Transmission-Blocking Vaccines against Schistosomiasis Japonica.

Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.

Schistosoma japonicum Tyrosine Hydroxylase is promising targets for immunodiagnosis and immunoprotection of Schistosomiasis japonica.

Identification of promising schistosome antigen targets is crucial for the development of anti-schistosomal strategies. Schistosomes rely on their neuromuscular systems to coordinate important locomotory behaviors. Tyrosine hydroxylase (TH) is critical in the initial rate-limiting step in biosynthesis of catecholamine, the important neuroactive agents, which promote the lengthening of the worm through muscular relaxation and are therefore of great importance to the movement of the organism both within and between its hosts. THs from both Schistosoma mansoni and Schistosoma japonicum and their enzyme activities have been discovered; however, the role of these proteins during infection have not been explored. Herein, a recombinant protein of the nonconserved fragment of S. japonicum TH (SjTH) was produced and the corresponding polyclonal antibody was generated. The expression and antigenicity of SjTH were detected by qRT-PCR, western blotting, immunofluorescence assays, and ELISA. Mice immunized with the recombinant SjTH were challenged with cercariae to evaluate the immunoprotective value of this protein. Our results showed SjTH not only distributed in the head associated with the central nervous system, but also expressed along the tegument and the intestinal intima, which are involved in the movement, coupling and digestion of the parasites and associated with the peripheral nervous system. This protein can effectively stimulate humoral immune responses in mammalian hosts and has high potential as a biomarker for schistosomiasis immunodiagnosis. Furthermore, immunization with recombinant SjTH showed to reduce the worm and egg burden of challenged mice, and to contribute to the systemic balance of the Th1/Th2 responses. Taken together, these results suggest that SjTH is an important pathogenic molecule in S. japonicum and may be a possible target for anti-schistosomal approaches.

Open-source environmental data as an alternative to snail surveys to assess schistosomiasis risk in areas approaching elimination.

BACKGROUND: Although the presence of intermediate snails is a necessary condition for local schistosomiasis transmission to occur, using them as surveillance targets in areas approaching elimination is challenging because the patchy and dynamic quality of snail host habitats makes collecting and testing snails labor-intensive. Meanwhile, geospatial analyses that rely on remotely sensed data are becoming popular tools for identifying environmental conditions that contribute to pathogen emergence and persistence. METHODS: In this study, we assessed whether open-source environmental data can be used to predict the presence of human Schistosoma japonicum infections among households with a similar or improved degree of accuracy compared to prediction models developed using data from comprehensive snail surveys. To do this, we used infection data collected from rural communities in Southwestern China in 2016 to develop and compare the predictive performance of two Random Forest machine learning models: one built using snail survey data, and one using open-source environmental data. RESULTS: The environmental data models outperformed the snail data models in predicting household S. japonicum infection with an estimated accuracy and Cohen's kappa value of 0.89 and 0.49, respectively, in the environmental model, compared to an accuracy and kappa of 0.86 and 0.37 for the snail model. The Normalized Difference in Water Index (an indicator of surface water presence) within half to one kilometer of the home and the distance from the home to the nearest road were among the top performing predictors in our final model. Homes were more likely to have infected residents if they were further from roads, or nearer to waterways. CONCLUSION: Our results suggest that in low-transmission environments, leveraging open-source environmental data can yield more accurate identification of pockets of human infection than using snail surveys. Furthermore, the variable importance measures from our models point to aspects of the local environment that may indicate increased risk of schistosomiasis. For example, households were more likely to have infected residents if they were further from roads or were surrounded by more surface water, highlighting areas to target in future surveillance and control efforts.

Systematic review of applied mathematical models for the control of Schistosoma japonicum.

BACKGROUND: Schistosoma japonicum remains endemic in China and the Philippines. Substantial progress has been made in the control of Japonicum in both China and the Philippines. China is reaching elimination thanks to a concerted effort of control strategies. Mathematical modelling has been a key tool in the design of control strategies, in place of expensive randomised-controlled trials. We conducted a systematic review to investigate mathematical models of Japonicum control strategies in China and the Philippines. METHODS: We conducted a systematic review on July 5, 2020, in four electronic bibliographic databases - PubMed, Web of Science, SCOPUS and Embase. Articles were screened for relevance and for meeting the inclusion criteria. Data extracted included authors, year of publication, year of data collection, setting and ecological context, objectives, control strategies, main findings, the form and content of the model including its background, type, representation of population dynamics, heterogeneity of hosts, simulation period, source of parameters, model validation and sensitivity analysis. Results After screening, 19 eligible papers were included in the systematic review. Seventeen considered control strategies in China and two in the Philippines. Two frameworks were identified; the mean-worm burden framework and the prevalence-based framework, the latter of which increasingly common. Most models considered human and bovine definitive hosts. There were mixed additional elements included in the models, such as alternative definitive hosts and the role of seasonality and weather. Models generally agreed upon the need for an integrated control strategy rather than reliance on mass drug administration alone to sustain reductions in prevalence. CONCLUSIONS: Mathematical modelling of Japonicum has converged from multiple approaches to modelling using the prevalence-based framework with human and bovine definitive hosts and find integrated control strategies to be most effective. Further research could investigate the role of other definitive hosts and model the effect of seasonal fluctuations in transmission.

Evolution of tetraspanin antigens in the zoonotic Asian blood fluke Schistosoma japonicum.

BACKGROUND: Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host's immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. METHODS: SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. RESULTS: Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host's ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host's immune system. CONCLUSION: Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development.

Praziquantel promotes protection against Schistosoma japonicum infection in mice.

Praziquantel (PZQ) is the first line drug for the treatment of schistosomiasis. Several studies have confirmed that PZQ regulates host immunity, and we have recently found that pretreatment with PZQ enhances resistance against Schistosoma japonicum infection in buffaloes. We speculate that PZQ induces physiological changes in mice that prevent S. japonicum infection. To test this hypothesis and provide a practical measure to prevent S. japonicum infection, we determined the effective dose (the minimum dose), protection period and onset time of protection by comparing the worm burden, female worm burden and egg burden in PZQ-pretreated mice and blank control mice. Morphological differences between parasites were observed by measuring the total worm length, oral sucker, ventral sucker and ovary. The levels of cytokines, nitrogen monoxide (NO), 5-hydroxytryptamine (5-HT) and specific antibodies were measured using kits or soluble worm antigens. Hematological indicators on day 0 were analyzed in mice that received PZQ on days -15, -18, -19, -20, -21 and -22. The PZQ concentrations in plasma and blood cells were monitored using high performance liquid chromatography (HPLC). The effective dose was found to be two oral administrations (interval of 24 h) at 300 mg/kg body weight (BW) or one injection at 200 mg/kg BW, and the protection period of PZQ injection was 18 days. The optimal preventive effect was observed at two days post-administration, with a >92% worm reduction rate and significant worm reduction until 21 days after administration. Adult worms from PZQ-pretreated mice were runtish showing a shorter length, smaller organs and fewer eggs in the uteri of females. Detection of cytokines, NO, 5-HT and hematological indicators showed that PZQ induced immune-physiological changes, including higher levels of NO, IFN-γ and IL-2, and a lower level of TGF-ß. No significant difference in the anti-S. japonicum specific antibody levels was observed. The PZQ concentrations in plasma and blood cells 8 and 15 days post-administration were lower than the detection limit. Our results confirmed that pretreatment with PZQ promotes the protection of mice against S. japonicum infection within 18 days. Although we observed some immune-physiological changes in the PZQ-pretreated mice, the exact mechanisms involved in the preventive effect require further study.

First bovine vaccine to prevent human schistosomiasis - a cluster randomised Phase 3 clinical trial.

OBJECTIVE: Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection. METHODS: A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines. RESULTS: Overall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection. CONCLUSION: This is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178).

[Comparison of the efficiency of different etiological assays for detection of Schistosoma japonicum infections in wild mice].

OBJECTIVE: To compare the efficiency of multiple etiological techniques for detection of Schistosoma japonicum infections in wild mice, so as to provide technical supports to assessment of schistosomiasis transmission risk. METHODS: Wild mice were captured with baited traps at night in Oncomelania hupensis snail-infested settings in schistosomiasis-endemic foci of Anhui Province from October to November, 2022. S. japonicum infections were detected in wild mice using microscopy of mouse liver tissues, microscopy of mouse mesenteric tissues, microscopy of mouse liver tissue homogenates, miracidial hatching test of mouse liver tissue homogenates, Kato-Katz technique and miracidial hatching test of mouse stool samples alone and in combinations. Identification of S. japonicum eggs or miracidia by any of these six assays was defined as an infection. The sensitivity of six assays alone or in combinations was compared for detection of S. japonicum infections in wild mice. RESULTS: A total of 1 703 wild mice were captured, with 366 wild mice detected positive for S. japonicum (21.49%). There were significant differences in the prevalence of S. japonicum infections in wild mice by six assays (Q = 529.33, P < 0.001) and in the sensitivity of six assays for detection of S. japonicum infections in wild mice (χ2 = 527.78, P < 0.001). In addition, the combination of microscopy of mouse liver tissues and mesenteric tissues, combination of microscopy of mouse liver tissues and liver tissue homogenates and combination of microscopy of mouse liver tissues, microscopy of mesenteric tissues, microscopy of liver tissue homogenates and Kato-Katz technique showed 86.61%, 87.16% and 97.27% sensitivities for detection of S. japonicum infections in wild mice, respectively. CONCLUSIONS: Diverse etiological assays show various efficiencies for detection of S. japonicum infections in wild mice. Combination of microscopy of mouse liver tissues and microscopy of mesenteric tissues, and combination of microscopy of mouse liver tissues and microscopy of liver tissue homogenates are potential approaches for field detection of S. japonicum infections in wild mice.

[Diagnostic efficacy of indirect haemagglutination assay for detection of Schistosoma japonicum infections among boatmen and fishermen in the Dongting Lake region].

OBJECTIVE: To evaluate the diagnostic efficacy of indirect haemagglutination assay (IHA) for detection of Schistosoma japonicum infections among boatmen and fishermen in Dongting Lake region, so as to provide insights into improving the schistosomiasis surveillance program among boatmen and fishermen. METHODS: The boatmen and fishermen were detected for S. japonicum infections using IHA and Kato-Katz technique or miracidium hatching test nylon gauze simultaneously at schistosomiasis testing sites in the anchor sites for boatmen and fishermen in the Dongting Lake region during the period from 2014 to 2016, and using IHA for serological screening followed by parasitological testing of seropositives during the period from 2017 to 2019. The sensitivity and specificity of IHA were evaluated for detection of S. japonicum infections among boatmen and fishermen, with the 2014-2016 parasitological testing results as a gold standard. In addition, the seroprevalence of S. japonicum infections was compared among boatmen and fishermen with different characteristics and among years. RESULTS: A total of 306 schistosomiasis testing sites were assigned for boatmen and fishermen, and a total of 143 360 person-time boatmen and fishermen were tested for S. japonicum infections in the Dongting Lake region from 2014 to 2019. The sensitivity and specificity of IHA were 69.9%, 97.3% and 96.1% (χ2 = 74.6, P < 0.05), and 70.9%, 74.5% and 71.9% for detection of S. japonicum infections from 2014 to 2016 (χ2 = 29.4, P < 0.05), respectively. The seroprevalence of S. japonicum infections reduced from 30.3% in 2014 to 1.8% in 2019 among boatmen and fishermen, appearing an overall tendency towards a decline (Z = 1 552.4, P < 0.05). In addition, male, individuals at ages of 45 to 60 years, full-time boatmen and fishermen were more likely to be seropositive for S. japonicum infections (all P values < 0.05). CONCLUSIONS: The seroprevalence of S. japonicum infections appeared a tendency towards a decline among boatmen and fishermen in the Dongting Lake region year by year from 2014 to 2019. IHA presented a high efficacy for screening of S. japonicum infections among boatmen and fishermen in the Dongting Lake region.

Molecular evidence on the presence of Schistosoma japonicum infection in snails along the Yangtze River, 2015-2019.

BACKGROUND: Due to sustained control activities, the prevalence of Schistosoma japonicum infection in humans, livestock and snails has decreased significantly in P. R. China, and the target has shifted from control to elimination according to the Outline of Healthy China 2030 Plan. Applying highly sensitive methods to explore the presence of S. japonicum infection in its intermediate host will benefit to assess the endemicity or verify the transmission interruption of schistosomiasis accurately. The aim of this study was to access the presence of S. japonicum infection by a loop-mediated isothermal amplification (LAMP) method through a 5-year longitudinal study in five lake provinces along the Yangtze River. METHODS: Based on previous epidemiological data, about 260 villages with potential transmission risk of schistosomiasis were selected from endemic counties in five lake provinces along the Yangtze River annually from 2015 to 2019. Snail surveys were conducted in selected villages by systematic sampling method and/or environmental sampling method each year. All live snails collected from field were detected by microscopic dissection method, and then about one third of them were detected by LAMP method to assess the presence of S. japonicum infection with a single blind manner. The infection rate and nucleic acid positive rate of schistosomes in snails, as well as the indicators reflecting the snails' distribution were calculated and analyzed. Fisher's exact test was used to examine any change of positive rate of schistosomes in snails over time. RESULTS: The 5-year survey covered 94,241 ha of environment with 33,897 ha of snail habitats detected accumulatively. Totally 145.3 ha new snail habitats and 524.4 ha re-emergent snail habitats were found during 2015-2019. The percentage of frames with snails decreased from 5.93% [45,152/761,492, 95% confidence intervals (CI): 5.88-5.98%] in 2015 to 5.25% (30,947/589,583, 95% CI: 5.19-5.31%) in 2019, while the mean density of living snails fluctuated but presented a downward trend generally from 0.20 snails/frame (155,622/761,492, 95% CI: 0.17-0.37) in 2015 to 0.13 snails/frame (76,144/589,583, 95% CI: 0.11-0.39) in 2019. A total of 555,393 live snails were collected, none of them was positive by dissection method. Totally 17 pooling snail samples were determined as positives by LAMP method among 8716 pooling samples with 174,822 of living snails, distributed in 12 villages of Hubei, Hunan, Jiangxi and Anhui provinces. The annual average positive rate was 0.41% (95% CI: 0.13-0.69%) in 2015, 0% in 2016, 0.36% (95% CI: 0.09-0.63%) in 2017, 0.05% (95% CI: 0-0.16%) in 2018, 0.05% (95% CI: 0-0.15%) in 2019, respectively, presenting a downward trend from 2015 to 2019 with statistical significance (χ2 = 11.64, P < 0.05). CONCLUSIONS: The results suggest that S. japonicum infection still persisted in nature along the Yangtze River and traditional techniques might underestimate the prevalence of schistosomiasis in its intermediate hosts. Exploring and integrating molecular techniques into national surveillance programme could improve the sensitivity of surveillance system and provide guidance on taking actions against schistosomiasis.

Schistosoma japonicum translationally controlled tumour protein, which is associated with the development of female worms, as a target for control of schistosomiasis.

Schistosomiasis is a globally important helminthic disease of both humans and animals, and is the second most common parasitic disease after malaria. Although praziquantel is extensively used for treatment of parasitic diseases, drug resistance has been reported. Therefore, new drugs and effective vaccines are needed for continuous control of schistosomiasis. Eggs produced by schistosomes are responsible for the occurrence and spread of schistosomiasis. Revealing the reproductive mechanism of schistosomes will help to control this disease. In this study, the proteomic profiles of single-sex infected female worms and bisexual infected mature female worms of Schistosoma japonicum at 18, 21, 23 and 25 days p.i. were identified with isobaric tags for relative quantitation-coupled liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subsequently used for bioinformatic analysis. Six highly expressed differentially expressed proteins in mature female worms were selected and long-term interference with small interfering RNA (siRNA) was conducted to determine biological functions. SiRNA against S. japonicum translationally controlled tumour protein (SjTCTP) resulted in the most significant effect on the growth and development of MF worms. Sjtctp mRNA expression gradually increased over time with a high level of expression maintained at 25-42 days p.i., while levels were significantly higher in mature female worms than male and SF worms. The subsequent animal immune protection experiments showed that recombinant SjTCTP (rSjTCTP) reduced the number of adults by 44.7% (P < 0.01), average egg burden per gram of liver by 57.94% (P < 0.01), egg hatching rate by 47.57% (P < 0.01), and oviposition of individual females by 43.16%. rSjTCTP induced higher levels of serum IgG, IL-2, and IL-10 in mice. Collectively, these results show that SjTCTP is vital to reproduction of female worms and, thus, is a candidate antigen for immune protection.

Novel Hepatic Schistosomula Antigens as Promising Targets for Immunodiagnosis and Immunoprotection of Schistosomiasis japonica.

BACKGROUND: Antigens of migrating schistosomula are promising candidates as schistosomiasis vaccine targets, since immune attack on hepatic schistosomula would interrupt the parasites life cycle and reduce egg burden on the host. METHODS: In this study, we report a collection of Schistosoma japonicum schistosomula proteins (SjScPs) that are highly expressed in hepatic schistosomula. The expression characteristics, antigenicity and immune protection of these proteins were studied by western blot, ELISA, immunofluorescence and challenge assays. RESULTS: We found that several of these SjScPs were highly antigenic and could effectively stimulate humoral immune responses in both human and other mammalian hosts. In particular, SjScP25, SjScP37, SjScP41, SjScP80, and SjScP88 showed high potential as biomarkers for schistosomiasis immunodiagnosis. Furthermore, we demonstrated that immunization with several of the recombinant SjScPs were able to protect mice from S japonicum challenge infection, with SjScP25 generating the most protective results. CONCLUSIONS: Our work represents a group of novel schistosome immunogens, which may be promising schistosomiasis japonica diagnosis and vaccine candidates.

Comparison of self-reported and observed water contact measures in Schistosoma japonicum-endemic villages in Leyte, The Philippines.

BACKGROUND: We compared individuals' self-reported water contact from a questionnaire to direct observation of water contact. Questionnaires that accurately capture water contact are necessary to risk-stratify individuals and communities at high risk for schistosomiasis. METHODS: Individuals (N=677) ages 7-30 y were included from three Schistosoma japonicum-endemic villages in Leyte, The Philippines. Each individual was observed for 12 d over the course of the 18-month study and the questionnaire was administered six times. A questionnaire index was derived that captured the number of self-reported contacts with water bodies for any purpose. An exposure index was created based on the sum of contacts that was weighted by the percentage of body surface area (BSA) exposed and exposure duration. RESULTS: Of 16 water contact activities, only bathing and washing clothes exhibited a significant, positive correlation between self-reported contacts and the observed exposure index related to those contacts. CONCLUSIONS: We found that only the reported frequencies of bathing and washing clothes were significantly related to an individual's overall observed exposure index, while use of all reported contacts was not related to the observed exposure. This study further supports the need for questionnaires to be augmented by some measure of how much BSA is exposed and/or time is spent in the water on average for a specific activity.

Diagnostic efficacy of indirect haemagglutination assay for detection of Schistosoma japonicum infections among boatmen and fishermen in the Dongting Lake region / 中国血吸虫病防治杂志

OBJECTIVE@#To evaluate the diagnostic efficacy of indirect haemagglutination assay (IHA) for detection of Schistosoma japonicum infections among boatmen and fishermen in Dongting Lake region, so as to provide insights into improving the schistosomiasis surveillance program among boatmen and fishermen.@*METHODS@#The boatmen and fishermen were detected for S. japonicum infections using IHA and Kato-Katz technique or miracidium hatching test nylon gauze simultaneously at schistosomiasis testing sites in the anchor sites for boatmen and fishermen in the Dongting Lake region during the period from 2014 to 2016, and using IHA for serological screening followed by parasitological testing of seropositives during the period from 2017 to 2019. The sensitivity and specificity of IHA were evaluated for detection of S. japonicum infections among boatmen and fishermen, with the 2014-2016 parasitological testing results as a gold standard. In addition, the seroprevalence of S. japonicum infections was compared among boatmen and fishermen with different characteristics and among years.@*RESULTS@#A total of 306 schistosomiasis testing sites were assigned for boatmen and fishermen, and a total of 143 360 person-time boatmen and fishermen were tested for S. japonicum infections in the Dongting Lake region from 2014 to 2019. The sensitivity and specificity of IHA were 69.9%, 97.3% and 96.1% (χ2 = 74.6, P < 0.05), and 70.9%, 74.5% and 71.9% for detection of S. japonicum infections from 2014 to 2016 (χ2 = 29.4, P < 0.05), respectively. The seroprevalence of S. japonicum infections reduced from 30.3% in 2014 to 1.8% in 2019 among boatmen and fishermen, appearing an overall tendency towards a decline (Z = 1 552.4, P < 0.05). In addition, male, individuals at ages of 45 to 60 years, full-time boatmen and fishermen were more likely to be seropositive for S. japonicum infections (all P values < 0.05).@*CONCLUSIONS@#The seroprevalence of S. japonicum infections appeared a tendency towards a decline among boatmen and fishermen in the Dongting Lake region year by year from 2014 to 2019. IHA presented a high efficacy for screening of S. japonicum infections among boatmen and fishermen in the Dongting Lake region.

Characterisation and preliminary functional analysis of N-acetyltransferase 13 from Schistosoma japonicum.

BACKGROUND: N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity. RESULTS: In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro. CONCLUSIONS: Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.

Schistosoma japonicum peptide SJMHE1 inhibits acute and chronic colitis induced by dextran sulfate sodium in mice.

BACKGROUND: Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We previously identified a small molecule peptide from Schistosoma japonicum and named it SJMHE1. SJMHE1 can suppress delayed-type hypersensitivity, collagen-induced arthritis and asthma in mice. In this study, we assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis. METHODS: Acute and chronic colitis were induced in C57BL/6 mice by DSS, following which the mice were injected with an emulsifier SJMHE1 or phosphate-buffered saline. The mice were then examined for body weight loss, disease activity index, colon length, histopathological changes, cytokine expression and helper T (Th) cell subset distribution. RESULTS: SJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and pathological damage to the colon and modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. In addition, SJMHE1 treatment reduced the percentage of Th1 and Th17 cells and increased the percentage of Th2 and regulatory T (Treg) cells in the splenocytes and mesenteric lymph nodes of mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of interleukin-10 (IL-10) mRNA, downregulated the expression of IL-17 mRNA and modulated the Th cell balance in mice with chronic colitis. CONCLUSIONS: Our data show that SJMHE1 provided protection against acute and chronic colitis by restoring the immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBDs without immunogenicity concerns.

[Surveillance of schistosomiasis in Xiaogan City from 2016 to 2020].

OBJECTIVE: To analyze the surveillance data of schistosomiasis in Xiaogan City, Hubei Province from 2016 to 2020, so as to provide the scientific evidence for understanding the epidemiological changes of schistosomiasis and evaluating the schistosomiasis control strategy. METHODS: A total of 16 surveillance sites were selected in the schistosomiasis endemic foci of Xiaogan City from 2016 to 2020, where Schistosoma japonicum infections in humans, livestock and Oncomelania snails and the schistosomiasis transmission risk were monitored. The schistosomiasis surveillance results were descriptively analyzed. RESULTS: During the period from 2016 to 2020, there was no schistosomiasis emergency epidemic in Xiaogan City. A total of 660 sero-positive individuals were identified in Xiaogan City during the 5-year period, and the seroprevalence of S. japonicum infections reduced from 2.08% in 2016 to 0.97% in 2020. Higher seroprevalence of S. japonicum infections was detected in men than in women, and in individuals at ages of over 60 years than in those at other age groups; however, no egg-positives were detected in humans or livestock. The mean density of living snails was 0.05 to 0.06 snails/0.1 m2 during the 5-year period, and the occurrence of frames with snails increased from 2.99% in 2016 to 3.92% in 2020; however, no S. japonicum infection was found in snails. CONCLUSIONS: The endemic situation of schistosomiasis remarkably decreases in Xiaogan City during the period from 2016 through 2020. Further improvements of the sensitive and effective schistosomiasis surveillance system are required with an emphasis on the monitoring of the schistosomiasis transmission risk and management of floating populations.

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype.

Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.

[Endemic situation of schistosomiasis in national surveillance sites of Zhejiang Province from 2015 to 2019].

OBJECTIVE: To analyze the endemic situation of schistosomiasis in national surveillance sites of Zhejiang Province, so as to provide the scientific evidence for formulating the new schistosomiasis surveillance program and consolidating schistosomiasis elimination achievements. METHODS: A total of 54 to 55 national surveillance sites and 6 risk monitoring sites were assigned in historical endemic regions of Zhejiang Province from 2015 to 2019, where the Schistosoma japonicum infections in humans, livestock, snails and wild feces were monitored. All data pertaining to the surveillance results were descriptively analyzed. RESULTS: There were 34 530 person-time local residents receiving serological screening for S. japonicum infections in national surveillance sites of Zhejiang Province from 2015 to 2019, and the seroprevalance of S. japonicum infections were 0.29% to 0.68%; however, no egg-positives were detected. During the period from 2015 to 2019, there were 62 086 person-time mobile populations receiving serological screening for S. japonicum infections in national surveillance sites of Zhejiang Province, and the seroprevalance of S. japonicum infections were 0.32% to 0.56%; additionally, there were 27 egg-positives identified, including 3 imported cases with schistosomiasis haematobia and one case with acute schistosomiasis japonica, indicating that the adjusted prevalence of Schistosoma infections were 0.01% to 0.07% among mobile populations. A total of 829 livestock were examined for S. japonicum infections, with no positives detected. There were 10.55 hm2 and 2.89 hm2 snail habitats found in national surveillance sites and risk monitoring sites of Zhejiang Province during the 5-year period, respectively; however, no S. japonicum infections were identified in snails. Moreover, a total of 305 wild feces were tested for S. japonicum infections, and no egg-positives were identified. CONCLUSIONS: The schistosomiasis elimination achievement have been consolidated in Zhejiang Province; however, the risk factors of re-emerging schistosomiasis have not been completely eliminated, such as residual snails and imported schistosomiasis cases. Further surveillance and control activities of snails and the source of S. japonicum infections should be reinforced.