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Onchocerciasis is a disease caused by the filarial nematode parasite Onchocerca volvulus and is transmitted by blackflies after they ingest larval offspring, microfilariae, found in the skin of infected people. The elimination of transmission within endemic communities in sub-Saharan Africa, the Americas, and Yemen depends on mass drug administration of ivermectin (MDAi) at high treatment coverage until the prevalence of the parasite in people or in blackflies reaches below a threshold value. In Africa, there are a number of communities where worms that are less susceptible to the effects of ivermectin, i.e., that are sub-optimally responding (SOR), appear to be contributing to the persistence of onchocerciasis despite high-coverage MDAi. We have incorporated this variation in an epidemiological model to explore how the presence of SOR worms impacts the prevalence of people with skin microfilariae, fitting the model to epidemiological data from a community in Ghana, Asubende, where SOR has been detected. Incorporating a cumulative effect of ivermectin into the model fits the data better than if no cumulative effect is assumed. Simulations indicate that elimination is possible under biannual MDAi even if SOR worms are present in the starting population unless the baseline prevalence is hyperendemic. In a hyperendemic region, elimination is predicted if there is no SOR, but when SOR worms are included in the model, elimination is not reached even after twenty years of biannual MDAi with a treatment coverage of 80%. Biannual MDAi increases the proportion of reproducing female worms that would be characterized as SOR compared to annual MDAi. However, when using mass drug administration with moxidectin (MDAm), elimination becomes possible with fewer rounds of MDA even if there are worms that suboptimally respond to moxidectin. Our results support concerns raised in the research community that SOR to ivermectin in O. volvulus could result in persistent transmission despite high-coverage, biannual MDAi, but that MDAm could pose a solution, should safety and efficacy trials support its distribution.

Background/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR-biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by 1H and 13C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC50/96 h values of 47.2 and 46.1 µM for male and female worms respectively, and totally suppressed egg laying with 60 µM, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control.

Large-scale treatment with praziquantel (PZQ) monotherapy is used to control schistosomiasis, leading to concerns about the emergence of PZQ-resistance. In Western Kenya, schistosome-infected patients frequently remain egg-positive following PZQ treatment, and several "hotspot" villages have been observed where transmission remains high, despite annual mass PZQ treatments. This project asks (i) whether PZQ-resistant parasites are found in Western Kenya and (ii) whether "hotspot" villages can be explained by a higher prevalence of PZQ-resistant parasites. We established a simple platform for directly assaying worm motility following in vitro PZQ-exposure in adult schistosomes isolated from a field setting. To do this, we established snail and hamster breeding colonies, and generated large populations of field-derived adult worms, by (i) harvesting S. mansoni eggs from multiple infected patients; (ii) infecting Biomphalaria spp snails with miracidia; (iii) infecting hamsters with released cercariae; (iv) perfusing adult worms from hamsters, and (iv) examining drug response following exposure to PZQ (1 µg/ml for 1 day) in individual S. mansoni worms using an automated movement assay. We measured PZQ-response in 1,800 adult male parasites, representing an estimated 185 parasite genotypes. We identified a single worm that remained motile after PZQ-exposure among the 185 parasite genotypes surveyed (frequency = 0.54%; 95% CI 0.01 - 2.97%, exact binomial) consistent with PZQ-resistant worms being extremely rare or absent. Our direct phenotypic screening results suggests that (i) PZQ-resistance is not currently an obstacle for S. mansoni control in Western Kenya, and (ii) that other factors explain the existence of persistent hotspots.

Global demand for raw materials is driving extensive mining projects with the consequent generation of mine waste, which contain potentially harmful elements including Pb and Zn. The rehabilitation of industrial residue sites and mine tailings represents an important environmental challenge for effective closure of tailings sites. While different rehabilitation strategies have been well studied based on plant performance and geochemical analyses, less is known about the impacts of mine tailings and their rehabilitation on soil infauna, including earthworms, despite their essential role in soil ecology. This study explores the bioavailability, potential transfer, and toxicity for key metal contaminants in the earthworm Eisenia fetida exposed different dilutions of Pb/Zn mine tailings. We performed chronic exposures following standard guidelines, measured element concentrations in worms, and investigated targeted stress biomarkers along with transcriptomics on earthworm coelomocytes. Earthworms accumulated potentially toxic levels of Arsenic (As), Lead (Pb) and Zinc (Zn). Biomarkers responses revealed an upregulation of Heat shock protein 70 (HSP70) expression which was correlated with bioaccumulated As levels and catalase (CAT) expression was decreased in the 75% mine tailings treatment. Our transcriptomics study provided the first high quality coelomocyte transcriptome for E. fetida with 98,553 genes. We identified 24 transcripts that were responsive to the mine tailings treatments including a non-receptor tyrosine protein kinase, upregulated across all treatments, genes involved in protease assembly, mitochondrial transport, a methylcytocine dioxygenase, and several transcripts with homology to arginase I. Overall, our results reveal that earthworms respond to Pb/Zn tailings through cellular stress responses in immune cells that are correlated with As bioaccumulation. These findings suggest that Pb/Zn mine tailing phytostabilisation is feasible and not likely to result in acute toxicity to soil infauna, but As levels should be monitored and methods to sequester or immobilize the As should be pursued to reduce chronic impacts.

Biocompatible hydrogel encapsulation of model organisms, such as Caenorhabditis elegans, is highly desirable over chemical or mechanical immobilization methods that can harm health and hinder long term imaging studies. This study introduces an automated, gentle method for continuous immobilization within hydrogel blocks, achieved through flow lithography and machine learning-assisted vision detection. To optimize this automated worm immobilization, we investigated operating parameters, such as flow rate, solution composition, and worm loading concentration. With 90% precision in AI worm detection, we achieved 86% encapsulation efficiency at low to moderate worm-loading concentrations (1-7 worms per μL). Higher loading concentrations of 10-15 worms per μL reduced the encapsulation efficiency to 71%. Worm loading concentration, composition, and flow-rate ratios of the two input solutions-the worm-suspended aqueous solution (WSAS) and the polyethylene glycol diacrylate (PEGDA) solution (PEGS)-significantly affected worm throughput, worm dehydration during encapsulation, and the viability of encapsulated worms. The WSAS-to-PEGS flow-rate ratio was set at 0.5, with a minimum WSAS flow rate of 1 μL min-1 required to avoid backflow. The PEGDA concentration in PEGS was kept below 50% to avoid worm dehydration. By varying the concentrations of hydrogel precursor, PEGDA, we enabled both partial and complete immobilization suitable for short term and long-term studies, respectively. Results show the encapsulated worm's viability over 3 days, highlighting this method's potential for long-term studies without compromising worm health or movement.

The filarial nematode, Dirofilaria immitis (Leidy) (Spirurida: Onchocercidae), is an obligate mosquito-borne pathogen transmitted by at least 26 species of mosquitoes in the United States. Due to its size and migration through mosquito tissues during its first 3 larval stages (L1-L3), it can damage the mosquito to the point of death, thereby hindering transmission to its vertebrate host (eg canids and other carnivores). Mosquito species vary in competency for D. immitis, where some species facilitate the development of more viable, infectious L3 worms (host tolerance), while others produce few to no worms (host resistance). Here, we investigated how resistance and tolerance may be impacted by larval rearing conditions (ie temperature and nutrition), specifically quantifying D. immitis burden and development in 2 mosquito species (Aedes triseriatus (Say) and Aedes albopictus (Skuse)). Post-emergence, we offered either a D. immitis positive or negative blood meal to adult female mosquitoes and tracked their development for 15 days before quantifying worm burdens. For both mosquito species, growth rates increased and adult size decreased under conditions with warmer temperatures and lower nutrition. Larval conditions did not have consistent effects on the burden or development of D. immitis, but a higher proportion of Ae. triseriatus developed L3 worms than Ae. albopictus. Poor survival to the end of the incubation period and low numbers of blood-fed mosquitoes for each treatment combination may have hindered our ability to detect significant effects of larval environment on worm transmission, highlighting important considerations for future studies.

Drowning represents one of the most frequent causes of accidental death; however, many submerged remains remain unrecovered or unidentified due to the challenges associated with aquatic decomposition. This process differs substantially from decomposition on land and is influenced by a complex array of factors, including temperature, oxygen availability, depth, and the presence of necrophagous organisms. In aquatic environments, decomposition follows a nonlinear trajectory and can be either slowed - under hypoxic conditions or at low temperatures - or accelerated by the activity of scavenging organisms. In marine ecosystems, key contributors to soft tissue degradation include crustaceans (such as crabs, shrimp, and lobsters), fish, and other invertebrates (e.g., polychaete worms and mollusks). Their activity leads to rapid skeletonization. Subsequently, the remains are colonized by fouling organisms (including barnacles and bivalves) and undergo bioerosion by specialized species such as the bone-devouring worms of the genus Osedax. In freshwater environments, the main participants in the process are leeches, flatworms, insects, and crustaceans. Their sequential succession ensures complete recycling of organic material. The rate of decomposition is highly variable, ranging from several days to several months, complicating the estimation of the postmortem submersion interval. Biological indicators, such as the developmental stage of barnacles, are used to address this challenge. Многие тела в водоемах остаются необнаруженными или неопознанными из-за сложностей, связанных с подводным разложением. Данный процесс существенно отличается от наземного разложения и зависит от комплекса факторов, включая температуру, доступность кислорода, глубину и присутствие некрофагов. В водной среде разложение протекает нелинейно и может как замедляться (в условиях гипоксии или низких температур), так и ускоряться вследствие деятельности падальщиков. В морских экосистемах ключевую роль в деградации мягких тканей играют ракообразные (крабы, креветки, омары), рыбы и другие беспозвоночные (многощетинковые черви, моллюски). Их активность приводит к быстрому скелетированию, и останки в дальнейшем колонизируется организмами-обрастателями (усоногие раки, двустворчатые моллюски) и подвергаются биоэрозии со стороны специализированных видов, таких как костные черви Osedax. В пресных водоемах основными участниками процесса являются пиявки, планарии, насекомые и ракообразные, последовательная сукцессия которых обеспечивает полную утилизацию органического вещества. Скорость разложения крайне вариабельна и может составлять от нескольких дней до месяцев, что затрудняет оценку времени пребывания тела в воде. Для ее установления используются биологические индикаторы, например стадия роста усоногих раков.

The nematode C. elegans does not have eyes but can respond to aversive UV and blue light stimulation and even distinguish colours. The gustatory receptor homolog LITE-1 was identified in forward genetic screens for worms that failed to respond to blue light stimulation. When LITE-1 is expressed in body-wall muscles, it causes contraction in response to blue light suggesting that LITE-1 is both necessary and sufficient for blue light response. Here we show that in addition to light avoidance, LITE-1 is also required for worms' avoidance of high concentrations of diacetyl, an odorant that is attractive at low concentrations. Like blue light, diacetyl causes muscle contraction in transgenic worms engineered to express LITE-1 in body-wall muscles. These data are consistent with a direct chemoreceptor function for LITE-1 which would make it a multimodal sensor of aversive stimuli.

This study aims to identify tapeworms found in a captive red-crowned crane (Grus japonensis) and local crucian carp (Carassius carassius) and to investigate their genetic relationships, with a focus on Digramma interrupta. Molecular analyses, including ITS and cox1 gene sequencing, were conducted to identify the parasite species. Phylogenetic analysis was performed using the ITS2 and cox1 sequences from tapeworms in both hosts. The ITS and cox1 sequences from the tapeworms in the red-crowned crane presented greater than 99.5% similarity to those from the crucian carp. Phylogenetic analyses suggest that tapeworm specimens recovered from both hosts likely correspond to the same species, D. interrupta. Our phylogenetic results also provide tentative support for the placement of the genus Digramma within Ligula. This study is the first to report a zoo-captive red-crowned crane likely infected with D. interrupta through the consumption of crucian carp. The overlapping habitats and dietary habits of the crane support the infection of D. interrupta via infected fish. These findings constitute a new documented case of D. interrupta infecting cranes via fish-eating bird infection pathways, supplying fresh evidence to understand its infection and spread, offering valuable insights for the monitoring, diagnosis, and prevention of avian tapeworm diseases and contributing to the effective management and protection of captive bird populations.

Gamma-decanolactone (GD) was found to exert neuroprotective and anticonvulsant effects in seizure rodent models induced by pentylenetetrazol (PTZ), although mechanisms of action remain to be determined. The aim of this study was to investigate GD-initiated (1) behavioral effects (2) protective activity against PTZ-induced paralysis in Caenorhabditis elegans, and (3) interaction with GABAergic system utilizing in silico analyses. Molecular docking demonstrated favorable binding energies between GD and key GABAergic proteins in C. elegans, including unc-25 (encodes glutamic acid decarboxylase), unc-47 (encodes the vesicular GABA transporter), and unc-49 (encodes the ionotropic GABA receptor subunit), with the strongest interaction observed for unc-47. Docking studies with human GABA(A) receptor subunits also indicated compatible binding within conserved receptor cavities. In mutant worms unc-29(e193) I, GD reduced body bends after pre-treatment, although this effect was reversed after 48 h. GD also diminished pharyngeal pumping in the cca-1(ad1650) X strain, but not wild-type N2 animals. Importantly, GD significantly decreased PTZ-induced paralysis in wild-type worms in a dose-dependent manner after 24 or 48 h. However, no marked protective effect was detected in mutant strains lacking unc-25, unc-47, or unc-49, suggesting that the anticonvulsant effects of GD appear to depend upon intact GABAergic signaling pathways.

With the rapid development of quantitative behavioral analysis, locomotion behaviors can be examined and described in greater detail. However, behavioral structures underlying the dysfunctions and locomotor defects observed with aging remain poorly understood. Here we recorded and analyzed worms' locomotion movement for both young and aged individuals. The results revealed distinct locomotion patterns between two groups. Compared to the young worms, aged individuals exhibited more disorganized forward locomotion, characterized by reduced periodicity and lower cycle stability. The time duration and frequency of backward locomotion did not differ significantly between the two groups, whereas turn behavior following reversals was significantly reduced. Moreover, the aged worms showed increased individual heterogeneity in the usage of behavioral repertoire with age. In summary, this study systematically characterizes the behavior defects of aged animals by quantifying changes in locomotor states, event transitions, and behavior organization.

The anthelmintics ivermectin, albendazole, and diethylcarbamazine are the backbone of mass drug administration (MDA) campaigns targeting human filariasis, yet their direct effects on parasites are still not fully defined or understood. The clinical effects of these drugs are stage dependent, resulting in effective clearance of circulating microfilariae but only limited activity against adult worms, a pattern that complicates disease surveillance and elimination efforts. Although molecular targets have been identified or proposed for some antifilarial drugs, their precise modes of action remain opaque, and conventional in vitro assays of motility or viability have generally failed to reflect pharmacologically relevant effects. There is growing evidence that cryptic phenotypes involving altered host-parasite interactions, including changes in parasite secretions, may help reconcile these discrepancies. Focusing on the causative species of lymphatic filariasis, we used high content imaging and quantitative mass spectrometry to enable deeper phenotypic profiling of drug responses in microfilariae and adult worms exposed to antifilarial compounds. In microfilariae, altered environmental conditions (temperature and salinity) lead to modest ivermectin effects on motility at therapeutic concentrations. In adult parasites, we show that drug responses vary with worm age and that different anthelmintics induce distinct changes in the secretory proteome. This improved phenotypic resolution advances our understanding of drug action in intra-host stages and highlights how antifilarial drugs can alter secretory cargo relevant to the detection of adult parasites that persist after drug treatment.

Improper disposal of contaminants in wastewater may adversely impact organisms across multiple biological levels, including exposure to pharmaceutical and personal care products (PPCPs). Venlafaxine (VFX), a frequently prescribed antidepressant, is a drug of concern due to its potential environmental and neurotoxic effects. The concentrations of VFX used in this study were selected to span a range relevant to both acute toxicological testing and higher-end environmental contamination scenarios. Higher concentrations may occur in wastewater effluent, hospital discharge, or pharmaceutical manufacturing waste streams. This study investigated the effects of early-in-life (pre-and neonatal) VFX exposure on Caenorhabditis elegans at concentrations of 0, 9.37, 18.75, 28.12, or 37.5 mg/L. Neurobehavioral and cholinergic endpoints were assessed at the L4 stage to assess long-term neurotoxicity. Data demonstrated that worms exposed to the highest concentration exhibited increased locomotor activity, while pharyngeal pumping was elevated at both 9.37 and 37.5 mg/L. Acetylcholinesterase (AChE) activity was decreased at 9.37 and 28.12 mg/L. Early-life VFX exposure also altered social feeding behavior, with worms showing a preference for bacterial lawn border (18.75 and 37.5 mg/L) and enhanced group feeding (28.12 and 37.5 mg/L). These results indicate that neonatal VFX exposure induces behavioral and neurochemical changes in C. elegans, associated with disruption of the cholinergic system.

Chemosensory signaling is crucial for organisms to respond to their environment and dysfunctions in these complex pathways have been implicated in diseases such as neurological disorders. The nematode C. elegans is a useful tool for studying chemosensation as it offers a fully-mapped nervous system with relatively simple chemosensory circuits. One of the most common methods to quantify chemosensory function in worms is through chemotaxis assays, which require extensive time and manual effort. In this work, we sought to capture novel chemosensory metrics and increase the throughput of these assays by combining rapid image acquisition with bioinformatics processing. In doing so, we have developed a Technique for Automating chemotaXis Investigations using Simple-Capture Approaches in Nematodes (TAXISCAN), a rapid acquisition platform that can be used to study natural chemosensory behavior as well as to characterize behavioral and locomotion phenotypes in half the time of standard assays.

Polyphenols are natural compounds with antioxidant properties that help prevent chronic diseases. Red onion (Allium cepa) peels are an underutilized source of polyphenols, offering a sustainable opportunity for the valorization of agricultural by-products. Polyphenol-rich extracts were obtained from red onion peels using subcritical water extraction and adsorption resin chromatography. Their biological effects were evaluated in Caenorhabditis elegans under oxidative stress conditions. A multi-omics approach integrating transcriptomics, metabolomics, and lipidomics was applied to assess molecular responses. The extract exhibited a high total phenolic content (>400 mg GAE/g) and strong antioxidant capacity, supporting a highly enriched polyphenolic profile. Survival assays confirmed the absence of toxicity at 100 µg/mL GAE. Transcriptomic analysis revealed 158 differentially expressed genes associated with stress response and metabolic regulation. Metabolomic profiling indicated a systematic reduction in amino acid levels alongside an increase in betaine in treated worms, suggesting adaptive metabolic reprogramming. Lipidomic analysis revealed significant lipid remodeling, characterized by decreased triglycerides, increased diacylglycerols, and changes in membrane phospholipids, indicating alterations in membrane composition and cellular responses associated with oxidative stress adaptation. Together, these results support a model in which red onion peel extracts induce coordinated transcriptional and metabolic adaptations associated with cellular resilience and stress adaptation. This study highlights the potential of agro-industrial by-products as functional bioactive ingredients and demonstrates the value of multi-omics approaches for uncovering system-level responses.

Glycogen is a highly conserved macromolecule across species, and its visualization provides critical insights into both physiological processes and disease states. Existing approaches for glycogen imaging in Caenorhabditis elegans rely primarily on traditional microscopy slides, which introduce variability in image acquisition and downstream data analysis, limit throughput, and require substantial hands-on time and technical expertise. Here, we present a standardized, cost-effective, and high-throughput imaging method that enables efficient visualization and quantification of glycogen in C. elegans. Our approach utilizes a custom-designed three-dimensional pad containing two to four chambers, allowing control and experimental samples to be processed simultaneously under identical conditions. Worms are exposed to iodine crystals, ensuring uniform staining while minimizing reagent use and handling variability. Imaging is performed using a simple binocular microscope, and analysis is conducted in Fiji, making the workflow accessible to laboratories with minimal specialized equipment or training. This method also reduces technical variability, shortens turnaround time, and requires only basic reagents and expertise, making it well-suited for both research and teaching laboratories. Importantly, the platform is readily adaptable to other nematode species and scalable for large-scale genetic or pharmacological screening applications. Together, this workflow minimizes technical variability and provides a robust platform for comparative glycogen analysis in C. elegans. Key features • Standardized glycogen staining method allows less data variability. • Provides a quantitative tool to measure glycogen buildup in C. elegans. • Requires a customized pad for imaging. • Macro is available for batch processing.

The earliest records of Trichinellosis might be found in bibles that recommend against pork consumption due to the spread of a disease that resembles what is now identified as Trichinellosis. Parasitic nematodes (round worms) of the genus Trichinella form a complex of at least 13 species with a broad geographic range. Herein, through data mining of transcriptomic data, and re-sequencing of the transcriptome of representative isolates, we demonstrate the presence of viruses within 10 recognized Trichinella species. We provide genome sequences of four viral species of negative sense RNA viruses that belong to the Family Lispiviridae, Order Mononegavirales, and of eight novel viruses of double-stranded RNA viruses that belong to a novel sub-order within the order Ghabrivirales. The integration of viral genome fragments within encapsulated Trichinella genomes demonstrates that these parasite-virus associations are ancient. Overall, viruses show co-diversification with their parasitic hosts. Yet the phylogenetic position of viruses revealed past host jump from an ancestral encapsulated Trichinella species to the ancestral T. pseudospiralis and challenges previous dogma on the phylogeny and biogeography of Trichinella species in North America. We are witnessing the emergence of a novel field of research focusing on viruses of parasites and their role in parasite pathogenicity. Herein, we describe the characterization of viruses within 10 recognized species of Trichinella. The viruses were distantly related to known viruses which led us to propose the creation of a novel genera and a novel sub-order. We demonstrated the integration of viral genome fragments within the genome of Trichinella species and an on-going process of birth and death of viral integration. Finally, we showed that virus phylogenetic analyses can provide fine-tuned information about their parasitic host evolutionary history. This study demonstrates the ancient and close association between Trichinella and viruses and strong species specificity. Further studies are now needed to determine whether the newly discovered viruses could be targeted for the development of novel diagnostic approaches.