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1.
Exp Parasitol ; 261: 108751, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38604302

RESUMO

Anisakiasis is a parasitic disease transmitted through the consumption of raw or undercooked fish and cephalopods that are infected with larvae of Anisakis simplex (sensu stricto) or Anisakis pegreffii. The purpose of this study was to investigate how A. simplex (s. s.) responds to the influence of anthelmintics such as ivermectin (IVM) and pyrantel (PYR). In vitro experiments were conducted using larvae at two developmental stages of A. simplex (s. s.) (L3 and L4) obtained from Baltic herring (Clupea harengus membras). Larvae were cultured with different concentrations of IVM or PYR (1.56, 3.125, and 6.25 µg/mL) for various durations (3, 6, 9, and 12 h) under anaerobic conditions (37 °C, 5% CO2). The gene expression of actin, ABC transporter, antioxidant enzymes, γ-aminobutyric acid receptors, and nicotinic acetylcholine receptors, as well as the oxidative status were analyzed. The results showed that A. simplex (s. s.) L3 stage had lower mobility when cultured with PYR compared to IVM. The analysis of relative gene expression revealed significant differences in the mRNA level of ABC transporters after treatment with IVM and PYR, compared to the control group. Similar patterns were observed in the gene expression of antioxidant enzymes in response to both drugs. Furthermore, the total antioxidant capacity (TAC) and glutathione S-transferase (GST) activity were higher in the treatment groups than in the control group. These findings suggest a relationship between the expression of the studied genes, including those related to oxidative metabolism, and the effectiveness of the tested drugs.


Assuntos
Anisakis , Anti-Helmínticos , Ivermectina , Larva , Pirantel , Animais , Anisakis/efeitos dos fármacos , Anisakis/genética , Anisakis/crescimento & desenvolvimento , Ivermectina/farmacologia , Larva/efeitos dos fármacos , Larva/genética , Anti-Helmínticos/farmacologia , Pirantel/farmacologia , Actinas/metabolismo , Actinas/genética , Actinas/efeitos dos fármacos , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/efeitos dos fármacos , Xenobióticos/farmacologia , Xenobióticos/metabolismo , Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Anisaquíase/parasitologia , Anisaquíase/veterinária , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/efeitos dos fármacos , Catalase/genética , Catalase/metabolismo , Catalase/efeitos dos fármacos , Peixes/parasitologia , Doenças dos Peixes/parasitologia
2.
Antimicrob Agents Chemother ; 68(5): e0121123, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563751

RESUMO

Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat Trichuris trichiura infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with T. trichiura. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A [ERR = 94%, 95% confidence interval (CI): 92-95; CR = 71%; 95% CI: 58-81] compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (P-value <0.001); decrease in ERR was significant for arms B and C (P-value <0.001). No statistical difference was observed in CR when comparing arms A and B (P-value =1.00) and C (P-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78-83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of T. trichiura.CLINICAL TRIALRegistered at ClinicalTrials.gov (NCT04326868).


Assuntos
Albendazol , Anti-Helmínticos , Mebendazol , Pirantel , Tricuríase , Trichuris , Humanos , Albendazol/uso terapêutico , Albendazol/efeitos adversos , Albendazol/administração & dosagem , Criança , Mebendazol/uso terapêutico , Tricuríase/tratamento farmacológico , Masculino , Feminino , Trichuris/efeitos dos fármacos , Animais , Pré-Escolar , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/administração & dosagem , Adolescente , Pirantel/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Contagem de Ovos de Parasitas
3.
Int J Parasitol Drugs Drug Resist ; 24: 100528, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38422764

RESUMO

This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March-April and in November-December) and the efficacy of pyrantel in one group once (in May-June). For each FECRT, the 90% confidence interval of the percentage faecal egg count reduction was calculated using the hybrid Frequentist/Bayesian analysis method. The resistance in strongylids was observed to fenbendazole, pyrantel and ivermectin in all the groups in which these drugs were tested. The number of animals in each group was sufficient to reach ≥80% power for the resistance test. The results highlight the first case of triple AH resistance in strongylids in France. Further studies involving more farms and equids are required to assess the prevalence of AH resistance in France and refine recommendations for owners.


Assuntos
Anti-Helmínticos , Doenças dos Cavalos , Animais , Feminino , Masculino , Anti-Helmínticos/farmacologia , Teorema de Bayes , Resistência a Medicamentos , Fazendas , Fezes/parasitologia , Fenbendazol/farmacologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/parasitologia , Cavalos , Ivermectina/farmacologia , Contagem de Ovos de Parasitas/veterinária , Pirantel/farmacologia
4.
Vet Parasitol Reg Stud Reports ; 48: 100985, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38316510

RESUMO

Hookworms are the most common intestinal nematode parasites of dogs in Australia. The control of these parasites relies mostly on regular deworming with anthelmintics, with pyrantel-based dewormers being a relatively low cost and readily-available option for dog owners. Pyrantel resistance in canine hookworms in Australia was first reported in 2007, however pyrantel-based dewormers are still used against hookworm infection in dogs across Australia. The present study was conducted to evaluate the efficacy of pyrantel against hookworms infecting dogs housed in a shelter facility in Southeast Queensland which receives rescued or surrendered animals from greyhound rescue centres and dog shelters across this region. A total of 10 dogs were examined using the faecal egg count reduction test (FECRT). There was no reduction in FEC in any of the dogs following pyrantel treatment, with drug efficacies ranging from -0.9% to -283.3%. Given that these dogs originated from various sites across Southeast Queensland, the present study suggests that pyrantel resistance is widespread in this region, and hence this anthelmintic may not be a useful option for treatment of hookworm infections in dogs.


Assuntos
Anti-Helmínticos , Doenças do Cão , Infecções por Uncinaria , Enteropatias Parasitárias , Cães , Animais , Pirantel/farmacologia , Pirantel/uso terapêutico , Ancylostomatoidea , Queensland/epidemiologia , Contagem de Ovos de Parasitas/veterinária , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Infecções por Uncinaria/tratamento farmacológico , Infecções por Uncinaria/epidemiologia , Infecções por Uncinaria/veterinária , Enteropatias Parasitárias/veterinária , Austrália/epidemiologia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia
5.
Parasit Vectors ; 17(1): 51, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308372

RESUMO

BACKGROUND: Babesia canis is a clinically relevant vector-borne pathogen in dogs, and its presence is expanding. The efficacy of Simparica Trio® (Zoetis) in the prevention of B. canis transmission was evaluated at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight. METHODS: Twenty-four (24) dogs were randomly allocated to either a placebo-treated group or one of two treatment groups with Simparica Trio. Dogs were infested with B. canis-infected Dermacentor reticulatus ticks 21 or 28 days after treatment administration. Blood samples for antibody and DNA detection were collected from each dog prior to tick infestation until 28 days after infestation. A dog was defined as being B. canis positive if it tested positive by both an indirect immunofluorescence assay (IFA) 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 IFA and PCR. None of the Simparica Trio-treated animals displayed any clinical symptoms or tested positive, resulting in a 100% efficacy in the prevention of canine babesiosis (P < 0.0001). CONCLUSIONS: A single treatment with Simparica Trio at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight prevents the transmission of B. canis by infected D. reticulatus to dogs for at least 28 days.


Assuntos
Acaricidas , Babesia , Babesiose , Doenças do Cão , Animais , Cães , Acaricidas/uso terapêutico , Administração Oral , Azetidinas , Babesia/genética , Babesiose/prevenção & controle , Dermacentor , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Macrolídeos , Pirantel/uso terapêutico , Compostos de Espiro , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária
6.
Parasit Vectors ; 16(1): 441, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012719

RESUMO

BACKGROUND: Infestation with Sarcoptes scabiei in dogs is a debilitating disease if left untreated and is transmissible to humans. Two field studies were conducted to confirm the efficacy of orally administered sarolaner in combination with moxidectin and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange in dogs. METHODS: Client-owned dogs with S. scabiei infestation were enrolled and received 2 monthly treatments. In the first, small-scale study, 12 dogs each were allocated randomly to treatment with either placebo or Simparica Trio®. Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, 44, and 60. Efficacy was calculated based on the percent reduction in arithmetic mean live mite counts relative to placebo. In the second, large-scale study, 75 dogs were allocated randomly to treatment with Simparica Trio® and 37 to treatment with afoxolaner + milbemycin oxime (NexGard Spectra®). Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, and 60. The parasitological cure rate (percentage of dogs without live mites) was determined and non-inferiority of Simparica Trio® to the control product was assessed. RESULTS: In the small-scale study, 2 monthly doses of Simparica Trio® resulted in a significant reduction (P ≤ 0.0050) in live S. scabiei mite numbers and provided a 99.2% reduction relative to placebo by Day 60. Clinical signs of sarcoptic mange improved throughout the study in Simparica Trio®-treated dogs. In the large-scale study, the parasitological cure rate on Days 30 and 60 was 97.3% and 100% in the Simparica Trio® group and 91.9% and 100% in the afoxolaner + milbemycin oxime group, respectively. The parasitological cure rate for Simparica Trio® was non-inferior to afoxolaner + milbemycin oxime at both time points. Clinical signs of sarcoptic mange improved throughout the study in both groups. CONCLUSIONS: Two-monthly doses of Simparica Trio® reduced S. scabiei mite counts by 99.2% relative to placebo in one study and eliminated S. scabiei mites in 100% of dogs in the second study, thus confirming that Simparica Trio® is highly effective in the treatment of sarcoptic mange in dogs caused by S. scabiei var. canis.


Assuntos
Acaricidas , Doenças do Cão , Infestações por Ácaros , Escabiose , Animais , Cães , Acaricidas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Pirantel/uso terapêutico , Sarcoptes scabiei , Escabiose/tratamento farmacológico , Escabiose/veterinária , Comprimidos/uso terapêutico , Resultado do Tratamento
7.
Parasit Vectors ; 16(1): 440, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012748

RESUMO

BACKGROUND: Compliant ectoparasiticide product use is a comprehensive way to control ticks and reduce the risk of tick-borne pathogen transmission to dogs. Because the systemically acting isoxazoline ectoparasiticides require tick attachment for drug delivery, fast speed of kill is essential to minimize tick-borne pathogen transmission risk. METHODS: Dogs of satisfactory tick-carrying capacity were randomly allocated to treatment groups and administered, per label instructions, Bravecto® Chews (minimum 25 mg/kg fluralaner), Simparica TRIO® (minimum 1.2 mg/kg sarolaner, 24 µg/kg moxidectin, 5 mg/kg pyrantel), or no treatment. Dogs were infested with approximately 50 unfed adult (35 female, 15 male) Ixodes scapularis on Day -2, 21 and 28. Live tick counts were performed at 4, 8, 12 and 24 h post-treatment (Day 0) and post-infestation on Day 21 and 28. Tick control efficacy was determined by comparing live tick means for each product-treated group to the untreated control group and each other at all time points using a linear mixed model. The percent of dogs free of live ticks was analyzed using the Fisher's exact test for treatment group comparison. RESULTS: The untreated control group maintained adequate tick infestations throughout the study. Using geometric means, an existing I. scapularis infestation was controlled by 99.7% and 93.0% 12 h post-treatment and by 100% and 99.5% 24 h post-treatment, for Bravecto® and Simparica TRIO®-treated dogs, respectively. Ixodes scapularis infestations were controlled more quickly for Bravecto®- compared to Simparica TRIO®-treated dogs on Day 21 at 8 h (efficacy 74.0% vs. 0.0%, p = 0.003) and 12 h (efficacy 99.2% vs. 39.4%, p < 0.001) post-infestation and Day 28 at 8 h (efficacy 92.2% vs. 0.0%, p < 0.001) and 12 h (efficacy 99.6% vs. 27.7%, p < 0.001) post-infestation. On Day 28 post-treatment, the efficacy of Bravecto® and Simparica TRIO® to control a new I. scapularis infestation was 100% and 96.6%, respectively, by 24 h post-infestation. Of product-treated dogs, 100% of Bravecto®-treated dogs were free of live ticks by 24 h post-treatment or post-infestation. No treatment-related adverse reactions occurred during the study. CONCLUSIONS: Ixodes scapularis infestations are controlled more quickly 21 and 28 days post-treatment for dogs administered a single dose of Bravecto® compared to dogs administered a single dose of Simparica TRIO®.


Assuntos
Acaricidas , Doenças do Cão , Ixodes , Infestações por Carrapato , Animais , Cães , Feminino , Masculino , Pirantel/uso terapêutico , Administração Oral , Resultado do Tratamento , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Fatores de Tempo , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Acaricidas/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-37979235

RESUMO

Consisting of approximately 50 different species, the cyathostomin parasites are ubiquitous in grazing horses. Co-infection with several species is common, and large burdens can cause the fatal disease of larval cyathostominosis. Due to intense anthelmintic drug use, cyathostomin resistance has developed to all available anthelmintic drug groups. Resistance to the anthelmintic drug pyrantel (PYR) has been documented in over 90% of studies published over the past two decades. In Sweden, a study performed in the early 2000s only confirmed resistance in 4.5% of farms. Further, prescription-only administration of equine anthelmintic drugs was enforced in Sweden in 2007. However, it is unknown if this conservative drug use has maintained PYR efficacy in cyathostomins. The aim of the present study was to investigate the effect of PYR on cyathostomin infection in Sweden using fecal egg count reduction tests (FECRTs). Further, the effect of PYR treatment on cyathostomin species composition was studied using metabarcoding. Sixteen farms with at least six horses excreting a minimum of 100 eggs per gram feces were included. Using the current World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines, PYR resistance was demonstrated in nine of farms, with seven farms showing full susceptibility. Farms with low biosecurity measures had significantly lower efficacy of PYR treatment. The most common cyathostomin species were Cylicocyclus nassatus, Cyathostomum catinatum, Cylicostephanus longibursatus, Cys. calicatus, Cys. goldi, Cys. minutus, Coronocyclus coronatus and Cya. pateratum, accounting for 97% of all sequence reads prior to treatment. Of these, Cyc. nassatus and Cya. catinatum had the highest occurrence, accounting for 68% of all sequence reads prior to PYR treatment. Treatment did not significantly affect the species composition. The results highlight the importance of drug efficacy testing when using PYR to treat cyathostomin infection, even when selective anthelmintic treatment and thus low treatment intensity, is used on the farm.


Assuntos
Anti-Helmínticos , Doenças dos Cavalos , Animais , Cavalos , Pamoato de Pirantel/uso terapêutico , Suécia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/parasitologia , Resistência a Medicamentos , Contagem de Ovos de Parasitas/veterinária , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia , Pirantel/uso terapêutico , Strongyloidea , Fezes/parasitologia
10.
Parasit Vectors ; 16(1): 119, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37004097

RESUMO

BACKGROUND: Assessment of the safety of heartworm preventatives in dogs with pre-existing patent heartworm (Dirofilaria immitis) infections is necessary because rapid adult worm and microfilarial death can lead to severe clinical complications, including thromboembolism and anaphylactic shock in dogs. The aim of this study was to determine the clinical safety of Simparica Trio® (sarolaner, pyrantel, moxidectin) in heartworm-infected dogs and the degree of microfilaricidal and adulticidal activity of three consecutive monthly treatments of Simparica Trio. METHODS: Twenty-four laboratory Beagle dogs were implanted with 10 male and 10 female D. immitis (ZoeKY isolate), and once infection was patent, they were randomized equally among three groups to receive no treatment, 1× or 3× the maximum recommended label dose of Simparica Trio. Dogs in the treated groups received Simparica Trio on days 0, 28 and 56. In-life assessments included body weight, physical examinations, clinical observations, daily general health observations, a quantitative estimate of food consumption and blood collections for pharmacokinetic (PK) analysis, microfilariae (MF) counts and D. immitis antigen testing. At the end of the study the heart, lungs and pleural and peritoneal cavities were examined for adult D. immitis worms. RESULTS: Simparica Trio was generally well tolerated. Emesis occurred at low frequency in all groups including control. Abnormal stool occurred occasionally in the 1× and 3× groups throughout the 3-month study. Fever (> 104 °F/40 °C) was recorded in one 1× and one 3× dog 1 day after the first dose and resolved by the following day. No severe hypersensitivity reactions occurred. The mean number of circulating microfilariae (MF) counts in the control group increased from 12,000/ml at study start (Day 0) to > 20,000/ml at Day 28 and remained > 20,000/ml for the duration of the study. The least squares means of circulating MF were reduced by 69.8% on Day 1 and 97.4% on Day 7 for the 1× group and remained at > 99% lower than the control group for the remainder of the study. Similarly, least squares means of circulating MF were reduced by 85.3% on Day 1 and 93.9% on Day 7 for the 3× group and remained > 98% lower than the control group for the remainder of the study. At the end of the study, the mean number of implanted adult worms recovered was < 10 per sex in all groups with 90%, 85% and 75% of live adult heartworms recovered in control, 1× and 3× treatment groups, respectively. Low numbers of dead adult worms were recovered in 1× and 3×, with none in control. Following each dose, the moxidectin and sarolaner AUC and Cmax had close to dose proportional increases. CONCLUSIONS: This study demonstrated that Simparica Trio (sarolaner, pyrantel, moxidectin) was well tolerated when administered to heartworm-positive dogs at 1× and 3× the maximum recommended dose at 28-day intervals for 3 consecutive months. Simparica Trio significantly reduced microfilaria counts in both treatment groups, without significant clinical consequences. At the doses administered, Simparica Trio had minor adulticidal activity but resulted in no clinical sequelae.


Assuntos
Dirofilaria immitis , Dirofilariose , Doenças do Cão , Animais , Cães , Feminino , Masculino , Administração Oral , Dirofilariose/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Macrolídeos/efeitos adversos , Microfilárias , Pirantel , Resultado do Tratamento
11.
Parasit Vectors ; 16(1): 149, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37106437

RESUMO

BACKGROUND: Compliance failure with administration of heartworm (HW) disease preventives has been reported as the main contributor to HW disease incidence in medicalized dogs. This study aimed to evaluate purchase compliance with different canine HW preventive products in the USA. METHODS: Anonymized transaction data from clinics throughout the USA served as the basis for two retrospective analyses. We first examined the monthly equivalent doses of HW preventive purchases from clinics that had implemented extended-release moxidectin injectables ProHeart® 6 (PH6) and/or ProHeart® 12 (PH12) compared to clinics that prescribed monthly HW preventatives (MHWP) only. In the second analysis, the purchase compliance in practices that dispensed only flea and tick (FT) and HW products separately but did not dispense combination products (dual-therapy practices) was compared to the purchase compliance with the combination product Simparica Trio® (sarolaner, moxidectin, and pyrantel chewable tablets), purchased in clinics having implemented combination therapy in their formulary (combination-therapy practices). In both analyses, the numbers of monthly doses dispensed annually per dog were calculated. RESULTS: Transaction data from 3,539,990 dogs in 4615 practices were included in the first analysis. In dogs administered PH12 or PH6, the numbers of monthly equivalent doses were 12 and 8.1, respectively. In both clinic types, the average annual number of MHWP doses totaled 7.3. In the second analysis, a total of 919 practices were identified as combination-therapy practices and 434 as dual-therapy-only practices. A total of 246,654 dogs (160,854 dogs in dual-therapy practices and 85,800 dogs in combination-therapy practices) were included in the calculation of the average annual number of monthly doses, which totaled 6.8 (HW preventive products) and 4.4 (FT products) in dual-therapy practices compared to 7.2 months for both FT and HW preventives with Simparica Trio® across both practice types. CONCLUSIONS: The injectable HW preventive PH12 is the only product that provides 12 months of heartworm disease prevention in a single veterinarian-administered injection. When choosing a monthly preventive, the combination therapy was associated with a greater purchase compliance compared with FT and HW products being dispensed separately.


Assuntos
Dirofilaria immitis , Dirofilariose , Doenças do Cão , Sifonápteros , Animais , Cães , Estados Unidos , Estudos Retrospectivos , Resultado do Tratamento , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Doenças do Cão/parasitologia , Macrolídeos/uso terapêutico , Dirofilariose/tratamento farmacológico , Dirofilariose/prevenção & controle , Dirofilariose/parasitologia , Pirantel , Adesão à Medicação
12.
Health Aff (Millwood) ; 42(3): 338-348, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36877909

RESUMO

Understanding the size and composition of the state and local governmental public health workforce in the United States is critical for promoting and protecting the health of the public. Using pandemic-era data from the Public Health Workforce Interests and Needs Survey fielded in 2017 and 2021, this study compared intent to leave or retire in 2017 with actual separations through 2021 among state and local public health agency staff. We also examined how employee age, region, and intent to leave correlated with separations and considered the effect on the workforce if trends were to continue. In our analytic sample, nearly half of all employees in state and local public health agencies left between 2017 and 2021, a proportion that rose to three-quarters for those ages thirty-five and younger or with shorter tenures. If separation trends continue, by 2025 this would represent more than 100,000 staff leaving their organizations, or as much as half of the governmental public health workforce in total. Given the likelihood of increasing outbreaks and future global pandemics, strategies to improve recruitment and retention must be prioritized.


Assuntos
COVID-19 , Saúde Pública , Humanos , Pirantel , Surtos de Doenças , Governo Local
14.
Parasit Vectors ; 16(1): 95, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36894954

RESUMO

BACKGROUND: Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects. METHODS: In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.0 mg/kg sarolaner), or a Simparica Trio-treated group (at the minimum dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel), based on pre-treatment mosquito counts. Treatments were administered orally once on day 0. Each dog was exposed to 50 unfed female adult A. aegypti mosquitoes for 1 h on days 1, 7, 14, 21, 28 and 35. After each exposure, mosquitoes were counted for each dog and characterized as live, moribund or dead, and as fed or unfed. Dead mosquitoes were counted and removed at 12, 24 and 48 h post-exposure in study 1 and at 24, 48, 72, 96 and 120 h post-exposure in study 2. In study 2, mosquito eggs were collected from 72 h post-exposure until 120 h post-exposure. Insecticidal efficacy was calculated based on the reduction of the arithmetic mean live fed-mosquito counts in each of the treated groups versus the untreated control group for every timepoint post-exposure. RESULTS: Adequate challenge was demonstrated in both studies, with arithmetic mean live fed-mosquito counts ranging from 35.5 to 45.0 for the untreated group. Mean mosquito counts for dogs treated with Simparica and Simparica Trio were significantly (P < 0.0001) reduced within 48 h after exposure on all study days. In study 1, Simparica treatment provided ≥ 96.8% reduction in the arithmetic mean live fed-mosquito counts for 28 days, and Simparica Trio treatment provided ≥ 90.3% reduction for 21 days. In study 2, Simparica treatment provided ≥ 99.4% reduction for 35 days (from 48 h onwards), and Simparica Trio treatment provided ≥ 97.8% reduction for 28 days (from 72 h onwards). CONCLUSIONS: Both studies demonstrated that a single oral dose of Simparica or Simparica Trio provides high efficacy against mosquitoes in dogs within 24-72 h after exposure for an entire month.


Assuntos
Aedes , Doenças do Cão , Inseticidas , Infestações por Carrapato , Animais , Cães , Feminino , Administração Oral , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Combinação de Medicamentos , Carga Parasitária , Pirantel , Infestações por Carrapato/veterinária , Resultado do Tratamento
15.
16.
Parasit Vectors ; 15(1): 370, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36244989

RESUMO

BACKGROUND: For a long time known as the oriental eyeworm, Thelazia callipaeda is a zoonotic nematode that infects the eyes of a wide range of vertebrate hosts including dogs, cats, wildlife carnivores, lagomorphs, and humans. The high occurrence of this infection in Europe and the first cases in the United States have increased scientific interest in the parasite, as it also represents a risk for people living in endemic areas. Therefore, treatment and prevention of thelaziosis in canine population are advocated to reduce the risk of human infection as well. Here, we assessed the efficacy of a formulation containing sarolaner/moxidectin/pyrantel (Simparica Trio®) administered orally at monthly intervals, for the prevention of establishment of infection with T. callipaeda in naturally infected dogs. In this formulation, moxidectin is expected to have efficacy against eyeworms, whereas sarolaner and pyrantel are not. METHODS: The study was conducted in eyeworm endemic areas of Italy and France, where dogs (n = 125) were assigned into two groups consisting of a negative control group (G1; n = 62), in which animals were treated monthly with a control product (sarolaner; Simparica®), and a treatment group (G2; n = 63) in which animals were treated monthly with Simparica Trio (sarolaner/moxidectin/pyrantel) from day 0 to day 150. In total, nine animals were withdrawn from the study (two animals became positive at day 30, and seven for reasons unrelated to eyeworm infection), resulting in 116 animals (n = 58 for G1; n = 58 for G2). RESULTS: In G1, 16 out of 58 animals (27.6%) were observed with eyeworms during the study, and none of the animals from G2 were ever observed with eyeworms, resulting in 100% efficacy (P < 0.0001) in the prevention of establishment of T. callipaeda infection. Adult nematodes and fourth-instar (L4)-stage larvae were recovered from the eyes of positive animals, counted, and morphologically identified as T. callipaeda. In addition, specimens from Italy were molecularly confirmed as belonging to the haplotype 1 (i.e., the only one circulating in Europe so far). CONCLUSIONS: Data presented herein demonstrated 100% efficacy of Simparica Trio for the prevention of T. callipaeda eyeworm infection in dogs from highly endemic areas of France and Italy. The use of this formulation is advantageous, as it is a licensed product in Europe with a wide efficacy spectrum against other nematodes, multiple tick species, and fleas. In addition, preventing the development of infection in dogs could also be a prophylaxis measure for zoonotic T. callipaeda infection in humans inhabiting endemic areas.


Assuntos
Doenças do Cão , Nematoides , Infecções por Spirurida , Thelazioidea , Animais , Azetidinas , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Macrolídeos , Pirantel/uso terapêutico , Compostos de Espiro , Infecções por Spirurida/tratamento farmacológico , Infecções por Spirurida/prevenção & controle , Infecções por Spirurida/veterinária
17.
Parasit Vectors ; 15(1): 81, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35277191

RESUMO

BACKGROUND: Administration of four to six consecutive monthly doses of 24 µg/kg moxidectin alone shows high effectiveness in preventing the maturation of macrocyclic lactone (ML)-resistant heartworm strains, Dirofilaria immitis JYD-34 and ZoeLA. This laboratory study evaluated the efficacy of six consecutive monthly oral doses of Simparica Trio® (moxidectin/sarolaner/pyrantel) compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis ZoeLA strain. METHODS: Beagle dogs were inoculated with 50 third-stage (L3) D. immitis larvae (ZoeLA) 30 days prior to the first treatment. Dogs were randomized to treatment (six animals in each group) with six monthly oral doses of placebo, Simparica Trio, Heartgard Plus, or Interceptor Plus at their respective label doses. Microfilaria (MF) and antigen tests were conducted periodically, and efficacy was evaluated by necropsy for adult heartworms approximately 9 months after L3 inoculation. RESULTS: Adult heartworms were recovered from all six placebo dogs, with a geometric mean of 35.5 worms (range, 23-48). Five of the six dogs treated with Simparica Trio were infected with a geometric mean of 1.0 worms (range, 0-3), and all remained MF-negative. All Heartgard Plus-treated dogs (six) were infected with a geometric mean of 32.5 worms (range, 22-38); five of these dogs were MF-positive at day 236. All Interceptor Plus-treated dogs (six) were infected with a geometric mean of 22.8 worms (range, 10-34); five of these dogs were MF-positive at day 236. The efficacy of six consecutive doses with Simparica Trio, Heartgard Plus, and Interceptor Plus against ZoeLA was 97.2, 8.5, and 35.9%, respectively. Adult worm counts for the Simparica Trio-treated group were significantly lower (P < 0.0001) than placebo control, Heartgard Plus, and Interceptor Plus-treated groups. Adult worm counts for Heartgard Plus and Interceptor Plus were not significantly different from placebo (P > 0.05). CONCLUSIONS: Simparica Trio prevented microfilaremia in all dogs and was highly effective (97.2%) and significantly better than either Heartgard Plus (8.5%) or Interceptor Plus (35.9%) in preventing the development of the ZoeLA ML-resistant heartworm strain when administered for six consecutive months in this comparative laboratory efficacy study.


Assuntos
Dirofilaria immitis , Dirofilariose , Doenças do Cão , Animais , Azetidinas , Dirofilariose/tratamento farmacológico , Dirofilariose/prevenção & controle , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Cães , Ivermectina/uso terapêutico , Lactonas/farmacologia , Macrolídeos , Pirantel/farmacologia , Compostos de Espiro
18.
Int J Parasitol Drugs Drug Resist ; 17: 107-117, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34492564

RESUMO

Ancylostoma caninum is the most prevalent nematode parasite of dogs. We confirmed multiple-drug resistance (MDR) in several A. caninum isolates to all anthelmintic drug classes approved for the treatment of hookworms in dogs in the USA. Cases of MDR hookworms appear to be highly overrepresented in greyhounds. The aims of this study were to evaluate the drug-resistant phenotypes and genotypes of the A. caninum infecting greyhounds. Fecal samples from greyhounds of the USA were acquired from two greyhound adoption kennels, one active greyhound racing kennel, and three veterinary practices. Fecal egg counts (FECs) were performed on fecal samples from 219 greyhounds, and despite treatment with anthelmintics, the mean FEC was 822.4 eggs per gram (EPG). Resistance to benzimidazoles and macrocyclic lactones were measured using the egg hatch assay (EHA) and the larval development assay (LDA), respectively. We performed 23 EHA and 22 LDA on either individual or pooled feces, representing 54 animals. Mean and median IC50 and IC95 values for the EHA were 5.3 µM, 3.6 µM, and 24.5 µM, 23.4 µM, respectively. For the LDA, the median IC50 value was >1000 nM. These values ranged 62-81 times higher than our susceptible laboratory isolate. Only post-treatment samples were available. For samples collected <10 days post-treatment with albendazole, moxidectin, or a combination of febantel-pyrantel-moxidectin, the mean FEC were 349, 333, and 835 EPG, respectively. We obtained DNA from hookworm eggs isolated from 70 fecal samples, comprised of 60 individual dogs and 10 pools. Deep sequencing of the isotype 1 ß-tubulin gene only revealed the presence of the F167Y (TTC>TAC) resistance polymorphism in 99% of these samples. These clinical, in vitro, and genetic data provide strong evidence that greyhound dogs in the USA are infected with MDR A. caninum at very high levels in prevalence and infection intensity.


Assuntos
Anti-Helmínticos , Doenças do Cão , Ancylostoma/genética , Ancylostomatoidea , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/epidemiologia , Cães , Resistência a Medicamentos , Resistência a Múltiplos Medicamentos , Fezes , Contagem de Ovos de Parasitas , Pirantel/uso terapêutico
19.
PLoS Pathog ; 17(2): e1008982, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33544769

RESUMO

In the absence of efficient alternative strategies, the control of parasitic nematodes, impacting human and animal health, mainly relies on the use of broad-spectrum anthelmintic compounds. Unfortunately, most of these drugs have a limited single-dose efficacy against infections caused by the whipworm, Trichuris. These infections are of both human and veterinary importance. However, in contrast to a wide range of parasitic nematode species, the narrow-spectrum anthelmintic oxantel has a high efficacy on Trichuris spp. Despite this knowledge, the molecular target(s) of oxantel within Trichuris is still unknown. In the distantly related pig roundworm, Ascaris suum, oxantel has a small, but significant effect on the recombinant homomeric Nicotine-sensitive ionotropic acetylcholine receptor (N-AChR) made up of five ACR-16 subunits. Therefore, we hypothesized that in whipworms, a putative homolog of an ACR-16 subunit, can form a functional oxantel-sensitive receptor. Using the pig whipworm T. suis as a model, we identified and cloned a novel ACR-16-like subunit and successfully expressed the corresponding homomeric channel in Xenopus laevis oocytes. Electrophysiological experiments revealed this receptor to have distinctive pharmacological properties with oxantel acting as a full agonist, hence we refer to the receptor as an O-AChR subtype. Pyrantel activated this novel O-AChR subtype moderately, whereas classic nicotinic agonists surprisingly resulted in only minor responses. We observed that the expression of the ACR-16-like subunit in the free-living nematode Caenorhabditis elegans conferred an increased sensitivity to oxantel of recombinant worms. We demonstrated that the novel Tsu-ACR-16-like receptor is indeed a target for oxantel, although other receptors may be involved. These finding brings new insight into the understanding of the high sensitivity of whipworms to oxantel, and highlights the importance of the discovery of additional distinct receptor subunit types within Trichuris that can be used as screening tools to evaluate the effect of new synthetic or natural anthelmintic compounds.


Assuntos
Antinematódeos/farmacologia , Proteínas de Helminto/antagonistas & inibidores , Pirantel/análogos & derivados , Receptores Colinérgicos/química , Tricuríase/tratamento farmacológico , Trichuris/efeitos dos fármacos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Feminino , Proteínas de Helminto/classificação , Proteínas de Helminto/metabolismo , Masculino , Pirantel/farmacologia , Receptores Colinérgicos/classificação , Receptores Colinérgicos/metabolismo , Suínos , Tricuríase/metabolismo , Tricuríase/parasitologia , Xenopus laevis/metabolismo
20.
Eur J Pharmacol ; 898: 173986, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33640406

RESUMO

The high-affinity choline transporter CHT1 mediates choline uptake, the rate-limiting and regulatory step in acetylcholine synthesis at cholinergic presynaptic terminals. CHT1-medated choline uptake is specifically inhibited by hemicholinium-3, which is a type of choline analog that acts as a competitive inhibitor. Although the substrate choline and the inhibitor hemicholinium-3 are well-established ligands of CHT1, few potent ligands other than choline analogs have been reported. Here we show that tetrahydropyrimidine anthelmintics, known as nicotinic acetylcholine receptor agonists, act as competitive inhibitors of CHT1. A ligand-dependent trafficking assay in cell lines expressing human CHT1 was designed to search for CHT1 ligands from a collection of biologically active compounds. We found that morantel as well as other tetrahydropyrimidines, pyrantel and oxantel, potently inhibits the high-affinity choline uptake activity of CHT1 in a competitive manner similar to the inhibitor hemicholinium-3. They also inhibit the high-affinity choline transporter from the nematode Caenorhabditis elegans. Finally, tetrahydropyrimidines potently inhibit the high-affinity choline uptake in rat brain synaptosomes at a low micromolar level, resulting in the inhibition of acetylcholine synthesis. The rank order of potency in synaptosomes is as follows: morantel > pyarantel > oxantel (Ki = 1.3, 5.7, and 8.3 µM, respectively). Our results reveal that tetrahydropyrimidine anthelmintics are novel CHT1 ligands that inhibit the high-affinity choline uptake for acetylcholine synthesis in cholinergic neurons.


Assuntos
Anti-Helmínticos/farmacologia , Encéfalo/efeitos dos fármacos , Proteínas de Transporte de Cátions/antagonistas & inibidores , Colina/metabolismo , Pirimidinas/farmacologia , Simportadores/antagonistas & inibidores , Animais , Anti-Helmínticos/metabolismo , Ligação Competitiva , Transporte Biológico , Encéfalo/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Feminino , Células HEK293 , Humanos , Ligantes , Camundongos , Morantel/metabolismo , Morantel/farmacologia , Ligação Proteica , Transporte Proteico , Pirantel/análogos & derivados , Pirantel/metabolismo , Pirantel/farmacologia , Pirimidinas/metabolismo , Simportadores/genética , Simportadores/metabolismo , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo
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