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

{"title":"Transcriptional responses to in vitro macrocyclic lactone exposure in Toxocara canis larvae using RNA-seq","authors":"Theresa A. Quintana ,&nbsp;Matthew T. Brewer ,&nbsp;Jeba R.J. Jesudoss Chelladurai","doi":"10.1016/j.ijpddr.2025.100614","DOIUrl":"10.1016/j.ijpddr.2025.100614","url":null,"abstract":"<div><div><em>Toxocara canis</em>, the causative agent of zoonotic toxocariasis in humans, is a parasitic roundworm of canids with a complex life cycle. While macrocyclic lactones (MLs) are successful at treating adult <em>T. canis</em> infections when used at FDA-approved doses in dogs, they fail to kill somatic third-stage larvae. In this study, we profiled the transcriptome of third-stage larvae derived from larvated eggs and treated <em>in vitro</em> with 10 μM of the MLs ivermectin and moxidectin. We analyzed transcriptional changes in comparison with untreated control larvae. In ivermectin-treated larvae, we identified 608 differentially expressed genes (DEGs), of which 453 were upregulated and 155 were downregulated. In moxidectin-treated larvae, we identified 1413 DEGs, of which 902 were upregulated and 511 were downregulated. Notably, many DEGs were involved in critical biological processes and pathways including transcriptional regulation, energy metabolism, body structure and function, physiological processes such as reproduction, excretory/secretory molecule production, host-parasite response mechanisms, and parasite elimination. We also assessed the expression of known ML targets and transporters, including glutamate-gated chloride channels (GluCls), and ATP-binding cassette (ABC) transporters, subfamily B, with a particular focus on P-glycoproteins (P-gps). We present gene names for previously uncharacterized <em>T. canis</em> GluCl and transporter genes using phylogenetic analysis of nematode orthologs to provide uniform gene nomenclature. Our study revealed that the expression of two GluCls and eight ABCB genes, particularly five P-gps were significantly altered in response to ML treatment. Compared to controls, <em>Tca-glc-3</em>, <em>Tca-avr-14</em>, <em>Tca-haf-10</em>, and <em>Tca-Pgp-13.2</em> were downregulated in ivermectin-treated larvae, while <em>Tca-abcb7</em>, <em>Tca-Pgp-11.2</em>, and <em>Tca-Pgp-2</em> were downregulated in moxidectin-treated larvae. Conversely, <em>Tca-haf-9, Tca-Pgp-11.3,</em> and <em>Tca-Pgp-16.3</em> were upregulated in moxidectin-treated larvae. These findings suggest that MLs broadly impact transcriptional regulation in <em>T. canis</em> larvae.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100614"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095077","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":"Development of a clinical risk scoring system for artesunate treatment failure prediction in malaria patients","authors":"Dasom Kim ,&nbsp;Da Hoon Lee ,&nbsp;Yubin Song ,&nbsp;Jung Sun Kim ,&nbsp;Hye Sun Gwak","doi":"10.1016/j.ijpddr.2025.100621","DOIUrl":"10.1016/j.ijpddr.2025.100621","url":null,"abstract":"<div><h3>Background</h3><div>Severe malaria remains a major cause of morbidity and mortality worldwide. Early identification of patients at high risk of poor response to treatment is essential, yet no simple clinical tool is currently available. This study aimed to develop a risk scoring system to predict failure to artesunate therapy.</div></div><div><h3>Methods</h3><div>This retrospective study included adult patients (aged ≥18 years) who received at least one dose of intravenous artesunate at the National Medical Center in South Korea between 2014 and 2023. Treatment failure (early or late clinical failure) was the response variable, which was defined according to WHO criteria. Candidate predictor variables included demographic, clinical, parasitological, and laboratory parameters. Odds ratios (ORs) and adjusted odds ratios (aORs) were calculated using univariate and multivariable logistic regression analyses, respectively. Final predictors were selected through backward elimination based on the Likelihood Ratio criterion, and a clinical risk scoring system was developed based on the adjusted ORs.</div></div><div><h3>Results</h3><div>Among 98 patients included in the final analysis, treatment failure occurred in 12 (12.2 %). Multivariable analysis identified female sex, parasitemia &gt;5 %, and impaired consciousness as independent risk factors. Using these variables, a risk-scoring system was constructed, and the predicted probabilities of treatment failure for patients with scores of 0, 1, 2, 3, and 4 points were 5 %, 16 %, 41 %, 72 %, and 90 %, respectively (AUROC = 0.768, 95 % CI: 0.605–0.931).</div></div><div><h3>Conclusions</h3><div>Parasitemia &gt;5 %, impaired consciousness, and female sex were predictive of artesunate treatment failure as defined by WHO clinical criteria. The developed risk scoring system provides a practical tool for identifying high-risk patients requiring intensified monitoring and alternative treatment strategies. These findings are derived from a South Korean cohort and should be interpreted with caution when extrapolated to endemic populations.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100621"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280105","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":"Recent advances in intestinal helminth parasites of horses in the Asia-Pacific region: Current trends, challenges and future directions","authors":"Ghazanfar Abbas ,&nbsp;Martin K. Nielsen ,&nbsp;Charles E-Hage ,&nbsp;Abdul Ghafar ,&nbsp;Ian Beveridge ,&nbsp;Jenni Bauquier ,&nbsp;Anne Beasley ,&nbsp;Edwina J.A. Wilkes ,&nbsp;Peter Carrigan ,&nbsp;Lucy Cudmore ,&nbsp;Caroline Jacobson ,&nbsp;Kristopher J. Hughes ,&nbsp;Abdul Jabbar","doi":"10.1016/j.ijpddr.2025.100622","DOIUrl":"10.1016/j.ijpddr.2025.100622","url":null,"abstract":"<div><div>Over the past 25 years, significant progress has been made in understanding and managing equine gastrointestinal parasites in the Asia-Pacific region, particularly in Australia and New Zealand. This review synthesises current knowledge of the epidemiology, diagnostic methods, anthelmintic resistance (AR), and control strategies for major equine intestinal parasites, including cyathostomins, <em>Parascaris</em> spp., <em>Anoplocephala perfoliata</em>, and <em>Strongyloides westeri</em>. Recent studies highlight substantial regional variation in parasite prevalence, egg shedding and cyathostomin population composition, shaped by diverse climatic conditions. Of increasing concern is the emergence of resistance to commonly used anthelmintics which is now evident in both <em>Parascaris</em> and cyathostomins, although data for <em>S. westeri</em> and <em>A. perfoliata</em> remain limited. High-throughput molecular diagnostics, such as next-generation sequencing, have advanced species-level characterisation in Australia and Thailand. ELISA-based tests for <em>A. perfoliata</em> and encysted cyathostomins are promising but remain unvalidated and underutilised regionally. The routine use of combination anthelmintics, including benzimidazoles, praziquantel, pyrimidines, and macrocyclic lactones, may accelerate resistance across nematode and cestode populations, emphasising the need for regular efficacy monitoring and improved antiparasitic stewardship. Findings from recent research on horse parasites in Australia have informed the development of country's first national equine parasite control guidelines which recommend targeted or selective treatment strategies. However, the effectiveness of these strategies requires ongoing evaluation, particularly in year-round grazing systems in tropical and subtropical regions. Sustainable parasite control will depend on the integration of non-chemical strategies along with the use of anthelmintics and the establishment of a national parasite surveillance database. This review highlights the need for climate-specific treatment protocols, strengthened collaborative research infrastructure, and continued investment in innovative diagnostic and control methods to preserve equine health and anthelmintic efficacy across the region.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100622"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358511","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":"Screening and hit evaluation of a microbial metabolite library against the pathogenic Plasmodium falciparum and Toxoplasma gondii parasites","authors":"Maria R. Gancheva ,&nbsp;Emma Y. Mao ,&nbsp;Ornella Romeo ,&nbsp;Daniel Vuong ,&nbsp;Ryan O'Handley ,&nbsp;Stephen W. Page ,&nbsp;Ernest Lacey ,&nbsp;Danny W. Wilson","doi":"10.1016/j.ijpddr.2025.100606","DOIUrl":"10.1016/j.ijpddr.2025.100606","url":null,"abstract":"<div><div>Frontline drug treatments for malaria are at risk of failing due to emerging resistance, meanwhile drugs used to treat toxoplasmosis have suboptimal efficacy and safety. As demonstrated by the success of clinically used antiparasitic drugs, the diverse structural complexity and biological activity of natural products holds great potential for drug discovery and development, to address the need for new compounds with novel mechanisms. Here we screened the BioAustralis Discovery Plates Series I library, a collection of 812 microbial natural product compounds including rare microbial metabolites, against <em>Plasmodium falciparum</em> erythrocytic stage and <em>Toxoplasma gondii</em> tachyzoite parasites. We identified 219 compounds that inhibited <em>P. falciparum</em> growth by at least 80 % at a concentration of 2 μg/mL (1–10 μM for &gt;90 % of compounds), whilst 149 compounds demonstrated equivalent activity against <em>T. gondii</em>. The active compounds were assigned based on chemical structure to more than 50 compound classes. After triaging active compounds for those with low mammalian cytotoxicity, we defined the <em>in vitro</em> half maximal inhibitory concentration (IC₅₀) of a selection of compounds against the parasites, identifying four compound groups with activity in the low nanomolar range. The macrocyclic lactone pladienolide B and cryptopleurine were found to be very potent against the parasites but also mammalian cells, warranting further structure-activity relationship investigation. Two groups, the monocyclic thiazole peptides, including micrococcin P1 and the thiocillins, and the pleuromutilins, exhibited both low antiparasitic IC₅₀ and low cytotoxicity, highlighting their potential for further analysis. This study defines the activity of the BioAustralis Discovery Plates Series I against two apicomplexan parasites of significant global importance, providing potential new tools to study parasite biology and possible starting points for novel antiparasitic development.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100606"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879267","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":"In vitro antiplasmodial activities of extract and fractions from Lepidobotrys staudtii against sensitive and resistant blood-stage parasites of Plasmodium falciparum","authors":"Jeannette Nina Magoudjou Pekam ,&nbsp;Noella Molisa Efange ,&nbsp;Lakshminarayana Mishro ,&nbsp;Rodrigue Keumoe ,&nbsp;Bruno Lenta Ndjakou ,&nbsp;Lawrence Ayong ,&nbsp;Frédéric Nico Njayou ,&nbsp;Paul Fewou Moundipa ,&nbsp;Vinoth Rajendran","doi":"10.1016/j.ijpddr.2025.100610","DOIUrl":"10.1016/j.ijpddr.2025.100610","url":null,"abstract":"<div><div>Antimalarial resistance is a primary challenge in the treatment of malaria. The ongoing search for novel drug sources remains a critical strategy for addressing this issue. This study evaluated the blood stage antiplasmodial and cytotoxic activities of the crude extract and fractions obtained from <em>Lepidobotrys staudtii</em>. The crude extract and all fractions exhibited promising antiplasmodial activity (IC₅₀ &lt; 10 μg/mL) against all the tested <em>Plasmodium falciparum</em> strains (<em>Pf</em>3D7 drug-sensitive and <em>Pf</em>INDO chloroquine-resistant). Notably, the hexane and ethyl acetate fractions exhibited the highest potency, with IC₅₀ values of 3.73 and 3.4 μg/mL (<em>Pf</em>3D7), respectively. No cytotoxic effects were observed at concentrations of up to 500 μg/mL. The ethyl acetate fraction displayed rapid action (12 h of exposure) against the <em>Pf</em>3D7 and <em>Pf</em>INDO strains. The ring stage parasites were particularly susceptible to the fractions, with IC₅₀ values ranging from 2.17 to 4.87 μg/mL (<em>Pf</em>3D7) and 2.27–6.27 μg/mL (<em>Pf</em>INDO). Additionally, combining the fraction with standard antimalarials at fixed sub-inhibitory concentrations significantly reduced IC₅₀ values. Only the hexane and crude extracts stimulated reactive oxygen species (ROS) production, whereas the other fractions neutralized the ROS. The most potent ethyl acetate fraction arrested parasite developmental progression and merozoite egress. Phytochemical analyses revealed the presence of phenols, flavonoids, tannins, alkaloids, saponins, carbohydrates, glycosides, and proteins. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis revealed that the fractions comprised a diverse array of compounds, resulting in varying levels of parasite-killing. This study emphasizes the blood-stage antiplasmodial properties of the stem bark extract and fractions of <em>L. staudtii</em>, underscoring their potential as a promising source of antimalarial agents.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100610"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010128","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":"Biological and molecular characterisation of in vitro selected miltefosine-resistant Leishmania amazonensis lines","authors":"Laura Fernanda Neira ,&nbsp;Héllida Marina Costa-Silva ,&nbsp;Juliana Martins Ribeiro ,&nbsp;Silvane Maria Fonseca Murta ,&nbsp;Patricia Escobar","doi":"10.1016/j.ijpddr.2025.100617","DOIUrl":"10.1016/j.ijpddr.2025.100617","url":null,"abstract":"<div><div>Miltefosine (MTF) is currently the only available oral treatment for leishmaniasis. However, increasing reports of therapeutic failure have raised concerns about emerging resistance. This study aimed to investigate the effects of reduced MTF susceptibility loss in the protozoan parasite <em>Leishmania (Leishmania) amazonensis</em>, with a particular focus on its impact on key biological and molecular parameters. Two distinct <em>Leishmania</em> lines (LaR-40 Line 1 and Line 2) were generated through stepwise <em>in vitro</em> selection with increasing concentrations of MTF, reaching up to 40 μM MTF. They were compared to their wild-type counterpart (LaWT). After 12 weeks of selection, LaR-40 promastigotes exhibited IC₅₀ values that were 4- to 8-fold higher than those of LaWT, with resistance remaining stable even after three months without drug pressure and following passage through BALB/c mice. No cross-resistance was detected against pentamidine, ketoconazole, or amphotericin B. MTF-resistant parasites exhibited reduced reactive oxygen species production, reduced lipid droplets (LD) abundance (in LaR-40 Line 1), delayed lesion onset, and smaller cutaneous lesions in mice, while maintaining normal infectivity in THP-1 macrophages. Quantitative RT-PCR analysis revealed consistent downregulation of the miltefosine transporter (<em>mt</em>) gene in both MTF-resistant lines, indicating that reduced drug uptake is the main mechanism underlying resistance. Line-specific changes, such as the upregulation of the serine palmitoyltransferase (<em>spt</em>) gene or the downregulation of the trypanothione reductase (<em>tryr</em>) gene, suggest that distinct metabolic pathways may act in a compensatory manner to reinforce resistance once transporter function is impaired. These findings indicate that MTF resistance in <em>L. amazonensis</em> is polygenic, stable, and adaptable. Routine monitoring of <em>mt</em> gene expression, combined with therapeutic strategies that target lipid or redox metabolism alongside drug uptake pathways, may help preserve the efficacy of current treatment regimens against leishmaniasis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100617"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185778","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":"Faecal egg count reduction test, deep amplicon sequencing of isotype-1 β-tubulin gene and in ovo larval development assay reveal susceptibility to benzimidazoles of porcine nematodes Oesophagostomum spp. and Ascaris suum in outdoor-reared pigs in Germany","authors":"Hannah RM. Fischer ,&nbsp;Jürgen Krücken ,&nbsp;Stefan Fiedler ,&nbsp;Stig M. Thamsborg ,&nbsp;Hendrik Nienhoff ,&nbsp;Stephan Steuber ,&nbsp;Ricarda Daher ,&nbsp;Georg von Samson-Himmelstjerna","doi":"10.1016/j.ijpddr.2025.100612","DOIUrl":"10.1016/j.ijpddr.2025.100612","url":null,"abstract":"<div><div><em>Oesophagostomum</em> spp. and <em>Ascaris suum</em> represent the most common porcine nematodes and anthelmintic resistance (AR) to various anthelmintics has been reported for <em>Oesophagostomum</em>. However, the current AR status for worm populations on German farms and practical methods facilitating reliable AR detection are missing. Herein, the efficacy of benzimidazoles (BZ) (fenbendazole, 5 mg/kg body weight, single dose) was analysed on 13 farms with outdoor access. The Faecal Egg Count Reduction Test (FECRT) estimates for strongyles on the farms (range 99.8–100 %) exceeded the target efficacy (99 %) of the new W.A.A.V.P. guideline for <em>Oesophagostomum dentatum.</em> Deep amplicon sequencing was used for the first time for porcine nematodes and revealed no polymorphisms associated with BZ-resistance in codons 134, 167, 198 and 200 of the isotype-1 β-tubulin gene. Nemabiome analysis using ITS-2 deep amplicon sequencing, based on two pre- and post-treatment samples, showed a significant increase (p &lt; 0.001) of <em>Oesophagostomum quadrispinulatum</em> after BZ treatment. For <em>A. suum,</em> the interpretation of FECRT estimates can be hindered due to coprophagy-associated false-positive egg counts in pigs. Therefore, two FECRT analysis for <em>A. suum</em> were pursued, the first analyses included all EPG data, the second considered EPGs &lt;200 pre- and post-treatment as negative. An <em>in ovo</em> larval development assay (LDA) was developed for the <em>in vitro</em> analysis of BZ-susceptibility in <em>A. suum</em>. Computed EC₅₀ values ranged from 1.50 to 3.36 μM thiabendazole (mean 2.24 μM). An EC₅₀ of 3.90 μM thiabendazole (mean EC₅₀ + 3 × SD) as provisional cut-off for detection of resistant populations is suggested. In conclusion, no AR was detected in <em>Oesophagostomum</em> using the FECRT and β-tubulin deep amplicon sequencing. For <em>A. suum</em> the FECRT results were ambiguous<em>,</em> in some cases even when excluding the low egg counts from calculations. With the <em>in ovo</em> LDA all investigated <em>A. suum</em> populations were identified as susceptible to BZ.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100612"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932528","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":"CRISPR-Cas13b mediated gene knockdowns in Leishmania infantum","authors":"Marine Queffeulou,&nbsp;Raouia Fakhfakh ,&nbsp;Fereshteh Fani ,&nbsp;Alex Dos Santos,&nbsp;Gabriel Reis Ferreira,&nbsp;Sophia Bigot,&nbsp;Chantal Godin,&nbsp;Philippe Leprohon,&nbsp;Barbara Papadopoulou,&nbsp;Marc Ouellette","doi":"10.1016/j.ijpddr.2025.100629","DOIUrl":"10.1016/j.ijpddr.2025.100629","url":null,"abstract":"<div><div>Chemotherapy is an effective means to control infections caused by the protozoan parasite <em>Leishmania</em>. However, available treatments are limited, expensive, and associated with considerable toxicity. Genomic strategies have contributed to a better understanding of <em>Leishmania</em>'s response to drugs and in the characterization of drug targets. Nonetheless, there is no knockdown system operational for <em>Leishmania</em>. In this study, we show that the CRISPR-Cas13 system can be an effective strategy to knockdown expression levels of both exogenous and endogenous transcripts. We succeeded in effectively knocking down the expression of the firefly luciferase gene integrated in the genome of <em>L. infantum</em>. This Cas13-mediated decrease in mRNA was paralleled with a significant reduction in both the luciferase protein level and its activity. Furthermore, we tested the effectiveness of the Cas13 system to target the endogenous miltefosine transporter (<em>MT</em>) and the aquaglyceroporin 1 (<em>AQP1</em>) genes. Knockdown was effective and parasites with less <em>MT</em> or <em>AQP1</em> mRNA levels exhibited reduced susceptibility to miltefosine or antimonials, respectively. While further optimization is warranted, this knockdown system has the potential to facilitate numerous studies related to various aspects of <em>Leishmania</em> biology.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100629"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714255","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":"Evaluating the efficacy of different praziquantel treatment regimens using egg and circulating anodic antigen (CAA) detection methods in a Schistosoma mansoni endemic area in northeastern Brazil","authors":"Rosangela Lima de Freitas Galvão ,&nbsp;Pytsje T. Hoekstra ,&nbsp;Paul L.A.M. Corstjens ,&nbsp;Marta Cristhiany Cunha Pinheiro ,&nbsp;Angela Maria da Silva ,&nbsp;Luciene Barbosa ,&nbsp;Sidney Lourdes César Souza Sá ,&nbsp;Govert J. van Dam ,&nbsp;Fernando Schemelzer de Moraes Bezerra","doi":"10.1016/j.ijpddr.2025.100628","DOIUrl":"10.1016/j.ijpddr.2025.100628","url":null,"abstract":"<div><div>This study evaluated the efficacy of different treatment regimens with PZQ against <em>S</em><em>chistosoma mansoni</em> infection. Residents of the Patioba and Colônia Miranda villages (Sergipe, Brazil) with a confirmed diagnosis of <em>S. mansoni</em> infection were randomized into one of the study groups and treated with a standard dose of PZQ (Group 1); with two doses spaced 24 hours apart (Group 2); or with two doses spaced 30 days apart (Group 3). Efficacy was assessed 30 days after the final treatment, based on the detection of eggs in feces using the Kato-Katz (KK) method and on the detection of CAA in urine using the Up-Converting Particle Lateral Flow (UCP-LF) assay. A total of 88 participants, who tested positive for infection by KK and UCP-LF CAA at baseline, were included in the statistical analysis. Cure rates (CRs) reached 100 % in all three study groups, according to KK. The UCP-LF CAA revealed that not all participants were cured, with the highest cure rate observed in Group 2 (69.6 %%), followed by Group 3 (57.7 %) and Group 1 (43.8 %). An Intensity Reduction Rate (IRR) of 100 % and &gt;97 % was observed in all groups, based on KK and UCP-LF CAA, respectively. Reduction in <em>S. mansoni</em> burden was observed over time, with the IRR in all groups exceeding the efficacy threshold established by the WHO (&gt;90 %). Cure rates varied according to the diagnostic method used, being overestimated when based on egg quantification, highlighting the importance of using more sensitive tools for the detection of active infections and monitoring the efficacy of PZQ.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100628"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668128","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":"Evaluation of the inhibitory effects of emodin on Neospora caninum invasion and proliferation in vitro","authors":"Feixue Liu ,&nbsp;Jianhua Li ,&nbsp;Xin Li,&nbsp;Xu Zhang,&nbsp;Liuzhenxiu Yan,&nbsp;Lanbi Gao,&nbsp;Zhenzhen Liu,&nbsp;Pengtao Gong,&nbsp;Nan Zhang,&nbsp;Xichen Zhang,&nbsp;Xiaocen Wang","doi":"10.1016/j.ijpddr.2025.100624","DOIUrl":"10.1016/j.ijpddr.2025.100624","url":null,"abstract":"<div><div>The impact of neosporosis on the livestock industry has worsening each year. Globally, annual losses were estimated to exceed $2.4 billion, with abortion rates reaching up to 47 % in affected herds. But no effective vaccines or drugs are currently available for prevention and treatment. This study aimed to investigate the inhibitory effects of emodin on <em>Neospora caninum</em> (<em>N</em>. <em>caninum</em>) infection and its potential mechanisms. The appropriates safe concentration of emodin was determined by the Cell Counting Kit-8 (CCK-8) assay. The anti-<em>N. caninum</em> effects of emodin in Vero cells, MDBK cells, macrophages, as well as the combined effects of emodin and niclosamide in Vero cells, were further verified using qPCR or Giemsa staining. Subsequently, the effects of direct incubation of tachyzoites with emodin on <em>N. caninum</em> invasion and proliferation were also examined. The activation of necroptosis by emodin was evaluated by measuring Lactate Dehydrogenase (LDH) levels in the supernatant and assessing cellular pMLKL levels. The CCK-8 results indicated that emodin exhibited low toxicity to Vero cells, MDBK cells, and macrophages. The qPCR results showed that emodin reduced the number of <em>N. caninum</em> in Vero cells, MDBK cells, and macrophages. Giemsa results showed that the number of tachyzoites within the parasitophorous vacuole was decreased accordingly. Notably, emodin directly affected tachyzoites, reducing its invasion capability by 55 %–63 % and its proliferation capacity by 62 %–88 %. Additionally, the combination of emodin with niclosamide significantly enhanced its antiparasitic effects compared with emodin alone. Western blot analysis showed that emodin significantly increased pMLKL levels and enhanced LDH release, assisting <em>N. caninum</em> in activating necroptosis. However, the inhibitory effects of emodin on <em>N. caninum</em> invasion and proliferation were not significantly altered in <em>Mlkl</em>^{<em>−/−</em>} macrophages. In conclusion, emodin inhibited <em>N. caninum</em> infection may through a necroptosis-independent mechanism by directly targeting the parasite, highlighting its potential as a therapeutic candidate for neosporosis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100624"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444678","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}