基本消灭血吸虫病后的螺情变化分析

基本消灭血吸虫病后的螺情变化分析云南省血防研究中心大理６７１０００邱宗林，杨文胜，吴兴，殷关林巍山县血防站毕绍增，段增巍山县自由村属于高原峡谷型中度流行区。１９８０年起被选为流行病学纵向观察试点村。经过五年防治，至１９８４年底全村有螺面积下降９８．２...

Effects of γ interferon on hepatic fibrosis of schistosoma japonicum infected mice *

AIM To probe the effect of γ IFN on hepatic fibrosis in schistosomiasis japonica.

Risk factors for hilar cholangiocarcinoma:A case-control study in China

AIM:To study the association between hilar cholangiocarcinoma(HC) and pre-existing medical conditions. METHODS:Three hundred and thirteen HC patients admitted to the Eastern Hepatobiliary Surgery Hospital(Shanghai,China) in 2000-2005 and 608 healthy controls were enrolled in this study.Association between HC and pre-existing medical conditions was studied with their adjusted odds ratio(OR) calculated by logistic regression analysis. RESULTS:The prevalence of choledocholithiasis(adjusted OR=2.704,P=0.039) ,hepatolithiasis(adjusted OR=3.278,P=0.018) ,cholecystolithiasis(adjusted OR =4.499,P<0.0001) ,cholecystectomy(adjusted OR =7.012,P=0.004) ,biliary ascariasis(adjusted OR= 7.188,P=0.001) ,liver fluke(adjusted OR=10.088,P =0.042) and liver schistosomiasis(adjusted OR=9.913,P=0.001) was higher in HC patients than in healthy controls. CONCLUSION:Biliary tract stone disease(choledocho-lithiasis,hepatolithiasis,cholecystolithiasis) and parasitic liver disease(biliary ascariasis,liver fluke,liver schistosomiasis) are the risk factors for HC in Chinese population.

Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum

AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection. METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunonassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type ?Ⅰ?and type Ⅲ collagen was detected by immunohistochemistry and multimedia color pathographic analysis system. RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05],reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type Ⅰand type Ⅲ collagen in mice with liver fibrosis. CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.

CHARACTERISTIC MAGNETIC RESONANCE ENHANCEMENT PATTERN IN CEREBRAL SCHISTOSOMIASIS

Objective To describe the characteristic magnetic resonance imaging （MRI） appearance of cerebral schistosomiasis. Methods Twenty-five patients whose diagnosis of central nervous system （CNS） schistosomiasis had been pathologically （n = 8 ） and clinically （n = 17） confLrmed were randomly selected. MRI was performed on a Signal 1.5T MRI scanner before and after the intravenous administration of gadopentetate dimeghimine constrast medium. We reviewed the MRI studies obtained at the time of initial presentation, as well as follow-up studies obtained during and after medical treatment Results ImmunoLogicaL tests in L5 patients indicated schistosomiasis haematobium. Contrast-enhanced TL-weighted images in 22 cases showed central linear enhancement surrounded by multiple enhancing punctate nodules, which ap- peared “arborized”. Through operation and pathological examination, 8 cases had the granuloma formation of schistoso- mal eggs extensive surrounded by inflammation and venous congestion. And 17 cases were treated with praziquantel and corticosteroid therapy. And they were followed up for 2 months by taking MRI, which turned out to be complete resolution of the enhancing structure and edema. At follow-up, all the patients＇ initial symptoms also resolved. Conclnsion The specified MRI enhancement pattern of cerebral schistosomiasis is common in most cases of CNS schistosomiasis, so it should be taken account into the diagnosis of cerebral schistosomiasis.

Osteopontin expression is associated with hepatopathologic changes in Schistosoma japonicum infected mice

AIM:To investigate osteopontin expression and its association with hepatopathologic changes in BALB/C mice infected with Schistosoma japonicum.METHODS:The schistosomal hepatopathologic mouse model was established by abdominal infection with schistosomal cercaria.Liver samples were obtained from mice sacrif iced at 6,8,10,14,and 18 wk after in-fection.Liver histopathological changes were observed with hematoxylin-eosin and Masson trichrome staining.The expression of osteopontin was determined with im-munohistochemistry,reverse transcription-polymerase chain reaction,and Western blotting.The expressionof α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)were determined by im-munohistochemistry.Correlations of osteopontin ex-pression with other variables(α-SMA,TGF-β1,hepato-pathologic features including granuloma formation and degree of liver f ibrosis)were analyzed.RESULTS:Typical schistosomal hepatopathologic changes were induced in the animals.Dynamic changes in the expression of osteopontin were observed at week 6.The expression increased,peaked at week 10(P<0.01),and then gradually decreased.Positive correla-tions between osteopontin expression and α-SMA(r=0.720,P<0.01),TGF-β1(r=0.905,P <0.01),granu-loma formation(r=0.875,P<0.01),and degree of liver f ibrosis(r=0.858,P<0.01)were also observed.CONCLUSION:Osteopontin may play an important role in schistosomal hepatopathology and may promote granuloma formation and liver fi brosis through an un-explored mechanism.

Schistosomal appendicitis:Incidence in Japan and a case report

Schistosomal appendicitis is very rare in developed countries like the USA,Europe,and Japan.The author reviewed 311 pathologic archival specimens of vermiform appendix over the past 10 years.One case of schistosomal appendicitis was recognized.Therefore,the incidence of this disease was 0.32% in all appendices surgically resected in our hospital.The patient was a 41-year-old woman presenting with lower abdominal pain.She was a sailor traveling to many countries including endemic areas.Physical examination,laboratory data,and imaging modalities suggested an acute appendicitis,and appendectomy was performed under the diagnosis of ordinary appendicitis.Histologically,numerous schistosomal eggs were present in the vasculatures throughout the appendiceal walls.Some of the eggs were calcified.Stromal foreign body reaction was also recognized.The appendicitis was phlegmonous consisting of severe infiltrations of neutrophils and eosinophils.Acute serositis was also noted.Examination of feces revealed numerous eggs of Schistosoma mansoni.Clinicians should be aware of schistosomal appendicitis.

Construction of a hepatic stellate cells subtracted cDNA library of differentially expressed genes in normal mice and mice with Schistosomiasis japonica

To construct a hepatic stellate cells (HSCs) subtracted cDNA library to find differentially expressed genes in normal mice and mice infected with Schistosoma japonicum (S. japonicum). Suppression subtractive hybridization (SSH) was used. The cDNA fragments of normal mouse were compared to those of schistosoma-infected mice to find differentially expressed genes. Then differentially expressed cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Amplification of the library was carried out with transformation of DH5α. The amplified library contained more than 400 positive bacterial clones, which were then hybridized with forward and backward subtracted probes for differential screening. One hundred positive bacterial clones were randomly selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. The subtracted cDNA library of differentially expressed genes of HSCs was constructed successfully, the library is efficient and lays foundation for screening and cloning new and specific genes of schistosomiasis.

Technique for Controlling Spread of Limnotic Oncomelania

Schistosomiasis is a parasitic disease mostly found in areas along the Changjiang River of China. The disease is spread solely through an intermediary named oncomelania, so its spread of schistosomiasis can be controlled by properly designing water intakes which prevent oncomelania from entering farming land or residential areas. This paper reports a successful design process and a new oncomelania free intake device. The design of the new intake is based on a sound research program in which extensive experimental studies were carried out to gain knowledge of oncomelania eco hydraulic behavior and detailed flow field information through CFD simulation.

Treatment of hepatitis C virus genotype 4 with peginterferon alfa-2a: Impact of bilharziasis and fibrosis stage

AIM： To evaluate pegylated interferon alpha2a （PegIFN-α2a） in Egyptian patients with HCV genotype 4, and the impact of pretreatment viral load, co-existent bilharziasis and histological liver changes on response rate. METHODS： A total of 73 nafve patients （61 with history of bilharziasis） with compensated chronic HCV genotype 4 were enrolled into： group A （38 patients） who received 180 mg PegIFN-alpha2a subcutaneously once weekly for a year and group B （35 patients） received IFN alpha-2a 3 MU 3 times weekly. Ribavirin was added to each regimen at a dose of 1200 mg. Patients were followed for 72 wk and sustained response was assessed. RESULTS： Significant improvement in both end of treatment response （ETR） （P 〈 0.002） and sustained response （SR） （P 〈 0.05） was noted with pegylated interferon, where ETR was achieved in 29 （76.3%） and 14 patients （40%） in both groups respectively, and 25 patients in group A （65.8%） and 9 （25.7%） in group B could retain negative viraemia by the end of follow up period. Sustained virological response （SVR） showed a significant negative correlation with age and positive correlation with pretreatment inflammation in patients receiving PegIFN. Viral clearance after 3 mo of therapy was associated with high incidence of ETR and SR （P 〈 0.001）, but without significant difference between both forms of interferon. Significant improvement in response was achieved in patients with high grade fibrosis （grade 3 and 4） with PegIFN-α2a, where SR was seen in 5 out of 13 patients in group A, but none in group B. There was no significant difference in response between bilharzial and non-bilharzial patients in both groups. In terms of safety and tolerability, neutropenia was the predominant side effect, both drugs were comparable. CONCLUSION： PegIFN-~2a combined with ribavirin results in improvement in sustained response in HCV genotype 4, irrespective of history of bilharzial infestation.

Curse of schistosomiasis on Egyptian liver

Schistosomiasis is a chronic parasitic disease caused by atrematode blood fluke of the genus schistosoma that belongsto the schistosomatidae family. The ancient Egyptianscontracted the disease more than 4 000 years ago. It wasrecognized through haematuria, the main sign of urinarybilharziasis was recorded in the Kahun papyrus 1900 B.C.' a-a-a-' disease.

Risk factors for post-hepatectomy liver dysfunction in primary liver cancer patients with concurrent hepatic schistosomiasis and chronic hepatitis

Objective:The purpose of this study was to analyze risk factors for development of post-hepatectomy liver dysfunction in primary liver cancer(PLC)patients with concurrent hepatic schistosomiasis and chronic hepatitis.Methods:A retrospective analysis of 73 PLC patients with concurrent hepatic schistosomiasis and chronic hepatitis,of which 16 patients developed liver dysfunction(persistent ascites or pleural effusion or occurrence of liver-related potentially fatal complications)following hepatectomy,was performed.After clinical characteristics were recorded,preoperative liver function parameters and surgery-related parameters in these patients were assessed.Seventeen potential risk factors for post-hepatectomy liver dysfunction were identified.The association between these potential risk factors and post-hepatectomy liver dysfunction then was analyzed.Results:Univariate analysis showed that liver cirrhosis,intraoperative blood loss,and preoperative total bilirubin were associated with the development of post-hepatectomy liver dysfunction.Multivariate logistic regression analysis of these three factors revealed that intraoperative blood loss≥600 mL and cirrhosis were two independent risk factors for post-hepatectomy liver dysfunction in PLC patients with concurrent hepatic schistosomiasis and chronic hepatitis.Conclusion:Keeping intraoperative blood loss below 600 mL can help avoid the development of post-hepatectomy liver dysfunction in liver cancer patients with concurrent hepatic schistosomiasis and chronic hepatitis.For patients with concomitant liver cirrhosis,every effort should be made to minimize potential liver function impairment induced by other adverse factors.

Comparative Study of the Impact of Climate Variability on Prevalence of Urinary Schistosomiasis： Cases at Sunyani Regional Hospital and among School Children in Atronie, Sunyani

A study has been conducted to determine the impact of climate variability on Schistosoma haematobium infection among patients and school children in Sunyani between 2006 and 2009. Urine samples from the subjects were collected and examined in the laboratory using the Filteration technique for the detection and quantification ofSchistosoma haematobium eggs. The prevalence rate of urinary schistosomiasis at the Sunyani Regional Hospital for 2006, 2007, 2008 and 2009 were found to be 0.24%, 0.55%, 0.55% and 0.75% respectively while that for Methodist Junior High School in 2008 and 2009 were 60.1% and 60.3% respectively. A decrease in the relative humidity and average annual rainfall were identified as factors contributory to the increase in urinary schistosomiasis prevalence rate. The temperature values obtained throughout the study period did not have any significant effect on the prevalence rate. The temperature values, however, were those that enhanced cercarial incubation （15-35 ℃） with a resultant increase in shedding of cercariae leading to more infections among water contacts. The infection rate due to the stream Amama was 20.1%, while that due to river Tano was 36.6%. The highest risk group was children aged 15-19 years. Praziquantel was administered to treat the infection, producing a cure rate of 93%. Recognition of urinary schistosomiasis as a public health problem in Ghana is the main challenge to prevention and control of the disease.

Dynamic changes in the collagen metabolism of liver fibrosis at the transcription level in rabbits with Schistosomiasis japonica

OBJECTIVE: To study the role of the synthesis and degradation of collagen at the transcription level during liver fibrogenesis due to schistosomiasis japonica in rabbits. METHODS: New Zealand rabbits challenged by cercariae of Schistosoma japonicum (S. japonicum) were served as animal models for liver fibrosis. Liver specimens were collected through operations at 4, 6, 8, 10, 12, 16, 20, 24 and 28 wks after challenge. Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels of liver tissue were detected by RT-PCR + Dot blot. The size of egg granulomas and the degree of liver fibrosis were measured by histopathological examinations. RESULTS: Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased simultaneously in the early stage after challenge. Most of them reached their peak at 10 weeks, and compared with normal controls, type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased by 12.0-, 11.0-, 6.6-, 10.0- and 11.0-fold, respectively, coinciding with the change of egg granulomas, i.e., the change in the inflammatory process. Then both collagen and collagenase mRNA levels decreased. Type I, III and IV collagen mRNA levels declined to 2-fold to 3-fold as compared with normal controls (P 0.05) at 28 wks. This study shows that the synthesis and degradation of collagen keep a dynamic balance at the early stage of schistosomiasis japonica challenge, while at the later stages the quantity of collagen synthesis was higher than that of collagen degradation. CONCLUSIONS: It was confirmed at transcription level that when the quantity of collagen synthesis was higher than that of collagen degradation liver fibrogenesis may be resulted in.

Establishment of a cerebral schistosomiasis experimental model in rabbits

Objective The present study aimed to establish a cerebral schistosomiasis model in rabbits,to provide a valuable tool for morphological analysis,clinical manifestation observation,as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis（NS）.Methods Sixty New Zealand rabbits were randomly assigned into operation,sham-operation and normal groups.Rabbits in the operation group received direct injection of dead schistosome eggs into the brain,while their counterparts in the sham-operation group received saline injection.Rabbits in the normal group received no treatment.Base on the clinical manifestations,rabbits were sacrificed on days 3,5,7,10,20,and 30 post injection,and brain samples were sectioned and stained with hematoxylin-eosin.Sections were observed under the microscope.Results The rabbits in the operation group exhibited various neurological symptoms,including anorexy,partial and general seizures,and paralysis.The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation,with very mild inflammation.On days 7-10 post operation,several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them.The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation.On day 30,the schistosome eggs were found to be in the healing-by-fibrosis stage,and the granuloma area was replaced by fibrillary glia through astrocytosis.The sham-operation group and the normal group showed negative results.Conclusion This method might be used to establish the cerebral schistosomiasis experimental model.Several factors need to be considered in establishing this model,such as the antigenic property of eggs,the time of scarification,and the clinical manifestations.

Development of artemisinin drugs in the treatment of autoimmune diseases

Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artemisininbased therapy for malaria. Beyond antimalaria, artemisinin and its derivatives are also being investigated in diseases like schistosomiasis, viral infection, cancers and inflammation. Over the past decades, the anti-inflammatory and immunomodulatory effects of artemisinin drugs have been comprehensively studied. In this article, we will briefly describe the development of artemisinin drugs, especially novel artemisinin derivatives, in the treatment of autoimmune diseases.

A Mathematical Model with Delays for Schistosomiasis Japonicum Transmission

A dynamic model of schistosoma japonicum transmission is presented that incorporates effects of the prepatent periods of the different stages of schistosoma into Baxbour＇s model. The model consists of four delay differential equations. Stability of the disease free equilibrium and the existence of an endemic equilibrium for this model are stated in terms of a key threshold parameter. The study of dynamics for the model shows that the endemic equilibrium is globally stable in an open region if it exists and there is no delays, and for some nonzero delays the endemic equilibrium undergoes Hopf bifurcation and a periodic orbit emerges. Some numerical results are provided to support the theoretic results in this paper. These results suggest that prepatent periods in infection affect the prevalence of schistosomiasis, and it is an effective strategy on schistosomiasis control to lengthen in prepatent period on infected definitive hosts by drug treatment （or lengthen in prepatent period on infected intermediate snails by lower water temperature）.

Mechanisms and Techniques of Agroforestry Ecosystem on Snail Control and Schistosomiasis Prevention

Schistosomiasis, an important parasitic disease, is severely harmful to human heath in China . The beach along the Yangtze River is a important habitat of snail that is Schistosomiasis＇s only intermediate host. program of afforesting for wiping out snail（Oncomelania hupensisi） and Schistosomiasis, comprehensive administration and exploitation of the three kinds of beaches proposed by Peng Zhenhna and Jiang Zehui is a pioneering.work hased on the ecological and economic theory. The development process of forestry for snail control and Schistosomiasis prevention is reviewed, and mechanisms and major afforesting techniques are summarized in this paper.

MODELING THE SCHISTOSOMIASIS ON THE ISLETS IN NANJING

A compartmental model is established for schistosomiasis infection in Qianzhou and Zimuzhou, two islets in the center of Yangtzi River near Nanjing, P. R. China. The model consists of five differential equations about the susceptible and infected subpopu- lations of mammalian Rattus norvegicus and Oncomelania snails. We calculate the basic reproductive number R0 and discuss the global stability of the disease free equilibrium and the unique endemic equilibrium when it exists. The dynamics of the model can be characterized in terms of the basic reproductive number. The parameters in the model are estimated based on the data from the field study of the Nanjing Institute of Para- sitic Diseases. Our analysis shows that in a natural isolated area where schistosomiasis is endemic, killing snails is more effective than killing Rattus norvegicus for the control of schistosomiasis.

A novel and effective hyperthermia method for Schistosomiasis japonica prevention and treatment

The emerging resistance to schistosoma has been paid much attention and is in urgent need for a novel strategy to control the prevalent parasitic zoonosis. In this study, the efficiency of hyperthermia therapy was investigated by the skin hyperthermia device. The survival rate of cercariae decreased from 68.15 % （37 ℃, 5 min） to 0 （49℃, 10 min） with the thermal dosages increased, which proved the preventing effect of hyperthermia therapy （P 〈 0.05）. Therapeutic effects were assessed in Schistosoma japonicum-infected BALB/c mice. When the cercarial contact region of the skin was treated at 45-49℃ for 5 min within 8 h of infection, worm reduction rate （WRR） reached 74 %-83 % （P 〈 0.01）. The sensitivity of adult schistosoma to heat was also investigated using microwave intraperitoneal hyperthermia （thermal dosages 42-43℃, 20 min）. The WRR, hepatic shift rates and egg reduction rates were 23.7 %, 40 % and 30 %, respectively, comparing with 80.2 %, 59.6 % and 53.9 % of praziquantel （PZQ）-treated group. Encouraging results have been obtained that hyperthermia can effectively kill schistosomula, especially with the appearance of cercarial dermatitis, while PZQ lacks efficacy against the cercariae. Thus, hyperthermia therapy would show significant benefit in preventing and treatment of schistosoma, especially in the early stage.