The neurotropic schistosome vs experimental autoimmune encephalomyelitis: are there any winners?

The incidences of multiple sclerosis have risen worldwide, yet neither the trigger nor efficient treatment is known. Some research is dedicated to looking for treatment by parasites, mainly by helminths. However, little is known about the effect of helminths that infect the nervous system. Therefore, we chose the neurotropic avian schistosome Trichobilharzia regenti, which strongly promotes M2 polarization and tissue repair in the central nervous system, and we tested its effect on the course of experimental autoimmune encephalomyelitis (EAE) in mice. Surprisingly, the symptoms of EAE tended to worsen after the infection with T. regenti. The infection did not stimulate tissue repair, as indicated by the similar level of demyelination. Eosinophils heavily infiltrated the infected tissue, and the microglia number increased as well. Furthermore, splenocytes from T. regenti-infected EAE mice produced more interferon (IFN)-γ than splenocytes from EAE mice after stimulation with myelin oligodendrocyte glycoprotein. Our research indicates that the combination of increased eosinophil numbers and production of IFN-γ tends to worsen the EAE symptoms. Moreover, the data highlight the importance of considering the direct effect of the parasite on the tissue, as the migrating parasite may further tissue damage and make tissue repair even more difficult.

Temperature and light effects on Trichobilharzia szidati cercariae with implications for a risk analysis.

BACKGROUND: Cercarial dermatitis (swimmer's itch) caused by bird schistosome cercariae, released from intermediate host snails, is a common disorder also at higher latitudes. Several cases were observed in the artificial Danish freshwater Ringen Lake frequently used by the public for recreational purposes. The lake may serve as a model system when establishing a risk analysis for this zoonotic disease. In order to explain high risk periods we determined infection levels of intermediate host snails from early spring to late summer (March, June and August) and elucidated the effect of temperature and light on parasite shedding, behavior and life span. RESULTS: Field studies revealed no shedding snails in March and June but in late summer the prevalence of Trichobilharzia szidati infection (in a sample of 226 pulmonate Lymnaea stagnalis snails) reached 10%. When investigated under laboratory conditions the cercarial shedding rate (number of cercariae shed per snail per day) was positively correlated to temperature raising from a mean of 3000 (SD 4000) at 7 °C to a mean of 44,000 (SD 30,000) at 27 °C). The cercarial life span was inversely correlated to temperature but the parasites remained active for up to 60 h at 20 °C indicating accumulation of cercariae in the lake during summer periods. Cercariae exhibited positive phototaxy suggesting a higher pathogen concentration in surface water of the lake during daytime when the public visits the lake. CONCLUSION: The only causative agent of cercarial dermatitis in Ringen Lake detected was T. szidati. The infection risk associated with aquatic activities is low during spring and early summer (March-June). In late summer the risk of infection is high since the release, behavior and life span of the infective parasite larvae have optimal conditions.

Interrelationships of vitelline and muscle cells within the vitelline follicles of the blood fluke Aporocotyle simplex (Digenea, Aporocotylidae) and morphological evidence for the modification of vitelline material for eggshell formation.

This study of the fish blood fluke Aporocotyle simplex represents the first detailed transmission electron microscopical (TEM) investigation of the vitellarium of an aporocotylid digenean blood fluke. It revealed some unusual characteristics in the cytoarchitecture of the vitelline follicles and demonstrated modifications of the vitelline granules for eggshell formation. The vitelline follicles consist of vitellocytes at different developmental stages surrounded by sarcoplasmic processes of myocytes which occur throughout each follicle. Sites of intimate contact occur between the vitellocytes and the myocytes. Individual vitelline globules (0.1-0.2 µm in diameter) accumulate in quite small clusters of 10-20 and have a dense, heterogeneous matrix possessing central and peripheral regions with a greater density. Modifications of the vitelline globules take place within the clusters and are first apparent when the vitellocytes reach the lumen of the vitelline duct and vitelline reservoir. Globules within the clusters become confluent, and, when the vitellocytes reach the lumen of the oviduct and proximal ootype, these consolidated clusters contain a shapeless, loosely packed, dense material which is released from the vitellocytes by exocytosis. This investigation has provided morphological evidence for shell formation from modified vitelline globules in the form of a discontinuous, thin layer (~ 0.07 µm in thickness) of electron-dense shell material around the fertilized ovum and associated vitellocytes in the proximal ootype. The eggshell of intra-uterine eggs acquires an additional thin, heterogeneous outer layer, increasing its thickness to ~ 0.1 µm. The cytoarchitecture of the vitellarium, modifications of the vitelline globules within the clusters and the structure of the eggshell of A. simplex may prove to be of value in studies examining relationships between the three distinct lineages of aporocotylid digeneans.

Sonographic findings of pinpoint hyperechoic foci in the small intestine, liver, and mesenteric lymph nodes are indicative of canine Heterobilharzia americana infection.

Canine schistosomiasis, caused by the trematode Heterobilharzia americana, can pose a diagnostic challenge due to nonspecific symptoms. The aim of this multicenter, retrospective, descriptive study was to compare the prevalence and extent of sonographic changes associated with schistosomiasis between affected and infection-free dogs. Medical records of two referral centers were searched for dogs with confirmed schistosomiasis that had undergone an abdominal ultrasound. Fifty-five cases fulfilled the inclusion criteria, and a contemporaneous control group was derived from dogs that tested negative for H. americana. Two blinded reviewers evaluated the images. The majority of Heterobilharzia-infected (further termed H-pos) dogs (82%) had ultrasonographic abnormalities in the small intestine ± liver. Abnormal layering of the small intestine was noted in 38 of 54 H-pos dogs, compared to six of 54 control dogs (P < .0001). Pinpoint hyperechoic foci were noted in the small intestinal submucosa or muscularis layers in 25 of 54 H-pos dogs, but only three controls (P < .0001). Heterogeneity of the hepatic parenchyma and pinpoint hyperechoic foci were more prevalent in H-pos dogs (65% vs 40%; P = .0213 and 44% vs 18%; P = .0068, respectively). Pinpoint hyperechoic foci within mesenteric lymph nodes were noted in seven H-pos dogs and none of the controls (P = .0128). The combination of heterogeneous small intestine wall layering and pinpoint hyperechoic foci in small intestine, liver, or mesenteric lymph nodes was the most reliable indication of infection (P = .0001; odds ratio = 36.87), with positive predictive value of 94%, yet modest sensitivity for the detection of infection (58%). Observing these sonographic features suggests schistosomiasis and should prompt further testing.

Direct onshore wind predicts daily swimmer's itch (avian schistosome) incidence at a Michigan beach.

Swimmer's itch (SI) is a painful rash caused by skin penetration by free-swimming infectious cercariae of avian schistosomes, snail-borne helminth parasites related to the causative agents of human schistosomiasis. The goal of this study was to determine if commonly collected environmental data could be used to predict daily fluctuations in SI incidence at an inland beach in northwestern Michigan. Lifeguards collected daily data over four summers, including the number of self-reported SI cases, total swimmers, water temperature, wind speed and wind direction. Mixed-effects binomial regression revealed that wind direction, wind speed and time of day were the best predictors of daily SI risk. Swimmers entering the water in the morning or on days with direct onshore wind perpendicular to the shoreline had the greatest SI risk. However, there was a negative effect of wind speed after accounting for direction, where SI risk was greatest on days with a gentle breeze originating directly offshore. These results suggest that at this beach, direct onshore winds generate a surface-water current that causes SI cercariae to aggregate in the shallow waters used by swimmers. Data are needed from additional sites to confirm whether the onshore wind is a generally important driver of SI incidence.

Snail defence responses to parasite infection: The Lymnaea stagnalis-Trichobilharzia szidati model.

Lymnaea stagnalis is a common freshwater gastropod. Importantly, the snail serves as the intermediate host for more than one hundred species of digenetic trematodes, including the avian schistosome Trichobilharzia szidati, a causative agent of cercarial dermatitis in humans. Infection of L. stagnalis by T. szidati initiates a dynamic confrontation between the host and the parasite that culminates in immunocompatibility ensuring survival and development of larvae. Unfortunately, the molecular mechanisms determining this immunocompatibility remain poorly characterised. By employing a variety of immune elicitors, including chemical compounds, PAMPs and bacteria, research in the last two decades has elucidated some of the molecular processes that regulate the snail internal defence response such as haemocyte signalling pathways. These discoveries provide a framework for future studies of molecular interactions between T. szidati and L. stagnalis to help elucidate factors and mechanisms enabling transmission of schistosome parasites. Moreover, support from recently available next generation sequence data and CRISPR-enabled functional genomics should further enable L. stagnalis as an important model for comparative immunology and contribute to a more comprehensive understanding of immune functions in gastropod molluscs.

Heads or tails? Differential translational regulation in cercarial heads and tails of schistosome worms.

Schistosomes are obligate helminths responsible for over 218 million cases of human schistosomiasis in 78 countries around the world. Infection occurs when free-swimming cercariae penetrate human skin and initiate developmental progression into parasitic obligate worms that consume red blood cells. Transcriptomic studies of infectious cercariae reveal abundant mRNAs associated with energy metabolism and host invasion. However, the cercaria is mostly transcriptionally quiescent, suggesting that most mRNAs are primed prior to cercarial escape from the snail host. The use of transcriptomics to understand protein expression presumes that transcription and translation are functionally coupled and the cercarial stage has categorically been treated as a single unit for -omic analysis. Per contra, the relationship between transcription and translation in infectious cercariae has not been described. To understand the correlation between transcription and translation in cercariae, we separately measured nascent translation levels in cercarial heads, cercarial tails and in the developing schistosomula, the next stage of its life cycle. The loss of the cercarial tail is essential for the transformation from a cercaria to a schistosomulum. We observed that translation was initially limited and the translation rate accelerated during the first 72-hours after tail loss. When we tested nascent translation in cercarial heads, cercarial tails, whole cercariae, and 4-hour schistosomula, we found that translation is significantly upregulated in the cercarial tail when compared to the cercarial head and that translation was undetectable in heads using immunofluorescent image quantification (p = .0005). These data represent a major shift in how we understand the cercarial stage. The cercarial head is mostly transcriptionally and translationally quiescent while being sufficient for progression into a schistosomulum. In addition, transcription and translation are not linked in Schistosoma mansoni cercaria. Thus, our current conceptual approach of treating the cercaria as a single functional unit for -omic studies may be insufficient to understand cercarial development.

Having bird schistosomes in mind-the first detection of Bilharziella polonica (Kowalewski 1895) in the bird neural system.

Nasal bird schistosomes can cause bilharziosis in birds and have the potential to cause swimmer's itch in humans. We determined the prevalence of bird schistosomes in 106 mallards (Anas plathyrhynchos) from 11 water sources in Germany from 2014. Dissections were performed focusing on parasitic infections of the neural system. Infections with Trichobilharzia regenti (Horák et al. 1998) were found in 21% of the birds (n = 22), whereas Bilharziella polonica (Kowalewski 1895) were found between the brain membranes (meninges) and the brain, in the spinal cord or in the intestine of 12% of the mallards (n = 13). No significant influence of sex, age, and body condition between infected and non-infected animals was observed. Our study provides the first description of B. polonica from the neural system of birds and provides an epidemiological understanding of a parasite of human health concern.

Historical analysis of the type species of the genus Trichobilharzia Skrjabin et Zakharov, 1920 (Platyhelminthes: Schistosomatidae).

Trichobilharzia Skrjabin & Zakharov, 1920 is known as the most species-rich genus of the blood fluke family Schistosomatidae. To date, more than 40 species have been described, even though validity of some of them is questionable (Horák et al. 2002). Members of the genus use various birds as final hosts, but they attract attention mostly as causative agents of hypersensitive skin reaction (cercarial dermatitis or swimmer's itch) in mammals including humans. As this is one of the.

Schistosomes with wings: how host phylogeny and ecology shape the global distribution of Trichobilharzia querquedulae (Schistosomatidae).

Migratory waterfowl play an important role in the maintenance and spread of zoonotic diseases worldwide. An example is cercarial dermatitis, caused when larval stages of schistosomes that normally develop in birds penetrate human skin. Members of the genus Trichobilharzia (Schistosomatidae), transmitted mainly by ducks, are considered to be major etiological agents of cercarial dermatitis globally. To better understand the diversity and distribution of Trichobilharzia spp., we surveyed ducks from the United States, eastern Canada, Argentina, South Africa and New Zealand. To aid in species identification of the Trichobilharzia worms recovered, regions of the Cox1, ND4 and ITS1 were sequenced. Furthermore, we provide molecular phylogenetic evidence for the cosmopolitan distribution and trans-hemispheric gene flow for one species, Trichobilharzia querquedulae, previously thought to be restricted to North America. These new samples from endemic non-migratory duck species indicate that T. querquedulae transmission occurs within each of the regions we sampled and that it is specific to the blue-winged+silver teal duck clade. Prevalence within this host group is >95% across the known range of T. querquedulae, indicating that transmission is common. Genetic divergence is evenly distributed among continents, and no phylogenetic structure associated with geography was observed. The results provide strong support for the global distribution and transmission of T. querquedulae and represent, to our knowledge, the first report of a cosmopolitan schistosome confirmed by genetic data. These data are the first known to support trans-hemispheric genetic exchange in a species responsible for causing cercarial dermatitis, indicating that the epidemiology of this group of poorly known zoonotic parasites is more complex than previously expected.

Pathophysiological responses to a schistosome infection in a wild population of mourning doves (Zenaida macroura).

The blood trematode Gigantobilharzia huronensis typically infects passerine birds and has not been reported in other orders of wild birds. However, in the summer of 2011 in Tempe, Arizona, USA, mourning doves (Zenaida macroura; order: Columbiformes) were collected with infections of G. huronensis. This is the first report of a natural schistosome infection found in wild populations of doves. We sought to determine if G. huronensis infections alter the general body condition and physiology of doves, a seemingly unlikely host for this parasite. Specifically, we hypothesized that birds infected with schistosomes would exhibit reduced weight as well as increased markers of stress and immune system activation. Adult male mourning doves (n=14) were captured using walk-in style funnel traps. After weighing the birds, blood and mesenteric tissue samples were collected. We measured biomarkers of stress including circulating heat shock proteins (HSPs) 60 and 70, as well as oxidized lipoproteins in schistosome-infected and non-infected birds. Indices of immune system reactivity were assessed using agglutination and lysis assays in addition to determining the leukocyte to erythrocyte ratios and prevalence of hemoparasite infections from blood smears. Schistosome-infected mourning doves had significantly increased oxidative stress and evidence of HSP70 mobilization. There was no evidence for weight loss in schistosome-infected birds nor evidence of significant immune system activation associated with schistosome infection. This may be a reflection of the small sample size available for the study. These findings suggest that schistosome infections have pathological effects in doves, but the lack of mature worms suggests that infected birds in this sampling may not have been suitable hosts for parasite maturation.

Distribution and characterization of Heterobilharzia americana in dogs in Texas.

Heterobilharzia americana is a trematode parasite (family Schistosomatidae) that infects a wide range of wild mammalian hosts. Canine cases have been reported in the Gulf coast and south Atlantic states, Kansas, and Oklahoma. A total of 238 canine H. americana cases in Texas were retrospectively collected for a period of approximately 22 years from case records at the Texas Veterinary Medical Diagnostic Laboratory and the Veterinary Medical Teaching Hospital pathology service, diagnostic parasitology service, and Gastrointestinal Laboratory at Texas A&M University College of Veterinary Medicine. Of these cases, 26 patients had 1-2 repeat positive tests for a total of 268 positive tests (26 biopsies, 39 necropsies, 160 fecal examinations, and 43 PCR). Multiple dogs were infected in 12 households. Cases were distributed primarily in the eastern region of Texas in 42 of 254 counties. Cases were seen as far west as Kerr county and in counties bordering Oklahoma, Louisiana, Mexico, and the Gulf of Mexico. The median dog age was 5.6 years (2.7 months to 17.2 years) and the median weight was 20.5 kg (1-61.6 kg). All American Kennel Club (AKC) breed groups were represented (n=186): crossbred (20%), herding (17.8%), sporting (16.1%), toy (10.8%), hounds (10.8%), working (10.1%), terrier (8.5%), non-sporting (4.9%), and miscellaneous (1%). No seasonal pattern of diagnosis was apparent. Clinical signs reported (n=90) were diarrhea (67%), weight loss (38%), anorexia/hyporexia (27%), vomiting (22%), hematochezia (20%), lethargy (17%), polyuria/polydipsia (6%), and collapse (3%). In 39 necropsy cases, trematode eggs were identified by histopathology in the small intestine (84%), liver (84%), large intestine (39%), pancreas (35%), lung (9%), lymph node (8%), spleen (4%), and stomach (3%). Adult parasites were identified histologically in four cases. Granulomatous inflammation associated with the eggs was the most commonly reported histopathologic change. Other changes reported were fibrosis, pigment in macrophages, and organ mineralization. Glomerulonephritis was identified in four cases. Of 20 necropsy cases where death was attributable to H. americana infection, only one case was diagnosed ante mortem. Eleven of these dogs were examined by a veterinarian but H. americana was included as a differential diagnosis in only two cases. Reported differential diagnoses included ethylene glycol toxicity, cholecalciferol toxicity, lymphoma, and pancreatitis. These data indicate that this parasite is more widely distributed and more common than is generally recognized. Increased awareness may aid in more diagnoses and timely therapy.

Discovery-based studies of schistosome diversity stimulate new hypotheses about parasite biology.

This review provides an update of ongoing efforts to expand our understanding of the diversity inherent within the Schistosomatidae, the parasites responsible for causing schistosomiasis and cercarial dermatitis. By revealing more of the species present, particularly among understudied avian schistosomes, we gain increased understanding of patterns of schistosome diversification, and their abilities to colonize new hosts and habitats. Schistosomes reveal a surprising ability to switch into new snail and vertebrate host species, into new intrahost habitats, and may adopt novel body forms in the process. Often these changes are not associated with deep splits or long branches in their phylogeny, suggesting some are of relatively recent origin. Several hypotheses prompted by the new observations are discussed, helping to focus thinking on processes influencing not only schistosome diversification but also their pathogenicity and abundance.

Hosts, parasites, and horizontal gene transfer.

Mendelian inheritance transfers genes vertically within lineages, whereas horizontal gene transfer (HGT) moves genetic material between or among lineages. Herein, we explore possible mechanisms of HGT between parasites and their hosts, as their intimate contact affords substantial opportunities for HGT. We review studies of host-parasite HGT, discussing their merits, their shortcomings, and the multiple lines of evidence needed to conclusively document HGT while avoiding false positives. We focus mainly on schistosomes and other parasites with complex life cycles as they provide numerous opportunities for HGT among the parasite, intermediate, and definitive host genomes. We also highlight future research directions that could prove illuminating with regard to the occurrence, prevalence, and overall importance of HGT in host-parasite coevolution.

[Trematodes of birds (Aves) from the Middle Volga region. 2. Orders Plagiorchiida, Renicolida, Strigeida, and Schistosomatida].

Data on trematodes of Plagiorchiida, Renicolida, Strigeida, and Schistosomatida, parasitizing in birds of the Middle Volga region are given. Proceedings of the different authors are supplemented by results of our research. Two species of trematodes (Brachylaima mesostoma and Mosesia amplavaginata) are specified for birds of the middle Volga region for the first time. New hosts were revealed for 2 trematode species: the great tit for Plagiorchis laricola and the common chaffinch for M. amplavaginata. The following characteristics for each parasite are given: it's systematic position, the spectrum of hosts, localization, collecting site, biology, the degree of host specificity and geographical range. The morphological description and original figures of 11 species of trematodes are presented.

New intermediate host records for the avian schistosomes Dendritobilharzia pulverulenta, Gigantobilharzia huronensis, and Trichobilharzia querquedulae from North America.

Here we provide the first North American report of a naturally infected snail, Gyraulus parvus, harboring the larval stages of the cosmopolitan, arterial schistosome, Dendritobilharzia pulverulenta. The relatively small cercariae of this species are shed in the early morning, are sticky, and adhere to the water's surface film. We also provide a report of the snail host, Physa gyrina, of the widespread North American passerine schistosome, Gigantobilharzia huronensis. Finally, we provide unambiguous documentation that Physa gyrina is a natural snail host for Trichobilharzia querquedulae, a schistosome primarily of dabbling ducks.

Morphology, biology and taxonomy of Dendritobilharzia loossi Skrjabin, 1924 (Trematoda: Bilharziellidae), a parasite of Pelecanus onocrotalus (Pelecanidae) and Anas plathyrinchos (Anatidae).

Life cycles of Dendritobilharzia loossi Skrjabin, 1924, a parasite of waterbirds, and its morphobiological traits are studied and described. Mollusks Anisus spirorbis, the infection rate of which in natural environments reaches 1.3-1.9%, were recorded as intermediate hosts under conditions of Uzbekistan. The development of this trematode in intermediate and definitive hosts lasts for 26 and 15 days, respectively. Diagnostic traits of the trematodes during all stages of their ontogeny are reviewed.

Mating system drives negative associations between morphological features in Schistosomatidae.

BACKGROUND: Sexual morphological features are known to be associated with the mating systems of several animal groups. However, it has been suggested that morphological features other than sexual characteristics could also be constrained by the mating system as a consequence of negative associations. Schistosomatidae are parasitic organisms that vary in mating system and can thus be used to explore links between the mating system and negative associations with morphological features. RESULTS: A comparative analysis of Schistosomatidae morphological features revealed an association between the mating system (monogamous versus polygynandrous) and morphological characteristics of reproduction, nutrition, and locomotion. CONCLUSIONS: The mating system drives negative associations between somatic and sexual morphological features. In monogamous species, males display a lower investment in sexual tissues and a higher commitment of resources to tissues involved in female transport, protection, and feeding assistance. In contrast, males of polygynandrous species invest to a greater extent in sexual tissues at the cost of reduced commitment to female care.

Penetration of cercariae into the living human skin: Schistosoma mansoni vs. Trichobilharzia szidati.

We studied the skin invasion of Schistosoma mansoni cercariae by placing gamma-irradiated and nonirradiated cercariae onto the living human skin and timing the behavior of 53 individuals. The skin invasion of S. mansoni was less efficient compared to the bird schistosome Trichobilharzia szidati. S. mansoni cercariae crept longer on the skin after attachment until they started penetration movements (median of 43 s [range of 15 s-6.58 min]; T. szidati, median of 8 s [range of 0-80 s]). Subsequent to this longer exploratory phase, 74% penetrated into wrinkles (T. szidati 84%), 22% into the smooth skin surface (T. szidati 0%), and 4% into hair follicles (T. szidati 16%). The S. mansoni cercariae needed, on average, 6.58 min (range of 1.57-13.13 min) for full entry, while T. szidati needed 4.0 min (range of 1.38-13.34 min); the fastest S. mansoni cercaria entered the skin within 94 s, while T. szidati entered within 83 s. Sixty percent of the S. mansoni cercariae had the tails still attached when the bodies disappeared in the skin whereas all T. szidati cercariae shed their tails within 0-105 s after the onset of penetration movements. The faster invasion of T. szidati may result from the more sophisticated host-finding mechanisms of this species. Regarding S. mansoni, cercarial dermatitis, as immediate skin response, developed after a sensitization period of 19 days.

Orientobilharzia species: neglected parasitic zoonotic agents.

Parasites of the genus Orientobilharzia belong to Platyhelminthes, Trematoda, Digenea, Schistosomatidae, and the type species is Orientobilharzia turkestanicum. O. turkestanicum was first described by Skrjabin from cattle in Russian Turkestan in 1913. Adult worms of Orientobilharzia species live in the portal veins or intestinal veins of cattle, sheep and other mammals, and often cause orientobilharziasis in China, India, Mongolia, Pakistan, Iraq, Iran in Asia, and Russia and Turkey in Europe. More importantly, the cercariae of Orientobilharzia species can infect humans and often cause cercarial dermatitis. Though Orientobilharzia species have been confirmed as zoonotic agents, they have been largely neglected, compared with other pathogens causing cercarial dermatitis, such as Trichobilharzia spp., Schistosoma spindale and Bilharziella sp., which have attracted considerable attention. Here we review the current status of knowledge on the taxonomy of Orientobilharzia spp., human and animal infections with Orientobilharzia spp., and address some considerations for further work on the systematics and pathogenesis of these organisms.