Genome assembly and transcriptome analysis provide insights into the antischistosome mechanism of Microtus fortis

Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.

Clinicopathological differences between patients with schistosomal appendicitis and non schistosomal appendicitis:A retrospectively study of past ten years

BACKGROUND Chronic schistosomiasis causes multiple organ and multiple system diseases,especially the digestive system.Schistosome eggs are mainly deposited in the stomach,liver and colorectal,but a few eggs are deposited in the appendix and cause disease.At present,there are few studies on schistosomal appendicitis.AIM To explore the differences in epidemiological,clinical and pathological characteristics between schistosomal appendicitis and non-schistosomal appendicitis over the past decade in order to assess the impact of schistosomiasis on appendicitis.METHODS The differences of general data,clinical data and laboratory examination data of patients with appendicitis from October 2013 to October 2023 were retrospectively analyzed.All patients were divided into two groups for analysis.There were 136 patients in schistosomal appendicitis group and 5418 patients in non-schistosomal appendicitis group.RESULTS Schistosomal appendicitis accounted for 2.45%of all patients with appendicitis,and the annual proportion in the past decade was 2.2%,2.9%,1.8%,1.9%,3.4%,3.1%,1.9%,1.6%,3%,2.6%,respectively.The prevalence of schistosomal appendicitis was middle-aged and elderly males,with an average age of 61.73±15.335 years.The main population of non-schistosomal appendicitis was middle-aged men,with an average age of 35.8±24.013 years(P<0.001).The distribution of pathological types of appendicitis was different between the two groups(P<0.001).The incidence of acute suppurative appendicitis in non-schistosomal appendicitis was higher than that in schistosomal appendicitis[odds ratio(OR)=0.504;95%confidence interval(CI):0.349-0.728;P<0.001].The proportion of acute attack of chronic appendicitis in schistosomal appendicitis was higher than that in non-schistosomal appendicitis(OR=2.614;95%CI:1.815-3.763;P<0.001).The proportion of schistosomal appendicitis patients complicated with colorectal cancer was higher than that of nonschistosomal appendicitis patients(OR=5.087;95%CI:1.427-18.132;P=0.012).There was no difference in clinical symptoms between the two groups.In the laboratory examination,there was a significant difference in white blood cells between schistosomal appendicitis and non-schistosomal appendicitis.The level of white blood cells in schistosomal appendicitis group was slightly higher than the upper limit of the normal range.Other statistically significant indicators were in the normal range.CONCLUSION Schistosomal appendicitis is a severe condition that is often associated with intestinal malignancies,potentially leading to a poor prognosis.Schistosomal appendicitis is more likely to be misdiagnosed and missed diagnosed in clinical work because of its nonspecific clinical manifestations and laboratory examination.It is crucial to differentiate schistosomal appendicitis in middle-aged and elderly male patients presenting with appendicitis,and to ensure early detection and treatment.

Schistosomal(bilharzial)polyps:Travel through the colon and beyond

Schistosomiasis(bilharziasis)is a major neglected tropical disease.It is endemic in many tropical and subtropical communities.Schistosomal polyps(S.polyps)are not uncommon presentation of this infection.Although the colon is the most commonly affected organ,many other organs are affected.S.polyps are associated with a variable range of morbidity independent of the Schistosomal infection.S.polyps are frequently described in endemic areas and increasingly reported in non-endemic areas mainly among immigrants and visitors to the endemic areas.This review aimed to increase awareness of practitioners,especially gastroenterologists,for this peculiar type of polyps caused by this neglected infection hence improving patient outcomes.Web-based search of different databases was conducted for the literature focusing the development of S.polyps in the colon and other organs with analysis of the clinical manifestations,diagnosis and treatment.The following key words were used in the search,“Schistosomiasis”OR“Bilharziasis”AND“Polyps”OR“Polyp”AND“Colon”OR“Small intestine”OR“Duodenum”OR“Stomach”OR“Esophagus”OR”Gallbladder”OR”Pharynx”OR“Larynx”OR“Trachea”OR”Urinary bladder”OR“Ureter”OR“Renal Pelvis”OR“Urethra”.All publication types including case reports,case series,original research,and review articles were retrieved and analyzed.S.polyps are not infrequent presentation of acute or chronic Schistosomal infection.S.polyps are described in many organs including the bowel,genitourinary tract,skin,gallbladder and the larynx.Presentation of S.polyps is variable and depends on the site,number as well as the polyp size.The relationship of S.polyps to malignant transformation is a matter of discussion.Presence of S.polyps is sometimes the only manifestation of Schistosomiasis.Small polyps can be treated medically with praziquantel,while large accessible polyps are amendable for endoscopic excision through different polyp resection techniques.However,huge,complicated,non-accessible and suspicious polyps are indicated for surgical management or advanced endoscopic resection when appropriate.Clinicians and endoscopists should be aware about these facts when treating patients living in,immigrated from or visiting endemic areas.

Schistosoma japonicum infection induces macrophage polarization

The role of macrophages （MФ） as the first line of host defense is well accepted. These cells play a central role in orchestrating crucial functions during schistosomal infection. Thus, understanding the functional diversity of these cells in the process of infection as well as the mechanisms underlying these events is crucial for developing disease control strategies. In this study, we adopted a Mqb polarization recognition system. M1 macrophage was characterized by expressing CD16/32, IL-12 and iNOS. M2 macrophage was characterized by expressing CD206, IL-10 and arg-1. In vivo （mouse peritoneal macrophages of different infection stages were obtained） and in vitro （different S. japonicum antigens were used to stimulate RAW264.7） were characterized by using the above mentioned system. NCA and ACA stimulated RAW264.7 express significantly higher levels of IL-12 while significantly higher levels of IL-10 were detected after soluble egg antigen （SEA） stimulation. The results showed that dramatic changes of antigen in the microenvironment before and after egg production led to macrophage polarization. Furthermore, through TLR blocking experiments, the TLR4 signaling pathway was found to play a role in the process of macrophage polarization toward M1. Our data suggest that macrophage polarization during S. japonicum infection had significant effects on host immune responses to S. japonicum.

Sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum:A case report

We report a case of sigmoid colonic carcinoma associated with deposited ova of Schistosoma japonicum. A 57-year old woman presented with a 10-mo history of left lower quadrant abdominal pain and a 2-mo history of bloody stools. She had a significant past medical history of asymptomatic schistosomiasis japonica and constipation. A colonoscopy showed an exophytic fragile neoplasm with an ulcerating surface in the sigmoid colon. During the radical operative procedure, we noted the partially encircling tumor was located in the distal sigmoid colon, and extended into the serosa. Succedent pathological analysis demonstrated the diagnosis of sigmoid colonic ulcerative tubular adenocarcinoma, and showed deposited ova of Schistosoma japonicum in both tumor lesions and mesenteric lymph nodes. Three days after surgery the patient returned to the normal bowel function with one defecation per day. These findings reveal that deposited schistosome ova play a possible role in the carcinogenesis of colorectal cancer.

Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis

BACKGROUND: Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type Ⅰ and Ⅲ collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis. METHODS: Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 μg/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of α-smooth muscle actin (α-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining. RESULTS: Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related α-SMA and thecontent of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of α-SMA around the hepatic sinusoids (P【0.01). The contents of type Ⅰ and Ⅲ collagens were significantly attenuated. The ratio of staining area to the whole field (10×3.3) under a polarized light microscope in the untreated and treated groups was 37.25±9.71 vs. 13.38±4.24 (P【0.01) and 9.66±3.52 vs. 6.23±1.81 (P【0.05), respectively. CONCLUSIONS: Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at least in part by inhibiting the activation of HSCs.

Phage displaying peptides mimic schistosoma antigenic epitopes selected by rat natural antibodies and protective immunity induced by their immunization in mice

AIM: To obtain the short peptides mimic antigenic epitopes selected by rat natural antibodies to schistosomes, and to explore their immunoprotection against schistosomiasis in mice.METHODS: Adults worm antigens (AWA) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and enzyme-linked transferred immunoblotting methods with normal SD rat sera (NRS). The killing effects on schistosomula with fresh and heat-inactivated sera from SD rats were observed. Then the purified IgG from sera of SD rats was used to biopan a phage random peptide library and 20 randomly selected positive clones were detected by ELISA and 2 of them were sequenced.Sixty female mice were immunized thrice with positive phage clones (0, 2nd, 4th wk). Each mouse was challenged with 40 cercariae, and all mice were killed 42 d after challenge. The worms and the liver eggs were counted. RESULTS: NRS could specifically react to the molecules of 75 000, 47 000, 34 500 and 23 000 of AWA. Sera from SD rats showed that the mortality rate of schistosomula was 76.2%, and when the sera were heat-inactivated in vitro, the mortality rate was decreased to 41.0% after being cultured for 48 h. The specific phages bound to IgG were enriched about 300-folds after three rounds of biopanning. Twenty clones were detected by ELISA, 19 of them bound to the specific IgG of rat sera. Immunization with these epitopes was carried out in mice. Compared with the control groups, the mixture of two mimic peptides could induce 34.9% (P = 0.000) worm reduction and 67.6% (P = 0.000) total liver egg reduction in mice. Two different mimic peptides could respectively induce 31.0% (P = 0.001), 14.5% (P = 0.074) worm reduction and 61.2% (P = 0.000), 35.7% (P = 0.000) total liver egg reduction. The specific antibody could be induced by immunization of the mimic peptides, and the antibody titer in immunized mice reached more than 1:6 400 as detected by ELISA.CONCLUSION: Specific peptides mimic antigenic molecules can be obtained by biopanning the phage random peptide library and a partially protective immunity against schistosome infection can be stimulated by these phage epitopes in mice.

Gut microbiota in parasite-transmitting gastropods

Background Gastropoda,the largest class within the phylum Mollusca,houses diverse gut microbiota,and some gastropods serve as intermediate hosts for parasites.Studies have revealed that gut bacteria in gastropods are associated with various biological aspects,such as growth,immunity and host-parasite interactions.Here,we summarize our current knowledge of gastropod gut microbiomes and highlight future research priorities and perspectives.Methods A literature search was undertaken using PubMed,Web of Science and CNKI for the articles on the gut microbiota of gastropods until December 31,2022.We retrieved a total of 166 articles and identified 73 eligible articles for inclusion in this review based on the inclusion and exclusion criteria.Results Our analysis encompassed freshwater,seawater and land snails,with a specific focus on parasite-transmitting gastropods.We found that most studies on gastropod gut microbiota have primarily utilized 16S rRNA gene sequencing to analyze microbial composition,rather than employing metagenomic,metatranscriptomic,or metabolomic approaches.This comprehensive review provided an overview of the parasites carried by snail species in the context of gut microbiota studies.We presented the gut microbial trends,a comprehensive summary of the diversity and composition,influencing factors,and potential functions of gastropod gut microbiota.Additionally,we discussed the potential applications,research gaps and future perspectives of gut microbiomes in parasite-transmitting gastropods.Furthermore,several strategies for enhancing our comprehension of gut microbiomes in snails were also discussed.Conclusions This review comprehensively summarizes the current knowledge on the composition,potential function,influencing factors,potential applications,limitations,and challenges of gut microbiomes in gastropods,with a specific emphasis on parasite-transmitting gastropods.These findings provide important insights for future studies aiming to understand the potential role of gastropod gut microbiota in controlling snail populations and snail-borne diseases.

Research development of the pathogenesis pathways for neuroschistosomiasis

The infection of the central nervous system （CNS） by schistosome may or may not have clinical manifestations. When symptomatic, neuroschistosomiasis （NS） is one of the most severe presentations of schistosome infection. Among the NS symptoms, cerebral invasion is mostly caused by Schistosoma japonicum （S. japonicum）, and the spinal cord symptoms are mainly caused by S. mansoni or S. haematobium. There are 2 main pathways by which schistosomes cause NS： egg embolism and worm migration, via either artery or vein system, especially the valveless perivertebral Batson＇s plexus. The adult worm migrates anomalously through the above pathways to the CNS where they lay eggs. Due to the differences in species of schistosomes and stages of infection, mechanisms vary greatly. The portal hypertension with hepatosplenic schistosomiasis also plays an important role in the pathogenesis. Here the pathways through which NS occurs in the CNS were reviewed.

Assessing stool quantities generated by three specific Kato-Katz thick smear templates employed in different settings

Background:The Kato-Katz technique is recommended for the diagnosis of helminth infections in epidemiological surveys,drug efficacy studies and monitoring of control interventions.We assessed the comparability of the average amount of faeces generated by three Kato-Katz templates included in test kits from two different providers.Methods:Nine hundred Kato-Katz thick smear preparations were done;300 per kit.Empty slides,slides plus Kato-Katz template filled with stool and slides plus stool after careful removal of the template were weighed to the nearest 0.1 mg.The average amount of stool that was generated on the slide was calculated for each template,stratified by standard categories of stool consistency(i.e.mushy,soft,sausage-shaped,hard and clumpy).Results:The average amount of stool generated on slides was 40.7 mg(95%confidence interval(CI):40.0–41.4 mg),40.3 mg(95%CI:39.7–40.9 mg)and 42.8 mg(95%CI:42.2–43.3 mg)for the standard Vestergaard Frandsen template,and two different templates from the Chinese Center for Disease Control and Prevention(China CDC),respectively.Mushy stool resulted in considerably lower average weights when the Vestergaard Frandsen(37.0 mg;95%CI:34.9–39.0 mg)or new China CDC templates(37.4 mg;95%CI:35.9–38.9 mg)were used,compared to the old China CDC template(42.2 mg;95%CI:40.7–43.7 mg)and compared to other stool consistency categories.Conclusion:The average amount of stool generated by three specific Kato-Katz templates was similar(40.3–42.8 mg).Since the multiplication factor is somewhat arbitrary and small changes only have little effect on infection intensity categories,it is suggested that the standard multiplication factor of 24 should be kept for the calculation of eggs per gram of faeces for all investigated templates.

Interaction Between the Neglected Tropical Disease Human Schistosomiasis and HCV Infection in Egypt:a Puzzling Relationship

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection and seropositivity worldwide, and it has been proposed that this enhanced susceptibility to HCV is related to coinfection with schistosomiasis. Although currently, there are no studies regarding the actual prevalence of both human schistosomiasis and schistosomiasis/HCV coinfection evi-dences strongly support that eliminating human schistoso-miasis from Egypt is necessary to reduce both HCV prevalence and liver pathology. The present review highlights the significant impact of the neglected tropical disease human schistosomiasis on both susceptibility of Egyptians to HCV coinfection, severity of the resulting liver pathology, and poor response to antiviral therapy. The immune evasion mechan-isms exerted by the HCV-NS3/4A protease domain, and the possible impact of immune evasion mechanisms exerted by proteases of larval, worm and egg stages of the parasite Schistosoma on human susceptibility to HCV infection are discussed. In addition, schistosome immune evasion mechanisms may include immunosuppression that in turn prevents clearance of HCV viremia and leads to relapsing HCV infection and severe liver pathology. I propose the generation of a replicon system from the most prevailing genotype (HCV-4a) in Egypt and establishing its replication on hepatoplas-toma or immune cells in presence of bilharzial antigens. Finally, the use of a humanized small animal model that can acquire both HCV and S. mansoni infections will be important to further understand in real time the impact of coinfection on both the immune system and liver pathology.