International Journal for Parasitology: Drugs and Drug Resistance最新文献

{"title":"Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury","authors":"Jing-Mei Lu ,&nbsp;Guang-Nan Jin ,&nbsp;Yan Xin ,&nbsp;Jing-Wen Ma ,&nbsp;Xin-Yu Shen ,&nbsp;Yan-Zhu Quan ,&nbsp;Yi-Ming Liu ,&nbsp;Jin-Yi Zhou ,&nbsp;Bing-Zhe Wang ,&nbsp;Ying-Biao Li ,&nbsp;Xiang Xu ,&nbsp;Lian-Xun Piao","doi":"10.1016/j.ijpddr.2024.100575","DOIUrl":"10.1016/j.ijpddr.2024.100575","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em>, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-<em>T. gondii</em> activity and reduces depression-like behaviors induced by <em>T. gondii</em> infection. This study aimed to enhance AG's brain-targeting and therapeutic efficacy by developing lactoferrin-modified nanoemulsions loaded with AG (Lf-AG-NEs). Lf-modified nanoemulsions were prepared and assessed using <em>in vivo</em> and <em>in vitro</em> infection models with the <em>T. gondii</em> RH strain, and a co-culture system of BV2 microglia and primary neuron cells. The effects of Lf-AG-NEs on <em>T. gondii</em>-induced neuronal injury were examined, and potential molecular mechanisms were elucidated through real-time quantitative PCR, western blotting, immunofluorescence, flow cytometry, immunohistochemistry, and Nissl staining. <em>In vitro</em> assessments showed significant increases in cellular uptake and blood-brain barrier penetration by Lf-AG-NEs. These nanoemulsions notably inhibited <em>T. gondii</em> proliferation in brain tissue and BV2 cells, surpassing the effects of free AG or AG-NEs alone. Additionally, Lf-AG-NEs substantially alleviated neuropathological changes and reduced microglial activation and neuroinflammation by downregulating the TLR4/NF-κB and TNFR1/NF-κB signaling pathways. Co-culturing BV2 cells with primary cortical neurons indicated that Lf-AG-NEs, similarly to CLI-095 and R7050, attenuated <em>T. gondii</em>-induced microglial activation and subsequent neuronal injury. In conclusion, the successfully prepared Lf-AG-NEs not only enhanced the anti-<em>T. gondii</em> effect but also strengthened the protective impact against neuronal injury induced by <em>T. gondii</em>, through the modulation of microglial signaling pathways.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100575"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK","authors":"K.E. Bull ,&nbsp;J. Hodgkinson ,&nbsp;K. Allen ,&nbsp;J. Poissant ,&nbsp;L.E. Peachey","doi":"10.1016/j.ijpddr.2024.100576","DOIUrl":"10.1016/j.ijpddr.2024.100576","url":null,"abstract":"<div><div>Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes. Previously, faecal egg count reduction tests (FECRT) on four UK Thoroughbred studs revealed multidrug resistant cyathostomins on one stud (A), with evidence of resistance to the macrocyclic lactones (MLs) ivermectin (IVM) and moxidectin (MOX), and to pyrantel (PYR). The remaining three studs (B-D) lacked resistance to IVM and MOX but had a shortened egg reappearance period post treatment.</div><div>To determine whether specific species could be associated with the observed resistance and shortened egg reappearance period, strongyle eggs collected from between six and 15 individual horses per stud were copro-cultured to third larval stage (L3), before and after anthelmintic treatment, over a three-year timeframe (2021–2023). Quantitative DNA metabarcoding of the ITS-2 region was carried out on all samples.</div><div>On stud A, single but differing species were found to be responsible for ML and pyrantel resistance in yearlings, <em>Cyathostomum catinatum</em> and <em>Cylicocyclus nassatus,</em> respectively. On studs B-D, with shortened egg reappearance periods, species composition remained largely unchanged post treatment.</div><div>This study is the first to quantitatively profile cyathostomin species composition pre- and post-treatment in a multidrug resistant population in the UK, revealing that resistance in cyathostomins was species specific. This raises the question of whether these species may be responsible for ML and PYR resistance more widely and indicates that anthelmintic resistance in cyathostomins may not be a multi-species phenomenon.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100576"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective activity of Tabebuia avellanedae against Giardia duodenalis infecting organoid-derived human gastrointestinal epithelia","authors":"Giulia Rigamonti ,&nbsp;Fabrizia Veronesi ,&nbsp;Elisabetta Chiaradia ,&nbsp;Petra Gosten-Heinrich ,&nbsp;Antonia Müller ,&nbsp;Leonardo Brustenga ,&nbsp;Stefano de Angelis ,&nbsp;Alessia Tognoloni ,&nbsp;Riccardo De Santo ,&nbsp;Christian Klotz ,&nbsp;Marco Lalle","doi":"10.1016/j.ijpddr.2025.100583","DOIUrl":"10.1016/j.ijpddr.2025.100583","url":null,"abstract":"<div><div><em>Giardia duodenalis</em> is a widespread intestinal protozoan that affects mammals, including humans. Symptoms can range from being subclinical to causing severe abdominal pain and diarrhoea. Giardiasis often requires repeated treatment with synthetic drugs like metronidazole. In recent years, treatment failures in clinical cases involving nitroimidazoles have been increasingly reported. Consequently, identifying therapeutic alternatives is necessary. Medicinal plants have traditionally been used as antiparasitic compounds, but systematic evaluation under controlled experimental conditions is often lacking. Here, we evaluated the <em>in vitro</em> efficacy of <em>Tabebuia avellanedae</em> dry and hydroalcoholic extracts, as well as one of its active compounds, β-lapachone, as potential treatment against <em>G. duodenalis</em> infection. We observed effective antigiardial activity for all tested compounds, with β-lapachone exhibiting lower IC₅₀ values than metronidazole. Cytotoxic effects often limit therapeutic concentration windows of opportunity, and choosing an informative model to assess them is not straightforward. In the present case, only <em>T. avellanedae</em> hydroalcoholic extract showed no cytotoxicity on tumoral human intestinal Caco-2 cell line, and only a trend of inhibition when tested on canine epithelial kidney MDCK cells. To introduce a more physiological test system, we used <em>in vitro G. duodenalis</em> infection experiments in a trans-well set-up using organoid derived monolayers (ODM) to assess at the same time drug efficacy against the parasite and safety on primary human intestinal epithelia, a likely surrogate for <em>in vivo</em> conditions. Our studies using this model point towards the potential therapeutic opportunity for non-systemic applications of <em>T. avellanedae</em> extracts and a relevant ingredient of these, β-lapachone. The data suggest that ODM co-cultures with <em>G. duodenalis</em> are suitable for testing antigiardial compounds, providing a more informative <em>in vitro</em> model before progressing to <em>in vivo</em> tests.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100583"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotransformation of anthelmintics in nematodes in relation to drug resistance","authors":"Ondřej Vosála ,&nbsp;Josef Krátký ,&nbsp;Petra Matoušková ,&nbsp;Nikola Rychlá ,&nbsp;Karolína Štěrbová ,&nbsp;Lucie Raisová Stuchlíková ,&nbsp;Ivan Vokřál ,&nbsp;Lenka Skálová","doi":"10.1016/j.ijpddr.2025.100579","DOIUrl":"10.1016/j.ijpddr.2025.100579","url":null,"abstract":"<div><div>In all organisms, the biotransformation of xenobiotics to less toxic and more hydrophilic compounds represents an effective defense strategy. In pathogens, the biotransformation of drugs (used for their elimination from the host) may provide undesirable protective effects that could potentially compromise the drug's efficacy. Accordingly, increased drug deactivation via accelerated biotransformation is now considered as one of the mechanisms of drug resistance. The present study summarizes the current knowledge regarding the biotransformation of anthelmintics, specifically drugs used to treat mainly nematodes, a group of parasites that are a significant health concern for humans and animals. The main biotransformation enzymes are introduced and their roles in anthelmintics metabolism in nematodes are discussed with a particular focus on their potential participation in drug resistance. Similarly, the inducibility of biotransformation enzymes with sublethal doses of anthelmintics is presented in view of its potential contribution to drug resistance development. In the conclusion, the main tasks awaiting scientists in this area are outlined.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100579"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Licochalcone a: A promising antiparasitic drug against giardiasis","authors":"Yingying Zhang ,&nbsp;Wenchao Zhao ,&nbsp;Haili Du ,&nbsp;Pitambar Dhakal ,&nbsp;Xinyi Chen ,&nbsp;Longfei Wu ,&nbsp;Xiaoying Li ,&nbsp;Rongjun Wang ,&nbsp;Longxian Zhang ,&nbsp;Sumei Zhang ,&nbsp;Junqiang Li","doi":"10.1016/j.ijpddr.2024.100573","DOIUrl":"10.1016/j.ijpddr.2024.100573","url":null,"abstract":"<div><div>Giardiasis, caused by <em>Giardia duodenalis</em>, is a prevalent and significant zoonotic disease. While nitroimidazole drugs are primarily used to treat giardiasis, the urgent need for the development and formulation of new drugs has arisen due to increasing drug resistance. Several plant derived medicine have been employed as antiparasitic drugs. This study has evaluated the anti-<em>Giardia</em> effect of Licochalcone A (Lic A) through both <em>in vitro</em> and <em>in vivo</em> experiments. We determined the 50% inhibitory concentration (IC₅₀) of Lic A, analyzed the adhesive ability of <em>G. duodenalis</em>, and assessed intestinal morphology and various indicators in the gerbil model. The <em>in vitro</em> assays demonstrated that the IC₅₀ value of Lic A against <em>G. duodenalis</em> was 27.42 μM. Additionally, Lic A significantly inhibited the adhesiveability of <em>G. duodenalis</em> trophozoites, impairing their cell structure and cytoskeleton. <em>In vivo</em> experiments showed that Lic A significantly mitigated weight loss due to <em>G. duodenalis</em> infection, and lowered the intestinal parasite load. Histopathological examinations in gerbils indicated that Lic A could reduce intestinal damage, increase the height of intestinal villi, decrease crypt depth, and maintain the integrity of intestinal structure. Furthermore, Lic A altered cytokine levels and enhanced the body's antioxidant capacity. In conclusion, Lic A exbibits significant anti-<em>Giardia</em> effects both <em>in vitro</em> and <em>in vivo</em>, suggesting its potential as a promising antiparasitic drug candidate against giardiasis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100573"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the threonine metabolism of Echinococcus multilocularis: The threonine dehydrogenase as a potential drug target in alveolar echinococcosis","authors":"Marc Kaethner ,&nbsp;Pascal Zumstein ,&nbsp;Joachim Müller ,&nbsp;Matías Preza ,&nbsp;Philipp Grossenbacher ,&nbsp;Anissa Bartetzko ,&nbsp;Laura Vetter ,&nbsp;Martin Lochner ,&nbsp;Stefan Schürch ,&nbsp;Clement Regnault ,&nbsp;Daniel Villalobos Ramírez ,&nbsp;Britta Lundström-Stadelmann","doi":"10.1016/j.ijpddr.2025.100581","DOIUrl":"10.1016/j.ijpddr.2025.100581","url":null,"abstract":"<div><div>Alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of the fox tapeworm <em>Echinococcus multilocularis</em>. We recently showed that <em>E. multilocularis</em> metacestode vesicles scavenge large amounts of L-threonine from the culture medium. This motivated us to study the effect of L-threonine on the parasite and how it is metabolized. We established a novel metacestode vesicle growth assay with an automated readout, which showed that L-threonine treatment led to significantly increased parasite growth. In addition, L-threonine increased the formation of novel metacestode vesicles from primary parasite cell cultures in contrast to the non-proteinogenic threonine analog 3-hydroxynorvaline. Tracing of [U-¹³C]-L-threonine and metabolites in metacestode vesicles and culture medium resulted in the detection of [U-¹³C]-labeling in aminoacetone and glycine, indicating that L-threonine was metabolized by threonine dehydrogenase (TDH). EmTDH-mediated threonine metabolism in the <em>E. multilocularis</em> metacestode stage was further confirmed by quantitative real-time PCR, which demonstrated high expression of <em>emtdh</em> in <em>in vitro</em> cultured metacestode vesicles and also in metacestode samples obtained from infected animals. EmTDH was enzymatically active in metacestode vesicle extracts. The compounds disulfiram, myricetin, quercetin, sanguinarine, and seven quinazoline carboxamides were evaluated for their ability to inhibit recombinantly expressed EmTDH. The most potent inhibitors, albeit not very strong or highly specific, were disulfiram, myricetin and sanguinarine. These compounds were subsequently tested for activity against <em>E. multilocularis</em> metacestode vesicles and primary parasite cells and only sanguinarine demonstrated significant <em>in vitro</em> activity. However, TDH is not its only cellular target, and it is also known to be highly toxic. Our findings suggest that additional targets of sanguinarine should be explored, and that it may serve as a foundation for developing more specific compounds against the parasite. Moreover, the EmTDH assay could be a valuable high-throughput, target-based platform for discovering novel anti-echinococcal compounds.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100581"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitroxoline evidence amoebicidal activity against Acanthamoeba castellanii through DNA damage and the stress response pathways","authors":"Lijun Chen ,&nbsp;Wei Han ,&nbsp;Wenwen Jing ,&nbsp;Meng Feng ,&nbsp;Qingtong Zhou ,&nbsp;Xunjia Cheng","doi":"10.1016/j.ijpddr.2025.100578","DOIUrl":"10.1016/j.ijpddr.2025.100578","url":null,"abstract":"<div><div><em>Acanthamoeba castellanii</em> is a widespread unicellular eukaryote found in diverse environments, including tap water, soil, and swimming pools. It is responsible for severe infections, such as <em>Acanthamoeba</em> keratitis and granulomatous amebic encephalitis, particularly in individuals with immunocompromisation. The ability of protozoans to form dormant and persistent cysts complicates treatment, as current therapies are ineffective against cyst stages and suffer from poor specificity and side effects. Nitroxoline, a quinoline derivative with well-established antibacterial, antifungal, and antiviral properties, is a promising therapeutic candidate. This study aimed to elucidate cellular signalling events that counteract the effects of nitroxoline. In this study, nitroxoline significantly reduced the viability of <em>A</em>. <em>castellanii</em> trophozoites in a dose- and time-dependent manner, inducing morphological changes and apoptosis. Transcriptomic analysis revealed substantial alterations in gene expression, including enrichment of metabolic pathways, DNA damage responses, and iron ion binding. Nitroxoline treatment upregulated genes involved in DNA repair and oxidative stress response while regulating genes in the methionine and cysteine cycles. It also decreased the mitochondrial membrane potential, H₂S production, and total iron amount in <em>A</em>. <em>castellanii</em>. Bioinformatic analyses and molecular docking studies suggest direct interactions between nitroxoline and several <em>A</em>. <em>castellanii</em> proteins. Our research provides a comprehensive molecular map of the response of <em>A</em>. <em>castellanii</em> to nitroxoline, revealing significant changes in gene expression related to the stress response and metabolic pathways. These findings underscore the potential of nitroxoline as a potent anti-<em>Acanthamoeba</em> agent, offering new insights into its mechanism of action and paving the way for effective combinational therapeutic strategies.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100578"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified dosing schedule efficacy of fosmidomycin and clindamycin against murine malaria Plasmodium berghei","authors":"Leah A. Walker,&nbsp;Vision Bagonza,&nbsp;Bryce Bobb,&nbsp;David J. Sullivan","doi":"10.1016/j.ijpddr.2024.100577","DOIUrl":"10.1016/j.ijpddr.2024.100577","url":null,"abstract":"<div><div>Fosmidomycin and clindamycin target the <em>Plasmodium</em> apicoplast. Combination clinical trials have produced mixed results with the primary problem being the recrudescent infection frequency by day 28. Given that antibiotic efficacy against bacterial infections often depends on the constant drug presence over several days, we hypothesized that the antimalarial blood or liver stage efficacy of fosmidomycin and clindamycin could be improved by implementing a more frequent dosing schedule. A blood stage murine malaria <em>P. berghei</em> GFP-luciferase low and high parasitemia model was implemented to follow pharmacodynamics and cure for modified dose, schedule and duration of individual and combination fosmidomycin and clindamycin. <em>P. berghei</em> sporozoites were used to investigate fosmidomycin during the 48 h murine liver stage. Here we observed that the same total dose of fosmidomycin and clindamycin, alone and in combination, are more efficacious when scheduled in smaller, more frequent doses. Fosmidomycin added measurably small additional killing in combination with clindamycin. Despite dosing every 6 h during liver stages, fosmidomycin was inhibitory, but noncurative even with addition of atorvastatin to decrease hepatocyte production of mevalonate. We have also demonstrated <em>in vitro</em> efficacy of fosmidomycin and clindamycin against <em>P. falciparum</em> C580Y with IC₅₀s similar to those for drug sensitive <em>P. falciparum</em>. The dosing schedule of quinoline and artemisinin partner drugs fosmidomycin or clindamycin targeting the apicoplast should maximize time above minimum inhibitory concentration.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100577"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of risk factors associated with Ancylostoma spp. infection and the benzimidazole F167Y resistance marker polymorphism in dogs from the United States","authors":"Pablo D. Jimenez Castro ,&nbsp;Jennifer L. Willcox ,&nbsp;Haresh Rochani ,&nbsp;Holly L. Richmond ,&nbsp;Heather E. Martinez ,&nbsp;Cecilia E. Lozoya ,&nbsp;Christian Savard ,&nbsp;Christian M. Leutenegger","doi":"10.1016/j.ijpddr.2025.100584","DOIUrl":"10.1016/j.ijpddr.2025.100584","url":null,"abstract":"<div><div><em>Ancylostoma caninum</em> is the most significant intestinal nematode parasite of dogs. We acquired fecal surveillance data from a large population of dogs in the United States (US). A diagnostic test using real-time PCR (qPCR) for <em>Ancylostoma</em> spp. and allele-specific qPCR detecting the SNP F167Y in the isotype 1 of the Beta-tubulin gene, was used in 885,424 randomized canine fecal samples collected between March 2022 and December 2023. Overall, <em>Ancylostoma</em> spp. had a prevalence of 1.76% (15,537/885,424), with the highest in the South 3.73% (10,747/287,576), and the lowest in the West 0.45% (632/140,282). Within the subset of <em>Ancylostoma</em> spp<em>.-</em>detected dogs used for further analysis, the F167Y SNP had an overall prevalence of 14.44% with the highest in the West and the lowest in the Midwest (10.76%). The greyhound exhibited a higher prevalence of <em>Ancylostoma</em> spp. infections (17.03%) and a higher prevalence of the F167Y polymorphism (33.6%) compared to non-greyhounds (13.7% and 2.08%), respectively, but were not associated with the highest risk for the F167Y polymorphism. Sex did not influence hookworm infection nor F167Y polymorphism prevalence. Intact dogs had a prevalence of hookworm infection and F167Y polymorphism of 3.88% and 15.66%, respectively. Puppies showed increased prevalence of hookworms (3.70%) and the F167Y SNP (17.1%). Greyhounds, bluetick coonhounds, and boerboels had the highest relative risks for hookworm infection, while Cavalier King Charles spaniels, Havanese, and shiba inus had the lowest. The top and bottom three with the highest and lowest RR for the F167Y SNP were the old English sheepdog, American foxhound, and toy poodle Toy, and shih tzu, Maltese, and Australian cattle dogs, respectively. This study highlights the value of an accessible diagnostic qPCR test with fast turnaround in unraveling the molecular epidemiology of hookworms and benzimidazole resistance, as well as explore potentially important risk factorsin dogs with routine veterinary care.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100584"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143222955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The faecal egg count reduction test: Will identification of larvae to species improve its utility?","authors":"Dave Leathwick,&nbsp;Peter Green,&nbsp;Charlotte Bouchet,&nbsp;Alex Chambers,&nbsp;Tania Waghorn,&nbsp;Christian Sauermann","doi":"10.1016/j.ijpddr.2025.100589","DOIUrl":"10.1016/j.ijpddr.2025.100589","url":null,"abstract":"<div><div>In the faecal egg count reduction test, visual identification of larvae cultured from faeces enables the egg counts to be apportioned to species/genera, resulting in a more accurate test. However, morphology cannot reliably differentiate some species meaning that, in some cases, efficacy can only be estimated at the genus or species-complex level. We investigated the benefits of identifying larvae to species using DNA to determine how often this would alter the diagnosis of resistance and whether increasing the number of larvae identified would alter the repeatability of an efficacy estimate.</div><div>Data on faecal nematode egg counts and the corresponding larval species mixes were acquired from tests conducted on commercial sheep farms. The proportion of each species present in faecal culture was determined using DNA. Efficacy was then compared for individual species and for those genera/species complexes which cannot reliably be differentiated visually. The proportion of each species present was subsequently resampled 10,000 times (repeated random sampling) and efficacy recalculated to produce the median efficacy, along with the 5 % and 95 % simulation percentiles. Subsequently, the number of larvae sampled to determine the species mix in each sample was varied from 50 to 6400 and the process repeated.</div><div>Of 152 comparisons of efficacy, 25 % of cases where genus-level identification resulted in a finding of ‘susceptible’ for that category, species-level identification returned at least one diagnosis of ‘resistant’ i.e., genus-level identification resulted in a 25 % false negative diagnosis.</div><div>When the number of larvae sampled for species identification was low (&lt;400) variation in efficacy estimates was high, however, as sample size increased the confidence interval around the efficacy estimate decreased.</div><div>The results indicate that identifying large numbers of larvae to species using DNA has the potential to increase the accuracy and confidence in efficacy estimates achieved using the faecal egg count reduction test.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100589"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}