Schistosomiasis, one of the neglected tropical diseases which affects both humans and animals, is caused by trematode worms of the genus Schistosoma. The disease is caused by several species of Schistosoma which affect several organs such as urethra, liver, bladder, intestines, skin and bile ducts. The life cycle of the disease involves an intermediate host (snail) and a mammalian host. It affects people who are in close proximity to water bodies where the intermediate host is abundant. Common clinical manifestations of the disease at various stages include fever, chills, headache, cough, dysuria, hyperplasia and hydronephrosis. To date, most of the control strategies are dependent on effective diagnosis, chemotherapy and public health education on the biology of the vectors and parasites. Microscopy (Kato-Katz) is considered the golden standard for the detection of the parasite, while praziquantel is the drug of choice for the mass treatment of the disease since no vaccines have yet been developed. Most of the previous reviews on schistosomiasis have concentrated on epidemiology, life cycle, diagnosis, control and treatment. Thus, a comprehensive review that is in tune with modern developments is needed. Here, we extend this domain to cover historical perspectives, global impact, symptoms and detection, biochemical and molecular characterization, gene therapy, current drugs and vaccine status. We also discuss the prospects of using plants as potential and alternative sources of novel anti-schistosomal agents. Furthermore, we highlight advanced molecular techniques, imaging and artificial intelligence that may be useful in the future detection and treatment of the disease. Overall, the proper detection of schistosomiasis using state-of-the-art tools and techniques, as well as development of vaccines or new anti-schistosomal drugs may aid in the elimination of the disease.

There is a great need to understand the impact of complex communities on the free-living parasite stages that are part of them. This task becomes more complex as nonnative species emerge, changing existing relationships and shaping new interactions in the community. A relevant question would be: Can the coexistence of nontarget snails with the target hosts contribute to trematodasis control? We used field and experimental approaches to investigate nonnative competitor-induced parasite dilution. During a three-year field study, we investigated digenean infection in Lymnaea stagnalis from eight Polish lakes inhabited or uninhabited by Potamopyrgus antipodarum. Additionally, we verified the presence of digenean infections in the populations of P. antipodarum. Moreover, we conducted an experimental infection of L. stagnalis with miracidia of Trichobilharzia szidati under increasing densities of P. antipodarum and aimed to infect P. antipodarum with them separately. The prevalence of avian schistosomes in lymnaeid snails was significantly higher in uninhabited lakes than in lakes inhabited by P. antipodarum. Our study indicates that waters with a higher density of invaders have a lower prevalence of avian schistosomes in lymnaeid hosts. The results of experimental studies confirmed that the presence of high densities of P. antipodarum reduces the probability of target host infection. Both field and experimental studies rule out the role of P. antipodarum as a source of avian schistosome cercariae. Here, a nonnative species was tested as a diluter, which in practice may be harmful to the local environment. This work is not a call for the introduction of nonnative species; it is intended to be a stimulus for researchers to continue searching for natural enemies of parasites because, as our results show, they exist. Finding natural enemies to the most dangerous species of human and animal parasites that will pose no threat to the local environment could be groundbreaking.

In this study, a simple and efficient miracidium hatching technique (MHT) protocol for preparing a single-genome DNA of Schistosoma japonicum was proposed. The protocol was designed with 96-well plates to collect a miracidium for single-genome DNA preparation, and the effects of lighting conditions on hatching rates were evaluated. The highest hatching rate was recorded under sunlight (92.4%), followed by fluorescent light (88.0%), and the lowest rate was recorded under the dark condition (4.7%). The results suggested for the first time, to our knowledge, that sunlight was efficient for this simple MHT protocol. Successful amplification of microsatellite marker genes using DNA isolated from a single miracidium also confirmed the quality of the single-genome DNA for subsequent applications.

The identification of extracellular vesicles (EVs) in Fasciola hepatica has provided a new way to understand parasite-host communication. Most of the studies on EVs have focused on the adult stage of F. hepatica, but recently, the presence of EVs from different developmental stages has been reported. To better understand the potential role of EVs in the biology of the parasite and in the infection process, the protein cargo of EVs from embryonated eggs and newly-excysted juvenile (NEJs) flukes cultured up to 28 days, has been analyzed. EVs were isolated by size exclusion chromatography and evaluated by nanoparticle tracking analysis and transmission electron microscopy. LC-MS/MS proteomic analysis of EVs revealed the presence of 23 different proteins from embryonated egg-derived EVs and 29 different proteins from NEJ-derived EVs. Most of the identified proteins had been previously described in EVs from F. hepatica adults, including cytoskeletal proteins, glycolytic enzymes, stress-related proteins and tetraspanins. Nevertheless, EVs from hatching eggs and NEJs exhibited qualitative differences in composition, when compared to EVs form adults, including the absence of cathepsin cysteine peptidases. The differential content of the EVs released by the different developmental stages of the parasite reflect the intense activity of NEJs at this early stage, with several proteins involved in membrane traffic and cell physiology. This new set of identified proteins could help to understand key metabolic, biochemical and molecular mechanisms mediated by EVs that take place upon egg hatching and after parasite excystment.

Schistosoma mansoni is the main causative agent of intestinal schistosomiasis which affects millions of people worldwide. At the larval stage, miracidia are released into bodies of water where they utilize their motility to successfully infect their intermediate host, snails. Here, we revisit the motility and survival of S. mansoni miracidia throughout its life span. Briefly, miracidia motility was monitored at 30-min and 60-min intervals under the presence/absence of natural/artificial light. Based on a subjective evaluation of activity, body shape and transparency, 6 categories of miracidia activity were established from its fully active stage to its immobile larva stage. The estimated life span of miracidia was 5.8 and 3.5 h in the experiments with 60-min and 30-min observation intervals, respectively. Death was defined by an absence of cilia and body movement. When mobility was used as a proxy for infectivity, infective miracidia were detected at 2.5 and 4.5 h, respectively. The present miracidia motility and survival re-evaluation supports parameters optimization for computational modelling of schistosomiasis transmission dynamics. Target control interventions, especially at late stages next to transmission interruption, may greatly benefit from improved modelling studies.

Fasciolosis is a zoonotic parasitic disease caused by the trematode Fasciola hepatica. The proteases are essential for the survival of parasites. The present study was aimed to determine serine proteases activities in miracidia of F. hepatica and evaluate the effects of pH and different inhibitors on the serine proteases activities. Adult F. hepatica helminths were removed from naturally infected livers of the slaughtered cattle and crushed. The eggs were incubated at 28.00 ˚C for 16 days. The released miracidia were homogenized and total proteolytic activity of the extract of miracidia at different pH values were evaluated. Serine proteases activities were determined using specific substrates. The inhibitory effects of chemical and herbal inhibitors on the enzymes were also assessed. The extract of miracidia hydrolyzed azocasein with optimum activity at pH 8.00. The optimum pH effect on serine proteases activities was found at alkaline pH. Phenylmethylsulfonyl fluoride and Bowman-Birk inhibitors inhibited and decreased the proteases activities in the miracidia extract. It was concluded that there were proteases activities in miracidia of F. hepatica which were inhibited by chemical and herbal inhibitors.

Schistosome eggs provoke the formation of granulomas, organized immune aggregates, around them. For the host, the granulomatous response can be both protective and pathological. Granulomas are also postulated to facilitate egg extrusion through the gut lumen, a necessary step for parasite transmission. We used zebrafish larvae to visualize the granulomatous response to Schistosomamansoni eggs and inert egg-sized beads. Mature eggs rapidly recruit macrophages, which form granulomas within days. Beads also induce granulomas rapidly, through a foreign body response. Strikingly, immature eggs do not recruit macrophages, revealing that the eggshell is immunologically inert. Our findings suggest that the eggshell inhibits foreign body granuloma formation long enough for the miracidium to mature. Then parasite antigens secreted through the eggshell trigger granulomas that facilitate egg extrusion into the environment. In support of this model, we find that only mature S. mansoni eggs are shed into the feces of mice and humans.

No effective method has yet been developed to prevent the threat posed by the emerging disease-cercarial dermatitis (swimmer\'s itch), caused by infective cercariae of bird schistosomes (Digenea: Schistosomatidae). In our previous studies, the New Zealand mud snail-Potamopyrgus antipodarum (Gray, 1853; Gastropoda, Tateidae)-was used as a barrier between the miracidia of Trichobilharzia regenti and the target snails Radix balthica. Since the presence of non-indigenous snails reduced the parasite prevalence under laboratory conditions, we posed three new research questions: (1) Do bird schistosomes show totally perfect efficacy for chemotactic swimming behavior? (2) Do the larvae respond to substances emitted by incompatible snail species? (3) Do the excretory-secretory products of incompatible snail species interfere with the search for a compatible snail host? The experiments were carried out in choice-chambers for the miracidia of T. regenti and T. szidati. The arms of the chambers, depending on the variant, were filled with water conditioned by P. antipodarum, water conditioned by lymnaeid hosts, and dechlorinated tap water. Miracidia of both bird schistosome species chose more frequently the water conditioned by snails-including the water conditioned by the incompatible lymnaeid host and the alien species, P. antipodarum. However, species-specific differences were noticed in the behavior of miracidia. T. regenti remained more often inside the base arm rather than in the arm filled with water conditioned by P. antipodarum or the control arm. T. szidati, however, usually left the base arm and moved to the arm filled with water conditioned by P. antipodarum. In conclusion, the non-host snail excretory-secretory products may interfere with the snail host-finding behavior of bird schistosome miracidia and therefore they may reduce the risk of swimmer\'s itch.

UNASSIGNED: Fascioliasis is a worldwide zoonotic disease caused by the trematodes Fasciola hepatica in humans and animals. Proteases are essential for the survival of parasites and have important activities such as penetration, tissue migration, and egg hatching. This study was conducted to analyze cysteine protease of the miracidia and eggs of F. hepatica, and to assess the effects of pH and temperature on the proteases activity and stability.
UNASSIGNED: Adults F. hepatica were isolated from infected livers and were morphologically identified in 2018. Eggs collected from the adults and incubated in distilled water at 28 °C for 16 d to produce miracidia. The extract was collected from miracidia and eggs. A substrate for cathepsin B (Z-Arg-Arg-Pna) was used to assess the enzyme activity at different (2-12) pH levels. After homogenization, protein level was measured with Bradford method. Estimation of optimum temperature and pH was performed in the temperature range of 10-90 ° C and pH values from 2-12.
UNASSIGNED: The highest activity of the miracidia and eggs enzyme extracts for Z-Arg-Arg-pNA was at pH 4. The miracidia extract was most stable at neutral pH and the eggs extract was most stable in acidic pH. The optimum temperature activity for both stages was 40 °C. These proteases were stable up to 40 °C.
UNASSIGNED: Upon the importance of pH and temperature in the life cycle of F. hepatica, the current findings can be used for induction of some modifications in pH and preventing the activity of the enzymes for decrement of the efficacy of miracidia penetration into the intermediate snails and egg hatching of this zoonotic parasite.

Tropical diseases remain severe threats to global health with acute or chronic debility. Public health issues are regularly monitored and reported by the WHO. Conditions with high prevalence and virulence such as Schistosomiasis or Malaria still need active treatment. Advances over the decades in the treatment and management of Schistosomiasis have reduced morbidity and mortality in patients. However, poverty, adverse environments, lack of education and awareness, with parasites and vectors that can thrive if uncontrolled, remain issues for the successful global eradication of Schistosomiasis. From the disease\'s discovery in 1850, the author relates historical details to its current status. Several countries previously affected, including Japan and Tunisia, have eliminated the disease while others seek the same goal. Africa remains the most severely affected continent with vulnerable women and children, although the infection persists in South America and the Far East of Asia as well. Realistic improvements for continuing health conditions are vogue and emphasized for those at risk or afflicted by the infection, illustrating success models of concerted efforts of extirpation. Constant proximity to infected water, with a parasite host, are hurdles in reducing exposure. Effective medication for acute treatment is available, and prophylaxis by vaccination is promising. Where endemic Schistosomiasis is prevalent, significant morbidity and mortality have far-reaching complications in multiple human organ systems, including irreversible pulmonary hypertension, renal, genitourinary, central nervous system conditions, and neoplasia. Two hundred and thirty million people are estimated to have contracted Schistosomiasis globally, with up to 700 million still at risk of infection, and 200,000 deaths occur annually. The disease may be more prevalent than thought after newer tests have shown increased sensitivity to pathological antigens. The author discusses infectivity risks, investigations, prognosis, treatment, and management, as well as morbidity and mortality.