World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of anticoccidial drugs in chickens and turkeys

These guidelines have been written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria species in chickens and turkeys. The information provided deals with many aspects of how to conduct controlled studies in battery cages (dose determination), floor pens (dose confirmation), and commercial facilities (field effectiveness studies), the selection of birds, housing, feeding, preparation of medicated rations, record keeping, diagnostic techniques, and methods for the preparation, maintenance and use of parasites. These guidelines are also intended to assist investigators in conducting specific studies, provide specific information for registration authorities involved in the decision-making process, assist in the approval and registration of new anticoccidial drugs, and facilitate the world-wide adoption of standard procedures.     

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of equine anthelmintics.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.     

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of equine anthelmintics

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp, which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.     

Effects of trypanocides on Herpetosoma in a mammalian feeder layer cell culture

Limited studies have been undertaken on the treatment of infections with trypanosomes of the subgenus Herpetosoma, either in comparative studies on the effects of trypanocidal drugs or as potential non-pathogenic models for evaluating trypanocidal activities. The development of an in vitro cell culture system is described which enabled testing of trypanocides against 5 different species of Herpetosoma. The trypanocides used were Samorin, Novidium, Trypacide and Berenil. Variations were observed in the trypanocidal activity of the drugs on the different Herpetosoma parasites, e.g. T. lewisi and Samorin and T. microti and Novidium, compared with other parasites. Minimum effective concentration of Trypacide and Berenil against 5 Herpetosoma trypanosomes were of the order 10 mg ml-1. The results indicate that these parasites are much less sensitive to the drugs used than pathogenic, salivarian trypanosomes.     

Methods in the evaluation of antiparasitic drugs in the horse.

The critical test is the primary method used for the efficacy evaluation of drugs against the major internal parasites (bots, ascarids, large strongyles, small strongyles, and pinworms) of the horse. The critical test determines: (1) spectrum of activity, (2) effectiveness of removal, (3) pattern of discharge, and (4) physical condition of each species of these parasites. General characteristics of the major parasitisms of the horse are discussed briefly. Criteria of the critical test also are considered including: (1) number of tests, (2) strain variation and drug resistance, (3) selection of test horses, (4) diagnosis of parasitic species, (5) numbers of parasites, (6) minimal efficacy requirements, and (7) other parasitic species. The controlled test principally is used on a selected basis for the small nematodes in the proximal portion of the digestive tract which cannot be properly evaluated by the critical test, or for other limited objectives. Clinical trials are discussed briefly but are invaluable supplements to the critical and controlled tests in the total assessment of a drug as a new product or for continued effectiveness in clinical use. Experimental procedures used in the conduct of drug evaluations should not be rigidly prescribed but should reflect input by the individual investigatior.     

The role of molecular biology in veterinary parasitology

The tools of molecular biology are increasingly relevant to veterinary parasitology. The sequencing of the complete genomes of Caenorhabditis elegans and other helminths and protozoa is allowing great advances in studying the biology, and improving diagnosis and control of parasites. Unique DNA sequences provide very high levels of specificity for the diagnosis and identification of parasite species and strains, and PCR allows extremely high levels of sensitivity. New techniques, such as the use of uniquely designed molecular beacons and DNA microarrays will eventually allow rapid screening for specific parasite genotypes and assist in diagnostic and epidemiological studies of veterinary parasites. The ability to use genome data to clone and sequence genes which when expressed will provide antigens for vaccine screening and receptors and enzymes for mechanism-based chemotherapy screening will increase our options for parasite control. In addition, DNA vaccines can have desirable characteristics, such as sustained stimulation of the host immune system compared with protein based vaccines. One of the greatest threats to parasite control has been the development of drug resistance in parasites. Our knowledge of the basis of drug resistance and our ability to monitor its development with highly sensitive and specific DNA-based assays for 'resistance'-alleles will help maintain the effectiveness of existing antiparasitic drugs and provide hope that we can maintain control of parasitic disease outbreaks.     

Trichomonas gallinae in budgerigars and columbid birds in Perth, Western Australia

Objective To estimate the prevalence of infection with Trichomonas gallinae and other parasites of the alimentary tract in psittacine and columbid birds in Perth and to determine in vitro the effectiveness of drugs commonly recommended for treating trichomoniasis.
Design and procedures Samples of crop contents were collected from aviary flocks of budgerigars (Melopsittacus undulatus) and other psittacine and columbid birds in both private and commercial collections in Perth. Similar samples from wild Senegal doves (Streptopelia senegalensis) also were collected. Crop contents were examined and cultured for Trichomonas gallinae and in vitro studies were conducted on the susceptibility of isolates to several drugs used commonly. Other parasites also were detected by faecal examination and/or necropsy.
Results T gallinae was recovered from birds in 1 of 13 private collections of budgerigars (2/289 birds in total). Direct wetmount examination of crop fluid identified 36.4% of samples at four commercial bird dealers which were later determined by culture to contain T gallinae . The prevalence of T gallinae infection ranged from 0 to 11.4% in budgerigars. The prevalence of T gallinae infection in wild Senegal doves was 46% and from one flock of racing pigeons was 59%. The in vitro minimum lethal concentrations of metronidazole, dimetridazole and ronidazole ranged from 40 to 96, 30 to 80 and 40 to 92 μg/mL respectively for six isolates of T gallinae . Other alimentary parasites detected during the survey included Spironucleus sp (syn Hexamita sp), coccidia, Ascaridia platycerci and Raillietina sp.
Conclusions Thirteen budgerigar flocks belonging to members of avicultural societies in Perth had a low prevalence of trichomoniasis and other parasitic infections. The dose rate currently recommended for ronidazole may not result in complete protozoacidal activity against T gallinae infection.     

顶复门原虫与细菌Ⅱ型丙二酰单酰辅酶A:ACP转酰基酶研究进展

大部分顶复门原虫与人畜重要寄生虫病密切相关.近年来,由于各类药物在寄生虫与细菌病防治中的广泛应用,甚至是滥用,造成了这类寄生虫与细菌的严重抗药性,急需一些新型抗感染性药物的出现.由于在一些顶复门原虫与细菌中广泛存在的Ⅱ型脂肪酸代谢途径在其脊椎动物宿主中并不存在,而丙二酰单酰辅酶A∶ACP转酰基酶(malonyl-CoA...     

抗弓形虫和新孢子虫药物体外筛选方法的研究进展

弓形虫和新孢子虫是2种在形态结构及生物学特征方面非常相似的细胞内寄生性原虫,二者引起的疾病对人和动物健康造成了严重危害。开发和筛选高效、低毒的抗弓形虫和新孢子虫药物一直是抗原虫药物研究领域的重要方向之一。药物筛选包括体外筛选和体内筛选,体外筛选的结果是进行体内筛选的依据和基础。对抗弓形虫和新孢子虫药物的体外筛选方法研究进展进行综述,以期为开发更加高效的抗弓形虫和新孢子虫药物体外筛选技术提供参考。     

顶复门原虫电子转移链代谢及Ⅱ型NADH脱氢酶研究进展

顶复门原虫是包括刚地弓形虫、疟原虫及球虫等在内的一大类寄生性原虫的总称,可引起重要的人畜寄生虫病.抗顶复门原虫药物的长期使用,甚至是滥用,使得这类寄生虫对现有药物产生了明显的抗药性,急需开发新型药物.Ⅱ型NAD(P)H脱氢酶是电子转移链途径中的关键酶,由于其仅存在于某些植物、细菌、真菌和寄生原虫等一些低等生物体内,而在高等动物体内缺失,是研发新型抗感染性药物的重要靶标.笔者主要针对顶复门原虫线粒体电子转移链代谢途径以及Ⅱ型NAD(P)H脱氢酶的研究概况进行综述.     

寄生虫乳酸脱氢酶研究进展

大多数体内寄生虫的生存必须依赖糖酵解途径将葡萄糖代谢为乳酸以提供能量。乳酸脱氢酶（lactate dehydrogenase, LDH）是糖酵解途径的末端酶,催化丙酮酸还原为乳酸及乳酸氧化为丙酮酸的可逆反应,与寄生虫生存密切相关。研究表明,各种寄生虫LDH在理化性质和分子结构方面均有独特的特性,是良好的诊断分子和潜在的药物作用靶标。对寄生虫LDH功能的研究,对于促进寄生虫病诊断、疫苗研究以及新抗虫药物的研发具有重要意义。本文对国内外寄生虫LDH的研究现状进行了综述。     

Caenorhabditis elegans: how good a model for veterinary parasites?

The organism about which most is known on a molecular level is a nematode, the free-living organism Caenorhabditis elegans. This organism has served as a reasonable model for the discovery of anthelmintic drugs and for research on the mechanism of action of anthelmintics. Useful information on mechanisms of anthelmintic resistance has also been obtained from studies on C. elegans. Unfortunately, there has not been a large-scale extension of genetic techniques developed in C. elegans to research on parasitic species of veterinary (or human) parasites. Much can be learned about the essentials of nematode biology by studying C. elegans, but discovering the basic biology of nematode parasitism can only be gained through comparative studies on multiple parasitic species.     

顶复门原虫3-磷酸甘油醛脱氢酶功能及其应用研究进展

糖酵解途径广泛存在于各类生物中,是顶复门原虫的主要供能方式。3-磷酸甘油醛脱氢酶是糖酵解途径的重要酶,与顶复门原虫的生存密切相关,可以作为抗寄生虫药物研发的重要靶标。文章主要从顶复门原虫糖酵解途径、3-磷酸甘油醛脱氢酶的基因分析、作用机理及应用等方面进行综述。     

FDA fast-tracking of pet population control drugs

Theriogenologists have been studying estrus prevention and termination of pregnancy in dogs for at least 2 decades. However, drugs approved for estrus suppression are few. No dog or cat abortifacients or male dog and cat sterilants have been approved. Marketed drugs with alternate indications that have antiestrus and antihormonal activity might be good candidates for study after obtaining an INAD from FDA. With the support of the original drug sponsor or manufacturer and appropriate safety and effectiveness studies, these products may be studied for additional label claims. New (not previously approved) drugs additionally need detailed information regarding the synthesis and manufacturing controls. Drugs offering substantial benefit over existing therapeutics may be eligible for expedited review. Prior to starting any studies in this area, clinical investigators and sponsors should communicate with FDA, an INAD must be granted, and the protocol submitted for evaluation. Approvability is evaluated after establishment of safety and effectiveness in clinical field trials.     

Research on avian coccidia: an update.

Despite the availability of many anticoccidial drugs, infections caused by species of Eimeria continue to be a source of significant economic loss to the poultry industry. After two decades in which the use world wide of ionophorous antibiotics gave unparalleled control of coccidiosis, drug resistance is once again tipping the balance in favour of the parasites. The realization that even the most spectacularly successful drugs might, after all, have a finite life if not used conservatively, has focused attention on ways in which the life span of drugs can be prolonged. Many drugs with different (if unknown) modes of action are available, and a variety of shuttle and rotation programmes can be considered. In view of the limitations of chemotherapy, particularly for the rearing of replacement flocks, there is considerable interest in the development of vaccines. Prospects for the introduction of live vaccines based on attenuated parasites are now very good, but the availability in the future of genetically engineered vaccines is more uncertain as little is known about the parasite molecules that stimulate protective immunity and, even if isolated, how they can be administered to the host so that it responds in the immunologically correct manner. Current research on Eimeria spp. in the chicken is broadly representative of that being done on other coccidia. Many lines of investigation are not connected with the development of new drugs or vaccination per se (and therefore have no obvious practical applications), but they are providing new insights into the biological complexity of the organisms and the ways in which they interact with their hosts. It remains possible, however, that a more detailed understanding and analysis of the molecules that are essential in the maintenance of the parasitic life style can be exploited in the future to provide alternative targets for chemical or immunological attack. The research topics considered in this review are arbitrarily grouped as studies on: (1) the basic biology of parasites, including aspects of the life cycle, and structure and function of the apical organelles; (2) the molecular biology of the parasites, including analyses of the number and structure of chromosomes, characterization of DNA sequences, and an account of the viral RNA that has been found in some species of Eimeria; and (3) control of coccidiosis, encompassing first immunity and the development of vaccines, and secondly, chemotherapy.     

Prolonged administration: A new concept for increasing the spectrum and effectiveness of anthelmintics

Cambendazole (CBZ), fenbendazole (FBZ), oxfendazole (OFZ) and thiabendazole (TBZ) all inhibited the fumarate stimulated oxidation of NADH in Haemonchus contortus mitochondria. These observations plus the phenomenon of cross resistance to benzimidazoles suggested that the different benzimidazole anthelmintics affect parasitic helminths in a similar manner.The variation in efficiency and spectrum of activity may therefore be due to differences in their pharmacokinetic behaviour. To test this hypothesis, the magnitude and duration of concentrations of TBZ, FBZ and OFZ in plasma and other body compartments after administration were compared with their effectiveness against parasites. The effects of similar doses against benzimidazole-resistant. Trichostrongylus colubriformis and H. contortus were found to correlate with the period high plasma concentrations were maintained.Further evidence of this relationship was obtained by infusion or multiple drenching of TBZ to cattle harbouring arrested Ostertagia ostertagi larvae, so as to maintain high circulating concentrations for an extended period. This resulted in the removal of 90% of the arrested larvae, whereas TBZ as normally administered is considered quite ineffective against these larvae.These observations suggest that the spectrum and effectiveness of benzimidazoles may be improved by extending the period during which parasites are exposed to toxic concentrations.     

Climatic influences on development and survival of free-living stages of equine strongyles: implications for worm control strategies and managing anthelmintic resistance

Development of resistance to anthelmintic drugs by horse strongyles constitutes a growing threat to equine health because it is unknown when new drug classes can be expected on the market. Consequently, parasite control strategies should attempt to maintain drug efficacy for as long as possible. The proportion of a parasite population that is not exposed to anthelmintic treatment is described as being "in refugia" and although many factors affect the rate at which resistance develops, levels of refugia are considered the most important as these parasites are not selected by treatment and so provide a pool of sensitive genes in the population. Accordingly, treatment should be avoided when pasture refugia are small because such treatments will place significant selection pressure for resistance on worm populations. Given this new paradigm for parasite control, it has become important to identify seasons and circumstances wherein refugia are diminished. Free-living stages of equine strongyles are highly dependent on climatic influences, and this review summarises studies of strongyle development and survival under laboratory and field conditions in Northern (cool) temperate, Southern (warm) temperate and subtropical/tropical climates. In Northern temperate climates, refugia are smallest during the winter. In contrast, refugia are lowest during the summer in warm temperate and subtropical/tropical climates. Although adverse seasonal changes clearly have significant effects on the ability of free living stages of strongyle nematode parasites to survive and develop, available data suggest that climatic influences cannot effectively "clean" pastures from one grazing season to the next.     

An evidence‐based approach to equine parasite control: It ain't the 60s anymore

Most veterinarians continue to recommend anthelmintic treatment programmes for horses that derive from knowledge and concepts more than 40 years old. However, much has changed since these recommendations were first introduced and current approaches routinely fail to provide optimal or even adequate levels of parasite control. There are many reasons for this. Recent studies demonstrate that anthelmintic resistance in equine parasites is highly prevalent and multiple‐drug resistance is common in some countries, but few veterinarians take this into account when making treatment decisions or when recommending rotation of anthelmintics. Furthermore, the current approach of treating all horses at frequent intervals was designed specifically to control the highly pathogenic large strongyle, Strongylus vulgaris. But this parasite is now quite uncommon in managed horses in most of the world. Presently, the cyathostomins (small strongyles) are the principal parasitic pathogens of mature horses. The biology and pathogenesis of cyathostomins and S. vulgaris are very different and therefore require an entirely different approach. Furthermore, it is known that parasites are highly over‐dispersed in hosts, such that a small percentage of hosts harbour most of the parasites. The common practices of recommending the same treatment programme for all horses despite great differences in parasite burdens, recommending prophylactic treatment of all horses without indication of parasitic disease or knowing what species of parasites are infecting the horses, recommending use of drugs without knowledge of their efficacy and failing to perform diagnostic (faecal egg count) surveillance for estimating parasite burdens and determining treatment efficacy, are all incompatible with current standards of veterinary practice. Consequently, it is necessary that attitudes and approaches to parasite control in horses undergo a complete overhaul. This is best achieved by following an evidence‐based approach that takes into account all of these issues and is based on science, not tradition.     

Drinking water treatment processes for removal of Cryptosporidium and Giardia

Major waterborne cryptosporidiosis and giardiasis outbreaks associated with contaminated drinking water have been linked to evidence of suboptimal treatment. Cryptosporidium parvum oocysts are particularly more resistant than Giardia lamblia cysts to removal and inactivation by conventional water treatment (coagulation, sedimentation, filtration and chlorine disinfection); therefore, extensive research has been focused on the optimization of treatment processes and application of new technologies to reduce concentrations of viable/infectious oocysts to a level that prevents disease. The majority of the data on the performance of treatment processes to remove cysts and oocysts from drinking water have been obtained from pilot-tests, with a few studies performed in full-scale conventional water treatment plants. These studies have demonstrated that protozoan cyst removal throughout all stages of the conventional treatment is largely influenced by the effectiveness of coagulation pretreatment, which along with clarification constitutes the first treatment barrier against protozoan breakthrough. Physical removal of waterborne Crytosporidium oocysts and Giardia cysts is ultimately achieved by properly functioning conventional filters, providing that effective pretreatment of the water is applied. Disinfection by chemical or physical methods is finally required to inactivate/remove the infectious life stages of these organisms. The effectiveness of conventional (chlorination) and alternative (chlorine dioxide, ozonation and ultra violet [UV] irradiation) disinfection procedures for inactivation of Cryptosporidium has been the focus of much research due to the recalcitrant nature of waterborne oocysts to disinfectants. This paper provides technical information on conventional and alternative drinking water treatment technologies for removal and inactivation of the protozoan parasites Cryptosporidium and Giardia.     

Drug therapy in cats: a therapeutic category approach

The third article of this 4-part series discusses drug therapy in cats by therapeutic category. Specifically, the use of drugs to control infections, pain, fever, inflammation, cancer, and selected parasites is described. In addition, the use of hormonally related drugs and selected miscellaneous drugs in cats is addressed. Drugs emphasized are those for which use in cats is frequently associated with adverse reactions or drugs for which use is limited to illnesses that tend to be unique in cats.