Toxascaris leonina in dogs - A nematode species of high prevalence in some regions of Eurasia.

A recent meta-analysis of studies from around the world had shown a global prevalence of Toxascaris leonina in stray dogs of about 7%. However, studies from Eurasian regions, where higher percentages of positive dogs were often found, were under-represented in this meta-analysis. This prompted the present study. Its main objective was to examine free-roaming dogs from the capital city of Kazakhstan to obtain information on the current occurrence of T. leonina egg shedding compared to Toxocara spp. Faecal samples from 500 free-roaming dogs from the city of Astana and its suburbs were collected 1-2 days after admission to the municipal animal shelter during three time periods (May to October 2019, September 2020, and April 2021). Samples were examined by a saline flotation method. Nematode egg-positive samples were subjected to a modified McMaster method to determine the number of eggs per gram of faeces (EPG). Toxascaris leonina eggs were found in 53.8% and Toxocara spp. eggs in 14.8% of the dogs examined. The prevalence of T. leonina egg shedding was significantly associated with age class but not with sex: dogs aged between 6 months and 2 years were more likely to be T. leonina egg positive than puppies. The intensity of T. leonina egg shedding was also age dependent: dogs aged between 6 months and 2 years had significantly higher EPGs compared to younger or older animals. In contrast, the prevalence of Toxocara spp. egg shedding was associated with both age class and sex: dogs older than 2 years were less likely to shed Toxocara spp. eggs than puppies, and females were less likely to be Toxocara spp. egg positive compared to males. The present results confirm those of other studies in Eurasian regions. It is therefore reasonable to assume that the global prevalence of T. leonina infection has been underestimated and should be revised accordingly.

Treatment of natural Protostrongylus rufescens lungworm infection in sheep with eprinomectin 5 mg/mL topical solution.

Parasitic respiratory infections in domestic sheep and goats are caused by Dictyocaulus filaria and various species belonging to the Protostrongylidae family of nematodes which frequently occur in mixed infections. Although the parasitism with protostrongylid lungworms is generally considered to be of low pathogenicity, there are reports of clinical disease including cases associated with Protostrongylus rufescens infection. The efficacy against P. rufescens of eprinomectin 5 mg/mL topical solution (EPRINEX® Multi, Boehringer Ingelheim) was thus evaluated in a clinical study compliant with GCP and VICH anthelmintic efficacy testing guidelines in adult sheep with naturally acquired infection. Following ranking on pre-treatment Protostrongylus fecal larval counts and forming into blocks of two animals, the sheep were randomly allocated to either remain untreated (control) or to be administered eprinomectin 5 mg/mL topical solution at 1 mL/5 kg body weight (equivalent to 1 mg eprinomectin per kg body weight) once as a pour-on. Fecal samples of the sheep were examined to monitor the larval excretion weekly for five weeks after treatment; then the animals were necropsied for lungworm recovery and count to determine the efficacy of the treatment. After treatment, Protostrongylus larval excretion decreased to zero within three weeks. Nematode counts demonstrated that the efficacy of the treatment with eprinomectin 5 mg/mL topical solution was 100 % against P. rufescens: no lungworms were recovered from any treated sheep while all controls harbored P. rufescens (range, 17-406) (p < 0.001). The treatment was well accepted; no treatment-related health problems were observed.

Gamithromycin in sheep: Pharmacokinetics and clinical evaluation against ovine footrot.

In the context of a development program to obtain the market authorization of injectable gamithromycin 15% w/v solution (Zactran®, Boehringer Ingelheim) for use in sheep against footrot, the pharmacokinetic profile of gamithromycin was established and the safety and efficacy of the treatment were confirmed in a multicenter field study in Europe. The basic pharmacokinetic parameters established in healthy young Merino sheep administered gamithromycin at 6 mg/kg body weight based on the analysis of plasma samples which were collected in intervals up to 12 days after subcutaneous injection were: area under the curve until last quantifiable concentration, 8.88 ± 2.33 µg*h/mL; maximum plasma concentration, 448 ± 180 ng/mL; terminal half-life, 42.5 ± 5.25 h. The safety and clinical efficacy against footrot of gamithromycin 15% w/v solution were evaluated in comparison to tilmicosin 30% w/v solution (Micotil®, Elanco) treatment in 364 sheep of various breeds, sex and age from commercial farms in the United Kingdom (2 sites), Germany (3 sites) and France (1 site). Animals were enrolled based on lesions characteristic of footrot and lameness associated with the presence of footrot-related bacterial pathogens and were randomly allocated and treated in a 1:1 ratio with a single subcutaneous dose of gamithromycin or tilmicosin at label dosage (6 or 10 mg/kg body weight, respectively). Lameness and footrot lesions were evaluated at five and 21 days after treatment; the injection site in all animals was examined the day after treatment and followed up daily in the animals with injection site reaction until complete injection site reaction resolution. Samples of 310 and 120 animals tested positive for Dichelobacter nodosus and Fusobacterium necrophorum, respectively, at inclusion, and data of 359 animals were included into the combined analyses (5 animals excluded for unintentional overdosing [1], lack of follow-up [1], concurrent antibiotic medication for non-footrot conditions [3]). Lameness scores at 21 days after treatment demonstrated a significantly (p = 0.0396) better success for the gamithromycin treatment compared to the tilmicosin treatment (97.8% vs. 93.3%). Post-dosing footrot lesion scores followed similar trends of rapid and marked decrease (improvement) for both treatments with similar (p = 0.127) treatment success for the gamithromycin and tilmicosin treatments (97.8% and 96.0%, respectively). Both treatments were safe; injection site reactions noted in 19 gamithromycin- and 25 tilmicosin-treated animals resolved within five days or six days of treatment, respectively. Gamithromycin 15% w/v solution administered once to sheep by subcutaneous injection at 6 mg/kg body weight demonstrated a pharmacokinetic profile similar to that reported previously in sheep and cattle and was confirmed to be a safe and efficacious treatment for naturally occurring ovine footrot in a multicenter clinical field study conducted in Europe.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Ixodes ricinus and Ixodes scapularis in cats.

Esafoxolaner is a purified enantiomer of afoxolaner with insecticidal and acaricidal properties. It is combined with eprinomectin and praziquantel in a novel topical endectoparasiticide formulation for cats. The efficacy of this novel formulation was evaluated in three Ixodes ricinus and two Ixodes scapularis experimental studies, with comparable designs. In each study, cats were randomly allocated, based on a pre-treatment tick infestation and count, to a placebo control group or a group treated with the minimum recommended dose of the novel formulation. Cats were infested two days before treatment and weekly thereafter. Immediate efficacy was evaluated 48 h after treatment; persistent efficacy was evaluated 48 h after new weekly infestations for at least one month after the treatment (in one of the studies, the first two weeks of persistent efficacy against I. ricinus were not tested). Efficacy was calculated at each timepoint by comparison of arithmetic means of live ticks found in the control and the treated groups. In the three studies targeting I. ricinus, immediate and persistent efficacies ranged between 91% and 100% for five weeks. In the two studies targeting I. scapularis, immediate and persistent efficacies ranged between 95% and 100%, and 98% and 100% for one month, respectively. These studies provide robust evidence of efficacy of the novel topical formulation of esafoxolaner, eprinomectin and praziquantel against experimental I. ricinus and I. scapularis infestations for at least one month in cats.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre Ixodes ricinus et Ixodes scapularis chez le chat. ABSTRACT: L'esafoxolaner est un énantiomère purifié de l'afoxolaner aux propriétés insecticides et acaricides. Il est associé à l'éprinomectine et au praziquantel dans une nouvelle formulation d'endectoparasiticide topique pour chats. L'efficacité de cette nouvelle formulation a été évaluée dans trois études expérimentales sur Ixodes ricinus et deux sur Ixodes scapularis, avec des conceptions comparables. Dans chaque étude, les chats ont été répartis au hasard, sur la base d'une infestation et d'un nombre de tiques avant le traitement, dans un groupe témoin placebo ou dans un groupe traité avec la dose minimale recommandée de la nouvelle formulation. Les chats ont été infestés deux jours avant le traitement et une fois par semaine par la suite. L'efficacité immédiate a été évaluée 48 heures après le traitement et l'efficacité persistante a été évaluée 48 heures après les nouvelles infestations hebdomadaires pendant au moins un mois après le traitement (dans l'une des études, les deux premières semaines d'efficacité persistante contre I. ricinus n'ont pas été testées). L'efficacité a été calculée à chaque temps d'évaluation par comparaison des moyennes arithmétiques des tiques vivantes trouvées dans les groupes témoins et traités. Dans les trois études ciblant I. ricinus, les efficacités immédiates et persistantes variaient entre 91 % et 100 % pendant cinq semaines. Dans les deux études ciblant I. scapularis, les efficacités immédiates et persistantes variaient respectivement entre 95 % et 100 % et 98 % et 100 % pendant un mois. Ces études fournissent des preuves solides de l'efficacité de la nouvelle formulation topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les infestations expérimentales par I. ricinus et I. scapularis pendant au moins un mois chez le chat.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against ear mite (Otodectes cynotis) infestations in cats.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel, nematodicidal and cestodicidal compounds, in NexGard® Combo, a novel topical endectoparasiticide formulation for cats. The efficacy of this formulation was assessed against Otodectes cynotis in two laboratory studies conducted in South Africa and in the USA with local isolates, and in one field trial conducted in Europe. In each study, cats were randomly allocated to a placebo-treated control group and a novel formulation-treated group. In the laboratory studies, cats were treated at the minimum recommended dose; in the field trial, cats were treated at label dose. All included cats were diagnosed positive for O. cynotis prior to treatment by otoscopy. The main variable of efficacy was a comparison of the number of live O. cynotis collected in both ear canals of all cats in the treated and control groups, one month after treatment. Efficacy of the novel topical formulation exceeded 97% in the three studies. These studies demonstrated the high effectiveness of NexGard® Combo in cats for the treatment of O. cynotis infestations. No health abnormalities were attributed to the treatment in any of the studies.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les infestations par l'acarien agent de la gale des oreilles Otodectes cynotis chez les chats. ABSTRACT: L'esafoxolaner, un énantiomère purifié d'afoxolaner aux propriétés insecticides et acaricides, est associé à l'éprinomectine et au praziquantel, composés nématodicides et cestodicides, dans NexGard® Combo, une nouvelle formulation endectoparasiticide topique pour chats. L'efficacité de cette formulation a été évaluée contre Otodectes cynotis dans deux études de laboratoire menées en Afrique du Sud et aux États-Unis avec des isolats locaux, et dans un essai sur le terrain mené en Europe. Dans chaque étude, les chats ont été répartis au hasard entre un groupe témoin traité par placebo et un groupe traité par la nouvelle formulation. Dans les études de laboratoire, les chats ont été traités à la dose minimale recommandée, et dans l'essai sur le terrain, les chats ont été traités à la dose indiquée sur l'étiquette. Tous les chats inclus ont été diagnostiqués positifs pour O. cynotis avant le traitement par otoscopie. La principale variable d'efficacité était une comparaison du nombre d'O. cynotis vivants, collectés dans les deux conduits auditifs de tous les chats, dans le groupe traité et dans le groupe témoin, un mois après le traitement. L'efficacité de la nouvelle formulation topique a dépassé 97 % dans les trois études. Ces études ont démontré la grande efficacité de NexGard® Combo chez les chats pour le traitement des infestations par O. cynotis. Aucune anomalie de santé n'a été attribuée au traitement dans aucune des études.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel in cats against Toxocara cati and Dipylidium caninum.

NexGard® Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard® Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard® Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard® Combo-treated cats were compared. The efficacy of NexGard® Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel chez le chat contre Toxocara cati et Dipylidium caninum. ABSTRACT: NexGard® Combo, un nouveau produit antiparasitaire topique pour chats combine l'insecticide/acaricide esafoxolaner avec le nématocide éprinomectine et le cestodicide praziquantel. L'efficacité de ce produit d'association a été évaluée contre deux endoparasites communs d'occurrence mondiale chez le chat, le nématode Toxocara cati et le cestode Dipylidium caninum, dans cinq études contrôlées utilisant des chats naturellement ou expérimentalement infectés par des parasites d'origine nord-américaine, sud-africaine ou européenne. Les chats évalués dans ces études présentaient une infection patente du parasite cible confirmée par un examen fécal avant le traitement. Dans chaque étude, les chats ont été répartis au hasard en deux groupes de taille égale (8 ou 10 chats par groupe et par étude), un groupe traité avec un placebo (huile minérale) et l'autre avec NexGard® Combo. Les deux traitements ont été administrés une fois par spot-on à 0,12 mL par kg de poids corporel pour délivrer la dose minimale indiquée sur l'étiquette (1,44 mg/kg d'esafoxolaner, 0,48 mg/kg d'éprinomectine et 10,0 mg/kg de praziquantel) pour les chats du groupe traité par NexGard® Combo. Pour déterminer l'efficacité, les nombres moyens géométriques de parasites sept à 12 jours après le traitement des chats traités par placebo (témoins) et des chats traités par NexGard® Combo ont été comparés. L'efficacité de NexGard® Combo était de 98,8 % et de 100 % contre T. cati adulte dans deux études, et de 98,0 %, 98,3 % et 93,2 % contre D. caninum dans trois études. Aucun événement indésirable lié au traitement n'a été observé tout au long des études. Ces études démontrent la grande efficacité contre ces principaux endoparasites félins et l'excellente acceptabilité de la nouvelle combinaison antiparasitaire topique d'esafoxolaner, d'éprinomectine et de praziquantel.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Notoedres cati mange in cats.

The therapeutic efficacy against notoedric mange of a topical combination of esafoxolaner, eprinomectin and praziquantel (Nexgard® Combo, Boehringer Ingelheim) was evaluated in a masked, controlled clinical study including 14 cats with natural or induced Notoedres cati infestation. Cats were allocated randomly to two groups of seven cats each, to be administered either mineral oil (placebo control) or NexGard® Combo. Each treatment was administered once as spot-on at 0.12 mL per kg body weight (representing the minimum label dosage of NexGard® Combo, i.e. 1.44 mg esafoxolaner, 0.48 mg eprinomectin, and 10.0 mg praziquantel per kg body weight). Live mites were counted in skin scrapings collected within seven days prior to and 14, 27/28, 42 and 56 days after treatment to calculate the percentage efficacy of NexGard® Combo based on the comparison of mean live mite counts of the two groups. Concurrently, mange lesions and clinical signs were scored to establish a clinical success valuation. No live mites were recovered from any NexGard® Combo-treated cats post-treatment, indicating 100% therapeutic efficacy following a single spot-on administration of the novel antiparasitic combination. The clinical success valuations in the NexGard® Combo-treated cats were 14.3%, 42.8%, 100% and 100% at 14, 27/28, 42 and 56 days after treatment, respectively. No health problems were observed throughout the study.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre la gale à Notoedres cati chez le chat. ABSTRACT: L'efficacité thérapeutique contre la gale notoédrique d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel (Nexgard® Combo, Boehringer Ingelheim) a été évaluée dans une étude clinique contrôlée et masquée portant sur 14 chats atteints d'une infestation naturelle ou induite par Notoedres cati. Les chats ont été répartis au hasard en deux groupes de sept chats chacun, traités soit avec de l'huile minérale (contrôle placebo), soit avec NexGard® Combo. Chaque traitement a été administré en une seule fois à raison de 0,12 mL par kg de poids corporel (représentant la posologie minimale indiquée sur l'étiquette de NexGard® Combo, c'est-à-dire 1,44 mg d'esafoxolaner plus 0,48 mg d'éprinomectine plus 10,0 mg de praziquantel par kg de poids corporel). Les acariens vivants ont été comptés par grattage de peau et recueillis dans les sept jours précédant le traitement et 14, 27/28, 42 et 56 jours après le traitement pour calculer le pourcentage d'efficacité de NexGard® Combo basé sur la comparaison du nombre moyen d'acariens vivants des deux groupes. Parallèlement, les lésions de la gale et les signes cliniques ont été mesurés pour établir une évaluation du succès clinique. Aucun acarien vivant n'a été retrouvé chez les chats traités par NexGard® Combo après le traitement, ce qui indique une efficacité thérapeutique de 100% après une administration ponctuelle unique de la nouvelle association antiparasitaire. L'évaluation du succès clinique chez les chats traités par NexGard® Combo était de 14,3 %, 42,8 %, 100 % et 100 %, respectivement 14, 27/28, 42 et 56 jours après le traitement. Aucun problème de santé n'a été observé tout au long de l'étude.

Efficacy of a topical combination of eprinomectin, praziquantel, fipronil and (S)-methoprene against developing and adult Troglostrongylus brevior lungworms (Nematoda, Crenosomatidae) in cats.

The efficacy of the eprinomectin, praziquantel, fipronil and (S)-methoprene combination parasiticide Broadline® (Boehringer Ingelheim Animal Health) was evaluated against developing larval and adult stages of Troglostrongylus brevior, a metastrongyloid pulmonary nematode which is reported to parasitize domestic cats in southern Europe with increasing frequency. Twenty four purpose-bred cats were experimentally infected with 100 third-stage T. brevior larvae each and randomly allocated to either remain untreated (control) or to be treated with the combination product when T. brevior were developing larval (6 days post inoculation, dpi) or adult nematodes (28 dpi) (eight cats per group). Treatments were administered topically at the minimum label dose of 0.12 mL/kg. Fecal samples of the cats were examined to confirm the presence of patent (adult) nematode infections prior to treatment at 28 dpi and to monitor the larval excretion. At necropsy (49 dpi), the weight of the pulmonary lymph nodes and lungs were determined, and T. brevior lungworms were recovered and counted. All control animals and cats to be treated at 28 dpi excreted T. brevior larvae 24 dpi and 26 dpi while no larvae were excreted by the cats treated at 6 dpi. Following treatment at 28 dpi, T. brevior larval excretion decreased immediatetly and ceased prior to necropsy. Nematode counts demonstrated that treatment with the combination product was 100 % efficacious against both developing larval and adult T. brevior: no lungworms were recovered from any treated cat while all control animals harbored T. brevior (range, 6-52) (p < 0.001). No treatment-related health problems or any other clinical signs were observed in the cats. However, significantly higher absolute and relative (organ weight to body weight ratio) pulmonary lymph node weights of the control animals compared with the treated cats at 6 dpi (p < 0.001 and p < 0.001, respectively) and at 28 dpi (p = 0.003 and p = 0.019, respectively) indicated the pathology of the T. brevior infection. In conclusion, the combination product was demonstrated to be 100 % efficacious against developing larval and adult T. brevior. Furthermore, it was demonstrated that indicators of impaired respiratory and immune systems resultant from T. brevior infection can be prevented with an efficacious treatment when administered during the pre-patent period of infection or are improving substantially within three weeks of treatment of cats harboring adult lungworms.

Efficacy of Broadline® in cats against induced infections with developing fourth-stage larval and adult Ancylostoma ceylanicum hookworms.

Ancylostoma ceylanicum hookworms parasitize dogs and cats in subtropical and tropical South East Asia and Pacific region, the Arab Peninsula, southern Africa and South America but cause patent infections in humans too. To evaluate the efficacy of Broadline®, a combination product comprising eprinomectin, fipronil, (S)-methoprene and praziquantel, against developing fourth-larval stage (L4) and adult A. ceylanicum in cats, a blinded, induced infection study was conducted. Following oral inoculation of 24 purpose bred cats with ˜300 infectious A. ceylanicum larvae each, cats were allocated to one of three groups of eight animals, each which served either as untreated controls or received Broadline® (once topically at the minimum label dose of 0.12 mL per kg bodyweight) when the hookworms were L4 (five days post inoculation, dpi) or adults (25 dpi). Efficacy was determined on nematode counts following necropsy of the cats. Fecal examination at 22 dpi confirmed that all cats of the control group and of the group to be treated when the hookworms were adult were excreting hookworm eggs (range, 100 to 1000 eggs per gram) while no eggs were recovered from the feces of the cats treated with Broadline® 5 dpi. Nematode counts established 35 dpi demonstrated that Broadline® treatment was 100% efficacious against both, developing L4 and adult A. ceylanicum: no hookworms were recovered from any Broadline®-treated cat while all control animals harbored A. ceylanicum (range, 8-35) (p < 0.001). No health problems were observed throughout the study.

Efficacy of a topical combination of eprinomectin, praziquantel, fipronil and (S)-methoprene against developing and adult Troglostrongylus brevior lungworms (Nematoda, Crenosomatidae) in cats.

The efficacy of the eprinomectin, praziquantel, fipronil and (S)-methoprene combination parasiticide Broadline® (Boehringer Ingelheim Animal Health) was evaluated against developing larval and adult stages of Troglostrongylus brevior, a metastrongyloid pulmonary nematode which is reported to parasitize domestic cats in southern Europe with increasing frequency. Twenty four purpose-bred cats were experimentally infected with 100 third-stage T. brevior larvae each and randomly allocated to either remain untreated (control) or to be treated with the combination product when T. brevior were developing larval (6 days post inoculation, dpi) or adult nematodes (28 dpi) (eight cats per group). Treatments were administered topically at the minimum label dose of 0.12mL/kg. Fecal samples of the cats were examined to confirm the presence of patent (adult) nematode infections prior to treatment at 28 dpi and to monitor the larval excretion. At necropsy (49 dpi), the weight of the pulmonary lymph nodes and lungs were determined, and T. brevior lungworms were recovered and counted. All control animals and cats to be treated at 28 dpi excreted T. brevior larvae 24 dpi and 26 dpi while no larvae were excreted by the cats treated at 6 dpi. Following treatment at 28 dpi, T. brevior larval excretion decreased immediatetly and ceased prior to necropsy. Nematode counts demonstrated that treatment with the combination product was 100 % efficacious against both developing larval and adult T. brevior: no lungworms were recovered from any treated cat while all control animals harbored T. brevior (range, 6-52) (p<0.001). No treatment-related health problems or any other clinical signs were observed in the cats. However, significantly higher absolute and relative (organ weight to body weight ratio) pulmonary lymph node weights of the control animals compared with the treated cats at 6 dpi (p<0.001 and p<0.001, respectively) and at 28 dpi (p=0.003 and p=0.019, respectively) indicated the pathology of the T. brevior infection. In conclusion, the combination product was demonstrated to be 100 % efficacious against developing larval and adult T. brevior. Furthermore, it was demonstrated that indicators of impaired respiratory and immune systems resultant from T. brevior infection can be prevented with an efficacious treatment when administered during the pre-patent period of infection or are improving substantially within three weeks of treatment of cats harboring adult lungworms.

Efficacy of Broadline® in cats against induced infections with developing fourth-stage larval and adult Ancylostoma ceylanicum hookworms.

Ancylostomaceylanicum hookworms parasitize dogs and cats in subtropical and tropical South East Asia and Pacific region, the Arab Peninsula, southern Africa and South America but cause patent infections in humans too. To evaluate the efficacy of Broadline®, a combination product comprising eprinomectin, fipronil, (S)-methoprene and praziquantel, against developing fourth-larval stage (L4) and adult A. ceylanicum in cats, a blinded, induced infection study was conducted. Following oral inoculation of 24 purpose bred cats with ˜300 infectious A. ceylanicum larvae each, cats were allocated to one of three groups of eight animals, each which served either as untreated controls or received Broadline® (once topically at the minimum label dose of 0.12mL per kg bodyweight) when the hookworms were L4 (five days post inoculation, dpi) or adults (25 dpi). Efficacy was determined on nematode counts following necropsy of the cats. Fecal examination at 22 dpi confirmed that all cats of the control group and of the group to be treated when the hookworms were adult were excreting hookworm eggs (range, 100 to 1000 eggs per gram) while no eggs were recovered from the feces of the cats treated with Broadline® 5 dpi. Nematode counts established 35 dpi demonstrated that Broadline® treatment was 100% efficacious against both, developing L4 and adult A. ceylanicum: no hookworms were recovered from any Broadline®-treated cat while all control animals harbored A. ceylanicum (range, 8-35) (p<0.001). No health problems were observed throughout the study.

Mice as paratenic hosts of Aelurostrongylus abstrusus.

BACKGROUND: Several species of nematodes included in the superfamily Metastrongyloidea are recognized agents of parasitic infections in felines. Aelurostrongylus abstrusus is the most prevalent species affecting the respiratory system of domestic cats. The route of infection in cats is supposed to be through ingestion of gastropod intermediate or paratenic hosts. However, because gastropods are not the preferred preys of cats, rodents were suggested to play an important role as paratenic hosts in the biological cycle of A. abstrusus and in the epidemiology of aelurostrongylosis. RESULTS: Two studies were conducted to document histopathological tissue lesions in mice experimentally infected with A. abstrusus third-stage larvae (L3) (Study 1), and to determine larval counts in their organs (Study 2). Additionally, cats were fed with experimentally infected mice to assess their infectivity. Aelurostrongylus abstrusus L3 were recovered from the liver, spleen, brain, skeletal muscle and gastrointestinal tract tissues by artificial digestion, and heart, spleen and brain tested positive for A. abstrusus at molecular diagnosis. Multifocal encephalitis and meningitis and glial nodules were the most common histopathological lesions found in mice inoculated with A. abstrusus. All cats shed first-stage larvae of A. abstrusus after ingestion of mice inoculated with this nematode. CONCLUSIONS: In this study, we provide information on the anatomical localization, histopathological alterations and rate of recovery of A. abstrusus L3 in mice, and confirm their infectivity to cats (definitive hosts) after feeding on infected mice (paratenic hosts). Data presented here add knowledge to further understand the biology of A. abstrusus in mice and underline the importance of mice as paratenic hosts of this nematode for the infection of cats.

Treatment of canine sarcoptic mange with afoxolaner (NexGard®) and afoxolaner plus milbemycin oxime (NexGard Spectra®) chewable tablets: efficacy under field conditions in Portugal and Germany.

The efficacy of NexGard® and NexGard Spectra® against sarcoptic mange in dogs was evaluated in a clinical field study. Skin scrapings from dogs presenting signs suggestive of sarcoptic mange were examined to confirm infestation. A total of 106 dogs were screened at eight sites in Portugal and Germany. In all, 80 dogs that had demonstrated ≥5 live Sarcoptes mites in five skin scrapings were enrolled, scored for specific clinical signs (pruritus; papules and crusts; alopecia), and allocated at random to receive either NexGard® or NexGard Spectra® twice, one month apart per label instructions. To determine efficacy, live Sarcoptes mites in five skin scrapings per dog were counted, and clinical signs were scored one month and two months after first treatment and compared to pre-treatment (baseline) values. Based on compliance, 65 dogs were determined to be evaluable cases at the end of the study. The efficacy, in terms of reduction of geometric mean live Sarcoptes mite counts, was 98.9% and 99.7% for NexGard®-treated (n = 38) and 99.6% and 100% for NexGard Spectra®-treated dogs (n = 27) at one month and two months after treatment initiation (p < 0.001, both treatments). Both treatments resulted in a significant improvement in pruritus, papules and crusts, and alopecia one month and two months after treatment initiation (p = 0.0001, both treatments). In conclusion, this field study confirms that both NexGard® and NexGard Spectra® administered twice one month apart provide an effective and safe treatment against sarcoptic mange in dogs.

Lungworms and gastrointestinal parasites of domestic cats: a European perspective.

With the exception of Aelurostrongylus abstrusus, feline lungworms have been poorly studied. Information on their distribution is patchy and mostly limited to case reports. In this study, the occurrence of feline lungworms and co-infecting gastrointestinal parasites has been investigated in 12 European countries (i.e. Austria, Belgium, Bulgaria, France, Greece, Hungary, Italy, Portugal, Romania, Spain, Switzerland and the United Kingdom). An average of 10 domestic cats, with regular outdoor access, was sampled each month for 12months, and freshly passed faeces were collected. Stools were processed using a McMaster assay and a quantitative Baermann-Wetzel method. Animals positive for lungworms and/or gastrointestinal parasites were treated with a formulation containing fipronil, (S)-methoprene, eprinomectin, and praziquantel (Broadline®, Merial), and re-sampled 28days post-treatment. The association between lungworm infection and risk factors was analysed using statistical medians/means and the efficacy of the treatment against each lungworm species was assessed. Of 1990 cats sampled, 613 (30.8%) were positive for at least one parasite, while 210 (10.6%) were infected by lungworms. The prevalence of lungworm infection varied between the sampled sites, with the highest recorded in Bulgaria (35.8%) and the lowest in Switzerland (0.8%). None of the cats from Austria or the United Kingdom were infected by lungworms. Aelurostrongylus abstrusus was the species most frequently detected (78.1%), followed by Troglostrongylus brevior (19.5%), Eucoleus aerophilus (14.8%) and Oslerus rostratus (3.8%). The overall efficacy of the treatment was 99% for A. abstrusus and 100% for T. brevior, O. rostratus and E. aerophilus. Data presented provide a comprehensive account of the diagnosis, epidemiology and treatment of feline lungworms in Europe, as well as of the occurrence of co-infections by gastrointestinal parasites.

Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe.

Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5 mg AFX + ≥0.5 mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5 mg MO + ≥5 mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21 days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7 % for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0 %, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98 % efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.

Efficacy of a topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline(®)) against naturally acquired infections with cestodes of the genus Joyeuxiella in cats.

Cats are host to dipylidiid cestodes of the genera Diplopylidium, Dipylidium and Joyeuxiella. Broadline(®), a topical broad-spectrum combination parasiticide containing fipronil (8.3 % w/v), (S)-methoprene (10 % w/v), eprinomectin (0.4 % w/v) and the cestocide praziquantel (8.3 % w/v), has previously been shown to be efficacious against Dipylidium caninum and Diplopylidium spp. in cats. To evaluate its efficacy against Joyeuxiella species, a blinded clinical efficacy study was conducted according to GCP. All cats had evidence for naturally acquired dipylidiid cestode infection as confirmed by pre-treatment examination. Cats were allocated randomly to two groups of 13 cats each based on bodyweight: Control (untreated) and Broadline(®) at 0.12 mL/kg bodyweight administered once topically. Based on the comparison of helminth counts in the treated and untreated cats seven days post treatment, Broadline(®) demonstrated >99 % efficacy (p < 0.01) against mature J. fuhrmanni and J. pasqualei, with 11 and 13 of the untreated cats harbouring 1 to 102 or 2 to 95 cestodes, respectively. In addition, parasite counts indicated 95.9 % efficacy (p = 0.006) against the rictularoid nematode Pterygodermatites cahirensis.

Release of lungworm larvae from snails in the environment: potential for alternative transmission pathways.

BACKGROUND: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. CONCLUSIONS: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context.

Efficacy of Broadline® spot-on against Aelurostrongylus abstrusus and Troglostrongylus brevior lungworms in naturally infected cats from Italy.

The increasing reports of Aelurostrongylus abstrusus infection and the new information on Troglostrongylus brevior have spurred the interest of the scientific community towards the research of pharmaceutical compounds effective against both pathogens. A novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline®, Merial) has been released for the treatment of a variety of feline parasitic infections. The present study reports the efficacy of this spot-on in treating cats naturally infected by feline lungworms. Client owned cats (n=191) were enrolled from three geographical areas of Italy and faecal samples were examined by floatation and Baermann techniques. Twenty-three individuals were positive for L1 of A. abstrusus (n=18) or T. brevior (n=3) or for both species (n=2) and they were topically treated with Broadline®. Seventeen of them were also concomitantly infected by other parasites. Four weeks after treatment, faecal samples were collected and examined to assess the efficacy of a single administration of the product. Based on lungworm larvae counts, the efficacy of the treatment was 90.5% or 100% for A. abstrusus or T. brevior, respectively. Cats released significantly lower amounts of lungworm larvae after treatment compared to pre-treatment (p<0.0001). All but three cats were negative for other nematodes after treatment and all cats recovered from respiratory signs. Results of this study indicate that a single administration of the topical combination fipronil, (S)-methoprene, eprinomectin and praziquantel is effective and safe for the treatment of A. abstrusus and/or T. brevior infections in cats living under field conditions.

Efficacy of Broadline against Capillaria aerophila lungworm infection in cats.

Capillaria aerophila is a globally distributed parasite of the respiratory system of carnivores and can be considered the second most common lungworm after Aelurostrongylus abstrusus in domestic cats in the northern hemisphere. To evaluate the efficacy of Broadline (Merial), a combination of fipronil 8.3% w/v, (S)-methoprene 10% w/v, eprinomectin 0.4% w/v and praziquantel 8.3% w/v against C. aerophila, a controlled study with 20 naturally infected cats was conducted. Following blocking by body weight, cats were allocated randomly to two groups of ten animals each: control (untreated) or treated once with Broadline according to the label instructions. For evaluation of efficacy, faeces were examined for capillarid egg shedding prior to and weekly for 3 weeks after treatment, when the cats were necropsied for C. aerophila recovery. Following single topical administration of Broadline, faecal capillarid egg counts were significantly reduced by 93.5 to 99.1% (p < 0.01) compared to the controls. Cats treated harboured significantly fewer C. aerophila lungworms compared to the untreated controls (efficacy 82.4%, p = 0.016). Results of this study demonstrate that Capillaria lungworm burdens can be markedly reduced and that faecal egg shedding can be substantially lowered or eliminated following a single treatment with Broadline.

Therapeutic efficacy of Broadline against notoedric mange in cats.

The efficacy of a novel topical combination of fipronil 8.3% w/v, (S)-methoprene 10 % w/v, eprinomectin 0.4% w/v, and praziquantel 8.3% w/v (Broadline, Merial) was evaluated in 18 cats naturally infested by Notoedres cati in a controlled, blinded clinical efficacy study. Cats were blocked on pretreatment bodyweight and randomly allocated to two groups of nine cats each. One group served as control (untreated) and one group was treated once topically with Broadline according to the label instructions. Skin scrapings (three scrapings per animal per occasion) were collected prior to treatment and every other week for 8 weeks thereafter and examined for live N. cati mites. In addition, lesions were evaluated at each sampling to monitor the clinical recovery. Based on live mite counts, efficacy against N. cati of a single topical administration with Broadline was >99%, and all treated cats recovered from clinical signs of notoedric mange. No treatment-related adverse events were observed.