Lethal and repellent effect of amitraz, eugenol and thymol against Triatoma infestans, the main vector of Trypanosoma cruzi in the southern of America.

The lethal and repellent effect of the synthetic insecticide amitraz and the botanical insecticides eugenol and thymol separately and together in binary mixtures was tested against late-stage nymphs of a susceptible strain of Triatoma infestans, the main vector of Trypanosoma cruzi, the etiological agent of Chagas disease, in the Southern Cone of America. For the lethality study, the LD50 was determined for each insecticide alone and in binary mixture by topical application. The combination index (CI) was established to quantify interactions occurring between the insecticides. The repellent effect was tested using the area preference technique. The lethal effect of amitraz was 11 and 34 times more potent than that of thymol and eugenol, respectively. Only the combination of eugenol and amitraz at high concentrations showed a synergistic effect (CI: 0.3). The repellent activity of monoterpenes after 30 min of exposure was significant at 780 and 78 µg/cm2 for eugenol and thymol, respectively. The residual repellent effect of eugenol lasted for one week at the concentrations of 1170 and 1560 µg/cm2 , whereas thymol managed to retain its repellent effect for two weeks at concentrations of 1560 and 3900 µg/cm2 .

Current status of resistance to ivermectin in Rhipicephalus sanguineus sensu stricto infesting dogs in three provinces in Argentina.

Intensive use of macrocyclic lactones for parasite control exerts strong selective pressure for arthropods such as ticks to become resistant to them. Rhipicephalus sanguineus sensu stricto is a tick and disease vector of significant public health and veterinary importance worldwide. We assessed the toxicological response to the macrocyclic lactone ivermectin (IVM) in R. sanguineus s.s. infesting dogs in Argentina. Samples of nine tick populations were obtained by inspecting dogs at veterinary clinics, hospitals, or rural areas in the provinces of San Luis, Rio Negro, and Buenos Aires. Pet owners were interviewed to gather data on the history of dog treatment with ectoparasiticides. The larval immersion test was used to assess the toxicological response of R. sanguineus s.s. to IVM. Dose-response mortality regressions, lethal concentrations (LC), and slope were calculated by probit analysis. The lowest LC concentrations were used to designate the reference susceptible population because a laboratory reference strain of R. sanguineus s.s. does not exist in Argentina. Compared with the most susceptible tick population in this study, six populations (66.66%) were classified as resistant to IVM. A clear interpopulation variation in the level of IVM resistance was present (resistance ratios at LC50% ranged from 1.0 to 18.33 and at LC99% ranged from 1.0 to 8.96). In San Luis Province, all tick populations were classified as resistant. The highest level of IVM resistance (resistance ratio at LC50%:18.83 and LC99%:8.96) was found in a population of R. sanguineus s.s. from a rural area in the province of Buenos Aires. It is concluded that populations of R. sanguineus s.s. from dogs in three provinces of Argentina were resistant to IVM. Clear interpopulation variation in the level of IVM resistance was present.

Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model.

Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.

A study of the effects of imidacloprid under laboratory and field conditions on nymphs of Triatoma infestans (Hemiptera: Reduviidae).

The aim of this study was to determine imidacloprid's lethal activity against fifth-instar nymphs of Triatoma infestans. In the first stage of this work, it was assayed the topical application of this insecticide on non-fed and repletion-fed nymphs. Results showed a DL50 three times greater in non-fed bugs than in those fully engorged. The presence of food determined less time for the insecticide's maximum lethal effect: 24 h post topical application in fed nymphs and 72 h in non-fed nymphs. In the study's second stage, we assayed a xenointoxication assay on dogs. The commercial products, Advantage®, Bayer (imidacloprid 10 % p/v) and Power Ultra®, Brouwer (imidacloprid 5.15 %, permethrin 40 % and piperonyl butoxide [PBO] 3%) were evaluated. Following administration of the insecticide, nymphs were fed on dogs 24, 72, 168, 240 and 336 h. Blood intake was similar in nymphs exposed to treated dogs versus controls. Although both commercial products showed low triatomicidal activity, a higher efficacy of the product combining imidacloprid with the synergist piperonyl butoxide and permethrin versus the product with imidacloprid as the only active ingredient was observed, causing in nymphs a mortality rate of 36.3 % and 20.7 %, respectively. Our results suggest that imidacloprid, alone or in combination with permethrin and PBO, is not an alternative for control of T. infestans.

Evaluation of the toxic effects of doramectin, ivermectin and eprinomectin against Triatoma infestans using a rat model.

INTRODUCTION: Pyrethroids have been frequently and intensively used for controlling the triatomine vectors of Trypanosoma cruzi. The emergence of resistance to these insecticides has resulted in an urgent need to identify novel, alternative and complementary control strategies. OBJECTIVE: To evaluate the toxic effects of ivermectin, doramectin and eprinomectin on the bloodfeeding behaviour of Triatoma infestans using a rodent model. MATERIALS AND METHODS: Fifth instar nymphs of T. infestans were fed at different times on Wistar rats pretreated with doramectin, ivermectin, eprinomectin or dimethylsulfoxide (excipient control) topically or orally administered. We determined the effects of each insecticide and of dimethyl sulfoxide on the amount of ingested blood, the volume of faecal discharge, and the mortality rates in triatomines. RESULTS: Only the rate of triatomine mortality was associated with the antiparasitic compounds administered and the route of administration utilized. Doramectin administration was associated with a higher mortality rate (21.5%) than ivermectin, eprinomectin and dimethylsulfoxide (16, 11 and 2.5%, respectively), and topical administration was found to be most effective for inducing mortality (23 vs. 9.3 %). CONCLUSION: These results demonstrate the toxic effects of the three assessed insecticides on T. infestans. The administration of ecto/endoparasiticides to domiciliary or peridomiciliary animals may serve as an interesting complementary strategy to the use of pyrethroids for the control of T. infestans.

Evaluación del efecto tóxico de la doramectina, la ivermectina y la eprinomectina sobre Triatoma infestans en un modelo de rata / Evaluation of the toxic effects of doramectin, ivermectin and eprinomectin against Triatoma infestans using a rat model

Resumen Introducción. La principal herramienta para el control de los triatominos, vectores de Trypanosoma cruzi, ha sido el uso masivo e intensivo de piretroides. La aparición de resistencia a estas moléculas ha planteado la necesidad de encontrar estrategias nuevas, alternativas y complementarias de control. Objetivo. Evaluar el efecto tóxico de la ivermectina, la doramectina y la eprinomectina sobre Triatoma infestans y sus consecuencias en la alimentación con sangre en un modelo de roedor. Materiales y métodos. Se alimentaron ninfas de quinto estadio de T. infestans en distintos momentos sobre ratas Wistar tratadas previamente con doramectina, ivermectina, eprinomectina o dimetilsulfóxido (excipiente de control), administrados tópicamente o por vía oral. Se determinó el efecto de cada endectocida y del dimeltilsulfóxido en la cantidad de sangre ingerida, el volumen de excreciones y el porcentaje de mortalidad. Resultados. Únicamente la mortalidad de los insectos dependió del endectocida suministrado a las ratas y de la vía de administración utilizada. La doramectina causó mayor mortalidad (21,5 %) comparada con la ivermectina, la eprinomectina y el dimetilsulfóxido (16, 11 y 2,5 %, respectivamente), y la administración tópica fue más efectiva que la vía oral (23 Vs. 9,3 %). Conclusión. Los resultados obtenidos demuestran el efecto tóxico de los tres endectocidas en T. infestans. Su utilización en animales domiciliarios o que viven en el peridomicilio podría ser una interesante estrategia complementaria de la aspersión con piretroides para el control de T. infestans.

Abstract Introduction: Pyrethroids have been frequently and intensively used for controlling the triatomine vectors of Trypanosoma cruzi. The emergence of resistance to these insecticides has resulted in an urgent need to identify novel, alternative and complementary control strategies. Objective: To evaluate the toxic effects of ivermectin, doramectin and eprinomectin on the blood-feeding behaviour of Triatoma infestans using a rodent model. Materials and methods: Fifth instar nymphs of T. infestans were fed at different times on Wistar rats pretreated with doramectin, ivermectin, eprinomectin or dimethylsulfoxide (excipient control) topically or orally administered. We determined the effects of each insecticide and of dimethyl sulfoxide on the amount of ingested blood, the volume of faecal discharge, and the mortality rates in triatomines. Results: Only the rate of triatomine mortality was associated with the antiparasitic compounds administered and the route of administration utilized. Doramectin administration was associated with a higher mortality rate (21.5%) than ivermectin, eprinomectin and dimethylsulfoxide (16, 11 and 2.5%, respectively), and topical administration was found to be most effective for inducing mortality (23 vs. 9.3 %). Conclusion: These results demonstrate the toxic effects of the three assessed insecticides onT. infestans. The administration of ecto/endoparasiticides to domiciliary or peridomiciliary animals may serve as an interesting complementary strategy to the use of pyrethroids for the control of T. infestans.

Residue depletion of ivermectin in broiler poultry.

Helminth infections are widespread in the poultry industry. There is evidence of extra-label use of some drugs, such as ivermectin (IVM), in broiler poultry. Pharmacokinetic and residual studies of IVM in poultry, however, are rather scarce. Our aim was to determine time restrictions for broiler chickens fed with balanced feed mixed with IVM for 21 days, and thus achieve acceptable residual levels for consumption as established by the European Union. Sixty 1-day-old chicks were fed with food supplemented with IVM at 5 mg kg-1 feed for 21 days. Groups of six treated animals were sacrificed at 0, 1, 2, 4, 8, 10, 15, 20 and 28 days after treatment. Liver, skin/fat, kidney and muscle samples were obtained. IVM were determined by liquid chromatography with fluorescence detection after automatic solid-phase extraction with SPE C18 cartridges. The highest concentrations were measured in the liver, which is logical given that IVM is a drug that undergoes extensive hepatic metabolism. The optimal withdrawal time for edible tissues of these animals to stay within the permitted residual levels were: 12 days for liver, 8 days for skin/fat, 0 days for muscle and 10 days for kidney.

Eficacia in vitro de tres endectocidas frente a Triatoma infestans / In vitro efficacy of three endectocides against Triatoma infestans

Introducción: distintos estudios han demostrado el papel preponderante que el peridomicilio cumple en la reinfestación de las viviendas por Triatoma infestans (vinchucas). Con el objetivo de eliminar focos residuales de T. infestans que habitan alrededor de los hogares se han desarrollado distintas estrategias. La administración de diferentes compuestos que tengan actividad contra T. infestans a los animales que habitan zonas cercanas a los domicilios y sirvan como fuente de alimentación a estos insectos, podría ser una buena manera de disminuir el riesgo de reinfestación domiciliaria. Objetivo: evaluar la eficacia in vitro de tres agentes antiparasitarios, doramectina (DRM), ivermectina (IVM) y eprinomectina (EPR) frente a ninfas de quinto estadio de Triatoma infestans. Métodos: se diseñaron alimentadores artificiales en donde se colocó sangre heparinizada y fortificada con distintas concentraciones de los tres endectocidas (100-0,4 ng/mL). Se utilizaron 600 ninfas de quinto estadio de T. infestans durante el experimento. Un grupo de vinchucas fue alimentada con sangre sin tratar (control). Luego de realizada la alimentación se observó el estado de los insectos cada 24 hs. durante el transcurso de una semana. Resultados: los tres endectocidas demostraron actividad frente a ninfas de quinto estadio de T. infestans. Comparando la actividad de las tres moléculas, DRM fue la que exhibió una mayor potencia contra los insectos, inclusive mantuvo su actividad frente T. infestans a 0,4 ng/mL (menor concentración evaluada). En el caso de IVM y EPR comenzaron a perder eficacia a concentraciones por debajo de los 6,25 y 3,15 ng/mL respectivamente, siendo totalmente inactivas a 0,4 ng/mL. Conclusiones: en base a estos resultados podemos aseverar que bajo nuestras condiciones experimentales, tanto IVM, EPR como DRM poseen una alta eficacia in vitro contra T. infestans, siendo la última la más efectiva de las tres evaluadas(AU)

Introduction: various studies have demonstrated the role that areas around the houses play in domiciliary re-infestation by Triatomainfestans (kissing bugs). With the aim of removing residual foci of T. infestans that inhabit in neighboring areas of houses, different strategies have been developed. The administration of different anti-T. infestans compounds to animals living in areas around the houses might be a good way to reduce the risk of domiciliary re-infestation. Objective: to evaluate the in vitro efficacy of three antiparasitic agents, doramectin (DRM), ivermectin (IVM) and eprinomectin (EPR) against fifth instar nymphs of Triatomainfestans. Methods: artificial feeders were designed , which contained heparinized and fortified blood with various concentrations of the three endectocides (100-0.4 ng/mL). We used 600 fifth instar nymphs of T. infestans during the experiment. A group of insects were fed with untreated blood (control). After feeding they were under observation to check their condition every 24 hours for a week. Results: the three molecules showed activity against T. infestans. In comparing the activity of the three molecules, DRM exhibited greater potency against insects, it even kept its activity against T. infestans at 0.4 ng/mL (lowest concentration tested). In the case of EPR and IVM, their efficacy began to lower at concentrations below 6.25 and 3.15 ng/mL respectively, being totally inactive at 0.4 ng/mL concentration. Conclusions: Based on these results, we can assert that under our experimental conditions, IVM, EPR and DRM show in vitro high efficacy against T. infestans, being the latter more effective than the other two molecules(AU)