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Veterinary Parasitology Feb 2022In the majority of mixed or sequential gazing studies with sheep, cattle performance remained unaffected. However, the treatment regime of the sheep in these studies was...
In the majority of mixed or sequential gazing studies with sheep, cattle performance remained unaffected. However, the treatment regime of the sheep in these studies was often intense and this may have limited cross-transmission of nematodes from sheep to cattle. We conducted a sequential grazing trial with cattle and sheep with moderate anthelmintic intervention. Twenty first season grazing steers were stratified to 10 couples according to their origin, egg excretion per gram faeces (EPG), metabolic weight and previous weight gain record. Thirty naturally infected ewe lambs were stratified to 5 groups according to metabolic live weight and EPG. Five pairs of the steers were sequentially grazed with the 5 groups of lambs whereas another five pairs of steers served as control. Grazing duration was 70 days with a subsequent indoor period of additional 35 days for the steers. Weight and EPG was recorded 3 days before and 27, 49, 70 and 105 days after trial start. The recorded live-weight of the sequentially grazed steers was 182 ± 14, 191 ± 11, 205 ± 15, 219 ± 15 and 236 ± 18 and the live-weight of the control steers was 180 ± 18, 193 ± 19, 203 ± 21, 217 ± 24 and 234 ± 24 kg respectively. The EPG of the sequentially grazed steers 3 days before grazing start and at day 27, 49, 70 and 105 was 94 ± 100, 95 ± 48, 49 ± 42, 58 ± 41 and 140 ± 73 EPG respectively. The EPG of the control steers at the same dates was 96 ± 82, 98 ± 24, 104 ± 77, 98 ± 71 and 270 ± 287 EPG respectively. The sequentially grazed steer groups did not differ from the control groups with regard to EPG, live weight and daily weight gain. However, the sequentially grazed steers showed elevated pepsinogen levels compared to the control steers (e.g. 3.34 ± 1.05 units tyrosine and 1.29 ± 0.50 units tyrosine after 70 days of grazing, respectively). Larval samples from individual steer coprocultures of both groups were tested PCR-positive for Cooperia oncophora, Ostertagia ostertagi and Haemonchus contortus. We conclude that short term sequential grazing of first season grazing steers with lambs excreting mainly eggs of Haemonchus spp. did not adversely affect steer performance despite increased pepsinogen values. However, hot and dry conditions may have had a suppressive effect on larval development, migration and finally uptake by the steers.
Topics: Animals; Anthelmintics; Cattle; Feces; Female; Haemonchus; Nematoda; Ovum; Parasite Egg Count; Sheep
PubMed: 35030350
DOI: 10.1016/j.vetpar.2021.109645 -
Parasites & Vectors Nov 2023Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic...
BACKGROUND
Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic drug is urgently needed. Echinococcus multilocularis-associated angiogenesis is required by the parasite for growth and metastasis; however, whether antiangiogenic therapy is effective for treating AE is unclear.
METHODS
The in vivo efficacy of sunitinib malate (SU11248) was evaluated in mice by secondary infection with E. multilocularis. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate treatment effects on serum IL-4 and vascular endothelial growth factor A (VEGFA) levels after SU11248 treatment. Gross morphological observations and immunohistochemical staining were used to evaluate the impact of SU11248 on angiogenesis and the expression of pro-angiogenic factors VEGFA and VEGF receptor 2 (VEGFR2) in the metacestode tissues. Furthermore, the anthelmintic effects of SU11248 were tested on E. multilocularis metacestodes in vitro. The effect of SU11248 on the expression of VEGFA, VEGFR2, and phosphorylated VEGFR2 (p-VEGFR2) in liver cells infected with protoscoleces in vitro was detected by western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The influence of SU11248 on endothelial progenitor cell (EPC) proliferation and migration was determined using CCK8 and transwell assays.
RESULTS
In vivo, SU11248 treatment markedly reduced neovascular lesion formation and substantially inhibited E. multilocularis metacestode growth in mice. Further, it exhibited high anti-hydatid activity as efficiently as albendazole (ABZ), and the treatment resulted in reduced protoscolex development. In addition, VEGFA, VEGFR2, and p-VEGFR2 expression was significantly decreased in the metacestode tissues after SU11248 treatment. However, no effect of SU11248 on serum IL-4 levels was observed. In vitro, SU11248 exhibited some anthelmintic effects and damaged the cellular structure in the germinal layer of metacestodes at concentrations below those generally considered acceptable for treatment (0.12-0.5 μM). Western blotting, RT-qPCR, and ELISA showed that in co-cultured systems, only p-VEGFR2 levels tended to decrease with increasing SU11248 concentrations. Furthermore, SU11248 was less toxic to Reuber rat hepatoma (RH) cells and metacestodes than to EPCs, and 0.1 μM SU11248 completely inhibited EPC migration to the supernatants of liver cell and protoscolex co-cultures.
CONCLUSIONS
SU11248 is a potential candidate drug for the treatment of AE, which predominantly inhibits parasite-induced angiogenesis. Host-targeted anti-angiogenesis treatment strategies constitute a new avenue for the treatment of AE.
Topics: Mice; Animals; Echinococcus multilocularis; Sunitinib; Vascular Endothelial Growth Factor A; Interleukin-4; Anthelmintics
PubMed: 37936208
DOI: 10.1186/s13071-023-05999-4 -
International Journal For Parasitology.... Aug 2023Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to...
Ancylostoma caninum is the most common and important gastrointestinal nematode of dogs in the United States. Despite recent reports of A. caninum isolates resistant to all classes of anthelmintics, little is known about the frequency and extent of this anthelmintic resistance. The study aim was to evaluate the efficacy of three commercial anthelmintic products in the treatment of foxhound dogs with a history of persistent A. caninum infections. In the first phase of this study, 35 foxhounds were randomly divided into three treatment groups: moxidectin/imidacloprid (MI), pyrantel pamoate/febantel/praziquantel (PFP), and emodepside/praziquantel (EP). Fecal samples were collected on day 0, 11, and 33 post-treatment (PT), and hookworm eggs were quantified using the mini-FLOTAC technique with a multiplication factor of 5 eggs per gram (EPG). The fecal egg count reduction (FECR) on day 11 PT was 65% (95% CI: 62%-68%) for MI, 69% (95% CI: 66%-72%) for PFP, and 96% (95% CI: 94%-97%) for EP. On day 33 PT, the FEC in the MI and PFP groups returned to almost the same values as on day 0, while in the EP group, the FEC remained low. Since MI and PFP proved ineffective, 32 animals were randomly divided into two groups in the second phase. They were treated either with a combination of MI/PFP or EP. The FECR at day 13 PT for the combination MI/PFP was 89% (95% CI: 87%-91%) and 99% (95% CI: 98%-99%) for EP. These results suggest that this A. caninum population is resistant to multiple anthelmintics. Although the combination of MI/PFP improved the anthelmintic efficacy, the FECR remained below 90%. Future studies are indicated to evaluate further the epidemiology of persistent hookworm infections in dogs in the US and to identify more effective treatment protocols as they pose a significant health risk to canine and human health.
Topics: Animals; Dogs; Ancylostoma; Ancylostomatoidea; Anthelmintics; Dog Diseases; Feces; Hookworm Infections; Nematoda; Parasite Egg Count; Praziquantel
PubMed: 37481894
DOI: 10.1016/j.ijpddr.2023.07.001 -
Genes Jun 2020Leishmaniasis ( species), sleeping sickness (), and Chagas disease () are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs... (Review)
Review
Leishmaniasis ( species), sleeping sickness (), and Chagas disease () are devastating and globally spread diseases caused by trypanosomatid parasites. At present, drugs for treating trypanosomatid diseases are far from ideal due to host toxicity, elevated cost, limited access, and increasing rates of drug resistance. Technological advances in parasitology, chemistry, and genomics have unlocked new possibilities for novel drug concepts and compound screening technologies that were previously inaccessible. In this perspective, we discuss current models used in drug-discovery cascades targeting trypanosomatids (from in vitro to in vivo approaches), their use and limitations in a biological context, as well as different examples of recently discovered lead compounds.
Topics: Animals; Anthelmintics; Cheminformatics; Drug Discovery; Genome, Protozoan; Genomics; Humans; Trypanosoma; Trypanosomiasis
PubMed: 32610603
DOI: 10.3390/genes11070722 -
International Journal For Parasitology.... Dec 2023Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the... (Review)
Review
Reports of Ascaridia galli in laying hens in Europe have increased since the ban on conventional battery cages in 2012. As this parasite is transmitted directly via the faecal-oral route by parasite eggs containing a larva, it is reasonable to assume that the escalating problem is related to the increased exposure now occurring in modern welfare-friendly cage-free housing systems. On many farms, A. galli reappears in subsequent flocks, even though the birds have no access to the outdoors, biosecurity is high and empty houses are cleaned and disinfected during downtime. Since the egg production cycle lasts only ≈80 weeks and recombinant antigen production for helminth vaccines has not yet been solved, the development of a vaccine seems to be an unrealistic option. Therefore, disrupting the life cycle of the parasite by other means, including the strategic use of dewormers, appears to be the key to controlling infection. Of concern is that only one class of anthelmintics is licenced for poultry in Europe and that are usually administered indiscriminately through the birds' drinking water and often too late when the parasite is already established. If current calendar-based parasite control strategies are not changed, there is a risk that resistance to anthelmintics may develop, as has already been demonstrated with nematodes in livestock. We insist that treatments can be more effective and the risk of developing drug resistance can be mitigated if we invest in a better understanding of A. galli responses to more prudent and judicious use of anthelmintics. This review identifies knowledge gaps and highlights aspects of sustainable parasite control that require further research to support commercial egg producers.
Topics: Animals; Female; Ascaridia; Ascaridiasis; Chickens; Anthelmintics; Feces
PubMed: 37516026
DOI: 10.1016/j.ijpddr.2023.07.003 -
Molecules (Basel, Switzerland) May 2019() Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although...
() Ridsdale (Leeaceae) is found in tropical and subtropical countries and has historically been used as a traditional medicine in local healthcare systems. Although extracts have been found to possess anthelmintic and antioxidant-related nephroprotective and hepatoprotective effects, little attention has been paid toward the investigation of phytochemical constituents of this plant. In the current study, phytochemical analysis of isolates from led to the identification of 24 compounds, including a novel phenolic glucoside, seven triterpenoids, eight flavonoids, two phenolic glycosides, four diglycosidic compounds, and two miscellaneous compounds. The phytochemical structures of the isolates from were elucidated using spectroscopic analyses including 1D- and 2D-NMR and ESI-Q-TOF-MS. The presence of triterpenoids and flavonoids supports the evidence for anthelmintic and antioxidative effects of
Topics: Anthelmintics; Antioxidants; Flavonoids; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medicine, Traditional; Molecular Structure; Phytochemicals; Plant Components, Aerial; Triterpenes; Vitaceae
PubMed: 31060200
DOI: 10.3390/molecules24091733 -
PLoS Pathogens Apr 2023Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens....
Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal of anthelmintic drugs that have historically reduced parasite burdens. However, anthelmintic resistance (AR) is increasing, and little is known about the molecular and genetic causes of resistance for most drugs. The free-living roundworm Caenorhabditis elegans has proven to be a tractable model to understand AR, where studies have led to the identification of molecular targets of all major anthelmintic drug classes. Here, we used genetically diverse C. elegans strains to perform dose-response analyses across 26 anthelmintic drugs that represent the three major anthelmintic drug classes (benzimidazoles, macrocyclic lactones, and nicotinic acetylcholine receptor agonists) in addition to seven other anthelmintic classes. First, we found that C. elegans strains displayed similar anthelmintic responses within drug classes and significant variation across drug classes. Next, we compared the effective concentration estimates to induce a 10% maximal response (EC10) and slope estimates of each dose-response curve of each strain to the laboratory reference strain, which enabled the identification of anthelmintics with population-wide differences to understand how genetics contribute to AR. Because genetically diverse strains displayed differential susceptibilities within and across anthelmintics, we show that C. elegans is a useful model for screening potential nematicides before applications to helminths. Third, we quantified the levels of anthelmintic response variation caused by genetic differences among individuals (heritability) to each drug and observed a significant correlation between exposure closest to the EC10 and the exposure that exhibited the most heritable responses. These results suggest drugs to prioritize in genome-wide association studies, which will enable the identification of AR genes.
Topics: Humans; Animals; Caenorhabditis elegans; Genome-Wide Association Study; Anthelmintics; Nematoda; Antinematodal Agents; Nematode Infections; Drug Resistance
PubMed: 37011090
DOI: 10.1371/journal.ppat.1011285 -
International Journal For Parasitology.... Dec 2016The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting,...
The second scientific meeting in the series: "Anthelmintics: From Discovery to Resistance" was held in San Diego in February, 2016. The focus topics of the meeting, related to anthelmintic discovery and resistance, were novel technologies, bioinformatics, commercial interests, anthelmintic modes of action and anthelmintic resistance. Basic scientific, human and veterinary interests were addressed in oral and poster presentations. The delegates were from universities and industries in the US, Europe, Australia and New Zealand. The papers were a great representation of the field, and included the use of C. elegans for lead discovery, mechanisms of anthelmintic resistance, nematode neuropeptides, proteases, B. thuringiensis crystal protein, nicotinic receptors, emodepside, benzimidazoles, P-glycoproteins, natural products, microfluidic techniques and bioinformatics approaches. The NIH also presented NIAID-specific parasite genomic priorities and initiatives. From these papers we introduce below selected papers with a focus on anthelmintic drug screening and development.
Topics: Animals; Anthelmintics; Drug Discovery; Drug Resistance; Helminthiasis; Humans
PubMed: 27814986
DOI: 10.1016/j.ijpddr.2016.09.002 -
Parasitology Oct 2022This work aimed to evaluate the anthelmintic effect of carvone nanoemulsions on . Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions...
This work aimed to evaluate the anthelmintic effect of carvone nanoemulsions on . Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions homogenized in a sonicator (UNAlg-son) and homogenized in an ultrahomogenizer (UNAlg-ultra) and sodium alginate-coated R-carvone (CNAlg-ultra). The physicochemical characterizations of the nanoemulsions were carried out. The anthelmintic activity was evaluated using egg hatch test (EHT), larval development test (LDT) and adult worm motility test (AWMT). Changes in cuticle induced in adult were evaluated by scanning electron microscopy (SEM). The results were subjected to analysis of variance and compared using the Tukey test ( < 0.05). The effective concentration to inhibit 50% (EC) of egg hatching and larval development was calculated. The particle sizes were 281.1 nm (UNAlg-son), 152.7 nm (UNAlg-ultra) and 557.8 nm (CNAlg-ultra), and the zeta potentials were −15 mV (UNAlg-son), −10.8 mV (UNAlg-ultra) and −24.2 mV (CNAlg-ultra). The encapsulation efficiency was 99.84 ± 0.01%. SEM of the nanoemulsions showed an increase in size. In EHT, the EC values of UNAlg-son, UNAlg-ultra and CNAlg-ultra were 0.19, 0.02 and 0.17 mg mL, respectively. In LDT, they were 0.29, 0.31 and 0.95 mg mL for UNAlg-son, UNAlg-ultra and CNAlg-ultra, respectively. The adult motility inhibition was 100% after 12 h of exposure to UNAlg-ultra and CNAlg-ultra, while for UNAlg-son, it was 79.16%. SEM showed changes in the buccal capsule and cuticular damage. It was concluded that R-carvone nanoemulsions showed antiparasitic action demonstrating promise for the control of infections caused by gastrointestinal nematodes in small ruminants.
Topics: Animals; Haemonchus; Haemonchiasis; Anthelmintics; Cyclohexane Monoterpenes; Larva; Plant Extracts
PubMed: 36052509
DOI: 10.1017/S0031182022001135 -
PLoS Pathogens Jan 2020
Topics: Animals; Anthelmintics; Humans; Nematoda; Nematode Infections; Osmoregulation; Water
PubMed: 31999796
DOI: 10.1371/journal.ppat.1008202