Frontiers in parasitology最新文献

{"title":"Effect of urine storage conditions on circulating anodic antigen detection using the UCP-LF CAA test.","authors":"Pytsje T Hoekstra, Govert J van Dam, Maureen Blokland-Flink, Danielle de Jong, Said M Ali, Mohammed N Ali, Naomi C Ndum, Stefanie Knopp, Paul L A M Corstjens, Lisette van Lieshout","doi":"10.3389/fpara.2026.1894516","DOIUrl":"10.3389/fpara.2026.1894516","url":null,"abstract":"<p><strong>Introduction: </strong>Schistosomiasis is a parasitic neglected tropical disease that remains a major public health problem in many African countries. Accurate diagnosis is essential for control, surveillance and elimination efforts. Conventional parasitological methods have limited sensitivity, particularly in low-intensity infections commonly observed after treatment or in low-endemic settings. Circulating anodic antigen (CAA), released by live <i>Schistosoma</i> worms, is a highly sensitive and specific marker of active infection. The up-converting reporter particle lateral flow (UCP-LF) CAA test enables non-invasive urine-based diagnosis and is increasingly applied in low-endemic and near-elimination settings. For operational feasibility, urine samples may need to be stored before testing, but the effect of different storage conditions on CAA detection has not been systematically evaluated.</p><p><strong>Methods: </strong>We investigated the effect of freezing and non-frozen storage on urine CAA detection using the UCP-LF CAA test, compared with freshly tested urine. The study was conducted among school-aged children in a near-elimination <i>Schistosoma haematobium</i> setting on Pemba, Tanzania. A total of 272 urine samples were tested fresh and after freezing at -20 °C for 5-7 days. For a subset of 153 samples with sufficient urine available, an additional aliquot was stored under non-frozen conditions (4-25 °C) and tested approximately 5 weeks after collection.</p><p><strong>Results: </strong>CAA positivity decreased from 44/272 (16.2%) in fresh urine to 35/272 (12.9%) after freezing. In the subset, positivity was 20/153 (13.1%) in fresh, 16/153 (10.5%) in frozen, and 24/153 (15.7%) in non-frozen stored urine. CAA concentrations showed strong correlation between storage conditions (Spearman's ρ = 0.86-0.93, p<0.0001). Freezing was associated with a small but significant reduction in CAA positivity (p=0.004), while CAA concentrations showed a non-significant trend towards lower values after freezing. Non-frozen stored samples showed generally comparable results to fresh urine.</p><p><strong>Discussion/conclusion: </strong>In conclusion, these findings suggest that flexible urine storage strategies may be feasible for delayed centralized CAA testing, although freezing may result in loss of detection among samples with CAA concentrations close to the assay cut-off.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1894516"},"PeriodicalIF":2.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of gastrointestinal parasites in <i>Sus scrofa domesticus</i> from Europe (2010 - 2026).","authors":"Alesia Cioacă, Diana Hoffman, Ioan Cristian Dreghiciu, Tiana Florea, Mirela Imre, Anamaria Plesko, Mălina Oprescu, Ion Oprescu, Gheorghe Dărăbuş, Marius Stelian Ilie","doi":"10.3389/fpara.2026.1950643","DOIUrl":"10.3389/fpara.2026.1950643","url":null,"abstract":"<p><strong>Introduction: </strong>Gastrointestinal parasitic infections remain an important concern in European pig production due to their potential impact on animal health, productivity, and, in the case of zoonotic species, public health. This systematic review investigated the occurrence of gastrointestinal helminths and enteric protists in domestic pigs across Europe and analysed the factors associated with their prevalence.</p><p><strong>Methods: </strong>A total of 28 studies published between 2010 and 2026 were included, identified through a structured search strategy conducted in three scientific databases.</p><p><strong>Results: </strong>The included studies reported a wide diversity of helminths and enteric protists in pigs raised under intensive, extensive, organic, and alternative production systems. Among helminths, <i>Ascaris suum, Trichuris suis</i>, and <i>Oesophagostomum</i> spp. were the most frequently identified species, whereas <i>Balantioides coli, Cryptosporidium</i> spp., <i>Cystoisospora suis</i>, and <i>Blastocystis</i> sp. represented the main enteric protists reported.</p><p><strong>Discussion: </strong>Overall, gastrointestinal parasites and enteric protists remain widely distributed in domestic pigs across Europe, with prevalence influenced by production system, management practices, host age, and diagnostic methodology. The identification of species with zoonotic potential also underlines the importance of continuous epidemiological surveillance within the One Health framework.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1950643"},"PeriodicalIF":2.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioaminergic signaling in parasitic flatworms: a perspective for linking GPCRs to behavior and drug discovery.","authors":"Erika Bistran, M Evelyn Carpenter, Daniel J Sprague","doi":"10.3389/fpara.2026.1933406","DOIUrl":"10.3389/fpara.2026.1933406","url":null,"abstract":"<p><p>Bioaminergic signaling regulates behaviors that are central to parasite survival, including movement, attachment, feeding, pairing, and reproduction, yet the molecular pathways linking bioamines to these phenotypes remain incompletely defined in parasitic flatworms. In this Perspective, we propose a pathway-to-phenotype framework for organizing future studies of flatworm aminergic signaling. This framework links six interconnected areas of investigation: the bioamine ligand, the receptor or transporter that detects or clears it, the downstream signaling pathway, the relevant cell type or tissue, the experimental perturbation used to test function, and the resulting parasite phenotype. Serotonin signaling through Sm5HTR in <i>Schistosoma mansoni</i> provides the clearest current example, connecting receptor activation to cAMP signaling, nervous-system localization, and movement. By contrast, dopaminergic, histaminergic, octopaminergic, tyraminergic, transporter-associated, and non-schistosome flatworm systems remain less completely mapped. We highlight these and other gaps, and discuss how comparative functional profiling across parasite lineages could reveal conserved signaling principles, parasite-selective pharmacology, and new opportunities for anthelmintic discovery.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1933406"},"PeriodicalIF":2.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GCMS profiling and larvicidal potentials of the extracts of <i>Terminalia catappa</i> leaf, <i>Eucalyptus citriodora</i> seed and stem against malarial, dengue and filarial vector mosquitoes (Diptera: Culicidae).","authors":"Eze Elijah Ajaegbu, Juliet Onyinye Nwigwe, Chidinma Claribel Chikezie, Nkeiru Catherine Enyi","doi":"10.3389/fpara.2026.1934443","DOIUrl":"https://doi.org/10.3389/fpara.2026.1934443","url":null,"abstract":"<p><p>The worldwide proliferation of vector-borne infections, coupled with advancing insect defense mechanisms against standard synthetic pesticides, compels the exploration of ecological, vegetation-derived countermeasures. This investigation sought to characterize the secondary metabolite distribution, prominent chemical fractions, and destructive impact of <i>Terminalia catappa</i> leaf ethyl acetate extract (TLEE), alongside <i>Eucalyptus citriodora</i> stem ethyl acetate extract (LSEE) and seed ethyl acetate extract (LEEE), against <i>Aedes aegypti</i>, <i>Anopheles gambiae</i>, and <i>Culex quinquefasciatus</i>. Mild ambient maceration of the leaf, seed and stem parts generated yield allocations of 3.3% TLEE, 2.8% LSEE, and 4.7% LEEE. Standardized larval mortality challenges captured survival dynamics across a 125 to 1000 ppm exposure gradient at 24 and 48 hours. Preliminary assays mapped basic compound groups, while gas chromatography-mass spectrometry (GC-MS) isolated individual volatile fractions within TLEE. Every prepared treatment produced distinct, concentration-dependent larval fatalities. For <i>Ae. aegypti</i>, LSEE demonstrated superior lethal efficiency, establishing an LC₅₀ threshold of 172.851 ppm at 24 hours. In 48-hour evaluations targeting <i>An. gambiae</i>, TLEE LC₅₀ is 13.271 ppm and LSEE LC₅₀ is 20.370 ppm induced a complete 100% elimination rate at a mere 250 ppm. <i>C. quinquefasciatus</i> exhibited marked vulnerability toward LEEE at 48 hours, registering an LC₅₀ value of 49.090 ppm. Tannic substances appeared across all specimens, whereas LSEE and LEEE exclusively concentrated alkaloids, flavonoids, resins, and steroids. Analytical profiling of TLEE resolved 16 discrete compounds. These metrics validate that TLEE, LSEE, and LEEE possess powerful bio-insecticidal attributes, offering sustainable, eco-safe options for suppressing target mosquito populations.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1934443"},"PeriodicalIF":2.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of <i>Plasmodium</i> DNA double strand repair by the combined action of 17-AAG and ML216.","authors":"Km Tanishka, Wahida Tabassum, Deepak Kumar Rout, Maria Mukherjee, Mrinal Kanti Bhattacharyya","doi":"10.3389/fpara.2026.1896831","DOIUrl":"10.3389/fpara.2026.1896831","url":null,"abstract":"<p><p>The RecQ helicase PfBlm from the human malaria parasite <i>Plasmodium falciparum</i> plays a critical role in maintaining genome integrity through its function in homologous recombination mediated DNA repair. Given its essential role in resolving recombination intermediates, PfBlm has emerged as a potential antimalarial drug target. Chemical inhibition of PfBlm helicase activity using the small-molecule inhibitor ML216 sensitize the parasites towards DNA damage inducing agents. Here, we investigated whether inhibition of the molecular chaperone PfHsp90 enhances the antimalarial efficacy of ML216. We demonstrate that the co-treatment with 17-AAG resulted in a marked reduction in the IC₅₀ of ML216, indicating potentiation of PfBlm inhibition upon PfHsp90 targeting. We report that PfHsp90 functionally associates with PfBlm and promotes UV irradiation-induced DNA repair by regulating PfBlm stability. Combined inhibition of PfHsp90 and PfBlm caused a pronounced and sustained defect in DNA repair that exceeded the effects of each of the individual inhibitors, consistent with a functional interaction. Together, these findings suggest that PfHsp90 contributes to PfBlm stability and activity, thus provide a rationale for simultaneously targeting PfHsp90 and PfBlm as a strategy to block parasite DNA repair and limit parasite survival.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1896831"},"PeriodicalIF":2.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular detection and genetic characterization of <i>Giardia duodenalis</i> in temple stray cats in Bangkok, Thailand.","authors":"Vy Thi Tuong Le, Pornkamol Phoosangwalthong, Minh-Trang Thi Hoang, Tawin Inpankaew","doi":"10.3389/fpara.2026.1948035","DOIUrl":"10.3389/fpara.2026.1948035","url":null,"abstract":"<p><strong>Introduction: </strong><i>Giardia duodenalis</i> is a ubiquitous enteric protozoan infecting humans, domestic animals, and wildlife worldwide. In Thailand, high densities of stray animals represent an important management challenge. However, molecular epidemiological data regarding stray cats remain limited. This study estimated the prevalence of <i>G. duodenalis</i>, characterized the identified genetic assemblages, and explored factors associated with PCR positivity in temple stray cats in Bangkok, Thailand.</p><p><strong>Methods: </strong>Fecal samples were collected from 500 stray cats residing across 43 temples in 24 districts of Bangkok. Detection of <i>G. duodenalis</i> was performed using nested PCR targeting the small subunit ribosomal RNA (SSU rRNA) gene. Positive samples were further characterized by genotyping at the glutamate dehydrogenase (<i>gdh</i>) and triosephosphate isomerase (<i>tpi</i>) loci. Phylogenetic analyses were conducted using the Maximum Likelihood method based on the Tamura 3-parameter model. Associated factors were evaluated using multivariable logistic regression.</p><p><strong>Results: </strong>The overall prevalence of <i>G. duodenalis</i> was 10.8% (54/500; 95% CI: 8.4-13.8%), with positive cases identified in 12 of the 24 surveyed districts and 19 of the 43 sampled temples. Eight isolates were successfully genotyped, identifying assemblage B (sub-assemblage BIV, n = 4), assemblage F (n = 3), and assemblage A (sub-assemblage AI, n = 1). The absence of human contact was identified as an exploratory variable associated with higher odds of PCR positivity (adjusted odds ratio [aOR] = 8.80; 95% CI: 2.15-35.98; <i>P</i> = 0.002), while demographic factors (age, sex), geographic zone, and deworming history showed no statistically significant associations.</p><p><strong>Discussion: </strong>Assemblages previously reported in humans and various animals were detected among a small number of successfully genotyped isolates, while the source, direction of transmission, and the reservoir status of temple stray cats could not be determined.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1948035"},"PeriodicalIF":2.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical inhibition of α-mannosidase in <i>S. mansoni</i> schistosomula leads to reshaped N-glycosylation associated with developmental alterations.","authors":"Eleonore B Kuhlemaijer, Tom Veldhuizen, Quirine C A Hoekstra, Jinthe A Umbach, Mathijs J Niezen, Josephine E Forde-Thomas, Gabriel Rinaldi, Karl F Hoffmann, Angela van Diepen, Cornelis H Hokke","doi":"10.3389/fpara.2026.1930872","DOIUrl":"10.3389/fpara.2026.1930872","url":null,"abstract":"<p><p>Schistosomes are parasitic flatworms that infect over 230 million people worldwide. As continuous exposure and high-reinfection rates cause severe disease in inhabitants of endemic areas, there is an urgent need for prophylactic vaccines or drugs that induce protective immunity. N-glycosylation is a conserved process in eukaryotes, including schistosomes, that affects various cellular and developmental biological processes. Schistosomes display characteristic developmental N-glycans that are important in parasite-host interaction and intra-mammalian development, which is associated with a changing N-glycan profile. In this study, we investigate whether application of the α-mannosidase inhibitors kifunensine and swainsonine during long-term <i>in vitro</i> culture of <i>S. mansoni</i> schistosomula leads to altered N-glycosylation and phenotypic changes in the parasite's development. We first analysed the effect of the inhibitors on schistosomula motility and phenotype, and showed that there was no overt toxicity linked to these compounds. Next, we examined the schistosomula N-glycosylation profiles during six weeks of culture. Within the first week (W1), the N-glycosylation changed dynamically in the schistosomula and exposure to inhibitors led to distinct profiles compared to the control. Control parasites were marked by oligomannose (30%) and complex (60%) N-glycans, kifunensine treatment led to a high proportion of oligomannose N-glycans (72%), specifically M8 and M9, and swainsonine-treated schistosomula were characterised by oligomannose (44%), hybrid (11%) N-glycans and free N-glycans with one core-GlcNAc (16%) at W1 post-compound treatment. Continued treatment conserved the distinct profiles, while discontinuation of treatment after W1 caused the N-glycans of kifunensine and swainsonine schistosomula to return to a profile similar to controls at W3. Interestingly, schistosomula treated continuously with kifunensine developed local oedema from W4 onwards, which was most profound at W6. However, discontinued treatment after W1 did not lead to a visible phenotype at W4 or later. In conclusion, prolonged alterations in schistosomula N-glycosylation led to disturbed development whereas short term glycan changes during the first week only, did not affect the parasite's normal development. Our data indicate that glyco-remodelled live schistosomes provide an attractive approach to study the contribution of glycans in intra-mammalian parasite development and survival.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1930872"},"PeriodicalIF":2.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149082893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: Isolated splenic hydatid cyst with negative serology managed by laparoscopic splenectomy.","authors":"Amine Ben Safta, Salsabil Nasri, Wejih Dougaz, Hazem Alouani, Meriem Ksentini, Hichem Jerraya, Ramzi Nouira","doi":"10.3389/fpara.2026.1956525","DOIUrl":"10.3389/fpara.2026.1956525","url":null,"abstract":"<p><strong>Background: </strong>Hydatid disease caused by Echinococcus granulosus is a zoonosis endemic in many parts of the world. While hepatic and pulmonary involvements are common, isolated splenic hydatidosis remains extremely rare, representing less than 4% of all cases. Diagnosis can be further complicated by false-negative serological tests.</p><p><strong>Case presentation: </strong>We report the case of a 31-year-old female presenting with isolated left upper quadrant pain. Physical examination and baseline laboratory tests were unremarkable. Abdominal ultrasound and computed tomography (CT) revealed a well-circumscribed, homogeneous, hypodense oval mass (50×57×56 mm) at the upper pole of the spleen with a thin wall displaying a focal calcification. Hydatid serology was negative. Given the high suspicion of a hydatid cyst, pre-splenectomy immunizations were administered, and the patient underwent an exploratory laparoscopy. Intraoperative findings confirmed a splenic hydatid cyst, and a total laparoscopic splenectomy was performed. The postoperative course was uneventful. Histopathological examination confirmed the diagnosis.</p><p><strong>Conclusion: </strong>Clinicians should maintain a high index of suspicion for hydatid disease in patients presenting with cystic splenic masses in endemic areas, even in the presence of negative serology. Laparoscopic splenectomy is a safe and effective approach when strict hydatid safety measures are respected.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1956525"},"PeriodicalIF":2.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zombies without puppeteers: Morgan's Canon and the passive manipulation hypothesis in <i>Xenos vesparum</i>/<i>Polistes dominula</i>.","authors":"Philip T Starks","doi":"10.3389/fpara.2026.1907843","DOIUrl":"10.3389/fpara.2026.1907843","url":null,"abstract":"<p><p>Parasite-associated changes in host behavior are often framed as manipulation, especially when altered behavior benefits parasite transmission. In the <i>Xenos vesparum</i>/<i>Polistes dominula</i> system, infected wasps abandon nests, aggregate before hibernation, overwinter, and later join established nests; a sequence often described through zombie or puppet-master metaphors. Recent studies have tied this phenotype to caste-related plasticity, gene expression, neuroanatomy, and ecological context, but the causal distinction between active parasite control and passive activation of host responses remains unresolved. Here I argue that passive manipulation should be treated as a useful null model and possible evolutionary starting point: infection may trigger pre-existing host responses that the parasite subsequently exploits. Archived pseudo-parasite observations are presented as an illustration: a sterile nylon implant, with no capacity for signaling, was associated with reduced energy use and nest desertion, whereas encapsulation intensity did not predict metabolic change. These observations do not prove passive manipulation by <i>X. vesparum</i>, but they show that early components of the infected phenotype can be induced without a living parasite. More broadly, parasite-benefiting behavior should not be treated as sufficient evidence for parasite-designed control. Distinguishing active from passive manipulation requires experiments that compare true infection, mechanical insult, parasite secretions, and naturally occurring host alternative phenotypes.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1907843"},"PeriodicalIF":2.1,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.","authors":"Kavithma Uduwela, Koshila Ranasinghe","doi":"10.3389/fpara.2026.1934996","DOIUrl":"10.3389/fpara.2026.1934996","url":null,"abstract":"<p><p>Protozoan parasitic infections, including malaria, leishmaniasis, and human African trypanosomiasis, remain major global public health challenges. In the absence of highly effective vaccines, disease control relies primarily on chemotherapy; however, the emergence and spread of drug-resistant parasite populations increasingly threaten treatment efficacy. This review synthesizes current evidence on the molecular mechanisms underlying drug resistance in <i>Plasmodium</i>, <i>Leishmania</i>, and <i>Trypanosoma</i> species through a systematic analysis of literature. The review identifies four interconnected mechanisms that drive the evolution of drug resistance. First, altered drug transport enables parasites to regulate intracellular drug concentrations through mutations, loss, or amplification of membrane transporters, including PfCRT in <i>Plasmodium</i> and AQP2 in <i>Trypanosoma brucei</i>. Second, target modification and genomic plasticity promote resistance through point mutations in drug targets, such as <i>dhfr</i> and <i>dhps</i> in <i>Plasmodium</i>, while kinetoplastids, particularly <i>Leishmania</i>, exploit extensive genomic plasticity, including aneuploidy, gene amplification, and translational reprogramming, to facilitate rapid adaptation under drug pressure. Third, metabolic reprogramming enhances parasite survival by increasing intracellular thiol production, strengthening antioxidant defense systems, and reshaping central carbon and lipid metabolism to mitigate drug-induced stress. Finally, stress response and persistence mechanisms enable subpopulations of parasites to enter dormant, persister-like states characterized by reduced metabolic activity and slowed proliferation, thereby evading both host immune responses and chemotherapeutic agents. Collectively, these findings demonstrate that drug resistance is a dynamic, multifactorial evolutionary process rather than a single molecular event. Addressing this growing challenge requires integrating genomic surveillance, molecular diagnostics, mathematical modeling of resistance transmission, and mechanistic insights into parasite persistence into future drug discovery and disease control strategies. Such an integrated approach is essential for improving the durability of antiprotozoal therapies and advancing global efforts to control neglected protozoan diseases.</p>","PeriodicalId":73098,"journal":{"name":"Frontiers in parasitology","volume":"5 ","pages":"1934996"},"PeriodicalIF":2.1,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}