In June 2022, at the XXXII Conference of the Italian Society of Parasitology, the parallels of the main endoparasitic infections of horses and donkeys were discussed. Although these 2 species are genetically different, they can be challenged by a similar range of parasites (i.e. small and large strongyles, and Parascaris spp.). Although equids can demonstrate some level of resilience to parasites, they have quite distinct helminth biodiversity, distribution and intensity among different geographical locations and breeds. Heavily infected donkeys may show fewer clinical signs than horses. Although parasite control is primarily provided to horses, we consider that there may be a risk of drug-resistance parasitic infection through passive infection in donkeys when sharing the same pasture areas. Knowing the possible lack of drug efficacy (<90 or 80%), it is advocated the use of selective treatment for both species based on fecal egg counts. Adult horses should receive treatment when the threshold exceeds 200–500 eggs per gram (EPG) of small strongyles. Moreover, considering that there are no precise indications in donkeys, a value >300 EPG may be a safe recommendation. We have highlighted the main points of the discussion including the dynamics of helminth infections between the 2 species.

Parasitic nematodes devastate human and animal health. The limited number of anthelmintics available is concerning, especially because of increasing drug resistance. Anthelmintics are commonly derived from natural products, e.g. fungi and plants. This investigation aimed to develop a high-throughput whole organism screening method based on a motility assay using the wMicroTracker system. Anthelmintic activity of extracts from Hawaiian fungi was screened against third-stage larvae of the parasitic nematode Angiostrongylus cantonensis, categorized according to the degree of motility reduction. Of the 108 crude samples and fractionated products, 48 showed some level of activity, with 13 reducing motility to 0–25% of the maximum exhibited, including two pure compounds, emethacin B and epicoccin E, neither previously known to exhibit anthelmintic properties. The process of bioassay-guided fractionation is illustrated in detail based on analysis of one of the crude extracts, which led to isolation of lamellicolic anhydride, a compound with moderate activity. This study validates the wMicroTracker system as an economical and high-throughput option for testing large suites of natural products against A. cantonensis, adds to the short list of diverse parasites for which it has been validated and highlights the value of A. cantonensis and Hawaiian fungi for discovery of new anthelmintics.

Paramphistomosis is a parasitic disease endemic in ruminants nearly worldwide. In the present study, an in vitro screening of the main anthelmintics used in Mexico was carried out to determine the mean lethal dose for rumen fluke eggs from cattle in a humid, warm region. Rumen flukes were obtained from cattle slaughtered in the states of Tabasco and Chiapas in Mexico. Eggs were collected using a 37-μm sieve and quantified. Then, an in vitro incubation study was performed: 100 eggs were placed into the wells of polystyrene microtiter plates. Anthelmintic products were tested on the eggs at concentrations ranging from 0.0015 to 3.0 mg/ml for rafoxanide, 0.0025 to 10.20 mg/ml for nitroxinil and 0.0015 to 3 mg/ml for closantel to determine the median lethal dose (LD50) and maximum lethal dose (LD99). A control group (water) was included in each plate. Three different species of rumen flukes (Calicophoron brothriophoron, Calicophoron clavula and Paramphistomum cervi) belonging to five isolates were identified. Nitroxinil had the highest efficacy against rumen fluke eggs, with an LD50 of 0.11 to 65 μg/ml, whereas rafoxanide showed the lowest efficacy with an LD50 ranging from 500 to 1713 μg/ml. Closantel showed high variability in the LD50 among the different analysed isolates (17 to 122 μg/ml). The evaluated flukicidal drugs presented differential efficacy against the development of rumen fluke eggs. The efficacy of the drugs will vary depending on the geographical area of origin of the animals.

The multifaceted interactions occurring between gastrointestinal (GI) parasitic helminths and the host gut microbiota are emerging as a key area of study within the broader research domain of host-pathogen relationships. Over the past few years, a wealth of investigations has demonstrated that GI helminths interact with the host gut flora, and that such interactions result in modifications of the host immune and metabolic statuses. Nevertheless, whilst selected changes in gut microbial composition are consistently observed in response to GI helminth infections across several host-parasite systems, research in this area to date is largely characterised by inconsistent findings. These discrepancies are particularly evident when data from studies of GI helminth-microbiota interactions conducted in humans from parasite-endemic regions are compared. In this review, we provide an overview of the main sources of variance that affect investigations on helminth-gut microbiota interactions in humans, and propose a series of methodological approaches that, whilst accounting for the inevitable constraints of fieldwork, are aimed at minimising confounding factors and draw biologically meaningful interpretations from highly variable datasets.

This study assessed the efficacy of closantel vis-à-vis herbal extracts with known anti-parasitic properties, against fenbendazole-resistant nematodes in goats maintained under a semi-intensive system of management at the University goat farm, Jabalpur. Fifty goats were randomly assigned to five groups, each comprising 10 animals, irrespective of their breed, age and sex. Each animal in Group I, II and III was orally administered with aqueous leaf extracts of neem (Azadirachta indica) at 1 g/kg body weight, sitaphal (Annona squamosa) at 1.5 g/kg body weight and tobacco (Nicotiana tabacum) at 1 g/kg body weight, respectively, whereas Group IV was an untreated control group. Each animal in Group V was orally treated with closantel at 10 mg/kg body weight. During the course of the study, all animals were maintained under an identical semi-intensive system of management. Compared to the untreated control group (Group IV), there was no conspicuous reduction in post-treatment (day 10) faecal egg counts (FEC) in animals administered with the herbal extracts (Groups I, II and III), which is suggestive of poor anti-parasitic activity. However, using the faecal egg count reduction test (FECRT), the overall efficacy of closantel was recorded as 95.64%. This supports the rotational use of closantel as a preferred choice over the benzimidazole group of anthelmintics and/or herbal extracts to meet the acute challenge of in situ development of drug-resistant gastrointestinal nematodes, especially Haemonchus contortus.

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.

In reproducing ewes, a periparturient breakdown of immunity is often observed to result in increased fecal egg excretion, making them the main source of infection for their immunologically naive lambs. In this study, we expanded a simulation model previously developed for growing lambs to explore the impact of the genotype (performance and resistance traits) and host nutrition on the performance and parasitism of both growing lambs and reproducing ewes naturally infected with Teladorsagia circumcincta. Our model accounted for nutrient-demanding phases, such as gestation and lactation, and included a supplementary module to manage the age structure of the ewe flock. The model was validated by comparison with published data. Because model parameters were unknown or poorly estimated, detailed sensitivity analysis of the model was performed for the sheep mortality and the level of infection, following a preliminary screening step. The parameters with the greatest effect on parasite-related outputs were those driving animal growth and milk yield. Our model enables different parasite-control strategies (host nutrition, breeding for resistance and anthelmintic treatments) to be assessed on the long term in a sheep flock. To optimize in silico exploration, the parameters highlighted by the sensitivity analysis should be refined with real data.

Infectious diseases are major constraint that hinders the poultry industry. Among them parasitic diseases are very common and Ascaridia galli is one of the most common parasitic roundworms found in poultry. Haemorrhages, diarrhoea and listlessness are signs of infection. Parasitic infections such as A. galli are treated with chemical anthelmintics (piperazine, albendazole, levamisole, Ivermectin, benzimidazoles and fenbendazole). These synthetic chemicals can promote resistance, so there is need for alternative ways to treat the disease. Medicinal plants have the potential to combat such parasitism and the development of anthelmintic resistance appears to be very slow against such treatment. This review covers the studies related to the screening of plant materials having in vitro and in vivo anthelmintic activities against A. galli throughout the world. Medicinal plants showing in vitro anthelmintic activity include Anacardium occidentale, Allium sativum, Tribulus terrestris, Bassia latifolia, Piper betle, Morinda citrifolia L.I, Cassia occidentalis L. and Aloe secundiflora while in vivo studies include the use of Psorelia corylifolia, Piper betle, Pilostigma thonningi, Caesalpinia crista, Ocimum gratissimum and Anacardium occidentale. In conclusion, medicinal plants appear to have good anthelmintic activities in poultry and may substitute conventionally used synthetic drugs, and their use may moderate drug resistance in endemic pathogen populations and drug residues in poultry meat.

Eight strains of mice, of contrasting genotypes, infected with Heligmosomoides bakeri were studied to determine whether the anthelmintic efficacy of papaya latex varied between inbred mouse strains and therefore whether there is an underlying genetic influence on the effectiveness of removing the intestinal nematode. Infected mice were treated with 330 nmol of crude papaya latex or with 240 nmol of papaya latex supernatant (PLS). Wide variation of response between different mouse strains was detected. Treatment was most effective in C3H (90·5–99·3% reduction in worm counts) and least effective in CD1 and BALB/c strains (36·0 and 40·5%, respectively). Cimetidine treatment did not improve anthelmintic efficacy of PLS in a poor drug responder mouse strain. Trypsin activity, pH and PLS activity did not differ significantly along the length of the gastro-intestinal (GI) tract between poor (BALB/c) and high (C3H) drug responder mouse strains. Our data indicate that there is a genetic component explaining between-mouse variation in the efficacy of a standard dose of PLS in removing worms, and therefore warrant some caution in developing this therapy for wider scale use in the livestock industry, and even in human medicine.

Fasciola hepatica is a pathogenic trematode parasite of ruminants with a global distribution. Here, we briefly review the current epidemiology of bovine fasciolosis in Europe and discuss the progress made over the last decade in the diagnosis, impact on production and prediction of F. hepatica in cattle. Advances in diagnosis have led to significantly improved coprological and serological methods to detect presence of infection. Diagnostic test results have been correlated with intensity of infection and associated production losses, unravelling the impact on carcass weight and milk yield in modern cattle production systems. The economic impact of fasciolosis may, however, go beyond the direct impacts on production as evidence shows that F. hepatica can modulate the immune response to some co-infections. Control of bovine fasciolosis remains hampered by the limitations of the currently available flukicidal drugs: few drugs are available to treat dairy cows, many have low efficacies against juvenile stages of F. hepatica and there is evidence for the development of drug resistance. This makes research into the prediction of risk periods, and thus the optimum application of available drugs more pertinent. In this field, the recent research focus has been on understanding spatial risk and delivering region-specific spatial distribution maps. Further advances in epidemiological and economic research on bovine fasciolosis are expected to deliver farm-specific economic assessments of disease impact, to leverage non-chemotherapeutic management options and to enhance a more targeted use of anthelmintics.

The cyclooctadepsipeptide PF1022A and the aminophenylamidines amidantel, deacylated amidantel (dAMD) and tribendimidine were tested as examples for drug classes potentially interesting for development as anthelmintics against human helminthiases. These compounds and levamisole were tested alone and in combination to determine their efficacy against the rat hookworm Nippostrongylus brasiliensis. After three oral treatments, intestinal worms were counted. Drug effects on parasite morphology were studied using scanning electron microscopy (SEM). Plasma pharmacokinetics were determined for tribendimidine and dAMD. All drugs reduced worm burden in a dose-dependent manner, however amidantel was significantly less active than the other aminophenylamidines. Combinations of tribendimidine and dAMD with levamisole or PF1022A at suboptimal doses revealed additive effects. While PF1022A caused virtually no changes in morphology, levamisole, dAMD and tribendimidine caused severe contraction, particularly in the hind body region. Worms exposed to combinations of PF1022A and aminophenylamidines were indistinguishable from worms exposed only to aminophenylamidines. After oral treatment with tribendimidine, only the active metabolite dAMD was detectable in plasma and concentrations were not significantly different for oral treatment with dAMD. The results support further evaluation of cyclooctadepsipeptides alone and in combination with cholinergic drugs to improve efficacy. Combining these with registered drugs may help to prevent development of resistance.

Administration to rats of tetramisole loaded into zeolite was more successful in killing adults of Nippostrongylus brasiliensis than the administration of tetramisole alone. The most successful treatment occurred in SPF (Specific Pathogen Free) rats dosed with tetramisole loaded into zeolite and no worms were present in this group at autopsy eight days post-infection. It is concluded that the slow release of drug from the zeolite matrix improved its efficacy, especially in removing worms from low-grade infections.

In an experimental larval infection of Ancylostoma caninum in mice, the efficacy of various anthelmintics against the larvae migrated and established in the brain is reported for the first time. Albendazole and flubendazole were the most effective drugs. Thiabendazole, benacil, phenacizole, oxfendazole and mebendazole showed significant larvicidal activity. Tetramisole, levamisole, fenbendazole, Sch 18099, pyrantel pamoate, morantel tartrate and oxantel pamoate did not show any significant activity even at relatively high dose levels.

Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals.

Cyclosporin A (CsA) acts as a powerful immunosuppressant through its binding to the cytosolic isomerase, cyclophilin (CyP), forming a complex which inhibits the phosphatase activity of calcineurin. The drug is also selectively anti-parasitic but its mode of action remains unknown. The mouse tapeworm, Hymenolepis microstoma is sensitive to CsA, but the rat tapeworm, H. diminuta is not susceptible either in rats, mice or in vitro. Using these two tapeworm models, the uptake and binding of CsA were examined in relation to parasite cyclophilins. Uptake and compartmentalization of the drug were markedly different in the two species: H. microstoma takes up more drug than does H. diminuta and sequesters more drug into intracellular compartments. Characterization of cyclophilins using both CsA binding and isomerase activity assays reveals that H. microstoma possesses two cyclophilin isoforms (Mr 17700 and 21400) with isomerase activity that is inhibited by CsA. Using identical assays, we have been unable to demonstrate CsA-binding proteins or CsA-sensitive isomerase activity in H. diminuta. These data suggest that the anthelmintic action of CsA relates in some way to the presence and function of parasite cyclophilins.

The in vivo effects of the anthelmintics taenifugin, VÚFB 14170 and VÚFB 15269 on the tegument of Hymenolepis fraterna have been examined by SEM, TEM and cytochemistry. The drugs were given to H. fraterna-infected mice on the 14th day post-infection in a single oral dose of 150, 200 and 200 mg/kg, respectively. By 72 h post-treatment, the drug-induced pathomorphological changes in the tegument indicated that all three drugs had a significant effect. Changes were most pronounced on the brush border and in the intercellular material. On the apical surface, there was blebbing as well as accumulation of membrane fragments over the microthrix tips and erosion of the brush border. The intercellular material was changed in structure, showing increased electron density in some areas and oedema of the intercellular spaces in other areas. There were also fractures of the tegument of variable depth, sometimes reaching to the parenchyma. These results suggest altered tegumental integrity and, occasionally, complete disruption of the selective permeability barrier created by the normal tegument. This suggestion is further supported by the penetration of ruthenium red into some tegumental areas and its distribution into the intercellular spaces, down to the parenchyma. The intrategumental lysosomes also appeared to be significantly activated. There was evidence of autophagy in both distal cytoplasm and tegumental cells. Mature and gravid proglottides were more susceptible to drug damage than those in the anterior strobila and neck.

The present review will examine epidemiological perspectives and be confined mainly to the results of those field studies published since 1975 in order to provide concrete scientific evidence of the effect of ascariasis on childhood malnutrition, particularly on growth. The field studies were done in many developing countries from Africa, Asia and Latin America, using cross-sectional and intervention studies in which anthelmintics were employed, with different dosing frequency and follow-up periods ranging from 33 days to 2 years. In general, a better nutritional status in terms of growth, lactose tolerance, vitamins A and C, and albumin levels were observed among Ascaris–free or treated than among Ascaris–infected or untreated children even in cross-sectional or non-randomized studies. More importantly, the improvement in weight or height after chemotherapeutic treatment was found to be significant particularly in those randomized controlled studies with an initially high prevalence of ascariasis and malnutrition, a low prevalence of other intestinal parasites, repetitive and regular treatments of children with tetramisole, levamisole or pyrantel, within a period of 12 or 24 months. Reasons for failures to detect improved growth in some studies are provided. This review strongly indicates that A. lumbricoides infection definitely retards childhood growth.

Efforts to curb production losses caused by nematode parasitism in sheep have led to the development of a number of control methods to complement or replace anthelmintics. The need for alternative control measures stems from the emergence of anthelmintic-resistant parasitic nematodes with reports of multi-class resistance to these drugs now emerging. A number of these control methods such as predacious microfungi, protein supplementation, plant extracts in feed and vaccines have demonstrated potential to control infection but require development and examination under natural conditions. Breeding for natural resistance to nematode infection has already shown success in controlling the disease under natural conditions. Selection for resistance is currently based on fecal egg count measurements but identification of genetic indicators of resistance will provide a more efficient method of selection. Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6. This paper reviews the current alternatives to anthelmintics to control infection, with an emphasis on breeding for host resistance and identification of genetic indicators of resistance.

The influence of density-dependent processes on the transmission of parasitic helminths is determined by both the severity of the regulatory constraints and the degree of parasite overdispersion among the host population. We investigate how overdispersed parasite distributions among humans influence transmission levels in both directly- and indirectly-transmitted nematodes (Ascaris lumbricoides and Onchocerca volvulus). While past work has assumed, for simplicity, that density dependence acts on the average worm load, here we model density-dependence as acting on individual parasite burdens before averaging across hosts. A composite parameter, which we call the effective transmission contribution, is devised to measure the number of transmission stages contributed by a given worm burden after incorporating overdispersion in adult worm mating probabilities and other density-dependent mechanisms. Results indicate that the more overdispersed the parasite population, the greater the effect of density dependence upon its transmission dynamics. Strong regulation and parasite overdispersion make the relationship between mean worm burden and its effective contribution to transmission highly non-linear. Consequently, lowering the intensity of infection in a host population using chemotherapy may produce only a small decline in transmission (relative to its initial endemic level). Our analysis indicates that when parasite burden is low, intermediate levels of parasite clustering maximize transmission. Implications are discussed in relation to existing control programmes and the spread of anthelmintic resistance.

Thirty crossbreed steer calves were randomly assigned to one of three feedlot treatment groups to evaluate the effectiveness of diatomaceous earth (DE) as an anthelmintic treatment and its effect on subsequent growth performance. Steers were adapted to a cereal-based diet for 15 days on the farm of origin and given an additional 21 days to adjust to the feedlot diet. Calves had not been dewormed prior to starting the study. On day 0 (2 January 1996) the positive control group of steers (CONV; no. = 11) was given 10 mg/kg of albendazole, a second group began receiving (on day 2) 0·3 kg of diatomaceous earth (DE; no. = 9) mixed daily with their food for 46 days and the negative control group (CTRL, no. = 9) received no anthelmintic treatment. Rectal faecal samples were collected upon arrival at the feedlot and the resulting egg counts showed that all steers were positive for nematodes and coccidia. Faecal samples were collected on days 0, 15, 28 and every 28 days thereafter to determine faecal egg counts. The last sample was taken on the day of slaughter. On day 0, the average count for all calves was over 70 eggs per g faeces (epg) for trichostrongyle type eggs; counts for Nematodirus sp., Strongyloides sp., Trichuris sp. and Capillaria sp. were negligible. CTRL and DE steers had higher parasite levels than CONV steers during the 1st (P < 0·01) and 2nd months (P < 0·05) after treatment. Egg counts for CTRL and DE groups decreased in March and none of the groups differed (P > 0·05) significantly for the remainder of the study. Coccidia levels decreased over time similarly for all groups. Offering 20 g DE per kg food intake for 46 days to beef steers on a high cereal -based diet had no effect (P > 0·05) on body weight, average daily gain, dry-matter intake, food conversion or days on food compared with the untreated control steers. Cumulative food conversion during the first 2 months was better for CONV than for DE and CTRL steers (P < 0·01) but did not differ between the latter two groups (P > 0·05). Cumulative food conversion for the rest of the study remained the same for all groups (P > 0·05). CONV calves required fewer days on food than DE calves (P < 0·05) but about the same number as CTRL calves (P > 0·10). Steers in the DE group required a similar number of days on food (230·22 ± 7·86 days) to reach target end points as CTRL steers (218·75 ± 8·34 days; P > 0·05) but more days than CONV calves (201·64 ± 7·11 days; P > 0·05).