Assessing anthelmintic resistance risk in the post-genomic era: a proof-of-concept study assessing the potential for widespread benzimidazole-resistant gastrointestinal nematodes in North American cattle and bison.

As genomic research continues to improve our understanding of the genetics of anthelmintic drug resistance, the revolution in DNA sequencing technologies will provide increasing opportunities for large-scale surveillance for the emergence of drug resistance. In most countries, parasite control in cattle and bison has mainly depended on pour-on macrocyclic lactone formulations resulting in widespread ivermectin resistance. Consequently, there is an increased interest in using benzimidazole drugs which have been used comparatively little in cattle and bison in recent years. This situation, together with our understanding of benzimidazole resistance genetics, provides a practical opportunity to use deep-amplicon sequencing to assess the risk of drug resistance emergence. In this paper, we use deep-amplicon sequencing to scan for those mutations in the isotype-1 ß-tubulin gene previously associated with benzimidazole resistance in many trichostrongylid nematode species. We found that several of these mutations occur at low frequency in many cattle and bison parasite populations in North America, suggesting increased use of benzimidazole drugs in cattle has the potential to result in widespread emergence of resistance in multiple parasite species. This work illustrates a post-genomic approach to large-scale surveillance of early emergence of anthelmintic resistance in the field.

Questionnaire survey on helminth control practices in horse farms in Ireland.

Knowledge regarding helminth control strategies and nematode infection of horses in Ireland is limited and only one study has been published recently. This present study was designed to investigate the current helminth control strategies followed by horse owners in Ireland. A questionnaire was formulated to collect data on general grazing, pasture management and deworming strategies including the use of fecal egg counts. Questionnaires were emailed to 700 members of the Irish Thoroughbred Breeders Association and Horse Sport Ireland. Only 78 questionnaires were returned. Respondents indicated that horses are grazed for 16-24 h day-1 during the summer and autumn (89% and 65%, respectively). Removing feces from the pasture was implemented by 37.6% of respondents. Few (22.2%) owners kept horses off pasture after worming. Overall, ivermectin and moxidectin were the most commonly administered anthelmintics in 2014 by 75% and 62% of respondents, respectively. Benzimidazole and pyrantel drugs were used by 53% and 35% of respondents, respectively. The majority of farms (81.4%) treated horses 4-5 times per year and 74.2% only estimated the weight of the horses visually. The findings of this study illustrates that many stud managers/owners do not follow best practice with regard to helminth control and more education is needed.

Effects of oral administration of copper capsules on helminth control in lactating dairy sheep: An effective alternative to replace conventional antiparasitics during lactation.

Two experiments were performed to determine whether oral administration of copper oxide capsules controlled helminthic infections in Lacaune sheep without acute collateral effects on animal health. In experiment 1, 48 multiparous lactating sheep (60.1 ±â€¯8.5 kg) were stratified according to initial number of eggs (Haemonchus contortus) per gram of feces (EPG) and were assigned randomly to 1 of two treatments (24 sheep/treatment): no oral administration (control) or oral administration of two copper capsules (treated; approximately 58 mg copper/kg body weight). Blood and fecal samples were collected on days 0, 15 and 45. Animals treated with copper capsules showed lower of EPG, eosinophils, acetylcholinesterase (AChE) in whole blood, and lower butyrylcholinesterase (BChE) activity in serum. Treated sheep had higher erythrocyte numbers, hemoglobin concentrations, hematocrit, and lymphocyte numbers. In experiment 2, 12 male lambs negative for helminths and coccidia were assigned randomly to one of two treatments (six lambs/treatment): control or treated (one copper capsule; approximately 58 mg copper/kg body weight); the experiment was designed to determine whether the results of experiment 1 were due to treatment or parasitism. Blood samples were collected on days 0, 5, 10 and 15 and fecal samples were collected on days 0, 7 and 15. Treated animals showed greater concentrations of lymphocytes; however, treatment had no effect on other hemogram variables, AChE and BChE activities, or levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, urea, albumin, total protein, and reactive oxygen species. These data suggest that copper capsules in dairy sheep efficiently controlled H. contortus infections. Treatment was not harmful to lambs during the first 15 days, i.e. there were no signs of acute toxicity.

Production responses and cost-benefit of long-acting pre-lambing anthelmintic treatment of yearling ewes in two commercial flocks in New Zealand.

AIMS: To investigate the production responses and cost-benefit of administering a controlled-release anthelmintic capsule (CRC) to pregnant yearling ewes prior to lambing. METHODS: Yearling ewes from two commercial sheep flocks (A, n=489; B, n=248) in the North Island of New Zealand were enrolled in the study. Prior to lambing, CRC containing albendazole and abamectin were administered to half the ewes while the other half remained untreated. Ewe liveweights and body condition scores were measured prior to lambing, at weaning and, for Flock B, prior to subsequent mating. Lambs were matched to dams shortly after birth and the weight and number of lamb weaned per ewe were determined. A cost-benefit analysis was undertaken for Flock B considering the increased weight of lamb weaned per ewe, and the weight of ewes at the next mating and the benefit in terms of lambs born. RESULTS: The mean weight at weaning of treated ewes was greater for treated than untreated ewes by 2.76 (95% CI 0.64-4.88) kg in Flock A (p<0.001) and 2.35 (95% CI -0.41-5.12) kg in Flock B (p=0.003); the weight of lamb weaned per ewe was greater for treated than untreated ewes by 1.43 (95% CI -0.71 to -3.49) kg in Flock A (p=0.041) and 3.97 (95% CI 1.59-6.37) kg in Flock B (p<0.001), and ewe liveweight prior to subsequent mating was greater for treated than untreated ewes in Flock B by 4.60 (95% CI 3.6-5.6) kg (p<0.001). There was no difference in the percentage of lambs reared to weaning between treated and untreated ewes in either flock (p>0.8). The overall cost-benefit of treatment for Flock B was NZ$9.44 per treated ewe. CONCLUSIONS AND CLINICAL RELEVANCE: Pre-lambing CRC administration to yearling ewes resulted in increased ewe weaning weights and weight of lamb weaned in both the flocks studied. There was an economic benefit in the one flock where this was assessed.

Control of helminth ruminant infections by 2030.

Helminth infections have large negative impacts on production efficiency in ruminant farming systems worldwide, and their effective management is essential if livestock production is to increase to meet future human needs for dietary protein. The control of helminths relies heavily on routine use of chemotherapeutics, but this approach is unsustainable as resistance to anthelmintic drugs is widespread and increasing. At the same time, infection patterns are being altered by changes in climate, land-use and farming practices. Future farms will need to adopt more efficient, robust and sustainable control methods, integrating ongoing scientific advances. Here, we present a vision of helminth control in farmed ruminants by 2030, bringing to bear progress in: (1) diagnostic tools, (2) innovative control approaches based on vaccines and selective breeding, (3) anthelmintics, by sustainable use of existing products and potentially new compounds, and (4) rational integration of future control practices. In this review, we identify the technical advances that we believe will place new tools in the hands of animal health decision makers in 2030, to enhance their options for control and allow them to achieve a more integrated and sustainable approach to helminth control in support of animal welfare and production.

Efficacy and toxicity of praziquantel in helminth-infected barbel (Barbus barbus L.).

This study evaluated efficacy and toxicity of the pyrazinoisoquinoline anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant biomarkers and the lipid peroxidation response in juvenile barbel post-treatment. The estimated 96-hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4-day bath treatment. Both concentrations were 100% effective against D. spathaceum and significantly (p < .01) affected the activity of catalase, superoxide dismutase, glutathione reductase and glutathione-S-transferase as well as levels of reduced glutathione in liver and muscle. The efficacy of orally administered PZQ was assessed in adult barbel naturally infected with P. laevis. Fish were administered 10, 30 and 50 mg/kg of body weight and examined via gut dissection after 6 days. The 50 mg/kg dose significantly decreased the intensity of infection. Praziquantel is a feasible bath treatment for barbel infected with D. spathaceum and has potential for oral treatment of broodfish infected with P. laevis.

Recombinant subunit vaccines for soil-transmitted helminths.

Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and be cost effective, recombinant subunit vaccines that include a minimum number of proteins produced in relatively simple and inexpensive expression systems are required. Here, we summarize all of the previous studies pertaining to recombinant subunit vaccines for STHs of humans and livestock with the goal of both informing the public of just how critical these parasites are, and to help guide future developments. We also discuss several key areas of vaccine development, which we believe to be critical for developing more potent recombinant subunit vaccines with broad-spectrum protection.

Helminth parasites of finfish commercial aquaculture in Latin America.

Latin America has tripled production by aquaculture up to 78 million tonnes in the past 20 years. However, one of the problems that aquaculture is facing is the presence of helminth parasites and the diseases caused by them in the region. In this review we have collected all the available information on helminths affecting commercial aquaculture in Latin America and the Caribbean (LAC), emphasizing those causing serious economic losses. Monogeneans are by far the most common and aggressive parasites affecting farmed fish in LAC. They have been recognized as serious pathogens in intensive fish culture because they reach high levels of infection rapidly, and can infect other phylogenetically related fish species. The next most important group comprises the larval stages of digeneans (metacercariae) such as Diplostomum sp. and Centrocestus formosanus, which cause serious damage to farmed fish. Since LAC aquaculture has been based mainly on exotic species (tilapia, salmon, trout and carp), most of their parasites have been brought into the region together with the fish for aquaculture. Recently, one of us (A.I.P.-T.) has suggested that monogeneans, which have generally been considered to be harmless, can produce serious effects on the growth of cultured Nile tilapia. Therefore, the introduction of fish together with their 'harmless' parasites into new sites, regions or countries in LAC should be considered a breakdown of biosecurity in those countries involved. Therefore, the application of quarantine procedures and preventive therapeutic treatments should be considered before allowing these introductions into a country.

An assessment of benzimidazole resistance against caprine nematodes in Central India.

Current status of resistance to benzimidazole (BZ) group of anthelmintic drugs against caprine nematodes in Central India at Amanala goat farm, Jabalpur, Madhya Pradesh (M. P.), was systematically investigated using faecal egg count reduction (FECR) test and egg hatch test (EHT). Besides, allele-specific PCR (AS-PCR) was deployed to ascertain the susceptible genotype (alleles) especially of the Haemonchus contortus. Randomly selected 30 goats, irrespective of age and sex, were divided into three groups of 10 each, to serve as treated and untreated controls. It was ensured that the animals were not administered with an anthelmintic drug for the past 3 months prior to undertaking the study, and faecal egg counts were estimated. FECR test evidenced fenbendazole resistance by partial elimination (24.90%) copro-egg counts in the treated group of animals vis-à-vis controls with a lower confidence interval of -26%. Further, EHT revealed ED-50 value of 0.335 µg of thiabendazole/ml, confirming benzimidazole resistance in the animals of that farm. AS-PCR showed that 62% of H. contortus larvae were homozygous resistant (rr), 24% heterozygous (rS) and 14% homozygous susceptible (SS). The genotypic frequencies of three genotypes (rr, rS and SS) were significantly (P < 0.01) different. The prevalence of benzimidazole resistance allele (r) was also significantly (P < 0.01) higher (74%) as compared to susceptible allele (S) (26%). The resistance to benzimidazole has been discussed while emphasizing improved managemental practices designed to reduce exposure of the goat population to parasites, minimize frequency of anthelmintic use at optimum dose and rotational use of different chemical groups of medicines with different mode of action, so as to overcome and combat the upcoming problem in the field.

Praziquantel treatment for yellowtail kingfish (Seriola lalandi): dose and duration safety study.

Regulatory approval is being sought to use praziquantel (PZQ) to treat flukes infecting yellowtail kingfish (YTK), but accurate safety data were not available. We investigated the effect of increased doses or prolonged exposure of orally administered PZQ on YTK by assessing changes in haematological and biochemical characteristics, and mortality. Fish were intubated daily for 3 days with 0, 100, 300 and 500 mg PZQ kg(-1) BW day(-1) or once daily for 9 days at 0 and 100 mg PZQ kg(-1) BW day(-1). Blood was taken 24 h after the cessation of treatment. There was no significant difference between any of the haematological or biochemical indices in YTK treated with PZQ and controls, indicating that PZQ is safe for use at 100 mg PZQ kg(-1) BW day(-1) in YTK and that exposure to high doses or prolonged duration does not have negative effects on the YTK haematological or biochemical parameters we measured.

Distribution of infective gastrointestinal helminth larvae in tropical erect grass under different feeding systems for lambs.

This study examined tropical pasture contamination dynamics under different feeding systems for finishing lambs. The experiment aimed to evaluate the vertical distribution of gastrointestinal helminth infective larvae (L3) in erect grass subjected to grazing and to assess the parasite load and its impact on lamb performance in three production systems. Three treatments based on Aruana grass (Panicum maximum cv. IZ-5) were as follows: T1, grass only; T2, grass with 1.5% of body weight (BW) nutrient concentrate supplementation; and T3, grass with 2.5% BW concentrate supplementation. The randomized block design had three replicates of three treatments, with six lambs per replicate. L3 were recovered from three pasture strata (upper, middle, and bottom), each representing one third of the sward height, and correlated with microclimatic data. Significant differences (P < 0.05) were observed among treatments in the L3 recovery. Despite different grass heights between treatments and microclimates within the sward, the L3 concentration generally did not differ significantly among the three strata within a treatment (P > 0.05). Pasture microclimate did not correlate with larval recovery. At the end of the experiment, the animal fecal egg count was similar among treatments (P > 0.05). The results indicated that different lamb feeding systems in a tropical erect grassland caused differences in grass height but did not affect the distribution of infective larvae among strata. Larvae were found from the base to the top of the grass sward.

Assessing the applications and efficacy of using helminthophagous fungi to control canine gastrointestinal parasites.

Helminths are a major challenge in dog breeding, particularly affecting young animals and posing a significant zoonotic risk. The widespread use of anthelmintics to treat gastrointestinal helminth infections in companion animals is common. However, these chemical products generate residues that can have adverse effects on animal, human and environmental health. In addition to the challenge of parasite resistance to treatment, there is an urgent need to explore and discuss complementary and sustainable methods of controlling helminthiases in these animals. In this context, nematophagous or helminthophagous fungi have emerged as a potential tool for the control of environmental forms of helminths. The purpose of this review is to emphasize the importance of these fungi in the control of free-living forms of helminth parasites in companion animals by highlighting the research that has been conducted for this purpose. In vitro experiments demonstrated the efficacy of fungi like Pochonia chlamydosporia, Arthrobotrys robusta, and Monacrosporium thaumasium in trapping and reducing helminth infective forms. These findings, along with soil contamination studies, suggest the feasibility of using helminthophagous fungi as a sustainable and effective strategy for environmental control. The current literature supports the potential of these fungi as an environmentally friendly solution for managing helminthiasis in dogs, benefiting both animal health and public welfare.

The immune response to parasitic helminths of veterinary importance and its potential manipulation for future vaccine control strategies.

Despite the increasing knowledge of the immunobiology and epidemiology of parasitic helminths of the gastrointestinal system and the cardiorespiratory system, complications arising from infections of animals and humans with these parasites are a major clinical and economic problem. This has been attributed to the high incidence of these parasites, the widespread emergence of multi-drug resistant parasite strains and the lack of effective vaccines. Efforts to develop and produce vaccines against virtually all helminths (with the exception of Dictyocaulus viviparus and some cestode species) have been hindered by the complexity of the host-parasite relationship, and incomplete understanding of the molecular and immune regulatory pathways associated with the development of protective immunity against helminths. Novel genomic and proteomic technologies have provided opportunities for the discovery and characterisation of effector mechanisms and molecules that govern the host-parasite interactions in these two body systems. Such knowledge provided clues on how appropriate and protective responses are elicited against helminths and, thus, may lead to the development of effective therapeutic strategies. Here, we review advances in the immune response to selected helminths of animal health significance, and subsequent vaccine potential. The topics addressed are important for understanding how helminths interact with host immune defences and also are relevant for understanding the pathogenesis of diseases caused by helminths.

Contrasting views of animal healthcare providers on worm control practices for sheep and goats in an arid environment.

A questionnaire survey was conducted to determine the worm control practices and anthelmintic usage of 150 key respondents involved in sheep and goat production in the arid Thal area of Pakistan. The information was collected by visiting farms, and interviewing the key respondents which included veterinary officers (n = 15), veterinary assistants (n = 51), traditional practitioners (n = 24), and small and large scale sheep/goat farm herders and owners (n = 60). Among all interviewed animal healthcare providers, the veterinary officers had the highest level of awareness of parasitic infection and advocated the use of modern available anthelmintics according to the predefined schedule. The farmers on the other hand, had the lowest level of knowledge about parasitic infections. They used modern anthelmintics at low frequencies (every six months) following an unusual practice of diluting the medicine. Veterinary assistants had a medium level of awareness about the parasitic infections using anthelmintic treatments when they deemed necessary rather than following a predefined treatment schedule. Traditional practitioners were also aware of parasitic infections and used traditional anthelmintics or a combination of the traditional and modern anthelmintics. The animal health providers had a different awareness and knowledge of parasitic infections which resulted in contrasting proposals for its' control. The farmers used worm control measures in accordance with their own views and those of animal healthcare advisors, combining modern and traditional treatments. This study provides the first insight into the differing views of those animal healthcare providers who form the basis for effective parasitic control within the sheep and goat industry of an arid region.

Current anthelmintic and antibiotic use in UK organic farming systems.

INTRODUCTION: The use of anthelmintic and antibiotic medicines is imperative to prevent the suffering of diseased stock in organic farming. However, their use must be minimised to comply with low input ideals and prevent the spread of resistance. Reducing such inputs first requires determining their current use, but information is lacking. The objective of this study was to benchmark the current use of anthelmintics and antibiotics in UK organic livestock farming. METHODS: Data were gathered by conducting a national survey of organic livestock farmers in the UK and by analysing records of requests for allopathic medicines. RESULTS: Key findings include (i) anthelmintics used in sheep constitute the greatest input of veterinary medicines in organic systems, (ii) farmers are incorporating alternative/support tools in helminth control to reduce anthelmintic requirements, (iii) the use of antibiotics is targeting individual animals, whereas the use of anthelmintics is targeting groups of animals. CONCLUSION: This study provides the first benchmark on the use of anthelmintics and antibiotics in UK organic livestock.

A questionnaire survey on helminth control on horse farms in Brandenburg, Germany and the assessment of risks caused by different kinds of management.

Control strategies for horse helminths are controversially discussed, and no ideal strategy exists. Presently, the spreading of anthelmintic resistance against all three classes of anthelmintics is of special concern. Advice on how to slow the development of anthelmintic resistance does not seem to have reached the majority of horse owners yet. In our study, we wanted to capture the current standard of helminth control and to analyse the effectiveness of these control strategies. Seven hundred horse farms in Brandenburg, Germany were sent a questionnaire in June/July 2006 asking various questions on farm structure and practices of helminth control. Two hundred thirty-five farms (33.6%) with 6,007 horses in total returned the questionnaire. The number of horses held on each farm varied from 1 to 320. From those returned questionnaires, a random sample of 126 horse farms and 1,407 horses was selected for faecal examination from August to December 2006. The questionnaire results from these farms were correlated with results from the faecal examination to perform risk analysis via multivariate regression. For each farm, results from faecal examination were summarized in index values. Risk was defined as an over-average level of strongyle egg shedding. Risk factors as established by multivariate regression analyses were integrated into three models. Rare deworming and infrequent cleaning of stables were identified as significant risk factors throughout all three models. Additional risk factors could be identified with respect to individual models: elevated percentage of young horses on a farm, not using macrocyclic lactones in the deworming process and dosing anthelmintics on the basis of weight and height. Pasture hygiene did not lead to significant risk reduction, indicating that such measures are inadequately performed on many farms. The questionnaire on its own gave us an insight into control strategies throughout a representative scope of farms in Brandenburg, Germany: faeces were collected from pasture on 22% of horse farms, 79% cleaned out the stables daily. A number of other measures were employed. With respect to anthelmintic use, 21% of the farms stated to use results from faecal examination as a criterion for deworming. We could also identify the most common deworming frequencies, with adult horses being dewormed two times a year (46% of farms) and foals being dewormed four times a year (35% of farms). The frequency ranged from 1 to 7 and 2 to 12 times, respectively.

A cross-sectional study of geriatric horses in the United Kingdom. Part 2: Health care and disease.

REASONS FOR PERFORMING STUDY: Geriatric horses (aged≥15 years) represent a substantial proportion of the equine population, yet very few studies have investigated the prevalence of diseases within the UK equine geriatric population. OBJECTIVES: To describe the provision of routine preventive health care measures, prevalence of clinical signs of disease and the prevalence of owner reported diseases. Additionally, the effect of increasing age on the provision of preventive health care and the presence or absence of clinical signs and disease was assessed. METHODS: A cross-sectional study was conducted, surveying a randomly selected sample of veterinary registered owners with horses aged≥15 years, using a self-administered postal questionnaire. RESULTS: As geriatric horses increased in age, there was a reduction in the provision of preventive health care measures, such as vaccination, farrier care and routine veterinary checks. Only 68.7% of horses had received a routine veterinary visit within the previous 12 months. Owners frequently observed clinical signs in their animals, with 77% reporting at least one clinical sign of disease. Increasing age was associated with increased reporting of many clinical signs of disease. Over half (58%) of horses had at least one episode of disease within the previous 12 months, yet only 31% of owners reported that their animal currently suffered from a known disease or disorder. CONCLUSIONS AND POTENTIAL RELEVANCE: Although owners frequently observed clinical signs in their aged horse, there may be incorrect or under recognition of many diseases and health problems. Reduced frequency of routine preventive health care measures, along with suboptimal owner recognition of health and welfare problems may lead to compromised welfare in the geriatric population.

Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites.

Proteases are pivotal to parasitism, mediating biological processes crucial to worm survival including larval migration through tissue, immune evasion/modulation and nutrient acquisition by the adult parasite. In haematophagous parasites, many of these proteolytic enzymes are secreted from the intestine (nematodes) or gastrodermis (trematodes) where they act to degrade host haemoglobin and serum proteins as part of the feeding process. These proteases are exposed to components of the immune system of the host when the worms ingest blood, and therefore present targets for the development of anti-helminth vaccines. The protective effects of current vaccine antigens against nematodes that infect humans (hookworm) and livestock (barber's pole worm) are based on haemoglobin-degrading intestinal proteases and act largely as a result of the neutralisation of these proteases by antibodies that are ingested with the blood-meal. In this review, we survey the current status of helminth proteases that show promise as vaccines and describe their vital contribution to a parasitic existence.

Endoparasite control management on horse farms--lessons from worm prevalence and questionnaire data.

REASONS FOR PERFORMING STUDY: Increasing prevalence of anthelmintic resistance in equine nematodes calls for a reexamination of current parasite control programmes to identify factors influencing control efficacy and development of resistance. OBJECTIVES: To investigate if associations occur between prevalence of parasitic nematodes and management practices. METHODS: German horse farms (n = 76) were investigated in 2003 and 2004. Information on farm and pasture management with respect to endoparasite control measures obtained using a questionnaire survey. Faecal examinations were performed in parallel. RESULTS: Horses (n = 2000) were examined by faecal nematode egg counts, grouped into foals, yearlings and mature individuals for statistical analyses. Farms were categorised into 3 types, riding, stud farms and small holdings. Count regression models were used to analyse strongyle faecal egg count data. Following dichotomisation of faecal egg count (FEC) data, prevalence of strongyle and Parascaris equorum infections were assessed by logistic regression models as a function from various management factors. Yearlings on stud farms showed a 2-fold higher risk of being positive for strongyle FEC, higher (i.e. > or =3 per year) anthelmintic drug treatment frequencies were associated with reduced strongyle infection rates only in mature individuals but not in foals or yearlings, foals on farms fertilising pastures with horse manure had a significantly higher risk of being P. equorum FEC positive and yearlings on stud farms were more often showing incomplete FECR following anthelmintic treatment compared to yearlings on other farm types. The mean yearly treatment frequencies per age group were: foals 4.52, yearlings 3.26 and mature horses 2.72 times, respectively. CONCLUSION AND POTENTIAL RELEVANCE: To delay the development of anthelmintic, resistance management should include additional nonchemotherapeutic parasite control strategies, FEC-monitoring, controlled quarantine treatment of new arrivals and control of efficacy by the faecal egg count reduction test on a regular basis.

Fifteen Years of Sm-p80-Based Vaccine Trials in Nonhuman Primates: Antibodies From Vaccinated Baboons Confer Protection in vivo and in vitro From Schistosoma mansoni and Identification of Putative Correlative Markers of Protection.

Recent advances in systems biology have shifted vaccine development from a largely trial-and-error approach to an approach that promote rational design through the search for immune signatures and predictive correlates of protection. These advances will doubtlessly accelerate the development of a vaccine for schistosomiasis, a neglected tropical disease that currently affects over 250 million people. For over 15 years and with contributions of over 120 people, we have endeavored to test and optimize Sm-p80-based vaccines in the non-human primate model of schistosomiasis. Using RNA-sequencing on eight different Sm-p80-based vaccine strategies, we sought to elucidate immune signatures correlated with experimental protective efficacy. Furthermore, we aimed to explore the role of antibodies through in vivo passive transfer of IgG obtained from immunized baboons and in vitro killing of schistosomula using Sm-p80-specific antibodies. We report that passive transfer of IgG from Sm-p80-immunized baboons led to significant worm burden reduction, egg reduction in liver, and reduced egg hatching percentages from tissues in mice compared to controls. In addition, we observed that sera from Sm-p80-immunized baboons were able to kill a significant percent of schistosomula and that this effect was complement-dependent. While we did not find a universal signature of immunity, the large datasets generated by this study will serve as a substantial resource for further efforts to develop vaccine or therapeutics for schistosomiasis.