International journal for parasitology最新文献

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 analogue 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 to 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.

Livestock production is vital to the economies and food security of African countries. Rising global demand for livestock-derived products intensifies the challenge of managing ticks and tick-borne diseases. This study aimed to optimize a Bm86-based vaccine for controlling Rhipicephalus microplus. Commercial Bm86-based vaccines show variable efficacy (0-100%), reflecting incomplete understanding of the antigen and the immune response elicited. To address this, homologous challenge was conducted in Holstein-Friesian calves with Bm86 formulated with Montanide™ ISA 71 VG (referred to as Montanide™) and a novel Alum-based adjuvant alternative in two separate vaccine trials. Antibody responses were determined utilising indirect ELISA. Vaccine efficacy was assessed through controlled R. microplus challenge. Immunoinformatics mapped the antigenic regions of Bm86, followed by ex vivo validation using antisera from vaccinated cattle. Both adjuvant formulations induced high levels of Bm86-specific total IgG antibodies. However, only the Montanide™ formulation induced a protective response of 88.2%, which correlated with total IgG antibody levels (r= 0.86). In contrast, the Alum-based adjuvant formulation induced low efficacy (2.3%) with a strong inverse correlation with total IgG antibodies (r= -0.95). Both formulations induced an IgG1-biased (i.e. T-helper 2) antibody response, but the Montanide™ formulation conferred a more balanced IgG1/IgG2 response. The efficacy induced by the Montanide™ formulation strongly correlated with the levels of IgG2 antibodies (r= 0.91), suggesting that a balanced Th1/Th2 response plays a key role in protection. Despite its efficacy, the Montanide™ formulation caused adverse injection site effects, highlighting the need for safer alternatives. Epitope mapping identified similar linear B-cell epitope regions recognised by total IgG antibodies induced by vaccination with both adjuvant formulations. These findings suggest that Bm86 vaccination activates broader immune pathways than previously understood, emphasizing the need for exploration of additional immune markers to improve vaccine performance.