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Background: Infections with Ascaris lumbricoides and Trichuris trichiura remain significant contributors to the global burden of neglected tropical diseases. Infection may in particular affect child development as they are more likely to be infected with T. trichiura and/or A. lumbricoides and to carry higher worm burdens than adults. Whilst the impact of heavy infections are clear, the effects of moderate infection intensities on the growth and development of children remain elusive. Field studies are confounded by a lack of knowledge of infection history, nutritional status, presence of co-infections and levels of exposure to infective eggs. Therefore, animal models are required. Given the physiological similarities between humans and pigs but also between the helminths that infect them; A. suum and T. suis, growing pigs provide an excellent model to investigate the direct effects of Ascaris spp. and Trichuris spp. on weight gain., Methods and Results: We employed a trickle infection protocol to mimic natural co-infection to assess the effect of infection intensity, determined by worm count (A. suum) or eggs per gram of faeces (A. suum and T. suis), on weight gain in a large pig population (n = 195) with variable genetic susceptibility. Pig body weights were assessed over 14 weeks. Using a post-hoc statistical approach, we found a negative association between weight gain and T. suis infection. For A. suum, this association was not significant after adjusting for other covariates in a multivariable analysis. Estimates from generalized linear mixed effects models indicated that a 1 kg increase in weight gain was associated with 4.4% (p = 0.00217) decrease in T. suis EPG and a 2.8% (p = 0.02297) or 2.2% (p = 0.0488) decrease in A. suum EPG or burden, respectively., Conclusions: Overall this study has demonstrated a negative association between STH and weight gain in growing pigs but also that T. suis infection may be more detrimental that A. suum on growth., Competing Interests: The authors have declared that no competing interests exist.

Infections with high doses of intestinal nematodes result in protective immunity based on robust type 2 responses in most mouse lines under laboratory conditions. Here, we report on cellular responses of wild house mice from northern Germany. We detected robust Th1 responses in wild house mice naturally infected with the whipworm Trichuris muris. In contrast, mice infected with pinworms (Syphacia, Aspiculuris) reported type-2 activity by elevated IgG1 levels and eosinophil counts, but also harbored high frequencies of Foxp3+ regulatory T cells, suggesting that natural whip- and pinworm infections induce distinct immunoregulatory as well as effector profiles., (Copyright © 2022. Published by Elsevier Ltd.)

Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche., (© 2022. The Author(s).)

The gastrointestinal tract is known as the largest endocrine organ that encounters and integrates various immune stimulations and neuronal responses due to constant environmental challenges. Enterochromaffin (EC) cells, which function as chemosensors on the gut epithelium, are known to translate environmental cues into serotonin (5-HT) production, contributing to intestinal physiology. However, how immune signals participate in gut sensation and neuroendocrine response remains unclear. Interleukin-33 (IL-33) acts as an alarmin cytokine by alerting the system of potential environmental stresses. We here demonstrate that IL-33 induced instantaneous peristaltic movement and facilitated Trichuris muris expulsion. We found that IL-33 could be sensed by EC cells, inducing release of 5-HT. IL-33-mediated 5-HT release activated enteric neurons, subsequently promoting gut motility. Mechanistically, IL-33 triggered calcium influx via a non-canonical signaling pathway specifically in EC cells to induce 5-HT secretion. Our data establish an immune-neuroendocrine axis in calibrating rapid 5-HT release for intestinal homeostasis., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

Whipworms of the genus Trichuris are nematode parasites that infect mammals and can lead to various intestinal diseases of human and veterinary interest. The most intimate interaction between the parasite and the host intestine occurs through the anterior region of the nematode body, inserted into the intestinal mucosa during infection. One of the most prominent structures of the nematode surface found at the infection site is the bacillary band, a surface domain formed by a number of cells, mostly stichocytes and bacillary glands, whose structure and function are still under debate. Here, we used confocal microscopy, field emission scanning electron microscopy, helium ion microscopy, transmission electron microscopy and FIB-SEM tomography to unveil the functional role of the bacillary gland cell. We analyzed the surface organization as well as the intracellular milieu of the bacillary glands of Trichuris muris in high pressure frozen/freeze-substituted samples. Results showed that the secretory content is preserved in all gland openings, presenting a projected pattern. FIB-SEM analysis showed that the lamellar zone within the bacillary gland chamber is formed by a set of lacunar structures that may exhibit secretory or absorptive functions. In addition, incubation of parasites with the fluid phase endocytosis marker sulforhodamine B showed a time-dependent uptake by the parasite mouth, followed by perfusion through different tissues with ultimate secretion through the bacillary gland. Taken together, the results show that the bacillary gland possess structural characteristics of secretory and absorptive cells and unequivocally demonstrate that the bacillary gland cell functions as a secretory structure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fermentable dietary fibers promote the growth of beneficial bacteria, can enhance mucosal barrier integrity, and reduce chronic inflammation. However, effects on intestinal type 2 immune function remain unclear. In this study, we used the murine whipworm Trichuris muris to investigate the effect of the fermentable fiber inulin on host responses to infection regimes that promote distinct Th1 and Th2 responses in C57BL/6 mice. In uninfected mice, dietary inulin stimulated the growth of beneficial bacteria, such as Bifidobacterium (Actinobacteria) and Akkermansia (Verrucomicrobia). Despite this, inulin prevented worm expulsion in normally resistant mice, instead resulting in chronic infection, whereas mice fed an equivalent amount of nonfermentable fiber (cellulose) expelled worms normally. Lack of expulsion in the mice fed inulin was accompanied by a significantly Th1-skewed immune profile characterized by increased T-bet + T cells and IFN-γ production in mesenteric lymph nodes, increased expression of Ido1 in the cecum, and a complete absence of mast cell and IgE production. Furthermore, the combination of dietary inulin and high-dose T. muris infection caused marked dysbiosis, with expansion of the Firmicutes and Proteobacteria phyla, near elimination of Bacteroidetes, and marked reductions in cecal short-chain fatty acids. Neutralization of IFN-γ during infection abrogated Ido1 expression and was sufficient to restore IgE production and worm expulsion in inulin-fed mice. Our results indicate that, whereas inulin promoted gut health in otherwise healthy mice, during T. muris infection, it exacerbated inflammatory responses and dysbiosis. Thus, the positive effects of fermentable fiber on gut inflammation appear to be context dependent, revealing a novel interaction between diet and infection., (Copyright © 2020 by The American Association of Immunologists, Inc.)

The soil transmitted whipworm, Trichuris trichiura affects about half a billion people globally. Diagnosis is based on identification of characteristic lemon-shaped eggs in stool samples. Occasionally large Trichuris eggs have been reported and have been ascribed to variation within T. trichiura or zoonotic infection with T. vulpis from dogs. We observed that the egg size profile changed markedly after anthelmintic treatment, and remained so, in a human individual self-infected with T. trichiura. The large eggs were detected with two standard diagnostic methods, Kato-Katz thick smear and salt-flotation (McMaster) method. It is therefore important to bear in mind that the morphology of parasite eggs may vary, e.g. in response to previous drug treatment. Large Trichuris eggs in human stool samples should not be diagnosed as T. vulpis infection without confirmation by other means., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Inflammatory mechanisms are implicated in the aetiology of autism spectrum disorder (ASD), and use of the immunomodulator Trichuris suis Ova (TSO) is a novel treatment approach. This pilot study determined the effect sizes for TSO versus placebo on repetitive behaviours, irritability and global functioning in adults with ASD. Methods: A 28-week double-blind, randomised two-period crossover study of TSO versus placebo in ten ASD adults, aged 17-35, was completed, with a 4-week washout between each 12-week period at Montefiore Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history of seasonal, medication or food allergies, Y-BOCS ≥6 and IQ ≥70 received 2,500 TSO ova or matching placebo every 2 weeks of each 12-week period. Results: Large effect sizes for improvement in repetitive behaviours ( d  = 1.0), restricted interests ( d  = 0.82), rigidity ( d  = 0.79) and irritability ( d  = 0.78) were observed after 12 weeks of treatment. No changes were observed in the social-communication domain. Differences between treatment groups did not reach statistical significance. TSO had only minimal, non-serious side effects. Conclusions: This proof-of-concept study demonstrates the feasibility of TSO for the treatment of ASD, including a favourable safety profile, and moderate to large effect sizes for reducing repetitive behaviours and irritability. Clinicaltrials.gov: NCT01040221.

Background: Schistosomiasis and infection by soil-transmitted helminths are some of the world's most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes., Methods: We built a spatial CRF to estimate infection risks for Ascaris lumbricoides, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Schistosoma mansoni using data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF's posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model's performance and prediction uncertainty., Results: Parasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence., Conclusions: Monitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.

Ecoimmunological patterns and processes remain understudied in wild primates, in part because of the lack of noninvasive methods to measure immunity. Secretory immunoglobulin A (sIgA) is the most abundant antibody present at mammalian mucosal surfaces and provides an important first line of defense against pathogens. Recent studies show that sIgA can be measured noninvasively in feces and is a good marker of mucosal immunity. Here we validated a commercial ELISA kit to measure fecal IgA in baboons, tested the robustness of its results to variation in collection and storage conditions, and developed a cost-effective in-house ELISA for baboon fecal IgA. Using data from the custom ELISA, we assessed the relationship between fecal IgA concentrations and gastrointestinal parasite burden, and tested how sex, age, and reproductive effort predict fecal IgA in wild baboons. We find that IgA concentrations can be measured in baboon feces using an in-house ELISA and are highly correlated to the values obtained with a commercial kit. Fecal IgA concentrations are stable when extracts are stored for up to 22 months at -20°C. Fecal IgA concentrations were negatively correlated with parasite egg counts (Trichuris trichiura), but not parasite richness. Fecal IgA did not vary between the sexes, but for males, concentrations were higher in adults versus adolescents. Lactating females had significantly lower fecal IgA than pregnant females, but neither pregnant nor lactating female concentrations differed significantly from cycling females. Males who engaged in more mate-guarding exhibited similar IgA concentrations to those who engaged in little mate-guarding. These patterns may reflect the low energetic costs of mucosal immunity, or the complex dependence of IgA excretion on individual condition. Adding a noninvasive measure of mucosal immunity will promote a better understanding of how ecology modulates possible tradeoffs between the immune system and other energetically costly processes in the wild., (© 2020 Wiley Periodicals, Inc.)

Background: The goal of soil-transmitted helminthiases (STH) control programmes is to eliminate STH-associated morbidity in the target population by reducing the prevalence of moderate- and heavy-intensity infections and the overall STH infection prevalence mainly through preventive chemotherapy (PC) with either albendazole or mebendazole. Endemic countries should measure the success of their control programmes through regular epidemiological assessments. We evaluated changes in STH prevalence in countries that conducted effective PC coverage for STH to guide changes in the frequency of PC rounds and the number of tablets needed., Methods: We selected countries from World Health Organization (WHO)'s Preventive Chemotherapy and Transmission control (PCT) databank that conducted ≥5 years of PC with effective coverage for school-age children (SAC) and extracted STH baseline and impact assessment data using the WHO Epidemiological Data Reporting Form, Ministry of Health reports and/or peer-reviewed publications. We used pooled and weighted means to plot the prevalence of infection with any STH and with each STH species at baseline and after ≥5 years of PC with effective coverage. Finally, using the WHO STH decision tree, we estimated the reduction in the number of tablets needed., Results: Fifteen countries in four WHO regions conducted annual or semi-annual rounds of PC for STH for 5 years or more and collected data before and after interventions. At baseline, the pooled prevalence was 48.9% (33.1-64.7%) for any STH, 23.2% (13.7-32.7%) for Ascaris lumbricoides, 21.01% (9.7-32.3%) for Trichuris trichiura and 18.2% (10.9-25.5%) for hookworm infections, while after ≥5 years of PC for STH, the prevalence was 14.3% (7.3-21.3%) for any STH, 6.9% (1.3-12.5%) for A. lumbricoides, 5.3% (1.06-9.6%) for T. trichiura and 8.1% (4.0-12.2%) for hookworm infections., Conclusions: Countries endemic for STH have made tremendous progress in reducing STH-associated morbidity, but very few countries have data to demonstrate that progress. In this study, the data show that nine countries should adapt their PC strategies and the frequency of PC rounds to yield a 36% reduction in drug needs. The study also highlights the importance of impact assessment surveys to adapt control strategies according to STH prevalence.

The yellow-necked mouse, Apodemus flavicollis, can be considered as a model for genetic polymorphism produced by the frequent presence of supernumerary or B chromosomes (Bs). Host genetic background is rarely taken into account in studies of parasite sex ratio. The main aim of this study was to investigate the range of infrapopulation sex ratios for nematode parasites of the yellow-necked mouse and to determine which factors most influence variation in parasite sex ratios. Six nematode species found in the collected yellow-necked mice were analysed. We confirmed the predominant pattern of female-biased sex ratios in vertebrate parasite infrapopulations. The presence of B chromosomes in host genomes played an important role in infrapopulations of Heligmosomoides polygyrus, Syphacia stroma and Trichuris muris, as hosts with B chromosomes carried a higher proportion of males. The relative increase of males in infrapopulations could result from a shift in parasite life history strategy, induced by adaptation to the specific host genotypes (Bs present). In a meta-analysis with previously published data, the sex determination system was demonstrated to play a significant role in nematode sex ratio variation, as well as specific life history patterns, such as the place of egg hatching.

Type 2 inflammation drives the clearance of gastrointestinal helminth parasites, which infect over two billion people worldwide. Basophils are innate immune cells that support host-protective type 2 inflammation during murine infection with the helminth Trichuris muris However, the mechanisms required for basophil function and gene expression regulation in this context remain unclear. We show that during T. muris infection, basophils localized to the intestine and up-regulated Notch receptor expression, rendering them sensitive to Notch signals that rapidly regulate gene expression programs. In vitro, Notch inhibition limited basophil cytokine production in response to cytokine stimulation. Basophil-intrinsic Notch signaling was required for T. muris -elicited changes in genome-wide basophil transcriptional programs. Mice lacking basophil-intrinsic functional Notch signaling had impaired worm clearance, decreased intestinal type 2 inflammation, altered basophil localization in the intestine, and decreased CD4 + T helper 2 cell responses following infection. These findings demonstrate that Notch is required for basophil gene expression and effector function associated with helminth expulsion during type 2 inflammation., (© 2019 Webb et al.)

The ability of helminths to manipulate the immune system of their hosts to ensure their own survival is often credited with affecting responses to other pathogens. We undertook co-infection experiments in mice to determine how infection with the intestinal helminth Heligmosomoides polygyrus affected the parasitological, immunological and physiological outcomes of a primary infection with a distinct species of helminth; the lung migratory parasite Nippostrongylus brasiliensis. We found that migrating N. brasiliensis larvae were killed in the lungs of H. polygyrus-infected mice by a process involving IL-33-activated CD4 + T cells that released IL-5 and recruited activated eosinophils. The lung pathology normally associated with N. brasiliensis larval migration was also reduced. Importantly, lung immunity remained intact in mice cleared of prior H. polygyrus infection and also occurred during infection with another entirely enteric helminth, Trichuris muris. This study identifies a cross-mucosal immune mechanism by which intestinal helminths may protect their hosts against co-infection by a different parasite at a distal site, via circulation of activated CD4 + T cells that can be triggered to release effector cytokines and mount inflammatory responses by tissue damage-associated alarmins, such as IL-33.

Throughout history, humans have been afflicted by parasitic worms, and eggs are readily detected in archaeological deposits. This study integrated parasitological and ancient DNA methods with a large sample set dating between Neolithic and Early Modern periods to explore the utility of molecular archaeoparasitology as a new approach to study the past. Molecular analyses provided unequivocal species-level parasite identification and revealed location-specific epidemiological signatures. Faecal-oral transmitted nematodes ( Ascaris lumbricoides and Trichuris trichiura ) were ubiquitous across time and space. By contrast, high numbers of food-associated cestodes ( Diphyllobothrium latum and Taenia saginata ) were restricted to medieval Lübeck. The presence of these cestodes and changes in their prevalence at approximately 1300 CE indicate substantial alterations in diet or parasite availability. Trichuris trichiura ITS-1 sequences grouped into two clades; one ubiquitous and one restricted to medieval Lübeck and Bristol. The high sequence diversity of T.t ITS-1 detected in Lübeck is consistent with its importance as a Hanseatic trading centre. Collectively, these results introduce molecular archaeoparasitology as an artefact-independent source of historical evidence., (© 2018 The Authors.)

Introduction: While using recreational areas, people take with them accompanying animals (dogs, cats). These animals are the main source and reservoir of dangerous zoonoses, including parasitoses caused by genera of nematodes, also called roundworms, Toxocara spp., Trichuris spp. and Ancylostoma spp. Attention should also be paid to the possibility of contamination of recreational areas with the eggs of intestinal parasites by wild animals (e.g. red fox)., Material and Methods: Sand was collected on beaches and leisure terrains located in recreational areas in Zwierzyniec, Rudka reservoir on the river Wieprz, 'Echo' reservoir, accessible to tourists to the Roztocze National Park, and the 'Florianiecki' reservoir, chich is inaccessible to tourists due to its location in the depths of the National Park. Material for the research was also collected from the 'Zemborzycki reservoir in Lublin, A total of 300 sand samples were collected. The samples, approximately 500 g each, were collected into plastic bags from the superficial layer of sand, at a depth up to 3 cm. For egg detection, flotation with the Wasylikowa metod and the modified Quinn method were used. In the Quinn metod, the flotation solution is NaCl saturated solution, in the Wasylikowa method, 5% solution of NaOH is used., Results: The most contaminated grounds were areas by the water 'Zemborzycki' reservoir in Lublin. The eggs of intestinal parasites were isolated from 13 out of 24 samples examined. In sand collected from the beach by the 'Echo', 'Florianiecki' and 'Rudka' water resevoirs in Zwierzyniec, no eggs of intestinal parasites were detected., Conclusions: Such a dissemination of results may indicate a connection between the degree of occurrence of geohelmint eggs and the intensity of human movement, together with accompanying animals, in places that can be used for recreation.

Multi-species interactions can often have non-intuitive consequences. However, the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species, and the outcomes of multi-parasite interactions are poorly understood. We investigated the effects of co-infection by four gastrointestinal helminth species on the development of cerebral malaria among Plasmodium falciparum-infected patients. We characterized associations among the helminth parasite infra-community, and then tested for independent (direct) and co-infection dependent (indirect) effects of helminths on cerebral malaria risk. We found that infection by Ascaris lumbricoides and Trichuris trichiura were both associated with direct reductions in cerebral malaria risk. However, the benefit of T. trichiura infection was halved in the presence of hookworm, revealing a strong indirect effect. Our study suggests that the outcome of interactions between two parasite species can be significantly modified by a third, emphasizing the critical role that parasite community interactions play in shaping infection outcomes., Competing Interests: The authors have declared that no competing interests exist.

Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description of helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different helminths have been characterized and their salient roles in parasite-host interactions have been highlighted. Here, we analyze EVs from the rodent parasite Nippostrongylus brasiliensis , which has been used as a model for human hookworm infection. N. brasiliensis EVs ( Nb -EVs) are actively internalized by mouse gut organoids, indicating a role in driving parasitism. We used proteomics and RNA-Seq to profile the molecular composition of Nb -EVs. We identified 81 proteins, including proteins frequently present in exosomes (like tetraspanin, enolase, 14-3-3 protein, and heat shock proteins), and 27 sperm-coating protein-like extracellular proteins. RNA-Seq analysis revealed 52 miRNA species, many of which putatively map to mouse genes involved in regulation of inflammation. To determine whether GI nematode EVs had immunomodulatory properties, we assessed their potential to suppress GI inflammation in a mouse model of inducible chemical colitis. EVs from N. brasiliensis but not those from the whipworm Trichuris muris or control vesicles from grapes protected against colitic inflammation in the gut of mice that received a single intraperitoneal injection of EVs. Key cytokines associated with colitic pathology (IL-6, IL-1β, IFNγ, and IL-17a) were significantly suppressed in colon tissues from EV-treated mice. By contrast, high levels of the anti-inflammatory cytokine IL-10 were detected in Nb -EV-treated mice. Proteins and miRNAs contained within helminth EVs hold great potential application in development of drugs to treat helminth infections as well as chronic non-infectious diseases resulting from a dysregulated immune system, such as IBD.

Intestinal dwelling parasites have evolved closely with the complex intestinal microbiota of their host, but the significance of the host microbiota for metazoan pathogens and the role of their own intestinal microbiota are still not fully known. We have found that the parasitic nematode Trichuris muris acquired a distinct intestinal microbiota from its host, which was required for nematode fitness. Infection of germ-free mice and mice monocolonized with Bacteroides thetaiotaomicron demonstrated that successful T. muris infections require a host microbiota. Following infection, T. muris -induced alterations in the host intestinal microbiota inhibited subsequent rounds of infection, controlling parasite numbers within the host intestine. This dual strategy could promote the long-term survival of the parasite within the intestinal niche necessary for successful chronic nematode infection.

Morocco is a country known for its vulnerability of water resources because of its arid and semi-arid climate. Thus, recycled wastewater has been suggested for agricultural activities, but contamination of these wastewaters is a major concern. The current study aims to determine the occurrence of helminth eggs in urban wastewater and to evaluate the removal of these pathogens by two sewage treatment systems: activated sludge and natural lagoons. The samples of wastewater and sludge were collected from two wastewater treatment plants (WWTP) located in Marrakech and Chichaoua, Morocco. Parasitological identification, according to the Bailenger technique, showed the presence of Nematodes and Cestodes, which are pathogenic to humans and animals and are responsible for helminthiasis. The wastewater and sewage sludge samples from Marrakech carried Ascaris lumbricoïdes, Ancylostoma duodenale, Trichuris trichiura, Capillaria spp., Taenia spp. and Hymenolepis spp., while the samples from Chichaoua carried Ascaris lumbricoïdes, Ancylostoma duodenale, Trichuris trichiura and Capillaria spp. The overall removal efficiency of eggs in the treatment plants ranged from 100% in the WWTP of Marrakech using activate sludge to 94.97% in the WWTP of Chichaoua using natural lagoons. These results were discussed according to health risk and the cost-effectiveness of both wastewater treatment techniques., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Roundworms belong to a diverse phylum (Nematoda) which is comprised of many parasitic species including whipworms (genus Trichuris). These worms have adapted to a biological niche within the host and exhibit unique morphological characteristics compared with other nematodes. Although these adaptations are known, the underlying molecular mechanisms remain elusive. The availability of genomes and transcriptomes of some whipworms now enables detailed studies of their molecular biology. Here, we defined and curated the full complement of an important class of enzymes, the protein kinases (kinomes) of two species of Trichuris, using an advanced and integrated bioinformatic pipeline. We investigated the transcription of Trichuris suis kinase genes across developmental stages, sexes and tissues, and reveal that selectively transcribed genes can be linked to central roles in developmental and reproductive processes. We also classified and functionally annotated the curated kinomes by integrating evidence from structural modelling and pathway analyses, and compared them with other curated kinomes of phylogenetically diverse nematode species. Our findings suggest unique adaptations in signalling processes governing worm morphology and biology, and provide an important resource that should facilitate experimental investigations of kinases and the biology of signalling pathways in nematodes., (Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.)

T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4 f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4 f/f CD11c-cre mice have fewer CD11b + migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b + CD103 + DCs induce Th2 responses in the small intestine, whereas CD11b + CD103 - DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.

Trichuris trichiura is a human parasitic whipworm infecting around 500 million people globally, damaging the physical growth and educational performance of those infected. Current drug treatment options are limited and lack efficacy against the worm, preventing an eradication programme. It is therefore important to develop new treatments for trichuriasis. Using Trichuris muris, an established model for T. trichiura, we screened a library of 480 novel drug-like small molecules for compounds causing paralysis of the ex vivo adult parasite. We identified a class of dihydrobenz[e][1,4]oxazepin-2(3H)-one compounds with anthelmintic activity against T. muris. Further screening of structurally related compounds and resynthesis of the most potent molecules led to the identification of 20 active dihydrobenzoxazepinones, a class of molecule not previously implicated in nematode control. The most active immobilise adult T. muris with EC50 values around 25-50μM, comparable to the existing anthelmintic levamisole. The best compounds from this chemotype show low cytotoxicity against murine gut epithelial cells, demonstrating selectivity for the parasite. Developing a novel oral pharmaceutical treatment for a neglected disease and deploying it via mass drug administration is challenging. Interestingly, the dihydrobenzoxazepinone OX02983 reduces the ability of embryonated T. muris eggs to establish infection in the mouse host in vivo. Complementing the potential development of dihydrobenzoxazepinones as an oral anthelmintic, this supports an alternative strategy of developing a therapeutic that acts in the environment, perhaps via a spray, to interrupt the parasite lifecycle. Together these results show that the dihydrobenzoxazepinones are a new class of anthelmintic, active against both egg and adult stages of Trichuris parasites. They demonstrate encouraging selectivity for the parasite, and importantly show considerable scope for further optimisation to improve potency and pharmacokinetic properties with the aim of developing a clinical agent.

Proinflammatory cytokines produced during immune responses to infectious stimuli are well-characterized to have secondary effects on the function of hematopoietic progenitor cells in the BM. However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell-associated, but not acute Th2 cell-associated, responses to chronic T. muris infection cause a major, transient expansion of CD48 - CD150 - multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN-γ signaling. Chronic T. muris infection also broadly stimulated proliferation of BM progenitor cells including CD48 - CD150 + hematopoietic stem cells. This shift in progenitor activity during chronic T. muris infection correlated with a functional increase in myeloid colony formation in vitro as well as neutrophilia in the BM and peripheral blood. In parallel, we observed an accumulation of CD4 + , CD8 + , and CD4 - CD8 - (double negative) T cells that expressed IFN-γ, displaying activated and central memory-type phenotypes in the bone marrow during chronic infection. Thus, these results demonstrate that Th1 cell-driven responses in the intestine during chronic helminth infection potently influence upstream hematopoietic processes in the BM via IFN-γ., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Editor's Note: This article discusses the experience, ingenuity, and determination of Sean Ahrens, a young patient with Crohn's disease who took it upon himself to treat his longstanding, symptomatic Crohn's disease with pig whipworm eggs. Reading this story will make some of you uncomfortable. You might question whether this work belongs in a medical journal or sends the wrong message to readers. However, we recognize that this topic is controversial and that N=1 reports cannot and should not change practice. The purpose of this story is not to encourage the use of pig whipworm or to demonstrate its efficacy (or lack thereof). We firmly believe that patients are uniquely qualified to provide insights into how they view their illnesses, weigh risks and benefits, and ultimately achieve self-efficacy. Stories like this are important for us to acknowledge and understand, even if they do not change our practice.

Objective: To investigate the prevalence and risk factors of helminthic infections including Schistosoma japonicum , Ascaris lumbricoides and Trichuris trichiura and human immunodeficiency virus (HIV), and find out the association among them in a rural community of southwestern China., Methods: A community-based cross sectional study was conducted. One town was selected randomly; the infections of S.japonicum , A.lumbricoides and T.trichiura were detected with the modified Kato-Katz thick smear method and HIV infection with the diagnostic Test Kit among all residents. A questionnaire survey was conducted to investigate the related risk factors., Results: Among the participants, the infection rates of HIV, S.japonicum , A.lumbricoides and T.trichiura were 2.33%, 2.05%, 13.47% and 30.59% respectively; 7.08% (31/438) were infected with both A.lumbricoides and T.trichiura ; 0.23% (1/438) were co-infected with HIV and A.lumbricoides , and the same with HIV and T.trichiura. The multivariate logistic regression analysis showed that sex (male, OR =3.26, 95% CI ：0.97, 10.95) and drug abuse ( OR =72.86, 95% CI ：18.51, 286.76) were significantly associated with HIV infection. Home toilet was negatively related to A.lumbricoides infection ( OR =0.52, 95% CI ：0.27, 0.98) and T.trichiura infection ( OR =0.48, 95% CI ：0.28, 0.80). Compared with the people in Villages Four, the people living in Village One were at a higher risk for A.lumbricoides infection ( OR =3.14, 95% CI ：1.35, 7.27), and compared with the people living in Village Four, the people living in Village Two and Village Three were more likely to be infected with T.trichiura ( OR =3.73, 95% CI ：1.92, 7.26; OR =4.53, 95% CI ：2.12, 9.68). The people aged between 11 and 20 years had a higher T.trichiura infection risk than the people aged more than 50 years ( OR = 3.72, 95% CI ：1.59, 8.67). There was a significant association between A.lumbricoides and T.trichiura infections ( OR = 3.11, 95% CI ：1.63, 5.93). There was no association between S.japonicum infection and related factors above mentioned., Conclusions: The infection rates of HIV, S.japonicum , A.lumbricoides and especially T.trichiura were rather high in this area, and therefore, the prevention and treatment of these diseases should be strengthened. Further studies on the relationship between HIV and the infections of helminths, especially S.japonicum are needed.

Using three isolates of the murine parasitic nematode Trichuris muris, E, E/J (the E isolate maintained in Japan), and S, I have previously demonstrated that when the embryonated eggs of the E/J and E isolates are incubated with the intestinal bacteria Escherichia coli and Staphylococcus aureus, they are induced to hatch in vitro. However, the eggs of the S isolate are unresponsive to these bacteria. In the present study, I investigated whether direct contact between the embryonated eggs of the E/J and E isolates and bacteria is required to induce their hatching. To do so, a new co-culture system for eggs and bacteria (E. coli or S. aureus) was developed to block any direct contact between the eggs and the bacteria. In the hatching experiment using the new system, when direct contact between the eggs and bacteria was completely prevented, the eggs still hatched. However, the peak levels of hatching without direct contact were about 20 % lower than those with direct contact, and peak hatching occurred later without direct contact. This evidence suggests that hatching occurs without direct contact between the eggs and bacteria, and that unidentified material derived from active bacteria induces the hatching of embryonated eggs of the E/J and E isolates of T. muris in vitro.

Infections caused by soil-transmitted helminthias (STHs) affect over a billion people worldwide, causing anaemia and having a large social and economic impact through poor educational outcomes. They are identified in the World Health Organization (WHO) 2020 goals for neglected tropical diseases as a target for renewed effort to ameliorate their global public health burden through mass drug administration (MDA) and water and hygiene improvement. In this chapter, we review the underlying biology and epidemiology of the three causative intestinal nematode species that are mostly considered under the STH umbrella term. We review efforts to model the transmission cycle of these helminths in populations and the effects of preventative chemotherapy on their control and elimination. Recent modelling shows that the different epidemiological characteristics of the parasitic nematode species that make up the STH group can lead to quite distinct responses to any given form of MDA. When connected with models of treatment cost-effectiveness, these models are potentially a powerful tool for informing public policy. A number of shortcomings are identified; lack of critical types of data and poor understanding of diagnostic sensitivities hamper efforts to test and hence improve models., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Soil-transmitted helminths, which affect the poorest communities, worldwide cause a range of symptoms and morbidity, yet few treatment options are available and drug resistance is a concern. To improve and accelerate anthelminthic drug discovery, novel drug screening tools such as isothermal microcalorimetry (IMC) have been tested with great potential. In this study, we used a novel microcalorimeter, the calScreener™, to study the viability on the hookworms Necator americanus and Ancylostoma ceylanicum as well as the whipworm Trichuris muris. Significant heat flow signals could be obtained with already one adult worm per channel for all three species. High-amplitude oscillations were observed for the hookworms; however, adult T. muris showed a twofold heat flow decrease during the first 24 h. Antinematodal effects of ivermectin and levamisole at 1, 10, and 100 μg/ml were evaluated on adult N. americanus and A. ceylanicum. Levamisole-treated hookworms showed a decline in heat flow and oscillation amplitude in a dose-response manner. Heat flow for ivermectin-treated hookworms increased proportionally with increased concentrations of ivermectin, though the wavelet analysis showed an opposite trend as observed by flatter wavelets. In conclusion, the calScreener™ is an excellent tool to study drug effects on intestinal hookworms at the adult worm stage as it offers a lower detection limit than other IMC devices and the possibility to monitor worm viability online.

Background: Neglected tropical diseases are of major concern to sub-Saharan African countries. Though efforts to monitor the prevalence and control are in place, these are mostly restricted to groups within the population. This study was performed to determine the prevalence among patients of a Ghanaian psychiatric hospital and find out whether there is a reason for active monitoring in this population., Methods: A cross-sectional study was performed to determine the prevalence of intestinal parasites among patients of a Ghanaian psychiatric hospital. Stool samples were collected and analyzed in addition to data., Results: Of the 111 patients studied, asymptomatic carriage of parasites was 13.5 % and was higher in males (18.8 %) than in females (4.8 %). Carriage of parasites decreased with age but increase with duration of admission., Conclusion: This is the first report of parasitic pathogens among patients of a psychiatric institution in Ghana. The data shows that there are risks of transmission of infectious diseases via the oral route hence, the need for regular monitoring and intervention is emphasized.

The aim of this study was to assess the effect of infection with the nematode whipworm Trichuris muris on the course of chemically induced acute ulcerative colitis in CBA/J mice, a strain proven to be highly resistant to infection with T. muris. Each mouse was infected with 50 embryonated eggs of T. muris by oral gavage. Acute colitis was triggered by administering 4% dextran sulphate sodium (DSS) in the drinking water for nine consecutive days at different times after infection. Concurrent infection and DSS administration exacerbate the severity of the colitis while favouring the permanence of parasites in the intestine. The induction of ulcerative colitis from days 54 to 62 post-infection (p.i.), when all worms had been expelled, ameliorated the course of the inflammatory disease. When ulcerative colitis was triggered earlier on, from days 27 to 35 p.i., the beneficial effects on inflammatory events were clearly shown with signs of mucosal epithelization and regeneration as early as day 1 after DSS administration. Previous infections by T. muris therefore accelerate recovery from subsequently induced inflammatory bowel disease and such an effect assists the nematode to persist in the intestinal niche.

Introduction: The inverse correlation between prevalence of auto-immune disorders like the chronic neuro-inflammatory disease multiple sclerosis (MS) and the occurrence of helminth (worm) infections, suggests that the helminth-trained immune system is protective against auto-immunity. As monocytes are regarded as crucial players in the pathogenesis of auto-immune diseases, we explored the hypothesis that these innate effector cells are prime targets for helminths to exert their immunomodulatory effects., Results: Here we show that soluble products of the porcine nematode Trichuris suis (TsSP) are potent in changing the phenotype and function of human monocytes by skewing classical monocytes into anti-inflammatory patrolling cells, which exhibit reduced trans-endothelial migration capacity in an in vitro model of the blood-brain barrier. Mechanistically, we identified the mannose receptor as the TsSP-interacting monocyte receptor and we revealed that specific downstream signalling occurs via protein kinase C (PKC), and in particular PKCδ., Conclusion: This study provides comprehensive mechanistic insight into helminth-induced immunomodulation, which can be therapeutically exploited to combat various auto-immune disorders.

Background: Eggs of the porcine whipworm Trichuris suis are currently explored in human clinical trials as a treatment of immune-mediated diseases. In this context, only the infective, embryonated eggs, constitute the Active Pharmaceutical Ingredient (API). The rodent whipworm, Trichuris muris is commonly used as a laboratory model to study Trichuris biology. The embryonated eggs (containing a fully developed larva) are biologically active and will invade the large intestinal mucosa of the host. This study aims to assess the in vitro hatching of T. muris and T. suis eggs in various bacterial cultures as a measure for their biological activity., Methods: Eggs of T. muris and T. suis were incubated with Escherichia coli strain (BL-21) at three concentrations in a slightly modified in vitro egg hatching assay previously developed for T. muris. Additionally, E. coli strains (M15, SG13009, PMC103, JM109, TUNER, DH5alpha, TOP10) and five Gram-positive bacteria (Enterococcus caccae, Streptococcus hyointestinalis, Lactobacillus amylovorus, L. murinus, and L. reuteri) were tested as a hatching stimulus for T. muris and T. suis eggs., Results: Whereas T. muris eggs hatched, T. suis did not, even when exposed to different concentrations and strains of E. coli after 4 and 24-hour incubation. When incubated with Gram-positive bacteria, only T. muris eggs showed noticeable hatching after 20 h, although with high variability., Conclusions: The observed difference in hatching of T. muris and T. suis eggs incubated with selected bacteria, indicate significant biological differences which may reflect specific adaptation to different host-specific gut microbiota.

Cross-species infection among humans, chimpanzees (Pan troglodytes) and baboons (Papio spp.) is potentially a significant public health issue in Africa, and of concern in the conservation of P. troglodytes. However, to date, no statistical comparisons have been made between the prevalence, richness and composition of parasite communities in sympatric populations of baboons and P. troglodytes. We compared parasite communities in sympatric P. troglodytes and Papio papio living in a wilderness site, in the Republic of Senegal, West Africa. We asked whether, in the absence of humans, there are significant differences between these hosts in their interactions with gastrointestinal parasites. We tested whether host, location, or time of collection accounted for variation in prevalence, richness and community composition, and compared prevalence across six studies. We concluded that, despite being closely related, there are significant differences between these two hosts with respect to their parasite communities. At our study site, prevalence of Balantidium, Trichuris and Watsonius was higher in P. papio. Papio papio harboured more parasites per host, and we found evidence of a positive association between Trichuris and Balantidium in P. troglodytes but not P. papio.

Trichuris suis ova (TSO) have shown promising results in the treatment of inflammatory bowel disease (IBD) but the mechanisms which underlies this therapeutic effect cannot be studied in mice and rats as T. suis fails to colonize the rodent intestine, whilst hatching in humans and rabbits. As a suitable rabbit IBD model is currently not available, we developed a rabbit colitis model by administration of dextran sodium sulphate (DSS). White Himalayan rabbits (n = 12) received 0.1% DSS in the daily water supply for five days. Clinical symptoms were monitored daily, and rabbits were sacrificed at different time points. A genomewide expression analysis was performed with RNA isolated from caecal lamina propria mononuclear cells (LPMC) and intestinal epithelial cells (IEC). The disease activity index of DSS rabbits increased up to 2.1 ± 0.4 (n = 6) at day 10 (controls <0.5). DSS induced a caecum-localized pathology with crypt architectural distortion, stunted villous surface and inflammatory infiltrate in the lamina propria. The histopathology score reached a peak of 14.2 ± 4.9 (n = 4) at day 10 (controls 7.7 ± 0.9, n = 5). Expression profiling revealed an enrichment of IBD-related genes in both LPMC and IEC. Innate inflammatory response, Th17 signalling and chemotaxis were among the pathways affected significantly. We describe a reproducible and reliable rabbit model of DSS colitis. Localization of the inflammation in the caecum and its similarities to IBD make this model particularly suitable to study TSO therapy in vivo., (© 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.)

Embryonated eggs of the pig whipworm Trichuris suis (TSOee) constitute the active pharmaceutical ingredient (API) in a medicinal product explored in human clinical trials against several immune-mediated diseases. The measurement of TSO biological potency (hatchability and infectivity) is a requirement for the assessment of TSO's pharmacological potency in human clinical trials. The present study aims to validate the dose-dependent establishment of T. suis larvae in Göttingen minipigs and eventual clinical implication of a dose range (1000-10,000 TSO). Four groups of 5 minipigs were inoculated with doses of 1000, 2500, 7500, and 10,000 TSOee, respectively, to evaluate a range of concentrations of TSOee in a minipig infectivity model. Unembryonated eggs (TSOue) were added to keep the total egg number in the inoculum constant at 10,000 eggs. Two groups received 2500 and 7500 TSOee per pig without the addition of TSOue as controls. The intestinal larval establishment at 21 days post inoculation (dpi) demonstrated a clear positive linear dose-response relationship between numbers of inoculated TSOee and recovered larvae. There was a low level of variation in larval counts in all study groups. Thus, the infectivity model in minipigs within the tested dose range offers a reliable, sensitive and accurate assay for testing biological potency of TSO., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Trichuriasis is a parasitic disease caused by the human whipworm, Trichuris trichiura. It affects millions worldwide, particularly in the tropics. This nematode parasite burrows into the colonic epithelium resulting in inflammation and morbidity, especially in children. Current treatment relies mainly on general anthelmintics such as mebendazole but resistance to these drugs is increasingly problematic. Therefore, new treatments are urgently required., Methods: The prospect of using the retinoid X receptor (RXR) antagonist HX531 as a novel anthelmintic was investigated by carrying out multiple viability assays with the mouse whipworm Trichuris muris., Results: HX531 reduced both the motility and viability of T. muris at its L3, L4 and adult stages. Further, bioinformatic analyses show that the T. muris genome possesses an RXR-like receptor, a possible target for HX531., Conclusions: The study suggested that Trichuris-specific RXR antagonists may be a source of much-needed novel anthelmintic candidates for the treatment of trichuriasis. The identification of an RXR-like sequence in the T. muris genome also paves the way for further research based on this new anthelmintic lead compound.

Background: In Brazil, preventive chemotherapy targeting soil-transmitted helminthiasis is being scaled-up. Hence, spatially explicit estimates of infection risks providing information about the current situation are needed to guide interventions. Available high-resolution national model-based estimates either rely on analyses of data restricted to a given period of time, or on historical data collected over a longer period. While efforts have been made to take into account the spatial structure of the data in the modelling approach, little emphasis has been placed on the temporal dimension., Methods: We extracted georeferenced survey data on the prevalence of infection with soil-transmitted helminths (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura) in Brazil from the Global Neglected Tropical Diseases (GNTD) database. Selection of the most important predictors of infection risk was carried out using a Bayesian geostatistical approach and temporal models that address non-linearity and correlation of the explanatory variables. The spatial process was estimated through a predictive process approximation. Spatio-temporal models were built on the selected predictors with integrated nested Laplace approximation using stochastic partial differential equations., Results: Our models revealed that, over the past 20 years, the risk of soil-transmitted helminth infection has decreased in Brazil, mainly because of the reduction of A. lumbricoides and hookworm infections. From 2010 onwards, we estimate that the infection prevalences with A. lumbricoides, hookworm and T. trichiura are 3.6%, 1.7% and 1.4%, respectively. We also provide a map highlighting municipalities in need of preventive chemotherapy, based on a predicted soil-transmitted helminth infection risk in excess of 20%. The need for treatments in the school-aged population at the municipality level was estimated at 1.8 million doses of anthelminthic tablets per year., Conclusions: The analysis of the spatio-temporal aspect of the risk of infection with soil-transmitted helminths contributes to a better understanding of the evolution of risk over time. Risk estimates provide the soil-transmitted helminthiasis control programme in Brazil with useful benchmark information for prioritising and improving spatial and temporal targeting of interventions.

Background: Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis., Methods: First, we assessed efficacy by means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of 450 μmol active CPs (CP450) against low (inoculum of 300 eggs) and high (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the second trial, we determined and compared the efficacy of a series of CP doses (45 [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] μmol) against high intensity infections., Results: CP450 was highly efficacious against both levels of infection intensity, resulting in ERR and WRR of more than 97%. For both levels of infection intensity, CP450 was significantly more efficacious compared to ALB by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant difference was only observed for high intensity infections, CP450 being more efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The efficacy of CPs increased as a function of increasing dose. When determined by ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450, the latter being more efficacious., Conclusions: A single dose of 450 μmol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB. Although these results highlight the possibility of papaya CPs for controlling human STH, further development is needed in order to obtain and validate an oral formulation for human application.

Background: The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known., Methodology: We studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species., Principal Findings: The motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6-17.2%) as compared to O. dentatum (0.8-0.9%)., Conclusion/significance: The general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum.

Foxp3(+) regulatory T cells (Tregs) have a well-characterized role in limiting autoimmunity and dampening deleterious immune responses. However, a potential consequence of the immunosuppressive function of Tregs can be the limitation of protective immunity to infectious pathogens. Parasitic infections are a potent stimulus for the generation of Treg responses, which may be beneficial to both the parasite and the host by promoting persistence of infection and limiting immune-mediated pathology, respectively. In this study, we explore the functional role of Tregs post-low-dose infection with the intestinal helminth parasite Trichuris muris, which yields a chronic infection because of inefficient induction of Th2 responses. Early Treg depletion postinfection resulted in expedited worm clearance, and was associated with reduced Th1-mediated inflammation of the intestinal environment. Interestingly, this protective immunity was lost, and worm burden enhanced if Tregs were depleted later once the infection was established. Early and late Treg depletion resulted in enhanced Th2 and reduced Th1 cytokine and humoral responses. Blockade of the Th2 cytokine IL-4 resulted in a moderate increase in Th1 but had no effect on worm burden. Our findings suggest that Tregs preferentially limit Th2 cell expansion, which can impact infections where clear immune polarity has not been established. Thus, the impact of Treg depletion is context and time dependent, and can be beneficial to the host in situations where Th1 responses should be limited in favor of Th2 responses.

The aim of the present study was to investigate the population dynamics and potential interactions between Trichuris suis and Oesophagostomum dentatum in experimentally co-infected pigs, by quantification of parasite parameters such as egg excretion, worm recovery and worm location. Forty-eight helminth naïve pigs were allocated into four groups. Group O was inoculated with 20 O. dentatum L3/kg/day and Group T with 10 T. suis eggs/kg/day. Group OT was inoculated with both 20 O. dentatum L3/kg/day and 10 T. suis eggs/kg/day, while Group C was kept as an uninfected control group. All inoculations were trickle infections administered twice weekly and were continued until slaughter. Faecal samples were collected from the rectum of all pigs at day 0, and twice weekly from 2 to 9 weeks post first infection (wpi). Six pigs from each group were necropsied 5 wpi and the remaining 6 pigs from each group were necropsied 10 wpi. The faecal egg counts (FEC) and total worm burdens of O. dentatum were dramatically influenced by the presence of T. suis, with significantly lower mean FECs and worm burdens at 5 and 10 wpi compared to single infected pigs. Furthermore, in the presence of T. suis we found that O. dentatum was located more posteriorly in the gut. The changes in the Trichuris population were less prominent, but faecal egg counts, worm counts 5 wpi (57% recovered vs. 39%) and the proportion of infected animals at 10 wpi were higher in Group OT compared to Group T. The location of T. suis was unaffected by the presence of O. dentatum. These results indicate an antagonistic interaction between T. suis and O. dentatum which is dominated by T. suis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The worldwide prevalence of geohelminths and their unique place in evolutionary biology have attracted research focus. These major soil-transmitted intestinal nematodes that cause human diseases are the nematode roundworm (Ascaris lumbricoides), the whipworm (Trichuris trichiura) and the two hookworms (Ancylostoma duodenale and Necator americanus), often collectively referred as geohelminths. Studies of geohelminthiasis in poorly nourished children in developing regions report that geohelminths contribute to stunted growth and cognitive impairment. Insights into immunology have shed light on the modulatory role of the parasite on the host immune system and have defined the role of T cells in controlling geohelminthic infection. Recent molecular biological techniques have created an opportunity to analyse the interaction between parasites and their hosts at the molecular level. This paper is a review of the recent literature that examined the prevalence of geohelminthiasis in developing countries, the association between geohelminths in relation to public health, parasitological/diagnostic features, and therapeutic and preventive aspects of these major soil-transmitted helminth (STH) pathogens in humans.

The mouse whipworm Trichuris muris has long been used as a tractable model of human Trichuriasis. Here we look back at the history of T. muris research; from the definition of the species and determination of its life cycle, through to the complex immune responses that we study today. We highlight the key research papers that have developed our understanding of immune responses to this parasite, and reflect on how original concepts have been transformed, as our knowledge of immunology has grown. Although we have a good understanding of host–parasite interactions in the context of the underlying cellular immunology, there are still many aspects of the biology of the Trichuris parasite that remain undefined. We predict that advances in parasite biology will be key in the future development of new and improved treatments for Trichuriasis.

Two models are proposed to explain Notch function during helper T (Th) cell differentiation. One argues that Notch instructs one Th cell fate over the other, whereas the other posits that Notch function is dictated by cytokines. Here we provide a detailed mechanistic study investigating the role of Notch in orchestrating Th cell differentiation. Notch neither instructed Th cell differentiation nor did cytokines direct Notch activity, but instead, Notch simultaneously regulated the Th1, Th2, and Th17 cell genetic programs independently of cytokine signals. In addition to regulating these programs in both polarized and nonpolarized Th cells, we identified Ifng as a direct Notch target. Notch bound the Ifng CNS-22 enhancer, where it synergized with Tbet at the promoter. Thus, Notch acts as an unbiased amplifier of Th cell differentiation. Our data provide a paradigm for Notch in hematopoiesis, with Notch simultaneously orchestrating multiple lineage programs, rather than restricting alternate outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neurodevelopmental pathologies. The main core symptoms are: dysfunctions in social interactions and communication skills, restricted interests, repetitive and stereotypic verbal and non-verbal behaviors. Several biochemical processes are associated with ASDs: oxidative stress; endoplasmic reticulum stress; decreased methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal dysbiosis; increased toxic metal burden; immune dysregulation. Current available treatments for ASDs can be divided into behavioral, nutritional and medical approaches, although no defined standard approach exists. Current drugs fail to benefit the ASD core symptoms and can have marked adverse effects, are mainly palliative and only sometimes efficacy in attenuating specific autistic behaviors. Helminthic therapy shows potential for application as anti-inflammatory agent. Several human diseases can be treated by helminths (i.e. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes). Trichuris suis ova (TSO) show strong immunomodulatory properties. Authors hypothesize that TSO could be useful in addressing ASD immune dysregulations. TSO could be a novel therapeutic option for ASD management., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The production of small numbers of large eggs among the standard-sized eggs of Trichuris trichiura is well known. Large eggs have also been observed in Trichuris muris, but they have not been studied previously. This paper compares the characteristics of the large eggs (LEs, ≥74.5 μm long) and standard-sized eggs (SEs, <74.5 μm long) in cultures of T. muris. Among 112,554 cultured eggs, LEs occurred at very low frequency (0.03 %, i.e., about three large eggs per 10(4) cultured eggs). Embryonated eggs represented 93.72 % of SEs, but only 25.00 % of LEs were embryonated. Embryonated LEs and SEs contained fully matured larvae. An atypical category of unembryonated egg, which contained an incompletely developed larva, an abnormal larva, or granular components, was common among the LEs. However, similar atypical unembryonated SEs were rarely observed. These observations suggest that the LEs that occur very infrequently in T. muris result from an abnormality of embryonation (larval development).

Background: Trichuriasis represents a major public health problem in the developing world and is regarded as a neglected disease. Albendazole and mebendazole, the two drugs of choice against trichuriasis display only moderate cure rates, hence alternative drugs are needed. To identify candidate compounds, in vitro drug sensitivity testing currently relies on the adult Trichuris muris motility assay. The objective of the present study was to develop a simple and cost-effective drug sensitivity assay using Trichuris muris first-stage larvae (L1)., Methods: Several potential triggers that induce hatching of T. muris were studied, including gastrointestinal enzymes, acidic environment and intestinal microflora. Next, optimal culture conditions for T. muris L1 were determined assessing a wide range of culture media. T. muris L1 were incubated in the presence of mebendazole, ivermectin, nitazoxanide, levamisole or oxantel pamoate at 37°C. The viability of the parasites was evaluated microscopically after 24 hours. The usefulness of fluorescent markers (resazurin, calcein AM, ethidium homodimer-1 or fluorescein-conjugated albumin) in drug sensitivity testing was also assessed., Results: The established L1 motility assay provided accurate and reproducible drug effect data in vitro. IC50 values for oxantel pamoate, levamisole and nitazoxanide were 0.05, 1.75 and 4.43 μg/mL, respectively. Mebendazole and ivermectin failed to show any trichuricidal effect on L1. No correlation was found between data from the four fluorescent markers and the comparative motility assay., Conclusions: The motility assay based on L1 was found suitable for drug sensitivity screening. It is rather simple, cost-effective, time-saving and sustains medium-throughput testing. Furthermore, it greatly reduces the need for the animal host and is therefore more ethical. None of the viability markers assessed in this study were found to be satisfactory.

Objective: To study nematode parasites morphology of Hystrix javanica (H. javanica), both through the feces and internal organs., Methods: Feces were observed by direct smear method, internal organs were observed after dissecting the host. Specimens for light microscopy examination were fixed with 70% warm alcohol, cleared and mounted in lactophenol for wet mounting. Specimens for SEM examination were postfixed in cacodylate buffer and glutaraldehyde, dehydrated through a graded series of alcohol and freeze dried. The specimens were attached to stubs with double cello-tape, coated with gold and observed with a JSM5310 LV electron microscope. Figures were made with the aid of a drawing tube attached to Olympus compound microscope, other figures were photographs of scanning electron microscope images. Measurements were given in micrometers as the mean followed by the range in parentheses, unless otherwise stated., Results: The nematode species found in the intestine of H. javanica are Gireterakis girardi and a new species, Trihuris landak. The new species differs with previously reported species from Hystrix because of having stylet and short cervical alae. The pattern of bacillary band is closed to Trichuris trichiurus, the species that infect human, but differs because the surface of its vulva is not covered with densely spine., Conclusions: The species of nematodes found on H. javanica were Gireterakis girardi and a new species Trichuris landak n.sp. Those two species are newly recorded in Indonesia.

Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.