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1.
Parasit Vectors ; 12(1): 509, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666109

RESUMO

BACKGROUND: Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of sarolaner (Simparica®, Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment. METHODS: Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days - 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs. RESULTS: There were no adverse reactions to treatment. A single dose of sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t(df) ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001). CONCLUSIONS: In this study, a single oral administration of sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment.


Assuntos
Antiparasitários/uso terapêutico , Vetores Aracnídeos , Azetidinas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ixodidae , Compostos de Espiro/uso terapêutico , Infestações por Carrapato/veterinária , Administração Oral , Animais , Antiparasitários/administração & dosagem , Azetidinas/administração & dosagem , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Cães , Compostos de Espiro/administração & dosagem , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle
2.
Parasit Vectors ; 12(1): 444, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506088

RESUMO

BACKGROUND: Moxidectin has previously shown limited efficacy (≤ 44.4%) against confirmed macrocyclic lactone (ML)-resistant Dirofilaria immitis strains at 3 µg/kg after single and multiple oral dosages. Three studies were conducted to evaluate higher oral moxidectin doses for efficacy against confirmed ML-resistant D. immitis strains. METHODS: Dogs were inoculated with 50 D. immitis L3 and randomly allocated to treatments. Study 1: 6 groups of dogs (n = 8) were inoculated with JYD-34 (Day - 30) and treated as follows: T01, negative control; T02-T05, moxidectin at 3, 6, 12 or 24 µg/kg, respectively, on Day 0 only; T06, moxidectin at 3 µg/kg on Days 0, 30 and 60. Study 2: 10 groups of dogs (n = 5) were inoculated (Day - 30) with either JYD-34 (T01, T03-05) or ZoeLA (T02, T06-T10) and treated as follows: T01 and T02, negative controls; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56; T06 and T09, moxidectin at 3 or 60 µg/kg on Day 0 only; T07, T08 and T10, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. Study 3: 5 groups of dogs (n = 5) were inoculated with ZoeMO (Day - 28) and treated as follows: T01, negative control; T02, moxidectin at 3 µg/kg moxidectin on Day 0 only; T03-T05, moxidectin at 24, 40 or 60 µg/kg, respectively, on Days 0, 28 and 56. All dogs were necropsied for adult heartworm recovery ~ 4-5 months post-inoculation. RESULTS: All moxidectin-treated dogs showed significantly lower worm counts than controls. The efficacy of moxidectin administered once at 3 µg/kg was 19% (JYD-34), 44.4% (ZoeLA) and 82.1% (ZoeMO). Increasing both the dose and the number of dosages of moxidectin improved efficacy, with 100% protection obtained using three dosages of moxidectin at either 40 µg/kg (JYD-34, ZoeMO) or 60 µg/kg (ZoeLA). Three dosages of 24 µg/kg were also highly effective, providing ≥ 98.8% efficacy for all three strains. CONCLUSIONS: Increasing both the dose and number of consecutive monthly dosages of moxidectin improved the efficacy against ML-resistant heartworms. Based on these data and other technical considerations, the 24 µg/kg dose was considered the optimal dose for further commercial development.


Assuntos
Antinematódeos/administração & dosagem , Quimioprevenção/métodos , Dirofilaria immitis/isolamento & purificação , Dirofilariose/prevenção & controle , Doenças do Cão/prevenção & controle , Macrolídeos/administração & dosagem , Administração Oral , Animais , Dirofilaria immitis/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Carga Parasitária , Resultado do Tratamento
3.
Parasit Vectors ; 12(1): 445, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31506094

RESUMO

BACKGROUND: Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA. METHODS: In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24-48 µg/kg moxidectin, 2-4 mg/kg sarolaner and 5-10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection. RESULTS: In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20-44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies. CONCLUSIONS: In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.


Assuntos
Antinematódeos/administração & dosagem , Azetidinas/administração & dosagem , Quimioprevenção/métodos , Dirofilariose/prevenção & controle , Doenças do Cão/prevenção & controle , Macrolídeos/administração & dosagem , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Administração Oral , Animais , Dirofilaria immitis/efeitos dos fármacos , Cães , Quimioterapia Combinada/métodos , Placebos/administração & dosagem , Resultado do Tratamento , Estados Unidos
4.
Vet Parasitol ; 270 Suppl 1: S38-S44, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31104940

RESUMO

The efficacy and safety of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated for the prevention of heartworm (Dirofilaria immitis) disease and the treatment of roundworm infection in cats enrolled as veterinary patients in two field studies conducted in Japan. In the heartworm field study, 91 cats negative for D. immitis antigen and anti-D. immitis antibody were enrolled and received 9 monthly topical treatments with selamectin plus sarolaner during the period of April to December 2015. Efficacy was assessed by testing post-treatment blood samples collected 8, 12, and 15 months after initiation of treatment for the presence of D. immitis antigen and anti-D. immitis antibody. Eighty-seven cats completed the entire study and were included in the determination of efficacy. No D. immitis antigen or anti-D. immitis antibody were detected in any of the post-treatment samples. In the roundworm field study, completed in the period from April to November 2015, 64 cats with ≥100 roundworm eggs per gram (EPG) of feces were enrolled and allocated randomly in a 1:1 ratio, to receive either selamectin plus sarolaner or emodepside plus praziquantel (Profender®, Bayer). Treatments were administered topically on Days 0 and 30, and efficacy was assessed by fecal EPG counts conducted on Days 14, 30, and 60. All cats completed the entire study. At enrollment, all cats were infected with Toxocara cati. Compared to pre-treatment, geometric mean T. cati EPG counts on Days 14, 30, and 60 were reduced by >99.9% in both treatment groups. There were no treatment-related adverse events in either study. Monthly topical administration of Revolution® Plus / Stronghold® Plus providing a minimum of 6 mg/kg selamectin and 1 mg/kg sarolaner was safe and effective in the prevention of heartworm disease and the treatment of roundworm infection in cats enrolled as veterinary patients in Japan.


Assuntos
Antiparasitários/administração & dosagem , Azetidinas/administração & dosagem , Doenças do Gato/prevenção & controle , Dirofilariose/prevenção & controle , Enteropatias Parasitárias/veterinária , Ivermectina/análogos & derivados , Infecções por Nematoides/veterinária , Compostos de Espiro/administração & dosagem , Administração Tópica , Animais , Doenças do Gato/tratamento farmacológico , Doenças do Gato/parasitologia , Gatos , Dirofilaria immitis/efeitos dos fármacos , Dirofilaria immitis/imunologia , Dirofilariose/tratamento farmacológico , Dirofilariose/parasitologia , Composição de Medicamentos/veterinária , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/parasitologia , Helmintíase/prevenção & controle , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/prevenção & controle , Ivermectina/administração & dosagem , Masculino , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Infecções por Nematoides/prevenção & controle , Contagem de Ovos de Parasitas/veterinária , Distribuição Aleatória , Toxocara/efeitos dos fármacos , Resultado do Tratamento
5.
Vet Parasitol ; 270 Suppl 1: S12-S18, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30914264

RESUMO

The efficacy of a single application of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated against fleas and ticks infesting cats enrolled as veterinary patients in two field studies conducted in Japan and against Haemaphysalis longicornis ticks on cats in a laboratory study. In the laboratory study, sixteen cats were ranked based on pre-treatment tick counts and allocated randomly to treatment on Day 0 with either selamectin plus sarolaner or placebo. Cats were infested with adult H. longicornis on Days -2, 5, 12, 19, 26 and 33. Efficacy relative to placebo was based on live attached tick counts conducted 48 h after treatment and subsequent re-infestations. Selamectin plus sarolaner reduced live, attached H. longicornis counts by 96.4% within 48 h of treatment, and by ≥91.7% within 48 h of weekly re-infestation for 35 days, based on arithmetic means. In the field studies, 67 client-owned cats harboring six or more live fleas and 63 cats harboring four or more live attached ticks were enrolled to evaluate selamectin plus sarolaner for efficacy and safety compared with a registered product. Cats were allocated randomly to treatment with selamectin plus sarolaner or fipronil plus (S)-methoprene based on order of presentation. Treatment was administered once on Day 0 and efficacy was assessed by parasite counts conducted on Days 14 and 30 compared to the pre-treatment count. In the flea field study, live flea counts on Days 14 and 30 were reduced by 99.5% and 99.9% in the selamectin plus sarolaner group, and by 97.6% and 98.6% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Clinical signs typically associated with flea allergy dermatitis improved following treatment. In the tick field study, live tick counts on Days 14 and 30 were reduced by 97.5% and 97.7% in the selamectin plus sarolaner group, and by 91.5% and 93.4% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Selamectin plus sarolaner was determined to be non-inferior to fipronil plus (S)-methoprene in both field studies. There were no treatment-related adverse events in any study. A single topical dose of Revolution® Plus / Stronghold® Plus providing a minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was confirmed to be effective against H. longicornis ticks on cats for one month and safe and effective in the treatment of fleas and ticks on cats enrolled as veterinary patients in Japan.


Assuntos
Azetidinas/administração & dosagem , Doenças do Gato/tratamento farmacológico , Infestações por Pulgas/veterinária , Ivermectina/análogos & derivados , Compostos de Espiro/administração & dosagem , Controle de Ácaros e Carrapatos , Infestações por Carrapato/veterinária , Acaricidas/administração & dosagem , Administração Tópica , Animais , Doenças do Gato/prevenção & controle , Gatos , Composição de Medicamentos/veterinária , Feminino , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/prevenção & controle , Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Japão , Masculino , Metoprene/administração & dosagem , Pirazóis/administração & dosagem , Distribuição Aleatória , Sifonápteros/efeitos dos fármacos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Carrapatos/efeitos dos fármacos , Resultado do Tratamento
6.
Ticks Tick Borne Dis ; 9(6): 1431-1436, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29983263

RESUMO

Ticks are known to transmit pathogens which threaten the health and welfare of companion animals and man globally. In the present study, mainly adult ticks were collected from dogs and cats presented at their local veterinary practice in Hungary, France, Italy, Belgium (dogs only) and Germany (cats only), and identified based on tick morphology. If more than one tick was collected from a host animal, ticks were pooled by tick species for DNA extraction and subsequent PCR examination for the presence of tick-borne pathogens. Out of 448 tick samples, 247 (95 from dogs and 152 from cats) were Ixodes ricinus, 26 (12 from dogs and 14 from cats) were I. hexagonus, 59 (43 from dogs and 16 from cats) were Dermacentor reticulatus and 116 (74 from dogs and 42 from cats) were Rhipicephalus sanguineus sensu lato (s.l.). In 17% of the I. ricinus samples Anaplasma phagocytophilum was found. Borrelia spp. were mainly identified in I. ricinus collected from cats (18%) and to a lesser extent in dog-sourced ticks (1%), with Borrelia afzelii (n = 11), B. garinii (n = 7), B. valaisiana (n = 5), B. lusitaniae (n = 3) and B. burgdorferi sensu stricto (n = 3) being identified. One I. hexagonus sample collected from a cat in France tested positive for B. afzelii. Babesia canis was detected in 20% of the D. reticulatus samples, mainly from Hungary. Rhipicephalus sanguineus s.l. was found positive for Hepatozoon canis (3%), A. platys (5%) and three Rickettsia species (7%; R. massiliae; R. raoultii and R. rhipicephali). Furthermore, a total of 66 R. sanguineus s.l. ticks were subjected to molecular analysis and were identified as R. sanguineus sp. II-temperate lineage, with seven haplotypes recorded. Amongst them, the most prevalent sequence types were haplotype XIII (n = 24; 69%) and haplotype XIV (n = 16; 52%) in France and in Italy, respectively, found both in cats and dogs. Although differences related to both country and host, were observed, the results of this study indicate that cats and dogs are exposed to tick-borne pathogen infected ticks, which may represent a medical risk to these host animals.


Assuntos
Doenças do Gato/epidemiologia , Doenças do Cão/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária , Carrapatos/microbiologia , Carrapatos/parasitologia , Animais , Doenças do Gato/microbiologia , Doenças do Gato/parasitologia , Gatos , Doenças do Cão/microbiologia , Doenças do Cão/parasitologia , Cães , Europa (Continente)/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/parasitologia , Carrapatos/virologia
7.
Parasit Vectors ; 10(Suppl 2): 482, 2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29143634

RESUMO

BACKGROUND: Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 µg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis. METHODS: A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28-30 days later with single oral doses of 3 µg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms. RESULTS: A single dose of 3 µg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 µg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 µg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years. CONCLUSIONS: A single oral dose (3 µg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.


Assuntos
Dirofilaria immitis/efeitos dos fármacos , Dirofilariose/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Filaricidas/administração & dosagem , Macrolídeos/administração & dosagem , Animais , Dirofilaria immitis/fisiologia , Dirofilariose/parasitologia , Doenças do Cão/parasitologia , Cães , Avaliação de Medicamentos , Resistência a Medicamentos
8.
Parasit Vectors ; 10(1): 415, 2017 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-28877743

RESUMO

BACKGROUND: Canine babesiosis is a clinically significant emerging vector-borne disease caused among others by the protozoan Babesia canis. The efficacy of sarolaner (Simparica®; Zoetis; at the minimum recommended label dose of 2.0 mg per kg bodyweight) in the prevention of babesiosis was evaluated in twenty-four dogs randomly allocated to either a placebo-treated group or one of two sarolaner-treated groups. At 21 or 28 days after treatment administration, dogs were infested with 50 ± 4 Dermacentor reticulatus ticks of which 25% were confirmed to be infected with Babesia canis. Blood samples were collected from each dog prior to tick infestation and weekly thereafter until 49 days after infestation. The blood was assayed for B. canis antibodies using an indirect immunofluorescence test (IFAT) and for B. canis DNA by PCR assay. A dog was a priori defined as B. canis-positive if it tested positive by both IFAT and PCR at any time during the study. RESULTS: No treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFAT and PCR. None of the sarolaner-treated animals displayed any clinical symptoms or tested positive on both IFAT and PCR, resulting in a 100% efficacy in the prevention of canine babesiosis (P = 0.0002). CONCLUSION: When given 21 or 28 days before tick infestation, a single treatment with sarolaner at the minimum recommended label dose of 2.0 mg per kg body weight prevented the transmission of B. canis by D. reticulatus to dogs.


Assuntos
Acaricidas/administração & dosagem , Vetores Aracnídeos/efeitos dos fármacos , Azetidinas/administração & dosagem , Babesiose/prevenção & controle , Dermacentor/efeitos dos fármacos , Doenças do Cão/prevenção & controle , Compostos de Espiro/administração & dosagem , Infestações por Carrapato/veterinária , Administração Oral , Animais , Anticorpos Antiprotozoários/sangue , Vetores Aracnídeos/parasitologia , Azetidinas/efeitos adversos , Babesia/genética , Babesia/imunologia , Babesia/isolamento & purificação , Babesiose/parasitologia , Babesiose/transmissão , DNA de Protozoário/genética , Dermacentor/parasitologia , Cães , Reação em Cadeia da Polimerase , Compostos de Espiro/efeitos adversos , Infestações por Carrapato/prevenção & controle
9.
Parasit Vectors ; 10(1): 390, 2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28814323

RESUMO

BACKGROUND: Amblyomma cajennense is the main vector of Rickettsia rickettsii which causes Brazilian spotted fever. This adult tick preferably infests horses and capybaras, but has low host specificity during its immature stages, thus posing a threat to humans and dogs. In this study, the efficacy of sarolaner (Simparic™/Simparica®, Zoetis) when administered once orally to dogs at 2 mg/kg was evaluated against induced infestations of A. cajennense nymphs for up to 35 days after treatment. METHODS: Based on pretreatment tick counts, 20 dogs were randomly allocated to treatment with sarolaner (Simparic™) dosed at 2 mg/kg of body weight or a placebo on Day 0 of the study. Artificial infestations were performed using laboratory raised A. cajennense nymphs on study days -2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 h post-treatment or post-infestation at each time point relative to the counts for dogs that received placebo. RESULTS: There were no adverse reactions to treatment. A single dose of sarolaner (Simparic™) provided 100% efficacy on study days 2, 7 and 14; and ≥ 99.6% on days 21, 28 and 35. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (P < 0.0001). CONCLUSIONS: Under the conditions of the present study, sarolaner (Simparic™) administered once orally at 2 mg/kg provided 100% efficacy against existing infestations and ≥ 99.6% efficacy within 48 h against weekly challenges of A. cajennense for at least 35 days after treatment.


Assuntos
Vetores Aracnídeos/efeitos dos fármacos , Azetidinas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Ixodidae/efeitos dos fármacos , Compostos de Espiro/uso terapêutico , Infestações por Carrapato/veterinária , Administração Oral , Animais , Vetores Aracnídeos/fisiologia , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Brasil , Doenças do Cão/parasitologia , Cães , Ixodidae/fisiologia , Ninfa/efeitos dos fármacos , Ninfa/fisiologia , Carga Parasitária , Febre Maculosa das Montanhas Rochosas/transmissão , Compostos de Espiro/administração & dosagem , Compostos de Espiro/efeitos adversos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Fatores de Tempo , Resultado do Tratamento
10.
Parasit Vectors ; 10(1): 387, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28814332

RESUMO

BACKGROUND: The efficacy and safety of a novel isoxazoline compound, sarolaner (Simparica®, Zoetis) and spinosad (Comfortis®, Elanco) as a positive control were evaluated for the treatment and control of natural flea infestations on dogs in two randomised, blinded, multi-centric clinical trials conducted in 11 veterinary clinics in northeastern and southeastern states of Australia. METHODS: A total of 162 client-owned dogs (80 in northern study and 82 in southern study) from 105 households were enrolled. Each household was randomly allocated to receive either sarolaner (Simparica®, Zoetis) or spinosad (Comfortis®, Elanco). Dogs were dosed on Days 0, 30 and 60 and physical examinations and flea counts were conducted on Days 0, 14, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0. RESULTS: In the northern study, at enrolment, primary dogs had flea counts ranging from 5 to 772. At the first efficacy assessment on Day 14, sarolaner resulted in 99.3% mean reduction in live flea counts relative to Day 0, compared to 94.6% in the spinosad group. On Day 30, the sarolaner-treated group had mean efficacy of 99.2% compared to 95.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.8%. In the southern study, at enrolment, primary dogs had flea counts ranging from 5 to 156. Both sarolaner and spinosad resulted in ≥ 96.7% mean reduction in live flea counts on Day 14. On Day 30, the sarolaner-treated group had mean efficacy of 99.5% compared to 89.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.6%. No treatment-related adverse events were observed in either study. CONCLUSIONS: A single monthly dose of sarolaner (Simparica®) administered orally at 2-4 mg/kg for three consecutive months was well tolerated and provided excellent efficacy against natural infestations of fleas under a range of Australian field conditions including different climatic and housing conditions. Similar efficacy was observed with spinosad (Comfortis®) after the second and third monthly treatments.


Assuntos
Azetidinas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Inseticidas/uso terapêutico , Sifonápteros/efeitos dos fármacos , Compostos de Espiro/uso terapêutico , Administração Oral , Animais , Azetidinas/administração & dosagem , Azetidinas/efeitos adversos , Ensaios Clínicos como Assunto , Doenças do Cão/parasitologia , Cães , Combinação de Medicamentos , Infestações por Pulgas/tratamento farmacológico , Inseticidas/administração & dosagem , Inseticidas/efeitos adversos , Macrolídeos/administração & dosagem , Macrolídeos/uso terapêutico , Carga Parasitária , Compostos de Espiro/administração & dosagem , Compostos de Espiro/efeitos adversos , Resultado do Tratamento
11.
Parasit Vectors ; 10(1): 98, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222813

RESUMO

BACKGROUND: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica®), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard®) for 5 weeks after a single oral dose. METHODS: Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means. RESULTS: At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments. CONCLUSIONS: In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs.


Assuntos
Azetidinas/farmacologia , Doenças do Cão/tratamento farmacológico , Isoxazóis/farmacologia , Ixodes/efeitos dos fármacos , Naftalenos/farmacologia , Compostos de Espiro/farmacologia , Infestações por Carrapato/veterinária , Animais , Austrália , Azetidinas/administração & dosagem , Cães , Isoxazóis/administração & dosagem , Ixodes/fisiologia , Naftalenos/administração & dosagem , Carga Parasitária , Placebos/administração & dosagem , Distribuição Aleatória , Compostos de Espiro/administração & dosagem , Análise de Sobrevida , Infestações por Carrapato/tratamento farmacológico , Fatores de Tempo
12.
Vet Parasitol ; 189(2-4): 308-16, 2012 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-22560330

RESUMO

The objective of the present studies was to evaluate the efficacy of a combined formulation (Startect(®) Dual Active Oral Solution for Sheep, Pfizer Animal Health) of derquantel (DQL) and abamectin (ABA) for the treatment of: (1) sheep experimentally infected with a moxidectin (MOX)-resistant isolate of Teladorsagia circumcincta, and (2) multi-drug resistant gastrointestinal nematode parasites under UK field conditions. In the first study, a total of 40 animals were allocated into 4 treatment groups, and were either left untreated or treated with DQL+ABA, MOX or ABA. Faecal samples were collected on days 1-5 and on day 7 after treatment to examine the reduction in faecal egg excretion and to evaluate the egg viability. On day 14 post treatment all animals were euthanised for abomasal worm counts. There was a 100% reduction in geometric mean worm counts for the DQL+ABA treated animals compared to the untreated control animals (P<0.0001), whereas the percentage reduction in worm counts for the MOX- (P>0.05) and ABA-treated (P=0.0004) animals was 12.4% and 71.8%, respectively. The data from the egg hatch assay (EHA) indicated that in the MOX-treated and the ABA-treated animals, the majority of the eggs hatched after treatment. In the field study, performed on four farms, animals were allocated into 6 groups of 11-15 animals each in order to conduct a faecal egg count reduction test (FECRT), based on arithmetic mean egg counts. One group of animals remained untreated, whereas the other animals were treated with DQL+ABA, MOX, fenbendazole (FBZ), levamisole (LV) or ivermectin (IVM). On each of the farms the reduction in egg excretion after treatment with FBZ, LV or IVM was below 95.0%, indicating anthelmintic resistance. The efficacy of DQL+ABA ranged from 99.1 to 100%, yielding significantly lower egg counts compared to the untreated control group (P ≤ 0.003). For MOX the egg counts were significantly (P ≤ 0.003) lower compared to the untreated group at each farm, with reductions varying from 98.2 to 100%. The post-treatment copro-cultures for larva identification indicated that T. circumcincta was the most abundant worm species after treatment (52-99% of the larvae). The results of these studies confirm the high efficacy of the DQL+ABA combination formulation against anthelmintic resistant nematodes in the UK.


Assuntos
Indóis/uso terapêutico , Ivermectina/análogos & derivados , Nematoides/efeitos dos fármacos , Infecções por Nematoides/veterinária , Oxepinas/uso terapêutico , Doenças dos Ovinos/parasitologia , Animais , Combinação de Medicamentos , Resistência a Medicamentos , Indóis/administração & dosagem , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Oxepinas/administração & dosagem , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/epidemiologia , Reino Unido/epidemiologia
13.
Vet Parasitol ; 186(3-4): 151-8, 2012 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-22245073

RESUMO

Combinations of anthelmintics with a similar spectrum of activity and different mechanisms of action and resistance are widely available in several regions of the world for the control of sheep nematodes. There are two main justifications for the use of such combinations: (1) to enable the effective control of nematodes in the presence of single or multiple drug resistance, and (2) to slow the development of resistance to the component anthelmintic classes. Computer model simulations of sheep nematode populations indicate that the ability of combinations to slow the development of resistance is maximised if certain prerequisite criteria are met, the most important of which appear to concern the opportunity for survival of susceptible nematodes in refugia and the pre-existing levels of resistance to each of the anthelmintics in the combination. Combinations slow the development of a resistant parasite population by reducing the number of resistant genotypes which survive treatment, because multiple alleles conferring resistance to all the component anthelmintic classes must be present in the same parasite for survival. Individuals carrying multiple resistance alleles are rarer than those carrying single resistance alleles. This enhanced efficacy leads to greater dilution of resistant genotypes by the unselected parasites in refugia, thus reducing the proportion of resistant parasites available to reproduce with other resistant adults that have survived treatment. Concerns over the use of anthelmintic combinations include the potential to select for resistance to multiple anthelmintic classes concurrently if there are insufficient parasites in refugia; the potential for shared mechanisms of resistance between chemical classes; and the pre-existing frequency of resistance alleles may be too high on some farms to warrant the introduction of certain combinations. In conclusion, anthelmintic combinations can play an important role in resistance management. However, they are not a panacea and should always be used in accordance with contemporary principles for sustainable anthelmintic use.


Assuntos
Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Infecções por Nematoides/veterinária , Doenças dos Ovinos/tratamento farmacológico , Animais , Combinação de Medicamentos , Nematoides , Infecções por Nematoides/tratamento farmacológico , Ovinos , Doenças dos Ovinos/parasitologia
14.
Vet Parasitol ; 181(2-4): 180-93, 2011 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-21684691

RESUMO

Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal and respiratory nematode parasites of sheep, as follows: ≥ 98.9% efficacy against Haemonchus contortus (adult and L4); Teladorsagia circumcincta (adult, L4 and hypobiotic L4); Teladorsagia trifurcata (L4); Trichostrongylus axei (adult and L4); Trichostrongylus colubriformis (adult and L4); Trichostrongylus falculatus (adult); Trichostrongylus rugatus (adult); Trichostrongylus vitrinus (adult and L4); Cooperia curticei (adult and L4); Cooperia oncophora (adult and L4); Nematodirus spathiger (adult); Nematodirus battus (adult); Nematodirus spp. (hypobiotic L4); Strongyloides papillosus (adult); Strongyloides spp. (L4); Chabertia ovina (adult); Oesophagostomum venulosum (adult); Dictyocaulus filaria (adult); and Protostrongylus rufescens (adult); ≥ 97.0% efficacy against Trichuris ovis (adult); and ≥ 95.9% efficacy against T. trifurcata (adult). Derquantel-abamectin is a highly effective combination anthelmintic, which will provide an important new tool for controlling helminths of sheep when used in conjunction with sustainable drenching practices.


Assuntos
Indóis/administração & dosagem , Indóis/uso terapêutico , Ivermectina/análogos & derivados , Infecções por Nematoides/veterinária , Doenças dos Ovinos/tratamento farmacológico , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/uso terapêutico , Feminino , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Larva/efeitos dos fármacos , Masculino , Estrutura Molecular , Nematoides/efeitos dos fármacos , Infecções por Nematoides/tratamento farmacológico , Ovinos , Doenças dos Ovinos/parasitologia
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