Flavio Echevarria - Academia.edu (original) (raw)

Papers by Flavio Echevarria

Research paper thumbnail of Detectando resistência anti-helmíntica

A verminose e um dos principais entraves na producao ovina da Regiao Sul do Brasil. Tratamentos q... more A verminose e um dos principais entraves na producao ovina da Regiao Sul do Brasil. Tratamentos quimioterapicos tem solucionado o problema, no entanto a crescente resistencia dos parasitas aos antihelminticos utilizados exige novas alternativas de controle.

Research paper thumbnail of Treatment of chronic fasciolosis in cattle

Estudou-se o efeito do tratamento da fasciolose crônica em vacas das raças Hereford, A. Angus e S... more Estudou-se o efeito do tratamento da fasciolose crônica em vacas das raças Hereford, A. Angus e Shorthorn naturalmente infectadas com Fasciola hepatica. Distribuíram-se os animais em dois grupos: grupo-controle, com 7,01 ovos por grama de fezes e peso médio de 294,7 kg ± 46,6, e grupo tratado, com 6,68 ovos por grama de fezes e peso médio de 288 kg ± 31,4. A pesquisa teve a duração de 232 dias, sendo, os animais, pesados e coletados bimestralmente. Nessas mesmas datas, o grupo tratado recebia Niclofolan 4% injetável na dose de 2 ml para cada 100 kg de peso vivo. Todos os animais foram abatidos, em frigorífico, 41 dias após a quarta medicação do lote tratado. Foram pesados os fígados, e colhidas as fascíolas. O grupo tratado não apresentou exemplar de F. hepatica, enquanto que o testemunha evidenciou uma média de 23,9 fascíolas/fígado. Ambos os grupos mostraram lesões crônicas e calcificações dos canais hepáticos. Não houve diferenças significativas (P<0,05) no peso das carcaças, ...

Research paper thumbnail of Anthelmintic resistance in Haemonchus contortus

ProQuest Dissertations & Theses,, 1991

Studies were carried out on possible control measures using different drugs or management procedu... more Studies were carried out on possible control measures using different drugs or management procedures which could help in the control of anthelmintic resistance in sheep nematodes, particularly that of ivermectin (IVM) resistance in Haemonchus contortus. Other aspects such as selection for IVM resistance, the effect of IVM on susceptible and resistant larval stages of H. contortus and the survival of their free-living stages under laboratory or field conditions were also investigated. In addition, a computer model to simulate the development of anthelmintic resistance in breeding ewes was examined incorporating Brazilian field data. Isoenzyme profiles of susceptible and resistant strains were also analysed. Three strains of H. contortus were mainly used in these studies: one susceptible to all of the common anthelmintics; the same strain selected for resistance to IVM under laboratory conditions and a field strain resistant to a wide range of anthelmintics, including IVM, which was isolated from a farm in South Africa. The IVM selected strain was derived experimentally from the susceptible strain serially passaged in lambs and submitted to successive doses of IVM at 0.02mg/kg. Although the drug was highly efficient until the seventh passage and treatment, the progeny of the adult worms which survived this treatment were highly resistant. Under controlled laboratory conditions, an experiment was set up to look at the development of eggs and larvae of the original susceptible strain in comparison to the selected strain. This showed that at 22°C the resistant strain had a higher percentage development v from eggs to the infective stage while at 27°C the results were reversed, i.e., a significantly higher percentage of larvae developed from eggs of the original susceptible strain. Under field conditions of Southern Brazil, eggs from two strains of H. contortus, one resistant and another susceptible to IVM, were seeded on to pasture plots during three summer months. The results of these field studies indicated that resistant larvae survived better after only one of the contamination periods; at other times there appeared to be no significant difference in development rates. In all cases the recovery rate was low, indicating that during the summer months in Southern Brazil there is limited survival and development of eggs and larvae on pasture and that most of the parasite population is present in sheep during this period. An experiment designed to exploit the residual anthelmintic effects of salicylanilide/substituted phenols, strategically administered during the summer in the conditions of Southern Brazil, was successful in controlling an IVM resistant population of H. contortus thus preventing the predictable outbreaks of haemonchosis in autumn. Of these drugs, nitroxynil gave the best results. Another approach examined as an alternative method in the control of sheep nematodes under Brazilian conditions was the use of "safe pastures", i.e., areas with a low level of infectivity where young susceptible sheep could be grazed with a low risk of infection. In this case an infected pasture, reseeded after a crop of soya bean, was tested for larval infectivity in spring using lamb and calf tracers. After harvesting a soya bean crop from this area, it was found to be virtually negative for H. contortus and other important vi viii LIST OF CONTENTS ACKNOWLEDGEMENTS DECLARATION SUMMARY LIST OF TABLES LIST OF FIGURES LIST OF APPENDICES CHAPTER 1-INTRODUCTION AND LITERATURE REVIEW CHAPTER 2-GENERAL MATERIAL AND METHODS CHAPTER 3-STUDIES ON FACTORS AFFECTING IVERMECTIN RESISTANT Haemonchus contortus IN SHEEP Exp. 3.1-Efficacy of other anthelmintics on ivermectin resistant adult Haemonchus contortus Exp. 3.2-The response to ivermectin treatment of parasitic stages of Haemonchus contortus resistant or susceptible to ivermectin Exp. 3.3-Could the strategic use of salicylanilides control an ivermectin resistant strain of Haemonchus contortus in grazing lambs in Brazil? Exp. 3.4-How effective are reseeded pastures as an aid in the control of gastrointestinal nematodes in sheep? CHAPTER 4-STUDIES ON THE BIOLOGY OF IVERMECTIN RESISTANT Haemonchus contortus Exp. 4.1-Laboratory selection for ivermectin resistance in Haemonchus contortus Exp. 4.2-The pattern of faecal egg output in lambs infected with a multiple resistant strain of Haemonchus contortus after treatment with albendazole Exp. 4.3-The survival and development of ivermectin resistant or susceptible strains of Haemonchus contortus under field and laboratory conditions Exp. 4.4-Isoenzyme analysis of Haemonchus contortus strains either resistant or susceptible to ivermectin CHAPTER 5-COMPUTER MODELLING FOR ANTHELMINTIC RESISTANCE i Exp. 5.1-A drug action model in genetic selection for anthelmintic resistance in Haemonchus contortus CHAPTER 6-GENERAL DISCUSSION AND CONCLUSIONS REFERENCES APPENDICES x 122 xii LIST OF FIGURES ig. 1.1 Life cycle of H. contortus 4 ig-1.2 Location of four epidemiological studies in Brazil 46 ig-1.3 Climatic conditions in Brazil-rainfall ig-1.4 Climatic conditions in Brazil-temperatures ig-1.5 Epidemiology in Bage-H. contortus ig-1.6 Epidemiology in Uruguaiana-H. contortus ig-1.7 Epidemiology in Guaiba-//. contortus ig. 1.8 Epidemiology in Itaqui-H. contortus ig-1.9 Epidemiology in Bage-other nematodes ig-1.10 Epidemiology in Uruguaiana-other nematodes ig-1.11 Epidemiology in Guaiba-other nematodes ig-1.12 Epidemiology in Itaqui-other nematodes ig. 3.3.1 Worm egg counts from permanent grazers in Zone 1 ig-3.3.2 Worm egg counts from permanent grazers in Zone 2 ig. 3.3.3 Packed cell volume (%) from permanent grazers in Zone 1 ig. 3.3.4 Packed cell volume (%) from permanent grazers in Zone 2 ig. 3.3.5 Body weights from permanent grazers in Zone 1 ig. 3.3.6 Body weights from permanent grazers in Zone 2 ig. 4.1.1 Worm egg counts after IVM treatment on R or S H. contortus ig. 4.2.1 Worm egg counts after ABZ treatment on a strain of H. contortus 131 ig. 4.2.2 Haemonchus infective larvae (L3) recoveries after albendazole treatment 131 ig. 4.3.1 Development of Haemonchus L3 at 22°C 146 x iii xiv

Research paper thumbnail of Nematódeos resistentes a anti-helmíntico em rebanhos de ovinos e caprinos do estado do Ceará, Brasil

Ciência Rural, 2003

O controle do parasitismo por nematódeos gastrintestinais é feito basicamente com a utilização de... more O controle do parasitismo por nematódeos gastrintestinais é feito basicamente com a utilização de anti-helmínticos. Falhas no controle são o primeiro sinal do aparecimento de resistência anti-helmíntica. A real situação da prevalência da resistência anti-helmíntica, em fazendas comerciais de criação de ovinos e caprinos no Brasil, é desconhecida. Esse experimento teve como objetivo, estimar a ocorrência de resistência ao oxfendazol, levamisol e ivermectina em propriedades comerciais de criação de ovinos e caprinos, na região do médio e baixo Jaguaribe, através do teste de redução na contagem de ovos nas fezes acompanhados de coproculturas. O trabalho foi realizado em 25 criações, sendo 16 de ovinos, 7 de caprinos e uma de ovinos e caprinos. Os dados obtidos foram analisados pelo programa estatístico RESO (1989). A prevalência de nematódeos resistentes ao oxfendazol, levamisol e ivermectina em ovinos foi de 88%, 41% e 59%, e em caprinos de 87,5%, 75% e 37,5%, respectivamente. Observo...

Research paper thumbnail of Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

Experimental Parasitology, 2004

The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazo... more The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n ¼ 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO 2) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO 2 were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (<24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.

Research paper thumbnail of The fitness of free-living stages of strains of Ostertagia spp., susceptible or resistant to benzimidazole anthelmintics

Research paper thumbnail of Tratamento de fasciolose crônica em bovinos

Pesquisa Agropecuaria Brasileira, 1979

Estudou-se o efeito do tratamento da fasciolose cronica em vacas das racas Hereford, A. Angus e S... more Estudou-se o efeito do tratamento da fasciolose cronica em vacas das racas Hereford, A. Angus e Shorthorn naturalmente infectadas com Fasciola hepatica . Distribuiram-se os animais em dois grupos: grupo-controle, com 7,01 ovos por grama de fezes e peso medio de 294,7 kg ± 46,6, e grupo tratado, com 6,68 ovos por grama de fezes e peso medio de 288 kg ± 31,4. A pesquisa teve a duracao de 232 dias, sendo, os animais, pesados e coletados bimestralmente. Nessas mesmas datas, o grupo tratado recebia Niclofolan 4% injetavel na dose de 2 ml para cada 100 kg de peso vivo. Todos os animais foram abatidos, em frigorifico, 41 dias apos a quarta medicacao do lote tratado. Foram pesados os figados, e colhidas as fasciolas. O grupo tratado nao apresentou exemplar de F. hepatica, enquanto que o testemunha evidenciou uma media de 23,9 fasciolas/figado. Ambos os grupos mostraram lesoes cronicas e calcificacoes dos canais hepaticos. Nao houve diferencas significativas (P<0,05) no peso das carcacas, no peso dos figados e no ganho de peso dos grupos. O grupo tratado ganhou, em media, 116,6 kg ± 15,4, e o testemunha, 114,3 kg ± 37,7. Tendo em vista os resultados obtidos, nao e economico o tratamento contra a fasciolose em animais adultos em regime de engorda que ja apresentam lesoes hepaticas cronicas e irreversiveis.

Research paper thumbnail of Uso de anti-helmíntico em bovinos pela via intra-ruminal

Pesquisa Agropecuaria Brasileira, 1980

Research paper thumbnail of Susceptibilidade de Haemonchus spp. em bovinos ao tratamento anti-helmíntico com albendazole e oxfendazole

Pesqui Vet Bras, Jun 1, 1990

Research paper thumbnail of Model predictions for anthelmintic resistance amongst Haemonchus contortus populations in southern Brazil

A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK she... more A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.

Research paper thumbnail of Lack of negative effects of the biological control agent Duddingtonia flagrans on soil nematodes and other nematophagous fungi

Journal of Helminthology, 2015

The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sh... more The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sheep nematodes were evaluated in two regions. Non-supplemented faeces and faeces from sheep supplemented with D. flagrans were deposited three times on pasture plots and samples were collected 7 and 14 days post-deposition. Samples were cultured in agar-water (2%) with Panagrellus spp. to recover D. flagrans and other nematophagous fungi, and soil nematodes were extracted using Baermann funnels and counted. No significant differences in the populations of soil nematodes and fungi colonizing sheep faeces (P > 0.05) were observed between supplemented and non-supplemented groups, except in one sample. The topsoil in contact with the faeces was sampled 1–4 months post-deposition, revealing that, with one exception, D. flagrans did not persist in soil beyond 2 months post-deposition. Duddingtonia flagrans does not affect faecal colonization by other fungi and soil nematodes and, once deploy...

Research paper thumbnail of Ação do Disofenol e do Niclofolan em bovinos

Pesquisa Agropecuaria Brasileira, 1979

Research paper thumbnail of Cobre no controle da verminose gastrintestinal em ovinos

Ciência Rural, 2004

Este estudo teve o objetivo de verificar o tempo de proteção do cobre contra reinfecções por helm... more Este estudo teve o objetivo de verificar o tempo de proteção do cobre contra reinfecções por helmintos gastrintestinais de ovinos em pastejo. Foram utilizados 32 ovinos da raça Corriedale, com aproximadamente 18 meses de idade, mantidos em campo nativo naturalmente contaminado por trichostrongilídeos. Os animais foram pesados e dosificados. Após, foram alocados a quatro grupos experimentais: T I (tratado com cobre e necropsiado no 28ºdia); T II (sem cobre e necropsiado no 28º dia); T III (tratado com cobre e necropsiado no 56ºdia); T IV (sem cobre e necropsiado no 56º dia). Os grupos T I e T III receberam, via oral, uma cápsula gelatinosa de quatro gramas, contendo 3,4 gramas de óxido de cobre. Os ovinos foram avaliados semanalmente através de contagem de ovos por grama de fezes (OPG), volume globular (VG), aspartato aminotransferase (AST) e concentrações de cobre no plasma. Ao abate, foram determinados: carga parasitária, concentrações de cobre no fígado e peso dos fígados. Os resu...

Research paper thumbnail of Laboratory selection for ivermectin resistance in Haemonchus contortus

Veterinary Parasitology, 1993

A strain of Haemonchus contortus, susceptible to ivermectin (IVM), was submitted to a selection p... more A strain of Haemonchus contortus, susceptible to ivermectin (IVM), was submitted to a selection procedure using IVM at 0.02 mg kg-1 during nine successive passages in lambs. Treatment reduced worm egg counts (epg) by more than 99% up to the seventh passage, but thereafter there was no significant reduction in epg. The efficacy of ivermectin against the ninth selected generation compared with the original susceptible strain was assessed. The results showed that animals infected with the selected strain and treated with IVM did not show any significant reduction (P &gt; 0.05) in epg compared with a 99.9% reduction in the susceptible group. At necropsy, post-treatment worm burdens confirmed that the selection pressure applied to the original strain had been successful in stimulating resistance to IVM.

Research paper thumbnail of Model predictions for anthelmintic resistance amongst Haemonchus cortortus populations in southern Brazil

Veterinary Parasitology - VET PARASITOL, 1993

A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK she... more A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.

Research paper thumbnail of Isoenzyme analysis of Haemonchus contortus resistant or susceptible to ivermectin

Veterinary Parasitology, 1992

Three different strains of Haemonchus contortus (susceptible to ivermectin, S-IVM; selected for r... more Three different strains of Haemonchus contortus (susceptible to ivermectin, S-IVM; selected for resistance to ivermectin, R-IVM; a multiple resistant strain, i.e. resistant to benzimidazole and ivermectin, R-IVM/SA) were examined for isoenzyme variation by starch gel electrophoresis. Using stains for seven enzymes separated in five different buffer systems, no differences in the electrophoretic mobility could be detected between any of the strains. Results demonstrate a low level of enzyme variation in H. contortus and no differences in enzyme electrophoretic profile between IVM-sensitive and IVM-resistant parasites. Differences between the ivermectin-sensitive and both ivermectin-resistant strains were observed with the propionyl esterases and although some of the differences are probably associated with benzimidazole resistance, others are associated with resistance to ivermectin. The three strains of H. contortus are generally identical; however, differences between all strains of H. contortus and a strain of Dictyocaulus viviparus were detected.

Research paper thumbnail of The efficacy of monepantel, an amino-acetonitrile derivative, against gastrointestinal nematodes of sheep in three countries of southern Latin America

Research paper thumbnail of Worm burden and immunological responses in Corriedale and Crioula Lanada sheep following natural infection with< i> Haemonchus contortus</i>

The effects of natural infection with Haemonchus contortus were compared in 15 Corriedale lambs a... more The effects of natural infection with Haemonchus contortus were compared in 15 Corriedale lambs and 18 Crioula Lanada lambs kept in the grazing conditions after weaning. The following parameters were assessed weekly for 9 consecutive weeks: number of eggs per gram of feces (EPG), packed cell volume (PCV), total serum proteins (TSP) and albumin (ALB). At 10 weeks, the animals

Research paper thumbnail of Nematodes resistant to anthelmintics in sheep and goat flock in the State of Ceará, Brazil

Ciência Rural, 2003

Nematódeos resistentes a anti-helmínticos em rebanhos de ovinos e caprinos do Estado do Ceará, Br... more Nematódeos resistentes a anti-helmínticos em rebanhos de ovinos e caprinos do Estado do Ceará, Brasil.

Research paper thumbnail of The prevalence of anthelmintic resistance in nematode parasites of sheep in Southern Latin America: Brazil

Veterinary Parasitology, 1996

South America has a large population of small ruminants. Currents estimates are approximately 100... more South America has a large population of small ruminants. Currents estimates are approximately 100 million sheep and 23 million goats. A large percentage of these flocks are raised in the humid tropics/sub-tropics. Nematode parasitism is singly the most important disease of these animals and typically farmers resort to frequent anthelmintic treatment in attempts to control this problem. Because of this reliance on drugs, price consideration is an important determinant in a farmer&#39;s choice of anthelmintic. In some circumstances, this has led to unethical practices of drug adulteration and substitution, or the offering to farmers of cheap, sub-standard generic products. The prevalence of anthelmintic resistance has not been investigated in any widespread sense in South America, although some of the first reports of resistance were made in southern Brazil almost 30 years ago. The following series of papers outline surveys conducted in the humid topics/sub-tropics of southern Latin America to assess the significance of resistance to the broad-spectrum anthelmintic groups in nematode parasites of sheep flocks.

Research paper thumbnail of Detectando resistência anti-helmíntica

A verminose e um dos principais entraves na producao ovina da Regiao Sul do Brasil. Tratamentos q... more A verminose e um dos principais entraves na producao ovina da Regiao Sul do Brasil. Tratamentos quimioterapicos tem solucionado o problema, no entanto a crescente resistencia dos parasitas aos antihelminticos utilizados exige novas alternativas de controle.

Research paper thumbnail of Treatment of chronic fasciolosis in cattle

Estudou-se o efeito do tratamento da fasciolose crônica em vacas das raças Hereford, A. Angus e S... more Estudou-se o efeito do tratamento da fasciolose crônica em vacas das raças Hereford, A. Angus e Shorthorn naturalmente infectadas com Fasciola hepatica. Distribuíram-se os animais em dois grupos: grupo-controle, com 7,01 ovos por grama de fezes e peso médio de 294,7 kg ± 46,6, e grupo tratado, com 6,68 ovos por grama de fezes e peso médio de 288 kg ± 31,4. A pesquisa teve a duração de 232 dias, sendo, os animais, pesados e coletados bimestralmente. Nessas mesmas datas, o grupo tratado recebia Niclofolan 4% injetável na dose de 2 ml para cada 100 kg de peso vivo. Todos os animais foram abatidos, em frigorífico, 41 dias após a quarta medicação do lote tratado. Foram pesados os fígados, e colhidas as fascíolas. O grupo tratado não apresentou exemplar de F. hepatica, enquanto que o testemunha evidenciou uma média de 23,9 fascíolas/fígado. Ambos os grupos mostraram lesões crônicas e calcificações dos canais hepáticos. Não houve diferenças significativas (P<0,05) no peso das carcaças, ...

Research paper thumbnail of Anthelmintic resistance in Haemonchus contortus

ProQuest Dissertations & Theses,, 1991

Studies were carried out on possible control measures using different drugs or management procedu... more Studies were carried out on possible control measures using different drugs or management procedures which could help in the control of anthelmintic resistance in sheep nematodes, particularly that of ivermectin (IVM) resistance in Haemonchus contortus. Other aspects such as selection for IVM resistance, the effect of IVM on susceptible and resistant larval stages of H. contortus and the survival of their free-living stages under laboratory or field conditions were also investigated. In addition, a computer model to simulate the development of anthelmintic resistance in breeding ewes was examined incorporating Brazilian field data. Isoenzyme profiles of susceptible and resistant strains were also analysed. Three strains of H. contortus were mainly used in these studies: one susceptible to all of the common anthelmintics; the same strain selected for resistance to IVM under laboratory conditions and a field strain resistant to a wide range of anthelmintics, including IVM, which was isolated from a farm in South Africa. The IVM selected strain was derived experimentally from the susceptible strain serially passaged in lambs and submitted to successive doses of IVM at 0.02mg/kg. Although the drug was highly efficient until the seventh passage and treatment, the progeny of the adult worms which survived this treatment were highly resistant. Under controlled laboratory conditions, an experiment was set up to look at the development of eggs and larvae of the original susceptible strain in comparison to the selected strain. This showed that at 22°C the resistant strain had a higher percentage development v from eggs to the infective stage while at 27°C the results were reversed, i.e., a significantly higher percentage of larvae developed from eggs of the original susceptible strain. Under field conditions of Southern Brazil, eggs from two strains of H. contortus, one resistant and another susceptible to IVM, were seeded on to pasture plots during three summer months. The results of these field studies indicated that resistant larvae survived better after only one of the contamination periods; at other times there appeared to be no significant difference in development rates. In all cases the recovery rate was low, indicating that during the summer months in Southern Brazil there is limited survival and development of eggs and larvae on pasture and that most of the parasite population is present in sheep during this period. An experiment designed to exploit the residual anthelmintic effects of salicylanilide/substituted phenols, strategically administered during the summer in the conditions of Southern Brazil, was successful in controlling an IVM resistant population of H. contortus thus preventing the predictable outbreaks of haemonchosis in autumn. Of these drugs, nitroxynil gave the best results. Another approach examined as an alternative method in the control of sheep nematodes under Brazilian conditions was the use of "safe pastures", i.e., areas with a low level of infectivity where young susceptible sheep could be grazed with a low risk of infection. In this case an infected pasture, reseeded after a crop of soya bean, was tested for larval infectivity in spring using lamb and calf tracers. After harvesting a soya bean crop from this area, it was found to be virtually negative for H. contortus and other important vi viii LIST OF CONTENTS ACKNOWLEDGEMENTS DECLARATION SUMMARY LIST OF TABLES LIST OF FIGURES LIST OF APPENDICES CHAPTER 1-INTRODUCTION AND LITERATURE REVIEW CHAPTER 2-GENERAL MATERIAL AND METHODS CHAPTER 3-STUDIES ON FACTORS AFFECTING IVERMECTIN RESISTANT Haemonchus contortus IN SHEEP Exp. 3.1-Efficacy of other anthelmintics on ivermectin resistant adult Haemonchus contortus Exp. 3.2-The response to ivermectin treatment of parasitic stages of Haemonchus contortus resistant or susceptible to ivermectin Exp. 3.3-Could the strategic use of salicylanilides control an ivermectin resistant strain of Haemonchus contortus in grazing lambs in Brazil? Exp. 3.4-How effective are reseeded pastures as an aid in the control of gastrointestinal nematodes in sheep? CHAPTER 4-STUDIES ON THE BIOLOGY OF IVERMECTIN RESISTANT Haemonchus contortus Exp. 4.1-Laboratory selection for ivermectin resistance in Haemonchus contortus Exp. 4.2-The pattern of faecal egg output in lambs infected with a multiple resistant strain of Haemonchus contortus after treatment with albendazole Exp. 4.3-The survival and development of ivermectin resistant or susceptible strains of Haemonchus contortus under field and laboratory conditions Exp. 4.4-Isoenzyme analysis of Haemonchus contortus strains either resistant or susceptible to ivermectin CHAPTER 5-COMPUTER MODELLING FOR ANTHELMINTIC RESISTANCE i Exp. 5.1-A drug action model in genetic selection for anthelmintic resistance in Haemonchus contortus CHAPTER 6-GENERAL DISCUSSION AND CONCLUSIONS REFERENCES APPENDICES x 122 xii LIST OF FIGURES ig. 1.1 Life cycle of H. contortus 4 ig-1.2 Location of four epidemiological studies in Brazil 46 ig-1.3 Climatic conditions in Brazil-rainfall ig-1.4 Climatic conditions in Brazil-temperatures ig-1.5 Epidemiology in Bage-H. contortus ig-1.6 Epidemiology in Uruguaiana-H. contortus ig-1.7 Epidemiology in Guaiba-//. contortus ig. 1.8 Epidemiology in Itaqui-H. contortus ig-1.9 Epidemiology in Bage-other nematodes ig-1.10 Epidemiology in Uruguaiana-other nematodes ig-1.11 Epidemiology in Guaiba-other nematodes ig-1.12 Epidemiology in Itaqui-other nematodes ig. 3.3.1 Worm egg counts from permanent grazers in Zone 1 ig-3.3.2 Worm egg counts from permanent grazers in Zone 2 ig. 3.3.3 Packed cell volume (%) from permanent grazers in Zone 1 ig. 3.3.4 Packed cell volume (%) from permanent grazers in Zone 2 ig. 3.3.5 Body weights from permanent grazers in Zone 1 ig. 3.3.6 Body weights from permanent grazers in Zone 2 ig. 4.1.1 Worm egg counts after IVM treatment on R or S H. contortus ig. 4.2.1 Worm egg counts after ABZ treatment on a strain of H. contortus 131 ig. 4.2.2 Haemonchus infective larvae (L3) recoveries after albendazole treatment 131 ig. 4.3.1 Development of Haemonchus L3 at 22°C 146 x iii xiv

Research paper thumbnail of Nematódeos resistentes a anti-helmíntico em rebanhos de ovinos e caprinos do estado do Ceará, Brasil

Ciência Rural, 2003

O controle do parasitismo por nematódeos gastrintestinais é feito basicamente com a utilização de... more O controle do parasitismo por nematódeos gastrintestinais é feito basicamente com a utilização de anti-helmínticos. Falhas no controle são o primeiro sinal do aparecimento de resistência anti-helmíntica. A real situação da prevalência da resistência anti-helmíntica, em fazendas comerciais de criação de ovinos e caprinos no Brasil, é desconhecida. Esse experimento teve como objetivo, estimar a ocorrência de resistência ao oxfendazol, levamisol e ivermectina em propriedades comerciais de criação de ovinos e caprinos, na região do médio e baixo Jaguaribe, através do teste de redução na contagem de ovos nas fezes acompanhados de coproculturas. O trabalho foi realizado em 25 criações, sendo 16 de ovinos, 7 de caprinos e uma de ovinos e caprinos. Os dados obtidos foram analisados pelo programa estatístico RESO (1989). A prevalência de nematódeos resistentes ao oxfendazol, levamisol e ivermectina em ovinos foi de 88%, 41% e 59%, e em caprinos de 87,5%, 75% e 37,5%, respectivamente. Observo...

Research paper thumbnail of Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

Experimental Parasitology, 2004

The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazo... more The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n ¼ 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO 2) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO 2 were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (<24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.

Research paper thumbnail of The fitness of free-living stages of strains of Ostertagia spp., susceptible or resistant to benzimidazole anthelmintics

Research paper thumbnail of Tratamento de fasciolose crônica em bovinos

Pesquisa Agropecuaria Brasileira, 1979

Estudou-se o efeito do tratamento da fasciolose cronica em vacas das racas Hereford, A. Angus e S... more Estudou-se o efeito do tratamento da fasciolose cronica em vacas das racas Hereford, A. Angus e Shorthorn naturalmente infectadas com Fasciola hepatica . Distribuiram-se os animais em dois grupos: grupo-controle, com 7,01 ovos por grama de fezes e peso medio de 294,7 kg ± 46,6, e grupo tratado, com 6,68 ovos por grama de fezes e peso medio de 288 kg ± 31,4. A pesquisa teve a duracao de 232 dias, sendo, os animais, pesados e coletados bimestralmente. Nessas mesmas datas, o grupo tratado recebia Niclofolan 4% injetavel na dose de 2 ml para cada 100 kg de peso vivo. Todos os animais foram abatidos, em frigorifico, 41 dias apos a quarta medicacao do lote tratado. Foram pesados os figados, e colhidas as fasciolas. O grupo tratado nao apresentou exemplar de F. hepatica, enquanto que o testemunha evidenciou uma media de 23,9 fasciolas/figado. Ambos os grupos mostraram lesoes cronicas e calcificacoes dos canais hepaticos. Nao houve diferencas significativas (P<0,05) no peso das carcacas, no peso dos figados e no ganho de peso dos grupos. O grupo tratado ganhou, em media, 116,6 kg ± 15,4, e o testemunha, 114,3 kg ± 37,7. Tendo em vista os resultados obtidos, nao e economico o tratamento contra a fasciolose em animais adultos em regime de engorda que ja apresentam lesoes hepaticas cronicas e irreversiveis.

Research paper thumbnail of Uso de anti-helmíntico em bovinos pela via intra-ruminal

Pesquisa Agropecuaria Brasileira, 1980

Research paper thumbnail of Susceptibilidade de Haemonchus spp. em bovinos ao tratamento anti-helmíntico com albendazole e oxfendazole

Pesqui Vet Bras, Jun 1, 1990

Research paper thumbnail of Model predictions for anthelmintic resistance amongst Haemonchus contortus populations in southern Brazil

A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK she... more A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.

Research paper thumbnail of Lack of negative effects of the biological control agent Duddingtonia flagrans on soil nematodes and other nematophagous fungi

Journal of Helminthology, 2015

The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sh... more The possible environmental effects of the massive use of Duddingtonia flagrans for controlling sheep nematodes were evaluated in two regions. Non-supplemented faeces and faeces from sheep supplemented with D. flagrans were deposited three times on pasture plots and samples were collected 7 and 14 days post-deposition. Samples were cultured in agar-water (2%) with Panagrellus spp. to recover D. flagrans and other nematophagous fungi, and soil nematodes were extracted using Baermann funnels and counted. No significant differences in the populations of soil nematodes and fungi colonizing sheep faeces (P > 0.05) were observed between supplemented and non-supplemented groups, except in one sample. The topsoil in contact with the faeces was sampled 1–4 months post-deposition, revealing that, with one exception, D. flagrans did not persist in soil beyond 2 months post-deposition. Duddingtonia flagrans does not affect faecal colonization by other fungi and soil nematodes and, once deploy...

Research paper thumbnail of Ação do Disofenol e do Niclofolan em bovinos

Pesquisa Agropecuaria Brasileira, 1979

Research paper thumbnail of Cobre no controle da verminose gastrintestinal em ovinos

Ciência Rural, 2004

Este estudo teve o objetivo de verificar o tempo de proteção do cobre contra reinfecções por helm... more Este estudo teve o objetivo de verificar o tempo de proteção do cobre contra reinfecções por helmintos gastrintestinais de ovinos em pastejo. Foram utilizados 32 ovinos da raça Corriedale, com aproximadamente 18 meses de idade, mantidos em campo nativo naturalmente contaminado por trichostrongilídeos. Os animais foram pesados e dosificados. Após, foram alocados a quatro grupos experimentais: T I (tratado com cobre e necropsiado no 28ºdia); T II (sem cobre e necropsiado no 28º dia); T III (tratado com cobre e necropsiado no 56ºdia); T IV (sem cobre e necropsiado no 56º dia). Os grupos T I e T III receberam, via oral, uma cápsula gelatinosa de quatro gramas, contendo 3,4 gramas de óxido de cobre. Os ovinos foram avaliados semanalmente através de contagem de ovos por grama de fezes (OPG), volume globular (VG), aspartato aminotransferase (AST) e concentrações de cobre no plasma. Ao abate, foram determinados: carga parasitária, concentrações de cobre no fígado e peso dos fígados. Os resu...

Research paper thumbnail of Laboratory selection for ivermectin resistance in Haemonchus contortus

Veterinary Parasitology, 1993

A strain of Haemonchus contortus, susceptible to ivermectin (IVM), was submitted to a selection p... more A strain of Haemonchus contortus, susceptible to ivermectin (IVM), was submitted to a selection procedure using IVM at 0.02 mg kg-1 during nine successive passages in lambs. Treatment reduced worm egg counts (epg) by more than 99% up to the seventh passage, but thereafter there was no significant reduction in epg. The efficacy of ivermectin against the ninth selected generation compared with the original susceptible strain was assessed. The results showed that animals infected with the selected strain and treated with IVM did not show any significant reduction (P &gt; 0.05) in epg compared with a 99.9% reduction in the susceptible group. At necropsy, post-treatment worm burdens confirmed that the selection pressure applied to the original strain had been successful in stimulating resistance to IVM.

Research paper thumbnail of Model predictions for anthelmintic resistance amongst Haemonchus cortortus populations in southern Brazil

Veterinary Parasitology - VET PARASITOL, 1993

A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK she... more A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.

Research paper thumbnail of Isoenzyme analysis of Haemonchus contortus resistant or susceptible to ivermectin

Veterinary Parasitology, 1992

Three different strains of Haemonchus contortus (susceptible to ivermectin, S-IVM; selected for r... more Three different strains of Haemonchus contortus (susceptible to ivermectin, S-IVM; selected for resistance to ivermectin, R-IVM; a multiple resistant strain, i.e. resistant to benzimidazole and ivermectin, R-IVM/SA) were examined for isoenzyme variation by starch gel electrophoresis. Using stains for seven enzymes separated in five different buffer systems, no differences in the electrophoretic mobility could be detected between any of the strains. Results demonstrate a low level of enzyme variation in H. contortus and no differences in enzyme electrophoretic profile between IVM-sensitive and IVM-resistant parasites. Differences between the ivermectin-sensitive and both ivermectin-resistant strains were observed with the propionyl esterases and although some of the differences are probably associated with benzimidazole resistance, others are associated with resistance to ivermectin. The three strains of H. contortus are generally identical; however, differences between all strains of H. contortus and a strain of Dictyocaulus viviparus were detected.

Research paper thumbnail of The efficacy of monepantel, an amino-acetonitrile derivative, against gastrointestinal nematodes of sheep in three countries of southern Latin America

Research paper thumbnail of Worm burden and immunological responses in Corriedale and Crioula Lanada sheep following natural infection with< i> Haemonchus contortus</i>

The effects of natural infection with Haemonchus contortus were compared in 15 Corriedale lambs a... more The effects of natural infection with Haemonchus contortus were compared in 15 Corriedale lambs and 18 Crioula Lanada lambs kept in the grazing conditions after weaning. The following parameters were assessed weekly for 9 consecutive weeks: number of eggs per gram of feces (EPG), packed cell volume (PCV), total serum proteins (TSP) and albumin (ALB). At 10 weeks, the animals

Research paper thumbnail of Nematodes resistant to anthelmintics in sheep and goat flock in the State of Ceará, Brazil

Ciência Rural, 2003

Nematódeos resistentes a anti-helmínticos em rebanhos de ovinos e caprinos do Estado do Ceará, Br... more Nematódeos resistentes a anti-helmínticos em rebanhos de ovinos e caprinos do Estado do Ceará, Brasil.

Research paper thumbnail of The prevalence of anthelmintic resistance in nematode parasites of sheep in Southern Latin America: Brazil

Veterinary Parasitology, 1996

South America has a large population of small ruminants. Currents estimates are approximately 100... more South America has a large population of small ruminants. Currents estimates are approximately 100 million sheep and 23 million goats. A large percentage of these flocks are raised in the humid tropics/sub-tropics. Nematode parasitism is singly the most important disease of these animals and typically farmers resort to frequent anthelmintic treatment in attempts to control this problem. Because of this reliance on drugs, price consideration is an important determinant in a farmer&#39;s choice of anthelmintic. In some circumstances, this has led to unethical practices of drug adulteration and substitution, or the offering to farmers of cheap, sub-standard generic products. The prevalence of anthelmintic resistance has not been investigated in any widespread sense in South America, although some of the first reports of resistance were made in southern Brazil almost 30 years ago. The following series of papers outline surveys conducted in the humid topics/sub-tropics of southern Latin America to assess the significance of resistance to the broad-spectrum anthelmintic groups in nematode parasites of sheep flocks.