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Journal of Wildlife Diseases Oct 2023Helminths, in particular eyeworms (Oxyspirura petrowi) and cecal worms (Aulonocephalus pennula), may be a factor influencing northern bobwhite (Colinus virginianus)... (Review)
Review
Helminths, in particular eyeworms (Oxyspirura petrowi) and cecal worms (Aulonocephalus pennula), may be a factor influencing northern bobwhite (Colinus virginianus) populations in Texas. Previous research has shown a discrepancy in helminth infections between the Rolling Plains and Rio Grande Plains of Texas, US, potentially caused by differences in intermediate host distribution and abundance. We explored an alternative hypothesis centered on plant diversity, given that many plants possess phytochemicals with anthelmintic properties. We predicted that plant diversity would be greater and bobwhite diet more diverse in the Rio Grande Plains than the Rolling Plains, which in turn would potentially expose bobwhites to more plants with anthelmintic properties and therefore result in lower parasite prevalence and intensity. We conducted a literature review of plant diversity, anthelmintic plants, and bobwhite diet in Texas to explore this hypothesis. We also quantified the relationship between helminth prevalence in bobwhites and latitude. We documented trends for higher plant species richness, greater number of anthelmintic plants, and more diverse bobwhite diet in the Rio Grande Plains compared to the Rolling Plains. In addition, we documented a trend for increasing helminth prevalence with latitude for eyeworms but not cecal worms. Our study provides circumstantial evidence supporting the plant-diversity hypothesis and warrants experimental testing.
Topics: Animals; Colinus; Prevalence; Bird Diseases; Thelazioidea; Anthelmintics
PubMed: 37846916
DOI: 10.7589/JWD-D-22-00124 -
Molecules (Basel, Switzerland) Jun 2020Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many...
Soil-transmitted nematodes (STN) infect 1-2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose-response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% ) and evaluated their anthelmintic activity on hookworms (, a rodent parasite (), and whipworm (. We identified YP-terpenes that were effective against all three parasites. Further, YP-terpenes overcame albendazole-resistant . These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
Topics: Albendazole; Ancylostoma; Ancylostomatoidea; Animals; Anthelmintics; Benzimidazoles; Humans; Nematoda; Nematode Infections; Saccharomyces cerevisiae; Terpenes
PubMed: 32605043
DOI: 10.3390/molecules25132958 -
Current Medicinal Chemistry 2022Bacterial infections are among the leading causes of death worldwide. The emergence of antimicrobial resistance factors threatens the efficacy of all current... (Review)
Review
Bacterial infections are among the leading causes of death worldwide. The emergence of antimicrobial resistance factors threatens the efficacy of all current antimicrobial agents, with some already made ineffective, and, as a result, there is an urgent need for new treatment approaches. International organizations, such as the World Health Organization and the European Centre for Diseases Control, have recognized infections caused by multi-drug-resistant (MDR) bacteria as a priority for global health action. Classical antimicrobial drug discovery involves in vitro screening for antimicrobial candidates, Structure-Activity Relationship analysis, followed by in vivo testing for toxicity. Bringing drugs from the bench to the bedside involves huge expenditures in time and resources. This, along with the relatively short window of therapeutic application for antibiotics attributed to the rapid emergence of drug resistance, has, at least until recently, resulted in a waning interest in antibiotic discovery among pharmaceutical companies. In this environment, "repurposing" (defined as investigating new uses for existing approved drugs) has gained renewed interest, as reflected by several recent studies, and may help to speed up the drug development process and save years of expensive research invested in antimicrobial drug development. The goal of this review is to provide an overview of the scientific evidence on potential anthelmintic drugs targeting Gram-negative bacilli (GNB). In particular, we aim to: (i) highlight the potential of anthelmintic drugs for treatments of GNB infections, (ii) review their mechanisms of action against these bacteria, (iii) summarize the outcome of preclinical studies investigating approved anthelmintic drugs that target these bacteria, (iv) provide critical challenges for further anthelmintic repurposing drugs development, and (v) list the specific anthelmintic drugs that may be more likely to be repurposed.
Topics: Humans; Anthelmintics; Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria
PubMed: 35838224
DOI: 10.2174/0929867329666220714092916 -
Veterinary Parasitology, Regional... Dec 2021Cyathostomins are the most common parasites of adult horses worldwide. Currently, the three classes of anthelmintics used to treat cyathostomin infections includes...
Cyathostomins are the most common parasites of adult horses worldwide. Currently, the three classes of anthelmintics used to treat cyathostomin infections includes benzimidazoles, pyrimidines and macrocyclic lactones. However, due to widespread overuse, cyathostomins have developed varying degrees of resistance to all classes of anthelmintics. Fecal egg count reduction tests (FECRT) are currently used to determine the presence of anthelmintic resistance (AR), while egg reappearance periods (ERP) are used to investigate early macrocyclic lactone resistance. The objective of this study was to investigate the prevalence of cyathostomin pyrantel pamoate and ivermectin resistance, and to determine ERP at Prince Edward Island (PEI), Canada horse farms. In addition, fecal cultures and larval identification were performed to evaluate the prevalence of small and large strongyle egg shedding in PEI. Fecal egg counts (FEC) were performed on 270 horses on 14 horse farms across PEI. Horses with≥ 200 eggs per gram (EPG) met the inclusion criteria and were enrolled in the study (n = 101). The median (range) horses per farm was 7.5 (4-11) and 6.0 (4-8) for pyrantel pamoate and ivermectin groups, respectively. Horses were initially treated with 6.6 mg/kg of pyrantel pamoate orally (n = 101). Fecal egg counts were conducted every two weeks for 8 weeks post treatment. Once individual FEC were ≥ 200 EPG, horses were dewormed with 0.2 mg/kg of ivermectin orally (n = 80), and FEC were performed every 2-3 weeks for seven weeks. In this study the ERP was defined as the week the mean FECR were 10% below the initial mean two-week post treatment FECR. Fecal egg count reduction tests and ERP were used to evaluate the efficacy of each anthelmintic. Fecal culture was performed to confirm the shedding of cyathostomin eggs. Fecal egg count reduction tests detected pyrantel pamoate resistance on 5/14 farms. No signs of ivermectin AR were detected, while reappearance of eggs occurred at 4-6 weeks and 7-9 weeks for pyrantel pamoate and ivermectin, respectively. Fecal culture detected large strongyles on 5/14 farms, which accounted for 0.3% of strongyle type eggs cultured. The prevalence of Strongylus vulgaris among individual horses in this study was 2.8% and was detected on 2/14 farms. These findings will allow us to educate owners and veterinarians on appropriate anthelmintic protocols in PEI and can be used as a baseline for continued monitoring of ERP and anthelmintic resistance in this region.
Topics: Animals; Anthelmintics; Drug Resistance; Horse Diseases; Horses; Parasite Egg Count; Prevalence; Prince Edward Island
PubMed: 34879940
DOI: 10.1016/j.vprsr.2021.100629 -
BMC Complementary Medicine and Therapies Jan 2023Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating...
BACKGROUND
Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses.
METHODS
LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential.
RESULTS
C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy.
CONCLUSION
Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.
Topics: Humans; Albendazole; Plant Extracts; Cyperus; Methanol; Anthelmintics; Ethers
PubMed: 36658562
DOI: 10.1186/s12906-023-03839-7 -
The Journal of Pharmacy and Pharmacology Mar 2021To evaluate the antibacterial, antifungal and anthelmintic activities of the ethanolic extract (EEMz), fractions (LPFMz and HPFMz) and compounds isolated from the leaves...
OBJECTIVES
To evaluate the antibacterial, antifungal and anthelmintic activities of the ethanolic extract (EEMz), fractions (LPFMz and HPFMz) and compounds isolated from the leaves of Manilkara zapota L. P. Royen.
METHODS
Extract and fractions were produced by turbolization. LPFMz fraction was analysed by gas chromatography-mass spectrometry. The isolated compounds from HPFMz were purified by flash and preparative chromatographic methods, and chemically characterised by UPLC-ESITOFMS, optical rotation, and one- and two-dimensional 1H and 13C NMR techniques. Anthelmintic against Strongyloides venezuelensis and antimicrobial activities against Candida albicans, Trichophyton rubrum and Staphylococcus aureus were evaluated.
KEY FINDINGS
EEMz showed mainly phenolic compounds and pentacyclic triterpenes from Δ12-oleane/Δ12-ursane series. Chlorogenic acid, myricetin-3-O-β-D-glucopyranoside, mearnsitrin, germanicol and germanicol acetate were reported to M. zapota leaves for the first time in this work. EEMz, HPFMz, LPFMz showed significative activity against C. albicans (16 µg/mL), while isolated flavonoids were active against S. aureus (<32 µg/mL). EEMz, phenolic-rich compounds (F2), and chlorogenic acid were potentially active against S. venezuelensis at 24 h.
CONCLUSIONS
M. zapota and its bioactive compound can be eligible such as a potential phytomedicine for the treatment of microbial and strongyloidiasis drug-resistant infections.
Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Antifungal Agents; Arthrodermataceae; Candida albicans; Female; Gas Chromatography-Mass Spectrometry; Male; Manilkara; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Staphylococcus aureus; Strongyloides
PubMed: 33793883
DOI: 10.1093/jpp/rgaa030 -
European Journal of Medicinal Chemistry May 2023Infections caused by parasitic helminths rank among the most prevalent infections of humans and animals. Toxocariasis, caused by nematodes of the genus Toxocara, is one... (Review)
Review
Infections caused by parasitic helminths rank among the most prevalent infections of humans and animals. Toxocariasis, caused by nematodes of the genus Toxocara, is one of the most widespread and economically important zoonotic parasitic infections that humans share with dogs and cats. Despite the completion of the Toxocara canis draft genome project, which has been an important step towards advancing the understanding of this parasite and the search for drug targets, the treatment of toxocariasis has been dependent on a limited set of drugs, necessitating the search for novel anthelmintic agents, specially against Toxocara larvae in tissues. Given that research, development, and innovation are crucial to finding appropriate solutions in the fight against helminthiasis, this paper reviews the progress made in the discovery of anthelmintic drug candidates for toxocariasis. The main compounds reported in the recent years regards on analogues of albendazole, reactive quinone derivatives and natural produts and its analogues. Nanoparticles and formulations were also reviewed. The in vitro and/or in vivo anthelmintic properties of such alternatives are herein discussed as well as the opportunities and challenges for treatment of human toxocariasis. The performed review clarify that the scarcity of validated molecular targets and limited chemical space explored are the main bottlenecks for advancing in the field of anti-Toxocara agents.
Topics: Animals; Humans; Cats; Dogs; Toxocariasis; Cat Diseases; Dog Diseases; Anthelmintics; Albendazole; Toxocara
PubMed: 36921525
DOI: 10.1016/j.ejmech.2023.115268 -
Parasite (Paris, France) 2021Anthelmintic overuse and failure to implement methods preventing the development and spread of anthelmintic resistance (AR) have led to an alarming increase of resistant...
Anthelmintic overuse and failure to implement methods preventing the development and spread of anthelmintic resistance (AR) have led to an alarming increase of resistant ovine trichostrongylids worldwide. The aim of the present study was to determine whether the routine anthelmintic treatment strategy was effective, to obtain insights into the frequency of AR in trichostrongylids of sheep in Austria, and to determine the presence of different trichostrongylid genera. On 30 sheep farms, the faecal egg count reduction test (FECRT) was performed with the Mini-FLOTAC technique in two consecutive studies. In study 1, only fenbendazole and moxidectin were tested, while different compounds and products were used in study 2. Overall, 33 treatment groups were formed: 11 groups were treated with benzimidazoles (fenbendazole and albendazole), 2 groups with avermectins (ivermectin, doramectin), 18 groups with moxidectin, and two groups with monepantel. Reduced efficacy was detected in 64%, 100%, 28% and 50% of these groups, respectively. The most frequently detected genus in larval cultures was Haemonchus, which had been barely detected in Austria previously, followed by Trichostrongylus. Multispecific resistance of trichostrongylids in Austria seems to be on the rise and H. contortus was detected unexpectedly frequently in comparison to previous studies. There is an urgent need to develop efficient communication strategies aimed at improving the engagement of farmers and veterinarians in sustainable parasite control.
Topics: Animals; Anthelmintics; Austria; Drug Resistance; Feces; Haemonchus; Ivermectin; Parasite Egg Count; Sheep; Sheep Diseases
PubMed: 34114948
DOI: 10.1051/parasite/2021048 -
Advances in Parasitology 2021Widespread resistance to currently-used anthelmintics represents a major obstacle to controlling parasitic nematodes of livestock animals. Given the reliance on... (Review)
Review
Widespread resistance to currently-used anthelmintics represents a major obstacle to controlling parasitic nematodes of livestock animals. Given the reliance on anthelmintics in many control regimens, there is a need for the continued discovery and development of new nematocides. Enabling such a focus are: (i) the major chemical diversity of natural products; (ii) the availability of curated, drug-like extract-, fraction- and/or compound-libraries from natural sources; (iii) the utility and practicality of well-established whole-worm bioassays for Haemonchus contortus-an important parasitic nematodes of livestock-to screen natural product libraries; and (iv) the availability of advanced chromatographic (HPLC), spectroscopic (NMR) and spectrometric (MS) techniques for bioassay-guided fractionation and structural elucidation. This context provides a sound basis for the identification and characterisation of anthelmintic candidates from natural sources. This chapter provides a background on the importance and impact of helminth infections/diseases, parasite control and aspects of drug discovery, and reviews recent work focused on (i) screening well-defined compound libraries to establish the methods needed for large-scale screening of natural extract libraries; (ii) discovering plant and marine extracts with nematocidal or nematostatic activity, and purifying bioactive compounds and assessing their potential for further development; and (iii) synthesising analogues of selected purified natural compounds for the identification of possible 'lead' candidates. The chapter describes some lessons learned from this work and proposes future areas of focus for drug discovery. Collectively, the findings from this recent work show potential for selected natural product scaffolds as candidates for future development. Developing such candidates via future chemical optimisation, efficacy and safety evaluations, broad spectrum activity assessments, and target identification represents an exciting prospect and, if successful, could pave the way to subsequent pre-clinical and clinical evaluations.
Topics: Animals; Anthelmintics; Biological Products; Drug Discovery; Drug Resistance; Helminthiasis, Animal; Livestock
PubMed: 33482975
DOI: 10.1016/bs.apar.2020.10.002 -
Veterinary Parasitology May 2022This revision of the original poultry guidelines has been prepared to assist in the planning, conduct and interpretation of studies designed to assess the anthelmintic... (Review)
Review
This revision of the original poultry guidelines has been prepared to assist in the planning, conduct and interpretation of studies designed to assess the anthelmintic efficacy of drugs (newly discovered or currently used) against helminth parasites of chickens and turkeys. The original set of poultry guidelines was published in 2003. The current version provides an update on procedures to study and quantify the most important helminth parasites of chickens and turkeys, and to integrate these poultry guidelines with a new series of general, reflective and host-specific guidelines relative to assessing anthelmintic efficacy in production and companion animals. General considerations required for the conduct of studies designed to evaluate anthelmintics regardless of animal host such as the selection of study animals, animal housing, feeding, study design, record keeping and statistical analysis are for the most part provided in the newly published general guidelines. Taken together, the general and poultry guidelines should help investigators and others design and conduct studies and evaluate data concerned with determining the efficacy and safety of anthelmintics in chickens and turkeys. Additionally, this revision draws attention to several timely considerations inherent to anthelmintic evaluations such as the need to properly collect helminth specimens for subsequent determinations (e.g. species and stage verification, helminth genotyping). The investigations addressed herein, will most likely provide the very first public record of a new product's abilities to effectively reduce targeted, helminth infections in animals, and particular attention should be focused on study excellence and accuracy. Due to changes in consumer preferences, and new regulatory requirements, poultry husbandry, especially regarding laying hens, has changed immensely in many countries since the publication of the first poultry guidelines. These changes have generally allowed for a much greater exposure of birds to the source of helminth challenge (litter and fields as opposed to cages). Parasitic helminthiosis of poultry has therefore greatly increased in incidence and magnitude; changes that accentuate the need for more effective anthelmintic intervention and an update on the means of determining anthelmintic efficacy.
Topics: Animals; Anthelmintics; Chickens; Female; Helminthiasis; Poultry; Turkeys
PubMed: 35487870
DOI: 10.1016/j.vetpar.2022.109711