Welfare assessment of Thoroughbred horses naturally infected with gastrointestinal parasites in Southern Brazil: Quantifying the host-parasite relationship.

Horse welfare assessment (HWA) does not account for individual or herd parasite infection. This study investigated the connection between HWA and individual parasite fecal egg count (FEC) in 90 Thoroughbred horses. All horses were naturally infected with gastrointestinal parasites and were evaluated for individual welfare indicators and FEC monthly, for 12 months. Horses were divided into three groups of 30 mares, 30 foals aged between 13 and 16 months (G2013), and 30 foals aged between two months and one year (G2014). A horse welfare protocol was developed and 1024 assessments were carried out by five trained assessors. FEC ranged from 0 to 5,760 with 98.8 % showing small strongyle eggs. Body condition scores were ideal in 94.4 % of the evaluations (n = 967), and 95.8 % of all horses had good clinical and behavioral indicators. Despite the variation in FEC, the data found no significant association between FEC and the behavioral indicators. The study suggests that FEC alone should not be used as a determinant of welfare when animals are managed with good nutritional and health management practices.

Fasciola hepatica infection in cattle and the use of simulation models for endemic areas.

Fasciolosis is a food-borne disease that causes great distress to a range of hosts, including humans. The objectives of this study were to (1) evaluate the liver damage and carcass weight of cattle naturally infected with Fasciola hepatica from the state of Rio Grande do Sul (RS), Brazil, and to (2) determine the distribution of adult flukes in 12,236 cattle liver from RS. The data from these experiments were used to calculate the overall economic loss due to F. hepatica infection. Eighteen adult Polled Hereford cows were divided into a triclabendazole (TbG) and a F. hepatica-positive group (FhG). For Experiment 1, a generalized linear mixed model revealed a statistical difference in carcass weight (49.8 kg) between TbG and FhG. The Monte Carlo analysis also revealed that the animals' weight differences were due to the disease. For Experiment 2, the prevalence of infected livers was above 16% (1904/12,236), mostly (20.1%) from the south-west region of RS. The Susceptible-infected-recovered (SIR) epidemic model revealed the evolution of the infection using a high infectivity and low recovery rate. Other distinctive scenarios that occur in RS were also established with different rates of infectivity. The economic assessment showed a potential loss of US$45 million to the beef cattle industry of RS, with an overall State cost of US$90.3 million. These novel findings reveal the importance of fasciolosis infection, which can cause a significant health condition and poor animal welfare.

Fasciola hepatica in Brazil: genetic diversity provides insights into its origin and geographic dispersion.

Fasciola hepatica is a trematode parasite that affects mammals, including humans. In Brazil, fascioliasis, a disease caused by the parasite, is of great importance. The disorder affects the welfare of the Brazilian population through impairing the agricultural production of cattle, where the disease causes weight loss as a result of liver damage. This study aimed to evaluate the genetic diversity of F. hepatica throughout Southern Brazil to determine its geographic origin and estimate the colonization route of the parasite. To accomplish these aims, flukes were collected from slaughterhouses in three endemic areas of Rio Grande do Sul and Paraná states. DNA was isolated using the phenol-chloroform protocol from single flukes and two mitochondrial genes, cytochrome oxidase subunit I (COI) and nicotinamide dehydrogenase subunit 1 (Nad1), were amplified and sequenced. Ten haplotypes of COI were found from 75 isolated parasites and the total haplotype and nucleotide diversity observed were 0.475 and 0.002, respectively. Using the Nad1 gene, we found 24 haplotypes from 79 samples, resulting in haplotype and nucleotide diversity values of 0.756 and 0.004, respectively. An analysis of molecular variance showed that 57.4% and 77.5% of variation was within populations (FST), while 9.0 and 36.8% of variation was among groups (FCT) when considering COI and Nad1 genes, respectively. For COI, the fixation index values of 0.425 and 0.368 were obtained for FST and FCT, respectively, while analysis of Nad1 0.225 and 0.089 index values were obtained for FST and FCT, respectively. We have determined that F. hepatica found in the two distinct areas originated from several geographical regions, since we found haplotypes that were shared with at least three different continents. These data are in accordance with the recent colonization of Brazil, and the recent import of cattle from South American, European and, possibly, some African countries. The observed FST and FCT values for COI and Nad1 genes of F. hepatica may be a result of limited movement of animals within states and support the lack of geographical structure of the parasite in Brazil, which are in agreement with the observed cattle production systems in this region.

Occurrence of gastrointestinal parasites in Spheniscus magellanicus (Foster, 1781) located in Pontal do Sul, PR, Brazil / Ocorrência de parasitas gastrintestinais em Spheniscus magellanicus (Foster, 1781) localizados em Pontal do Sul, PR, Brasil

Gastrointestinal parasitism is the main health problem faced by Spheniscus magellanicus, known as Magellanic penguins, in route on the Brazilian coast. The aim of this research was to report the occurrence and intensity of gastrointestinal parasites in S. magellanicus that reached Pontal do Sul, Paraná, South of Brazil. The study was performed at the Marine Study Center of the Federal University of Parana (CEM-UFPR) with 38 specimens, 31 were necropsied and seven were examined alive with coproparasitological exams. From the necropsied animals, 93.5% (29/31) were parasitized with at least one parasite species. Contracaecum pelagicum was the most prevalent 93,5% (29/31) parasite, followed by Cardiocephaloides physalis (64.5%) and Tetrabothrius lutzi (51.6%). Only one animal was free of parasites and the most infected bird had 1.076 parasites with an average of 194 worms. Willis-Mollay method revealed that 57.1% (4/7) had C. pelagicum eggs. In conclusion, the high rate of gastrointestinal parasites in S. magellanicus confirms the clinical exams, when animals had poor health conditions when they were found in the cost of Paraná. This study provides data to enrich the literature regarding the helminth fauna of the Magellanic penguins, assisting sanitary control programs in Rehabilitation Centers for Marine Animals.(AU)

As parasitoses gastrintestinais são o principal problema sanitário enfrentado pelo Spheniscus magellanicus, conhecido como pinguim-de-magalhães, que faz rota no litoral brasileiro. O objetivo desta pesquisa foi relatar a ocorrência e a intensidade de parasitas gastrintestinais em Spheniscus magellanicus encontrados em Pontal do Sul, Paraná, Sul do Brasil. O estudo foi realizado no Centro de Estudos Marinhos da Universidade Federal do Paraná, CEM-UFPR, com 38 espécimes; 31 dos quais foram necropsiados, e em sete aves vivas foram realizados exames coproparasitológicos. Do total analisado, 93,5% (29/31) aves estavam parasitadas com pelo menos uma espécie, sendo o Contracaecum pelagicum o mais prevalente, 93,5% (29/31), seguido de Cardiocephaloides physalis (64,5%) e de Tetrabothrius lutzi (51,6%). Somente um animal estava livre de parasitas e a ave mais infectada possuía 1.076 parasitas; a média foi em 194 vermes. No exame de Willis-Mollay, foi observada positividade em 57,1% (4/7) para C. pelagicum. Conclui-se que o alto índice de parasitas gastrintestinais em S. magellanicus confirma os exames clínicos que eles apresentaram, de baixa condição sanitária, quando foram encontrados no litoral do Paraná. Este estudo fornece dados que irão enriquecer a literatura sobre a helminto fauna do pinguim-de-magalhães, auxiliando programas de controle sanitário em Centros de Reabilitação de Animais Marinhos.(AU)

Modelling the spatial distribution of Fasciola hepatica in bovines using decision tree, logistic regression and GIS query approaches for Brazil.

Fascioliasis is a condition caused by the trematode Fasciola hepatica. In this paper, the spatial distribution of F. hepatica in bovines in Brazil was modelled using a decision tree approach and a logistic regression, combined with a geographic information system (GIS) query. In the decision tree and the logistic model, isothermality had the strongest influence on disease prevalence. Also, the 50-year average precipitation in the warmest quarter of the year was included as a risk factor, having a negative influence on the parasite prevalence. The risk maps developed using both techniques, showed a predicted higher prevalence mainly in the South of Brazil. The prediction performance seemed to be high, but both techniques failed to reach a high accuracy in predicting the medium and high prevalence classes to the entire country. The GIS query map, based on the range of isothermality, minimum temperature of coldest month, precipitation of warmest quarter of the year, altitude and the average dailyland surface temperature, showed a possibility of presence of F. hepatica in a very large area. The risk maps produced using these methods can be used to focus activities of animal and public health programmes, even on non-evaluated F. hepatica areas.

Duddingtonia flagrans no controle de nematoides gastrintestinais de equinos em fases de vida livre / Control of free living gastrointestinal nematodes of horses using Duddingtonia flagrans

O objetivo deste estudo foi avaliar a atividade predatória do fungo Duddingtonia flagrans contra larvas infectantes (L3) de nematoides gastrintestinais na pastagem e no bolo fecal de equinos, em um período de 21 dias. O delineamento experimental foi inteiramente ao acaso, com três grupos tratados (G1, G2 e G3) e um controle (C), com oito animais/grupo. Os tratados receberam 1,5x105; 3x105 e 6x105 clamidósporos de D. flagrans/kg-1peso vivo animal, G1, G2 e G3, respectivamente, durante 21 dias, com administração a cada três dias. Foram delimitadas 36 áreas de 1m2 cada, equivalendo a repetições em triplicata para cada grupo. As fezes foram coletadas dos animais nos dias 0 (D0), 15 (D15) e 30 (D30 = sete dias após a última administração dos tratamentos) e depositadas nessas áreas de pastagem. O número de larvas presentes nos bolos fecais e na pastagem foi avaliado após 14 e 21 dias de cada etapa de deposição. A avaliação da atividade predatória de D. flagrans na pastagem e nos bolos fecais demonstrou que a redução do número de L3 nos bolos fecais foi acompanhada pelo aumento da variável na pastagem. Não se constatou diferença significativa entre os grupos avaliados em decorrência da temperatura média registrada durante o período. As avaliações realizadas em um curto período podem ser insuficientes para a avaliação do efeito do fungo.(AU)

The aim of this study was to evaluate the predatory activity of the fungus Duddingtonia flagrans against infective larvae (L3 ) of gastrointestinal nematodes of horses in the pasture and dung patch during a period of 21 days. The experimental design was completely randomized, with three groups treated (G1, G2 and G3) and a control (C), with eight animals/group. The treated animals received G1: 1.5x105; G2: 3x105 and G3: 6x105 chlamydospores of D. flagrans/kg body weight during 21 days. The experiment ran in the environment using 36 areas of 1 m2 delimited on pasture, where stool samples were distributed for each group, in triplicates. Feces were collected from the animals at days 0 (D0), 15 (D15) and 30 (D30) and deposited on the pasture areas. After 14 and 21 days of each deposition step , the number of L 3 present in dung and pasture was evaluated. The number of L3 in the dung was accompanied by increase of the same variable in the pasture. The evaluation recorded in a short period may be insufficient to evaluate fungus development.(AU)

Atividade ovicida e larvicida do extrato hidroalcoólico de Artemisia annua sobre parasitas gastrintestinais de bovinos / Ovicidal and larvicidal activity of Artemisia annua hydroalcoholic extract against gastrointestinal parasites in cattle

Os parasitas gastrintestinais causam enorme prejuízo econômico na bovinocultura, tanto nacional como mundial, ocasionado principalmente por Bunostumom sp., Cooperia sp. e Trichostrongylus sp. O objetivo deste trabalho foi determinar a eficácia in vitro do extrato hidroalcoólico de Artemisia annua (H.7) frente a esses endoparasitas. O H.7 foi produzido com sete dias de percolação a 4ºC e posteriormente liofilizado. Com esse fitoterápico, realizaram-se testes de eclodibilidade de ovos (TEO) e de migração larvar em ágar (TMLA), com seis repetições, com concentrações crescentes (0,78 a 50mg/mL). Para analisar a composição química do fitoterápico, procedeu-se à marcha fitoquímica completa. No TEO, a eficácia variou de 94,08±2,58% na maior concentração a 15,67±0,97% na menor concentração. Já no TMLA os valores encontrados variaram de 90,05±0,55% a 4,12±0,46%. Nas análises fitoquímicas, foram encontrados diversos compostos com propriedades de combater os nematódeos, tanto direta como indiretamente. Os resultados obtidos nos testes in vitro evidenciam que o extrato produzido possui potencial de combater nematódeos gastrintestinais de bovinos. Novos estudos devem ser realizados buscando maximizar a eficácia do H.7 e de outras extrações obtidas a partir de A. annua, uma vez que foram demonstrados excelentes resultados em ambos os experimentos.

Gastrointestinal parasites cause economic losses to the cattle production, in Brazil and worldwide, mainly caused by Bunostumom sp., Cooperia sp. and Trichostrongylus sp. The aim of this study was to determine the in vitro efficacy of hydroalcoholic extract of Artemisia annua (H.7) against these parasites. The H.7 was produced after 7 days of storage at 4°C and then lyophilized. With this herbal the egg hatch test (EHT) and larval migration inhibition (LMI) were performed,in six replicates with different concentrations (0.78 to 50mg/mL). To analyze the chemistry composition the complete phytochemical screening was done. In EHT efficiency ranged from 94.08±2.58% at the highest concentration to 15.67± 0.97% in the lowest concentration. In LMI test the values ranged from 90.05±0.55% to 4.12±0.46%. Phytochemical tests showed many chemical compounds with anthelmintic properties. The results obtained in biochemical tests together with those found in in vitro tests showed that the extract produced has the potential to combat intestinal nematodes of cattle. Further studies should be conducted to maximize the effectiveness of H.7 and other extractions from A. annua, because it demonstrated excellent results in both experiments.

Alternativas para o controle de nematoides gastrintestinais de pequenos ruminantes / Alternative techniques for the control of gastrointestinal nematodes in small ruminants

Sheep and goat farming requires an efficient management program, due to losses caused by parasites in susceptible animals. Many factors may collaborate to improve infection tolerance in the herd, such as: genetics, nutrition, physiological status, and age. The problem caused by resistance to antihelmintic agents has led to the spread of alternative techniques for parasite controls. The latest strategies include selective treatment with the FAMACHA method, phytotherapy, biological control with predatory fungi, and strategies that still await scientific confirmation, such as homeopathy, the dilution of resistance with the introduction of susceptible parasites, and the combination of drugs without antihelmintic effect. The main objective of these methods is to reduce the usage of antiparasitic agents, thus slowing the development of resistance and promoting the better use of effective products and newly released products. The objective of this article is to describe techniques for controlling nematodes in small ruminants, and it is aimed at technicians interested in increasing their knowledge about the mechanisms of resistance to antihelmintic agents as well as alternatives to the use of these products.

A criação de ovinos e caprinos depende de um manejo eficiente, devido, principalmente, ao prejuízo causado por parasitos em animais susceptíveis. Vários fatores colaboram para que os animais tolerem as infecções parasitárias, como: genética, nutrição, estado fisiológico e idade. O grave problema causado pela resistência anti-helmíntica promoveu a difusão de técnicas alternativas de controle parasitário. Dentre essas novas estratégias incluem-se a adoção do tratamento parcial seletivo com o método FAMACHA, fitoterapia, controle biológico com o uso de fungos nematófagos e estratégias que ainda necessitam de mais dados como a homeopatia, a diluição da resistência com a introdução de parasitos sensíveis e a combinação de produtos químicos sem efeito antiparasitário. O objetivo central destes métodos é reduzir o uso de antiparasitários, retardando o desenvolvimento da resistência, e promover melhor utilização de produtos ainda eficazes na propriedade e de novos produtos que venham a ser lançados. Este artigo abordará as técnicas descritas acima para o controle de nematoides de pequenos ruminantes e é direcionado aos técnicos interessados em ampliar seu conhecimento sobre os mecanismos de resistência dos parasitos aos anti-helmínticos e de alternativas ao uso desses produtos.

Avaliação do sistema integrado de controle parasitário em uma criação semi-intensiva de caprinos na região de Santa Catarina / Evaluation of the integrated parasite control in a semi-intensive goat farming in the region of Santa Catarina

O objetivo deste trabalho foi subsidiar um programa sustentável de controle parasitário em um rebanho caprino em São Francisco do Sul, SC, aplicando o Sistema Integrado de Controle Parasitário (SICOPA). Foram utilizados 63 caprinos, distribuídos em nove grupos para teste de eficácia de anti-helmínticos, exames de contagem de ovos por grama de fezes (OPG), coprocultura, grau Famacha, micro-hematócrito, escore corporal e contagem de larvas no pasto. A redução da OPG 15 dias pós-tratamento com closantel, albendazole, nitroxinil, levamisole, ivermectina+levamisole+albendazol, moxidectina, ivermectina, abamectina e sulfóxido de albendazol foi de 89, 83, 65, 63, 57, 37, 31, 0 e 0%, respectivamente. A média de graus Famacha 1 e 2 no estudo foi de 81%, e de graus 3, 4 e 5 foi de 19%, e não se observou correlação com os valores do micro-hematócrito em razão da prevalência de Trichostrongylus sp. (92%). A contagem de larvas infectantes (L3) na pastagem apresentou valores abaixo de 1000 L3/kg/MS, predominando Trichostrongylus sp. Nenhuma das drogas testadas foi considerada eficaz, evidenciando resistência parasitária múltipla. A aplicação de ferramentas do SICOPA e a adoção de estratégias de manejo e nutrição adequados são fundamentais para estabelecer um programa sanitário sustentável.

The objective of this study was to subsidize a sustainable parasite control program in a flock of goats in São Francisco do Sul, SC, Brazil, applying the integrated system for parasite control. Sixty three adult animals were used in nine groups to perform an anthelmintic efficacy test, faecal egg count (FEC), Famacha method, haematocrit, body condition score, coproculture, and the presence of larvae on pasture. Drug efficacy measured by FEC 15 days post-treatment with closantel, ivermectin + Levamisole + albendazole, albendazole, nitroxinyl, levamisol, abamectin, ivermectin, moxidectin and albendazole was 85, 57, 83, 65, 63, 31, 28, 24 and 0%, respectively. The Famacha score 1 or 2 was given to 81% and scores 3, 4 or 5 were given to 19%, without significant correlation with haematocrit values since the predominant was Trichostrongylus sp. (92%). The count of infective larvae levels on pasture revealed values below 1000 L3/kg/DM predominantly Trichostrongylus sp. None of the tested drugs was effective, showing multiple parasitic resistance. The correct application of the SICOPA and adoption of management strategies and proper nutrition are essential to establish a sustainable health program.

Mapping risk of bovine fasciolosis in the south of Brazil using Geographic Information Systems.

Fasciolosis, caused by Fasciola hepatica, is an endemic disease of ruminants that occurs in several countries of South America where it can lead to decreased production and fertility and, in severe cases, animal death. Although very prevalent, information on the epidemiology of the disease is incomplete in Brazil. The objective of the present study was to define the prevalence of F. hepatica in the livers of cattle from slaughterhouses and correlate the data with the animal's origin (climate and altitude) using a Geographic Information System (GIS). The data was used to create an epidemiological map of fasciolosis by state (Rio Grande do Sul, Santa Catarina, Paraná), by municipality (n=530) and by year (2003-2008). Information was analyzed using a databank from slaughterhouses with Federal Inspection Services of the Ministry of Agriculture. The highest cattle infection rate was found in the two most Southern states of Rio Grande do Sul (18.7%) and Santa Catarina (10.1%). Animals from the Campanha region of Rio Grande do Sul and from the central coast area of Santa Catarina had prevalences of greater than 40%. Cattle from low altitudes municipalities were significantly more likely to have the disease (p<0.05). No significant differences were found between high or low prevalence and ambient temperatures. Risk maps resulting from this study provide information on the epidemiology and transmission of F. hepatica in Southern Brazil needed for design of appropriate control measures to control economic impacts. F. hepatica may represent an important source of zoonotic infection of humans as well; therefore these findings may be complemented by future studies on human infections in high risk areas.

Frequency of treatment and production performance using the FAMACHA method compared with preventive control in ewes.

The rapid escalation of anthelmintic resistance in parasites suggests the adoption of different strategies for parasite control in small ruminants instead of relying only on the use of chemicals. The integrated system of parasite control (SICOPA) program uses the FAMACHA method, which is used to separately identify sheep that are resistant/resilient or susceptible to Haemonchus contortus, or together with other management practices, such as pasture rotation or the monitoring of drug efficacy. The objective of this work was to compare two methods of parasite control in ewes. A flock of ewes (n=90) of Ile de France and Texel breeds was monitored from August 2001 to July 2003 under suppressive treatment (45-day treatment interval) and from August 2003 to July 2006 under the partial selective regimen based on FAMACHA evaluations. Fecal samples were collected for fecal egg counts (EPG) and larval identification to monitor infection during the 5-year period. After the partial selective evaluations, an average of 19% of the animals was treated each year between 2003 and 2006. The reproductive indexes of parturition (89%), birth rate (119%), lamb weight (4.1 kg) and lamb mortality (5.2%) were similar under the partial selective regimen and the previous suppressive treatment period. H. contortus was the most prevalent species, and EPG values were not statistically different across periods or among treatment regimes. The results demonstrate that the FAMACHA method allowed a large number of naturally infected ewes to be raised with reduced anthelmintic treatment without a negative impact on their reproductive indexes. It is indicated, though, that this method be applied together with other available strategies. Culling was based on clinical signs and ranged from 5.5 to 20% per year. The results suggest that an important host-specific effect may have regulated the rate of infection, expressing the resistant/resilient characteristic within the flock with an important economical benefit.

Suppressive treatment of abamectin against Dictyocaulus viviparus and the occurrence of resistance in first-grazing-season calves.

Dictyocaulus viviparus cause severe lung infections and are endemic in some areas of temperate and tropical countries. Treatment is based on strategic nematode control programs using potent compounds with no reports of drug failure. Macrocyclic lactones (MLs) are available at different concentrations and combinations and have being used heavily by producers. The objective of this work was to determine the efficacy of the MLs ivermectin, moxidectin, doramectin, and abamectin, and the combination ivermectin plus abamectin in naturally infected calves (n=70). Initial infection was determined by necropsy of tracer animals. Faecal larval counts determined that none of the compounds used was able to eliminate D. viviparus for up to 28 days after treatment. The "Area Nova" strain was isolated for future work.

Novel approaches to control of parasites­a workshop.

With the advent of helminth parasite populations that have developed resistance to anthelmintics over the last decade or so, especially in small ruminants, sustainable productivity has been threatened. This workshop on novel approaches to control was held at the 19th International Conference of the World Association for the Advancement of Veterinary Parasitology (WAAVP) at New Orleans,LA, USA, during 10­14 August 2003. The workshop was organized and chaired by J.E. Miller and P.J. Waller. Novel or alternative approaches to control have been the focus of research (basic and applied) in many parts of the world. The objective of the workshop was to discuss where we have been and what direction(s) appears to be viable for both the short and long term future. In the long term, all represented regions at the workshop have promulgated programs where breeding for resistance may be the best approach as genes for resistance can be fixed in host populations. However,it does take many years to achieve results and the question of tradeoff concerning alteration of production traits needs further evaluation. Vaccination, especially against Haemonchus contortus,has been a thrust of laboratories in Scotland and Australia where natural "hidden gut" antigens have shown promise, but recombinant products have yet to be developed. In Europe, North and South America, Australia, South Africa and Asia, biocontrol using the nematode-trapping fungus Duddingtonia flagrans has been shown to be effective under experimental conditions, but some field evaluations have been disappointing. Most recently, the FAMACHA system was developed in South Africa. This system is directly and immediately applicable to all regions where H. contortus is a problem. Although not a new or novel approach, copper-oxide wire particles have been revived as a means to control H. contortus.Work being done in Europe, North and South America,South Africa and Australia have shown very encouraging results and can probably be considered the best short term approach available. However, caution needs to be considered in sheep to avoid potential copper toxicity problems. Work in New Zealand, Scotland and the US with forages and feeds containing condensed tannins have shown some limited control. Many laboratories have demonstrated that adequate and balanced nutrition programs are also important to maintain mechanisms that combat infections. Overall, no one approach alone is the answer. Approaches that are integrated, including "smart" use of anthelmintics, are necessary.

Tick control: an industry point of view.

The development of new acaricides is a long and very expensive process. Worryingly, there is increasing resistance to available acaricides worldwide leading to the real possibility that our dwindling supply of effective acaricides will be exhausted unless action is taken to increase the number of new acaricidal products and reduce the rate of resistance development. In 1995, eight major animal health pharmaceutical companies formed the Veterinary Parasite Resistance Group (VPRG) to act as an expert consultative group to guide the FAO in resistance management and collaborate in the prudent use of acaricides. In this paper, members of the VPRG discuss the problems and processes in acaricide development, resistance in the field to commonly used acaricides and the different considerations when targeting the cattle and pet market, and give their view of the future for tick control from the perspective of the animal health industry.

Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep.

P-Glycoprotein (P-GP) is a transport protein that participates in the mechanism of active secretion of different molecules from the bloodstream to the gastrointestinal tract. The aim of the current work was to evaluate the effect of verapamil, a P-GP substrate, on the pharmacokinetic behaviour of the anthelmintics ivermectin and moxidectin in sheep. Thirty-two sheep were divided into four groups and treated orally with either ivermectin or moxidectin alone (200 micro g/kg) or co-administered with verapamil at 3 mg/kg (three times at 12 h intervals). Blood samples were collected over 30 days post-treatment and plasma was analysed to determine ivermectin and moxidectin concentrations by HPLC. The ivermectin peak concentration was significantly higher ( P=0.048) after ivermectin plus verapamil, compared with the ivermectin alone treatment. Ivermectin plasma availability was significantly higher following co-administration ( P=0.022). Verapamil had no effect on the kinetics of moxidectin. The significant alteration in the plasma disposition of ivermectin in sheep induced by verapamil, possibly due to interference with a P-GP-mediated elimination mechanism, may have an important impact on efficacy against resistant- or rate-limiting-parasites and on the persistency of its antiparasitic activity.

Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus).

The development of anthelmintic resistance is making parasite control in small ruminants problematic. Following the discovery that the drug transporter P-glycoprotein may be involved in macrocyclic lactone resistance in Haemonchus contortus, we determined the effect of two multidrug-resistance modulators, verapamil and CL347,099, on the efficacy of ivermectin and moxidectin against unselected and drug-selected strains of H. contortus. CL347,099 is an analog of verapamil that has multidrug-resistance properties but weaker calcium-channel-blocking activity than the parent drug. The combinations of verapamil with either ivermectin or moxidectin significantly reduced worm counts of the selected strains as compared with the untreated controls, whereas ivermectin or moxidectin alone did not significantly reduce worm counts as compared with the untreated controls. The CL347,099 plus moxidectin combination was significantly more efficacious than moxidectin alone against the ivermectin-selected strain. The drug-combination regimes were without adverse effect on the jirds. However, higher levels of verapamil (> or =40 mg/kg) produced some toxicity.

Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations.

Ivermectin resistance in the nematode Haemonchus contortus has been reported in many parts of the world and many ivermectin resistant isolates have been found to have reduced sensitivity to moxidectin. However, it is unclear whether parasites that are selected with moxidectin would demonstrate reduced sensitivity to ivermectin. In this study, the effects of moxidectin and ivermectin on an unselected strain and a strain of H. contortus derived from the unselected strain but selected over 14 generations with moxidectin, were compared in jirds. The recovery of adult worms and fourth stage (L4) larvae following treatment were compared between strains and anthelmintics. Moxidectin-selected H. contortus showed reduced sensitivity to ivermectin as well as to moxidectin. Doses of 0.1 mg/kg of moxidectin and 0.4 mg/kg of ivermectin were necessary to obtain an efficacy of 95% or above against the moxidectin-selected strain of H. contortus compared with 0.025 mg/kg for moxidectin and 0.1 mg/kg for ivermectin required for a similar efficacy in the unselected strain.

Persistent efficacy of doramectin pour-on against artificially induced infections of nematodes in cattle.

Two studies were conducted to determine the persistent efficacy of doramectin pour-on against an artificial, trickle challenge of mixed nematodes in calves. In each study, 42, 4-8 months old calves were randomly assigned into four groups of 10 animals each (T1-T4), plus two larval-viability monitor animals. All animals were treated with fenbendazole (10 mg kg(-1)) 14 days prior to the start of the study to clear any existing infection. Doramectin pour-on at 500 microg kg(-1) was used on each animal in Groups T2, T3, and T4 with intervals of 1 week (Day 0, 7, and 14, respectively). Calves in Group T1 were treated with saline solution on Day 0 and at the same volumetric rate (1 ml 10 kg(-1)) as the doramectin treated animals. All treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Subsequently, trickle inoculations with infective larvae were administered to all calves for 22 consecutive days (Days 14-35). Doramectin pour-on provided > or = 91.9% efficacy against challenge with Dictyocaulus viviparus, Haemonchus spp., and Ostertagia ostertagi for up to 35 days post-treatment and against challenge with Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum for up to 28 days post-treatment.