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

{"title":"Changes in molecular markers of Plasmodium falciparum drug resistance between 2017 and 2024 in Southern Benin.","authors":"Francis Emmanuel Towanou Bohissou, Diolinda Nahum, Juliana Inoue, Paul Sondo, Lazare Hounsou, Gethaime Sondjo, Nicaise Denis Codjo Djègbè, Robinson Woli, Salomon Dossou, Charlotte Kpohonnou, Halidou Tinto, Jana Held","doi":"10.1016/j.ijpddr.2026.100670","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2026.100670","url":null,"abstract":"<p><strong>Background: </strong>Benin remains highly burdened by malaria, and data on antimalarial resistance surveillance are limited. This study assesses the evolution of molecular markers associated with antimalarial resistance in southern Benin between 2017 and 2024.</p><p><strong>Methods: </strong>We analysed 358 dried blood spot samples collected from children in southern Benin (Kétonou, Kpomè and Klouékanmè) in 2017 and 2024. Molecular markers in the PfKelch13, Pfmdr1, Pfcrt, Pfdhfr, and Pfdhps genes associated with antimalarial drug resistance were investigated. Pfcrt haplotypes were characterised using quantitative PCR, while the remaining markers were analysed by nested PCR followed by Sanger sequencing.</p><p><strong>Results: </strong>None of the detected non-synonymous PfKelch13 mutations (7/281) was a WHO-validated, candidate or potential marker of artemisinin partial resistance. The Pfcrt CVIET haplotype declined significantly from 88.1% (59/67) in 2017 to 35.4% (101/285) in 2024 (p < 0.001). The Pfmdr1 N86Y decreased from 11.6% (8/69) to 6.0% (17/285), while the NFD haplotype increased slightly from 56.9% (37/65) to 61.9% (169/273). No mutations were observed at Pfdhfr I164L or Pfdhps K540E. The Pfdhfr triple-mutant IRNI haplotype remained nearly fixed over time at 97.0% (64/66) in 2017 vs 96.4% (268/278) in 2024. A similar trend was observed for Pfdhps A437G at 98% in 2017 and 2024. The Pfdhps I431V rose from 8.3% (5/60) in 2017 to 10.5% (29/275) in 2024, whereas Pfdhps A581G remained stable at 8%. The combined Pfdhfr/PfdhpsIRN_G haplotype remained highly prevalent (96.5% vs 94.6%). Aside from the significant decline in CVIET, none of the other changes was statistically significant.</p><p><strong>Conclusion: </strong>Our findings show no mutations compromising ACT efficacy, nor any immediate threat to the continued use of SP. In addition, the observed re-emergence of chloroquine-sensitive genotypes suggests a shift in parasite population dynamics over time. Nevertheless, continuous molecular surveillance remains essential for detecting emerging resistance and informing timely policy decisions.</p>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"32 ","pages":"100670"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891577","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":"Symbiotic Stenotrophomonas maltophilia is associated with ivermectin resistance in the parasitic nematode Haemonchus contortus via metabolic detoxification.","authors":"Simin Wu, Chunqun Wang, Juncheng Li, Lisha Ye, Fuqiang Liu, Waresi Tuersong, Junyan Li, Juan Zhang, Yao Zhang, Hui Liu, Min Hu","doi":"10.1016/j.ijpddr.2026.100668","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2026.100668","url":null,"abstract":"<p><p>Anthelmintic resistance constitutes a global threat to the control of parasitic nematodes. Current research has primarily focused on parasite-intrinsic genetic mechanisms, while the contribution of the symbiotic microbial community remains a key knowledge gap. Here, we report that ivermectin (IVM) resistance in the gastrointestinal nematode Haemonchus contortus is associated with the abundance of the bacterium Stenotrophomonas maltophilia. A representative strain, designated SM1, was isolated from resistant populations, and its abundance was associated with the resistant phenotype. Depletion of SM1 increased larval susceptibility to IVM, whereas reintroduction of the bacterium partially enhanced IVM tolerance. Metabolic analysis indicated that SM1 converts IVM into demethylated and oxo-derivatives (M1, M4, and M7). Using in silico analysis, the putative cytochrome P450 monooxygenase (Cmp08160) with a possible participation in IVM biotransformation was identified. Collectively, these findings suggest that symbiotic bacteria can influence IVM susceptibility in H. contortus and highlight the relevance of considering host-microbiota interactions in studies of anthelmintic resistance.</p>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"32 ","pages":"100668"},"PeriodicalIF":3.5,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874055","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":"Evolutionary and epidemiological considerations for anthelmintic treatments in ruminant livestock.","authors":"Neil Philip Hobbs, John Graham-Brown, Eric R Morgan, Hannah Rose Vineer","doi":"10.1016/j.ijpddr.2026.100669","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2026.100669","url":null,"abstract":"<p><p>Anthelmintic drug resistance is a concern for the sustained control of gastrointestinal nematodes (GINs) in ruminant livestock globally. Evolutionary-epidemiological modelling, which considers both parasite dynamics and resistance dynamics in response to interventions, can be useful in determining which anthelmintic resistance management (ARM) strategies may be effective without compromising parasite control. We address two key questions in ARM. First, how to improve the measurement of AR in populations. Second, identifying effective ARM strategies to slow the spread of AR while maintaining effective parasite control. We developed a simulation framework which tracks the weather-dependent epidemiology of GINs and AR evolution, providing a highly flexible methodology to evaluate multiple ARM strategy options in a single modelling framework, allowing for novel insights due to direct comparisons between strategies. Simulations to refine our understanding of anthelmintic resistance management evaluated the impact of key areas of uncertainty, including transmission intensity, resistance intensity, resistance frequency, drug decay and linking faecal egg count reduction tests (FECRT) to resistance allele frequency. Large-scale simulations present a methodologically thorough evaluation of how treatment choices simultaneously impact epidemiological and evolutionary outcomes. Phenotypic classifications of resistance status using FECRT failed to capture fine scale changes in resistance allele frequency. The pharmacokinetics of drug decay strongly influenced ARM outcomes, and trade-offs between ARM and effective parasite control depends on genetic factors underpinning resistance. Combination therapies appear to be the most effective resistance management strategy evaluated. Our findings suggest practical implementations to manage anthelmintic resistance must simultaneously consider parasite transmission, pharmacology and parasite genetics to be robust and sustainable. We provide a rigorous simulation framework to enable such discussions allowing for a refinement into our understanding of parasite control in the presence of resistance evolution.</p>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"32 ","pages":"100669"},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864161","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":"Mitomycin C potentiates metronidazole activity in resistant Trichomonas vaginalis through suppression of thioredoxin reductase","authors":"Yuan-Ming Yeh,&nbsp;Po-Jung Huang,&nbsp;Yu-Lo Wu,&nbsp;Chun-Hsien Chen,&nbsp;Pei-Yun Chen,&nbsp;Yu-Tzu Hsu,&nbsp;Wei-Hung Cheng","doi":"10.1016/j.ijpddr.2026.100661","DOIUrl":"10.1016/j.ijpddr.2026.100661","url":null,"abstract":"<div><div>Metronidazole (MTZ) remains the first-line therapy for trichomoniasis; however, increasing resistance in <em>Trichomonas vaginalis</em> threatens treatment efficacy. Because iron availability enhances MTZ sensitivity, we investigated whether MTZ-induced parasite death involves ferroptosis-related mechanisms and explored alternative pathways contributing to drug resistance. Exposure of metronidazole-sensitive and -resistant isolates to ferroptosis inducers reduced parasite viability, yet neither ferroptosis inhibition nor iron chelation restored survival, and lipid peroxidation was not detected. These findings indicate that MTZ-associated cytotoxicity does not proceed via canonical ferroptotic pathways in <em>T. vaginalis</em>. Instead, resistant parasites exhibited elevated expression of thioredoxin-associated transcripts, consistent with enhanced redox defense capacity. Functional suppression of thioredoxin reductase (TrxR) activity by mitomycin C (MMC) significantly enhanced MTZ-mediated killing and produced a synergistic antiparasitic effect in resistant isolates. Although selective TrxR inhibition alone was insufficient to fully reproduce this phenotype, these findings implicate thioredoxin-dependent redox regulation as a contributor to MTZ susceptibility. Combination treatment was accompanied by selective metabolic reprogramming, including upregulation of pentose phosphate pathway genes linked to NADPH generation. Collectively, our results demonstrate that MTZ induces a non-ferroptotic form of cell death and identify thioredoxin-dependent redox buffering as a resistance-associated vulnerability. Targeting redox homeostasis through rational combination therapy may represent a mechanistically guided strategy to overcome metronidazole resistance in trichomoniasis.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"31 ","pages":"Article 100661"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535759","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":"Discovery of thienopyrimidine analog G-18 as a novel anti-trichomonal agent","authors":"Yao Zhang,&nbsp;Bingqian Zhang,&nbsp;Daiqian Zhu,&nbsp;Xiaolong Fu,&nbsp;Fengxu Wu,&nbsp;Yanggen Hu,&nbsp;Jian Li","doi":"10.1016/j.ijpddr.2026.100665","DOIUrl":"10.1016/j.ijpddr.2026.100665","url":null,"abstract":"<div><div>Trichomoniasis, caused by <em>Trichomonas vaginalis</em>, is the most prevalent nonviral sexually transmitted infection worldwide. The occurrence of treatment failure with metronidazole (MTZ) and the adverse effects of currently available nitroimidazoles underscore the necessity for novel therapeutic candidates. From a library of synthetic thienopyrimidine derivatives, G-18 was identified as a lead compound. G-18 exhibited potent anti-<em>T. vaginalis</em> activity against the tested <em>T. vaginalis</em> isolate, with a minimum inhibitory concentration (MIC) of 4 μg/mL and a half-maximal inhibitory concentration (IC₅₀) of 1 μg/mL at 24 h, and it significantly reduced trophozoite viability within 2 h. Flow cytometry confirmed a higher proportion of propidium iodide (PI)-positive parasites following G-18 treatment compared to MTZ treatment (51.2% vs. 10.4%). G-18 demonstrated limited cytotoxicity towards mammalian cells under the tested conditions. Scanning and transmission electron microscopy revealed pronounced ultrastructural damage, including surface roughening, membrane disruption, and organelle disorganization. These findings support G-18 as a promising anti-trichomonal lead compound with rapid in vitro activity and a preliminary selectivity profile under the tested conditions.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"31 ","pages":"Article 100665"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697439","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":"Three-year evaluation of anthelmintic treatment efficacy against equine strongyles in France using FECRT","authors":"Gabin Brucelle,&nbsp;Marie Delerue,&nbsp;Kenza Bourrier,&nbsp;Camille Gaudens,&nbsp;Sophie Lefebvre,&nbsp;Aurélie Merlin","doi":"10.1016/j.ijpddr.2026.100663","DOIUrl":"10.1016/j.ijpddr.2026.100663","url":null,"abstract":"<div><div>Reduced anthelmintic efficacy against strongyles in equids is a widespread concern, but up-to-date field data are scarce. The aim of this study was to evaluate, over a three-year period, the efficacy of the anthelmintic (AH) molecules available in France (fenbendazole, pyrantel, ivermectin and moxidectin) against strongyles in equids using faecal egg count reduction tests (FECRTs). A total of 104 complete FECRTs (i.e., required sample size reached) were conducted in 98 groups, involving 749 equids kept in 70 facilities. Fenbendazole-resistant populations were detected in 8/9 groups (89%) from 7/8 facilities (88%; upper 90% CI range: 30.5%-83%) and pyrantel-resistant populations in 15/22 groups (68%) from 12/17 facilities (71%; upper 90% CI range: 56%-97%). Regarding macrocyclic lactone efficacy, ivermectin-resistant populations were identified in 14/51 groups (27%) kept in 11/41 facilities (27%; upper 90% CI range: 85.6%-99.9%) and moxidectin-resistant populations in 5/22 groups (23%) kept in 4/18 facilities (22%; upper 90% CI range: 85.3%-99.7%). Resistance was mainly detected in the Normandy region and in breeding farms (25/70), but also in riding schools offering boarding services (3/70), experimental platforms (2/70), and a zoological park (1/70).</div><div>In conclusion, this study provides the first evidence in France of resistance to all four available AH molecules and documents the spread of these resistances across the facilities. It also highlights the urgent need for regulatory changes requiring the use of AH only after a diagnostic assessment (e.g., targeted selective treatment based on faecal egg count results) in order to reduce the selective pressure exerted on parasite populations.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"31 ","pages":"Article 100663"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619952","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":"Histone deacetylase inhibitors enhance the amoebicidal activity of amphotericin B against Naegleria fowleri","authors":"Hae-Ahm Lee,&nbsp;Hye-Jeong Jo,&nbsp;Ji-Youn Hong,&nbsp;Fu-Shi Quan,&nbsp;Eun-Kyung Moon","doi":"10.1016/j.ijpddr.2026.100664","DOIUrl":"10.1016/j.ijpddr.2026.100664","url":null,"abstract":"<div><div><em>Naegleria fowleri</em> is a free-living amoeba that causes a rare but almost always fatal brain infection known as primary amoebic meningoencephalitis (PAM). Although amphotericin B (AmB) is considered the primary treatment for PAM, it is often recommended in combination with several other drugs due to side effects associated with high concentrations. In this study, we investigated whether histone deacetylase inhibitors (HDACis) enhance the amoebicidal activity of AmB against <em>N. fowleri</em>. Anti-proliferative and cytotoxic activities were assessed using the cell counting kit and lactate dehydrogenase assays, respectively, and apoptosis induction was evaluated by flow cytometry. Class-specific HDACis, including class I inhibitors MS275 and MGCD0103 and a class II inhibitor MC1568, showed minimal effects on trophozoite viability. In contrast, the pan-HDACis SAHA and JNJ significantly reduced trophozoite viability in a dose- and time-dependent manner. Furthermore, 10 μM SAHA and JNJ significantly reduced the encystation ratio of <em>N. fowleri</em>. Combined treatment with low doses of HDACi (1 μM) and AmB (0.5 μM) produced stronger amoebicidal and pro-apoptotic effects than either agent alone. These combination treatments also exhibited low cytopathic effects on human brain tumor cells. These findings suggest that SAHA and JNJ, particularly in combination with AmB, hold promise as therapeutic candidates against <em>N. fowleri</em> infection while potentially mitigating the severe side effects associated with AmB.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"31 ","pages":"Article 100664"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678458","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":"Evolutionary diversity of the pfmdr1 hinge region and association with antimalarial drug resistance mutations post ACT introduction","authors":"Emma Filtenborg Hocke,&nbsp;Helle Hansson,&nbsp;Ana Chopo-Pizarro,&nbsp;Louise Wellmann,&nbsp;Gauthier Mesia Kahunu,&nbsp;Hypolite Muhindo Mavoko,&nbsp;Papy Mandoko Nkoli,&nbsp;Eric Mukomena Sompwe,&nbsp;Destin Mbongi,&nbsp;Patrick Mitashi,&nbsp;Innocent Mbulli Ali,&nbsp;Akindeh Nji,&nbsp;Wilfred Mbacham,&nbsp;Azizath Moussiliou,&nbsp;Codjo Dandonougbo,&nbsp;Augustin Kpemasse,&nbsp;Cyriaque Affoukou,&nbsp;Martin Akogbeto,&nbsp;Corine Ngufor,&nbsp;Khalid Beshir,&nbsp;Michael Alifrangis","doi":"10.1016/j.ijpddr.2026.100662","DOIUrl":"10.1016/j.ijpddr.2026.100662","url":null,"abstract":"<div><div>The <em>Plasmodium falciparum</em> multidrug resistance-1 (<em>pfmdr1</em>) gene, which encodes the ABC P-glycoprotein homolog PgH1, accumulates mutations that result in amino acid changes, namely single-nucleotide polymorphisms at codons N86Y, Y184F, and D1246Y, associated with altered parasite susceptibility to multiple antimalarial drugs. Among these antimalarials are compounds used in artemisinin-based combination (ACT) therapies, which combine a fast-acting but rapidly clearing artemisinin with a longer-lasting partner drug. The <em>in vitro</em> susceptibility of each of these drugs varies with the <em>pfmdr1</em> genotype of the treated parasites.</div><div>This study characterized sequence diversity within the <em>pfmdr1</em> hinge domain and the association with <em>pfmdr1</em> point mutations at codons 86, 184 and 1246 in population samples from Cameroon, the Democratic Republic of Congo, and Benin, two decades after the introduction of ACTs. The data were evaluated and compared with similar data reported before or during the early implementation of ACT-based treatment strategies.</div><div>Among 780 successfully sequenced isolates, a high diversity of Arginine-rich repeats in the hinge domain was observed. A significant correlation between the (Asn-Asp-Asn) 7-2-9 variant and both the 86Y and the 1246Y mutation was observed (p &lt; 0.005, OR = 12.6, respectively). We also uncovered, when examining haplotypes across the N86Y, Y184F, and D1246Y codons, that an accumulation of mutations was inversely correlated with diversity in the hinge region. The data suggest patterns consistent with selective pressure and/or linkage with reduced diversity as a potential result of ACT implementation.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"31 ","pages":"Article 100662"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684362","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":"Efficacy of phosphonium amphiphilic salts against Acanthamoeba genotype T4","authors":"Miloš Lukáč ,&nbsp;Martin Pisárčik ,&nbsp;Mária Garajová ,&nbsp;Julia Walochnik ,&nbsp;Daniela Ošustová ,&nbsp;Eva Vatrtová ,&nbsp;Iryna Bondar ,&nbsp;Ferdinand Devínsky ,&nbsp;Martin Mrva","doi":"10.1016/j.ijpddr.2026.100636","DOIUrl":"10.1016/j.ijpddr.2026.100636","url":null,"abstract":"<div><div>Acanthamoebae are opportunistic pathogens causing serious human infections, including granulomatous amoebic encephalitis (GAE) and <em>Acanthamoeba</em> keratitis (AK). The treatment of those infections is limited and difficult to date. Recent research demonstrated high antimicrobial activity of phosphonium amphiphilic salts. In the present work we aimed to investigate the anti-<em>Acanthamoeba</em> effect of a series of 16 phosphonium salts. The structure of these synthesized cationic amphiphiles was modified in both the polar and nonpolar parts of the surfactant molecule. The compounds have different alkyl chain lengths (C12 - C18) and different numbers of methyl and phenyl groups (0 - 3) attached to the quaternary phosphorus atom. The following basic physicochemical properties of the compounds were determined: critical micelle concentration (cmc), the surface tension value at the cmc and the surface area per surfactant head group. The cmc values, which express the degree of lipophilicity of compounds, were correlated with biological activities. The effects of phosphonium salts on trophozoites of <em>Acanthamoeba quina</em> and <em>Acanthamoeba hatchetti</em> (both strains of genotype T4) and human erythrocytes were studied. The highest trophocidal activity was recorded for the compound <strong>C₁₆P(Me)₂PhBr</strong> with the minimal trophocidal concentration (MTC) of 7.8 μM for the <em>A. quina</em> strain and 15.6 μM for the <em>A. hatchetti</em> strain, after 24 h. Its activity was comparable or higher than the activity of drugs currently used in the treatment of <em>Acanthamoeba</em> keratitis. Therefore, this compound is a promising candidate in the fight against infections caused by <em>Acanthamoeba</em>.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100636"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142452","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":"Ferrostatin-1 alleviates experimental cerebral malaria by regulating immune cell functions and brain endothelial ferroptosis","authors":"Shijie Yao ,&nbsp;Xiaoliang Zhou ,&nbsp;Ting Liao ,&nbsp;Chao Yao ,&nbsp;Mengna Sun ,&nbsp;Haojie Gou ,&nbsp;Xueyuan Hu ,&nbsp;Junyu Liu ,&nbsp;Li Zheng ,&nbsp;Yan Zhao ,&nbsp;Yaming Cao","doi":"10.1016/j.ijpddr.2025.100630","DOIUrl":"10.1016/j.ijpddr.2025.100630","url":null,"abstract":"<div><div>Cerebral malaria (CM), a life-threatening complication of <em>Plasmodium falciparum</em> infection, is characterized by dysregulated immune responses and blood-brain barrier (BBB) damage. In this study, we found that iron metabolic disorders occurred in the spleen and brain tissues in response to <em>Plasmodium berghei</em> ANKA (PbA) infection in a murine CM model. PbA infection promoted lipid peroxidation and induced ferroptosis, manifested as the accumulation of iron ion, elevation of reactive oxygen species and lipid peroxide, upregulated expression of the ferroptosis-related protein TFRC and ACSL4, and downregulated expression of SLC7A11 and GPX4. Ferrostatin-1 (Fer-1), is widely used as a reference compound as a synthetic radical-trapping antioxidant, which inhibits ferroptosis by suppressing lipid peroxide formation. Intervention with Fer-1 ameliorated iron metabolic disorders, reduced lipid peroxidation, decreased parasitemia, extended survival time, alleviated neurological symptoms, and improved BBB integrity. Mechanistically, Fer-1 exerted dual-axis regulation: firstly, enhancing the antigen-presenting capacity of dendritic cells (DCs) by upregulating MHC II, CD80/86, promoting M1 polarization of macrophages, modulating CD4⁺ T cell responses to increase IFN-γ⁺ Th1 cells and Treg cell proportions for balancing pro-inflammatory and anti-inflammatory reactions; secondly inhibiting ferroptosis in brain microvascular endothelial cells, downregulating chemokines CXCL9/CXCL10 and adhesion molecules ICAM-1/VCAM-1, and reducing cerebral infiltration of CD8⁺ T cells. Our study confirms that Fer-1 alleviates ECM pathological progression through dual mechanisms \"immune activation-endothelial protection\", providing a novel ferroptosis-targeted strategy for CM prevention and treatment.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100630"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789971","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}