Assessment of the in vitro acaricidal activity of Bravecto® (fluralaner) and a proposed orange oil-based formulation vehicle for the treatment of Sarcoptes scabiei.

BACKGROUND: Sarcoptic mange is a serious animal welfare concern in bare-nosed wombats (Vombatus ursinus). Fluralaner (Bravecto®) is a novel acaricide that has recently been utilised for treating mange in wombats. The topical 'spot-on' formulation of fluralaner can limit treatment delivery options in situ, but dilution to a volume for 'pour-on' delivery is one practicable solution. This study investigated the in vitro acaricidal activity of Bravecto, a proposed essential oil-based diluent (Orange Power®), and two of its active constituents, limonene and citral, against Sarcoptes scabiei. METHODS: Sarcoptes scabiei were sourced from experimentally infested pigs. In vitro assays were performed to determine the lethal concentration (LC50) and survival time of the mites when exposed to varying concentrations of the test solutions. RESULTS: All compounds were highly effective at killing mites in vitro. The LC50 values of Bravecto, Orange Power, limonene and citral at 1 h were 14.61 mg/ml, 4.50%, 26.53% and 0.76%, respectively. The median survival times of mites exposed to undiluted Bravecto, Orange Power and their combination were 15, 5 and 10 min, respectively. A pilot survival assay of mites collected from a mange-affected wombat showed survival times of < 10 min when exposed to Bravecto and Orange Power and 20 min when exposed to moxidectin. CONCLUSIONS: These results confirm the acaricidal properties of Bravecto, demonstrate acaricidal properties of Orange Power and support the potential suitability of Orange Power and its active constituents as a diluent for Bravecto. As well as killing mites via direct exposure, Orange Power could potentially enhance the topical delivery of Bravecto to wombats by increasing drug penetration in hyperkeratotic crusts. Further research evaluating the physiochemical properties and modes of action of Orange Power and its constituents as a formulation vehicle would be of value.

seco-Pregnane Glycosides from Australian Caustic Vine (Cynanchum viminale subsp. australe).

Cynanchum viminale subsp. australe, more commonly known as caustic vine, is a leafless succulent that grows in the northern arid zone of Australia. Toxicity toward livestock has been reported for this species, along with use in traditional medicine and its potential anticancer activity. Disclosed herein are novel seco-pregnane aglycones cynavimigenin A (5) and cynaviminoside A (6), together with new pregnane glycosides cynaviminoside B (7) and cynavimigenin B (8). Cynavimigenin B (8) contains an unprecedented 7-oxobicyclo[2.2.1]heptane moiety in the seco-pregnane series, likely arising from a pinacol-type rearrangement. Interestingly, these isolates displayed only limited cytotoxicity in cancer and normal human cell lines, in addition to low activity against acetylcholinesterase and Sarcoptes scabiei bioassays, suggesting that 5-8 are not associated with the reported toxicity of this plant species.

Lemongrass (Cymbopogon citratus) oil: A promising miticidal and ovicidal agent against Sarcoptes scabiei.

BACKGROUND: Essential oils may represent an alternative strategy for controlling scabies, a neglected tropical disease caused by the infestation of mite from the species Sarcoptes scabiei. Lemongrass (Cymbopogen citratus) oil is reported to possess pharmacological properties including antiparasitc, antioxidant, antimicrobial and anti-inflammatory. The aim of the present study was to assess the potential efficacy of lemongrass oil against the mites and eggs of Sarcoptes scabiei. METHODOLOGY/PRINCIPAL FINDINGS: Mass spectrometry analysis confirmed that the main component presented in lemongrass oil was citral. Lemongrass oil at concentrations of 10% and 5% killed all Sarcoptes mites within 10 and 25 min, respectively. The median lethal concentration value was 1.37%, 1.08%, 0.91%, 0.64%, and 0.48% at 1, 3, 6, 12, and 24 h, respectively. Lemongrass oil at all concentrations (10%, 5%, 1%, 0.5%, 0.1%) was able to significantly decrease the hatching rate of Sarcoptes eggs. CONCLUSIONS/SIGNIFICANCE: Lemongrass oil should be considered as a promising miticidal and ovicidal agent for scabies control.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

BACKGROUND: Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. METHODOLOGY/PRINCIPAL FINDINGS: Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

The effects of different plant extracts on intestinal cestodes and on trematodes.

In the present study, chloroform, aqueous, (polyethylene glycol/propylene carbonate) PEG/PC extracts were made from coconut, onion, garlic, fig, date tree, chicory, ananas, and cistrose. These extracts were tested in vivo and in vitro on their anthelmintic activity against cestodes (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and trematodes (Fasciola hepatica, Echinostoma caproni). In all in vitro tests, the target parasites died. It turned out that the treatment of mice and rats with a combination of onion and coconut extracts (with PEG/PC) eliminated all cestodes from their final hosts. In addition, the same composition was effective against the intestinal fluke E. caproni, but not against the liver fluke F. hepatica in the final host, while both worms were killed in vitro. Inoculation of fluids of coconut eliminated T. taeniaeformis tapeworms from naturally infected cats. This goal was not reached with oil of cistrose.

The effects of different plant extracts on nematodes.

The anthelminthic efficacy of some differently obtained extracts of several plants was tested in vivo in laboratory animals and in vitro. The extracts were obtained by ethanolic, methanolic, aqueous, or chloroform, respectively, acetonitrile polyethylenglycol (PEG) and/or propylencarbonate (PC) elution at room temperature or at 37°C. The plants used were bulbs of onions, garlic, chives, coconut, birch tree, ananas, cistrose, banana, chicory, date palm fruit, fig, pumpkin, and neem tree seeds. The worm systems tested both in vivo and in vitro were Trichuris muris and Angiostrongylus cantonensis but only in vivo Toxocara cati. The tests clearly showed that the different extraction methods eluted different components and different mass amounts, which had different efficacies against the above-cited worms. In vitro effects against A. cantonensis and T.muris were best with aqueous extracts, followed by chloroform extracts. The other plant extracts showed only low or no effects on A. cantonensis in vitro. In the case of T. muris, best results were obtained in vivo and in vitro with PEG/PC extracts of the onion followed by the aqueous extract of coconut. The complete elimination of worms in the in vivo experiments with T. muris was obtained when infected mice were treated with a 1:1 mixture of extracts of coconut and onion being produced by elutions with a mixture of 1:1 PEG and PC and fed daily for 8 days. T. cati in a naturally infected cat was eliminated by daily oral application of 6 ml coco's fluid for 5 days. This study shows that a broad spectrum of plants has anti-nematodal activities, the intensity of which, however, depends on the mode of extraction. This implicates that, if results should be really comparable, the same extraction methods at the same temperatures have to be used. Furthermore, efficacy in in vitro systems does not guarantee as good--if at all--efficacy in vivo.