International journal for parasitology最新文献

Early identification of people at risk of schistosomiasis infection is critical to interrupting disease transmission. We develop and validate an explainable machine learning prediction model that integrates demographic, behavioral, and environmental factors to identify these individuals. A total of 103,707 individuals were included to train and internally validate the model, and 16,574 individuals were used for external validation. The Random Forest (RF) model demonstrated the best discriminative performance among the five machine learning models evaluated. It accurately predicted schistosomiasis seropositivity in both internal validation (AUC = 0.943, F1 score = 0.809) and external validation (AUC = 0.897, F1 score = 0.770) and has been translated into a practical tool to support real-world application. Feature importance analysis indicated that the most significant predictors of schistosomiasis seropositivity included the presence of schistosomiasis symptoms, history of exposure to infected water, endemicity types of the village, gender, and village risk category. Furthermore, the SHapley Additive exPlanation (SHAP) method was employed to explain how these variables influence the prediction outcomes. This study provides a reference for early identification of high-risk populations and facilitates the translation of theoretical modeling studies into practical work applications.

Heterozygosity-fitness correlations (HFCs) are widely used to explore the effects of inbreeding in wild populations. However, the biological significance of HFCs has been the subject of intense debate, and it has been suggested that the magnitude and direction of these correlations may be context-dependent (e.g., vary with different host characteristics or environmental conditions). We tested this hypothesis in a free-ranging population of Grant's gazelles (Nanger granti). Specifically, we tested for associations between standardized multilocus heterozygosity (sMLH) and endoparasite infections, and examined how these relationships varied with animal age, sex and environmental context (e.g., seasonality). We used three approaches: a cross-sectional approach focusing on 103 individuals sampled at a single time point, a longitudinal approach focusing on 25 naturally infected individuals sampled over 12 months, and an experimental approach in which 15 individuals were cleared of their parasites and parasite re-accumulation was tracked over 12 months. We found that the presence of heterozygosity-parasite associations varied with study design and context. Cross-sectional patterns varied with environmental context, whereas the longitudinal analysis revealed host trait-specific HFCs, and the experiment established a causal link between heterozygosity and parasitism. Overall, our longer-term study approaches indicated that higher levels of heterozygosity are associated with lower parasite burdens, underscoring the value of longitudinal and experimental approaches for detecting HFCs in wild populations.

The potential of natural history collections to address biological questions has been increasingly recognized with the advent of high-throughput sequencing (HTS) and museomics approaches. However, their use remains largely underexplored for most taxonomic groups. This is particularly true for proteocephalid cestodes (Onchoproteocephalidea I), for which extensive material is available in helminthological collections. Here, we subjected ethanol-preserved specimens deposited in two helminthological collections to HTS using a genome skimming approach. This allowed us to recover dozens of mitogenomes and nuclear ribosomal transcription units (rTUs) and to place them within a phylogenetic framework. We generated 88 complete or partial mitogenomes and rTUs. These samples correspond to 78 species in 43 genera from all continents except Antarctica, including parasites of fishes (86 %), snakes, monitor lizards, and the common opossum. Comparative analyses revealed highly conserved mitochondrial content and architecture, following the typical pattern recognized for proteocephalid cestodes. Phylogenetic reconstructions based on concatenated mitogenomes and rTUs datasets were largely concordant with the most comprehensive phylogenies published to date, with several informal clades also recognized in this study: the "Proteocephalus-aggregate", the "African fish clade", Clade K of the "cosmopolitan reptilian clade", and the "Neotropical fish superclade". However, improved resolution was obtained in the parsimony analyses for early-diverging lineages represented by Old World cestodes of the subfamilies Acanthotaeniinae and Gangesiinae. Also, we identified the MT-ND5 gene as the most informative under the parsimony criterion, whereas the most frequently sampled MT-CO1 proved far less phylogenetically informative. The data generated here provide a solid foundation for future multilocus phylogenetic and comparative studies of cestodes and highlight the value of genome skimming using decades-old archived samples. New avenues for exploring the evolutionary history of proteocephalid cestodes are discussed.

The emergence and spread of Plasmodium falciparum resistance to current antimalarial drugs underscores the urgent need for new therapies with novel mechanisms of action and broad therapeutic potential. The purine salvage pathway in P. falciparum is a validated drug target and the import of purines into the parasite, mediated by Equilibrative Nucleoside Transporters (PfENTs), is a critical step in this pathway. Despite emerging as drug targets, the genetic diversity of PfENTs remains poorly characterized. Understanding this diversity is crucial for optimizing a potential purine-based drug development. Here, we report the genetic diversity in PfENT1 and PfENT4 in P. falciparum field isolates from geographical regions worldwide. Illumina-generated sequences and Variant Call Format (VCF) files for over 7,000 isolates were retrieved from the European Nucleotide Archive and Malaria Genomic Epidemiology Network data repositories respectively. VCF files were filtered to detect single nucleotide polymorphisms (SNPs) and insertions/deletions (InDels) in PfENT1 and PfENT4. Additionally, Illumina-generated sequences were analyzed to identify copy number variations (CNVs) in these genes. In both PfENT1 and PfENT4, only SNPs were identified as no InDels or CNVs were found. The frequency of missense variants in PfENT1 and PfENT4 was 4.5 % and 6.2 % respectively. Three common genetic variants, F36S,V129I, andL133F, were identified in PfENT1, with minor allele frequencies (MAF) of 4.0 %, 4.1 %, and 3.0 %, respectively. Additionally, four common genetic variants, I188F, N209I, A260T, and S383A, were found in PfENT4, with MAF of 2.2 %, 1.6 %, 1.5 %, and 38.9 %, respectively. In both genes, most genetic variants substituted non-polar amino acid residues with similar residues. The allele frequencies of the SNPs identified are similar (p > 0.05) in rural and urban areas. In conclusion, this study revealed that PfENT1 and PfENT4 are highly conserved with low genetic diversity, emphasizing their importance and suitability as drug targets.

Parasites are integral components of biodiversity, shaping host populations, food web dynamics, and ecosystem stability. However, they are influenced by environmental conditions and face growing threats. Despite growing evidence of global declines in parasite populations, the impacts of contaminants on their fitness in freshwater ecosystems remains poorly understood. In this study we investigated how environmental variability, host traits, and pollutant exposure affect the fitness and infection patterns of acanthocephalan parasites in chub (Squalius cephalus). Using a mesocosm approach, we assessed parasite infection intensity, size, and reproductive traits in relation to host size, body condition, site of capture, and seasonality, acknowledging that natural infections introduce variability. Moreover, we experimentally exposed chub to ubiquitous freshwater contaminants, including the pesticide imidacloprid, the pharmaceutical compounds paracetamol and diclofenac, and the herbicide S-metolachlor, at environmentally relevant concentrations. Our results indicate that host size was a key driver of parasite infection intensity. Parasite size increased over time but was independent of host condition and parasite density. While larger parasites produced more eggs, overall reproductive output declined in fish with better body condition and over time. Pollutant exposure yielded complex effects: chronic imidacloprid exposure (15 ng·g^-1) reduced parasite size, while acute paracetamol exposure (16 μg·g^-1) resulted in larger parasites but completely inhibited egg production. Other tested pollutants had no significant effects. These findings highlight the sensitivity of parasites to environmental stressors, the influence of host and environmental context, and the importance of accounting for natural variability and host-parasite interactions in ecotoxicological assessments of freshwater ecosystems.

Advances in multicellular two-dimensional (2D) and three-dimensional (3D) cell culture systems are providing parasitologists with new tools to investigate host-parasite interactions in vitro. These models offer tissue-specific and, increasingly, host-specific alternatives to traditional 2D monoculture and animal systems, with applications across protozoan and helminth biology. Spheroids, organoids, and emerging assembloid platforms capture key aspects of tissue architecture and function, enabling co-culture of parasites and their products, including dynamic analysis of interactions at defined host interfaces. In recent years, these systems have been adapted to model infection processes, parasite development, immune modulation and tissue remodelling across a range of parasite taxa and tissue types, particularly of the gastrointestinal tract. This review outlines applications of multicellular 2D and 3D cell culture systems in parasitology, drawing on examples from both human and veterinary research. We highlight lessons learned from published works to date that have accelerated the uptake and refinement of these approaches. We also examine technical challenges, including issues of standardisation, scalability, model accessibility, and species representation, particularly for livestock hosts. Looking ahead, the integration of immune, stromal, and microbial components into these models, as well as advances in imaging and omics technologies, and CRISPR-Cas9-mediated engineering of host organoids, promise increasingly sophisticated platforms for studying parasite biology, host tissue responses and pathogenesis. With continued investment and cross-disciplinary collaboration, multicellular culture systems are poised to play a central role in reducing animal use, improving model predictiveness, and supporting the development of next-generation antiparasitic therapies and interventions, including drugs and vaccines.

Callunene, a natural component of heather (Calluna vulgaris) nectar, has previously been shown to protect bumblebees from infection by the trypanosomatid Crithidia bombi. Here, we demonstrate that callunene exhibits antiparasitic activity against several trypanosomatid species, including Crithidia bombi, Leishmania mexicana, and Trypanosoma brucei. Notably, callunene's in vitro efficacy against T. brucei was comparable to that of nifurtimox, although its cytotoxicity toward human cells may limit direct therapeutic application. Using a biotinylated callunene analog in the pull-down assay, we identified NIPSNAP, a mitochondrial protein involved in mitophagy regulation, as a primary molecular target of this compound in C. bombi. Moreover, callunene alters acidocalcisome abundance, further connecting its role to regulation of mitochondrial physiology. Given its effects on mitochondria and ability to interact with NIPSNAP, callunene represents a promising chemical probe for studying mitophagy, a poorly understood process in trypanosomatids, and may provide new insights into mitochondrial biology of these parasites.

Different parasite challenge models have been used over many years in the development of novel vaccines against gastrointestinal nematodes of livestock. Typically, following vaccination with either native or recombinant proteins, the host animal is then given a bolus challenge of infective nematode larvae (iL3) or a trickle challenge where smaller numbers of iL3 are given at regular intervals over a period of time. The bolus method may be a robust test of whether high levels of vaccine-induced immunity translate to protection against a large pathogen insult, whereas the trickle infection method may be more appropriate to test the impacts of an exposure-induced anamnestic response. In the work presented here, three different models of testing gastrointestinal nematode vaccine efficacy were compared. Lambs (4-5 months old) were vaccinated with the excretory/secretory products collected from ex-vivo Teladorsagia circumcincta fourth stage larvae (L4ESP) and then challenged with a bolus of 5,000 iL3 or with a trickle infection where 2,000 iL3 were administered 3 times per week for 4 weeks (truncated trickle) or continuously challenged for 9 weeks (trickle) until post-mortem. Monitoring of faecal egg counts following challenge demonstrated that there was no significant impact of vaccination on cumulative faecal egg count (cFEC) following bolus challenge but, during the period of regular ingestion of iL3 in both trickle challenge models, statistically-significant reductions in the cFEC [(40-46 % reduction in mean cFEC (P < 0.05); 68-71 % reduction in median cFEC)] were observed. Shortly after cessation of the iL3 challenge in the truncated trickle challenge group, this protective effect of the vaccine on cFEC was lost whereas vaccine efficacy was maintained in the model with continued regular ingestion of iL3 (trickle challenge model, which most accurately reflect the parasite challenge in a field situation). In conclusion, the choice of challenge model had a profound impact on the ability to measure vaccine efficacy.

The Plasmodium circumsporozoite surface protein (CSP) is the best characterized pre-erythrocytic vaccine target for malaria. It is a multifunctional protein important for sporozoite mobility, mosquito salivary gland invasion, and hepatocyte invasion. We analyzed diversity of  Plasmodium vivax CSP gene (pvcsp) during the 2022-2023 malaria resurgence in northwestern Thailand and assessed how pvcsp haplotypes may affect parasite development in the mosquitoes. Amplicon sequencing of 69 P. vivax isolates revealed both canonical pvcsp variants: VK210 (n = 66) and VK247 (n = 3). The VK210 type exhibited high polymorphism within the central repeat region, with 21 haplotypes (H1-H21) composed of 13-20 repeat motifs. Haplotype H2 was the most common, accounting for half of all VK210 sequences, and in membrane feeding assays with Anopheles dirus, appeared to produce more salivary-gland sporozoites per oocyst than other haplotypes, suggesting that repeat-region variation may modulate vector competence. Together, these findings report contemporary pvcsp diversity in Thailand's highest transmission area, provide functional evidence that repeat-region polymorphisms shape vector-parasite interactions, and highlight three globally prevalent motifs (GDRADGQPA, GDRAAGQPA, ANGAGNQPG) as prime targets for future PvCSP vaccines.

Cyathostomins are the most prevalent and currently considered the most pathogenic gastrointestinal nematodes in horses. Their life cycle includes an encystment phase within the large intestinal mucosa, where up to 90 % of the total worm burden resides. Clinical disease ranges from chronic protein-losing enteropathy to acute, sometimes fatal, typhlocolitis. Despite their significance, the ecological interplay between cyathostomins, the host immune response, and the gut microbiota remains poorly understood. To our knowledge, this is the first study to investigate these interactions at the mucosal level. Eleven horses were randomly selected from an abattoir survey. Samples were collected from the caecum, right ventral colon, and left dorsal colon. Parasitological assessments included faecal egg counts, luminal worm enumeration, and mucosal larval counts. Immunological analysis comprised histopathology and immunohistochemistry, while microbiota profiling was performed using bioinformatics. All horses were infected with cyathostomins, including those with zero faecal egg counts. Mucosal larval burdens were highest in the caecum and right ventral colon, while luminal adult worms predominated in the ventral and dorsal colon. T lymphocytes and macrophages were the dominant immune cells in the mucosa; eosinophils and goblet cell hyperplasia showed no correlation with parasite load. Larval invasion of the submucosa was observed only in horses with high mucosal burdens, suggesting density-dependent tissue penetration. Microbiota analysis revealed increasing divergence along the intestinal tract, with caecal and faecal samples showing the greatest differences. These findings highlight regional specialization and suggest that faecal samples may not accurately reflect mucosal microbiota composition. This descriptive study provides novel insights into the spatial dynamics of cyathostomin infection, mucosal immunity, and microbiota composition in the equine large intestine, offering a foundation for future research into equine gastrointestinal health and parasitology.