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Background The invasive tick species, Haemaphysalis longicornis , is becoming established in the USA, presenting a growing threat to dogs and cats. Two 90-day studies were initiated, the same protocol in each, to confirm the efficacy of a single application of two fluralaner formulations against H. longicornis infestations of cats. Methods Cats were randomized among three groups in a 1:1:1 ratio (10 cats/group). Group 1 cats were untreated controls; Group 2 cats were treated with a topical fluralaner formulation (Bravecto®); Group 3 cats received a topical formulation containing fluralaner and moxidectin (Bravecto® Plus). Treatments were administered once (Day 0) at the label dose rates. Each cat was infested with 50 H. longicornis ticks on Day −7 for study qualification and also infested with 50 ticks on Days −2, 28, 58 and 88. Tick counts were completed on Days −5, 2, 30, 60 and 90. The primary objective was based on percentage reductions in arithmetic mean tick counts. Results Pre-study infestations showed all study cats were susceptible to tick challenge. Except for Day 2 in one study, at least six control cats retained ≥ 25% of each challenge, demonstrating an adequate infestation for efficacy assessments. Across studies on Days 2, 30, 60 and 90, the mean live tick infestation rate (number of ticks recovered from each cat/infesting challenge to each cat) of Group 1 cats ranged from 25.0 to 69.6%. Efficacy of each formulation, based on live tick counts, was 100% on Day 2 and > 95 to 100% at each subsequent assessment. Between-group differences were statistically significant ( P  < 0.0001) for each treatment versus control comparison. Conclusion At the label dose rate, both topical fluralaner formulations were 100% effective in eliminating H. longicornis ticks from cats infested at the time of treatment. Efficacy of > 95 to 100% was then maintained through 90 days following a single application. Fluralaner is therefore a treatment of choice for protecting cats against this invasive tick species. Graphical Abstract

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0–t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Moxidectin (MXD) is an antiparasitic drug used extensively in veterinary clinics. In this study, to develop a new formulation of MXD, a thermosensitive gel of MXD (MXD-TG) was prepared based on poloxamer 407/188. Furthermore, the gelation temperature, the stability, in vitro release kinetics and in vivo pharmacokinetics of MXD-TG were evaluated. The results showed that the gelation temperature was approximately 27 °C. MXD-TG was physically stable and can be released continuously for more than 96 h in vitro. The Korsmeyer–Peppas model provided the best fit to the release kinetics, and the release mechanism followed a diffusive erosion style. MXD-TG was released persistently for over 70 days in sheep. Part of pharmacokinetic parameters had a difference in female and male sheep (p < 0.05). It was concluded that MXD-TG had a good stability, and its release followed the characteristics of a diffusive erosion style in vitro and a sustained release pattern in vivo.

Ovine psoroptic mange (sheep scab) is an infection of substantial economic and animal welfare concern in the UK. Its prevalence has increased rapidly over the last 20 years and management is dependent on a small number of acaricidal compounds, many of which are also used to control a range of other endoparasites and ectoparasites. Here, the effects of the macrocyclic lactone (ML) moxidectin was considered using in vitro assays against mites from four farm populations where persistent treatment failure had been reported: two in West Wales, one from the England/Wales border and one in Herefordshire. The data demonstrate resistance in mites from all four farms. This is the first quantitative evidence of ML resistance in Psoroptes mites in the UK. Given the similarities in their mode of action it is highly likely that cross-resistance across the range of this class of compound will be found. The development of resistance to moxidectin is of considerable concern given the already high prevalence of scab infection in some regions; major difficulties in scab management should be anticipated if ML resistance becomes widely established in the UK.

Abstract Background Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined. Methods A Phase II, randomized, placebo-controlled, dose-finding trial was conducted in 2 secondary schools on Pemba Island, Tanzania. Using a computer-generated list, T. trichiura–infected adolescents were randomly assigned to 7 treatment arms: 8, 16, or 24 mg of moxidectin monotherapy; 8, 16, or 24 mg of moxidectin plus 400 mg of albendazole combination therapy; or placebo. The primary outcome was cure rate (CR) against T. trichiura, analyzed 13 to 20 days after treatment by quadruple Kato-Katz thick smears. Results A total of 290 adolescents were enrolled (41 or 42 per arm). CRs against T. trichiura were 43, 46, and 44% for 8, 16, and 24 mg of moxidectin alone, respectively; 60, 62, and 66% for the same moxidectin dosages plus 400 mg of albendazole, respectively; and 12% for placebo. The moxidectin-albendazole arms also revealed higher CRs and egg reduction rates against hookworm than the monotherapy arms. Moxidectin and its combination with albendazole were well tolerated. Conclusions Moxidectin-albendazole is superior to moxidectin. There is no benefit of using doses above 8 mg, which is the recommended dose for onchocerciasis. The moxidectin-albendazole combination of 8 mg plus 400 mg should be investigated further to develop recommendations for appropriate control of STH infections. Clinical Trials Registration NCT03501251. Our randomized dose-finding trial of 290 adolescents in Tanzania found that a moxidectin-albendazole combination is superior to moxidectin alone for curing Trichuris trichiura and hookworm infections. A flat, dose-response relationship was observed for both treatments.

Background Two main Dirofilaria species infect dogs: D. immitis and D. repens . While D. immitis has a worldwide distribution, D. repens is currently found only in Europe, Asia, and Africa. Adult D. repens are located in subcutaneous tissues of natural hosts where they survive for long periods of time. First-stage larvae, microfilariae, circulate in the peripheral bloodstream, where they are taken up by the mosquito intermediate hosts. Infected mosquitoes then transmit infective third-stage (L3) larvae to new hosts through the blood meal. In dogs, most infections are asymptomatic, although cutaneous disorders such as pruritus, dermal swelling, subcutaneous nodules, and ocular conjunctivitis can be observed. Currently, two factors have increased the concerns about this parasitic infection 1) its spread throughout the European countries and to other continents and its prevalence in dog populations, where in some cases it has overcome D. immitis; and 2) its zoonotic potential, which is much greater than that of D. immitis . Results Different hypotheses can be put forward to explain these concerns. First, climate change has allowed more favorable conditions for survival of culicid vectors. Second, accidental hosts such as humans may have a less efficient immune reaction against a parasite that is located in subcutaneous tissues, and thus less exposed to the host’s immune response than, for instance, D. immitis . Furthermore, the absence of clinical signs in the majority of canine infections and the difficulty in diagnosing the infection, due to the lack of serologic tests and thus the reliance on the identification of microfilariae and differentiation from D. immitis to confirm the presence of the parasite, favor the further spread of this species. Finally, among the macrocyclic lactones currently used to prevent heartworm infection, only moxidectin has been found to be fully effective against the infective larvae transmitted by mosquitoes and partially effective (efficacy 96%) against adult D. repens in experimental studies. Conclusions Dirofilaria repens infection is much more difficult than D. immitis to diagnose and control in the reservoir population (microfilaremic dogs). In addition, lack of familiarity with D. repens infection could lead to lack of vigilance underestimation for this parasite . The number of human cases in Europe and Asia is currently a serious public health concern. Medical doctors and veterinarians must collaborate closely for better control and surveillance of D. repens infection.

The southern cattle fever tick (SCFT) Rhipicephalus (Boophilus) microplus, is considered the most important ectoparasite of livestock in the world because of high financial losses associated with direct feeding and transmission of the hemoparasites Babesia bovis, B. bigemina, and Anaplasma marginale. Unfortunately, SCFT in many parts of the world have evolved resistance to all market-available pesticides thus driving development of new control technologies. Vaccination against ticks using the tick gut protein Bm86 has been shown to be effective against acaricide-resistant ticks. This technique has been successfully implemented in Puerto Rico for the control of acaricide-resistant R. microplus on dairy and beef cattle. Observations from Puerto Rico indicate a potentially positive interaction between anti-tick vaccination when used in conjunction with systemic acaricide treatment. In this project, controlled animal studies were completed directly comparing efficacy of anti-tick vaccination with and without systemic acaricide. Results show that the Bm86 anti-tick vaccine in combination with the macrocyclic lactone, Moxidectin, expressed a synergistic interaction, providing greater and longer efficacy than either treatment alone.

The aim was to assess the efficacy of ivermectin vs moxidectin for treating Strongyloides stercoralis infection. Ovid MEDLINE, Embase and Web of Science databases were searched for studies comparing ivermectin and moxidectin from inception to February 2024. The outcomes: elimination of infection or parasitological cure, mortality and serious adverse events. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data. Heterogeneity was assessed using Chi2 test for statistical heterogeneity and results of the I 2 statistic. Two trials met the inclusion criteria that included 821 adult participants. Both studies were conducted in southeast Asia (Cambodia and Laos). Neither trial included immunocompromised patients. The mean age of the participants ranged from 40 to 45 years old, with a similar distribution of males and females. For all participants, S. stercoralis infection was confirmed by Baermann method. The evidence was moderate for parasitological cure rate. Certainty was downgraded by 1 level because of imprecision. Moxidectin was not inferior to ivermectin: OR 0.67, 95% CI 0.36–1.25 ( P = 0.21), I 2 = 0%, 821 participants. No deaths were reported in either trial. One trial reported mild adverse events. In total, 153/726 (21%) participants had an adverse event. The most reported symptoms were abdominal pain and headache. There is evidence for moderate quality that moxidectin is non-inferior to, and as safe as ivermectin; however, more high-quality and well-designed trials are needed. For patients with some underlying immunosuppressive disorder, or in patients who are very young or very old, current data are insufficient to be recommended.

Orally delivered, host-targeted, systemic acaricide treatment has potential to be an effective areawide tick abatement strategy. Past efforts using ivermectin for livestock were reported effective at controlling both Amblyomma americanum (L.) and Ixodes scapularis Say on Odocoileus virginianus (Zimmermann). However, the labeled 48-day withdrawal period for human consumption largely prevented utilization of this strategy targeting I. scapularis in autumn, when peak adult host-seeking activity coincides with regulated white-tailed deer hunting seasons. The modern-day compound moxidectin is the active ingredient in the pour-on formulation Cydectin (5 mg moxidectin/ml; Bayer Healthcare LLC), with a labeled 0-day withdrawal period for human consumption of treated cattle. We sought to re-examine the systemic acaricide approach for tick management by determining if we could successfully deliver Cydectin to free-ranging white-tailed deer. Over 2 yr in late spring/early summer, coinciding with adult and nymphal A. americanum activity, we fed Cydectin-coated corn to free-ranging white-tailed deer in coastal Connecticut. Through serum analysis, we documented moxidectin levels at or above those previously reported effective for control of ectoparasites (5–8 ppb for moxidectin and ivermectin) in 24 of 29 white-tailed deer captured (83%) while exposed to treated corn. While we did not document differences in burdens of parasitizing A. americanum based on moxidectin sera levels, we did document fewer engorged specimens on deer with increased sera levels. The systemic use of moxidectin for tick management in critical reproductive hosts has the potential to be effective in an areawide capacity while also permitting human consumption of treated venison.

The aim of present study was to examine the potency of moxidectin solution (Cydectin 1 %; Zoetis) and commercially available oral moxidectin gel (Equest®; Zoetis) to suppress the excretion of strongyle eggs in horses over a 6-week period. The horses naturally infected with strongyle nematodes (>500 eggs/g of feces) were divided into two comparable groups according age, sex and weight. On day 0 of the study, horses in Group OT (oral treatment; N=5) were dewormed with moxidectin gel (Equest®; Zoetis; 0.4 mg/kg of b.w.) according to the manufacturer’s instructions, and horses in Group IT (intramuscular treatment; N=4) were dewormed with moxidectin injectable solution (Cydectin 1 %; Zoetis; 0.2 mg/kg of b.w.). Stool samples were collected rectally, on day 0, 17, 28, 35, and 42 of the study and examined using a modifi ed McMaster technique ( ) with modifi cations. The mean strongyle egg excretion has signifi cantly decreased in Group IT (P<0.01) and Group OT (P<0.001) on day 17 post treatment as compared to those on day 0. The effi cacy of oral gel (99.43 %) and injectable moxidectin (99.32 %) formulations was therefore high and comparable and no resistance of strongylids to moxidectin was recorded. On day 35 (P<0.001) and 42 (P<0.05) post treatment, the mean effi cacy was signifi cantly higher in Group IT as compared to Group OT. The present study contributes to the existing knowledge and providing more information on the use of injectable MOX solution for the treatment of strongylid infection in horses.