{"title":"Promising efficacy of nitrogen-containing bisphosphonates against the infection of Cryptosporidium spp.","authors":"Wenyan Hou, Xinyi Chen, Yingying Zhang, Longfei Wu, Songying Sun, Jiaye Guo, Wenchao Zhao, Junqiang Li, Sumei Zhang, Longxian Zhang, Xiaoying Li","doi":"10.1016/j.ijpddr.2025.100607","DOIUrl":"10.1016/j.ijpddr.2025.100607","url":null,"abstract":"<p><p>Cryptosporidiosis is a major diarrheal disease that affects both humans and animals. Fully effective drug for treating cryptosporidiosis is still lacking. Nitrogen-containing bisphosphonates have been reported to inhibit Cryptosporidium growth in vitro; however, the in vivo efficacy against Cryptosporidium remain unevaluated. This study determined the anti-Cryptosporidium effect of three nitrogen-containing bisphosphonates risedronate, ibandronate, and zoledronate through both in vitro and in vivo experiments. It was determined that risedronate exhibited the highest therapeutic index of 39.10 among the three compounds, with the median effective concentration low to 17.44 μM against Cryptosporidium parvum infection in vitro. In vivo experiments showed that the high dose (10 mg/kg/d) of risedronate and ibandronate significantly reduced the shedding of Cryptosporidium tyzzeri oocyst, with no toxicity in ICR mice. Histopathological examinations of ICR mice indicated that high and medium (2 mg/kg/d) doses of the bisphosphonates could reduce intestinal damage, recover the height of intestinal villi and crypt depth, led to more intact intestinal structures, and risedronate showed the most promising effects. Furthermore, the three compounds modulated the elevated levels of IL-2, IL-4, and TNF-α cytokines, induced by C. tyzzeri infection, towards normalcy in a dose-dependent manner. In conclusion, the efficacy of three nitrogen-containing bisphosphonates against the in vitro and in vivo infection of Cryptosporidium spp. was assessed. Risedronate show promising effect for further development of new anticryptosporidial drugs.</p>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"100607"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812014","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}
C.L. Brosnahan , D. Warburton , N. Cotter , J.C. Tanner , A.W. Greer
{"title":"Trialling the SmartWorm® application in New Zealand sheep farms","authors":"C.L. Brosnahan , D. Warburton , N. Cotter , J.C. Tanner , A.W. Greer","doi":"10.1016/j.ijpddr.2025.100616","DOIUrl":"10.1016/j.ijpddr.2025.100616","url":null,"abstract":"<div><div>Gastrointestinal nematodes (GIN) remain a major health and productivity challenge for grazing livestock globally, including New Zealand where widespread anthelmintic resistance has been reported. This was a pilot study evaluating the effectiveness of SmartWorm®, an app-based decision-support tool for Targeted Selective Treatment (TST) of internal parasites to reduce drench use without compromising lamb growth under New Zealand conditions.</div><div>A total of 1738 ewe lambs across three commercial farms were allocated to either a TST or Blanket Treatment (BT) group (treated every 28 days) and monitored over a 90-day period. All animals were drenched at the start of the trial, after which BT animals received treatment at each subsequent weighing. SmartWorm was used to determine drenching need for TST animals based on individual animal performance relative to expectation. Faecal egg counts (FEC), weight gain, and treatment frequency were assessed.</div><div>Across all farms, TST reduced anthelmintic use by 37–57 % compared with BT, with no significant differences in liveweight gain (P = 0.510). There was a weak but significant treatment effect on FEC (P = 0.01), and a linear relationship (R<sup>2</sup> = 0.8951, P < 0.001 with one outlier removed) between BT group FEC and TST rate, indicating the system's responsiveness to parasite challenge.</div><div>This study demonstrates that implementing TST using this app can enable reduced anthelmintic use without compromising performance—an important step towards sustainable parasite management on New Zealand sheep farms.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100616"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154724","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}
Theresa A. Quintana , Matthew T. Brewer , Jeba R.J. Jesudoss Chelladurai
{"title":"Transcriptional responses to in vitro macrocyclic lactone exposure in Toxocara canis larvae using RNA-seq","authors":"Theresa A. Quintana , Matthew T. Brewer , 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}
Wisam A. Dawood , Gillian M. Fisher , Josefa Kremeyer , Fabian Fischer , Jessica L. Home , Christopher D. Goodman , Kwong Sum Lam , Alexander G. Maier , Thomas Kurz , Katherine T. Andrews
{"title":"Antiplasmodial activity of pentyloxyamide-based histone deacetylase inhibitors against Plasmodium falciparum parasites","authors":"Wisam A. Dawood , Gillian M. Fisher , Josefa Kremeyer , Fabian Fischer , Jessica L. Home , Christopher D. Goodman , Kwong Sum Lam , Alexander G. Maier , Thomas Kurz , Katherine T. Andrews","doi":"10.1016/j.ijpddr.2025.100608","DOIUrl":"10.1016/j.ijpddr.2025.100608","url":null,"abstract":"<div><div>Malaria is caused by <em>Plasmodium</em> parasites and remains a significant health concern for almost half the world's population. There are estimated to be > 240 million malaria cases and approximately 600,000 malaria-related deaths annually, mainly due to infection with <em>P. falciparum</em> parasites. Parasite drug resistance is impacting malaria prevention and control efforts, and as part of the malaria eradication agenda, new drugs with novel mechanisms of action are needed. Histone/lysine deacetylase (HDAC) enzymes play essential roles in <em>Plasmodium</em> biology and are potential targets for the development of new antiplasmodial agents. In this study, a panel of 24 HDAC inhibitors with hydroxamic acid zinc binding group, a pentyloxyamide connecting unit linker region and substituted 4-phenyl and 4(pyridinyl)thiazole cap groups were investigated for <em>in vitro</em> activity against asexual intraerythrocytic stage <em>P. falciparum</em> parasites, the life cycle stage responsible for the clinical symptoms of malaria. The most potent compound (<strong>4o</strong>) had a <em>P. falciparum</em> IC<sub>50</sub> of 20 nM and >250-fold greater selectivity for <em>P. falciparum</em> versus human cells. Compound <strong>4o</strong> was also active against exoerythrocytic stage parasites (IC<sub>50</sub> 24 nM), which are a target for malaria prevention. In contrast, <strong>4o</strong> lacked potent activity against late-stage gametocytes (IC<sub>50</sub> > 2 μM), which are a target for malaria transmission-blocking drugs. Compound <strong>4o</strong> and analogues caused <em>in situ</em> hyperacetylation of <em>P. falciparum</em> histone H4, indicating deacetylase inhibition. Furthermore, <strong>4o</strong> was found to stabilise <em>Pf</em>HDAC1 in <em>P. falciparum</em> protein lysates using solvent-induced protein stability Western blot assays with anti-<em>Pf</em>HDAC1 antibody. Together, these data provide new structure-activity relationship and mechanistic insights on pentyloxyamide-based HDAC inhibitors as potential therapeutic starting points for malaria.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100608"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890187","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}
Dasom Kim , Da Hoon Lee , Yubin Song , Jung Sun Kim , Hye Sun Gwak
{"title":"Development of a clinical risk scoring system for artesunate treatment failure prediction in malaria patients","authors":"Dasom Kim , Da Hoon Lee , Yubin Song , Jung Sun Kim , 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 >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 >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}
Maria R. Gancheva , Emma Y. Mao , Ornella Romeo , Daniel Vuong , Ryan O'Handley , Stephen W. Page , Ernest Lacey , Danny W. Wilson
{"title":"Screening and hit evaluation of a microbial metabolite library against the pathogenic Plasmodium falciparum and Toxoplasma gondii parasites","authors":"Maria R. Gancheva , Emma Y. Mao , Ornella Romeo , Daniel Vuong , Ryan O'Handley , Stephen W. Page , Ernest Lacey , 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 >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 (IC<sub>50</sub>) 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 IC<sub>50</sub> 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 , Noella Molisa Efange , Lakshminarayana Mishro , Rodrigue Keumoe , Bruno Lenta Ndjakou , Lawrence Ayong , Frédéric Nico Njayou , Paul Fewou Moundipa , 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 (IC<sub>50</sub> < 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 IC<sub>50</sub> 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 IC<sub>50</sub> 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 IC<sub>50</sub> 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}
Laura Fernanda Neira , Héllida Marina Costa-Silva , Juliana Martins Ribeiro , Silvane Maria Fonseca Murta , Patricia Escobar
{"title":"Biological and molecular characterisation of in vitro selected miltefosine-resistant Leishmania amazonensis lines","authors":"Laura Fernanda Neira , Héllida Marina Costa-Silva , Juliana Martins Ribeiro , Silvane Maria Fonseca Murta , 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 IC<sub>50</sub> 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}
Ghazanfar Abbas , Martin K. Nielsen , Charles E-Hage , Abdul Ghafar , Ian Beveridge , Jenni Bauquier , Anne Beasley , Edwina J.A. Wilkes , Peter Carrigan , Lucy Cudmore , Caroline Jacobson , Kristopher J. Hughes , Abdul Jabbar
{"title":"Recent advances in intestinal helminth parasites of horses in the Asia-Pacific region: Current trends, challenges and future directions","authors":"Ghazanfar Abbas , Martin K. Nielsen , Charles E-Hage , Abdul Ghafar , Ian Beveridge , Jenni Bauquier , Anne Beasley , Edwina J.A. Wilkes , Peter Carrigan , Lucy Cudmore , Caroline Jacobson , Kristopher J. Hughes , 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}
Hannah RM. Fischer , Jürgen Krücken , Stefan Fiedler , Stig M. Thamsborg , Hendrik Nienhoff , Stephan Steuber , Ricarda Daher , Georg von Samson-Himmelstjerna
{"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 , Jürgen Krücken , Stefan Fiedler , Stig M. Thamsborg , Hendrik Nienhoff , Stephan Steuber , Ricarda Daher , 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 < 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 <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 EC<sub>50</sub> values ranged from 1.50 to 3.36 μM thiabendazole (mean 2.24 μM). An EC<sub>50</sub> of 3.90 μM thiabendazole (mean EC<sub>50</sub> + 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}