Evaluation of Therapeutic Approaches for the Treatment of Spironucleus muris in Mice.

Spironucleus muris is an intestinal protozoal pathogen that can infect various species of rodents. The infection can have a wide range of clinical presentations, from no signs of disease to death. In addition, this pathogen can adversely affect research results, especially immunologic and gastrointestinal studies. For these reasons, institutions may exclude Spironucleus muris. However, despite rigorous efforts to keep this pathogen out, it can be common in rodent colonies. The current recommended approach to eradicating this pathogen is by testing and culling positive animals. A similar organism, Giardia muris, has been effectively eliminated by using chemotherapeutics. Therefore, the objective of this study was to determine whether S. muris is also susceptible to chemotherapeutics. Naturally infected mice were randomized to treatment groups after confirmation of positive infection via PCR. Mice received either metronidazole, fenbendazole, a combination of metronidazole-fenbendazole, or acidified water (control) treatments for a period of 4 wk. Each week fecal testing of S. muris was performed via PCR to evaluate the effectiveness of the treatments. At the end of the 4 wk period, mice were euthanized via CO2 inhalation and segments of the proximal gastrointestinal tract were submitted for histopathologic analysis. Treatment with metronidazole or fenbendazole alone or in combination, failed to clear S. muris infected mice. After 4 wk of treatment, none of the mice given fenbendazole via sucralose medicated gel were positive by either PCR or histopathology; however, this finding is most likely due to intermittent shedding rather than chemotherapeutic success. Therefore, the recommendation remains to test-and-cull or rederive mice as necessary to eliminate S. muris from laboratory animal facilities.

Current anthelmintic treatment is not always effective at controlling strongylid infections in German alpaca herds.

BACKGROUND: Endoparasites are considered a major health problem of South American camelids as shown in a recent survey among German and Austrian camelid owners. Although prophylactic and therapeutic measures such as application of anthelmintics are commonly used, treatment efficacy is usually not assessed. Owners have expressed significant concerns regarding the effect of antiparasitic therapy, so this study aimed to evaluate the outcome of anthelmintic treatment in German alpaca herds with different drugs. RESULTS: Overall, 617 samples from 538 clinically healthy alpacas > 1 year-old from 27 farms (n = 11-157 animals/herd) were examined. The most common parasites detected by flotation were Eimeria spp. (75.1%) followed by strongylids (55.0%), Nematodirus spp. (19.3%), cestodes (3.1%) and Trichuris (2.7%). After initial coproscopical examination by flotation and strongylid egg quantification by the McMaster technique, positive animals excreting at least 150 eggs per gram of faeces were included in a faecal egg count reduction test (FECRT) using fenbendazole (n = 71 samples), moxidectin (n = 71) or monepantel (n = 66). Pre-treatment larval cultures (n = 23 positive pooled farm samples) revealed Haemonchus (87% of the farms), Cooperia (43.5%), Trichostrongylus (21.7%), Ostertagia (13.0%), Nematodirus and Oesophagostomum (4.3% each). Fenbendazole treatment reduced egg excretion by 45%, moxidectin by 91% and monepantel by 96%. On the farm level, 13/18 farms that used fenbendazole, 6/6 farms that used moxidectin and 2/5 farms that used monepantel had individual FECR values < 90% (fenbendazole) or < 95% (moxidectin, monepantel). Haemonchus and Cooperia were overrepresented on the farms with reduced treatment efficacy. CONCLUSIONS: Gastrointestinal strongylids are common in German alpacas and fenbendazole in particular was not sufficiently effective to reduce strongylid egg excretion. Although the FECRT could not unambiguously determine anthelmintic resistance in the present study, the finding that small ruminant strongylids, especially Haemonchus, are common in alpacas indicates that determination of effective anthelmintic doses, monitoring of efficacy and adapted (selective) treatment regimens must be implemented as part of sustainable deworming practices in this species in accordance with recommendations for ruminants.

Evaluation and Correlation of Multiple Anthelmintic Resistances to Gastrointestinal Nematodes Using Different Fecal Egg Count Reduction Methods in Small Ruminants of Punjab, India.

PURPOSE: Concordance of multiple anthelmintic resistances for gastrointestinal nematodes in small ruminants by three average-based and two individually based fecal egg count reduction (FECR) tests was evaluated and corrected. METHODS: Sheep and goats (≥ 8 weeks) from five farms were randomly assigned to three treatment groups (I, II, III; n = 10 per group) and one untreated control group (Group IV; n = 10). Group I received fenbendazole at the dose rate of 5 and 10 mg/kg, Group II received ivermectin at the dose rate of 0.2 and 0.4 mg/kg, and Group III received levamisole at the dose rate of 8 and 12 mg/kg body weight orally for sheep and goat, respectively. Three average-based methods of FECR (FECR1, FECR2 and FECR3) and two individually based methods of FECR (iFECR1 and iFECR2) were evaluated. RESULTS: For fenbendazole resistance, Spearman correlation coefficient for FECR1 was non-significant with other formulae, but for FECR2 with FECR3, FECR3 with iFECR1 and iFECR1 with iFECR2 coincidence was significant at 1%, while for FECR2 with iFECR2 and FECR3 with iFECR2 it was significant at 5%. Spearman correlation coefficients for ivermectin resistance were significant at 1% level and for levamisole it showed significant coincidence at 1% for FECR1 with FECR2 and iFECR1, FECR2 with FECR3 and iFECR1, and iFECR1 with iFECR2, while for FECR1 with FECR3 and iFECR2 coincidence was significant at 5% level. Concordance of kappa values indicated that the coincidence of the prevalence of anthelmintic resistance (95% CI) among the five farms was non-significant. CONCLUSIONS: Concordance between the standard average-based FECR and individually based methods suggests that either method could be applied to small ruminant farms.

Effect of strategic deworming on Ascaris suum exposure and technical performance parameters in fattening pigs.

The aim of this study was to investigate the effect of a strategic deworming program on Ascaris suum infection levels and technical performance parameters in fattening pigs. Eighteen fattening stables were selected and divided into two groups. Group 1 consisted of 9 stables in which the fattening pigs tested seropositive for Ascaris, indicative for the presence of Ascaris eggs in the stable, whereas group 2 consisted of 9 stables in which the fattening pigs tested seronegative for Ascaris, indicating of a low or absent environmental contamination with Ascaris eggs. The production in each stable was monitored for a period of 7 consecutive fattening rounds. The first of these 7 fattening rounds (i.e. round 0), during which no intervention took place in the deworming strategy applied in the stable, served as a historical control. A deworming program using 200 mg/ml fenbendazole oral suspension in drinking water for 2 days every 6 weeks was implemented for a period of 6 consecutive fattening rounds. For each fattening round and for each stable, technical performance parameters including average daily growth, feed conversion ratio, days in fattening and the percentage of affected livers were obtained from the producers. Blood was collected from 10 randomly selected animals per stable at the end of each fattening round and evaluated for the presence of anti-Ascaris antibodies using 2 different serological tests, namely the AsHb- and the L3-Lung ELISA. The serological results obtained indicated a lower exposure of the animals to Ascaris after the implementation of a strategic deworming program. A significant decline in anti-Ascaris antibody levels was detectable in the stables that originally tested positive for Ascaris and was already visible after one treatment round. The outcomes of hierarchical linear mixed models indicated that the level of L3-Lung antibody reactivity was a significant predictor of decreased ADG, increased FCR and prolonged DIF for the Ascaris-positive herds, indicating an effect of Ascaris infections on productivity.

Effects of fenbendazole and triclabendazole on the expression of cytochrome P450 1A and flavin-monooxygenase isozymes in bovine precision-cut liver slices.

Combinations of the anthelmintics fenbendazole (FBZ) and triclabendazole (TCBZ) have shown enhanced efficacy against the liver fluke Fasciola hepatica. This study aimed to measuring the constitutive expression of CYP1A1, CYP1A2, FMO1 and FMO3, thought to be involved in the metabolism of those compounds, by using an absolute quantitative real time (RT)-PCR approach in bovine precision-cut liver slices (PCLS). It also aimed to characterize the effects of FBZ and TCBZ (alone and in combination) on the expression and activity of the aforementioned isozymes. Both FMO1 and FMO3 were equally represented in control PCLS, whereas CYP1A2 was expressed more than CYP1A1 (P<0.05). PCLS cultured in the presence of beta naphthoflavone (ß-NF; CYP1A inducer) had higher mRNA levels of CYP1A1, CYP1A2, FMO1 and FMO3 (P<0.05). No clear-cut evidence of transcriptional effects of the anthelmintics were recorded. After incubation of PCLS with FBZ, there was a significant increase (P<0.05) vs. controls and TBCZ was observed for CYP1A1. PCLS treated with FBZ showed a higher (P<0.05) expression of CYP1A2 compared to controls, TCBZ alone, and the combination FBZ+TCBZ. The gene expression profiles of FMO1 and FMO3 were not affected by the presence of the anthelmintics; the only exception was an upregulation of FMO3 by TCBZ alone. The observed transcriptional effects of the xenobiotics were not mirrored by increased enzyme activities using prototypical substrates of the isozymes under study. Although further confirmatory studies are needed, these results suggest that PCLS represent an alternative in vitro tool for studies on the expression, regulation and function of relevant xenobiotic-metabolizing enzymes in cattle.

Estimating the impact of administration of dewormers on smallholder chickens in Odisha State, India.

Helminth infections, in particular infections with nematodes are highly prevalent and an impediment to the productivity of chickens in smallholder settings. Infections can be easily and cheaply treated using dewormers. We present an empirical framework for estimating the impact of administration of locally available dewormers on chicken weight in a smallholder setting in Odisha State of India. We recruited 1,040 chickens aged between 40 and 70 d from 168 households in 13 village groups in Odisha. Chickens were randomly assigned to treatment with a dewormer (fenbendazole), or non-treatment. Each chicken was tagged with 2 legbands and weighed, then followed up after 28 and 56 d and reweighed. To account for the local variations in exposure and for variations between flocks, the data were analyzed in a multilevel mixed model with flock within village as nested random effects. After 56 d, the modeled results showed that all chickens had gained a mean of 288.3 g but heavier chickens at the baseline gained more weight than lighter chickens. In addition to this, the treated chickens had gained an additional mean of 90.55 g relative to non-treated chickens (P < 0.001). In this setting, we have demonstrated that administration of dewormers has a clear beneficial impact on chicken weight, but it also indicates that other management practices can have a substantial impact on chicken weight.

Effects of Fenbendazole-impregnated Feed and Topical Moxidectin during Quarantine on the Gut Microbiota of C57BL/6 Mice.

To protect the biosecurity of research rodent colonies, research institutions frequently require a quarantine period for live animals transferred into their facilities. Quarantine practices often include antibiotic and antiparasitic treatment with drugs such as fenbendazole and macrolide lactones. The influence of these compounds on the resident gut microbiota of mice is unknown, and any effects might subsequently affect model reproducibility. To test the influence of standard quarantine procedures on the composition of the microbiota, C57BL/6 mice, purchased from 2 different commercial suppliers, were randomly assigned to treatment groups (n = 12) by vendor and treated with fenbendazole-supplemented feed, topical moxidectin, both treatments, or no treatment (control), according to our institution's standard treatment regimen and duration. Feces were collected on arrival, immediately after completing the 8-wk treatment, and at 2 and 4 wk after treatment. Fecal DNA was extracted, sequenced, and analyzed to compare the changes in the microbiota of treated and control groups. Although significant main effects of time and treatment and interactions between those variables were detected in comparisons of richness, α-diversity, and ß-diversity, the effect sizes associated with any particular treatment were consistently much smaller than that associated with acclimation to a new facility in the absence of any quarantine treatments. This outcome, along with the visual evaluation of principal coordinate analysis based on multiple similarity indices, suggests that time or institution plays a larger role in alterations of the murine gut microbiota than do quarantine treatments on its composition.

Development and analytical characterization of a new antiparasitic fenbendazole compound tablet and pharmacokinetic investigations after its oral administration to dogs.

The objective of this study was to prepare a new compound fenbendazole tablet containing 29.7 % fenbendazole, 1.50 % praziquantel and 0.059 % ivermectin for oral administration. The tablets were successfully prepared using mannitol as filler agent, polyvinyl polypyrrolidone as disintegrant, 5 % povidone (PVAK30) as a binder agent and magnesium stearate as lubricant. The appearance, hardness, fragility, time limit of disintegration and fenbendazole dissolution at 45 min all met the technical standards of the Ministry of Agriculture for the People's Republic of China. We used high performance liquid chromatography and electrospray-mass spectrometry for drug detection. Oral administration of 100 mg/kg fenbendazole, 5 mg/kg praziquantel and 0.2 mg/kg ivermectin using a non-compartmental model defined peak plasma concentrations (Cmax) of 495, 826, 73 ng/mL, and 218 ng/mL for the metabolite oxfendazole, respectively. The area under the curve (AUClast) values for these drugs were 4653, 1045, 1971 and 5525 h×ng/mL, respectively. This study enriches the pharmacokinetic data of compound fenbendazole tablets using dogs as a model system. The new tablet formulation was assimilated quickly and systemically and this study will be beneficial for the clinical application of parasite treatments in dogs.

Safety of fenbendazole in common peafowl (Pavo cristatus).

The present study was undertaken to find out the safety levels of fenbendazole in common peafowl. This bird, raised on aviaries and zoos, can be severely parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm) along with other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic in animals. The objective of this work was to provide target animal safety data in young peafowl and to demonstrate reproductive safety in adult birds. During the experimental study, diets containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three times the normal treatment duration). Data for feed consumption, feed conversion rate, and body weights were recorded for each bird in each group. Drug concentrations in different tissues of birds were determined to correlate concentrations with clinical observations, clinical pathology, and histologic findings. There were no morbidities or mortalities after study day 21. Additionally, there were no statistically significant treatment-related differences among above mentioned parameters. Analysis of fenbendazole concentrations in kidney, liver, leg/thigh, and breast muscle and skin with associated fat revealed that, even at the highest dose level used and with no feed withdrawal, fenbendazole concentrations were relatively low in these tissues. These findings indicate that fenbendazole has a relatively wide margin of safety in young peafowl and that the proposed dose of 100 ppm in the feed for 7 consecutive days is well within the margin of safety. In the reproductive safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days and collected data on hatching percentage of peahen eggs before and after treatment. Reproductive performance in peahen was not adversely affected.

A comparison of two different anthelmintic treatment regimens against natural gastrointestinal nematode infections on two Lithuanian sheep farms.

BACKGROUND: According to targeted treatment (TT), the whole flock is dewormed based on knowledge of the risk, or parameters that quantify the mean level of infection, whereas according to targeted selective treatment (TST), only individual animals within the grazing group are treated, based on parasitological, production and/or morbidity parameters. The aim of this study was to compare two different treatment protocols on sheep farms in Lithuania. The study was conducted from 15 April to 31 October 2014 on three sheep farms. On the TT (the whole flock) and T(S)T (with FECs ≥ 300, respectively) farms all adult animals were treated orally with fenbendazole irrespective of EPG counts before the grazing season. The second treatment was applied with injectable ivermectin on both farms. However, on the TT farm all sheep were also treated on 2nd August regardless of their EPG counts, while on the T(S)T farm only those animals with an EPG ≥ 300 were treated on 1 July using a threshold of ≥ 300 EPG. No treatments were administered on the control farm (n = 1) during the study. RESULTS: Spring treatment of ewes significantly reduced nematode faecal egg counts (FEC) both on the TT and T(S)T farms, with the benefit of lowering pasture contamination with infective L3 stage larvae at the start of grazing season, while it remained significantly higher on the control farm. The positive effect of the spring treatment of ewes was reflected by increased body weight gains (BWG) in lambs in the first half of the grazing season. Following the second treatment, the weight gains in lambs on the T(S)T farm were higher compared to lambs on the TT farm, while BWG in the control lambs started to decrease. The difference was also substantiated by the body condition scores (BCS) and dag scores (DS) of lambs, which were highest on the T(S)T farm compared with those on the control and TT farms. CONCLUSIONS: The results of this study show that both treatment strategies were useful in reducing clinical effects (BCS and DS) of gastrointestinal nematode parasitism and increasing the performance in lambs. Furthermore, on the T(S)T farm some of animals were left in refugia, helping to slow down the development of anthelmintic resistance (AR) in future.

Pilot Study to Assess the Efficacy of Ivermectin and Fenbendazole for Treating Captive-Born Olive Baboons (Papio anubis) Coinfected with Strongyloides fülleborni and Trichuris trichiura.

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 µg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.

Effect of fenbendazole in water on pigs infected with Ascaris suum in finishing pigs under field conditions.

The husbandry of pigs for meat production is a constantly developing industry. Most studies on the effects of Ascaris suum infection in pigs and its prevention with anthelmintics are over a decade old. We examined the effect of 2.5mg fenbendazole per kg bodyweight administered in drinking water for two consecutive days on A. suum infection 1 and 6 weeks after pigs arrived to fattening units. We hypothesised that the treatment would reduce the presence of A. suum-infections, improve the average daily weight gain of pigs, reduce the percentage of liver rejections in pens by 50% and increase the lean meat percentage at slaughter by 1%. The study included a placebo group (427 pigs) and a treatment group (420 pigs) spanning four different farms previously reporting ≥15% liver rejection. The treatment was given for 2 consecutive days 1 and 6 weeks after the pigs arrived to the fattening unit. Faecal samples were collected during weeks 1, 6 and 12 from all pigs and examined for A. suum eggs. Blood was collected during weeks 1 and 12 from a subgroup of the pigs and examined for anti-A. suum antibodies and clinical blood parameters. Data on liver rejection and lean meat percentage were collected post-mortem. The proportion of Ascaris seropositive pigs changed from 8.6% to 22.2% and 20.3% to 16.3% in the placebo and treatment group respectively. Fenbendazole reduced the presence of A. suum eggs in faeces the percentage of liver rejections by 69.8%. The treatment did not affect daily weight gain or lean meat percentage. Pigs with A. suum eggs in faeces at week 6 had a lower average daily weight gain of 61.8g/day compared with pigs without parasite eggs. Fenbendazole treatment may be a useful option for farms struggling with persistent A. suum problems and demonstrate a beneficial effect on the weight gain of the animals shedding eggs in faeces and result in fewer condemned livers at slaughter.

Synergistic effects of fenbendazole and metronidazole against Giardia muris in Swiss mice naturally infected.

In this study were proposed different protocols for the treatment of mice naturally infected with Giardia muris. Male Swiss mice were divided into seven groups, with five animals each, in a blind, controlled, randomized by drawing lots and once-repeated experiment. Parasite detection and cure control were performed using the Faust method and search by trophozoites in the intestinal mucosa. Clinical parameters (weight, water and feed consumption, elimination of excreta, aspect of the fur and feces) were also evaluated. All animals were treated with metronidazole (M), fenbendazole (F), and probiotics (P), administered intragastrically, during 7 days. M1, FM1, and F1 groups were treated 1×/day; M3, FM3, and PM3 groups 3×/day; and ST (control group) received only water. After the 5th and 7th days of treatment, the animals in FM1/FM3 and PM3/M3 groups presented, respectively, negative results and remained negative in the following 10 days. Animals in F1 group consumed less water (p = 0.00010) compared with FM1/FM3/PM3. The animals in M1 group compared with FM3/M3, F1 compared with M3, and ST compared with FM1/FM3/M3/PM3 consumed a larger amount of feed (p = 0.00001). The animals in F1 group compared with FM3/M1/M3/PM3, FM1 compared with FM3, and ST compared with FM3/M1/M3/PM3 eliminated lower volume of excreta (p = 0.00001). The results show that the association between F and M potentiates the effects, indicating a synergistic action of these two drugs, and FM1 is the best protocol due to early negativity in the animals, lower concentrations of the drugs, lower risk of toxicity and stress, and less alterations in clinical parameters.

[(IMPACT OF LUNGWORM INFESTATION ON THE BIOCHEMICAL PARAMETERS OF ANIMALS DURING COMBINATION TREATMENT WITH ALBENDAZOLE AND T- AND B-ACTIVIN)].

Lungworm infection is caused by a Dictyocaulus filaria nematode parasitizing the bronchi and bronchioles of sheep and goats. Various anthelmintics, including albendazole, levamisole, fenbendazole, ivermectins, and others, are used to treat the animals. The aim of this investigation was to study the impact of lungworm infestation on the biochemical parameters of animals during combination treatment with albendazole and T- and B-activin. Experiments were carried out in 20 uninfected mongrel lambs aged 4-5 months. Infectious D.filaria larvae were given with water to 15 lambs once orally at a dose of 1000 larvae per head. 5 uninfected lambs served as a control group. The time course of changes in serum bio- chemical parameters was studied in animals. Treatment with Albena in combination with T- and B-activin in lambs ex- perimentally infested with lungworm was found to restore their biochemical reactivity. After sheep treatment with Albena alone, biochemical parameters were noted to tend to normalize, but their normal full recovery did not take place.

Ivermectin failure in the control of Oxyuris equi in a herd of ponies in France.

Drug resistance in equine gastro-intestinal parasitic nematodes has been reported throughout the world. While the focus is usually put on cyathostomins, observations of macrocylic lactone failure against Oxyuris equi have accumulated over the last decade. Here we report the failure of ivermectin in the control of O. equi in an experimental Welsh pony herd. In a first trial, 6 ponies previously drenched with moxidectin and showing patent O. equi infections were administered ivermectin and subsequently monitored for O. equi egg excretion over one month. This trial demonstrated a failure of ivermectin to control O. equi egg excretion as half of ponies demonstrated recurrent egg excretion in the peri-anal region during 21days after treatment. One year later, six female Welsh ponies drenched with moxidectin demonstrated signs of itching and scratching in their peri-anal region with worms being found transiently in fecal materials three weeks later. Ponies were allocated to three treatment groups, i.e. ivermectin, pyrantel embonate and fenbendazole and monitored for egg excretion over five weeks. Fenbendazole and pyrantel embonate broke ivermectin suboptimal efficacy as soon as 8 and 14days respectively after treatment, while egg excretion remained constant throughout the 41-day long trial in the ivermectin-treated ponies. This is the first report of ivermectin failure against O. equi in France. In the absence of critical efficacy test, it remains unclear whether true resistance is at stake or if these observations confound a constitutive suboptimal efficacy of ivermectin against O. equi.

Development and evaluation of a protocol for control of Giardia duodenalis in a colony of group-housed dogs at a veterinary medical college.

OBJECTIVE To develop and evaluate a protocol for control of Giardia duodenalis in naturally infected group-housed dogs at a veterinary medical college. DESIGN Prospective evaluation study. ANIMALS 34 dogs. PROCEDURES All dogs were tested for evidence of G duodenalis infection. Dogs were treated with fenbendazole on study days 1 through 10. On day 5, dogs were bathed and moved into clean, disinfected kennels in a different room to allow for disinfection and drying of their assigned kennels at 26.7°C (80°F) for 24 hours on day 6. After treatment, dogs were returned to their original housing; fecal samples were collected weekly from days 8 through 41 and then every 3 weeks until day 209. Samples were fixed in formalin and examined by direct immunofluorescence assay. Additionally, 1 pretreatment sample underwent PCR assay and DNA sequencing to determine the assemblage (genotype) of the organism. Normal handling routines for the dogs and their use in teaching activities were not changed. RESULTS Initially, all dogs in the colony shed G duodenalis cysts. During and immediately after treatment (days 8 and 13), no cysts were detected in any dogs. On day 20, 1 cyst was observed in the fecal sample from 1 dog; results for all subsequent fecal analyses were negative. The G duodenalis cysts collected from the pretreatment sample had an assemblage C genotype. CONCLUSIONS AND CLINICAL RELEVANCE The integrated protocol was successful in controlling G duodenalis infection in this dog colony, despite exposure of dogs to a variety of environments and frequent handling by multiple individuals. Sequence analysis identified an assemblage typically found in dogs but not in people, indicating that zoonotic transmission would be unlikely.

Influence of sustained deworming pressure on the anthelmintic resistance status in strongyles of sheep under field conditions.

Anthelmintic resistance (AR) status in Madras Red sheep from selected field flocks of a government funded scheme, covered by regular, sustained anthelmintic treatment for more than 10 years was determined. Parameters such as fecal egg count reduction test (FECRT), larval paralysis assay (LPA), and allele-specific-PCR (AS-PCR) were used to test the efficacy of fenbendazole, tetramisole, and ivermectin at recommended doses, in two seasons. Sheep belonging to non-beneficiary farmers were used as controls. Mean FECRT values of beneficiary group during winter and summer seasons were 77.77 and 76.04, 93.65 and 92.12, and 95.37 and 98.06 %, respectively, for fenbendazole, tetramisole, and ivermectin. In the non-beneficiary groups, the corresponding values were 74.82 and 81.09 %, 96.05 and 97.40 %, and 97.26 and 98.23 %, respectively. The results revealed resistance to fenbendazole, suspect resistance to tetramisole and susceptibility to ivermectin in beneficiary flock. In non-beneficiary flock, while resistance was noticed against fenbendazole, both tetramisole and ivermectin were effective. FECR values were found to be significantly different between beneficiary and non-beneficiary groups against tetramisole. The results of LPA confirmed this finding, as 50 % of the Haemonchus contortus larvae were paralyzed at the concentration of 0.0156 µg/ml in the beneficiary group, while those of non-beneficiary groups required lower concentrations of 0.0078 µg/ml. AS-PCR revealed the predominance of heterozygous susceptible population of H. contortus in the beneficiary group. In this study, resistance to fenbendazole was confirmed in both the beneficiary and non-beneficiary groups and this could be attributed to frequent use of benzimidazoles as seen from the deworming records. Emergence of tetramisole resistance was detected in the beneficiary group, where the drug was used continuously for 4 years. Ivermectin was found to be effective in all the flocks. It is recommended that the practice of routine deworming of three to four times a year should be avoided, as it can lead to emergence of anthelmintic resistance.

Experimental insight into the process of parasite community assembly.

Community assembly is a fundamental process that has long been a central focus in ecology. Extending community assembly theory to communities of co-infecting parasites, we used a gastrointestinal nematode removal experiment in free-ranging African buffalo to examine the community assembly patterns and processes. We first asked whether reassembled communities differ from undisturbed communities by comparing anthelmintic-treated and control hosts. Next, we examined the temporal dynamics of assembly using a cross-section of communities that reassembled for different periods of time since last experimental removal. Next, we tested for evidence of assembly processes that might drive such reassembly patterns: environmental filtering based on host traits (i.e. habitat patches), interspecific interactions, priority effects and chance dispersal from the environmental pool of infective stages (i.e. the regional species pool). On average, reassembled parasite communities had lower abundance, but were more diverse and even, and these patterns varied tightly with reassembly time. Over time, the communities within treated hosts progressively resembled controls as diversity and evenness decreased, while total abundance increased. Notably, experimental removal allowed us to attribute observed differences in abundance, diversity and evenness to the process of community assembly. During early reassembly, parasite accumulation was biased towards a subordinate species and, by excluding stochastic assembly processes (i.e. chance dispersal and priority effects), we were able to determine that early assembly is deterministic. Later in the reassembly process, we established that host traits, as well as stochastic dispersal from the environmental pool of infective stages, can affect the community composition. Overall, our results suggest that there is a high degree of resiliency and environmental dependence to the worm communities of buffalo. More generally, our data show that both deterministic and stochastic processes may play a role in the assembly of parasite communities of wild hosts, but their relative importance may vary temporally. Consequently, the best strategy for managing reassembling parasite communities may also need to shift over time.

Efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats.

Trichinellosis is a zoonotic disease caused by nematode species of the genus Trichinella. Anthelmintics targeting the intestinal adults and muscle-dwelling larvae of Trichinella spp. have been tested, with limited success. This study was aimed at determining the efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats. Forty-two Sprague-Dawley rats, with an average weight of 270 g and 180 g for males and females respectively, were infected with T. zimbabwensis larvae. Infected rats were randomly assigned to three groups which were subjected to single treatments with each of maslinic acid, fenbendazole and a combination of both on day 25 post-infection (pi), and three groups which were subjected to double treatments with each of these drugs and a combination on days 25 and 32 pi. The untreated control group received a placebo. In single-treatment groups, the efficacy of each treatment, measured by rate of reduction in muscle larvae, was significant (P0.05). We conclude that the efficacy of maslinic acid against larval stages of T. zimbabwensis in rats was comparable to that of fenbendazole, with no side-effects observed, making maslinic acid a promising anthelmintic against larval stages of Trichinella species.

Comparison of the larvicidal efficacies of moxidectin or a five-day regimen of fenbendazole in horses harboring cyathostomin populations resistant to the adulticidal dosage of fenbendazole.

Despite widespread acknowledgement of cyathostomin resistance to adult icidal dosages of benzimidazole (BZD) anthelmintics, many strongyle control programs continue to feature regularly scheduled larvicidal treatment with fenbendazole (FBZ). However, no studies have been conducted to evaluate the efficacy of larvicidal regimens against encysted cyathostomins in a BZD-resistant (BZD-R) population. A masked, randomized, controlled clinical study was conducted with 18 juvenile horses harboring populations of cyathostomins that were considered BZD-R on the basis of fecal egg count reduction (FECR). Horses were blocked by prior history, ranked by egg counts, and allocated randomly to one of three treatment groups: 1--control, 2--FBZ >10mg/kg once daily for five consecutive days, or 3--moxidectin (MOX) >0.4 mg/kg once. Fecal samples were collected prior to treatment and seven and 14 days after the final dose of anthelmintic. On Days 18-20, complete replicates of horses were euthanatized and necropsied, and 1% aliquots of large intestinal contents were recovered for determination of complete worm counts. The cecum and ventral colon were weighed, and measured proportions of the respective organ walls were processed for quantitation and characterization of encysted cyathostomin populations. The five-day regimen of FBZ achieved 44.6% fecal egg count reduction, had 56.4% activity against luminal adults and larvae, and was 38.6% and 71.2% effective against encysted early third stage (EL3) and late third stage/ fourth stage (LL3/L4) cyathostomin larvae, respectively. In contrast, MOX provided 99.9% FECR, removed 99.8% of luminal stages, and exhibited 63.6% and 85.2% efficacy against EL3 and LL3/L4 mucosal cyathostomins, respectively. Although BZD-R was the most feasible explanation for the lower larvicidal efficacies of FBZ, mean larval counts of moxidectin-treated horses were not significantly different from controls or those treated with FBZ. The lack of significant differences between larvicidal treatments was partially attributed to a small sample size and high variability among worm burdens. Historical differences in the time intervals between treatment and necropsy were identified as a confounding factor for accurate estimation of larvicidal efficacy. Determining appropriate post-treatment intervals for measuring larvicidal efficacy remains a critical regulatory and scientific challenge for this therapeutic area.