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1.
Vet Parasitol Reg Stud Reports ; 51: 101028, 2024 Jun.
Article En | MEDLINE | ID: mdl-38772650

In Australian pastoral dairy systems, a variety of 'routine' anthelmintic programs are used in lactating cows varying from nil anthelmintic use to bi-annual application. Anthelmintic resistance has been repeatedly diagnosed on dairy farms and studies have indicated variable milk production benefits from anthelmintics internationally. We aimed to identify the predominant gastrointestinal parasites in recently calved dairy cows in south-west Victoria and examined the relationship between individual faecal egg counts (FEC) and other cow and management factors such as body condition score, age, and historical anthelmintic use. This study included 18 pasture-based dairy farms in south-west Victoria. FECs were measured in recently calved primiparous and multiparous cows. Individual FEC tests with a minimum detectable FEC of 2.5 eggs per gram of faeces (epg) and group larval cultures were completed. Farm management data and cow information was recorded for data analysis with the Jamovi statistical package. Overall, 35% of all cows had FEC ≥ 2.5 epg (26% of multiparous and 45% of primiparous). Ostertagi ostertagi was the predominant gastrointestinal nematode in all cohorts. Cooperia pectinata or C. punctata were also present in mixed infestations alongside C. oncophora. Multiparous cows in low body condition score post calving (<4) were more likely to have a FEC of >5 epg. Faecal egg counts at a minimum detectable FEC of 2.5 epg are effective indicators of parasitism in recently calved primiparous and poorly conditioned multiparous dairy cows. Increasing the test sensitivity (minimum detectable count) of FECs from 10 epg to 2.5 epg resulted in increasing the overall positive FEC rate from 15% to 35%. Further investigation of sensitive FECs and their relevance to production along with the timing and value of anthelmintic use in dairy cattle is warranted.


Anthelmintics , Cattle Diseases , Dairying , Feces , Parasite Egg Count , Animals , Cattle , Feces/parasitology , Female , Parasite Egg Count/veterinary , Cattle Diseases/parasitology , Cattle Diseases/epidemiology , Cattle Diseases/drug therapy , Victoria/epidemiology , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Australia
2.
BMC Complement Med Ther ; 24(1): 183, 2024 May 04.
Article En | MEDLINE | ID: mdl-38704537

BACKGROUND: Highlighting affordable alternative crops that are rich in bioactive phytoconstituents is essential for advancing nutrition and ensuring food security. Amaranthus blitum L. (AB) stands out as one such crop with a traditional history of being used to treat intestinal disorders, roundworm infections, and hemorrhage. This study aimed to evaluate the anthelmintic and hematologic activities across various extracts of AB and investigate the phytoconstituents responsible for these activities. METHODS: In vitro anthelmintic activity against Trichinella spiralis was evaluated in terms of larval viability reduction. The anti-platelet activities were assessed based on the inhibitory effect against induced platelet aggregation. Further, effects on the extrinsic pathway, the intrinsic pathway, and the ultimate common stage of blood coagulation, were monitored through measuring blood coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT), respectively. The structures of isolated compounds were elucidated by spectroscopic analysis. RESULTS: Interestingly, a previously undescribed compound (19), N-(cis-p-coumaroyl)-ʟ-tryptophan, was isolated and identified along with 21 known compounds. Significant in vitro larvicidal activities were demonstrated by the investigated AB extracts at 1 mg/mL. Among tested compounds, compound 18 (rutin) displayed the highest larvicidal activity. Moreover, compounds 19 and 20 (N-(trans-p-coumaroyl)-ʟ-tryptophan) induced complete larval death within 48 h. The crude extract exhibited the minimal platelet aggregation of 43.42 ± 11.69%, compared with 76.22 ± 14.34% in the control plasma. Additionally, the crude extract and two compounds 19 and 20 significantly inhibited the extrinsic coagulation pathway. CONCLUSIONS: These findings extend awareness about the nutritional value of AB as a food, with thrombosis-preventing capabilities and introducing a promising source for new anthelmintic and anticoagulant agents.


Amaranthus , Anthelmintics , Anticoagulants , Phytochemicals , Plant Extracts , Platelet Aggregation Inhibitors , Animals , Anthelmintics/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytochemicals/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Anticoagulants/pharmacology , Larva/drug effects
3.
Nat Commun ; 15(1): 3367, 2024 May 08.
Article En | MEDLINE | ID: mdl-38719808

Soil-transmitted helminths (STHs) are major pathogens infecting over a billion people. There are few classes of anthelmintics and there is an urgent need for new drugs. Many STHs use an unusual form of anaerobic metabolism to survive the hypoxic conditions of the host gut. This requires rhodoquinone (RQ), a quinone electron carrier. RQ is not made or used by vertebrate hosts making it an excellent therapeutic target. Here we screen 480 structural families of natural products to find compounds that kill Caenorhabditis elegans specifically when they require RQ-dependent metabolism. We identify several classes of compounds including a family of species-selective inhibitors of mitochondrial respiratory complex I. These identified complex I inhibitors have a benzimidazole core and we determine key structural requirements for activity by screening 1,280 related compounds. Finally, we show several of these compounds kill adult STHs. We suggest these species-selective complex I inhibitors are potential anthelmintics.


Anthelmintics , Caenorhabditis elegans , Electron Transport Complex I , Ubiquinone/analogs & derivatives , Animals , Anthelmintics/pharmacology , Anthelmintics/chemistry , Electron Transport Complex I/antagonists & inhibitors , Electron Transport Complex I/metabolism , Caenorhabditis elegans/metabolism , Benzimidazoles/pharmacology , Benzimidazoles/chemistry , Species Specificity , Quinones/chemistry , Quinones/pharmacology , Quinones/metabolism , Biological Products/pharmacology , Biological Products/chemistry
4.
Parasitol Res ; 123(5): 215, 2024 May 21.
Article En | MEDLINE | ID: mdl-38771511

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.


Amiodarone , Disease Models, Animal , Praziquantel , Schistosoma mansoni , Schistosomiasis mansoni , Animals , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/parasitology , Mice , Schistosoma mansoni/drug effects , Praziquantel/therapeutic use , Praziquantel/pharmacology , Amiodarone/therapeutic use , Amiodarone/pharmacology , Female , Spironolactone/therapeutic use , Spironolactone/pharmacology , Schistosomicides/therapeutic use , Schistosomicides/pharmacology , Male , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Treatment Outcome , Drug Therapy, Combination , Liver/parasitology
5.
Fish Shellfish Immunol ; 149: 109613, 2024 Jun.
Article En | MEDLINE | ID: mdl-38710341

Aporocotylids (Trematoda: Digenea), also known as fish blood flukes infect the circulatory system of fish leading to serious health problems and mortality. Aporocotylids are a particular concern for farmed fish as infection intensity can increase within the farming environment and lead to mortalities. In the context of managing these infections, one of the most crucial aspects to consider is the host response of the infected fish against these blood flukes. Understanding the response is essential to improving current treatment strategies that are largely based on the use of anthelmintic praziquantel to manage infections in aquaculture. This review focuses on the current knowledge of farmed fish host responses against the different life stages of aporocotylids. New treatment strategies that are able to provide protection against reinfections should be a long-term goal and is not possible without understanding the fish response to infection and the interactions between host and parasite.


Aquaculture , Fish Diseases , Fishes , Trematoda , Trematode Infections , Animals , Trematode Infections/veterinary , Trematode Infections/immunology , Trematode Infections/parasitology , Trematode Infections/drug therapy , Fish Diseases/immunology , Fish Diseases/parasitology , Trematoda/physiology , Fishes/immunology , Fishes/parasitology , Host-Parasite Interactions , Anthelmintics/therapeutic use , Anthelmintics/pharmacology
6.
Parasit Vectors ; 17(1): 225, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755679

BACKGROUND: The giant roundworm Ascaris is an intestinal nematode, causing ascariasis by infecting humans and pigs worldwide. Recent estimates suggest that Ascaris infects over half a billion people, with chronic infections leading to reduced growth and cognitive ability. Ascariasis affects innumerable pigs worldwide and is known to reduce production yields via decreased growth and condemnation of livers. The predominant anthelminthic drugs used to treat ascariasis are the benzimidazoles. Benzimidazoles interact with ß-tubulins and block their function, and several benzimidazole resistance-associated mutations have been described in the ß-tubulins of ruminant nematodes. Recent research on ascarids has shown that these canonical benzimidazole resistance-associated mutations are likely not present in the ß-tubulins of Ascaris, Ascaridia or Parascaris, even in phenotypically resistant populations. METHODS: To further determine the putative absence of key ß-tubulin polymorphisms, we screened two ß-tubulin isotypes of Ascaris, highly expressed in adult worms. Using adult and egg samples of Ascaris obtained from pigs and humans worldwide, we performed deep amplicon sequencing to look for canonical resistance-associated mutations in Ascaris ß-tubulins. Subsequently, we examined these data in closer detail to study the population dynamics of Ascaris and genetic diversity within the two isotypes and tested whether genotypes appeared to partition across human and pig hosts. RESULTS: In the 187 isolates, 69 genotypes were found, made up of eight haplotypes of ß-tubulin isotype A and 20 haplotypes of isotype B. Single nucleotide polymorphisms were seen at 14 and 37 positions for ß-tubulin isotype A and isotype B, respectively. No evidence of any canonical benzimidazole resistance-associated mutations was found in either human- or pig-derived Ascaris isolates. There was, however, a difference in the genetic diversity of each isotype and distribution of ß-tubulin genotypes between human- and pig-derived Ascaris. Statistical tests of population differentiation show significant differences (p < 0.001) between pig- and human-derived worms; however, more diversity was seen between worms from different populations than worms from different hosts. CONCLUSIONS: Our work suggests an absence of canonical ß-tubulin mutations within Ascaris, but alternative modes of anthelminthic resistance may emerge necessitating continued genetic scrutiny alongside monitoring of drug efficacy.


Anthelmintics , Ascariasis , Ascaris , Benzimidazoles , Drug Resistance , Mutation , Tubulin , Tubulin/genetics , Animals , Benzimidazoles/pharmacology , Drug Resistance/genetics , Ascariasis/parasitology , Ascariasis/veterinary , Ascariasis/drug therapy , Anthelmintics/pharmacology , Swine , Ascaris/genetics , Ascaris/drug effects , Humans , Swine Diseases/parasitology , Swine Diseases/drug therapy
7.
J Helminthol ; 98: e40, 2024 May 13.
Article En | MEDLINE | ID: mdl-38738533

In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.


Albendazole , Echinococcosis , Plant Extracts , Pomegranate , Animals , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Pomegranate/chemistry , Mice , Echinococcosis/drug therapy , Echinococcosis/parasitology , Albendazole/pharmacology , Albendazole/administration & dosage , Anthelmintics/pharmacology , Anthelmintics/administration & dosage , Disease Models, Animal , Microscopy, Electron, Transmission , Interferon-gamma/blood , Female , Male
8.
ACS Infect Dis ; 10(5): 1664-1678, 2024 May 10.
Article En | MEDLINE | ID: mdl-38686397

In this study, we have identified and optimized two lead structures from an in-house screening, with promising results against the parasitic flatworm Schistosoma mansoni and its target protease S. mansoni cathepsin B1 (SmCB1). Our correlation analysis highlighted the significance of physicochemical properties for the compounds' in vitro activities, resulting in a dual approach to optimize the lead structures, regarding both phenotypic effects in S. mansoni newly transformed schistosomula (NTS), adult worms, and SmCB1 inhibition. The optimized compounds from both approaches ("phenotypic" vs "SmCB1" approach) demonstrated improved efficacy against S. mansoni NTS and adult worms, with 2h from the "SmCB1" approach emerging as the most potent compound. 2h displayed nanomolar inhibition of SmCB1 (Ki = 0.050 µM) while maintaining selectivity toward human off-target cathepsins. Additionally, the greatly improved efficacy of compound 2h toward S. mansoni adults (86% dead worms at 10 µM, 68% at 1 µM, 35% at 0.1 µM) demonstrates its potential as a new therapeutic agent for schistosomiasis, underlined by its improved permeability.


Cathepsin B , Schistosoma mansoni , Schistosoma mansoni/drug effects , Schistosoma mansoni/enzymology , Schistosoma mansoni/genetics , Animals , Cathepsin B/antagonists & inhibitors , Cathepsin B/metabolism , Schistosomiasis mansoni/drug therapy , Drug Design , Humans , Phenotype , Structure-Activity Relationship , Anthelmintics/pharmacology , Anthelmintics/chemistry , Helminth Proteins/antagonists & inhibitors
9.
Parasitology ; 151(5): 523-528, 2024 Apr.
Article En | MEDLINE | ID: mdl-38571299

Dipylidium caninum is a common tapeworm of dogs. Two cases of praziquantel resistance have been described in D. caninum in the United States. No further reports have been published to the authors' knowledge. Here, the case of a dog imported to Switzerland from Spain with a history of chronic excretion of tapeworm proglottids and unresponsiveness to praziquantel treatments is reported. Clinical signs were mild (restlessness, tenesmus, anal pruritus, squashy feces) and flea infestation could be ruled out. Infection with D. caninum was confirmed through morphological and genetic parasite identification. Different subsequently applied anthelmintic compounds and protocols, including epsiprantel, did not confer the desired effects. Proglottid shedding only stopped after oral mebendazole administration of 86.2 mg kg−1 body weight for 5 consecutive days. Clinical signs resolved and the dog remained coproscopically negative during a follow-up period of 10 months after the last treatment. This case represents the first reported apparent praziquantel and epsiprantel resistance in D. caninum in Europe. Treatment was extremely challenging especially due to the limited availability of efficacious alternative compounds.


Anthelmintics , Cestode Infections , Dog Diseases , Drug Resistance , Praziquantel , Animals , Praziquantel/therapeutic use , Praziquantel/pharmacology , Praziquantel/administration & dosage , Dogs , Dog Diseases/parasitology , Dog Diseases/drug therapy , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Cestode Infections/drug therapy , Cestode Infections/veterinary , Cestode Infections/parasitology , Switzerland , Cestoda/drug effects , Spain , Feces/parasitology , Male
10.
Exp Parasitol ; 261: 108751, 2024 Jun.
Article En | MEDLINE | ID: mdl-38604302

Anisakiasis is a parasitic disease transmitted through the consumption of raw or undercooked fish and cephalopods that are infected with larvae of Anisakis simplex (sensu stricto) or Anisakis pegreffii. The purpose of this study was to investigate how A. simplex (s. s.) responds to the influence of anthelmintics such as ivermectin (IVM) and pyrantel (PYR). In vitro experiments were conducted using larvae at two developmental stages of A. simplex (s. s.) (L3 and L4) obtained from Baltic herring (Clupea harengus membras). Larvae were cultured with different concentrations of IVM or PYR (1.56, 3.125, and 6.25 µg/mL) for various durations (3, 6, 9, and 12 h) under anaerobic conditions (37 °C, 5% CO2). The gene expression of actin, ABC transporter, antioxidant enzymes, γ-aminobutyric acid receptors, and nicotinic acetylcholine receptors, as well as the oxidative status were analyzed. The results showed that A. simplex (s. s.) L3 stage had lower mobility when cultured with PYR compared to IVM. The analysis of relative gene expression revealed significant differences in the mRNA level of ABC transporters after treatment with IVM and PYR, compared to the control group. Similar patterns were observed in the gene expression of antioxidant enzymes in response to both drugs. Furthermore, the total antioxidant capacity (TAC) and glutathione S-transferase (GST) activity were higher in the treatment groups than in the control group. These findings suggest a relationship between the expression of the studied genes, including those related to oxidative metabolism, and the effectiveness of the tested drugs.


Anisakis , Anthelmintics , Ivermectin , Larva , Pyrantel , Animals , Anisakis/drug effects , Anisakis/genetics , Anisakis/growth & development , Ivermectin/pharmacology , Larva/drug effects , Larva/genetics , Anthelmintics/pharmacology , Pyrantel/pharmacology , Actins/metabolism , Actins/genetics , Actins/drug effects , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Receptors, Nicotinic/metabolism , Receptors, Nicotinic/genetics , Receptors, Nicotinic/drug effects , Xenobiotics/pharmacology , Xenobiotics/metabolism , Gene Expression/drug effects , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Anisakiasis/parasitology , Anisakiasis/veterinary , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/drug effects , Catalase/genetics , Catalase/metabolism , Catalase/drug effects , Fishes/parasitology , Fish Diseases/parasitology
11.
Exp Parasitol ; 261: 108768, 2024 Jun.
Article En | MEDLINE | ID: mdl-38679124

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus.


Anthelmintics , Catalase , Gerbillinae , Glutathione , Haemonchiasis , Haemonchus , Oxidative Stress , Plant Extracts , Plant Leaves , Superoxide Dismutase , Animals , Haemonchus/drug effects , Plant Leaves/chemistry , Oxidative Stress/drug effects , Haemonchiasis/veterinary , Haemonchiasis/drug therapy , Haemonchiasis/parasitology , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Anthelmintics/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Superoxide Dismutase/metabolism , Catalase/metabolism , Catalase/analysis , Glutathione/metabolism , Glutathione/analysis , Gas Chromatography-Mass Spectrometry , Male , Parasite Egg Count/veterinary , Biomarkers , Glutathione Peroxidase/metabolism , Female
12.
Vet Parasitol ; 328: 110182, 2024 Jun.
Article En | MEDLINE | ID: mdl-38603925

Anthelmintic performance against equine cyathostomins can be evaluated by two different non-terminal measures; the Fecal Egg Count Reduction Test (FECRT) and the Egg Reappearance Period (ERP). Most available FECRT and ERP data have been determined in populations of young horses, and very little information is available from mature and senior horses. Furthermore, it is unknown how commonly occurring equine endocrine disorders such as Insulin dysregulation (ID) and Pituitary pars intermedia dysfunction (PPID) may interfere with these measurements, but it has been suggested that horses with these conditions could be more susceptible to parasitic infections. A research population of senior horses and horses with or without PPID, ID, or both were enrolled in this study. All strongylid egg count positive horses were included in an ivermectin (200 µg/kg) efficacy study. These were distributed among the following groups: ID: six, PPID: three, PPID and ID: seven, and healthy controls: three. Strongylid fecal egg counts were determined on the day of ivermectin administration, at two weeks post deworming, and on weekly intervals until eight weeks post treatment. Determination of FECRT and ERP were carried out following World Association for the Advancement of Veterinary Parasitology guidelines. Results revealed high ivermectin efficacy with mean egg count reduction at 99.7% or above in all groups at two weeks post treatment. Egg reappearance was documented at six and seven weeks in the ID and PPID/ID groups, respectively, whereas the PPID and healthy control groups both had ERP at 8 weeks. Statistical analysis found no significant differences in egg count levels between groups during the study. The expected ERP for ivermectin is 8-10 weeks, meaning that two of the groups displayed shortened ERPs. However, due to the small group sizes, these data should be interpreted with caution. Nonetheless, results do indicate a need for further investigation of the possible influence of endocrine disorders on anthelmintic performance in horses.


Feces , Horse Diseases , Ivermectin , Parasite Egg Count , Animals , Horses , Ivermectin/therapeutic use , Ivermectin/pharmacology , Horse Diseases/drug therapy , Horse Diseases/parasitology , Parasite Egg Count/veterinary , Feces/parasitology , Female , Endocrine System Diseases/veterinary , Endocrine System Diseases/drug therapy , Male , Anthelmintics/therapeutic use , Anthelmintics/pharmacology , Antiparasitic Agents/therapeutic use , Antiparasitic Agents/pharmacology
13.
J Ethnopharmacol ; 328: 118132, 2024 Jun 28.
Article En | MEDLINE | ID: mdl-38565411

ETHNOPHARMACOLOGICAL RELEVANCE: Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. AIM OF THE STUDY: The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt ß-tubulin function in helminths. METHODS: The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the ß-tubulin protein target (PDB ID: 1SA0). RESULTS: The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol. CONCLUSION: Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.


Anthelmintics , Haemonchus , Helminthiasis , Limonins , Plants, Medicinal , Adult , Animals , Humans , Plants, Medicinal/chemistry , Tubulin , Anthelmintics/pharmacology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytochemicals/pharmacology , Colchicine
14.
Parasit Vectors ; 17(1): 173, 2024 Apr 03.
Article En | MEDLINE | ID: mdl-38570858

BACKGROUND: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides. METHODS: The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite. RESULTS: After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation. CONCLUSIONS: BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds.


Anthelmintics , Fasciola hepatica , Fascioliasis , Animals , Humans , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Benzimidazoles/pharmacology , Benzimidazoles/therapeutic use , Fascioliasis/parasitology , Antinematodal Agents/therapeutic use
15.
BMC Genomics ; 25(1): 341, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575858

BACKGROUND: Parasitic nematodes, significant pathogens for humans, animals, and plants, depend on diverse organ systems for intra-host survival. Understanding the cellular diversity and molecular variations underlying these functions holds promise for developing novel therapeutics, with specific emphasis on the neuromuscular system's functional diversity. The nematode intestine, crucial for anthelmintic therapies, exhibits diverse cellular phenotypes, and unraveling this diversity at the single-cell level is essential for advancing knowledge in anthelmintic research across various organ systems. RESULTS: Here, using novel single-cell transcriptomics datasets, we delineate cellular diversity within the intestine of adult female Ascaris suum, a parasitic nematode species that infects animals and people. Gene transcripts expressed in individual nuclei of untreated intestinal cells resolved three phenotypic clusters, while lower stringency resolved additional subclusters and more potential diversity. Clusters 1 and 3 phenotypes displayed variable congruence with scRNA phenotypes of C. elegans intestinal cells, whereas the A. suum cluster 2 phenotype was markedly unique. Distinct functional pathway enrichment characterized each A. suum intestinal cell cluster. Cluster 2 was distinctly enriched for Clade III-associated genes, suggesting it evolved within clade III nematodes. Clusters also demonstrated differential transcriptional responsiveness to nematode intestinal toxic treatments, with Cluster 2 displaying the least responses to short-term intra-pseudocoelomic nematode intestinal toxin treatments. CONCLUSIONS: This investigation presents advances in knowledge related to biological differences among major cell populations of adult A. suum intestinal cells. For the first time, diverse nematode intestinal cell populations were characterized, and associated biological markers of these cells were identified to support tracking of constituent cells under experimental conditions. These advances will promote better understanding of this and other parasitic nematodes of global importance, and will help to guide future anthelmintic treatments.


Anthelmintics , Nematoda , Humans , Animals , Caenorhabditis elegans , Intestines , Nematoda/genetics , Gene Expression Profiling , Anthelmintics/pharmacology , Anthelmintics/therapeutic use
16.
BMC Vet Res ; 20(1): 137, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575964

OBJECTIVES: Fasciolosis is of significant economic and public health importance worldwide. The lack of a successful vaccine and emerging resistance in flukes to the drug of choice, triclabendazole, has initiated the search for alternative approaches. In recent years, metallic nanoparticles have been extensively investigated for their anthelmintic effects. This study investigates the in vitro anthelmintic activity of copper oxide and zinc oxide nanoparticles against Fasciola hepatica. METHODS: The in vitro study was based on egg hatchability test (EHA), adult motility inhibition tests, DNA damage, ROS levels, as well as several biomarkers of oxidative stress, including glutathione peroxidase (GSH) and glutathione S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). For this purpose, different concentrations of copper oxide nanoparticles (CuO-NPs) and Zinc oxide nanoparticles (ZnO-NPs) (1, 4, 8, 12, and 16 ppm) were used to evaluate the anthelmintic effect on different life stages, including egg and adults of Fasciola hepatica, over 24 h. RESULTS: In vitro treatment of F. hepatica worms with both CuO-NPs and ZnO-NPs could significantly increase ROS production and oxidative stress induction (decreased SOD, GST and GSH and increased MDA) compared to control group. CONCLUSIONS: Based on the results, it seems that CuO-NPs and ZnO-NPs may be effective in the control and treatment of F. hepatica infection. Further research is needed to investigate their potential for in vivo use in the treatment of parasitic infections.


Anthelmintics , Fasciola hepatica , Metal Nanoparticles , Nanoparticles , Zinc Oxide , Animals , Zinc Oxide/pharmacology , Copper/pharmacology , Reactive Oxygen Species , Oxidative Stress , Anthelmintics/pharmacology , DNA Damage , Superoxide Dismutase/metabolism , Biomarkers
17.
Parasitology ; 151(4): 421-428, 2024 Apr.
Article En | MEDLINE | ID: mdl-38576256

Cystic echinococcosis (CE), caused by the larval stage of the cestode Echinococcus granulosus, is one of the most widespread zoonoses in Mediterranean countries. Baiting not-owned dogs with praziquantel (PZQ), due to their key role in the maintaining the transmission of CE, currently appears to be the most effective way to limit the transmission of CE, as well as an important aspect to introduce for the control of this parasitic disease. Therefore, this study aims to test 3 types of PZQ-based baits by evaluating different parameters (integrity over time, attractiveness and palatability for dogs, and mechanical resistance after release to different altitudes) and the bait acceptance in field by target animals, i.e. not-owned dogs, by using camera traps. The double PZQ-laced baits (with a double layer of highly palatable chews) showed the greatest resistance in the environment while also preserving the attractiveness and palatability up to 10 days, also withstood heights of 25 m, thus resulting as the most suitable also for drone delivery. The results on the field showed that most of the baits were consumed by not-owned dogs (82.2%), while the remaining were consumed by wild boars (8.9%), foxes (6.7%), badgers (1.1%) and hedgehogs (1.1%), confirming the specific and high attractiveness of the double PZQ-laced baits for the target population and highlights how an anthelmintic baiting programme may be a viable tool for the management of E. granulosus among free-ranging dog populations in endemic rural areas.


Dog Diseases , Echinococcosis , Echinococcus granulosus , Praziquantel , Animals , Dogs , Echinococcus granulosus/drug effects , Echinococcosis/veterinary , Echinococcosis/prevention & control , Echinococcosis/parasitology , Dog Diseases/parasitology , Dog Diseases/prevention & control , Praziquantel/pharmacology , Anthelmintics/pharmacology , Zoonoses/parasitology , Swine
18.
PLoS One ; 19(4): e0301920, 2024.
Article En | MEDLINE | ID: mdl-38593129

The use of anthelminthic drugs has several drawbacks, including the selection of resistant parasite strains. Alternative avenues to mitigate the negative effects of helminth infection involve dietary interventions that might affect resistance and/or tolerance by improving host immunity, modulating the microbiota, or exerting direct anthelmintic effects. The aim of this study was to assess the impact of diet on strongyle infection in horses, specifically through immune-mediated, microbiota-mediated, or direct anthelmintic effects. Horses that were naturally infected with strongyles were fed either a high-fiber or high-starch diet, supplemented with either polyphenol-rich pellets (dehydrated sainfoin) or control pellets (sunflower and hay). When horses were fed a high-starch diet, they excreted more strongyle eggs. Adding sainfoin in the high-starch diet reduced egg excretion. Additionally, sainfoin decreased larval motility whatever the diet. Moreover, the high-starch diet led to a lower fecal bacterial diversity, structural differences in fecal microbiota, lower fecal pH, lower blood acetate, and lower hematocrit compared to the high-fiber diet. Circulating levels of Th1 and Th2 cytokines, lipopolysaccharides, procalcitonin, and white blood cells proportions did not differ between diets. Overall, this study highlights the role of dietary manipulations as an alternative strategy to mitigate the effect of helminth infection and suggests that, in addition to the direct effects, changes in the intestinal ecosystem are the possible underlying mechanism.


Anthelmintics , Microbiota , Animals , Horses , Diet/veterinary , Intestine, Large , Feces/microbiology , Starch , Anthelmintics/pharmacology
19.
Vet Parasitol ; 328: 110184, 2024 Jun.
Article En | MEDLINE | ID: mdl-38643645

This study applied the in vitro rumen exsheathment test (IVRET) to evaluate the exsheathment kinetics of Haemonchus contortus infective larvae (L3) incubated in ruminal liquor (RL) containing acetone:water extracts of Acacia pennatula (AP), Gymnopodium floribundum (GF), Havardia albicans (HA) or Lysiloma latisiliquum (LL). The role of polyphenols in the biological activity of the evaluated extracts was also determined. Larvae were incubated in RL either alone or added with a different plant extract (AP, GF, HA, or LL) at 1200 µg/mL. Polyethylene glycol (PEG) was added to block polyphenols in each treatment (RL+PEG, AP+PEG, GF+PEG, HA+PEG, and LL+PEG). After incubation times of 0, 1, 3, 6, 9, and 24 h, the exsheathment process was stopped to count the number of ensheathed and exsheathed L3. A Log-Logistic model was used to determine the L3 exsheathment kinetics in the different RL treatments. The inflection point of the respective kinetic curves, which indicates the time to reach 50 % exsheathed L3 (T50), was the only parameter that differed when comparing the exsheathment models (99 % probability of difference). The T50 values obtained for GF, HA, and LL treatments (T50 = 7.11 - 7.58 h) were higher in comparison to the T50 of RL (5.72 h) (≥ 70 % probability of difference). The L3 incubated in RL added with GF, HA, and LL extracts delayed their exsheathment at 3 and 6 h of incubation (28.71 - 48.06 % exsheathment reduction) compared to the RL treatment. The T50 value for AP, AP+PEG, GF+PEG, HA+PEG, and LL+PEG were similar to RL and RL+PEG (T50 = 5.34 - 6.97 h). In conclusion, the IVRET can be used to identify plants with the potential to delay the exsheathment of H. contortus L3 in the ruminal liquor. The acetone:water extracts of G. floribundum, H. albicans, and L. latisiliquum delayed the T50 of H. contortus exsheathment, which was evident at 3 and 6 h of incubation in ruminal liquor. The observed exsheathment delay was attributed to the polyphenol content of the extracts.


Haemonchus , Larva , Plant Extracts , Rumen , Animals , Haemonchus/drug effects , Rumen/parasitology , Plant Extracts/pharmacology , Plant Extracts/chemistry , Larva/drug effects , Haemonchiasis/veterinary , Haemonchiasis/parasitology , Anthelmintics/pharmacology , Anthelmintics/chemistry
20.
Vet Parasitol Reg Stud Reports ; 50: 101015, 2024 05.
Article En | MEDLINE | ID: mdl-38644039

In Benin, livestock breeders frequently use medicinal plants to treat gastrointestinal diseases in small ruminants. The aim of this review is to list the plants traditionally used in this context and to present the scientific findings on the efficacy of these plants. An extensive search was carried out using PubMed, Scopus, ScienceDirect, Biomed Central and Google Scholar databases to collect data, with combinations of relevant french and english keywords such as "ethnobotanical survey", "anthelmintic properties", "medicinal plants", "gastrointestinal parasites", "digestive strongyles", "Haemonchus", "Trichostrongylus", "small ruminants", "sheep", "goats" and "Benin". A total of 45 published articles met the eligibility criteria. This review listed 123 plants used by breeders to treat gastrointestinal ailments in small ruminants. The most commonly used parts are leaves and barks, and the most common forms are decoction, maceration and powder. Scientific studies have demonstrated the anthelmintic properties of 18 plants, including Zanthoxylum zanthoxyloides, Newbouldia laevis, Mitragyna inermis and Combretum glutinosum. The powders or leaf extracts of these plants showed in vivo significant reductions of over 50% in egg excretion, larval establishment, viability and fertility of gastrointestinal strongyles in small ruminants. Extracts of these plants also revealed in vitro inhibitory activity of over 50% on egg hatching, larval migration and motility of gastrointestinal strongyles. This manuscript highlights the traditional use of anthelmintic plants in small ruminants in Benin and provides scientific results supporting the efficacy of these plants.


Anthelmintics , Gastrointestinal Diseases , Goat Diseases , Goats , Plants, Medicinal , Sheep Diseases , Animals , Benin , Anthelmintics/pharmacology , Anthelmintics/therapeutic use , Plants, Medicinal/chemistry , Sheep Diseases/drug therapy , Sheep Diseases/parasitology , Gastrointestinal Diseases/veterinary , Gastrointestinal Diseases/drug therapy , Gastrointestinal Diseases/parasitology , Sheep , Goat Diseases/drug therapy , Goat Diseases/parasitology , Phytotherapy/veterinary , Ruminants/parasitology , Medicine, African Traditional
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