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

BACKGROUND: A 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. METHODS: Thirty 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. RESULTS: Fleas 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%. CONCLUSIONS: These 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.

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® Plus).

BACKGROUND: A 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. METHODS: To 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. RESULTS: There 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. CONCLUSIONS: This 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.

Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.

Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 µg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes.

Biological activity of bleached kraft pulp mill effluents before and after activated sludge and ozone treatments.

Eucalyptus bleached kraft pulp production, an important sector of the Brazilian national economy, is responsible for generating large volume, high pollutant load effluents, containing a considerable fraction of recalcitrant organic matter. The objectives of this study were to quantify the biological activity of the effluent from a eucalyptus bleached kraft pulp mill, characterize the nature of compounds responsible for biological activity and assess the effect of ozone treatment on its removal. Primary and secondary effluents were collected bimonthly over the course of one year at a Brazilian bleached eucalypt kraft pulp mill and their pollutant loads (biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbon (TOC), adsorbable organic halogen (AOX), lignin, extractives) and biological activity (acute and chronic toxicity and estrogenic activity) quantified. The effluent studied did not present acute toxicity to Daphnia, but presented the chronic toxicity effects of algal growth inhibition and reduced survival and reproduction in Ceriodaphnia, as well as estrogenic activity. Chronic toxicity and estrogenic activity were reduced but not eliminated during activated sludge biological treatment. The toxicity identification evaluation revealed that lipophilic organic compounds (such as residual lignin, extractives and their byproducts) were responsible for the toxicity and estrogenic activity. Ozone treatment (50 mg/L O(3)) of the secondary effluent eliminated the chronic toxicity and significantly reduced estrogen activity.

Evaluation of topical application of 10% imidacloprid-1% moxidectin to prevent Bartonella henselae transmission from cat fleas.

OBJECTIVE: To determine whether monthly topical administration of a combination of 10% imidacloprid and 1% moxidectin would lessen flea (Ctenocephalides felis) transmission of Bartonella henselae among cats. DESIGN: Controlled trial. ANIMALS: 18 specific pathogen-free cats housed in 3 groups of 6. PROCEDURES: 3 enclosures were separated by mesh to allow fleas to pass among groups yet prevent cats from contacting one another. One group was inoculated IV with B henselae, and after infection was confirmed, the cats were housed in the middle enclosure. This infected group was flanked by a group that was treated topically with 10% imidacloprid-1% moxidectin monthly for 3 months and by an untreated group. On days 0, 15, 28, and 42, 100 fleas/cat were placed on each of the 6 cats in the B henselae-infected group. Blood samples were collected from all cats weekly for detection of Bartonella spp via PCR assay, bacterial culture, and serologic assay. RESULTS: B henselae infection was confirmed in the cats infected IV and in all untreated cats after flea exposure; none of the cats treated with the imidacloprid-moxidectin combination became infected. CONCLUSIONS AND CLINICAL RELEVANCE: In this setting, monthly topical administration of 10% imidacloprid-1% moxidectin reduced flea infestation, compared with infestation in untreated cats, and thus prevented flea transmission of B henselae to treated cats. Regular monthly use of this flea control product in cats may lessen the likelihood of humans acquiring B henselae infection.

Atividade residual in vitro do pelo de cobertura de cães tratados com dinotefuran sobre larvas e adultos de Ctenocephalides felis felis (Bouché, 1835) (Siphonaptera: pulicidae) / Residual activity in vitro of treated dog's hair coat with dinotefuran on larvae and adults of Ctenocephalides felis felis (Bouché, 1835) (Siphonaptera: Pulicidae)

The aim of this study was to evaluate the residual activity of treated dog's hair coat with dinotefuran on larvae and adults of Ctenocephalides felis felis. Three female Beagle dogs were used. One female dog was treated with 0.834 percent dinotefuran spray, the second was treated with 30 percent dinotefuran strip-on and the third was not treated. Some areas of dog's hair were clipped on days 2, 9, 16, 23, 30, 37 and 44 after treatment. For the evaluation of adulticidal and larvicidal activities, flea adults and larvae from the laboratory colony were used. Six repetitions were used with 10 samples of each flea stage per day, placed in assay tubes. In each repetition we added 0.02 g of treated or untreated dog's hair and larval diet for the immature stage. Flea adult assay was evaluated with 24 hours and the flea larvae 20 days after treatment. The residue on hair coat of both treated dogs showed efficacy on the flea larvae control for 44 days. Regarding the flea adults control the spray and strip-on formulations showed efficacy until days 16 and 23, respectively.

O objetivo deste trabalho foi avaliar a atividade in vitro do resíduo em pelo de cobertura de cães tratados com dinotefuran sobre larvas e adultos de Ctenocephalides felis felis. Foram utilizadas três cadelas da Raça Beagle: a nº 1 foi tratada com uma formulação spray de dinotefuran a 0,834 por cento, a nº 2 com uma formulação "strip-on" de dinotefuran a 30 por cento e a nº 3 foi mantida sem tratamento. Pequenas áreas foram tricotomizadas nos dias 2, 9, 16, 23, 30, 37 e 44 após o tratamento. Para avaliação adulticida e larvicida, foram utilizados pulgas de uma colônia mantida em laboratório. Seis repetições com cada uma contendo 10 exemplares de C. f. felis, acondicionados em tubos de ensaio, da etapa correspondente foram utilizados por dia de desafio. Em cada repetição foi adicionado 0,02 gramas de pelo de cada área tricotomizada e dieta na etapa de larvas. O material da etapa adulto foi avaliado num período de 24 horas, o da etapa larvas foi avaliado após 20 dias de cada desafio. O resíduo no pêlo de cães tratados com ambas as formulações de dinotefuran foi eficaz no controle de larvas por um período de 44 dias, e no controle de adultos as formulações spray e a "strip-on" foram eficazes por um período de 16 e 23 dias, respectivamente.

Mystery of the toxic flea dip: an interactive approach to teaching aerobic cellular respiration.

We designed an interrupted case study to teach aerobic cellular respiration to major and nonmajor biology students. The case is based loosely on a real-life incident of rotenone poisoning. It places students in the role of a coroner who must determine the cause of death of the victim. The case is presented to the students in four parts. Each part is followed by discussion questions that the students answer in small groups prior to a classwide discussion. Successive parts of the case provide additional clues to the mystery and help the students focus on the physiological processes involved in aerobic respiration. Students learn the information required to solve the mystery by reading the course textbook prior to class, listening to short lectures interspersed throughout the case, and discussing the case in small groups. The case ends with small group discussions in which the students are given the names and specific molecular targets of other poisons of aerobic respiration and asked to determine which process (i.e., glycolysis, citric acid cycle, or the electron transport chain) the toxin disrupts.

Tungiasis: tratamiento de un caso con invermectina / Tungiasis: case report treated with ivermectin

Se presenta un paciente con tungiasis múltiple que fue tratado con ivermectina por vía oral y se obtuvo una excelente respuesta terapéutica, sin efectos colaterales indeseables, Este fármaco hasta el momento no fue utilizado en el tratamiento de esta enfermedad. Se efetúa una revisión de la tungiasis, así como de las indicaciones y mecanismo de acción de la ivermectina

[The action of a juvenile hormone synthetic analog--ether-farnesol on Xenopsylla cheopis fleas]. / Deistvie sinteticheskogo analoga iuvenil'nogo gormona--éfir-farnazola na blokh Xenopsylla cheopis.

The authors tested the effect of the analogue of juvenile hormone (AJH), ether-farnesol, synthesized at the Institute of Chemistry of the Academy of Sciences of ESSR (the city of Tallin), on immature stages of X. cheopis. When testing the following doses of AJH (0.0025, 0.00025, 0.000025, 0.0000025 ml per lg of substrate, consisting of sand and dry bull blood, for feeding larvae) it was established that the dose of 0.0025 ml/g causes 100% mortality of insects on the 2nd day of the experiment. 10 fold decrease in ether-farnesol dose causes the mortality of the majority of larvae. Only 13.6% of them formed cocoons, which failed to produce mature individuals. A repeated 10 and 100 fold decrease of AJH caused mortality in 50.0 and 46.7% of insects, respectively. The effect of the preparation stipulated the disturbance of the normal course of metamorphosis (changes in the data of phases replacement and the mortality of insects during their moulting).

Studies on host-flea relationship. IV. Progesterone and cortisone do not influence the reproductive potentials of rat fleas Xenopsylla cheopis (Rothschild) and X. astia (Rothschild).

Experiments carried out to study the influence of progesterone and cortisone on the initiation of ovarian maturation, fecundity rate and fertility of the two species of rat fleas Xenopsylla cheopis (Rothschild) and X. astia (Rothschild) indicated that these hormones do not exert any influence on their reproductive potentials. This along with earlier observations show that the factors which regulate ovarian maturation and fecundity in these rat fleas are different from those of the rabbit flea Spilopsyllus cuniculi (Dale).