Bird schistosomes: do they die in mammalian skin?

The cercariae of bird schistosomes, released from the intermediate water snail host, actively penetrate the skin of both birds and mammals. Whereas in birds the infection leads to worm maturation and egg production, in the mammalian hosts skin invasion is accompanied by cercarial dermatitis (swimmer's itch, clam-digger's disease) and the fate of the parasites is not clear. Here, we review bird schistosomes as causative agents of cercarial dermatitis, underline adaptations of bird schistosomes to their life in vertebrate hosts, and discuss potential risks caused by the parasites migrating in humans.     

Clearance of schistosome parasites by resistant genotypes at a single genomic region in Biomphalaria glabrata snails involves cellular components of the hemolymph

Schistosomiasis is one of the most detrimental neglected tropical diseases. Controlling the spread of this parasitic illness requires effective sanitation, access to chemotherapeutic drugs, and control over populations of the freshwater snails, such as Biomphalaria glabrata, that are essential intermediate hosts for schistosomes. Effectively controlling this disease, while minimising ecological implications of such control, will require an extensive understanding of the immunological interactions between schistosomes and their molluscan intermediate hosts. Here we histologically characterise the clearance of schistosome larvae by snails that exhibit allelic variation at a single genomic region, the Guadeloupe resistance complex. We show that snails with a resistant Guadeloupe resistance complex genotype clear schistosomes within the first 24–48?h, and that this resistance can be transferred to susceptible snails via whole hemolymph but not cell-free plasma. These findings imply that Guadeloupe resistance complex-coded proteins help to coordinate hemocyte-mediated immune responses to schistosome infections in Guadeloupean snails.     

Sexing schistosome larvae

Biological and immunological factors may influence changes in sex ratios at different points of the schistosome life cycle, resulting in the fact that female schistosomes are significantly outnumbered by males in chronic infections of snails and mammalian hosts. Analysis of this phenomenon has long been hampered by shortcomings in the methods used to determine sex ratios. Here, Robin Gasser describes recently developed molecular methods for sexing schistosome larvae. These have opened the way towards understanding why sex ratios become male biased and allow a proper assessment of its consequences in the epidemiology, diagnosis and pathology of infection.     

Penetration of Trichobilharzia cercariae into mammals: dangerous or negligible event?

Bird schistosomes and cases of human cercarial dermatitis occur worldwide, but the number of cases is not monitored. Experiments with two schistosomes, namely Trichobilharzia szidati and T. regenti, show that they possess potent tools to penetration bird and mammalian skin, as well as exhibit species-specific migration patterns within vertebrate bodies. Therefore, the infections may affect different organs/tissues e.g. lungs or spinal cord. In this minireview, the adaptations and pathogenic effects of bird schistosomes in experimental mammals are discussed, and some ideas/hypotheses on risks to humans from exposure to bird schistosome cercariae are expressed.     

Failure of in vitro-cultured schistosomes to produce eggs: how does the parasite meet its needs for host-derived cytokines such as TGF-β?

When adult schistosome worm pairs are transferred from experimental hosts to in vitro culture they cease producing viable eggs within a few days. Female worms in unisexual infections fail to mature, and when mature adult females are separated from male partners they regress sexually. Worms cultured from the larval stage are also permanently reproductively defective. The cytokine transforming growth factor beta derived from the mammalian host is considered important in stimulating schistosome female worm maturation and maintenance of fecundity. The means by which schistosomes acquire TGF-β have not been elucidated, but direct uptake in vivo seems unlikely as the concentration of free, biologically active cytokine in host blood is very low. Here we review the complexities of schistosome development and male–female interactions, and we speculate about two possibilities on how worms obtain the TGF-β they are assumed to need: (i) worms may have mechanisms to free active cytokine from the latency-inducing complex of proteins in which it is associated, and/or (ii) they may obtain the cytokine from alpha 2-macroglobulin, a blood-borne protease inhibitor to which TGF-β can bind. These ideas are experimentally testable.     

Leaky livers, portal shunting and immunity to schistosomes

In mice, concomitant immunity to schistosomes seems to be largely dependent on factors that lack immunological specificity. In this review Alan Wilson describes the anatomical changes stimulated in the host's vasculature after the formation of granulomas around schistosome eggs in the liver. The blockage of portal venules by the granulomas leads to portal hypertension and the development of anastomoses that direct blood flow, schistosomula and eggs from the liver. An intact portal vasculature is required for schistosome maturation; some strains of mice appear to be resistant to schistosome infection because they have a predisposition to form anastomoses in the absence of infection.     

Schistosoma mansoni: TGF-beta signaling pathways

Schistosome parasites have co-evolved an intricate relationship with their human and snail hosts as well as a novel interplay between the adult male and female parasites. We review the role of the TGF-beta signaling pathway in parasite development, host-parasite interactions and male-female interactions. The data to date support multiple roles for the TGF-beta signaling pathway throughout schistosome development, in particular, in the tegument which is at the interface with the host and between the male and female schistosome, development of vitelline cells in female worms whose genes and development are regulated by a stimulus from the male schistosome and embryogenesis of the egg. The human ligand TGF-beta1 has been demonstrated to regulate the expression of a schistosome target gene that encodes a gynecophoric canal protein in the schistosome worm itself. Studies on signaling in schistosomes opens a new era for investigation of host-parasite and male-female interactions.     

Invasion by schistosome cercariae: neglected aspects in Schistosoma japonicum

Skin invasion by schistosome cercariae was recently discussed in Trends in Parasitology. However, only Schistosoma mansoni was considered, possibly because this species predominates in laboratory studies (at least outside China). One may be tempted to extrapolate from the "model" S. mansoni to other schistosomes, but Schistosoma japonicum must not be neglected. This schistosome is distinguishable from others (particularly S. mansoni) by virtue of its remarkable speed and success of migration, as well as by specific biochemical and immunological features. This leads to the hypothesis that S. japonicum is atypical with respect to the enzymes that facilitate skin penetration.     

Microarray Analysis of Gene Expression Profiles of Schistosoma japonicum Derived from Less-Susceptible Host Water Buffalo and Susceptible Host Goat

Background

Water buffalo and goats are natural hosts for S. japonicum in endemic areas of China. The susceptibility of these two hosts to schistosome infection is different, as water buffalo are less conducive to S. japonicum growth and development. To identify genes that may affect schistosome development and survival, we compared gene expression profiles of schistosomes derived from these two natural hosts using high-throughput microarray technology.

Results

The worm recovery rate was lower and the length and width of worms from water buffalo were smaller compared to those from goats following S. japonicum infection for 7 weeks. Besides obvious morphological difference between the schistosomes derived from the two hosts, differences were also observed by scanning and transmission electron microscopy. Microarray analysis showed differentially expressed gene patterns for parasites from the two hosts, which revealed that genes related to lipid and nucleotide metabolism, as well as protein folding, sorting, and degradation were upregulated, while others associated with signal transduction, endocrine function, development, immune function, endocytosis, and amino acid/carbohydrate/glycan metabolism were downregulated in schistosomes from water buffalo. KEGG pathway analysis deduced that the differentially expressed genes mainly involved lipid metabolism, the MAPK and ErbB signaling pathways, progesterone-mediated oocyte maturation, dorso-ventral axis formation, reproduction, and endocytosis, etc.

Conclusion

The microarray gene analysis in schistosomes derived from water buffalo and goats provide a useful platform to disclose differences determining S. japonicum host compatibility to better understand the interplay between natural hosts and parasites, and identify schistosome target genes associated with susceptibility to screen vaccine candidates.     

持续性疾病流行和血吸虫病在多个脊椎动物宿主中的瞬时振动

血吸虫是一种寄生在脊椎动物上有助于消化的地方或血管中的寄生虫．它们共有复杂的生活史,其中包括中间阶段的软体动物和一个脊椎动物宿主．根据MacDonald和May的工作,我们研究了一个基于血吸虫生活史的多个时滞的动力学模型,并且包含了一个由May和Wo11house提出的交配函数,当我们改变交配函数中的一个参数,血吸虫病的动力学行为从一个持久的疾病传播变成了疾病消失．如果增加雌性血吸虫的成熬周期,或交配周期和产卵周期,我们能够观察到长时间疾病传播的瞬时振动,这说明了对疾病的预测不依赖在一个特定时间的疾病水平,而是依赖一个充分长时间的疾病水平。     

Transgenesis of schistosomes: approaches employing mobile genetic elements

Draft genome sequences for Schistosoma mansoni and Schistosoma japonicum are now available. However, the identity and importance of most schistosome genes have yet to be determined. Recently, progress has been made towards the genetic manipulation and transgenesis of schistosomes. Both loss-of-function and gain-of-function approaches appear to be feasible in schistosomes based on findings described in the past 5 years. This review focuses on reports of schistosome transgenesis, specifically those dealing with the transformation of schistosomes with exogenous mobile genetic elements and/or their endogenous relatives for the genetic manipulation of schistosomes. Transgenesis mediated by mobile genetic elements offers a potentially tractable route to introduce foreign genes to schistosomes, a means to determine the importance of schistosome genes, including those that could be targeted in novel interventions and the potential to undertake large-scale forward genetics by insertional mutagenesis.     

Update on paramyosin in parasitic worms

Paramyosin was first identified as a structural component of invertebrate muscle. Analysis of crude, native, adult schistosome worm preparations identified a highly immunogenic protein which was later identified as paramyosin. Early vaccination/challenge studies with native paramyosin produced encouraging levels of protective efficacy against schistosomes, which led to the question as to how a sub-tegumental (muscular) protein could provide a target for vaccine-mediated immunological attack. Immunolocalisation studies of schistosomes confirmed the presence of paramyosin within the post-acetabular glands of cercariae and on the tegumental surface of lung schistosomula. Here we present an update on the more recent research on paramyosin in parasitic worms that has focused primarily in two directions: (i) further testing of the vaccine potency of paramyosin against schistosomes and other parasitic worms; and (ii) characterisation of the protein at the molecular and biochemical levels.     

Mechanisms of immunity in hydatid disease: implications for vaccine development

The Echinococcus organisms, the cause of echinococcosis (hydatid disease), are parasitic helminths with life cycles involving a carnivorous definitive host (usually dog or fox) and an intermediate host (human, ungulate, or rodent). They are complex multicellular pathogens that, despite being under constant barrage by the immune system, are able to modulate antiparasite immune responses and persist and flourish in their mammalian hosts. Understanding how the immune system deals with these parasites is a major challenge. Recent application of modern molecular and immunological approaches has revealed insights on the nature of immune responses generated during the course of hydatid infection, although many aspects of the Echinococcus-host interplay remain unexplored. This review summarizes current understanding of the immunology of echinococcosis, indicates areas where information is lacking, and shows how knowledge of host protective immunity has been translated into the design and development of anti-Echinococcus vaccines for application in intermediate hosts.     

Biological methods for the control of freshwater snails

As a result of the advent of new drugs and diagnostic techniques, the emphasis in the control of schistosomiasis has changed from snail control to chemotherapy for infected individuals. However, chemotherapy does not prevent reinfection and there remains a need to reduce snail densities in human water supplies. In the past, treatment with molluscicides has proved ineffective, expensive and has had environmental drawbacks. Here, Henry Madsen describes research into alternative methods of snail control. As yet, little is known of the predators and parasites of schistosome intermediate hosts, but such agents could be suitable as biocontrol agents. To date, the most promising results have been obtained from experimental introductions of competitive snail species, but this strategy still has its drawbacks under many environmental conditions and the development of a universal method of biological control for the intermediate hosts of schistosomes is still a long way off.     

Bioenergetic theory predicts infection dynamics of human schistosomes in intermediate host snails across ecological gradients

Epidemiological dynamics depend on the traits of hosts and parasites, but hosts and parasites are heterogeneous entities that exist in dynamic environments. Resource availability is a particularly dynamic and potent environmental driver of within‐host infection dynamics (temporal patterns of growth, reproduction, parasite production and survival). We developed, parameterised and validated a model for resource‐explicit infection dynamics by incorporating a parasitism module into dynamic energy budget theory. The model mechanistically explained the dynamic multivariate responses of the human parasite Schistosoma mansoni and its intermediate host snail to variation in resources and host density. At the population level, feedbacks mediated by resource competition could create a unimodal relationship between snail density and human risk of exposure to schistosomes. Consequently, weak snail control could backfire if reductions in snail density release remaining hosts from resource competition. If resource competition is strong and relevant to schistosome production in nature, it could inform control strategies.     

Piggybacking schistosome invasion: similarities are only skin deep

Schistosomes cause significant morbidity and mortality. In this article, we discuss recent findings regarding how different schistosome species infect and manipulate immune responses in their hosts through the evolution and use of different protease classes. The advent of transgenic schistosomes is explored in relation to the biology of these important molecules.     

Discussion of the relationships between Schistosoma and their intermediate hosts, assessment of the degree of host-parasite compatibility and evaluation of schistosome taxonomy.

Studies of the spectrum of the intermediate hosts of schistosomes and the relationships between parasites and intermediate host snails have been carried out with each researcher using different methods. A comparison between compatibility studies has therefore been impossible. The following three basic problems in these kind of studies are discussed in this paper: (1) the standardization of experimental materials such as schistosomes, intermediate and final hosts, (2) the methods involved in the experiments, and (3) the sort of data which must be collected. Standardized methods and materials are described in this paper. The relationships between the genus Schistosoma and the intermediate host snails belonging to the two genera Biomphalaria and Bulinus, and the mechanisms behind the process resulting in various degrees of compatibility between the two involved organisms are reviewed and discussed. Why certain combinations of schistosomes and snails result in the production of cercariae and others do not is still unknown, but there is now some indication of a camouflage behaviour during the intramolluscan stages, e.g., the larvae in the snails cover themselves with snail material and are not recognized as foreign objects. The same mechanism has already been found in the schistosomules in the final host. Much of the confusion in the discussion of the relationships between schistosomes and intermediate hosts is the result of a lack of an objective way to describe and assess the compatibility between the two. Based on a series of experiments with S. haematobium, S. intercalatum, S. bovis, S. mansoni, and several species of possible intermediate hosts, the following index for estimating the degree of compatibility is proposed: the total cercarial production from 100 exposed snails (TCP/100 exposed snails). Seven classes have been suggested: the first one (Class 0) with a TCP/100 exposed snails of zero, is called 'refractory'; the next one (Class I) called 'not very compatible' has a TCP /100 exposed snails between 1 and 10,000; the last group (Class IV) called 'extremely compatible' produced more than 500,001 per 100 exposed snails during the entire lifespan. The ability to use a spectrum of intermediate hosts and the compatibility in the taxonomy of schistosomes is discussed. The results for the different species of schistosomes indicated that each species consists of strains with 'hybrid populations' in between.     

Helminth parasite proteomics: from experimental models to human infections

Schistosomiasis is a major human helminth infection endemic in developing countries. Urogenital schistosomiasis, caused by S. haematobium, is the most prevalent human schistosome disease in sub-Saharan Africa. Currently control of schistosome infection is by treatment of infected people with the anthelmintic drug praziquantel, but there are calls for continued efforts to develop a vaccine against the parasites. In order for successful vaccine development, it is necessary to understand the biology and molecular characteristics of the parasite. Ultimately, there is need to understand the nature and dynamics of the relationship between the parasite and the natural host. Thus, my studies have focused on molecular characterization of different parasite stages and integrating this information with quantitative approaches to investigate the nature and development of protective immunity against schistosomes in humans. Proteomics has proved a powerful tool in these studies allowing the proteins expressed by the parasite to be characterized at a molecular and immunological level. In this review, the application of proteomic approaches to understanding the human-schistosome relationship as well as testing specific hypotheses on the nature and development of schistosome-specific immune responses is discussed. The contribution of these approaches to informing schistosome vaccine development is highlighted.