Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats

Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ​ml/kg to cats, tigolaner reached mean peak concentrations of 1352 ​μg/l with a Tmax of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 ​l/kg and plasma clearance was low with 0.005 ​l/h/kg. Overall plasma exposure was 1566 ​mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared via the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 ​μg/l and 48 ​μg/l (reached after 1.5 days and 5 ​h, respectively). Overall plasma exposures were 20.6 and 3.69 ​mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks

Two Severe Cases of Tungiasis in Goat Kids in Uganda

Tungiasis ensues from the penetration and burrowing of female sand fleas (Tunga spp.; Siphonaptera: Tungidae) in the skin of mammals. There are few case reports of severe tungiasis in goats and in these cases the Tunga species were not in most cases clearly identified. Two cases of severe tungiasis caused by Tunga penetrans in goat kids from tungiasis-endemic rural Uganda are reported. These are the first severe cases of tungiasis in goats reported from outside South America

Animal Reservoirs of Zoonotic Tungiasis in Endemic Rural Villages of Uganda

Animal tungiasis is believed to increase the prevalence and parasite burden in humans. Animal reservoirs of Tunga penetrans differ among endemic areas and their role in the epidemiology of tungiasis had never been investigated in Uganda. To identify the major animal reservoirs of Tunga penetrans and their relative importance in the transmission of tungiasis in Uganda, a cross sectional study was conducted in animal rearing households in 10 endemic villages in Bugiri District. T. penetrans infections were detected in pigs, dogs, goats and a cat. The prevalences of households with tungiasis ranged from 0% to 71.4% (median 22.2) for animals and from 5 to 71.4% (median 27.8%) for humans. The prevalence of human tungiasis also varied among the population of the villages (median 7%, range 1.3-37.3%). Pig infections had the widest distribution (nine out of 10 villages) and highest prevalence (median 16.2%, range 0-64.1%). Pigs also had a higher number of embedded sand fleas than all other species combined (p<0.0001). Dog tungiasis occurred in five out of 10 villages with low prevalences (median of 2%, range 0-26.9%). Only two goats and a single cat had tungiasis. Prevalences of animal and human tungiasis correlated at both village (rho = 0.89, p = 0.0005) and household (rho = 0.4, p<0.0001) levels. The median number of lesions in household animals correlated with the median intensity of infection in children three to eight years of age (rho = 0.47, p<0.0001). Animal tungiasis increased the odds of occurrence of human cases in households six fold (OR = 6.1, 95% CI 3.3-11.4, p<0.0001). Animal and human tungiasis were closely associated and pigs were identified as the most important animal hosts of T. penetrans. Effective tungiasis control should follow One Health principles and integrate ectoparasites control in animals

Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci

This is an Open Access article. © 2015 The Author(s). Published by Springer Berlin Heidelberg.The susceptibility of 12 field-collected isolates and 4 laboratory strains of cat fleas, Ctenocephalides felis was determined by topical application of some of the insecticides used as on-animal therapies to control them. In the tested field-collected flea isolates the LD50 values for fipronil and imidacloprid ranged from 0.09 to 0.35 ng/flea and 0.02 to 0.19 ng/flea, respectively, and were consistent with baseline figures published previously. The extent of variation in response to four pyrethroid insecticides differed between compounds with the LD50 values for deltamethrin ranging from 2.3 to 28.2 ng/flea, etofenprox ranging from 26.7 to 86.7 ng/flea, permethrin ranging from 17.5 to 85.6 ng/flea, and d-phenothrin ranging from 14.5 to 130 ng/flea. A comparison with earlier data for permethrin and deltamethrin implied a level of pyrethroid resistance in all isolates and strains. LD50 values for tetrachlorvinphos ranged from 20.0 to 420.0 ng/flea. The rdl mutation (conferring target-site resistance to cyclodiene insecticides) was present in most field-collected and laboratory strains, but had no discernible effect on responses to fipronil, which acts on the same receptor protein as cyclodienes. The kdr and skdr mutations conferring target-site resistance to pyrethroids but segregated in opposition to one another, precluding the formation of genotypes homozygous for both mutations.Peer reviewedFinal Published versio

Controlling Tungiasis in an Impoverished Community: An Intervention Study

Tungiasis is a disease caused by the sand flea Tunga penetrans, a parasite prevalent in many impoverished communities in developing countries. The female sand flea penetrates into the skin of animals and humans where it grows rapidly in size, feeds on the host's blood, produces eggs which are expelled into the environment, and eventually dies in situ. The lesions become frequently superinfected and the infestation is associated with considerable morbidity. Clearly, tungiasis is a neglected disease of neglected populations. We investigated the impact of a package of intervention measures targeted against on-host and off-host stages of T. penetrans in a fishing community in Northeast Brazil. These measures decreased disease occurrence only temporarily, but had a sustained effect on the intensity of the infestation. Since infestation intensity and morbidity are correlated, presumably the intervention also lowered tungiasis-associated morbidity. Control measures similar to the ones used in this study may help to effectively control tungiasis in impoverished communities

recommendations from the CVBD World Forum

The human-animal bond has been a fundamental feature of mankind's history for millennia. The first, and strongest of these, man's relationship with the dog, is believed to pre-date even agriculture, going back as far as 30,000 years. It remains at least as powerful today. Fed by the changing nature of the interactions between people and their dogs worldwide and the increasing tendency towards close domesticity, the health of dogs has never played a more important role in family life. Thanks to developments in scientific understanding and diagnostic techniques, as well as changing priorities of pet owners, veterinarians are now able, and indeed expected, to play a fundamental role in the prevention and treatment of canine disease, including canine vector-borne diseases (CVBDs).The CVBDs represent a varied and complex group of diseases, including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, leishmaniosis, rickettsiosis and thelaziosis, with new syndromes being uncovered every year. Many of these diseases can cause serious, even life-threatening clinical conditions in dogs, with a number having zoonotic potential, affecting the human population.Today, CVBDs pose a growing global threat as they continue their spread far from their traditional geographical and temporal restraints as a result of changes in both climatic conditions and pet dog travel patterns, exposing new populations to previously unknown infectious agents and posing unprecedented challenges to veterinarians.In response to this growing threat, the CVBD World Forum, a multidisciplinary group of experts in CVBDs from around the world which meets on an annual basis, gathered in Nice (France) in 2011 to share the latest research on CVBDs and discuss the best approaches to managing these diseases around the world.As a result of these discussions, we, the members of the CVBD Forum have developed the following recommendations to veterinarians for the management of CVBDs

Vector-Borne Diseases - constant challenge for practicing veterinarians: recommendations from the CVBD World Forum

The human-animal bond has been a fundamental feature of mankind's history for millennia. The first, and strongest of these, man's relationship with the dog, is believed to pre-date even agriculture, going back as far as 30,000 years. It remains at least as powerful today. Fed by the changing nature of the interactions between people and their dogs worldwide and the increasing tendency towards close domesticity, the health of dogs has never played a more important role in family life. Thanks to developments in scientific understanding and diagnostic techniques, as well as changing priorities of pet owners, veterinarians are now able, and indeed expected, to play a fundamental role in the prevention and treatment of canine disease, including canine vector-borne diseases (CVBDs)

Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats

Felpreva® for cats contains the new acaricidal/insecticidal active ingredient tigolaner in a fixed combination with the nematocidal and cestocidal compounds emodepside and praziquantel, respectively. The plasma pharmacokinetics of tigolaner, emodepside, and praziquantel were evaluated in clinically healthy cats following topical (spot-on) treatment as fixed combination Felpreva®. For the determination of bioavailability intravenous administration of single active ingredients was also performed. After a single topical administration of Felpreva® using the target dose volume of 0.148 ​ml/kg to cats, tigolaner reached mean peak concentrations of 1352 ​μg/l with a Tmax of 12 days and a mean half-life of 24 days. Simulation of repetitive topical administration every 91 days indicates only a low risk of accumulation after reaching steady state within two to three administrations. The volume of distribution calculated after intravenous dosing was 4 ​l/kg and plasma clearance was low with 0.005 ​l/h/kg. Overall plasma exposure was 1566 ​mg∗h/l after topical administration, providing an absolute bioavailability of 57%. Tigolaner was mainly cleared via the faeces (54% within 28 days), renal clearance was neglectable (< 0.5% within 28 days). Emodepside and praziquantel showed mean peak concentrations of 44 ​μg/l and 48 ​μg/l (reached after 1.5 days and 5 ​h, respectively). Overall plasma exposures were 20.6 and 3.69 ​mg∗h/l, respectively. The elimination half-life was 14.5 days for emodepside and 10 days for praziquantel after topical administration. After topical administration of Felpreva® using 2.5× and 5× dose multiples an almost proportional increase of plasma exposure was observed for all three active ingredients. With the addition of tigolaner, Felpreva® combines the established pharmacokinetic (PK) characteristics of emodepside and praziquantel contained in Profender® spot-on for cats with the favourable PK of tigolaner suitable for a 3-months protection against fleas and ticks

Efficacy and safety of Felpreva®, a spot-on formulation for cats containing emodepside, praziquantel and tigolaner against experimental infestation with the Australian paralysis tick Ixodes holocyclus

The Australian paralysis tick Ixodes holocyclus continues to be a serious threat to companion animals along Australia’s east coast. The tick produces a potent neurotoxin which causes a rapidly ascending flaccid paralysis, which if left untreated, can result in the death of the animal. There is currently only a limited number of products registered in Australia for the treatment and control of paralysis ticks in cats. Felpreva® is an effective spot-on combination containing emodepside, praziquantel and tigolaner. To investigate the therapeutic and long-term persistent efficacy of Felpreva® (2.04% w/v emodepside, 8.14% w/v praziquantel and 9.79% w/v tigolaner) against experimental infestation with I. holocyclus in cats, two studies were undertaken. Fifty cats were included in the studies on study Day -17. These cats were immunized against paralysis tick holocyclotoxin prior to the study commencing. Immunity to holocyclotoxin was confirmed with a tick carrying capacity (TCC) test conducted prior to treatment. Cats were treated once on Day 0. Group 1 cats were treated with the placebo formulation and Group 2 cats were treated with Felpreva®. Cats were infested on Days -14 (tick carrying capacity test), 0, 28, 56, 70, 84 and 91 (weeks 4, 8, 10, 12 and 13). Ticks were counted on cats 24 h, 48 h and 72 ​h post-treatment and infestation, except during the tick carrying capacity test when they were counted approximately 72 ​h post-infestation only. The 24-h and 48-h assessments were conducted without removing the ticks. The ticks were assessed, removed and discarded at the 72-h assessment time-points. Significant differences in total live tick counts at ∼24 h, ∼48 h and ∼72 ​h post-infestation were observed between the treatment and control group. Differences were significant (P ​< ​0.05 to ​< ​0.001) in all instances. Treatment efficacies of 98.1–100% were observed ∼72 ​h post-infestation through to 13 weeks (94 days) post-treatment. These results show that a single application of Felpreva® provides effective treatment and control against induced infestation with paralysis ticks for 13 weeks