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

{"title":"Prevalence of antimalarial drug resistance molecular markers in Makenene, central Cameroon","authors":"Nelly Armanda Kala-Chouakeu , Joel Djoufounna , Nicolas Benoit , Timoléon Tchuinkam , Océane Delandre , Lionel Almeras , Roland Bamou , Christophe Antonio-Nkondjio , Marylin Madamet , Bruno Pradines","doi":"10.1016/j.ijpddr.2026.100633","DOIUrl":"10.1016/j.ijpddr.2026.100633","url":null,"abstract":"<div><h3>Background</h3><div>Antimalarial drug resistance remains a significant challenge in the fight against malaria in Cameroon. Given the high prevalence of malaria in Makenene in central Cameroon and the limited knowledge of drug resistance profiles in the area, the prevalence of <em>Plasmodium falciparum</em> drug resistance genetic markers was assessed.</div></div><div><h3>Methods</h3><div>185 samples from asymptomatic individuals with <em>P. falciparum</em> parasitaemia collected between September and October 2021 were sequenced for the <em>Pfdhfr</em>, <em>Pfdhps</em>, <em>Pfcrt</em>, <em>Pfmdr1,</em> and <em>PfK13</em> genes.</div></div><div><h3>Results</h3><div>One hundred percent of the samples harboured parasites with triple mutant <em>Pfdhfr</em> <strong>I</strong><sub>51</sub><strong>R</strong><sub>59</sub><strong>N</strong><sub>108</sub>I<sub>164</sub> (<strong>IRN</strong>I), associated with high level of resistance to pyrimethamine. The septuple mutant <em>Pfdhfr</em> <strong>IRN</strong>I and <em>Pfdhps</em> <strong>A</strong><sub>436</sub><strong>G</strong><sub>437</sub>K<sub>540</sub><strong>G</strong><sub>581</sub><strong>S</strong><sub>613</sub> (<strong>AG</strong>K<strong>GS</strong>), associated with resistance to sulfadoxine-pyrimethamine, was detected in 62.0 % of the isolates. The new <em>Pfdhps</em> I431V mutation was observed in 18.8 %. The octuple mutant <strong>IRN</strong>I + <strong>VAG</strong>K<strong>GS</strong> haplotype, overrepresented in pregnant women taking intermittent preventive treatment with sulfadoxine-pyrimethamine, was found in 17.4 %. The <em>Pfdhps</em> K540E mutation, linked to “super” resistance to sulfadoxine, was only detected in 1.9 %. The <em>Pfcrt</em> C<sub>72</sub>V<sub>73</sub><strong>I</strong><sub>74</sub><strong>E</strong><sub>75</sub><strong>T</strong><sub>76</sub> haplotype, implicated in chloroquine resistance, was absent in Makenene. The <em>Pfmdr1</em> N<sub>86</sub><strong>F</strong><sub>184</sub> haplotype, selected in parasites with a recrudescence in patients treated with artemether-lumefantrine, was found in 73.2 %. No isolate harboured the <strong>Y</strong><sub>86</sub>Y<sub>184</sub> haplotype, selected in parasites with recrudescence in patient treated with dihydroartemisinin-piperaquine. Moreover, no mutation associated with artemisinin partial resistance was detected in <em>PfK13</em>.</div></div><div><h3>Conclusions</h3><div>The in-depth analysis of genetic mutations associated with antimalarials resistance in this study, notably those with a high prevalence of mutations on the <em>Pfdhfr</em> and <em>Pfdhps</em> genes, highlights the immediate need for proactive strategies to combat resistance in Makenene. Continuous monitoring, including molecular and in vivo surveillance is crucial to uphold the effectiveness of current treatments and, more particularly, artemisinin-based combination therapies, and to enable better decision-making on effective treatment policy i","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100633"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022784","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":"Anti-cryptosporidial efficacy of tricyclic carbazole aminoalcohols in vitro and in vivo","authors":"Mingxiao Liu ,&nbsp;Weisi Wang ,&nbsp;Qi Zheng ,&nbsp;Di Zhang ,&nbsp;Dongqiang Wang ,&nbsp;Chenchen Wang ,&nbsp;Jigang Yin ,&nbsp;Liping Duan ,&nbsp;Guan Zhu","doi":"10.1016/j.ijpddr.2026.100631","DOIUrl":"10.1016/j.ijpddr.2026.100631","url":null,"abstract":"<div><div>Cryptosporidiosis is a major cause of diarrheal disease in humans and animals, yet there are no fully effective drugs, particularly for immunocompromised patients. Carbazole aminoalcohols (CAAs) are a relatively unexplored chemical class with reported broad-spectrum antiparasitic activities. Here, we systematically evaluated 36 CAA derivatives for anti-cryptosporidial efficacy. In vitro screening using a 44-h <em>Cryptosporidium parvum</em> infection assay identified eight compounds with low-micromolar EC₅₀ values (1.53–6.86 μM). The three most potent hits (H1402 at 25 mg/kg/d, and YFM1 and YFM3 at 15 mg/kg/d) were selected for in vivo evaluation in a chronic <em>C. tyzzeri</em> mouse model. Daily oral treatment with these compounds for 7 days reduced fecal oocyst shedding by 55.9–59.1 % compared with a 247.5 % increase in vehicle controls (<em>P</em> &lt; 0.01). Paromomycin at 1000 mg/kg/d, used as a positive control, produced an 84.2 % reduction. All three CAAs were generally well tolerated, with only minor weight loss observed in H1402-treated mice. Together, these results demonstrate that CAAs possess reproducible in vitro activity and significant in vivo efficacy against cryptosporidial infection, supporting their potential as lead scaffolds for anti-cryptosporidial drug development. Structural optimization to improve potency, selectivity, and pharmacokinetic properties is warranted to advance CAAs toward preclinical development.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100631"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911301","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 and evaluation of quadruplex droplet digital PCR assay for rapid detection of molecular markers associated with macrocyclic lactone resistance and susceptibility in Dirofilaria immitis","authors":"Sohini Kumar,&nbsp;Isabelah Kassandra Lalicon,&nbsp;Roger K. Prichard,&nbsp;Thavy Long","doi":"10.1016/j.ijpddr.2025.100625","DOIUrl":"10.1016/j.ijpddr.2025.100625","url":null,"abstract":"<div><div>Due to climate change and human interventions, there has been an increase in <em>D. immitis</em> infections, underscoring the necessity for monitoring the spread and extent of resistance. In our prior research, we introduced a rapid test utilizing four predominant SNP markers at loci 15709 (SNP1), 30575 (SNP2), 21554 (SNP3), and 9400 (SNP7) linked to ML resistance. Our findings highlighted SNP1 and SNP2 as potent predictive markers, offering suitability for the rapid detection and monitoring of drug resistance. Therefore, we developed a cost-effective test using droplet digital PCR (ddPCR) technology to perform a quadruplex assay to assess alternate allele frequency. Our assay can identify both SNP1 and SNP2 wildtype and mutant targets in a single sample. We tested the performance of our 4-plex assay on 8 laboratory-maintained isolates, including Missouri (MO), Berkeley, JYD-34, Metairie-2014, Yazoo-2013, GA-2, GA-3, and Big Head, and further validated the sensitivity using clinical isolates from the United States. Our assay demonstrated consistent results compared to the standard MiSeq sequencing and ddPCR duplex assay. Notably, we showcased the utility of ddPCR for direct genotyping of <em>D. immitis</em> infected whole blood from two well-characterized isolates, MO and JYD-34. This approach streamlined the assay workflow and lowered costs, thus enhancing affordability for larger genotyping studies.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100625"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010173","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":"The EamA metabolite transporter does not affect antileishmanial drug susceptibility","authors":"Rokaya Ahmad ,&nbsp;Gaia Gastoldi ,&nbsp;Sin-Ting Wong ,&nbsp;Alvaro Baeza Garcia ,&nbsp;Guy Caljon","doi":"10.1016/j.ijpddr.2026.100632","DOIUrl":"10.1016/j.ijpddr.2026.100632","url":null,"abstract":"<div><div>Leishmaniasis is a major neglected tropical disease, exists in 98 countries and constitutes a global public health threat. As chemotherapy is confronted with drug resistance and treatment failure, understanding the underlying mechanisms and continued drug discovery efforts are needed in the fight against leishmaniasis. A previous cosmid-based overexpression study suggested a role for EamA (LINF_020008400), annotated as a putative drug-metabolite transporter, in resistance to novel antileishmanial oxaboroles. To assess fitness cost and drug susceptibility, gene deficient <em>Leishmania infantum</em> lines were generated using CRISPR-Cas9 gene editing and overexpression from the <em>ssu</em> locus was achieved using the pLEXSY system. While <em>in vitro</em> parasite growth and survival were unchanged compared to control lines, the intracellular burden of the null mutant was lower. <em>In vitro</em> exposure to current antileishmanial drugs and several novel leads revealed an unchanged drug sensitivity profile in extracellular and intramacrophage assays. Similarly, the overexpression lines showed a significantly lower infection rate, but their drug susceptibility profiles showed no significant differences from the control. Collectively, these data suggest that -under the tested conditions- LINF_020008400 is not essential for parasite fitness, host cell infectivity and survival following exposure to antiparasitic drugs.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100632"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922183","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":"Meclonazepam sensitivity of parasitic flatworms correlates with TRPMMCLZ sensitivity to meclonazepam","authors":"Claudia M. Rohr ,&nbsp;Paul McCusker ,&nbsp;Marc Kaethner ,&nbsp;Rebecca Armstrong ,&nbsp;Emily Robb ,&nbsp;Sang-Kyu Park ,&nbsp;Daniel J. Sprague ,&nbsp;Aaron G. Maule ,&nbsp;Mostafa Zamanian ,&nbsp;Britta Lundström-Stadelmann ,&nbsp;John D. Chan ,&nbsp;Jonathan S. Marchant","doi":"10.1016/j.ijpddr.2026.100634","DOIUrl":"10.1016/j.ijpddr.2026.100634","url":null,"abstract":"<div><div>The ionotropic portfolio of parasitic flatworms affords considerable opportunity for development of new anthelmintics. In this regard, transient receptor potential ion channels (TRP channels), cation channels responsive to various physiochemical cues, have emerged as promising druggable targets. This is based on the recent discovery that two members of a TRP channel subfamily (TRP melastatin or TRPM channels) are selectively activated by the clinical drug praziquantel (TRPM_PZQ), or the anthelmintic benzodiazepine meclonazepam (TRPM_MCLZ). Here, the efficacy of meclonazepam was investigated in a trematode (the liver fluke, <em>Fasciola hepatica</em>) and a cestode (<em>Echinococcus multilocularis</em>) model, in which an observed lack of meclonazepam sensitivity correlated with the lack of efficacy of meclonazepam on TRPM_MCLZ in these different parasites. Such correlations support assignment of TRPM_MCLZ as the meclonazepam target. Bioinformatic analysis of all available parasitic flatworm genomes allowed prediction of the meclonazepam binding pocket in over sixty different TRPM_MCLZ orthologs. Mutagenesis and functional profiling analyses highlighted the importance of a key residue in the S4 transmembrane helix of TRPM_MCLZ that impacts meclonazepam potency and efficacy. Variation of this residue and overall binding pocket architecture between different parasitic flatworm TRPM_MCLZ orthologs restricts meclonazepam action to a subset of schistosome species.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100634"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022785","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":"Illuminating the druggability of the Giardia duodenalis kinome through reannotation and high-throughput screens","authors":"Alexander Y.F. Lam ,&nbsp;Isabelle S. Lucet ,&nbsp;Aaron R. Jex ,&nbsp;Samantha J. Emery-Corbin","doi":"10.1016/j.ijpddr.2025.100619","DOIUrl":"10.1016/j.ijpddr.2025.100619","url":null,"abstract":"<div><div><em>Giardia duodenalis</em> (syn <em>Giardia intestinalis, Giardia lamblia</em>) is a neglected, microaerophilic gastrointestinal parasite reliant on broad spectrum anti-microaerophilic/-anaerobic nitroheterocyclic antibiotics (metronidazole) which have been in use for over 70 years. New drugs which avoid their predecessor’s shortfalls of toxic and adverse effects, as well as circumvent its increasing treatment failure, are urgently required to lower global rates of up to 200 million symptomatic cases annually. Kinases are essential regulatory enzymes that primarily catalyse the phosphorylation post-translational modification involved in dynamic cellular processes. Kinases are well-validated and attractive drug targets, with many kinase inhibitors demonstrating great success in the clinic as anticancer therapeutics. In <em>G. duodenalis</em>, its intriguing set of minimal “core” protein kinases and the highly expanded <em>Giardia</em>-specific Never-in-Mitosis-A related kinases (Neks) emerge as a novel druggable space. We propose this kinome as an understudied and underutilised space to explore novel antigiardial targets. Intriguingly, despite over 15 years of advances in kinase biology and new annotation tools, there are limited functional evidence on the existence of ‘Neks’ in <em>G. duodenalis</em>. To incentivise new efforts, we provide an updated kinome reannotation and examination of the giardial core and specific sub-kinomes using novel bioinformatic tools, suggesting a nomenclature and providing insights in a drug-discovery context. Lastly, we have conducted a high-throughput screening of 430 compounds, covering 53 kinase targets and 51 chemical scaffolds, identifying 83/430 antigiardial kinase inhibitors of which 33 true positives could be validated in a subset subjected to drug-susceptibility testing, highlighting intriguing spaces for further development and molecular probes to further explore kinase regulatory pathways in this parasite.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100619"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258123","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 screening of the open-access Pandemic Response Box reveals ESI-09 as a compound with activity against Echinococcus multilocularis","authors":"Pascal Zumstein ,&nbsp;Anissa Bartetzko ,&nbsp;Marc Kaethner ,&nbsp;Laura Vetter ,&nbsp;Andrew Hemphill ,&nbsp;Trix Zumkehr ,&nbsp;Benoît Laleu ,&nbsp;Matías Preza ,&nbsp;Britta Lundström-Stadelmann","doi":"10.1016/j.ijpddr.2025.100609","DOIUrl":"10.1016/j.ijpddr.2025.100609","url":null,"abstract":"<div><div>Alveolar echinococcosis (AE) is a life-threatening disease caused by the metacestode stage of the fox tapeworm <em>Echinococcus multilocularis</em>, primarily in the liver. Current drug treatments rely on benzimidazoles, which are not parasiticidal, requiring life-long therapy with significant side effects. Therefore, novel drug treatments are urgently needed. Drug repurposing offers a strategy to identify novel therapies against the neglected disease AE. We report on the <em>in vitro</em> screening of the Pandemic Response Box, an open-access compound library composed of 400 drug-like molecules assembled by Medicines for Malaria Venture (MMV) and the Drugs for Neglected Disease Initiative (DNDi), against <em>E. multilocularis</em>. An overview screen at 10 μM using the metacestode vesicle damage-marker release assay (based on release of phosphoglucose isomerase, PGI) and metacestode vesicle viability assay (based on ATP measurement) identified 37 active compounds. Reassessment in triplicates resulted in five active compounds (alexidine, carbendazim, ESI-09, MMV1581545, oxfendazole) displaying anti-metacestode activity. The parasiticidal activity of these five compounds was evaluated by ATP measurement in germinal layer cells. One compound, ESI-09, acted specifically against <em>E. multilocularis</em> (IC₅₀ on metacestode vesicles 6.06 ± 3.18 μM by PGI release assay and 2.09 ± 0.56 μM by metacestode vesicle viability assay as well as an IC₅₀ of 2.45 ± 0.86 μM on germinal layer cells) with a broad therapeutic window when compared to mammalian cell toxicity. Further experiments applying Seahorse technology and tetramethylrhodamine ethyl ester (TMRE) assay revealed that ESI-09 acts as a mitochondrial uncoupler in parasite cells. However, transmission electron microscopy showed no significant ultrastructural changes in parasite mitochondria, though increased secretion of extracellular vesicle-like structures between the tegument and the laminated layer was observed. In summary, screening of the Pandemic Response Box identified ESI-09 as a potential drug candidate for the treatment of AE. Further experiments are needed to evaluate the efficacy of ESI-09 <em>in vivo</em>.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"29 ","pages":"Article 100609"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908231","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":"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":3.5,"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}

{"title":"Trialling the SmartWorm® application in New Zealand sheep farms","authors":"C.L. Brosnahan ,&nbsp;D. Warburton ,&nbsp;N. Cotter ,&nbsp;J.C. Tanner ,&nbsp;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 (R² = 0.8951, P &lt; 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}

{"title":"Antiplasmodial activity of pentyloxyamide-based histone deacetylase inhibitors against Plasmodium falciparum parasites","authors":"Wisam A. Dawood ,&nbsp;Gillian M. Fisher ,&nbsp;Josefa Kremeyer ,&nbsp;Fabian Fischer ,&nbsp;Jessica L. Home ,&nbsp;Christopher D. Goodman ,&nbsp;Kwong Sum Lam ,&nbsp;Alexander G. Maier ,&nbsp;Thomas Kurz ,&nbsp;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 &gt; 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> IC₅₀ of 20 nM and &gt;250-fold greater selectivity for <em>P. falciparum</em> versus human cells. Compound <strong>4o</strong> was also active against exoerythrocytic stage parasites (IC₅₀ 24 nM), which are a target for malaria prevention. In contrast, <strong>4o</strong> lacked potent activity against late-stage gametocytes (IC₅₀ &gt; 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}