Status of Rhipicephalus microplus resistance to ivermectin, fipronil and fluazuron in Mato Grosso do Sul, Brazil / Status da resistência de Rhipicephalus microplus a ivermectina, fipronil e fluazuron em Mato Grosso do Sul

Abstract Southern cattle tick resistance to pour-on and injectable acaricides has yet to be evaluated on a broader scope, and the paucity of information on the subject may hinder efforts to control this parasite. The objective of this study was to evaluate the resistance profile of ten populations of Rhipicephalus microplus to the acaricides fluazuron, fipronil and ivermectin in cattle herds in Mato Grosso do Sul, Brazil. The larval immersion test (LIT) was used to evaluate susceptibility to ivermectin and fipronil and the adult immersion test (AIT) was performed to evaluate fluazuron. Samples were randomly obtained in ten farms, and in general, we found resistance in five samples to fluazuron and in four samples to ivermectin and fipronil. Six samples showed incipient resistance to ivermectin and fipronil. Five of the ten evaluated samples showed resistance and/or incipient resistance to all the active ingredients, and the other five to two active ingredients. Among the samples classified as resistant, the average resistance ratio for ivermectin was 2.75 and 3.26 for fipronil. These results demonstrate the advanced status of resistance to the most modern chemical groups for the control of R. microplus in the state of Mato Grosso do Sul.

Resumo A resistência do carrapato-do-boi a acaricidas com modo de aplicação "pour-on" e injetáveis é pouco avaliada em estudos mais abrangentes, e essa escassez de informação pode resultar falhas no seu controle. Este estudo teve como objetivo avaliar o perfil de resistência em dez populações de Rhipicephalus microplus aos acaricidas fluazuron, fipronil e ivermectina, em rebanhos bovinos em Mato Grosso do Sul, Brasil. A caracterização fenotípica da resistência foi realizada por meio do teste de imersão de adultos (AIT) para o fluazuron, e teste de imersão de larvas (LIT) para fipronil e ivermectina. As amostras foram obtidas aleatoriamente em dez fazendas, sendo diagnosticada resistência em cinco amostras ao fluazuron e em quatro amostras à ivermectina e fipronil. Seis amostras apresentaram resistência incipiente à ivermectina e fipronil. Cinco das dez amostras avaliadas apresentaram resistência e / ou resistência incipiente a todos os princípios ativos, e as outras cinco a dois princípios ativos. Entre as amostras classificadas como resistentes, a média do fator de resistência para ivermectina foi de 2,75 e de 3,26 para fipronil. Esses resultados demonstram o avançado estado de resistência aos mais modernos grupos químicos para o controle de R. microplus em Mato Grosso do Sul.

Sublethal effect of Abamectin in the functional response of the predator Phytoseiulus persimilis (Athias-Henriot) on Tetranychus urticae (Koch) (Acari: Phytoseiidae, Tetranychidae) / Efeito subletal da Abamectina na resposta funcional do predador Phytoseiulus persimilis (Athias-Henriot) em Tetranychus urticae (Koch) (Acari: Phytoseiidae, Tetranychidae)

Abstract The biological control used for the control of Tetranychus urticae (Koch) is the predator mite Phytoseiulus persimilis (Athias-Henriot). It is important to the know the effects of acaricides on the biological behavior the Abamectin on the functional response of P. persimilis. The functional response of the predator was of type II exposed to concentration of Abamectin, the functional response parameters: successful attack rate (a'), handling time (Th), search efficiency and the maximum predation theory (T/Th) were affected by the acaricide. The predator spends more time in persecute, dominate, consume and prepair it self to the next searching comparing with the proof subject an the predation ability was affected.

Resumo O controle biológico utilizado para o controle de Tetranychus urticae (Koch) é o acaro predador Phytoseiulus persimilis (Athias-Henriot). É importante conhecer os efeitos dos acaricidas sobre o comportamento biológico do predador. Foi avaliado o efeito tóxico de a Abamectina na resposta funcional de P. persimilis. A resposta funcional do predador foi tipo II exposta a concentrações subletais de Abacmetina, os parâmetros da resposta funcional: taxa de ataque (a'), tempo de manipulação (Th), a eficiência na procura e predação teórica máxima (T/Th) foram afetados pelo acaricida. O predador passa mais tempo na procura, dominar, consumir e se preparar para a próxima procura em comparação com a testemunha e sua capacidade de predação foi afetada.

Differences in protein expression associated with ivermectin resistance in Caenorhabditis elegans / Diferenças na expressão de proteínas associadas à resistência à ivermectina em Caenorhabditis elegans

Abstract The indiscriminate administration of synthetic anthelmintics such as ivermectin contributes to the selection of subpopulations capable of resisting the drugs' effects. To understand the mechanisms of ivermectin resistance in Caenorhabditis elegans, this study attempted to identify molecular targets. C. elegans lineages that were sensitive and resistant to ivermectin were used. Collected nematodes were added to an extraction buffer and macerated in liquid nitrogen for protein extraction. The extracted proteins were separated according to molecular weight by SDS-PAGE to verify their integrity. Subsequently, proteins from both lineages were separated using two-dimensional electrophoresis. The gels were analyzed and the relevant spots were excised and identified by mass spectrometry (NanoESI-Q-TOF and MASCOT®) and subsequently assessed by GO enrichment and STRING® analyses. The increased expression of proteins associated with high metabolic activity, such as ATP-2 and ENOL-1, which are responsible for ATP synthesis, was observed. Furthermore, proteins with involvement in mediating muscular function (MLC-1, ACT-1, and PDI-2), signaling (FAR-1 and FAR-2), and embryo development (VHA-2) were identified. Protein interaction analysis indicated that the majority of the identified proteins in the resistant lineages participated in the same reaction triggered by ivermectin.

Resumo A administração indiscriminada de anti-helmínticos sintéticos, como a ivermectina, contribui para a seleção de subpopulações capazes de resistir ao efeito das drogas. Para entender os mecanismos de resistência à ivermectina em Caenorhabditis elegans, este estudo visou identificar alvos moleculares. Portanto, linhagens de C. elegans sensíveis e resistentes à ivermectina foram utilizadas. Os nematóides coletados foram adicionados ao tampão de extração e macerados em nitrogênio líquido para obtenção das proteínas. As proteínas extraídas foram separadas por peso molecular em SDS-PAGE para verificar sua integridade. Posteriormente, as proteínas de ambas as linhagens foram separadas por eletroforese bidimensional. Os géis foram analisados, os spots relevantes foram excisados e identificados por espectrometria de massa (NanoESI-Q-TOF e MASCOT®), em seguida, analisados ​​em seus termos de GO e STRING®. A expressão aumentada de proteínas associadas à alta atividade metabólica, como as proteínas ATP-2 e ENOL-1, responsáveis ​​pela síntese de ATP, foi observada. Além disso, foram identificadas as proteínas responsáveis ​​pelo controle da função muscular (MLC-1, ACT-1 e PDI-2), sinalização (FAR-1 e FAR-2) e desenvolvimento embrionário (VHA-2). A análise das interações proteicas indicou que a maioria das proteínas identificadas na cepa resistente participa da mesma reação desencadeada pela ivermectina.

In vitro evaluation of ivermectin, moxidectin, albendazole and pyrantel against cyathostomins of horses / Avaliação in vitro da ivermectina, moxidectina, albendazole e pirantel contra ciatostomíneos de equinos

Abstract Cyathostomins are the most prevalent nematodes of horses, and multidrug resistance has been reported worldwide. There is a need to implement alternative drug monitoring analytical tests. The objective of this study was to determine the consistency (5 repetitions) of the larval migration on agar test (LMAT) using ivermectin, moxidectin, pyrantel or albendazole against cyathostomin infective-stage larvae in eight different concentrations. LMAT showed a strong coefficient of determination (R2 > 0.91), between the test repetitions (n=5). The average 50% effective concentration (EC50) for ivermectin, moxidectin, pyrantel and albendazole were 0.0404, 0.0558, 0.0864 and 0.0988 nMol, respectively. The results of the EC50 for albendazole showed the greatest range of concentration. Ivermectin and moxidectin had the lowest in between-test variation. In the future, internationally certified susceptible isolates could be used for screening new drug candidates, or to follow up the pattern of drug efficacy from field populations.

Resumo Ciatostomíneos são os nematodas mais prevalentes em equinos e a resistência múltipla foi relatada em todo o mundo. Existe a necessidade de implementar o monitoramento dos produtos com testes analíticos alternativos. O objetivo deste estudo foi determinar a consistência (5 repetições) do teste de migração larval em ágar (TMLA) usando ivermectina, moxidectina, pirantel e albendazole contra larvas infectantes de ciatostomíneos em oito concentrações diferentes. O TMLA demonstrou um coeficiente de determinação (R2) acima de 0,91 entre as repetições do teste. A concentração efetiva para 50% (CE50) para ivermectina, moxidectina, pirantel e albendazole foi de 0,0404; 0,0558; 0,0864 e 0,0988 nMol, respectivamente. A CE50 do albendazole demonstrou a maior amplitude entre os testes. A ivermectina e a moxidectina tiveram as menores variações das doses entre as repetições. No futuro, isolados certificados susceptíveis poderão ser testados com o TMLA para indicação de novos produtos e mesmo para acompanhar o perfil de eficácia de populações do campo.

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.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control / Suscetibilidade in vitro de fungos nematófagos à antiparasitários: interações e implicações para o controle biológico

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 μg/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 μg/mL para o levamisol, e entre 0,625 e 0,034 μg/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

Antiparasitic drugs: in vitro tests against nematophagous fungi / Antiparasitários: teste in vitro contra fungos nematófagos

Abstract The use of biological agents has been intensified in recent years against eggs and larvae of gastrointestinal nematodes as an alternative control method in pasture plant health management, with the concomitant use with antiparasitic drugs still occurring. The aim of this study was to test the in vitro activity of the following antiparasitic drugs: Ivermectin and albendazole against the following nematophagous fungi: Paecilomyces fumosoroseus, Paecilomyces lilacinus and Paecilomyces variotii. The agar diffusion test was performed using an initial concentration of 0.0016g/mL of each drug, after solidification of the culture medium containing the drug concentration each nematophagous fungi was inoculated. The results showed that in a concentration of 80μg/mL, the fungal growth decreased, however, with the concentration of 160μg/mL, there was no fungal growth in both drugs, compared to the control, which indicates an inhibition in the development of the nematophagous fungi studied when they come in contact with ivermectin and albendazole.

Resumo O uso de agentes biológicos que atuam em ovos e larvas de nematódeos gastrintestinais como uma alternativa para o manejo de pastagens de saúde tem se intensificado nos últimos anos, bem como o uso concomitante com outros medicamentos antiparasitários. O objetivo deste estudo foi testar o efeito in vitro dos fármacos Ivermectina e Albendazol em fungos nematófagos Paecilomyces fumosoroseus, Paecilomyces lilacinus e Paecilomyces variotii. Foi utilizada a técnica de difusão em agar, sendo preparado a partir de uma concentração inicial de 0,0016g/mL de cada uma das drogas e diluídas em meio de cultura, com posterior semeadura dos fungos nematófagos. Os resultados mostraram que na concentração de 80μg/mL, o crescimento diminuiu, no entanto, com a concentração de 160μg/mL de ambas as drogas, não houve crescimento de fungos durante o período de estudo, em comparação com o controle, indicando a inibição do desenvolvimento dos fungos nematófagos estudados quando em contato com a Ivermectina e Albendazol.

Rhipicephalus (Boophilus) microplus resistant to acaricides and ivermectin in cattle farms of Mexico / Rhipicephalus (Boophilus) microplus resistentes aos acaricidas e ivermectina nas fazendas de gado do México

Ticks and the diseases they transmit cause great economic losses to livestock in tropical countries. Non-chemical control alternatives include the use of resistant cattle breeds, biological control and vaccines. However, the most widely used method is the application of different chemical classes of acaricides and macrocyclic lactones. Populations of the cattle tick, Rhipicephalus (Boophilus) microplus, resistant to organophosphates (OP), synthetic pyrethroids (SP), amitraz and fipronil have been reported in Mexico. Macrocyclic lactones are the most sold antiparasitic drug in the Mexican veterinary market. Ivermectin-resistant populations of R. (B.) microplus have been reported in Brazil, Uruguay and especially in Mexico (Veracruz and Yucatan). Although ivermectin resistance levels in R. (B.) microplus from Mexico were generally low in most cases, some field populations of R. (B.) microplus exhibited high levels of ivermectin resistance. The CHPAT population showed a resistance ratio of 10.23 and 79.6 at lethal concentration of 50% and 99%, respectively. Many field populations of R. (B.) microplus are resistant to multiple classes of antiparasitic drugs, including organophosphates (chlorpyrifos, coumaphos and diazinon), pyrethroids (flumethrin, deltamethrin and cypermethrin), amitraz and ivermectin. This paper reports the current status of the resistance of R. (B.) microplus to acaricides, especially ivermectin, in Mexican cattle.

Carrapatos e as doenças por eles transmitidas causam grandes perdas econômicas ao gado dos países tropicais. Alternativas não-químicas incluem o uso de raças de gado que sejam resistentes, controle biológico e vacinas. No entanto, o método mais utilizado é a aplicação de diferentes classes químicas de acaricidas e lactonas macrocíclicas. Populações de piolhos de gado, Rhipicephalus (Boophilus) microplus, resistentes aos organofosfatos (OP), piretoides sintéticos (SP), amitraz e fipronil, foram descritas no México. Lactonas macrocíclicas são as drogas antiparasitárias mais vendidas no mercado veterinário mexicano. Populações de R. (B.) microplus resistentes à irvemectina foram relatadas no Brasil, Uruguai e especialmente no México (Veracruz e Yucatan). Embora os níveis de resistência à ivermectina no R. (B.) microplus do México tenha sido relativamente baixa, na maioria dos casos, algumas populações campestres de R. (B.) microplus mostraram altos níveis de resistência à ivermectina. A população CHPAT mostrou uma razão de resistência de 10,23 e 79,6 na concentração letal de 50% e 99%, respectivamente. Muitas populações campestres de R. (B.) microplus são resistentes a múltiplas classes de drogas antiparasitárias, incluindo organofosfatos (clorpirifós, coumafos e diazinon), piretoides (flumetrina, deltametrina e cipermetrina), amitraz e ivermectina. Este artigo relata o estado atual de resistência do R. (B.) microplus aos acaricidas, especialmente ivermectina, no gado mexicano.

Effect of ivermectin on the survival and fecundity of Euoniticellus intermedius (Coleoptera: Scarabaeidae)

The State of Veracruz in Mexico is one of the main cattle producers, and uses several veterinary products for disease and parasite control. For parasite control, ivermectin is one of the most frequently used substances. Nevertheless, even though previous research conducted in other countries has found that this product has negative effects on beneficial coprophagous fauna, no studies have descry ibed its effects on coprophagous insects at a local scale in Veracruz, Mexico. This study evaluated Euoniticellus intermedius survival, fecundity, fertility and preimaginal development under laboratory conditions when ivermectin was added to cattle dung at three different concentrations. The design included two controls (spiked dung), and the following product concentrations: 0.01, 1.0 and 100ppm, which were homogenized with wet cattle dung. 20 female-male E. intermedius couples between five and 15 days old were used and kept at 27°C, 70% RH, and 12h light for 10 days. The survival of all specimens, the fertility of 20 females and the gonadal maturity of 17 males were verified. The larval development in 162 pieces of brood-mass was examined, and a total of 974 larvae developed and reached adulthood. The highest ivermectin concentration was toxic at 1.0ppm dose, the survival of adults was reduced to almost the half, and at 100ppm, total mortality was observed. The effects on specimen reproductive systems showed that the ovary was not affected, that the testicle size increased, and that the fecundity and weight of brood-masses were reduced. Pre-imaginal development increased 0.5 times at 0.01ppm concentration, and the width of the cephalic capsule in third instar larvae diminished. The prolonging of development time may cause a phase lag in the field activity cycle, this lag may reduce the number of E. intermedius individuals and the efficiency of the environmental services that they provide.

El estado de Veracruz en México, es uno de los principales productores de ganado vacuno en México, asimismo utiliza diversas medicinas veterinarias para el control de enfermedades y parásitos. La ivermectina es una de las substancias más utilizadas para el control de parásitos. Sin embargo, se sabe por estudios hechos en otros países, que esta substancia tiene efectos negativos sobre la fauna coprófaga benéfica como los escarabajos del estiércol, pero no se han estudiado sus efectos sobre la fauna coprófaga de Veracruz o de México. Este estudio se realizó en condiciones de laboratorio, en donde se utilizó el estiércol vacuno a tres diferentes concentraciones de ivermectina para determinar su efecto sobre la supervivencia, fecundidad, fertilidad y desarrollo preimaginal de Euoniticellus intermedius. Por lo tanto, las tres concentraciones que se emplearon fueron: 0.01, 1.0 y 100ppm de ivermectina homogeneizada en estiércol vacuno fresco y dos testigos. Además, se utilizaron 20 parejas hembramacho por tratamiento, entre cinco y 15 días de edad y mantenidos por 10 días a 27°C, 70% HR y 12hr luz. Se determinó la supervivencia de todos, la fertilidad en 20 hembras y el estado de madurez gonádica en 17 machos. Se determinó el desarrollo preimaginal en 162 masas-nido y 974 se dejaron continuar el desarrollo hasta la emergencia de los adultos. La ivermectina es tóxica a mayor concentración. La supervivencia de adultos se redujo casi a la mitad a dosis de 1.0ppm y fue nula a 100ppm. El ovario no fue afectado. Los testículos incrementaron de tamaño. La fecundidad y el peso de las masas-nido se redujeron. El desarrollo preimaginal se incrementó 0.5 veces a concentración 0.01ppm y las larvas del tercer estadio redujeron el ancho de la cápsula cefálica. El alargamiento del tiempo de desarrollo puede causar desfase de su ciclo de actividad en campo, lo que podría reducir su número y la eficiencia de los servicios ambientales que proporcionan.

Sensibilidad de trofozoítos de Entamoeba histolytica a ivermectina / Sensibility of Entamoeba histolytica trophozoites to ivermectin

La amibiasis producida por Entamoeba histolytica es un problema de salud pública. Las formas clínicas más frecuentes son la disentería y el absceso hepático amibiano. En el mundo se notifican anualmente 50 millones de casos y más de 100 000 muertes por esta enfermedad. El ciclo de vida de E. histolytica tiene dos fases: trofozoíto y quiste. Los trofozoítos son los responsables de producir enfermedad. El tratamiento actual para la amibiasis incluye medicamentos con efectos colaterales serios. La ivermectina es un macrólido con actividad contra endoparásitos y ectoparásitos causantes de strongiloidosis, filariasis, oncocercosis, sarna y pediculosis. Su uso está extendido a casi todo el mundo y se lo reconoce como un medicamento seguro. El objetivo de este trabajo fue determinar la sensiblidad in vitro de trofozoítos de E. histolytica al tratamiento con ivermectina. Para determinar su sensibilidad a la droga, se utilizaron trofozoítos de E. histolytica cultivados en medio PEHPS. Durante su fase de crecimiento logarítmico se expusieron a diferentes concentraciones de ivermectina. Como controles se usaron otras drogas antiparasitarias. Se prepararon diluciones seriadas de cada droga, luego se agregaron a tubos con parásitos (2 x 10(4) células/ml). Se incubó por 72 h y luego se determinó el porcentaje de inhibición de crecimiento calculado por análisis Probit. La ivermectina tiene actividad contra trofozoítos de E. histolytica. La dosis de ivermectina que produjo el 50% de inhibición de crecimiento fue de 6.40 mg/ml. Esta dosis fue mayor a la encontrada con otras drogas antiparasitarias. Falta demostrar su actividad in vivo en modelos animales.

Amebiasis caused by Entamoeba histolytica is a problem of public world health. The most frequent clinical presentation are the dysentery and the amebic liver abscess. Fifty millions of cases and more than 100.000 deaths for this disease are reported annually worldwide. The life cycle of E. histolytica has two phases: trophozoite and cyst. Trophozoites are the causal agent of disease. The effective treatment for the amebiasis includes drugs with serious collateral effects. Ivermectin is a macrolid with activity against endoparasites and ectoparasites causing strongiloidosis, filariasis, oncocercosis, scabiasis and pediculosis. The use of ivermectin has been extended almost worldwide; it is recognized as a safe drug. The main objective of this study was to determine in vitro sensibility of trophozoites of E. histolytica was to the treatment with ivermectin. To determine the sensibility of the parasites to the drug, E. histolytica was cultivated in PEHPS medium. During its logarithmic growth phase the trophozoites were exposed to different concentrations of ivermectin. As controls other antiparasitic drugs were used. For each drug, serial dilutions were prepared, and mixed in culture tubes with parasites (2 x 10(4) cells/ml). They were incubated for 72 h and then the percentage of growth inhibition was calculated by Probit analysis. Ivermectin showed activity against trophozoites of E. histolytica. The 50% of growth inhibition of ivermectin was 6.40 mg/ml. This dose was higher than for other anti parasitic drugs. Its activity in vivo in animal models remains to be demonstrated.

Lack of in vitro effect of ivermectin on Plasmodium falciparum.

The in vitro activity of ivermectin was assessed against the K1 isolate of Plasmodium falciparum. The mean IC50 and IC90 of ivermectin were 8.0 and 35.0 microg/ml, respectively. These results indicate that ivermectin has a very low activity against P. falciparum in vitro.

Tratamento da sarna crostosa com ivermectina / Crusted scabies treatment with ivermectin

O tratamento da sarna crostosa (SC) usualmente representa um desafio. Uma paciente portadora de SC foi tratada com sucesso com duas doses de ivermectina por via oral. Entretanto, houve recidiva do quadro um mês após, evidenciando tanto a importância do tratamento dos contactantes quanto o fato de a ivermectina näo possuir efeito residual após um mês. A ivermectina é droga promissora no tratamento da escabiose, principalmente de sua variante crostosa

The onchocerciasis elimination program for the Americas: a history of partnership

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US$2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US$ 4 million grant provided through the Inter-American Development Bank, the OEPA's capacity to support the regional initiative is assured through 1999

Assessment of ivermectin therapeutic efficacy on third-stage larvae of Lagochilascaris minor in mice experimentally infected

Avaliou-se a acao da ivermectina sobre larvas de terceiro estadio, tanto em fase de migracao, quanto larvas encistadas em tecidos de camundongos infectados experimentalmente com Lagochilascaris minor. Foram utilizados 120 camundongos (grupos I e II), sendo que cada animal foi inoculado, por via oral, com 1.000 ovos do parasito. Para verificar a acao da ivermectina sobre larvas em migracao, o grupo I (60 animais) foi dividido igualmente em tres subgrupos: I-A, I-B e I-C. No setimo dia apos a inoculacao (DAI), cada animal foi tratado com ivermectina na dosagem de 200 ug/Kg (subgrupo I-A) e 1.000 ug/Kg/dose unica/via sc (subgrupo I-B). Com o objetivo de verificar a acao das drogas sobre larvas encistadas, os animais do grupo II foram divididos igualmente em tres subgrupos: II-A, II-B e II-C...

Effects of ivermectin on Culex quinquefasciatus larvae

Os efeitos da ivermectina, uma droga semi-sintetica amplamente utilizada para o tratamento de doencas parasitarias do gado, foram observados em larvas de Culex quinquefasciatus. Os efeitos toxicos e a avaliacao da mortalidade foram investigados apos 5,15 30 e 60 minutos de exposicao a 1, 5 ou 10 ppm de solucao de ivermectina. As observacoes foram realizadas 24 e 48 horas apos o inicio do experimento, e perda de mobilidade, paralisia progressiva e alta mortalidade de larvas foram registradas. Os efeitos da ivermectina observados nas larvas de mosquito estao provavelmente correlacionados com a ativacao de canais de Cloro em membranas celulares

In vitro drug susceptibility of Acanthamoeba castellani to chloroquine, ivermectin and fungizon.

In vitro sensitivity of Acanthamoeba castellani was tested to three drugs: Chloroquine, ivermectin and fungizone (amphotericin B). Sensitivity was demonstrated to the latter two compounds but not to chloroquine. Thus ivermectin and amphotericin B show promise as therapeutic agents against this parasite.

Effect of mebendazole and ivermectin in experimental hepatic capillariasis: parasitological, scanning electron microscopy and immunological studies

In this study, mebendazole and ivermectin were tried during three different phases of C. hepatica infection. At an early phase when immature forms were present, both drugs were effective in causing destruction and degeneration of the larvae, thus, preventing subsequent growth and maturation and consequently, the complete absence of eggs. During the second phase which is found to be the most critical period, the two drugs used led to degeneration and resorption of most of adult worms. In the third phase, both mebendazole and ivermectin were effective in decreasing the mean number of eggs. After treatment, the topographic changes were in the form of disorganized cuticle of the worms and the absence of surface uniformity. Such a disorganized cuticle is vulnerable to be attacked. C. hepatica eggs showed irregularities and longitudinal grooves indicated shrinkage of the shell. The effect of the two drugs indicated that both of them were effective in the treatment of hepatic capillariasis

Neuropharmacological effects of ivermectin in mice.

Neuropharmacological effects (Spontaneous locomotor activity, forced locomotor activity and anticonvulsant activity) of invermectin were studied at 400, 800 and 1600 micrograms/kg (administered, subcutaneously). Spontaneous locomotor activity was reduced at all the dose levels but forced locomotor activity was slightly reduced at 800 and 1600 micrograms/kg. The drug did not exhibit any anticonvulsant potential at any of the dose levels studied.

Efeitos da ivermectina sobre o fechamento do palato e sobre o desenvolvimento do germe dental de camundongos / Effects of ivermectin on palate closure and tooth germ development

Camundongos fêmeas prenhes foram injetadas no 14§ dia de gestaçäo com 200 µg/kg de peso corporal de ivermectina. Os filhotes foram sacrificados 1, 5 e 10 dias após o nascimento, e as cabeças processadas histologicamente para análise do palato e dos germes dentais. Os resultados näo mostraram diferenças no desenvolvimento, pois o palato estava fechado e os germes dentais dos animais tratados eram semelhantes aos dos animais controle. Desse modo, nas condiçöes experimentais deste trabalho, a ivermectina näo se mostrou tóxica às células, permitindo um desenvolvimento das estruturas analisadas com características compatíveis com as encontradas nos animais controle e com as descritas na literatura