Enhancement of protective efficacy through adenoviral vectored vaccine priming and protein boosting strategy encoding triosephosphate isomerase (SjTPI) against Schistosoma japonicum in mice.

BACKGROUND: Schistosomiasis japonica is a zoonotic parasitic disease; developing transmission blocking veterinary vaccines are urgently needed for the prevention and control of schistosomiasis in China. Heterologous prime-boost strategy, a novel vaccination approach, is more effective in enhancing vaccine efficacy against multiple pathogens. In the present study, we established a novel heterologous prime-boost vaccination strategy, the rAdV-SjTPI.opt intramuscular priming and rSjTPI subcutaneous boosting strategy, and evaluated its protective efficacy against Schistosoma japonicum in mice. METHODOLOGY/PRINCIPAL FINDINGS: Adenoviral vectored vaccine (rAdV-SjTPI.opt) and recombinant protein vaccine (rSjTPI) were prepared and used in different combinations as vaccines in a mouse model. The specific immune responses and protective efficacies were evaluated. Furthermore, the longevity of protective efficacy was also determined. Results showed that the rAdV-SjTPI.opt priming-rSjTPI boosting strategy elicited higher levels of specific IgG responses and broad-spectrum specific cellular immune responses. The protective efficacy could reach up to nearly 70% and 50% of protection could be observed at 10 weeks after the last immunization in mice. CONCLUSIONS/SIGNIFICANCE: The rAdV-SjTPI.opt intramuscular priming-rSjTPI subcutaneous boosting vaccination strategy is a novel, highly efficient, and stable approach to developing vaccines against Schistosoma japonicum infections in China.

Allograft inflammatory factor-1 alleviates liver disease of BALB/c mice infected with Schistosoma japonicum.

Allograft inflammatory factor-1 (AIF-1) plays an important role in various inflammatory conditions. Our previous study demonstrated that AIF-1 was over-expressed in the liver of BALB/c mice infected with Schistosoma japonicum and played significant role in the pathogenesis of schistosomiasis. The aim of this study was to focus on the effect of AIF-1 treatment on liver fibrosis and necrosis of BALB/c mice infected with S. japonicum. Seventy-two BALB/c mice were infected with cercariae of S. japonicum and then divided into three groups: AIF-1-treated group, saline-treated group, and control group. The vital signs, liver function, egg load, and hepatic pathological changes of the mice were assessed, and the levels of AIF-1 and TNF-α in the liver and spleen were measured at 5, 8, and 14 weeks postinfection. The treatment of AIF-1 on the mice infected with S. japonicum suppressed the expression of TNF-α and increased the effectiveness of AIF-1 in the liver and spleen at 14 weeks postinfection. Histopathological analysis and Masson trichrome staining for the liver tissues showed that the liver fibrosis and necrosis were alleviated previously compared with other infected mice at 14 weeks postinfection. The treatment of AIF-1 on the mice infected with S. japonicum can alleviate hepatic fibrosis and necrosis which indicate that AIF-1 use may prevent and cure the liver fibrosis.

[Causes of death of advanced schistosomiasis patients in Jiaxing City from 1998 to 2008].

OBJECTIVE: To understand the causes of death of advanced schistosomiasis patients in Jiaxing City from 1998 to 2008, so as to provide the evidence for improving the diagnosis and treatment of advanced schistosomiasis patients. METHODS: The data of advance schistosomiasis inpatients from April 1998 to March 2008 were collected, analyzed and combined with the following up to understand the epidemic characteristics and the causes of death of advance schistosomiasis patients. RESULTS: There were 2 004 of advanced schistosomiasis inpatients and 202 patients died. Among the 202 cases, 39.60% of patients were 60-70 years old and 34.65% 70-80 years old. The death causes included upper gastrointestinal hemorrhage (69 cases, 34.16%), hepatic encephalopathy (45 cases, 22.84%), and others. CONCLUSION: The upper gastrointestinal hemorrhage and hepatic encephalopathy were the main causes of death of advanced schistosomiasis patients in Jiaxing City during the past 10 years.

[Burden of disease in schistosomiasis japonica. II. Measurement of health inequalities due to chronic schistosomiasis].

OBJECTIVE: To measure and evaluate the health inequalities due to chronic schistosomiasis japonica. METHODS: Based on years lived with disability (YLD) caused by chronic schistosomiasis, a concentration index and Gini index, along with a concentration curve and Lorenz curve, the health inequalities between sexes, age groups or endemicities were identified and quantified. RESULTS: The age concentration index was 0.395 of females and 0.380 of males, with no significant difference between them. More than 60% of YLD was contributed by those aged > or = 45 years old who accounted for about a third of total population in both sexes. Gini index was 0.666 of Dangtu County and 0.451 of Hanshou County, and 60% of YLD was contributed by the highly endemic villages. CONCLUSIONS: The concentration index and Gini index could quantify the magnitude of health inequalities well. The priority of morbidity control should be given to those aged > or = 45 years old and living in highly endemic villages.

A diagnostic challenge for Schistosomiasis japonica in China: consequences on praziquantel-based morbidity control.

Worldwide schistosomiasis continues to be a serious public health problem. Over the past five decades, China has made remarkable progress in reducing Schistosoma japonicum infections in humans to a relatively low level. Endemic regions are currently circumscribed in certain core areas where re-infection and repeated chemotherapy are frequent. At present, selective chemotherapy with praziquantel is one of the main strategies in China's National Schistosomiasis Control Program, and thus diagnosis of infected individuals is a key step for such control. In this paper we review the current status of our knowledge about diagnostic tools for schistosomiasis japonica. A simple, affordable, sensitive, and specific assay for field diagnosis of schistosomiasis japonica is not yet available, and this poses great barriers towards full control of schistosomiasis. Hence, a search for a diagnostic approach, which delivers these characteristics, is essential and should be given high priority.

Expression, purification, and human antibody response to a 67 kDa vaccine candidate for schistosomiasis japonica.

Schistosomiasis remains a leading cause of morbidity and mortality in the developing tropical world, and vaccines to prevent these infections remain a scientific and public health priority. Sj67 is a 67 kDa Schistosoma japonicum surface membrane protein homologous to a family of actin-binding proteins. Sj67 is recognized by a mouse monoclonal antibody (mAb 6) that confers resistance to challenge infection in passive transfer experiments. These data support Sj67 as a potential vaccine candidate for schistosomiasis japonica. In the present study, we report the ligation-independent cloning of a cDNA encoding thioredoxin/elastin-like polypeptide (ELP)/rSj67 into a pET-32 Xa/LIC vector. Soluble recombinant fusion protein (Thio-ELP-rSj67) was expressed and purified using anion-exchange and size exclusion chromatography. rSj67 was cleaved from the Thio-ELP fusion partner by digestion with Factor Xa protease and purified using hydroxyapatite column chromatography. Endotoxin was reduced by absorption to a polymyxin support. Purified rSj67 had a molecular weight of 67 kDa and N-terminal sequencing confirmed that the first five amino acids of the recombinant protein matched the predicted sequence for the Sj67 gene. In Western blot analysis, rSj67 was recognized by the Sj67 specific mAb 6 antibody. IgG antibodies in sera from schistosomiasis infected volunteers living in an endemic area of the Philippines (n = 13) recognized rSj67 with 4.7-fold greater median fluorescence compared to uninfected North American controls (n = 5) (p < 0.009). Together, these data confirm the expression and purification of recombinant Sj67 and its immuno-reactivity with sera from S. japonicum infected humans.

[Effect of experimental infection with Schistosoma japonicum on the pregnancy of mice].

OBJECTIVE: To understand the effect of Schistosoma infection on the gestation in mice. METHODS: Female mice infected with Schistosoma japonicum cercariae, and mated with male mice (uninfected) at 40 d and 100 d post-infection, the changes during pregnant period and the growth of offspring were observed until birth. The serum level of estradiol and progesterone of the infected mice was measured by RIA at oestrus. RESULTS: The level of estradiol and progesterone, and the pregnant rate were much lower in schistosome infected group than that of the control. The rate of abortion, the mortality of pregnant mice and the death rate due to abortion of infected mice increased significantly. The mortality increased with the time of merging male and female mice in one cage prolonged. The body weight and length of the offspring in both infected and control groups were found no significant difference. CONCLUSION: The results revealed that schistosome infection may suppress estradiol and progesterone secretion, decrease the rate of pregnancy, and that it may also increase the complications and mortality during the gestation periods.

[Evaluation of the effect of causes of death of advanced schistosomiasis patients on the life span of population by using potential years of life lost analysis].

AIM: To evaluate the effect of the causes of death of advanced schistosomiasis patients on the life span of population in an area where schistosomiasis had been under control by applying the indicators of potential years of life lost (PYLL) and rate of PYLL (PYLLR). METHODS: Using the formula of calculation of PYLL and PYLLR, the causes of death of 487 patients of advanced schistosomiasis in 3 previously endemic townships of Shanghai suburb. RESULTS: Of 487 cases who died between 1955 and 1995, the PYLLR of all causes of death was 256.3@1000. The main causes of death were hepatic failure (100.3@1000), liver carcinoma (43.4@1000) and cancer of other organs (24.8@1000). In the 1960s, the PYLLR of advanced schistosomiasis complicated with hepatic failure and upper digestive tract hemorrhage was 222.2@1000 and 34.5@1000, the PYLLR of the complications of schistosomal liver cirrhosis, hepatic failure and hemorrhage accounted for 67.5% of the total PYLLR, being apparently higher in the non-splenectomy group than in the splenctomty group. After the schistosomiasis was under control, both PYLL and PYLLR decreased linearly. As compared with the 1960s, the PYLLR of all causes of death and the causes of death of the complications of schistosomal liver cirrhosis in the 1990s has declined by 62.9% and 83.2%, respectively, the PYLLR of upper digestive tract hemorrhage was found only 0.3@1000 in the last 5 years. CONCLUSION: PYLL and PYLLR analysis could be used to quantify the effect of complications of advanced schistosomiasis and other causes of death on the life span of population.

A study and analysis of the deaths due to advanced Schistosoma japonicum infection in the Dongting Lake area of China.

This study collected records of 245 cases of death due to advanced schistosomiasis japonica in the eastern Dongting Lake area between 1985 and 1990. The mean survival of the patients was 5.16 years. The patients with ascitic type had a shorter expected life while the life span of splenomegalic type patient markedly improved after splenectomy. The HBsAg positive rate was 43.64%; the rate of those complicated with carcinoma of liver was 19.18%. The latter group had a HBV infection rate as high as 61.70%.

An attempt to study the case fatality rate in Schistosoma japonicum infection in the Philippines.

As a sequence to a cross-sectional study on the clinical gradient of the disease by Pesigan et al., (1965) a follow-up of the subjects in that study was made after 12 years. Of the 135 untreated cases followed up, 23 (17.04%) died from various causes of which 12 (8.89%) had signs and symptoms attributable to schistosomiasis as the immediate cause or one of the main causes of death. This occurred in 1 to 11 years with an average of 5 years, which corresponds roughly to 1.78% of the infected cases per year. This is considered a conservative estimate because in the other deaths due to other diseases, schistosomiasis is a contributory cause. A diminishing severity of the disease was observed among the surviving patients which could imply that they must have developed some degree of immunity to the disease.