Moxidectin Group Research Articles

Alleviating lesions of chronic progressive lymphedema in Belgian draft horses by successfully treating Chorioptes bovis infestation with moxidectin 0.5% pour-on

The aim of this prospective, randomized, single-blinded, and placebo-controlled clinical trial was to investigate the efficacy of a moxidectin pour-on solution for the treatment of Chorioptes bovis infestation in Belgian draft horses, and in addition, to evaluate the effect of this treatment on the clinical signs and lesions associated with chronic progressive lymphedema (CPL). Nineteen privately owned Belgian draft horses were randomly assigned to either a treatment group (moxidectin pour-on formulation, n = 10) or a placebo group (phosphate-buffered saline (PBS), n = 9). On Day 0, all 19 horses tested positive for the presence of C. bovis in superficial skin scrapings. Prior to treatment, all feathering on the distal limbs of the horses was clipped. Treatment was applied twice (Day 0 and 7). Pour-on moxidectin (Cydectin 0.5% Pour-On; Zoetis) was evenly distributed over the distal legs of the horses at a dose of 1.5 mg moxidectin/kg body weight. Animals in the placebo group were treated with PBS. Pretreatment and follow-up examinations consisted of counting living mites in superficial skin scrapings, scoring pruritus, and scoring mange-associated and CPL-associated lesions (skinfold score and skin lesion score). Horses in the placebo group and moxidectin group were followed up to 8 weeks and 24 weeks after the first treatment, respectively. On Day 14, no living mites were found in any of the horses in the moxidectin group (p = 0.013). These horses continued to remain free of mites, until the final sampling conducted at 24 weeks following the initial application of moxidectin, when three horses again showed living mites in skin scrapings. Treatment with moxidectin resulted in a significant reduction of both CPL-associated skin lesion scores (p = 0.003) and pruritus scores (p = 0.001) after only seven days. By Day 56, still no signs of pruritus (p < 0.0001) were detected, with significant improvement of mange-associated lesions (p < 0.0001). Although the skinfold score did not show a significant reduction by Day 56, the score for skin lesions associated with CPL had significantly improved (p < 0.0001). In conclusion, the results of this study demonstrate that pour-on moxidectin, at a high dose and applied directly to the mite predilection site, was an effective treatment for C. bovis infestation in feathered draft horses, providing positive effects on CPL lesions, pruritus and mange-associated lesions. Furthermore, these findings emphasize the therapeutic significance of addressing mange in the management of CPL-affected draft horses.

Efficacy and safety of moxidectin compared with ivermectin against Strongyloides stercoralis infection in adults in Laos and Cambodia: a randomised, double-blind, non-inferiority, phase 2b/3 trial

Infection with the soil-transmitted helminth Strongyloides stercoralis affects up to 600 million people globally, most of whom live in rural areas with poor sanitation. If untreated, infection leads to long-lasting morbidity and might even be life-threatening. Moxidectin might be a promising alternative to ivermectin, the only currently recommended single-dose treatment. We aimed to assess whether moxidectin is non-inferior in terms of efficacy and safety compared with ivermectin. In this randomised, double-blind, parallel-group, non-inferiority, phase 2b/3 trial in communities in Laos and Cambodia, adults aged 18-65 years were screened for the presence of S stercoralis larvae in their stool via sextuplicate quantitative Baermann assays. Using computer-generated group allocation (block randomisation stratified by infection intensity), parasitologically (two or more positive Baermann assays) and clinically eligible participants were randomly assigned (1:1) to receive single oral doses of either moxidectin (8 mg) and ivermectin-matched placebo, or ivermectin (200 μg/kg bodyweight) and moxidectin-matched placebo. The primary endpoint was cure rate assessed at 14-21 days after treatment, using the available-case population analysed according to intention-to-treat principles. Moxidectin was considered non-inferior to ivermectin if the lower limit of the two-sided 95% CI of the difference was greater than the non-inferiority margin of -10 percentage points. Safety endpoints were assessed before treatment, and at 2-3 h, 24 h, and 14-21 days after treatment. This trial is registered at ClinicalTrials.gov, NCT04056325 and NCT04848688. Between Dec 6, 2020, and May 21, 2022, 4291 participants were screened, 726 of whom were enrolled and randomly assigned to moxidectin (n=363) or ivermectin (n=363). For the participants with primary outcome data, we observed a cure rate of 93·6% (95% CI 90·5 to 96·0; 324 of 346 participants) in the moxidectin group and 95·7% (93·0 to 97·6; 335 of 350 participants) in the ivermectin group, resulting in a between-group difference of -2·1 percentage points (95% CI -5·5 to 1·3). The most common adverse events were abdominal pain (32 [9%] of 363 with moxidectin vs 34 [9%] of 363 with ivermectin) and headache (25 [7%] vs 30 [8%]), which were predominantly mild and transient. Moxidectin was non-inferior to ivermectin in terms of efficacy in the treatment of strongyloidiasis. Additionally, both drugs had a similar safety profile. The fixed dose and lower cost of moxidectin compared with ivermectin make it a valuable alternative for people with strongyloidiasis. Swiss National Science Foundation.

Pharmacokinetics of macrocyclic lactone endectocides in indigenous Zebu cattle and their insecticidal efficacy on Anopheles arabiensis

Outdoor biting, outdoor resting, and early evening biting of Anopheles arabiensis is a challenge in current malaria control and elimination efforts in Africa. Zooprophylaxis using livestock treated with macrocyclic lactones is a novel approach to control zoophilic vectors. Therefore, the present study aimed to investigate the pharmacokinetics and insecticidal efficacy of ivermectin (IVER), doramectin (DORA), and moxidectin (MOXI) subcutaneous (SC) formulations in treated calves. The study was conducted using indigenous (Bos indicus) calves treated with SC formulation at a dosage of 0.5, 0.2 or 0.05 mg/kg body weight (BW) IVER or DORA and 0.2 or 0.05 mg/kg BW MOXI. Direct skin feeding of mosquitoes and animal blood sampling were performed at 4, 8, 12, and 24 h and on days 2, 3, 5, 7, 10, 14, 21, 28, and 35 post treatment. The survival of fully fed A. arabiensis mosquitoes was monitored for 10 days. Plasma samples were analyzed using UHPLC-MS/MS. A. arabiensis mortality percentages in the 0.5 mg/kg BW DORA and IVER groups were 65.74% (95% CI: [54.98; 76.50]) and 64.53% (95% CI: [53.77; 75.29]), respectively, over 35 days post treatment. At the recommended dose (0.2 mg/kg BW), promising overall A. arabiensis mortality rates of 61.79% (95% CI: [51.55; 72.03]) and 61.78% (95% CI: [51.02; 72.54]) were observed for IVER and DORA, respectively. In contrast, A. arabiensis mortality in the MOXI group was 50.23% (95% CI: [39.87, 60.58]). At 0.2 mg/kg BW dose, area under the plasma concentration versus time curve (AUC0−inf) values for IVER, DORA, and MOXI were 382.53 ± 133.25, 395.41 ± 132.12, and 215.85 ± 63.09 ng day/mL, respectively. An extended elimination half-life (T1/2el) was recorded for DORA (4.28 ± 0.93 d), at 0.2 mg/kg BW dose level, compared to that for IVER (3.16 ± 1.47 d). The T1/2el of MOXI was 2.17 ± 0.44 day. A maximum plasma concentration (Cmax) was recorded earlier for MOXI (10 h) than for IVER (1.6 days) and longer for DORA (3.0 days). For DORA and IVER, significant differences were found in T1/2el (P<0.05), Cmax (P<0.01), and AUC0−inf (P<0.01) between the higher 0.5 mg/kg BW and the lower 0.05 mg/kg BW doses. The T1/2el and AUC0−inf of DORA and IVER in the present study were significantly (p < 0.05) correlated with the observed insecticidal efficacy against A. arabiensis mosquitoes at 0.2 mg/kg a dose. Therefore, treating cattle with IVER or DORA could complement the malaria vector control interventions, especially in Ethiopia, where the zoophilic malaria vector A. arabiensis majorly contribute for residual malaria transmission.

Caprine Roundworm Nematode Resistance to Macrocyclic Lactones in Northeastern Thailand

Roundworm nematodes are a significant problem in goat meat farming worldwide. These parasites can cause production losses, reduce feed efficiency and compromise animal health and welfare. Macrocyclic lactones (MLs) are common anthelmintic drugs to treat roundworm nematode infection in livestock. The objective of study was to detect roundworm resistance to MLs in meat goats in Northeast Thailand. One hundred and nineteen goats from 6 herds were studied from June to December 2022. Each herd was randomly allocated to control (n=21), epinomectin (n=34), ivermectin (n=40) and moxidectin (n=24) groups. Anthelmintic resistance (AR) was assessed based on the Fecal Egg Count Reduction Test (FECRT) and larva culture at pre-treatment (D0) and 14 days post-treatment (D14). Prevalence of Strongyle nematodes and Trichuris spp. infection was 100% (6/6 herd), and 66.7% (4/6 herd), respectively. The number of Strongyle eggs was significantly reduced in the eprinomectin group (p &lt; 0.01). In contrast, the ivermectin group was significantly increased (p &lt; 0.01). The prevalence of ML resistance of Strongyle nematodes and Trichuris spp. was 83.3% (5/6 herd) and 25.0% (1/4 herd), respectively. The dominant larva was Haemonchus contortus at pre- and post-treatment in every herd. This study demonstrated the presence of ML resistant Strongyle nematodes as H. contortus and Trichuris spp. in this area. To reduce ML resistance it can be useful to use drugs in combination or rotate MLs with other classes of anthelmintics or in targeted treatment programs and integrated parasite management strategies. Consequently, the efficacy of anthelmintic drugs in small ruminants needs to be monitored and surveilled in this area.

Evaluation of Orally Administered Anthelmintic Treatment Options for Dentostomella translucida in Naturally Infected Mongolian Gerbils (Meriones unguiculatus)

This study aimed to evaluate the efficacy of eprinomectin, moxidectin and fenbendazole for treating Dentostomella translucida infections in naturally infected Mongolian gerbils (Meriones unguiculatus). A total of 28 gerbils were placed in individually numbered cages to determine the individual animal parasite load. Eggs per gram (EPG) counts were used to estimate the efficacy of the drugs. The day before the anthelmintic administration was denoted as day 0, and the EPG counts were determined by the McMaster technique from the stool removed from the cage bottom on days 7, 14, 21 and 28. The animals were assigned to one of four treatment groups according to their day 0 EPG counts. The orally administered drugs in the treatment groups were eprinomectin (15 mg/kg), moxidectin (0.4 mg/kg) and fenbendazole (12 mg/kg) for groups 1-3, respectively. The fourth group served as the control (without any drug administration). Treatment efficacy was evaluated based on weekly EPG counts. The values decreased to zero in the fenbendazole group at 4 weeks of follow-up after treatment, and no parasite was found in any of the repeated examinations. The eprinomectin and moxidectin groups exhibited a fluctuating EPG state on both individual and group basis. D. translucida, which is known as the specific parasite of gerbils, can easily affect other members of the animal colony; thus, the control of its presence in gerbil breeding units is necessary. Therefore, the reported effective drug treatments are important for the fight against the investigated parasitic infection.

79 Evaluation of extended release eprinomectin efficacy on multiparous beef cow performance

Abstract Internal parasitism inevitability prompts economic loss in beef cattle production by decreasing growth performance and reproductive traits. Previous studies have conflicting results on the macrocyclic lactones (ML) efficacy against internal parasitism. The objective of this study was to evaluate the efficacy of milbeymycin and avermectin sub groups of ML on cow performance. Multiparous fall calving, crossbred beef cows (n = 106) were allocated randomly to 1 of 3 anthelmintic treatments: 1) Negative control (CON), in which cows did not receive an anthelmintic, 2) Injectable moxidectin (MOX) and 3) Injectable extended release eprinomectin (ERE). Body weights (BW), body condition scores (BCS), and fecal egg counts (FEC) were taken throughout the duration of the calving season to weaning on d0, d80, d162, and d217, with weaning occurring on d217. Performance data were analyzed using the MIXED procedures of SAS, and pregnancy data were analyzed using the GENMOD procedures of SAS. Significance was fixed at P &amp;lt; 0.05 and tendencies were established from 0.05 ≤ P ≤ 0.10. There was no effect of anthelmintic treatment on cow BW (P ≥ 0.57) or cow BCS (P ≥ 0.22) during the 217 d study; however, CON cows tended to have lower BCS (P = 0.08) throughout the duration of the study. Cows treated with ERE had fewer FEC compared to MOX and CON groups (P ≤ 0.001), and tended to improve pregnancy rates (c2 = 0.0546). Calf weaning weight was similar among treatments averaging 216, 225, and 223 kg regarding CON, MOX, and ERE cow treatments, respectively.

80 Evaluation of extended release eprinomectin efficacy on multiparous beef cow performance

Abstract Internal parasitism inevitability prompts economic loss in beef cattle production by decreasing growth performance and reproductive traits. Previous studies have conflicting results on the macrocyclic lactones (ML) efficacy against internal parasitism. The objective of this study was to evaluate the efficacy of milbeymycin and avermectin sub groups of ML on cow performance. Multiparous fall calving, crossbred beef cows (n = 106) were allocated randomly to 1 of 3 anthelmintic treatments: 1) Negative control (CON), in which cows did not receive an anthelmintic, 2) Injectable moxidectin (MOX) and 3) Injectable extended release eprinomectin (ERE). Body weights (BW), body condition scores (BCS), and fecal egg counts (FEC) were taken throughout the duration of the calving season to weaning on d0, d80, d162, and d217, with weaning occurring on d217. Performance data were analyzed using the MIXED procedures of SAS, and pregnancy data were analyzed using the GENMOD procedures of SAS. Significance was fixed at P &amp;lt; 0.05 and tendencies were established from 0.05 ≤ P ≤ 0.10. There was no effect of anthelmintic treatment on cow BW (P ≥ 0.57) or cow BCS (P ≥ 0.22) during the 217 d study; however, CON cows tended to have lower BCS (P = 0.08) throughout the duration of the study. Cows treated with ERE had fewer FEC compared to MOX and CON groups (P ≤ 0.001) and tended to improve pregnancy rates (c2 = 0.0546). Calf weaning weight was similar among treatments averaging 216, 225, and 223 kg regarding CON, MOX, and ERE cow treatments, respectively.

Bugs and drugs: a systems biology approach to characterising the effect of moxidectin on the horse\u2019s faecal microbiome

BackgroundAnthelmintic treatment is a risk factor for intestinal disease in the horse, known as colic. However the mechanisms involved in the onset of disease post anthelmintic treatment are unknown. The interaction between anthelmintic drugs and the gut microbiota may be associated with this observed increase in risk of colic. Little is known about the interaction between gut microbiota and anthelmintics and how treatment may alter microbiome function. The objectives of this study were: To characterise (1) faecal microbiota, (2) feed fermentation kinetics in vitro and (3) metabolic profiles following moxidectin administration to horses with very low (0 epg) adult strongyle burdens. Hypothesis: Moxidectin will not alter (1) faecal microbiota, (2) feed fermentation in vitro, or, (3) host metabolome.ResultsMoxidectin increased the relative abundance of Deferribacter spp. and Spirochaetes spp. observed after 160 h in moxidectin treated horses. Reduced in vitro fibre fermentation was observed 16 h following moxidectin administration in vivo (P = 0.001), along with lower pH in the in vitro fermentations from the moxidectin treated group. Metabolic profiles from urine samples did not differ between the treatment groups. However metabolic profiles from in vitro fermentations differed between moxidectin and control groups 16 h after treatment (R2 = 0.69, Q2Y = 0.48), and within the moxidectin group between 16 h and 160 h post moxidectin treatment (R2 = 0.79, Q2Y = 0.77). Metabolic profiles from in vitro fermentations and fermentation kinetics both indicated altered carbohydrate metabolism following in vivo treatment with moxidectin.ConclusionsThese data suggest that in horses with low parasite burdens moxidectin had a small but measurable effect on both the community structure and the function of the gut microbiome.

Efficacy of imidacloprid 10%/moxidectin 2.5% spot on (Advocate®, Advantage Multi®) and doxycycline for the treatment of natural Dirofilaria immitis infections in dogs

Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart.The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24.Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae and antigens sooner when compared to melarsomine in the present study and to dogs treated with doxycycline combined with ivermectin in studies previously published.

Efficacy of a spot-on combination of fluralaner plus moxidectin (Bravecto\xae Plus) in cats following repeated experimental challenge with a field isolate of Ctenocephalides felis

BackgroundA spot-on formulation of fluralaner plus moxidectin has been designed to provide long-term protection against fleas and ticks, prevent heartworm disease and treat gastrointestinal nematode infections in cats. The objective of this study was to determine the efficacy of this product against fleas collected from a household with repeated fipronil failures following owner-administered treatments.MethodsThirty cats were randomized to three equal groups: (A) untreated controls; (B) to receive a single application of fluralaner plus moxidectin (Bravecto® Plus) at 40 mg/kg and 2 mg/kg body weight, respectively; and (C) three applications at one month intervals with a spot-on formulation of fipronil and (S)-methoprene (Frontline® Plus) at 0.5 ml manufacturer recommended dose. Flea challenges were completed on Days −6 (for randomization), −1, 7, 14, 28, 42, 56, 70, 77, 84 and 91. Flea counts were completed 48 hours after initial treatment and 48 hours following each subsequent challenge.ResultsFleas were found on all control and all fipronil and (S)-methoprene treated cats at every assessment. From Day 2 to Day 93, all cats in the fluralaner plus moxidectin group were flea-free, with one exception (Day 58; three fleas counted on one cat); control group flea counts ranged between 34–109, and fipronil and (S)-methoprene group counts ranged between 1–79. At each assessment after Day 0, compared to the control group, geometric mean flea counts were significantly lower in the fipronil and (S)-methoprene group (P ≤ 0.04) and in the fluralaner plus moxidectin group (P < 0.001), and mean flea counts in the fluralaner plus moxidectin group were significantly lower than those of the fipronil and (S)-methoprene group (P < 0.001). The efficacy of fluralaner plus moxidectin, based on geometric means, was 100% at each assessment post-Day 0 except on Day 58 when efficacy was 99.7%. In the fipronil and (S)-methoprene group efficacy ranged between 30.6–65.6%.ConclusionsThese findings demonstrate complete efficacy of fluralaner plus moxidectin against a flea isolate that was not controlled by fipronil and (S)-methoprene. This study provides confirmation of the consistent, sustained efficacy of topically applied fluralaner in the treatment and control of flea infestations in cats.

Pharmacokinetic profile and anthelmintic efficacy of moxidectin administered by different doses and routes to feedlot calves

We evaluated the comparative plasma disposition kinetics and efficacy of moxidectin (MXD), administered by the intraruminal (IR) or subcutaneous (SC) route at two different dosage levels (0.2 and 1 mg/kg) in feedlot calves. Additionally, the efficacy was compared to an ivermectin (IVM, SC administration) treated group. This study was divided into two separate studies, the “Pharmacokinetic (PK) study” and the “Efficacy study”. The “PK study” involved 24 calves free of gastrointestinal nematodes (GIN), which were allocated into 4 groups (n = 6) and treated with MXD by either the SC or the IR route at the therapeutic (MXDSC0.2, MXDIR0.2, respectively) or at fivefold the therapeutic dose (MXDSC1.0, MXDIR1.0, respectively). Blood samples were collected from 3 h up to 14 days post-treatment. MXD concentrations in plasma samples were analyzed by HPLC. The “Efficacy study” included 125 calves naturally infected with GIN, which were allocated into five experimental groups (n = 25 each); the same four MXD-treated groups described for the “PK study”, and an additional group treated by the SC route with IVM (IVMSC0.2). The efficacy of IVM given at its therapeutic dose and the different MXD groups at the therapeutic and fivefold the therapeutic dose was calculated by analysis of the individual efficacy using the package eggCounts-2.1-1' on the R software environment, version 3.5.0 (R Core Team, 2018). Daily weight gain (DWG) was also measured over the first 47 days of the fattening cycle. Independently of the administration route, MXD peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were higher in groups treated with the higher dose (1.0 mg/kg), whereas a longer time to reach Cmax (Tmax) was observed after the IR treatments. The observed MXD efficacies were 85% (MXDSC0.2), 94% (MXDSC1.0), 84% (MXDIR0.2) and 99% (MXDIR1.0), at day +27. At day +27, all MXD-treated groups showed higher efficacies than the group having received IVM (45%). The post-treatment Cooperia spp. L3 counts were particularly low in the groups MXDSC1.0 and MXDIR1.0. All of the groups treated with MXD showed better DWG than the IVMSC0.2 group (P = 0.01). Dose and administration route modifications effectively improved the anthelmintic and productive performance of MXD. A high dose of MXD improved the control of IVM-resistant GIN in feedlot calves. However, this practice must be taken with caution, since MXD resistance could rapidly emerge, especially in grazing cattle.

Efficacy and safety of a combination of selamectin plus sarolaner for the treatment and prevention of flea infestations and the treatment of ear mites in cats presented as veterinary patients in the United States

Two randomised, single-masked, multi-center field studies were conducted in the United States in cats presented as veterinary patients. The first study evaluated the efficacy and safety of a topically applied formulation of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus, Zoetis) against natural flea infestations; the second study evaluated its efficacy against natural ear mite infestations. The product was administered topically by the cats’ owners at the dose range provided in the market product of 6.0–12.0 mg selamectin and 1.0–2.0 mg sarolaner per kg bodyweight. Imidacloprid plus moxidectin (Advantage® Multi for Cats, Bayer) was used as a positive control in both studies at the label dosage. In the flea study, treatments were administered on Days 0, 30, and 60. Efficacy was calculated based on the mean percent reduction of live flea counts on Days 30, 60, and 90 relative to the pre-treatment count. In the ear mite study, a single treatment was applied on Day 0 and efficacy was determined on Days 14 and 30 based on the presence or absence of ear mites. In both studies, patients were randomly allocated to treatments in the ratio of 2:1, selamectin plus sarolaner: imidacloprid plus moxidectin.In the two studies, 405 cats received treatment with selamectin plus sarolaner; of these, 256 cats received three monthly treatments in the flea study. There were no serious adverse reactions to treatment with selamectin plus sarolaner; health issues noted were typical of the normal ailments or minor traumatic injuries expected in the general cat population and were similar in both treatment groups. Efficacy against fleas based on geometric (arithmetic) means was 97.2% (95.9%), 99.5% (99.4%), and 99.8% (99.8%) in the selamectin plus sarolaner group and was 79.7% (70.5%), 91.4% (77.3%), and 95.5% (87.4%) in the imidacloprid plus moxidectin group on Days 30, 60, and 90, respectively. Flea counts for the selamectin plus sarolaner group were significantly lower than the counts for the imidacloprid plus moxidectin group at all time-points after treatment administration on Day 0 (P < 0.001). Treatment reduced the clinical signs of flea allergy dermatitis (alopecia, dermatitis/pyodermatitis, erythema, pruritus, scaling, and papules) in affected cats by 86.7%–100% in the selamectin plus sarolaner group and by 66.7%–100% in the imidacloprid plus moxidectin group.In the ear mite study, a single application of selamectin plus sarolaner resulted in the clearance of mites from 87.5% of cats within 14 days and 94.4% of cats within 30 days of treatment. The respective percentages of mite-free cats in the imidacloprid plus moxidectin group were 64.0% and 72.0%. There were significantly more cats with no mites noted in the selamectin plus sarolaner group than in the imidacloprid plus moxidectin group on Day 14 and Day 30 (P ≤ 0.018).Selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) administered topically at monthly intervals for three months was well tolerated and highly effective for the treatment and prevention of natural infestations of fleas on cats presented as veterinary patients. Clinical signs of flea allergy dermatitis improved in affected cats following treatment administration. A single topical treatment was also safe and highly effective for the treatment of ear mite infestations in naturally infested cats.

Field effectiveness and safety of fluralaner plus moxidectin (Bravecto\xae Plus) against ticks and fleas: a European randomized, blinded, multicenter field study in naturally-infested client-owned cats

BackgroundA spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) has been developed to provide broad spectrum parasite protection for cats. The effectiveness and safety of this product against ticks and fleas was assessed in a randomized, controlled, 12-week study in client-owned cats in Germany and Spain.MethodsEligible households containing at least one cat with at least two fleas and/or two ticks were allocated randomly in a 2:1 ratio to a single treatment with fluralaner plus moxidectin on Day 0, or three 4-weekly treatments with fipronil (Frontline®). Veterinary staff, masked to treatment, completed tick and flea counts on each cat at 14 ± 2 (2 weeks), 28 ± 2 (4 weeks), 56 ± 2 (8 weeks) and 84 ± 2 days (12 weeks) after the initial treatment.ResultsIn total, 707 cats (257 with ticks) from 332 households (236 with fleas) were included. Ixodes ricinus (78%) and Rhipicephalus sanguineus complex (18%) ticks were the most commonly identified. Tick and flea counts were lower in the fluralaner plus moxidectin group than in the fipronil group throughout the study and the efficacy of fluralaner plus moxidectin exceeded 97 and 98%, respectively. At 12 weeks, 94.1 and 93.3% of cats from the fluralaner plus moxidectin and 92.2 and 60.3% of cats from the fipronil group were free of ticks and fleas, respectively. Fluralaner plus moxidectin was non-inferior to fipronil (P < 0.0001) at all assessments and superior to fipronil at 2 and 8 weeks for the proportion of cats free of ticks (P < 0.0001). Fluralaner plus moxidectin was superior to fipronil for the proportion of both households and cats free of fleas (P < 0.0001). Both products were safe and well tolerated.ConclusionsA single application of fluralaner plus moxidectin spot-on was well tolerated by cats and highly effective for 12 weeks against ticks and fleas. Fluralaner plus moxidectin was non-inferior to fipronil for the proportion of ectoparasite-free and consistently superior to fipronil in controlling fleas.

A randomized, blinded, controlled, multi-centered field study assessing the treatment of gastrointestinal nematode infections in cats with fluralaner plus moxidectin spot-on solution (Bravecto\xae Plus)

BackgroundA spot-on formulation containing fluralaner (280 mg/ml) plus moxidectin (14 mg/ml) (Bravecto® Plus) was developed for the treatment of nematode infections as well as providing 12 weeks of protection against insect and acarine parasites in cats. The effectiveness and safety of this product against feline gastrointestinal nematodes was assessed in naturally-infested, client-owned cats under field conditions in Albania, Bulgaria, Germany and Hungary.MethodsTo be eligible for enrollment in this investigator-blinded study cats had to be at least 10 weeks-old, weigh at least 1.2 kg, be clinically healthy, and have a faecal sample testing positive for nematodes no more than eight days prior to treatment. Cats were stratified into blocks of three in order of presentation at each center and randomly allocated in a 2:1 ratio to be treated topically on Day 0 with fluralaner plus moxidectin (minimum dose rates 40 mg/kg and 2 mg/kg, respectively) or emodepside plus praziquantel (minimum dose rates 3 mg/kg and 12 mg/kg, respectively) (Profender®). Faecal samples were collected from cats prior to treatment and 14 ± 4 days later.ResultsThere were 182 cats randomized to the fluralaner plus moxidectin group, and 91 to the emodepside plus praziquantel group. Prior to treatment the most commonly identified nematode egg was Toxocara cati, found in 79.1 and 82.4% of cats in the fluralaner plus moxidectin and emodepside plus praziquantel groups, respectively. Eggs of Toxascaris leonina were found in 8.2 and 6.6% of cats; of hookworms in 30.8 and 24.2%; and of Capillaria spp. in 7.1 and 4.3%, respectively. After treatment, faecal samples from 98.3% of fluralaner plus moxidectin treated and 96.6% of emodepside plus praziquantel-treated cats were free of nematode ova. Geometric mean faecal egg count reductions for T. cati, the only eggs found in post-treatment faecal samples, were 99.97% and 99.93%, respectively. Treatment with fluralaner plus moxidectin was non-inferior to emodepside plus praziquantel. Both products were safe and well tolerated by cats treated under field conditions.ConclusionsThis field study confirms that, in addition to 12-week extended duration flea and tick control, fluralaner plus moxidectin provides broad spectrum treatment of nematodes in cats.

Evaluation of the mucosal inflammatory responses to equine cyathostomins in response to anthelmintic treatment

Members of Cyathostominae are pervasive parasites of equids that can cause larval cyathostominosis, a potentially life-threatening disease that occurs when a multitude of encysted larvae synchronously excyst from the wall of the large intestine. Moxidectin and fenbendazole are the two current labeled drugs that target the encysted larval stages; however, there is limited knowledge of the local inflammatory response to the larvae and to the two treatments in clinically healthy horses. This study is the first to evaluate the local inflammatory response to cyathostomin larvae and to larvicidal treatment at 2 and 5 weeks post treatment. Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into 3 groups: Group 1, fenbendazole at 10 mg/kg for 5 days, Group 2, a single dose of moxidectin at 0.4 mg/kg, and Group 3, untreated controls. Tissue samples from the cecum and dorsal and ventral colons were used for histopathological and immunohistochemical evaluation. Tissues were stained with routine hematoxylin and eosin (H&E) for light microscopy and immunohistochemically for MAC387, CD20, and CD3 for differentiation of activated macrophages, B cells, and T cells, respectively. Semiquantitative scores were assigned for all inflammatory cell types and fibrous connective tissue. Larvae observed by light microscopy were enumerated and classified by stage. Mucosal ulcerations and submucosal granulomas were also enumerated. Mean macrophage scores were higher in the moxidectin group than the fenbendazole group (p = 0.0185) and the control group had a higher activated macrophage score than both treatment groups (p = 0.0104, p = 0.0004). T lymphocyte scores were higher in the moxidectin group when compared to the control group (p = 0.0069). Goblet cell hyperplasia scores were elevated at 5 weeks post treatment compared to 2 weeks post treatment (p = 0.0047) and were elevated in the ventral colon compared to the dorsal colon (p = 0.0301). Eosinophil scores were elevated surrounding degenerative larvae when compared to intact larvae (p = 0.0001). Mucosal ulcerations were found only in the control group at 2 weeks post treatment. This study found subtle inflammatory differences between treatment groups but provided new information about goblet cells and eosinophils in relation to encysted cyathostomin larvae.

Cyathostominae Egg Reappearance Period After Treatment With Major Horse Anthelmintics in Donkeys

The Egg Reappearance Period (ERP) is considered an early indicator of anthelmintic resistance. The aims of the present study were to determine the field efficacy and evaluate the ERP of four broad-spectrum anthelmintic drugs administered at horse dose rate in donkeys naturally infected by Cyathostominae. The trials were conducted in two farms (A and B). Forty-eight female crossbreed donkeys, 24 animals for each farm, were selected on the basis of Fecal Egg Count (FEC) > 300 eggs per gram and allocated to four treatment groups of six animals: pyrantel group (PYR), fenbendazole group (FBZ), ivermectin group (IVM), and moxidectin group (MOX). FEC was performed from the first to the 12th week after treatment. In the farm A at 2 weeks after treatment, the Fecal Egg Count Reduction Test (FECRT) showed high efficacy for all drugs (PYR 99.3%, FBZ 99.8, and IVM/MOX 100%), and ERP rates were not shorter than those expected. In the farm B at 2 weeks after treatment, FECRT showed high efficacy for IVM/MOX (100%), suspect resistance (86.3%), and resistance (83.9%) to PYR and FBZ, respectively; only in the MOX group a shortened ERP was detected (9 weeks). No adverse reactions were observed at clinical examination. The results demonstrate that the major anthelmintic classes, administered orally at horse dose, are effective and safe for treatment of Cyathostominae in donkeys, although resistance development is possible and could be correlated to the high treatment frequency and the extra-label use of anthelmintic licensed for ruminants. Furthermore, a shortened ERP may be the early indicator of developing anthelmintic resistance in donkeys.

Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial

SummaryBackgroundThe morbidity and socioeconomic effects of onchocerciasis, a parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated large morbidity and transmission control programmes. Annual community-directed ivermectin treatment has substantially reduced prevalence. Elimination requires intensified efforts, including more efficacious treatments. We compared parasitological efficacy and safety of moxidectin and ivermectin.MethodsThis double-blind, parallel group, superiority trial was done in four sites in Ghana, Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged ≥12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who were not co-infected with Loa loa or lymphatic filariasis microfilaraemic. Participants were randomly allocated, stratified by sex and level of infection, to receive a single oral dose of 8 mg moxidectin or 150 μg/kg ivermectin as overencapsulated oral tablets. The primary efficacy outcome was skin microfilariae density 12 months post treatment. We used a mixed-effects model to test the hypothesis that the primary efficacy outcome in the moxidectin group was 50% or less than that in the ivermectin group. The primary efficacy analysis population were all participants who received the study drug and completed 12-month follow-up (modified intention to treat). This study is registered with ClinicalTrials.gov, number NCT00790998.FindingsBetween April 22, 2009, and Jan 23, 2011, we enrolled and allocated 998 participants to moxidectin and 501 participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which 947 and 480 were included in primary efficacy outcome analyses. At 12 months, skin microfilarial density (microfilariae per mg of skin) was lower in the moxidectin group (adjusted geometric mean 0·6 [95% CI 0·3–1·0]) than in the ivermectin group (4·5 [3·5–5·9]; difference 3·9 [3·2–4·9], p<0·0001; treatment difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%) of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated participants, including ocular reactions (moxidectin 113 [12%] participants and ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415 [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse events were considered to be related to treatment.InterpretationSkin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination.FundingUNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

Anthelmintic therapy of equine cyathostomin nematodes – larvicidal efficacy, egg reappearance period, and drug resistance

Cyathostomins are ubiquitous in grazing horses across the world, and anthelmintic resistance has been reported with increasing levels over past decades. The aims of the present study were (i) to investigate the efficacy against encysted larval stages of moxidectin (0.4 mg/kg) and fenbendazole (10 mg/kg daily for five consecutive days) and compare these regimens at 2 and 5 weeks post-treatment, (ii) to investigate individual cyathostomin species associated with shortened egg reappearance periods, and (iii) to document species exhibiting decreased susceptibility to the evaluated compounds. Thirty-six ponies were allocated to treatment groups with half euthanatized 2 weeks post-treatment, and the remainder necropsied after 5 weeks. Luminal and mucosal worm counts were conducted and strongyle egg counts were determined at weekly intervals. At 2 weeks, mean reductions of early L3s were 50.4% and 73.8% for fenbendazole and moxidectin, respectively. At 5 weeks, the respective efficacies were 51.3% and 71.8%. Two week efficacies against late L3s and L4s (LL3s/L4s) were 70.8% and 74.6% for fenbendazole and moxidectin, respectively, whereas very low numbers were found in all three groups at 5 weeks. None of the mucosal counts were significantly different between treatment groups. Fenbendazole and moxidectin reduced luminal worm counts by 93.2% and 98.3% at 2 weeks following administration, with moxidectin group adult counts being significantly lower than the other two groups (P < 0.0001). Both treatment groups had increased counts 3 weeks later (P = 0.0415). A moxidectin ERP of 4 weeks was associated with surviving luminal L4s, and adult species contributing to this were Cyathostomum catinatum, Cylicostephanus longibursatus, Cylicocyclus ashworthi and Cylicocyclus nassatus. This study documented (i) larvicidal efficacy of fenbendazole much lower than historical standards, (ii) survival of luminal immatures (L4) following moxidectin administration, and (iii) new information about cyathostomin species associated with these phenomena.

Resistance to a triple-combination anthelmintic in Trichostrongylus spp. on a commercial sheep farm in New Zealand

AIM: To evaluate resistance to anthelmintics containing abamectin, levamisole, and oxfendazole (AB-LEV-OX), derquantal and abamectin (DEQ-AB), moxidectin, and monepantel in naturally acquired gastrointestinal nematodes present on a sheep farm.METHODS: Faecal nematode egg count reduction tests (FECRT) were carried out on lambs that were approximately 7 months-old and infected with naturally acquired nematodes. Lambs were randomly allocated to one of five groups (n=15 per group): treatment with 2 mg/kg derquantel and 0.2 mg/kg abamectin; 0.2 mg/kg abamectin, 8 mg/kg levamisole HCl and 4.5 mg/kg oxfendazole; 2.5 mg/kg monepantel; 0.2 mg/kg moxidectin, or no treatment. Post-treatment samples were collected 12 days later. Abomasa and small intestines were collected from two slaughtered lambs from each of the DEQ-AB, AB-LEV-OX, moxidectin and control groups 15 days after treatment, for nematode counting.RESULTS: The FECRT demonstrated that efficacy was 90.3 (95% CI=84.2–94.1)% for AB-LEV-OX, 54.5 (95% CI=28.4–71.1)% for moxidectin, 99.2 (95% CI=97.4–99.8)% for DEQ-AB and 100% for monepantel, across all genera. For Trichostrongylus spp. efficacy was 85.5% for AB-LEV-OX and 46.7% for moxidectin. Haemonchus spp. were fully susceptible to all treatments. Post-treatment nematode counts indicated that the resistant Trichostrongylus spp. were from the small intestine.CONCLUSIONS: Anthelmintic resistance to both AB-LEV-OX and moxidectin was present in the Trichostrongylus genus on a commercial sheep farm. Monepantel and DEQ-AB were both effective against Trichostrongylus spp. based on FECRT results.CLINICAL RELEVANCE: This finding of resistance to an AB-LEV-OX triple-combination anthelmintic in the Trichostrongylus genus in sheep in New Zealand further limits anthelmintic treatment options available, and calls into question whether this combination is suitable for use as a quarantine treatment.

Helminthiasis characterization and anthelmintic efficacy for ewes and lambs raised in tropical semiarid region.

In this study the helminthiasis and anthelmintic effectiveness in ewes and lambs were evaluated in a semiarid region of Brazil. Twelve sheep farms were investigated using semi-structured questionnaires and fecal egg count (FEC) reduction test was employed to analyze the profile of anthelmintic resistance. Groups of at least 10 animals with FEC≥300 were selected. After 12h of fasting, homogeneous groups of lambs or ewes were treated with albendazole, levamisole moxidectin, or oxfendazole and control groups were not treated. Feces were collected before treatments and 14days after, and larvae genera were identified after cuprocultures in both periods. Extensive grazing was the predominant creation system, using hybrid Santa Ines animals. The separation by age was promoted in 75% of herds; however, maternity pickets there were only in three farms. The strategic treatments were performed only in 8.4% of sheep farms and 16.6% used the anthelmintic efficacy test and alternated anthelmintic classes after 1year. The initial FEC means for lambs were significantly higher than ewe FEC averages. For lamb tests, moxidectin and levamisole showed higher efficacy (p≤0.05) than benzimidazoles. For ewe tests, moxidectin and levamisole showed efficiencies >75%. Haemonchus spp. and Trichostrongylus spp. were the most frequent nematodes before treatments and the genus Haemonchus was the most prevalent after anthelmintic treatments (p<0.05). Variations of anthelmintic susceptibility were observed for categories and herds evaluated, which emphasizes the importance of the effectiveness tests for the choice of anthelmintics for ewes and lambs.