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

{"title":"Corrigendum to \"Evolutionary and epidemiological considerations for anthelmintic treatments in ruminant livestock\" [Int. J. Parasitol.: Drugs Drug Resist. 32 (2026) 100669].","authors":"Neil Philip Hobbs, John Graham-Brown, Eric R Morgan, Hannah Rose Vineer","doi":"10.1016/j.ijpddr.2026.100671","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2026.100671","url":null,"abstract":"","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":" ","pages":"100671"},"PeriodicalIF":3.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060439","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}

{"title":"Pharmacokinetics of fenbendazole and its bioactive metabolite oxfendazole in northern bobwhite administered an anthelmintic feed","authors":"Hannah N. Suber ,&nbsp;Dhavalkumar Patel ,&nbsp;Timothy B. Arlowe ,&nbsp;Ashley Kaskocsak ,&nbsp;Henry Valencia ,&nbsp;Kaya Kinsey ,&nbsp;Will R. Robinson ,&nbsp;Ronald J. Kendall","doi":"10.1016/j.ijpddr.2026.100640","DOIUrl":"10.1016/j.ijpddr.2026.100640","url":null,"abstract":"<div><div>The northern bobwhite (<em>Colinus virginianus</em>) has experienced significant population declines across its native range. Parasitic nematodes are increasingly being recognized as contributing factors. QuailGuard®, an anthelmintic feed that uses fenbendazole (FBZ) as the active ingredient, has shown promise in field studies for reducing parasite loads in wild quail. However, little is known about the pharmacokinetics of FBZ in bobwhite, limiting accurate assessments of therapeutic exposure. This study investigated the pharmacokinetic profile of FBZ and its bioactive metabolite, oxfendazole (OFZ), in bobwhite fed QuailGuard®. Plasma concentrations were measured at multiple time points during (1, 2, 4, 8, and 24 h) and after (2, 4, 8, 24, and 32 h) feed administration using LC/MS-MS. Key pharmacokinetic parameters, including estimated area under the curve (AUC), apparent elimination rate, half-life, and mean residence time (MRT) were calculated using composite sampling. Peak average plasma concentrations of FBZ (2.3701 μg/mL) and OFZ (0.5526 μg/mL) occurred at 8 h post-ingestion. Estimated AUCs were 47.782 μg h/mL for FBZ and 12.783 μg h/mL for OFZ, with respective half-lives of 3.83 and 4.03 h. Combined drug exposure approached levels associated with the lethality of <em>Oxyspirura petrowi</em> in prior studies, indicating that intake over multiple weeks may achieve therapeutic efficacy. While sex did not affect analyte accumulation during treatment, females exhibited faster OFZ apparent elimination than males. FBZ and OFZ were rapidly absorbed and eliminated, which supports the safety of QuailGuard® for use in wild populations. These findings establish foundational pharmacokinetic data necessary for optimizing field treatment regimens and improving parasite control strategies in declining bobwhite populations.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"30 ","pages":"Article 100640"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616142","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":"Prevalence of antimalarial drug resistance molecular markers in Makenene, central Cameroon","authors":"Nelly Armanda Kala-Chouakeu ,&nbsp;Joel Djoufounna ,&nbsp;Nicolas Benoit ,&nbsp;Timoléon Tchuinkam ,&nbsp;Océane Delandre ,&nbsp;Lionel Almeras ,&nbsp;Roland Bamou ,&nbsp;Christophe Antonio-Nkondjio ,&nbsp;Marylin Madamet ,&nbsp;Bruno Pradines","doi":"10.1016/j.ijpddr.2026.100633","DOIUrl":"10.1016/j.ijpddr.2026.100633","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;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 &lt;em&gt;Plasmodium falciparum&lt;/em&gt; drug resistance genetic markers was assessed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;185 samples from asymptomatic individuals with &lt;em&gt;P. falciparum&lt;/em&gt; parasitaemia collected between September and October 2021 were sequenced for the &lt;em&gt;Pfdhfr&lt;/em&gt;, &lt;em&gt;Pfdhps&lt;/em&gt;, &lt;em&gt;Pfcrt&lt;/em&gt;, &lt;em&gt;Pfmdr1,&lt;/em&gt; and &lt;em&gt;PfK13&lt;/em&gt; genes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;One hundred percent of the samples harboured parasites with triple mutant &lt;em&gt;Pfdhfr&lt;/em&gt; &lt;strong&gt;I&lt;/strong&gt;&lt;sub&gt;51&lt;/sub&gt;&lt;strong&gt;R&lt;/strong&gt;&lt;sub&gt;59&lt;/sub&gt;&lt;strong&gt;N&lt;/strong&gt;&lt;sub&gt;108&lt;/sub&gt;I&lt;sub&gt;164&lt;/sub&gt; (&lt;strong&gt;IRN&lt;/strong&gt;I), associated with high level of resistance to pyrimethamine. The septuple mutant &lt;em&gt;Pfdhfr&lt;/em&gt; &lt;strong&gt;IRN&lt;/strong&gt;I and &lt;em&gt;Pfdhps&lt;/em&gt; &lt;strong&gt;A&lt;/strong&gt;&lt;sub&gt;436&lt;/sub&gt;&lt;strong&gt;G&lt;/strong&gt;&lt;sub&gt;437&lt;/sub&gt;K&lt;sub&gt;540&lt;/sub&gt;&lt;strong&gt;G&lt;/strong&gt;&lt;sub&gt;581&lt;/sub&gt;&lt;strong&gt;S&lt;/strong&gt;&lt;sub&gt;613&lt;/sub&gt; (&lt;strong&gt;AG&lt;/strong&gt;K&lt;strong&gt;GS&lt;/strong&gt;), associated with resistance to sulfadoxine-pyrimethamine, was detected in 62.0 % of the isolates. The new &lt;em&gt;Pfdhps&lt;/em&gt; I431V mutation was observed in 18.8 %. The octuple mutant &lt;strong&gt;IRN&lt;/strong&gt;I + &lt;strong&gt;VAG&lt;/strong&gt;K&lt;strong&gt;GS&lt;/strong&gt; haplotype, overrepresented in pregnant women taking intermittent preventive treatment with sulfadoxine-pyrimethamine, was found in 17.4 %. The &lt;em&gt;Pfdhps&lt;/em&gt; K540E mutation, linked to “super” resistance to sulfadoxine, was only detected in 1.9 %. The &lt;em&gt;Pfcrt&lt;/em&gt; C&lt;sub&gt;72&lt;/sub&gt;V&lt;sub&gt;73&lt;/sub&gt;&lt;strong&gt;I&lt;/strong&gt;&lt;sub&gt;74&lt;/sub&gt;&lt;strong&gt;E&lt;/strong&gt;&lt;sub&gt;75&lt;/sub&gt;&lt;strong&gt;T&lt;/strong&gt;&lt;sub&gt;76&lt;/sub&gt; haplotype, implicated in chloroquine resistance, was absent in Makenene. The &lt;em&gt;Pfmdr1&lt;/em&gt; N&lt;sub&gt;86&lt;/sub&gt;&lt;strong&gt;F&lt;/strong&gt;&lt;sub&gt;184&lt;/sub&gt; haplotype, selected in parasites with a recrudescence in patients treated with artemether-lumefantrine, was found in 73.2 %. No isolate harboured the &lt;strong&gt;Y&lt;/strong&gt;&lt;sub&gt;86&lt;/sub&gt;Y&lt;sub&gt;184&lt;/sub&gt; haplotype, selected in parasites with recrudescence in patient treated with dihydroartemisinin-piperaquine. Moreover, no mutation associated with artemisinin partial resistance was detected in &lt;em&gt;PfK13&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The in-depth analysis of genetic mutations associated with antimalarials resistance in this study, notably those with a high prevalence of mutations on the &lt;em&gt;Pfdhfr&lt;/em&gt; and &lt;em&gt;Pfdhps&lt;/em&gt; 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}