Hybrids between Schistosoma haematobium and Schistosoma bovis contribute to human and animal infections, highlighting complex interspecies interactions that facilitate schistosomiasis transmission. Schistosoma bovis infects multiple ruminant hosts, promoting cross-species transmission and increasing zoonotic risk. This study explores transcriptomic plasticity as a mechanism enabling hybrid schistosomes to adapt to different definitive hosts. We analysed two contexts: (1) introgressed S. haematobium × S. bovis hybrids, which exhibited higher virulence in sheep than parental S. bovis; and (2) S. bovis infecting different mammalian hosts. Introgression, the transfer of genetic material between species through hybridization and repeated backcrossing, was associated with 366 differentially expressed genes (4% of coding genes) between introgressed hybrids and S. bovis in sheep. Additionally, S. bovis showed host-dependent transcriptomic changes, with 30% of genes differentially expressed between infections in hamsters and sheep. Enriched biological processes shared across introgression and host adaptation included nuclear mRNA catabolism and inner mitochondrial membrane organization, indicating increased gene expression plasticity and metabolic adaptation to environmental stress. These findings suggest that transcriptomic plasticity enhances the adaptability of S. bovis and hybrid worms, increasing their zoonotic potential. This raises concerns for schistosomiasis control, as such plasticity could expand transmission capacity and complicate intervention strategies. This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.

Abstract Helminths systemically suppress host immunity, yet whether they impose immune tolerance by rewiring host-associated microbial metabolism remains unclear. Here we show that Trichinella spiralis infection remodels intestinal tryptophan metabolism to generate an AhR-dependent regulatory immune state. T. spiralis infection enriched the commensal bacterium Ligilactobacillus murinus , which converted tryptophan into indole-3-lactic acid (ILA), a microbial metabolite that directly engaged the aryl hydrocarbon receptor. Antibiotic-mediated microbiota depletion abolished infection-induced ILA accumulation, AhR activation and Treg/Th17 rebalancing, whereas fecal microbiota transplantation from infected donors or supplementation with L. murinus or ILA restored these effects. Pharmacological blockade or genetic deletion of AhR eliminated the ability of T. spiralis , L. murinus and ILA to restrain LPS-induced cytokine-storm-like lung inflammation, establishing AhR as an essential host node in this circuit. Extending these findings to viral inflammatory disease, oral ILA improved survival and reduced pulmonary immunopathology in SARS-CoV-2-infected K18-hACE2 mice. Re-analysis of human COVID-19 metabolomic data further revealed reduced circulating ILA in severe disease. These findings define a helminth-remodeled microbial tryptophan metabolic pathway that promotes disease tolerance and identify the ILA–AhR axis as a candidate postbiotic strategy for limiting hyperinflammatory tissue injury.

Trichinella spiralis (T. spiralis), a zoonotic nematode that causes severe myositis and systemic morbidity, sustains chronic muscle parasitism through evolutionary adaptations; however, this globally prevalent disease lacks targeted therapies to disrupt chronic infection. Although the heme transport protein HRG-1 has been characterized as an intervention target in free-living species (e.g., Caenorhabditis elegans) and hematophagous parasites (e.g., Haemonchus contortus), the molecular machinery governing heme acquisition in the nonhematophagous parasite T. spiralis remains uncharacterized, and no drugs targeting HRG-1 have been reported until now. Herein, we demonstrate that T. spiralis, a parasite that lacks the ability to synthesize heme autonomously, has evolved a sophisticated mechanism to scavenge and utilize heme from its host. By employing an aspartic protease to degrade host hemoglobin and myoglobin in the parasitic niche, T. spiralis is able to liberate heme for its own growth and survival. The structurally and functionally conserved Ts-HRG-1 protein plays a key role in transporting heme to the entire worm, particularly to functional organs, such as the cuticle and stichosome. More importantly, we discovered that the interaction between Ts-HRG-1 and Ts-ATP6V0C results in the formation of a functional complex that is essential for the parasite's heme acquisition. The intervention effect achieved by Ts-ATP6V0C RNAi or inhibiting the activity of Ts-ATP6V0C with bafilomycin A1 (BafA1) was consistent with Ts-HRG-1 RNAi, resulting in impaired heme uptake, developmental arrest and a reduced larval burden in mouse hosts. These findings enhance our understanding of the parasite's heme acquisition mechanism and identify the development of drugs that target proteins that interact with HRG-1 as a new direction in anthelminthic drug research.

Human schistosomiasis is a zoonotic disease, meaning that wild animals or livestock can serve as reservoirs for the disease. This sustains active parasite transmission in regions where extensive treatment initiatives are underway, potentially undermining efforts to combat schistosomiasis. In multi-host and multi-parasite systems, achieving disease elimination necessitates the incorporation of all reservoir hosts. For this reason, animal diagnosis is crucial to enable accurate targeting of treatment. However, methods for diagnosing animals remain underdeveloped. We have evaluated two commercially available serological diagnostics, the Schistosoma IgG ELISA produced by Bordier Affinity Products, and the Schisto II Western Blot IgG kit produced by LDBIO Diagnostics which are commonly employed for human diagnosis. The diagnostics were carried out on a collection of 175 sheep serum samples from 35 sheep experimentally infected with S. haematobium, S. bovis and various strains resulting from mate crossing between these two species. The diagnosis of these samples was possible using the two methods tested, with an adaptation of the protocol of both methods by replacing the conjugate. The kappa coefficient highlights substantial agreement between each newly tested method and the adult worm recovery during animal necropsy, suggesting robust consistency in the results obtained with the two serological diagnostics. In both instances, further studies are required for validation and standardization to facilitate field application and to specify the specificity of the Western-Blot.

This document presents the opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), established from the work of its BIORISK Expert Committee. Two questions were presented to ANSES by the French Directorate General for Food, relating to the establishment of a risk profile for Toxocara spp. in wild boar meat and the proposal of control measures for risk management. An expert appraisal was requested in light of the recent discovery of Toxocara spp. larvae in inspected wild boar carcasses in France. The document begins by describing the parasite cycle, modes of transmission, and clinical forms of toxocariasis in humans. The discussion particularly focuses on the relative importance of foodborne transmission in comparison to other transmission methods. The wild boar meat-processing sector is also described. In addition, there is an assessment of various methods for inactivating Toxocara spp. in meats, including freezing, cooking, and curing. The opinion draws conclusions from the risk profile for the continuation of work on toxocariasis on one hand, and the assessment of microbiological risks for wild boar meat on the other. Control measures that may be effective against Toxocara spp. are also presented. A series of recommendations aimed at various stakeholders (processing facilities, hunters, and consumers) is provided by the document.

Background There is an increase in the global incidence of allergies. The hygiene hypothesis and the old friend hypothesis reveal that helminths are associated with the prevalence of allergic diseases. The therapeutic potential of Trichinella spiralis is recognized; however, the stage at which it exerts its immunomodulatory effect is unclear.Methods We evaluated the differentiation of bone marrow-derived macrophages stimulated with T spiralis excretory-secretory products. Based on an ovalbumin-induced murine model, T spiralis was introduced during 3 allergy phases. Cytokine levels and immune cell subsets in the lung, spleen, and peritoneal cavity were assessed.Results We found that T spiralis infection reduced lung inflammation, increased anti-inflammatory cytokines, and decreased Th2 cytokines and alarms. Recruitment of eosinophils, CD11b+ dendritic cells, and interstitial macrophages to the lung was significantly suppressed, whereas Treg cells and alternatively activated macrophages increased in T spiralis infection groups vs the ovalbumin group. Notably, when T spiralis was infected prior to ovalbumin challenge, intestinal adults promoted proportions of CD103+ dendritic cells and alveolar macrophages.Conclusions T spiralis strongly suppressed type 2 inflammation, and adults maintained lung immune homeostasis. Trichinella spiralis adults maintain lung immune homeostasis by increasing the proportion of alveolar macrophages and CD103+ dendritic cells while reducing the recruitment of interstitial macrophages. They promote the development of Treg cells and alternatively activated macrophages to alleviate allergic inflammation.

Trichinella spiralis infection is associated with the formation of cysts within host skeletal muscle cells, thereby enabling immune evasion and subsequent growth and development; however, the pathogenic factors involved in this process and their mechanisms remain elusive. Here, we found that Ts-RNF secreted by T. spiralis is required for its growth and development in host cells. Further study revealed that Ts-RNF functions as an E3 ubiquitin ligase that targets the UBA domain of SQSTM1/p62 by forming K63-type ubiquitin chains. This modification interferes with autophagic flux, leading to impaired mitochondrial clearance and abnormal myotube differentiation and fusion. Our results established that T. spiralis increases its escape by interfering with host autophagy via the secretion of an E3 ubiquitin ligase.

We are currently witnessing the endemization of urogenital schistosomiasis in southern Europe. The incriminated parasite is a hybrid between a human parasite and a livestock parasite. Using an experimental evolutionary protocol, we created hybrid lines from pure strains of both parasite species. We showed that the host spectrum of the human parasite is enlarged to the livestock parasite after genomic introgression. We also evidenced that the tropism of the parasites within the host changes and that some hybrid lines are more virulent than the parental strains. These results engage a paradigm shift from human to zoonotic transmission of urogenital schistosomiasis.

Recently, CRISPR/Cas associated biosensors have been shown to have great potential in sensing applications due to their high sensitivity and high base resolution. However, the signal reporter system containing two organic fluorescent dye pair is limited by high cost and less stability. In contrast, functional nanomaterials exhibit robust stability, excellent optical properties and low preparation cost, making them suitable reporters. In this study, a MoS2 nanosheets (NSs) improved CRISPR/Cas12a-based biosensing platform was constructed for the first time to detect food-borne parasites. MoS2 NSs were used as fluorescence quenchers and single-stranded DNA (ssDNA) discriminated carrier to construct CRISPR/Cas signal reporter system. The combination of recombinase polymerase amplification with MoS2 NSs modulated CRISPR/Cas12a helped achieve attomolar sensitivity for nucleic acid detection within 35 min. Moreover, the results were obtained using a portable apparatus, enabling visual detection at the point of care. The practical applicability of this biosensing platform was successfully achieved through the detection of anisakis in real samples. This study provides novel insights into exploring the feasibility of two-dimensional nanomaterials based reporter in the CRISPR/Cas12a system, as well as offers a reliable tool for on-site monitoring of parasites.

We describe a small family outbreak of trichinellosis caused by the consumption of raw ham from a wild boar (Sus scrofa) hunted in the northern Alps of France in February 2022. Out of the six people, aged 3–69 years, who consumed the meat, three were confirmed cases, and three were suspected cases. Eosinophilia detected in four people was the hallmark that drove the diagnosis. Three patients presented with myalgia, two with intense and prolonged chest pain, and one with elevated troponin. One patient presented with dermographism during treatment. Anti-Trichinella IgG were detected in three symptomatic individuals after about ten weeks. One patient had negative serology and no symptoms, but was on long-term corticosteroid therapy. Trichinella britovi larvae (8.3 larvae/g) were detected in the wild boar meat remnants. Trichinellosis is rare in France, but this family outbreak is reminiscent of the circulation of this pathogen in wild animals, highlighting the need to inform hunters about the risk of infection linked to the consumption of raw meat of game animals, and about the need for veterinary inspection of game meat. The consumption of raw meat outside controlled circuits is a practice not devoid of risks, which justifies raising the awareness of hunters, doctors, and medical biologists.

Centuries of scientific breakthroughs have brought us closer to understanding and managing the spread of parasitic diseases. Despite ongoing technological advancements in the detection, treatment, and control of parasitic illnesses, their effects on animal and human health remain a major concern worldwide. Aptamers are single-stranded oligonucleotides whose unique three-dimensional structures enable them to interact with high specificity and affinity to a wide range of targets. In recent decades, aptamers have emerged as attractive alternatives to antibodies as therapeutic and diagnostic agents. Due to their superior stability, reusability, and modifiability, aptamers have proven to be effective bioreceptors for the detection of toxins, contaminants, biomarkers, whole cells, pathogens, and others. As such, they have been integrated into a variety of electrochemical, fluorescence, and optical biosensors to effectively detect whole parasites and their proteins. This review offers a summary of the various types of parasite-specific aptamer-based biosensors, their general mechanisms and their performance.

Cryptosporidiosis is a significant disease in calves caused by the parasitic protist Cryptosporidium. The infection results in severe symptoms such as diarrhea, dehydration, delayed growth, and weight loss, often leading to mortality and economic losses. This study aimed to detect Cryptosporidium spp. in fecal samples from calves in five Algerian provinces. A total of 65 fecal samples from calves were collected from 12 dairy cattle farms in the north-east of Algeria. The presence of the parasites was established by microscopic screening of the oocysts following an immunofluorescence assay (IFA). IFA-positive samples were analyzed by 18S rRNA PCR-RFLP (restriction fragment length polymorphism) to determine the species. Cryptosporidium parvum was subtyped by sequence analysis of the 60 kDa glycoprotein gene. Cryptosporidium oocysts were detected microscopically in 41/65 (63%) samples, of which 26/41 (63.4%) were positive by 18S rRNA PCR-RFLP. Two Cryptosporidium species were detected in 24 samples; C. parvum (20/24) and C. bovis (4/24). C. parvum isolates from IIa and IId zoonotic subtype families were detected: IIaA16G2R1 (9/24), IIdA16G1 (4/24), and IIaA15G2R1 (1/24). Thus, calves are reservoirs of zoonotic C. parvum subtypes and represent a public health concern.

The gut microbiota plays an important role in parasite-host interactions and the induction of immune defense responses. Trichinella spiralis is an important zoonotic parasite that can directly or indirectly interact with the host in the gut. Changes in the gut microbiota following infection with T. spiralis and the role of the gut microbiota in host immune defense against T. spiralis infection were investigated in our study. 16S rRNA sequencing analysis revealed that infection with T. spiralis can reduce the diversity of the gut microbiota and alter the structure of the gut microbiota during early infection, which was restored when the worm left the gut. Antibiotic treatment (ABX) and fecal bacterial transplantation (FMT) were used to investigate the role of the gut microbiota in the host expulsion response during infection with T. spiralis. We found that ABX mice had a higher burden of parasites, and the burden of parasites decreased after fecal bacterial transplantation. The results of flow cytometry and qPCR revealed that the disturbance of the gut microbiota affects the proportion of CD4+ T cells and the production of IL-4, which weakens Th2 responses and makes expulsion difficult. In addition, as the inflammatory response decreased with the changes of the microbiota, the Th1 response also decreased. The metabolomic results were in good agreement with these findings, as the levels of inflammatory metabolites such as ceramides were reduced in the ABX group. In general, T. spiralis infection can cause changes in the gut microbiota, and the presence or absence of microbes may also weaken intestinal inflammation and the expulsion of T. spiralis by affecting the immune response of the host.

Trichinellosis caused by Trichinella spiralis is a serious zoonosis with a worldwide distribution. Lentinan (LNT) is known to modulate the intestinal environment with noted health benefits, yet the effect of LNT against intestinal helminth is unknown. In our study, we first observed that LNT could trigger worm expulsion by promoting mucus layer functions through alteration of gut microbiota. LNT restored the abundance of Bacteroidetes and Proteobacteria altered by T. spiralis infection to the control group level. Interestingly, LNT triggered the production of butyrate. Then, we determined the deworming capacity of probiotics (butyrate-producing bacteria) in mice. Collectively, these findings indicated that LNT could modulate intestinal dysbiosis by T. spiralis, drive the expulsion of intestinal helminth and provided an easily implementable strategy to improve the host defence against T. spiralis infection.

Inflammatory bowel disease and allergic asthma, as typical immune-mediated inflammatory diseases (IMIDs), are associated with immune imbalance caused by complex interactions among environmental, genetic and bacterial factors. The changing immune imbalance of IMIDs not only causes serious pathological damages but also increases the difficulty of treatment. Helminths or helminth-derived molecules have been increasingly employed to treat IMIDs due to their immunoregulatory ability. Since helminth infection is not an appropriate treatment direction due to the complex immunoregulation and safety concerns, one of the new therapies is to harness the immunoregulation induced by the identified helminth-derived molecules using immune indexes as a guide. This review discusses the pathogenesis of inflammatory bowel disease and allergic asthma, and summarizes the therapeutic effect of helminths and the immunoregulatory mechanisms induced by helminth-derived molecules proposing therapeutic regimens.

Parasites have developed many strategies to ensure their development, multiplication, and dissemination, including the use of reservoir hosts that are often nondomesticated species. Despite drastic reductions in their populations, wild birds remain widespread worldwide and could constitute some of these reservoirs. We focused on the identification of wild bird species harboring parasite stages in their muscles. Breast muscles of 327 birds of 27 different species were collected at three different sites in France. After artificial digestion, isolated nematode larvae were identified by PCR sequencing or restriction fragment length polymorphism (PCR-RFLP). Toxocara cati was identified mainly in birds of prey. The presence of anti-Toxoplasma antibodies was investigated by modified agglutination test on muscle fluids. Anti-Toxoplasma antibodies were detected in 65 out of 166 samples from various bird species. Avifauna, particularly birds of prey, could help on the surveillance of parasite circulation and play a role as sentinel species.

The inflammasome is a key line of immune defense against invading infectious pathogens. However, knowledge of the role of nod-like receptor pyrin domain containing 3 (NLRP3) in Trichinella spiralis infection which characteristically induces T-helper 2 (Th2) immune responses is sparse. In this study, we investigated the role of NLRP3 in the protection against T. spiralis infection through the Th2 immune response. We show that NLRP3 expression in CD4+ T cells was significantly increased at 7 days post-infection of T. spiralis. Compared to wild-type (WT) CD4+ T cells, the expression of IL-4 mRNA was reduced in NLRP3-/- CD4+ T cells, however, the expression of IFN-γ mRNA was comparable between the two groups. Consistently, ELISA and flow cytometry analysis showed that NLRP3-/- CD4+ T cells secreted lower levels of IL-4 than CD4+ T cells from WT mice, whilst the levels of IFN-γ secreted by NLRP3-/- CD4+ T cells were of similar levels to those secreted by WT CD4+ T cells. In addition, we observed a significant reduction of IL-4 and IL-13 by ELISA in NLRP3 -/- mice at 1, 2 and 4 weeks post-infection. Furthermore, we found that adult worm survival was substantially prolonged and muscle larvae burden was significantly increased in NLRP3 -/- mice. We further show that NLRP3 promotes the host defense against T. spiralis through its participation in the differentiation of Th2 cells. These findings provide novel insights into parasite expulsion and highlight the importance of NLRP3 in the host defense against T. spiralis.

Trichinella spiralis is recognized for its ability to regulate host immune responses via excretory/secretory (ES) products. Serine protease inhibitors (serpins) play an important role in ES product-mediated immunoregulatory effects during T. spiralis infection. In this study, the immunoregulatory properties of a serpin derived from T. spiralis (Ts-serpin) were explored in BALB/c mice. The results showed that naturally occurring Ts-serpin was detected in the stichosomes of muscle larvae and adult worms. Moreover, enhancing (by injection of a soluble-expressed recombinant Ts-serpin [rTs-serpin]) or blocking (by passive immunization with anti-rTs-serpin serum) the effects of Ts-serpin changed the levels of cytokines related to inflammation induced by T. spiralis infection in the serum, mesenteric lymph nodes, and peritoneal cavity, which then led to a change in the adult worm burden in early T. spiralis infection. Moreover, the phenotypic changes in peritoneal macrophages were found to be related to Ts-serpin- mediated immunoregulation. Furthermore, a STAT6 activation mechanism independent of IL-4R alpha has been found to regulate protein-mediated alternative activation of bone marrow-derived macrophages and mimic the immunoregulatory role of Ts-serpin in T. spiralis infection. Finally, the anti-inflammatory properties of rTs-serpin and bone marrow-derived macrophage alternative activation by rTs-serpin were demonstrated using a trinitrobenzene sulfonic acid-induced inflammatory bowel disease model. In summary, a protein-triggered anti-inflammatory mechanism was found to favor the survival of T. spiralis in the early stage of infection and help to elucidate the immunoregulatory effects of T. spiralis on the host immune response.

Parasites are complex pathogens, particularly in terms of their antigens, which can vary with life cycle stage and location in the host. Three main biological stages in Trichinella genus were described but it is an oversimplification of the complex Trichinella cycle. Trichinella antigens and immunodominant epitopes have been studied using various strategies requiring immunological reagents or the selection of specific gene targets to be expressed in several systems. Here, we review the Trichinella antigens used for vaccine development and their temporal and spatial variation with the parasite life cycle and in the parasite body. The first antigen studies were devoted to defining antigen profiles reacting with serum samples from various hosts. Trichinella antigens have been classified according to their immunoreactivity with different monoclonal antibodies obtained with various immunization protocols. Based on our knowledge of the Trichinella genome, specific targets have been evaluated. The first fully analyzed immunodominant epitope was ß-tyvelose (3,6-dideoxy-d-arabinohexose), a carbohydrate initially found only in the Trichinella genus, but several other linear peptide epitopes have also been described. We discuss their use in vaccine developments taking into account the specific challenge of a foodborne zoonotic parasite. Recently, new data obtained from the use of recombinant antigens offer new challenges for vaccine development, but most studies focus only on rodent models and are far from the scale-up development stage. Adjuvants are of utmost importance in vaccine development and must be well designed to the target host. RNA vaccines may be more appropriate in the future. Ultimately, nematodes with an aborted cycle may be the ideal vaccine candidate in target animals with a local protective immune response and strong immunity, as in natural infection.

Ethnopharmacological Relevance: An ethnobotanical survey was conducted in three regions of the country (two rural and one urban), using a questionnaire focussing on anti-diarrheal therapeutic habits. Methodology: Information about the plants has been recorded (local name, organs or part(s) of the plant used, therapeutic indications, harvesting methods, methods of administration, side effects, etc.). Collection of the plants was done in collaboration with traditional practitioners and identification of the specimens was conducted at the National Floristic Center (Ivory coast). During the ethnobotanical survey, twelve traditional healers and nine breeders were interviewed which all declared to treat diarrhoea with plants. During this survey, twenty-seven species belonging to eighteen different families of plants were reported for anti-diarrhoeal use in humans or animals. They were all harvested on the field and a herbarium of each species was prepared in duplicate, one stored at the National Floristic Centre of the Felix Houphouët-Boigny University and the other at the Pasteur Institute of Ivory coast. Results: Decoction was the most common mode of preparation used by practionioners and the oral route remained also the main way of administration of plants by healers. These plants are also used in other countries for the same or other purpose. Conclusion: This study shows that traditional medicinal plants play an important role in the treatment of diarrhoea in Ivory coast. It provides basis for future studies to assess, biological and chemical potential of these plants.