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1.
PLoS One ; 15(8): e0236143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790679

RESUMO

The focus of gastro-intestinal parasite control in the sheep industry is increasingly on finding a balance between maintaining productivity of the flock whilst minimising selection for anthelmintic resistance to preserve anthelmintic efficacy for the future. Periparturient ewes represent the major source of gastro-intestinal parasites for growing lambs and are therefore a priority for parasite control. This study examines the impact on ewe faecal egg counts (FECs), lamb FECs, lamb daily live weight gains (DLWGs) and pasture larval counts of treating groups of ewes two weeks prior to lambing with either, a long-acting moxidectin treatment, short-acting doramectin or control. Six groups of twenty ewes were allocated to individual paddocks, two groups allocated to each treatment, and weekly faecal sampling was performed throughout from the ewes and from six weeks after the start of lambing in the lambs. Treatment group was found to have a significant effect on both ewe FEC (p<0.001) and lamb FEC (p = 0.001) with the group receiving the long-acting anthelmintic having the lowest ewe and lamb FECs. There was no significant effect on the DLWGs of the lambs. Pasture larval counts at the end of the study period were lowest in the long-acting wormer treatment group. The use of long-acting moxidectin may be helpful as part of a parasite control programme by reducing the worm burdens of ewes and their lambs, decreasing the number of anthelmintic treatments required in that year and by reducing pasture contamination for those sheep which will graze the pasture in the next year. However, like all anthelmintics, its use should be judicious to avoid selection for resistance.


Assuntos
Criação de Animais Domésticos/métodos , Anti-Helmínticos/administração & dosagem , Infecções por Nematoides/veterinária , Doenças dos Ovinos/tratamento farmacológico , Ovinos/parasitologia , Animais , Anti-Helmínticos/farmacocinética , Fazendas , Fezes/parasitologia , Feminino , Meia-Vida , Ivermectina/administração & dosagem , Ivermectina/análogos & derivados , Ivermectina/farmacocinética , Larva , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Nematoides/isolamento & purificação , Infecções por Nematoides/diagnóstico , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas/veterinária , Período Pós-Parto , Gravidez , Doenças dos Ovinos/diagnóstico , Doenças dos Ovinos/parasitologia
2.
Parasitol Res ; 119(9): 3099-3104, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627079

RESUMO

The first case of feline ocular Thelazia callipaeda infection and two new canine imported infections in West Germany are here described. The three animals had a history of recent travel to/from other countries. The young adult cat imported from Spain presented an intermittent unilateral ocular discharge. During in-depth ophthalmic examination, a single alive nematode was removed from the conjunctival compartment of the affected eye. Referring to the canine cases, an adult female dog originated from Kenya presented epiphora and mucous whitish-grey discharge of the right eye. During flushing of the nasolacrimal duct two small, thin and long nematodes were removed. Furthermore, a male Borzoi racing dog with regular visit to racing tracks in different countries presented ocular mucous discharge. At ophthalmologic examination, two transparent-whitish vital nematodes were removed. All nematode specimens of the three cases were morphologically identified as adult T. callipaeda parasites. The animals were treated orally with milbemycin oxime (2.0 mg/kg; cat) or milbemycin oxime/praziquantel (0.5 mg/kg and 5.0 mg/kg; dogs) twice with 1-week interval resulting in complete resolution of symptoms. The repeated introduction of patent T. callipaeda-infected animals, especially from southern and eastern endemic countries, will ease the establishment of ophthalmic thelaziosis in Northern Europe. The male fruit fly, Phortica variegata, an intermediate host of T. callipaeda, is endemic within European countries. Considering the clinical and zoonotic relevance of ophthalmic thelaziosis, enhanced disease awareness of European medical and veterinarian doctors and in-depth eye examination for proper detection of T. callipaeda are crucial for appropriate anthelmintic treatments and to limit spreading of the infection.


Assuntos
Doenças do Gato/parasitologia , Doenças do Cão/parasitologia , Infecções Oculares Parasitárias/parasitologia , Infecções por Spirurida/veterinária , Thelazioidea/isolamento & purificação , Animais , Anti-Helmínticos/administração & dosagem , Doenças do Gato/tratamento farmacológico , Gatos , Cães , Infecções Oculares Parasitárias/tratamento farmacológico , Feminino , Alemanha , Macrolídeos/administração & dosagem , Masculino , Infecções por Spirurida/tratamento farmacológico , Infecções por Spirurida/parasitologia , Thelazioidea/genética , Thelazioidea/fisiologia
3.
An Acad Bras Cienc ; 92(2): e20200466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32556054

RESUMO

COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the "Spanish flu" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.


Assuntos
Antibacterianos/administração & dosagem , Antiparasitários/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Macrolídeos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Inibidores de Serino Proteinase/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Antivirais/química , Antivirais/farmacologia , Humanos , Macrolídeos/química , Macrolídeos/farmacologia , Pandemias , Inibidores de Serino Proteinase/química , Inibidores de Serino Proteinase/farmacologia
4.
Int J Infect Dis ; 97: 374-379, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534142

RESUMO

OBJECTIVES: To report atypical pathogens from clinical trial data comparing delafloxacin to moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia (CABP). METHODS: Multiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen. RESULTS: The microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520). Overall, 13.1% (68/520) had a monomicrobial atypical infection and 2.3% (12/520) had polymicrobial all-atypical infections. Among patients with polymicrobial infections, Streptococcus pneumoniae was the most frequently occurring co-infecting organism and Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism. For Mycoplasma pneumoniae and Legionella pneumophila, serology yielded the highest number of diagnoses. Delafloxacin and moxifloxacin had similar in vitro activity against M. pneumoniae and delafloxacin had greater activity against L. pneumophila. Two macrolide-resistant M. pneumoniae isolates were recovered. No fluoroquinolone-resistant M. pneumoniae were isolated. The rates of microbiological success (documented or presumed eradication) at test-of-cure were similar between the delafloxacin and moxifloxacin groups. There was no evidence of a correlation between minimum inhibitory concentration (MIC) and outcome; a high proportion of favorable outcomes was observed across all delafloxacin baseline MICs. CONCLUSIONS: Delafloxacin may be considered a treatment option as monotherapy for CABP in adults, where broad-spectrum coverage including atypical activity is desirable.


Assuntos
Antibacterianos/administração & dosagem , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fluoroquinolonas/administração & dosagem , Moxifloxacina/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Adulto , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Legionella pneumophila/efeitos dos fármacos , Legionella pneumophila/crescimento & desenvolvimento , Legionella pneumophila/isolamento & purificação , Macrolídeos/administração & dosagem , Masculino , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/crescimento & desenvolvimento , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia Bacteriana/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Adulto Jovem
5.
Medicine (Baltimore) ; 99(19): e19987, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384451

RESUMO

This study aimed to investigate the inner linkage and mechanism of Mycoplasma pneumoniae (MP) infection and Kawasaki disease (KD), as well as the risk factors of outcome in this cohort of patients.A retrospective study was performed in 210 patients diagnosed with KD complicated with community acquired pneumonia (CAP) in Children's Hospital, Zhejiang University School of Medicine from January 2014 to December 2017. They were divided into two groups based on MP infection: MP infection group (n = 97) and non-MP infection group (n = 113). We compared the variables of these two groups based on medical records.The MP infection group had higher ESR than the non-MP infection group. During hospitalization, the non-MP infection group had higher levels of WBC during hospital, LDH, PCT, and lower HB when compared to the MP infection group. No differences were found in the hs-CRP level, N%, PLT, ALT, CKMB, and cytokine levels (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) between MP and non-MP infection group. Likewise, no difference was found in fever duration or hospital stays between them. Totally 19 patients in the infection group had CAA with a rate of 19.59%; and 27 (23.89%) patients had CAA in the non-MP infection group. Unfortunately, no difference was found in CAA rate between the two groups.MP infection may occur simultaneously in children with Kawasaki disease. KD patients with MP infection tended to occur in older population. MP infection may not increase the risk of CAA, which still needs further large-scaled studies to confirm. Clinicians should be alert to KD patients with high level of ESR. MP should be screened and early treatment with macrolides should be given timely.


Assuntos
Sedimentação Sanguínea , Cardiopatias , Macrolídeos/administração & dosagem , Síndrome de Linfonodos Mucocutâneos , Pneumonia por Mycoplasma , Antibacterianos/administração & dosagem , Pré-Escolar , China/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Comorbidade , Citocinas/sangue , Intervenção Médica Precoce/métodos , Feminino , Cardiopatias/etiologia , Cardiopatias/prevenção & controle , Humanos , Lactente , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/terapia , Pneumonia por Mycoplasma/sangue , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Estudos Retrospectivos , Avaliação de Sintomas/métodos , Avaliação de Sintomas/estatística & dados numéricos
6.
Am J Trop Med Hyg ; 103(3): 1319-1328, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32342837

RESUMO

Recent evidence indicates mass drug administration with azithromycin may reduce child mortality. This study uses verbal autopsy (VA) to investigate the causes of individual deaths during the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial in Malawi. Cluster randomization was performed as part of MORDOR. Biannual household visits were conducted to distribute azithromycin or placebo to children aged 1-59 months and update the census to identify deaths for VA. MORDOR was not powered to investigate mortality effects at individual sites, but the available evidence is presented here for hypothesis generation regarding the mechanism through which azithromycin may reduce child mortality. Automated VA analysis was performed to infer the likely cause of death using two major analysis programs, InterVA and SmartVA. A total of 334 communities were randomized to azithromycin or placebo, with more than 130,000 person-years of follow-up. During the study, there were 1,184 deaths, of which 1,131 were followed up with VA. Mortality was 9% lower in azithromycin-treated communities than in placebo communities (rate ratio 0.91 [95% CI: 0.79-1.05]; P = 0.20). The intention-to-treat analysis by cause using InterVA suggested fewer HIV/AIDS deaths in azithromycin-treated communities (rate ratio 0.70 [95% CI: 0.50-0.97]; P = 0.03) and fewer pneumonia deaths (rate ratio 0.82 [95% CI: 0.60-1.12]; P = 0.22). The use of the SmartVA algorithm suggested fewer diarrhea deaths (rate ratio 0.71 [95% CI: 0.51-1.00]; P = 0.05) and fewer pneumonia deaths (rate ratio 0.58 [95% CI: 0.33-1.00]; P = 0.05). Although this study is not able to provide strong evidence, the data suggest that the mortality reduction during MORDOR in Malawi may have been due to effects on pneumonia and diarrhea or HIV/AIDS mortality.


Assuntos
Síndrome de Imunodeficiência Adquirida/mortalidade , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Causas de Morte , Infecções por HIV/mortalidade , Pneumonia/mortalidade , Autopsia , Mortalidade da Criança , Pré-Escolar , Diarreia/mortalidade , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Macrolídeos/administração & dosagem , Malaui/epidemiologia , Masculino , Administração Massiva de Medicamentos
7.
Am J Trop Med Hyg ; 103(3): 1283-1290, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32342840

RESUMO

The recent Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial reported a reduction in child mortality following biannual azithromycin mass drug administration (MDA). Here, we investigate the financial costs and cost-effectiveness from the health provider perspective of azithromycin MDA at the MORDOR-Malawi study site. During MORDOR, a cluster-randomized trial involving biannual azithromycin MDA or placebo to children aged 1-59 months, fieldwork-related costs were collected, including personnel, transport, consumables, overheads, training, and supervision. Mortality rates in azithromycin- and placebo-treated clusters were calculated overall and for the five health zones of Mangochi district. These were used to estimate the number needed to treat to avert one death and the costs per death and disability-adjusted life year (DALY) averted. The cost per dose of MDA was $0.74 overall, varying between $0.63 and $0.94 in the five zones. Overall, the number needed to treat to avert one death was 1,213 children; the cost per death averted was $898.47, and the cost per DALY averted was $9.98. In the three zones where mortality was lower in azithromycin-treated clusters, the number needed to treat to avert one death, cost per death averted, and cost per DALY averted, respectively, were as follows: 3,070, $2,899.24, and $32.31 in Monkey Bay zone; 1,530, $1,214.42, and $13.49 in Chilipa zone; and 344, $217.98, and $2.42 in Namwera zone. This study is a preliminary cost-effectiveness analysis that indicates azithromycin MDA for reducing child mortality has the potential to be highly cost-effective in some settings in Malawi, but the reasons for geographical variation in effectiveness require further investigation.


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Mortalidade da Criança , Mortalidade Infantil , Macrolídeos/administração & dosagem , Administração Massiva de Medicamentos/economia , Pré-Escolar , Análise Custo-Benefício , Feminino , Geografia , Humanos , Lactente , Malaui , Masculino , Anos de Vida Ajustados por Qualidade de Vida
9.
Thorax ; 75(5): 405-406, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303622

RESUMO

The British Thoracic Society (BTS) guideline on the use of long-term macrolides in adults with respiratory disease has been published. It indicates where there is evidence to support the use of long-term low-dose macrolides and where there is not. It discusses the potential benefits of such therapy for patients and also describes the potential risks to individuals and wider populations. It seeks to provide a pragmatic approach for clinicians considering long-term macrolide therapy for their patients. This guideline has also acted as a learning exercise for the BTS in introducing the Grading of Recommendations Assessment, Development and Evaluation approach to guideline development, which will be used going forwards.


Assuntos
Antibacterianos/uso terapêutico , Macrolídeos/uso terapêutico , Doenças Respiratórias/tratamento farmacológico , Administração Oral , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Humanos , Macrolídeos/administração & dosagem , Macrolídeos/efeitos adversos , Guias de Prática Clínica como Assunto , Fatores de Tempo
10.
BMC Vet Res ; 16(1): 81, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138735

RESUMO

BACKGROUND: Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. RESULTS: Gamithromycin was well absorbed and fully bioavailable (87.2-101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC24h/MIC ratio correlated well with ex vivo efficacy (R2 = 0.97). The AUC24h/MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (COPD) was determined to be 0.25 mg/L. CONCLUSION: The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.


Assuntos
Infecções por Haemophilus/veterinária , Haemophilus parasuis/efeitos dos fármacos , Macrolídeos/farmacologia , Doenças dos Suínos/tratamento farmacológico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Área Sob a Curva , Infecções por Haemophilus/tratamento farmacológico , Injeções Intramusculares/veterinária , Injeções Subcutâneas/veterinária , Macrolídeos/administração & dosagem , Macrolídeos/farmacocinética , Masculino , Testes de Sensibilidade Microbiana/veterinária , Sus scrofa , Suínos
11.
Parasit Vectors ; 13(1): 57, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113466

RESUMO

BACKGROUND: Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs. METHODS: Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) on Day 0. All dogs were infested with approximately 100 unfed, adult fleas (C. felis or C. canis) prior to treatment and weekly for 5 weeks post-treatment. In Studies 1, 2 and 3, the number of viable fleas were comb-counted at 24 h after treatment and after each weekly infestation; Study 2 also included groups treated with tablets containing sarolaner-alone (1.2 mg/kg), moxidectin-alone (24 µg/kg) or pyrantel-alone (5 mg/kg). In Study 4, flea counts were conducted at 3, 4, 8 and 12 h after treatment and subsequent weekly infestations to establish speed of kill. In Study 5 (flea reproduction), dogs were housed in an enclosure designed to facilitate collection of flea eggs. RESULTS: Efficacy of Simparica Trio™ against C. felis was ≥ 99.7% and against C. canis was 100% at 24 h after treatment and after subsequent infestations for at least 35 days. Treatment with sarolaner-alone had similar efficacy to Simparica Trio™, while moxidectin-alone and pyrantel-alone were no different from placebo at most time points. In Study 4, significant flea killing started at 4 h after treatment; by 8 h after treatment, all treated dogs were free of fleas. Following weekly re-infestation, the combination product reduced fleas by ≥ 97.8% within 12 h for 28 days. Simparica Trio™ reduced flea egg-laying by 100% for 35 days. No treatment-related adverse reactions occurred in any study. CONCLUSIONS: A single dose of Simparica Trio™ at the recommended minimum dose provided highly efficacious and rapid treatment within 4 h of existing flea infestations and persistent control of fleas on dogs for 5 weeks. The efficacy against fleas resulted in 100% prevention of flea reproduction for over a month following a single oral dose.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Ctenocephalides/fisiologia , Doenças do Cão/prevenção & controle , Cães , Combinação de Medicamentos , Feminino , Infestações por Pulgas/tratamento farmacológico , Infestações por Pulgas/prevenção & controle , Macrolídeos/administração & dosagem , Masculino , Carga Parasitária , Pirantel/administração & dosagem , Reprodução/efeitos dos fármacos , Compostos de Espiro/administração & dosagem , Fatores de Tempo , Resultado do Tratamento
12.
Parasit Vectors ; 13(1): 100, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113468

RESUMO

BACKGROUND: Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe. METHODS: Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation. RESULTS: There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days. CONCLUSIONS: These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Carrapato/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Cães , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Europa (Continente) , Feminino , Ixodidae/classificação , Macrolídeos/administração & dosagem , Masculino , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Comprimidos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Fatores de Tempo , Resultado do Tratamento
13.
Parasit Vectors ; 13(1): 70, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113470

RESUMO

BACKGROUND: Gastrointestinal nematodes are parasites that commonly infect dogs, and infections can be subclinical or may cause considerable clinical disease. Some species are zoonotic and may also cause clinical disease in humans. Year-round treatment of dogs is recommended to eliminate existing infections, which also indirectly reduces the potential for subsequent human exposure to zoonotic species. Here we present two studies that evaluated the safety and efficacy of a novel chewable oral tablet containing sarolaner, moxidectin and pyrantel against gastrointestinal nematode infections in dogs presented as veterinary patients in Europe and the USA. METHODS: Dogs naturally infected with Toxocara canis, Toxascaris leonina, Ancylostoma caninum and/or Uncinaria stenocephala were enrolled in the European study, and dogs naturally infected with T. canis were enrolled in the USA study. The animals were treated once orally with Simparica Trio™ tablets to provide 1.2-2.4 mg/kg sarolaner, 24-48 µg/kg moxidectin and 5-10 mg/kg pyrantel (as pamoate salt) or with a commercially available product according to the label directions as positive control. Efficacy was based on the post-treatment reduction in geometric mean egg counts (per gram feces) 7 or 10 days after treatment compared to pre-treatment egg counts. RESULTS: Simparica Trio™ was well tolerated in both studies. In the European study, geometric mean egg counts for T. canis, T. leonina, A. caninum and U. stenocephala were reduced by ≥ 98.3% in the Simparica Trio™ group and by ≥ 97.4% in the afoxolaner + milbemycin oxime group. In the USA study, geometric mean egg counts for T. canis were reduced by 99.2% in the Simparica Trio™ group and by 98.6% in the ivermectin + pyrantel group. In the USA study, 48 and 10 dogs in the Simparica Trio™ and the ivermectin + pyrantel group, respectively, were co-infected with A. caninum and the reduction in the post-treatment mean fecal egg counts were 98.6% and 74.7%, respectively. CONCLUSIONS: A single oral administration of Simparica Trio™ chewable tablets was well tolerated and was effective in the treatment of dogs with naturally occurring gastrointestinal nematode infections presented as veterinary patients in Europe and the USA.


Assuntos
Antinematódeos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Enteropatias Parasitárias/veterinária , Nematoides/efeitos dos fármacos , Infecções por Nematoides/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Cães , Combinação de Medicamentos , Europa (Continente) , Feminino , Enteropatias Parasitárias/tratamento farmacológico , Macrolídeos/administração & dosagem , Masculino , Nematoides/classificação , Infecções por Nematoides/tratamento farmacológico , Contagem de Ovos de Parasitas , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Resultado do Tratamento , Estados Unidos
14.
Parasit Vectors ; 13(1): 99, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113471

RESUMO

BACKGROUND: Ancylostomatids ('hookworms') are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™), against induced larval (L4), immature adult (L5) and adult A. caninum, and adult U. stenocephala infections in dogs. METHODS: Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. RESULTS: Based on geometric mean worm counts, efficacy of Simparica Trio™ was ≥ 98.4% against L4 larval stage of A. caninum, ≥ 99.8% against immature adult (L5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. CONCLUSIONS: These studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against L4 larval and immature adult (L5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.


Assuntos
Antinematódeos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infecções por Uncinaria/veterinária , Administração Oral , Ancylostomatoidea/crescimento & desenvolvimento , Animais , Azetidinas/administração & dosagem , Doenças do Cão/parasitologia , Cães , Combinação de Medicamentos , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/parasitologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Macrolídeos/administração & dosagem , Carga Parasitária , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Comprimidos , Resultado do Tratamento
15.
Parasit Vectors ; 13(1): 98, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113472

RESUMO

BACKGROUND: One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs. METHODS: Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or afoxolaner (NexGard®, Boehringer-Ingelheim) at the label dose. One dog per household was selected as the primary dog for efficacy evaluations. Treatments were dispensed and dogs were dosed in their home environment on Day 0 and on approximately Day 30. Flea counts and examination for clinical signs of flea allergy dermatitis (FAD) were performed at the initial visit the day before or on Day 0 prior to treatment and on Days 30 and 60. Additionally, all dogs were examined for general health at each visit and blood and urine were collected for clinical pathology at screening and Day 60. RESULTS: Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food. CONCLUSIONS: Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Dermatite/tratamento farmacológico , Dermatite/veterinária , Cães , Combinação de Medicamentos , Feminino , Infestações por Pulgas/tratamento farmacológico , Hospitais Veterinários , Isoxazóis/administração & dosagem , Macrolídeos/administração & dosagem , Masculino , Naftalenos/administração & dosagem , Carga Parasitária , Pirantel/administração & dosagem , Sifonápteros , Compostos de Espiro/administração & dosagem , Comprimidos , Resultado do Tratamento , Estados Unidos
16.
Parasit Vectors ; 13(1): 76, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113473

RESUMO

BACKGROUND: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs. METHODS: Dogs were allocated randomly based on host suitability tick counts to treatment with a single dose of either placebo or Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days -2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation. RESULTS: No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28. CONCLUSIONS: A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Carrapato/veterinária , Administração Oral , Animais , Vetores Aracnídeos , Azetidinas/administração & dosagem , Cães , Combinação de Medicamentos , Feminino , Ixodes , Macrolídeos/administração & dosagem , Masculino , Carga Parasitária , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Infestações por Carrapato/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
17.
Parasit Vectors ; 13(1): 77, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113476

RESUMO

BACKGROUND: The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus. METHODS: Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45-55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively. RESULTS: No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35. CONCLUSIONS: A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Carrapato/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Cães , Combinação de Medicamentos , Ixodidae/classificação , Macrolídeos/administração & dosagem , Carga Parasitária , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
18.
Parasit Vectors ; 13(1): 71, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113482

RESUMO

BACKGROUND: Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced immature adult (L5) and adult T. canis, and adult T. leonina infections in dogs. METHODS: Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7-10 days after treatment compared to placebo control. RESULTS: Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. CONCLUSIONS: These studies confirm the efficacy of a single dose of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.


Assuntos
Antinematódeos/administração & dosagem , Infecções por Ascaridida/veterinária , Doenças do Cão/tratamento farmacológico , Enteropatias Parasitárias/veterinária , Administração Oral , Animais , Infecções por Ascaridida/tratamento farmacológico , Azetidinas/administração & dosagem , Cães , Combinação de Medicamentos , Feminino , Enteropatias Parasitárias/tratamento farmacológico , Macrolídeos/administração & dosagem , Masculino , Contagem de Ovos de Parasitas , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Comprimidos , Toxascaris/efeitos dos fármacos , Toxascaris/fisiologia , Toxocara canis/efeitos dos fármacos , Toxocara canis/fisiologia , Resultado do Tratamento
19.
Parasit Vectors ; 13(1): 64, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113483

RESUMO

BACKGROUND: Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specific clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may offer a safe means to protect dogs against infection. The efficacy of a novel oral endectocide containing moxidectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebo-controlled, randomized, masked studies. The initial study (Study 1) determined the efficacious dosage of moxidectin in the combination product by evaluating three different dose levels, and two follow-up studies (Studies 2 and 3) confirmed the efficacy of the selected moxidectin dose. METHODS: Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efficacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo. RESULTS: In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efficacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confirmed that the efficacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio™ was ≥ 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product provided effective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs. CONCLUSIONS: A single oral treatment of dogs with Simparica Trio™ providing moxidectin at a minimum dose of 24 µg/kg was efficacious in the prevention of angiostrongylosis.


Assuntos
Angiostrongylus/efeitos dos fármacos , Antinematódeos/administração & dosagem , Doenças do Cão/prevenção & controle , Infecções por Strongylida/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Cães , Combinação de Medicamentos , Feminino , Macrolídeos/administração & dosagem , Masculino , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Infecções por Strongylida/prevenção & controle , Resultado do Tratamento
20.
Parasit Vectors ; 13(1): 72, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32113486

RESUMO

BACKGROUND: A novel chewable oral tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe. METHODS: Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ tablets (flea study: n = 297; tick study: n = 189) to provide 1.2-2.4 mg/kg sarolaner, 24-48 µg/kg moxidectin and 5-10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog's entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog's entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies. RESULTS: Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered. CONCLUSIONS: A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.


Assuntos
Acaricidas/administração & dosagem , Doenças do Cão/tratamento farmacológico , Infestações por Pulgas/veterinária , Infestações por Carrapato/veterinária , Administração Oral , Animais , Azetidinas/administração & dosagem , Dermatite/tratamento farmacológico , Dermatite/veterinária , Cães , Combinação de Medicamentos , Feminino , Infestações por Pulgas/tratamento farmacológico , Macrolídeos/administração & dosagem , Masculino , Carga Parasitária , Pirantel/administração & dosagem , Compostos de Espiro/administração & dosagem , Comprimidos , Infestações por Carrapato/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento
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