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.
CONCLUSIONS: 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).

Schistosoma japonicum infections, which lead to local inflammatory responses to schistosome eggs trapped in host tissues, can result in long-term, severe complications. The development of schistosomiasis may result from a complex interaction between the pathogenic, environmental, and host genetic components. Notably, the genetic factors that influence the development of schistosomiasis complications are poorly understood. Here we performed a genome-wide association study on multiple schistosomiasis-related phenotypes of 637 unrelated schistosomiasis patients in the Chinese population. Among three indicators of liver damage, we identified two novel, genome-wide significant single-nucleotide polymorphisms (SNPs) rs34486793 (P = 1.415 × 10-8) and rs2008259 (P = 6.78 × 10-8) at locus 14q32.2 as well as a gene, PMEPA1, at 20q13.31 (index rs62205791, P = 6.52 × 10-7). These were significantly associated with serum levels of hyaluronic acid (HA). In addition, RASIP1 and MAMSTR at 19q13.33 (index rs62132778, P = 1.72 × 10-7) were significantly associated with serum levels of aspartate aminotransferase (AST), and TPM1 at 15q22.2 (index rs12442303, P = 4.39 × 10-7) was significantly associated with serum levels of albumin. In schistosomiasis clinical signs, ITIH4 at 3p21.1 (index rs2239548) was associated with portal vein diameter (PVD) class, an indicator of portal hypertension, and OGDHL at 10q11.23 (index rs1258172) was related to ascites grade. We also detected an increased expression of these six genes in livers of mice with severe schistosomiasis. Summary data-based Mendelian randomization analyses indicated that ITIH4, PMEPA1 and MAMSTR were pleiotropically associated with PVD class, HA and AST, respectively.

The construction of spatio-temporal models can be either descriptive or dynamic. In this study we aim to evaluate the differences in model fitting between a descriptive model and a dynamic model of the transmission for intestinal schistosomiasis caused by Schistosoma japonicum in Guichi, Anhui Province, China. The parasitological data at the village level from 1991 to 2014 were obtained by cross-sectional surveys. We used the fixed rank kriging (FRK) model, a descriptive model, and the integro-differential equation (IDE) model, a dynamic model, to explore the space-time changes of schistosomiasis japonica. In both models, the average daily precipitation and the normalized difference vegetation index are significantly positively associated with schistosomiasis japonica prevalence, while the distance to water bodies, the hours of daylight and the land surface temperature at daytime were significantly negatively associated. The overall root mean square prediction error of the IDE and FRK models was 0.0035 and 0.0054, respectively, and the correlation reflected by Pearson\'s correlation coefficient between the predicted and observed values for the IDE model (0.71; p<0.01) was larger than that for the FRK model (0.53; p=0.02). The IDE model fits better in capturing the geographic variation of schistosomiasis japonica. Dynamic spatio-temporal models have the advantage of quantifying the process of disease transmission and may provide more accurate predictions.

BACKGROUND: Schistosomiasis japonica remains an important public health concern due to its potential to cause severe outcomes and long-term sequelae. An integrated control strategy implemented in the Peoples\' Republic of China has been shown to be effective to control or interrupt the transmission of schistosomiasis. The objective of this study is to estimate the disease burden of schistosomiasis and assess the cost-effectiveness of the integrated control strategy focused on different major interventions at three stages for schistosomiasis control in a lake setting, to provide reference for policy making or planning.
METHODS: Annual cost data of schistosomiasis control during 2009-2019 were obtained from the control program implementers in Jiangling County, Hubei Province, China. Economic costs are provided in constant 2009 Chinese Yuan (CNY). Epidemiological data of schistosomiasis were collected from the Jiangling county station for schistosomiasis control. Disease burden of schistosomiasis was assessed by calculating years of life lost (YLLs) owing to premature death, years lived with disability (YLDs) and disability-adjusted life years (DALYs). DALYs were calculated as the sum of YLLs and YLDs. We then conducted a rudimentary cost-effectiveness analysis by determining the ratio by dividing the difference between the average cost of integrated control strategy at transmission control (2013-2016) or transmission interruption (2017-2019) and the average cost at stage of infection control (2009-2012) with the difference between the DALYs of schistosomiasis at different control stages. Descriptive statistics on the costs and DALYs were used in the analysis.
RESULTS: The total economic costs for schistosomiasis control in Jiangling County from 2009 to 2019 were approximately CNY 606.88 million. The average annual economic costs for schistosomiasis prevention and control at stages of infection control (2009-2012), transmission control (2013-2016), and transmission interruption (2017-2019) were approximately CNY 41.98 million, CNY 90.19 million and CNY 26.06 million respectively. The overall disease burden caused by schistosomiasis presented a downward trend. Meanwhile, the disease burden of advanced cases showed an upward trend with the DALY increased from 943.72 to 1031.59 person-years. Most disease burden occurred in the age group over 45 years old (especially the elderly over 60 years old). Taking the infection control stage as the control, the incremental cost-effectiveness ratio of integrated control strategy was CNY 8505.5 per case averted, CNY 60 131.6 per DALY decreased at transmission control stage and CNY -2217.6 per case averted, CNY -18 116.0 per DALY decreased at transmission interruption stage.
CONCLUSIONS: The disease burden of schistosomiasis decreased significantly with the implementation of the integrated prevention and control strategy. Surveillance and management on elder population should be strengthened to decrease diseases burden. There remains a need for well-conducted studies that examine the long-term cost-effectiveness of the integrated control strategy for schistosomiasis. GRAPHIC ABSTARCT.

In areas endemic to schistosomiasis, fetal exposure to schistosome antigens prime the offspring before potential natural infection. Praziquantel (PZQ) treatment for Schistosoma japonicum infection in pregnant women has been demonstrated to be safe and effective. Our objectives were to evaluate whether maternal PZQ treatment modifies the process of in utero sensitization to schistosome antigens potentially impacting later risk of infection, as well as immune response to S. japonicum. We enrolled 295 children at age six, born to mothers with S. japonicum infection who participated in a randomized control trial of PZQ versus placebo given at 12-16 weeks gestation in Leyte, The Philippines. At enrollment, we assessed and treated current S. japonicum infection and measured serum cytokines. During a follow-up visit four weeks later, we assessed peripheral blood mononuclear cell (PBMC) cytokine production in response to soluble worm antigen preparation (SWAP) or soluble egg antigen (SEA). Associations between maternal treatment group and the child\'s S. japonicum infection status and immunologic responses were determined using multivariate linear regression analysis. PZQ treatment during pregnancy did not impact the prevalence (P = 0.12) or intensity (P = 0.59) of natural S. japonicum infection among children at age six. Among children with infection at enrollment (12.5%) there were no significant serum cytokine concentration differences between maternal treatment groups. Among children with infection at enrollment, IL-1 production by PBMCs stimulated with SEA was higher (P = 0.03) in the maternal PZQ group compared to placebo. Among children without infection, PBMCs stimulated with SEA produced greater IL-12 (P = 0.03) and with SWAP produced less IL-4 (P = 0.01) in the maternal PZQ group compared to placebo. Several cytokines produced by PBMCs in response to SWAP and SEA were significantly higher in children with S. japonicum infection irrespective of maternal treatment: IL-4, IL-5, IL-10, and IL-13. We report that maternal PZQ treatment for S. japonicum shifted the PBMC immune response to a more inflammatory signature but had no impact on their offspring\'s likelihood of infection or serum cytokines at age six, further supporting the safe use of PZQ in pregnant women. Trial Registration: ClinicalTrials.gov NCT00486863.

BACKGROUND: Several studies have assessed the role of gut microbiota in various cirrhosis etiologies, however, none has done so in the context of Schistosoma japonicum infection in humans. We, therefore, sought to determine whether gut microbiota is associated with S. japonicum infection-induced liver cirrhosis.
METHODS: From December 2017 to November 2019, 24 patients with S. japonicum infection-induced liver cirrhosis, as well as 25 age- and sex-matched controls from the Zhejiang Province, China, were enrolled. Fecal samples were collected and used for 16S rRNA gene sequencing (particularly, the hypervariable V4 region) using the Illumina MiSeq system. Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis.
RESULTS: Eight hundred and seven operational taxonomic units (OTUs) were detected, of which, 491 were common between the two groups, whereas 123 and 193 were unique to the control and cirrhosis groups, respectively. Observed species, Chao, ACE, Shannon, Simpson, and Good\'s coverage indexes, used for alpha diversity analysis, showed values of 173.4 ± 63.8, 197.7 ± 73.0, 196.3 ± 68.9, 2.96 ± 0.57, 0.13 ± 0.09, and 1.00 ± 0.00, respectively, in the control group and 154.0 ± 68.1, 178.6 ± 75.1, 179.9 ± 72.4, 2.68 ± 0.76, 0.19 ± 0.18, and 1.00 ± 0.00, respectively, in the cirrhosis group, with no significant differences observed between the groups. Beta diversity was evaluated by weighted UniFrac distances, with values of 0.40 ± 0.13 and 0.40 ± 0.11 in the control and cirrhosis groups, respectively (P > 0.05). PCA data also confirmed this similarity (P > 0.05). Meanwhile, the relative abundance of species belonging to the Bacilli class was higher in cirrhosis patients [median: 2.74%, interquartile range (IQR): 0.18-7.81%] than healthy individuals (median: 0.15%, IQR: 0.47-0.73%; P < 0.01), and that of Lactobacillales order was also higher in cirrhosis patients (median: 2.73%, IQR: 0.16-7.80%) than in healthy individuals (median: 0.12%, IQR: 0.03-0.70%; P < 0.05).
CONCLUSIONS: Cumulatively, our results suggest that the gut microbiota of S. japonicum infection-induced liver cirrhosis patients is similar to that of healthy individuals, indicating that bacterial taxa cannot be used as non-invasive biomarkers for S. japonicum infection-induced liver cirrhosis.

The gut microbiota has been demonstrated to associate with protection against helminth infection and mediate via microbial effects on the host humoral immunity. As a non-permissive host of Schistosoma japonicum, the Microtus fortis provides an ideal animal model to be investigated, because of its natural self-healing capability. Although researches on the systemic immunological responses have revealed that the host immune system contributes a lot to the resistance, the role of gut microbiome remains unclear. In this study, we exposed the M. fortis to the S.japonicum infection, carried out a longitudinal research (uninfected control, infected for 7 days, 14 days, 21 days, and 31 days) on their colonic microbiota based on the 16S rRNA gene amplicon sequencing. The bacterial composition disclosed a disturbance-recovery alteration followed by the resistance to S. japonicum. The alpha diversity of colon microbiota was reduced after the infection, but it gradually recovered along with self-healing process. Further LEfSe analysis revealed that phyla shifted from Firmicutes to Bacteroidetes, which were mainly driven by an increase of Ruminococcaceae and a depletion of Muribaculaceae in the family level along the Control-Infection-Recovery (CIR) process. We identified a temporary blooming of Lactobacillaceae and Lactobacillus in the mid infection stage (D14). As a recognized probiotics repository, we speculate the increased abundance of Lactobacillaceae in M. fortis colonic microbiota might relate to the natural resistance to the schistosome. Besides, potential microbial functions were also significantly changed in the resistance process. These results demonstrate the remarkable alterations of reed vole colonic microbiota in both community structure and potential functions along with the resistance to S. japonicum infection. The identified microbial biomarkers might offer new ways for drug development to conquer human schistosomiasis.

OBJECTIVE: To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum.
METHODS: Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy.
RESULTS: The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production.
CONCLUSIONS: Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.
［摘要］ 目的 鉴定日本血吸虫表皮生长因子受体基因 (SjEGFR), 并阐明其在日本血吸虫生长和生殖发育中的作用。方法 通过 5′-RACE 和 3′-RACE 扩增、测序获取 SjEGFR 基因全长片段。采用荧光定量PCR (qPCR) 技术检测该基因在日 本血吸虫不同发育阶段 (16、18、20、22、24、26 d) 表达情况。使用整条虫体原位杂交法对感染 24 d 的日本血吸虫雌、雄虫 SjEGFR 基因转录本进行定位。通过体内持续RNA干扰 (RNAi) 技术特异性敲低 SjEGFR 基因, 待虫体发育至 30 d 收集虫 体。统计分析雌、雄虫回收数量以及虫体长度, 通过明矾卡红染色观察虫体生长发育情况。结果 首次鉴定了 SjEGFR 基因, 其结构具有一个保守的酪氨酸激酶位点。整条虫体原位杂交定位显示该基因转录本在虫体各处均有表达, 在雌、雄虫肠道部位呈现出明显着色的高表达。体内RNAi显示, SjEGFR 基因表达被特异性敲低后, 雌、雄虫生长受阻。RNAi 组雌虫子宫内无虫卵, 肠道内无色素沉积、卵黄腺发育迟滞、卵巢发育受阻; 雄虫呈现睾丸个数减少、体积变小, 出现了更 多未成熟的精母细胞。结论 特异性敲低 SjEGFR 基因表达可影响日本血吸虫生长和生殖发育, 阻滞虫卵产生。.

OBJECTIVE: To clarify unique non-contrast CT (NCCT) characteristics for early recognition of Schistosomal associated appendicitis (SAA) differentiating from Non-schistosomal associated appendicitis (NSA).
METHODS: Clinical and pathological data of 50 cases with SAA and 60 cases with NSA who underwent emergency appendectomy were retrospectively compared to pre-surgical NCCT features such as direct and indirect signs of acute appendicitis as well as appendicoliths, colon calcifications as diagnostic criteria. Statistical methods such as Chi-square (χ2), t-tests, Principal component analysis (PCA), Binary Logistic regression (LR) and Factor Analysis (FA) were utilized to observe differences and isolate recognizable CT features of SAA. Pre and post hoc diagnostic performance of all criteria was calculated as sensitivity, specificity, and the Odds Ratio (OR).
RESULTS: Age > 50 years, diameter > 13 mm, pneumatosis, peri appendiceal abscess, focal wall defect, perforation; Orbital, linear and point types of appendicular wall calcifications; sigmoid colon and cecal curvilinear calcifications were observed as unique characteristics with a sensitivity of 84-95% and specificity of 91-98% in predicting SAA by OR of 6.2 times. Pre and post hoc hypothetical analysis did not show any significance for all other factors.
CONCLUSIONS: Factors such as elderly age, CT features such as larger appendicular diameter, appendicular wall calcifications along with sigmoid colon, and cecal calcifications, signs of perforation or abscess are characteristic for early recognition of SAA.

OBJECTIVE: To compare the approaches used for the assessment of disability adjust life years (DALYs) for advanced schistosomiasis japonica, so as to provide scientific evidence for accurate assessment of the burden of advanced schistosomiasis japonica.
METHODS: The patients with advanced schistosomiasis japonica receiving treatment and assistance programs in Hunan Province in 2017 were enrolled, and the years lived with disability (YLD) for the patients with advanced schistosomiasis japonica was calculated using the common global burden of disease (GBD) estimation method, the modified GBD method with addition of common syndromes of advanced schistosomiasis japonica, and the quality of life assessment method.
RESULTS: The YLDs of patients with advanced schistosomiasis japonica, the mean YLDs per capita, and the percentages of YLD were 673.94, 728.77 person-years and 1 761.99 person-years; 0.181, 0.196 person-years and 0.474 person-years; and 10.61, 11.48 person-years per 100 thousand persons and 27.75 person-years per 100 thousand persons with the common GBD method, modified GBD method and the quality of life method, respectively. The YLDs of the patients with advanced schistosomiasis japonica in Hunan Province estimated with the modified GBD method and the quality of life method were 8.14% and 2.61 times higher than that with the common GBD method. Of the major symptoms included in the calculation, the 5 symptoms with the greatest contribution to the burden of advanced schistosomiasis japonica included ascites, moderate anemia, severe anemia, diarrhea and hematochezia.
CONCLUSIONS: The quality of life method may more comprehensively assess the YLDs in patients with advanced schistosomiasis japonica than the common and modified GBD methods.
[摘要] 目的 比较晚期血吸虫病 (晚血) 伤残调整寿命年 (Disability-adjusted life year, DALY) 的评价方法, 为准确评价 晚血疾病负担提供依据。方法 以 2017 年湖南省晚血救助病例为研究对象, 分别采用全球疾病负担 (The global burden of disease and injury, GBD) 通用症状法、增加晚血常见症状后的改良 GBD 法和基于患者生命质量评价的生命质量法, 计 算晚血患者健康寿命损失年 (Years lived with disability, YLDs)。结果 GBD 通用症状法计算得出湖南省晚血患者 YLDs 为 673.94 人·年, 人均 YLDs 为 0.181 人·年, YLDs 率为 10.61 人·年/10万人; 改良 GBD 法计算得出晚血患者 YLDs 为 728.77 人·年, 人均 YLDs 为 0.196 人·年, YLDs 率为 11.48 人·年/10万人; 生命质量法计算得出晚血患者 YLDs 为 1 761.99 人·年, 人均 YLDs 为 0.474 人·年, YLDs 率为 27.75 人·年/10万人。改良 GBD 法计算所得湖南省晚血患者 YLDs 较 GBD 通用症状 法高 8.14%, 生命质量法计算所得 YLDs 是 GBD 通用症状法的 2.61 倍。在纳入计算的各种主要晚血症状中, 按照对晚血 疾病负担贡献的高低排序, 依次为腹水、中度贫血、重度贫血、腹泻和便血。结论 与 GBD 通用症状法、改良 GBD 法相 比, 生命质量法能更全面地评估晚血患者的 YLDs。.