279.7 in group A, B, C and D, respectively having five animals each. The results of larval culture examination revealed the presence of Haemonchus, Trichostrongylus, Oesophagostomum, Bunostomum and Strongyloides spp. in these animals. Faecal egg counts of the animals treated with fenbendazole (group A), levamisole (group B) and ivermectin (group C) were reduced by 23.66, 63.70 and 98.11%, respectively on day 14 post-treatment. [ABSTRACT FROM AUTHOR]

The worldwide increased difficulty to counteract gastrointestinal nematode (GIN) infection in sheep, due to progressing anthelmintic resistance, has led to the evaluation of other alternative helminth control options, mainly from plants. The anthelmintic efficacy of an aqueous Punica granatum macerate was evaluated in sheep naturally infected by GIN in southern Italy. The macerate was chemically characterized by chromatographic analysis coupled with high-resolution mass spectrometry (LC/HRMS) and an aliquot was concentrated to obtain a dry extract. A part was characterized, the remaining washed with methanol to obtain an insoluble residue and methanol phase. In the methanol fraction, the quantitatively predominant gallic acid was purified to obtain the pure molecule. The three fractions thus obtained were used for in vitro studies (i.e., egg hatch test) to verify anthelmintic efficacy. For this purpose, fecal samples were collected from sheep naturally infected by GINs. Fractions were diluted in H2O/DMSO 0.5% at 1.00, 0.5, 0.25, 0.125, 0.05, and 0.005 mg/mL concentrations. Thiabendazole (0.25 and 0.5 mg/mL) and deionized water were used as positive and negative controls, respectively. Egg hatch test results indicated that all fractions caused a significant (p < 0.05) egg hatch inhibition within 48 h of exposure highlighting a high (>82%) efficacy in vitro at all tested doses. Maximal egg hatching inhibition effect was exhibited by the methanol fraction (99.3% and 89.3% at 1 and 0.005 mg/mL concentrations), followed by the insoluble residue and gallic acid (94.7% and 85.3% and 94.0% and 82.7% at 1 and 0.005 mg/mL, respectively). The current study validated the anthelmintic potential of traditional P. granatum macerate against GIN infection in sheep, thus highlighting the role of gallic acid as principal component and justifying a need to undertake further in vivo studies on these ethno-veterinary remedies. [ABSTRACT FROM AUTHOR]

Species of Gyrodactylus are common monogenean ectoparasites of fish and can result in severe economic losses in aquaculture. To find effective and environmentally acceptable therapies to control gyrodactylosis in aquaculture, anthelmintic efficacy of 35 kinds of herbal medicines was investigated against Gyrodactylus kobayashii infecting goldfish (Carassius auratus), and the promising herbal medicines were further isolated by bioassay-guided fractionation. Among the tested extracts, the methanol extract of Paris polyphylla was the most effective and showed 100% anthelmintic activity against G. kobayashii at 20 mg/L, and had a therapeutic index (TI) of 37.9, which is higher than that of widely used formaldehyde-based parasiticides in aquaculture. According to high-performance liquid chromatography (HPLC) analysis, six active compounds were identified: dioscin, polyphyllin I, gracillin, polyphyllin II, polyphyllin VII and polyphyllin VI; among these active compounds, dioscin was the most effective in eliminating Gyrodactylus infections, with EC 50 value of 0.17 mg/L and TI value of 8.18, and exhibiting 100% anthelmintic efficacy at 0.5 mg/L. In order of efficacy, polyphyllin I and gracillin had EC 50 values of 0.21 and 0.19 mg/L and TI values of 5.35 and 4.97, respectively. These findings suggested that dioscin, polyphyllin I and gracillin are effective and safe in the treatment of G. kobayashii infections and might become leading natural compounds for the synthesis and development of therapeutic agents against monogenean parasites in aquaculture. Interestingly, the methanol extract of P. polyphylla had a higher TI value of 37.9 compared to the abovementioned active compounds, although it required higher concentrations to reach 100% anthelmintic efficacy. The results indicated the methanol extract of P. polyphylla was less toxic to fish than the three compounds mentioned above, and although its anthelmintic activity was inferior to that of these compounds, the methanol extract was a relatively safe and beneficial agent for practical application to treat gyrodactylosis in aquaculture. • The methanol extract of P. polyphylla showed 100% anthelmintic activity against G. kobayashii at 20 mg/L. • Dioscin, polyphyllin I and gracillin exhibited high anthelmintic efficacy against G. kobayashii. • The methanol extract of P. polyphylla is a relatively safe and beneficial agent to treat gyrodactylosis in aquaculture. [ABSTRACT FROM AUTHOR]