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Background: Schistosomiasis, an ancient and neglected tropical disease, which poses a huge threat to over 200 million people globally. It is necessary to have a general summary of schistosomiasis research after the new roadmap 2021-2030 issued by WHO. This study analyzes the current status of schistosomiasis research from the perspective of the One Health concept by analyzing important research literature published from 2011 to 2020, while further highlighting research priorities, difficulties, and research directions in order to propose suggestions for tropical disease studies research., Methods: Published literature related to schistosomiasis was searched from the Web of Science Core Collection (WoSCC) database. Focusing on a visual analysis of the main research literature in the field of schistosomiasis, CiteSpace software was used to conduct co-occurrence analysis with keywords, countries, institutions, and authors. Moreover, clustering and burst analyses of keywords and co-citation analysis of authors, publications, and journals were performed., Results: A total of 6638 schistosomiasis-related articles were published from 2011 to 2020, all of which can be sourced from the WoSCC database. The publication of schistosomiasis research has remained stable over the past 10 years, and contains studies in the area of human epidemiology, animal surveillance and the environment. The top five high-frequency keywords included Schistosoma mansoni, schistosomiasis, infection, praziquantel, and Schistosoma japonicum. The keywords formed nine clusters, including praziquantel, epidemiology, Schistosoma japonicum, helminths, protein, diagnosis, schistosomiasis, response, and haematobium. In recent years, most research studies focused on the mechanism of liver fibrosis, eliminating schistosomiasis, controlling risk factors, and the relationship between schistosomiasis infection and host immunity. The most productive countries include the United States, China, and Brazil, and the most productive institutions are the University of Basel, the Swiss Tropical and Public Health Institute, and the University of São Paulo. Highly productive authors include Jürg Utzinger and Donald P. McManus. At the time of writing, the author with the highest co-citation frequency (993 times) was Peter Hotez, and the journal with the highest co-citation frequency (3,720 times) was PLoS Neglected Tropical Diseases. Human schistosomiasis, published by Colley et al. (2014), was the most frequently co-cited publication (494 times)., Conclusions: This study provides a preliminary description of the current status of schistosomiasis research and an initial exploration of future research directions. The One Health concept was applied in the field of schistosomiasis control, as confirmed by this bibliometric analysis. Our study provides guidance for the development of research on schistosomiasis and other neglected tropical diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Oncomelania hupensis snails along the Yangtze River and the low positive rate and infectiosity of human and livestock schistosomiasis still pose a threat to public health in China. Adult blood flukes were recognized as Schistosoma japonicum, which are found in the portal system of the sentinel mice bred in the laboratory for 35 days after contact with the water. However, 35 days was too long from the field test to dissection, and the dissection in the laboratory was also time-consuming and labor-intensive. Serum peptides in mice at different times after infection were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. ClinProTool was used to establish the proteomic detection pattern (PDP), based on the differentially expressed peptide between the infection and healthy control groups. Under experimental conditions, characteristic PDP were detected in 5 % (3/60), 35 % (21/60), 75 % (45/60), 87.93 % (51/58), and 98.15 % (53/54) of infected mice from weeks 1 to 5 post-infection, whereas ELISA and dissection examination for adult blood flukes missed the first 2 weeks. At 35 days post-infection, the infectiosity assay showed 40 % (4/10), 50 % (5/10), and 80 % (8/10) positivity with the PDP test in mice infected with 4, 6, and 10 cercariae, respectively, as well as 100 % (10/10) positivity in mice infected with 14, 18, and 22 cercariae. Five stored sera of positive sentinel mice with parasite detection were verified correctly in the PDP test. The results confirm that PDP can be used as a rapid and early detection method for S. japonicum infection in experimental mice, which are expected to apply in early surveillance for schistosomiasis.

As one of the three major human pathogens that cause schistosomiasis, Schistosoma japonicum is the only one that is endemic in China. Despite great progress on schistosomiasis control over the past 50 years in China, S. japonicum transmission still occurs in certain endemic regions, which causes significant public health problems and enormous economic losses. During different life stages, parasites are able to survive dramatic osmolality changes between its vector, fresh water, and mammal host. However, the molecular mechanism of parasite osmoregulation remains unknown. To address this challenging question, we report the first cloning of an S. japonicum aquaglyceroporin (SjAQP) from an isolate from Jiangsu province, China. Expressing SjAQP in Xenopus oocytes facilitated the permeation of water, glycerol, and urea. The water permeability of SjAQP was inhibited by 1 mM HgCl 2 , 3 mM tetraethylammonium, 1 mM ZnCl 2 , and 1 mM CuSO 4 . SjAQP was constitutively expressed throughout the S. japonicum life cycle, including in the egg, miracidia, cercaria, and adult stages. The highest expression was detected during the infective cercaria stage. Our results suggest that SjAQP plays a role in osmoregulation throughout the S. japonicum life cycle, especially during cercariae transformation, which enables parasites to survive osmotic challenges.

Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following S. japonicum infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by S. japonicum infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Metabolomics, as an emerging technology, has been demonstrated to be a very powerful tool in the study of the host metabolic responses to infections by parasites. Schistosomiasis is a parasitic infection caused by schistosoma worm via the direct contact with the water containing cercaria, among which Schistosoma japonicum (S. japonicum) is endemic in Asia. In order to characterize the schistosome-induced changes in the host metabolism and further to develop the strategy for early diagnosis of schistosomiasis, we performed comprehensive LC-MS-based metabolomics analysis of serum from mice infected by S. japonicum for 5 weeks. With the developed diagnosis strategy based on our metabolomics data, we were able to successfully detect schistosomiasis at the first week post-infection, which was 3 weeks earlier than "gold standard" methods and 2 weeks earlier than the methods based on 1H NMR spectroscopy. Our metabolomics study revealed that S. japonicum infection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, DNA and RNA biosynthesis, phospholipid metabolism, depression of energy metabolism, glucose uptake and metabolism, and disruption of gut microbiota metabolism. In addition, we identified seventeen specific metabolites whose down-regulated profiles were closely correlated with the time-course of schistosomiasis progression and can also be used as an indicator for the worm-burdens. Interestingly, the decrease of these seventeen metabolites was particularly remarkable at the first week post-infection. Thus, our findings on mechanisms of host-parasite interaction during the disease process pave the way for the development of an early diagnosis tool and provide more insightful understandings of the potential metabolic process associated with schistosomiasis in mice. Furthermore, the diagnosis strategy developed in this work is cost-effective and is superior to other currently used diagnosis methods. [ABSTRACT FROM AUTHOR]

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Abstract: Objective: The objective of this study was to identify proteomic patterns in sera for the early detection of Schistosoma japonicum infections in a rabbit model. Proteomic patterns were to be established by profiling serum proteins using magnetic bead (MB) separation and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods: Forty rabbits were randomly allocated to two groups. One group was infected with 1500 S. japonicum cercariae, the other served as non-infected control. An additional group of Toxoplasma gondii-infected rabbits served as specificity control group. Sera were obtained from each rabbit once a week post-infection and were subject to weak cation exchange beads (MB-WCX) treatment, followed by MALDI-TOF MS analysis. The proteomic pattern of infected and control rabbits was established 7 weeks post-infection with the ClinProTool MS data analysis program. Results: Seven peaks with a clear difference in amplitude between the infected and control groups were detected, 4 peaks with mass charge ratio (m/z) of 1787, 2834, 3484 and 3531 were up-regulated and 3 peaks with a m/z of 1715, 3151 and 4018 were down-regulated in infected rabbits. The established diagnostic proteomic pattern was highly sensitive and specific. In weeks 1–4 post-infection, characteristic proteomic patterns could be detected in 30%, 55%, 75% and 80% of the infected rabbits, whereas ELISA testing resulted in positive results from week 3 onwards. All T. gondii control sera were classified S. japonicum negative. Conclusions: MALDI-TOF MS coupled with MB separation enables early, rapid and accurate diagnosis of schistosomiasis in a rabbit model. [ABSTRACT FROM AUTHOR]