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

{"title":"Trichuris muris egg-hatching assay for anthelminthic drug discovery and characterization","authors":"Anastasia Schärer ,&nbsp;Stefan Biendl ,&nbsp;Jennifer Keiser","doi":"10.1016/j.ijpddr.2023.10.001","DOIUrl":"10.1016/j.ijpddr.2023.10.001","url":null,"abstract":"<div><p>Trichuriasis is a neglected tropical disease widely distributed among tropical and sub-tropical areas and associated with poverty and lack of access to safe drinking water, sanitation and hygiene. Existing drugs have limited efficacy and face a constant risk of developing resistance, necessitating the search for alternative treatments. However, drug discovery efforts are sparse and little research has been performed on anthelminthic effects on embryonated eggs, the infectious life stage of <em>Trichuris</em> spp.</p><p>We examined bacterial species dependent egg hatching of the murine model parasite <em>Trichuris muris</em> and identified <em>Escherichia coli, Pseudomonas aeruginosa</em> and <em>Enterobacter hormaechei</em> effective as hatching inducers, resulting in hatching yields of 50–70%. <em>Streptococcus salivarius,</em> reported to be associated with reduced drug efficacy of ivermectin-albendazole coadministration in <em>Trichuris trichiura</em> infected patients, did not promote egg hatching <em>in vitro</em>. We optimized hatching conditions using <em>E. coli</em> grown in luria broth or brain-heart infusion media to reach consistently high hatching yields to provide a sensitive, robust and simple egg-hatching assay. Oxantel pamoate demonstrated the strongest potency in preventing hatching, with an EC₅₀ value of 2–4 μM after 24 h, while pyrantel pamoate, levamisole and tribendimidine exhibited only moderate to weak inhibitory effects. Conversely, all tested benzimidazoles and macrolide anthelminthics as well as emodepside failed to prevent hatching (EC₅₀ &gt; 100 μM).</p><p>Our study demonstrates that egg-hatching assays complement larval and adult stage drug sensitivity assays, to expand knowledge about effects of current anthelminthics on <em>Trichuris</em> spp. Further, the developed <em>T. muris</em> egg-hatching assay provides a simple and cheap screening tool that could potentially lead to the discovery of novel anthelminthic compounds.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 63-70"},"PeriodicalIF":4.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thieno[3,2-b]pyrrole 5-carboxamides as potent and selective inhibitors of Giardia duodenalis","authors":"Christopher JS. Hart ,&nbsp;Andrew G. Riches ,&nbsp;Snigdha Tiash ,&nbsp;Rebecca Abraham ,&nbsp;Keely Fayd’Herbe ,&nbsp;Ellis Joch ,&nbsp;Bilal Zulfiqar ,&nbsp;Melissa L. Sykes ,&nbsp;Vicky M. Avery ,&nbsp;Jan Šlapeta ,&nbsp;Sam Abraham ,&nbsp;John H. Ryan ,&nbsp;Tina S. Skinner-Adams","doi":"10.1016/j.ijpddr.2023.09.002","DOIUrl":"10.1016/j.ijpddr.2023.09.002","url":null,"abstract":"<div><p><em>Giardia duodenalis</em> is the causative agent of the neglected diarrhoeal disease giardiasis. While often self-limiting, giardiasis is ubiquitous and impacts hundreds of millions of people annually. It is also a common gastro-intestinal disease of domestic pets, wildlife, and livestock animals. However, despite this impact, there is no vaccine for <em>Giardia</em> currently available. In addition, treatment relies on chemotherapies that are associated with increasing failure rates. To identify new treatment options for giardiasis we recently screened the Compounds Australia Scaffold Library for new chemotypes with selective anti-<em>Giardia</em> activity, identifying three compounds with sub-μM activity and promising selectivity. Here we extended these studies by examining the anti-<em>Giardia</em> activity of series CL9569 compounds. This compound series was of interest given the promising activity (IC₅₀ 1.2 μM) and selectivity demonstrated by representative compound, SN00798525 (<strong>1</strong>). Data from this work has identified an additional three thieno [3,2-b]pyrrole 5-carboxamides with anti-<em>Giardia</em> activity, including <strong>2</strong> which displayed potent cytocidal (IC₅₀ ≤ 10 nM) and selective activity against multiple <em>Giardia</em> strains, including representatives from both human-infecting assemblages and metronidazole resistant parasites. Preclinical studies in mice also demonstrated that <strong>2</strong> is well-tolerated, does not impact the normal gut microbiota and can reduce <em>Giardia</em> parasite burden in these animals.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 54-62"},"PeriodicalIF":4.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/5b/main.PMC10560980.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41178748","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":"Suramin action in African trypanosomes involves a RuvB-like DNA helicase","authors":"Anna Albisetti ,&nbsp;Silvan Hälg ,&nbsp;Martin Zoltner ,&nbsp;Pascal Mäser ,&nbsp;Natalie Wiedemar","doi":"10.1016/j.ijpddr.2023.09.003","DOIUrl":"10.1016/j.ijpddr.2023.09.003","url":null,"abstract":"<div><p>Suramin is one of the oldest drugs in use today. It is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused by <em>Trypanosoma brucei rhodesiense,</em> and it is also used for surra in camels caused by <em>Trypanosoma evansi</em>. Yet despite one hundred years of use, suramin's mode of action is not fully understood. Suramin is a polypharmacological molecule that inhibits diverse proteins. Here we demonstrate that a DNA helicase of the pontin/ruvB-like 1 family, termed <em>T. brucei</em> RuvBL1, is involved in suramin resistance in African trypanosomes. Bloodstream-form <em>T. b. rhodesiense</em> under long-term selection for suramin resistance acquired a homozygous point mutation, isoleucine-312 to valine, close to the ATP binding site of <em>T. brucei</em> RuvBL1. The introduction of this missense mutation, by reverse genetics, into drug-sensitive trypanosomes significantly decreased their sensitivity to suramin. Intriguingly, the corresponding residue of <em>T. evansi</em> RuvBL1 was found mutated in a suramin-resistant field isolate, in that case to a leucine. RuvBL1 (Tb927.4.1270) is predicted to build a heterohexameric complex with RuvBL2 (Tb927.4.2000). RNAi-mediated silencing of gene expression of either <em>T. brucei</em> RuvBL1 or RuvBL2 caused cell death within 72 h. At 36 h after induction of RNAi, bloodstream-form trypanosomes exhibited a cytokinesis defect resulting in the accumulation of cells with two nuclei and two or more kinetoplasts. Taken together, these data indicate that RuvBL1 DNA helicase is involved in suramin action in African trypanosomes.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 44-53"},"PeriodicalIF":4.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/38/main.PMC10520940.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111395","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":"Increased copy number of the target gene squalene monooxygenase as the main resistance mechanism to terbinafine in Leishmania infantum","authors":"Jade-Éva Potvin ,&nbsp;Fereshteh Fani ,&nbsp;Marine Queffeulou,&nbsp;Élodie Gazanion,&nbsp;Philippe Leprohon,&nbsp;Marc Ouellette","doi":"10.1016/j.ijpddr.2023.09.001","DOIUrl":"10.1016/j.ijpddr.2023.09.001","url":null,"abstract":"<div><p>We use here two genomic screens in an attempt to understand the mode of action and resistance mechanism of terbinafine, an antifungal contemplated as a potential drug against the parasite <em>Leishmania</em>. One screen consisted in <em>in vitro</em> drug evolution where 5 independent mutants were selected step-by-step for terbinafine resistance. Sequencing of the genome of the 5 mutants revealed no single nucleotide polymorphisms related to the resistance phenotype. However, the <em>ERG1</em> gene was found amplified as part of a linear amplicon, and transfection of <em>ERG1</em> fully recapitulated the terbinafine resistance phenotype of the mutants. The second screen, Cos-seq, consisted in selecting a gene overexpression library with terbinafine followed by the sequencing of the enriched cosmids. This screen identified two cosmids derived from loci on chromosomes 13 and 29 encoding the squalene monooxygenase (ERG1) and the C8 sterol isomerase (ERG2), respectively. Transfection of the <em>ERG1</em>-cosmid, but not the <em>ERG2</em>-cosmid, produced resistance to terbinafine. Our screens suggest that ERG1 is the main, if not only, target for terbinafine in <em>Leishmania</em> and amplification of its gene is the main resistance mechanism.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 37-43"},"PeriodicalIF":4.0,"publicationDate":"2023-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/b7/main.PMC10502319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10634126","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":"Identification of new drug candidates against Trichomonas gallinae using high-throughput screening","authors":"Shengfan Jing ,&nbsp;Qingxun Zhang ,&nbsp;Yi Li ,&nbsp;Han Chang ,&nbsp;Chen Xiang ,&nbsp;Shuyi Han ,&nbsp;Guohui Yuan ,&nbsp;Jinghui Fan ,&nbsp;Hongxuan He","doi":"10.1016/j.ijpddr.2023.08.001","DOIUrl":"10.1016/j.ijpddr.2023.08.001","url":null,"abstract":"<div><p><em>Trichomonas gallinae</em> is a protozoan parasite that is the causative agent of trichomoniasis, and infects captive and wild bird species throughout the world. Although metronidazole has been the drug of choice against trichomoniasis for decades, most <em>Trichomonas gallinae</em> strains have developed resistance. Therefore, drugs with new modes of action or targets are urgently needed. Here, we report the development and application of a cell-based CCK-8 method for the high-throughput screening and identification of new inhibitors of <em>Trichomonas gallinae</em> as a beginning point for the development of new treatments for trichomoniasis. We performed the high-throughput screening of 173 anti-parasitic compounds, and found 16 compounds that were potentially effective against <em>Trichomonas gallinae</em>. By measuring the median inhibitory concentration (IC₅₀) and median cytotoxic concentration (CC₅₀), we identified 3 potentially safe and effective compounds against <em>Trichomonas gallinae</em>: anisomycin, fumagillin, and MG132. In conclusion, this research successfully established a high-throughput screening method for compounds and identified 3 new safe and effective compounds against <em>Trichomonas gallinae</em>, providing a new treatment scheme for trichomoniasis.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 19-27"},"PeriodicalIF":4.0,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d0/0f/main.PMC10424085.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358345","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":"Therapeutic advantages of the combined use of closantel and moxidectin in lambs parasitized with resistant gastrointestinal nematodes","authors":"Gonzalo Suárez ,&nbsp;Daniel Castells ,&nbsp;Fernanda Imperiale ,&nbsp;Pietro Fagiolino ,&nbsp;Candela Canton ,&nbsp;Carlos Lanusse ,&nbsp;Luis Alvarez","doi":"10.1016/j.ijpddr.2023.07.004","DOIUrl":"10.1016/j.ijpddr.2023.07.004","url":null,"abstract":"<div><p>The serious widespread development of nematode resistance has motivated the use of combined anthelmintic formulations. However, the advantages/disadvantages of the combined use of anthelmintics require further scientific characterization. The goals of the current trial were a) to characterize the pharmacokinetics of closantel (CLO) and moxidectin (MXD) administered both subcutaneously (sc) and orally either separately or co-administered (CLO + MXD) to lambs; b) to compare the nematodicidal activity of both molecules given individually or co-administered to lambs infected with resistant nematodes. Seventy (70) Corriedale lambs naturally infected with multiple resistant gastrointestinal nematodes were involved in the pharmacokinetic and efficacy trials. The animals were allocated into six groups (n = 10) and treated with either CLO, MXD, or with the CLO + MXD combined formulation by both the oral and sc routes. Additionally, an untreated control group (n = 10) was included for the efficacy trial. The efficacy was estimated by the faecal egg count reduction test (FECRT). Higher systemic exposure of both CLO and MXD was observed after the sc compared to the oral administration in lambs. The combined administration of CLO + MXD did not markedly alter their disposition kinetics. At 13 days post-treatment, the administration of both molecules as a single active principle reached efficacy levels ranging between 80% (MXDoral), 84% (CLOoral), 85% (CLOsc), and 92% (MXDsc). The combined oral and sc treatments reached 99% efficacy. No adverse effects were observed after the combined treatment of CLO + MXD, and their co-administration did not show any adverse pharmacokinetic interaction. The combined effect of CLO + MXD successfully restored the maximum efficacy levels, which were not reached by the individual active ingredients.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"23 ","pages":"Pages 28-36"},"PeriodicalIF":4.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/43/main.PMC10448036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447170","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":"Genomic analysis of Indian isolates of Plasmodium falciparum: Implications for drug resistance and virulence factors","authors":"Deepak Choubey ,&nbsp;Bhagyashree Deshmukh ,&nbsp;Anjani Gopal Rao ,&nbsp;Abhishek Kanyal ,&nbsp;Amiya Kumar Hati ,&nbsp;Somenath Roy ,&nbsp;Krishanpal Karmodiya","doi":"10.1016/j.ijpddr.2023.05.003","DOIUrl":"10.1016/j.ijpddr.2023.05.003","url":null,"abstract":"<div><p>The emergence of drug resistance to frontline treatments such as Artemisinin-based combination therapy (ACT) is a major obstacle to the control and eradication of malaria. This problem is compounded by the inherent genetic variability of the parasites, as many established markers of resistance do not accurately predict the drug-resistant status. There have been reports of declining effectiveness of ACT in the West Bengal and Northeast regions of India, which have traditionally been areas of drug resistance emergence in the country. Monitoring the genetic makeup of a population can help to identify the potential for drug resistance markers associated with it and evaluate the effectiveness of interventions aimed at reducing the spread of malaria. In this study, we performed whole genome sequencing of 53 isolates of <em>Plasmodium falciparum</em> from West Bengal and compared their genetic makeup to isolates from Southeast Asia (SEA) and Africa. We found that the Indian isolates had a distinct genetic makeup compared to those from SEA and Africa, and were more similar to African isolates, with a high prevalence of mutations associated with antigenic variation genes. The Indian isolates also showed a high prevalence of markers of chloroquine resistance (mutations in Pfcrt) and multidrug resistance (mutations in Pfmdr1), but no known mutations associated with artemisinin resistance in the PfKelch13 gene. Interestingly, we observed a novel L152V mutation in PfKelch13 gene and other novel mutations in genes involved in ubiquitination and vesicular transport that have been reported to support artemisinin resistance in the early stages of ACT resistance in the absence of PfKelch13 polymorphisms. Thus, our study highlights the importance of region-specific genomic surveillance for artemisinin resistance and the need for continued monitoring of resistance to artemisinin and its partner drugs.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"22 ","pages":"Pages 52-60"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249728","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":"Pantothenate biosynthesis in Toxoplasma gondii tachyzoites is not a drug target","authors":"Vanessa M. Howieson ,&nbsp;Joy Zeng ,&nbsp;Joachim Kloehn ,&nbsp;Christina Spry ,&nbsp;Chiara Marchetti ,&nbsp;Matteo Lunghi ,&nbsp;Emmanuel Varesio ,&nbsp;Andrew Soper ,&nbsp;Anthony G. Coyne ,&nbsp;Chris Abell ,&nbsp;Giel G. van Dooren ,&nbsp;Kevin J. Saliba","doi":"10.1016/j.ijpddr.2023.03.003","DOIUrl":"10.1016/j.ijpddr.2023.03.003","url":null,"abstract":"<div><p><em>Toxoplasma gondii</em> is a pervasive apicomplexan parasite that can cause severe disease and death in immunocompromised individuals and the developing foetus. The treatment of toxoplasmosis often leads to serious side effects and novel drugs and drug targets are therefore actively sought. In 2014, Mageed and colleagues suggested that the <em>T. gondii</em> pantothenate synthetase, the enzyme responsible for the synthesis of the vitamin B₅ (pantothenate), the precursor of the important cofactor, coenzyme A, is a good drug target. Their conclusion was based on the ability of potent inhibitors of the <em>M. tuberculosis</em> pantothenate synthetase to inhibit the proliferation of <em>T. gondii</em> tachyzoites<em>.</em> They also reported that the inhibitory effect of the compounds could be antagonised by supplementing the medium with pantothenate, supporting their conclusion that the compounds were acting on the intended target. Contrary to these observations, we find that compound SW314, one of the compounds used in the Mageed et al. study and previously shown to be active against <em>M. tuberculosis</em> pantothenate synthetase <em>in vitro</em>, is inactive against the <em>T. gondii</em> pantothenate synthetase and does not inhibit tachyzoite proliferation, despite gaining access into the parasite <em>in situ</em>. Furthermore, we validate the recent observation that the pantothenate synthetase gene in <em>T. gondii</em> can be disrupted without detrimental effect to the survival of the tachyzoite-stage parasite in the presence or absence of extracellular pantothenate. We conclude that the <em>T. gondii</em> pantothenate synthetase is not essential during the tachyzoite stage of the parasite and it is therefore not a target for drug discovery against <em>T. gondii</em> tachyzoites.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"22 ","pages":"Pages 1-8"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102396/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9893538","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":"Stepwise in vitro screening of MMV pathogen box compounds against Plasmodium falciparum to identify potent antimalarial candidates","authors":"Haddijatou Mbye ,&nbsp;Fatoumata Bojang ,&nbsp;Fatou Kene Jaiteh ,&nbsp;Aminata Jawara ,&nbsp;Bekai Njie ,&nbsp;Simon Correa ,&nbsp;Umberto D'Alessandro ,&nbsp;Alfred Amambua-Ngwa","doi":"10.1016/j.ijpddr.2023.05.005","DOIUrl":"10.1016/j.ijpddr.2023.05.005","url":null,"abstract":"<div><p>Development of resistance to deployed antimalarial drugs is inevitable and needs prompt and continuous discovery of novel candidate drugs. Therefore, the antimalarial activity of 125 compounds from the Medicine for Malaria Ventures (MMV) pathogen box was determined. Combining standard IC₅₀ and normalised growth rate inhibition (GR₅₀) analyses, we found 16 and 22 compounds had higher potencies than CQ respectively. Seven compounds with relatively high potencies (low GR₅₀ and IC₅₀) against <em>P. falciparum</em> 3D7 were further analysed. Three of these were tested on 10 natural <em>P. falciparum</em> isolates from The Gambia using our newly developed parasite survival rate assay (PSRA).</p><p>According to the IC₅₀, GR₅₀ and PSRA analyses, compound MMV667494 was most potent and highly cytotoxic to parasites. MMV010576 was slow acting but more potent than dihydroartemisinin (DHA) 72 h after exposure. MMV634140 was potent against the laboratory-adapted 3D7 isolate, but 4 out of 10 natural Gambian isolates survived and replicated slowly despite 72 h of exposure to the compound, suggesting potential drug tolerance and risk of resistance development.</p><p>These results emphasise the usefulness of <em>in vitro</em> testing as a starting point for drug discovery. Improved approaches to data analyses and the use of natural isolates will facilitate the prioritisation of compounds for further clinical development.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"22 ","pages":"Pages 81-87"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/8f/main.PMC10394470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9931091","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":"Apparent treatment failure of praziquantel and pyrantel pamoate against anoplocephalid tapeworms","authors":"M.K. Nielsen","doi":"10.1016/j.ijpddr.2023.06.002","DOIUrl":"10.1016/j.ijpddr.2023.06.002","url":null,"abstract":"<div><p>Anoplocephalid tapeworms are commonly occurring in grazing horses around the world. Two currently available anthelmintics have documented high efficacy against <em>Anoplocephala perfoliata</em>; praziquantel in various dosages ranging from 1.0 to 2.5 mg/kg and pyrantel pamoate administered at 13.2 mg base/kg. Anthelmintic resistance has not been reported in <em>A. perfoliata</em>, but anecdotal reports made during 2022 have suggested a possible loss of efficacy for both actives. This paper reports fecal egg count data from a Thoroughbred operation in Central Kentucky in 2023. Fifty-six yearlings were first dewormed with a combination of ivermectin (200 μg/kg) and praziquantel (1.5 mg/kg) and subsequently treated with pyrantel pamoate (13.2 mg base/kg). Fecal egg counts were determined at the day of treatment and again 14 days post-treatment. Two groups of mares (n = 39 and 45) were also treated with ivermectin/praziquantel and examined pre- and post-treatment. Low efficacy of ivermectin and pyrantel pamoate was demonstrated against strongylid parasites in the yearlings with mean Fecal Egg Count Reductions (FECRs) at 75.6% or below and upper 95% credible interval (CI) limits below 90% in all cases. Overall anti-cestodal FECR levels in the yearlings were 23.5% (95% CI: 11.2–48.0) for praziquantel and 50.9% (20.5–72.0) for pyrantel pamoate. Praziquantel eliminated anoplocephalid eggs from three of 17 yearlings, but another 5 yearlings went from negative to positive status following treatment. Pyrantel pamoate failed to eliminate anoplocephalid eggs from any of 14 treated tapeworm-positive yearlings. Nine of 84 mares tested positive for anoplocephalid eggs, and seven of these were still positive post praziquantel treatment. These findings sharply contrast data from historic field efficacy studies conducted for both actives and raise concern about anthelmintic resistance having possibly developed. This emphasizes the need for developing and refining antemortem methodologies for evaluating anti-cestodal treatment efficacy and for searching for possible alternative treatment options.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"22 ","pages":"Pages 96-101"},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/5b/main.PMC10331019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9889388","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}