Identification and characterization of Schistosoma mansoni antigens recognized by T and B lymphocytes of humans with early active intestinal and/or urinary schistosomiasis.

Schistosome antigens selected as vaccine candidates should induce in the majority of humans T and B cell-mediated immunity that results in protection against infection. As a first step towards the identification of such antigens, we attempted to define and characterize the soluble adult Schistosoma mansoni worm antigen (SAWA) bands that are recognized by serum antibodies and/or peripheral blood mononuclear cells of Egyptian children with early active S. mansoni and/or S. haematobium infection. Considerable inter-subject variation was observed in the SAWA bands recognized by antibodies and T lymphocytes, as demonstrated by Western blotting and T cell Western assays, respectively. The humoral response rate for the separated SAWA bands varied between 0% and 88% of infected subjects. The bands of 153, 144, 38 and 32 kDa reacted with the sera of 60 to 88% of infected subjects but not with the sera of uninfected controls. The bands of 144, 38, 32 and 18 kDa elicited proliferative responses in the lymphocytes of 42-63% of infected subjects. It was thus concluded that the SAWA bands of 144, 38 and 32 kDa are likely to carry T and B cell epitopes that could stimulate immune responses in a majority of individuals. The selected bands (144, 38 and 32 kDa) were found to include glycoproteins containing D-mannopyranosyl or glycosyl residues, and respectively 62.5, 46 and 55% amino acids by weight. The amino acid molar ratios of these bands were completely different.

Application of immunodiagnostic assays: detection of antibodies and circulating antigens in human schistosomiasis and correlation with clinical findings.

In an initial cross-sectional survey, serum, urine, and stool samples were collected from 370 participants representing about 10% of the population (n = 4,438) in Behbeet village, 50 km south of Cairo, Egypt, an area well known to be endemic solely for Schistosoma haematobium. Diagnosis was approached in two parallel ways. The first approach, which simulated actual conditions in many endemic areas in Egypt, was based on physical examination and urine and stool microscopic analysis. The second approach was based on two advanced immunodiagnostic assay systems. One system detected antibodies to species-specific microsomal antigens, the other detected circulating schistosomal antigens. Microsomal antigens from S. haematobium and S. mansoni were used to detect antibodies in the Falcon assay screening test (FAST)-ELISA and the enzyme-linked immunoelectrotransfer blot (EITB). Circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were quantified in serum and urine samples in a sandwich ELISA using monoclonal antibodies. Parasitologically, the prevalence of S. haematobium was 7.01% in females and 25.82% in males, giving an overall prevalence of 15.8%. The combination of urine CCA and serum CAA for detecting circulating antigens and the combination of the S. haematobium adult worm microsomal antigens (HAMA) FAST-ELISA and the HAMA EITB for detecting antibodies significantly improved the sensitivity of detecting S. haematobium circulating antigens and antibodies. Also, including a medical examination as an integral part of field studies and correlating immunodiagnostic results with other clinical and investigational data allowed us to calculate an accurate estimation of S. haematobium prevalence in this area of low endemicity.

Neobladder long term follow-up.

UNLABELLED: One of the commonest forms of orthotopic bladder substitution for bladder cancer survivors, used in our institute, is the use of ileocecal segment. Sometimes, the need for Indiana pouch heterotropic continent diversion arises. AIM: To compare the long-term effect of orthotopic ileocecal bladder and heterotropic Indiana pouch following radical cystectomy in bladder cancer patients. PATIENTS AND METHODS: Between January 2008 and December 2011, 91 patients underwent radical cystectomy/anterior pelvic exentration and orthotopic ileocecal bladder reconstruction (61 patients) and Indiana pouch (30 patients), when orthotopic diversion could not be technically or oncologically feasible. RESULTS: Convalescence was uneventful in most patients. All minor and major urinary leakage cases, in both diversions groups, where successfully conservatively treated. Only one patient in the ileocecal group with major urinary leak required re-exploration with successful revision of uretro-colonic anastomosis. Only one patient in the Indiana pouch group had accidentally discovered sub-centimetric stone, which was simply expelled. The overall survival proportion of ileocecal group was 100% compared to 80% in the Indiana pouch group (p<0.001). The disease free survival proportion of ileocecal group was 90.8% compared to 80% in the Indiana pouch group (p=0.076). Effective comparative daytime and nighttime urinary continence as well as renal function deterioration were not statistically significant between both reconstruction types. CONCLUSION: Both ileocecal bladder and Indiana pouch are safe procedures in regard to long-term effects over kidney function following radical cystectomy.

Schistosoma infection inhibits cellular immune responses to core HCV peptides.

Patients coinfected with hepatitis C virus (HCV) and the trematode, Schistosoma mansoni, have an increased incidence of viral persistence and accelerated fibrosis. To investigate immunological mechanisms responsible for this more aggressive natural history of HCV, the core HCV-specific T-cell responses were analysed in 44 donated blood units rejected because they had antibodies to HCV (anti-HCV). Half also had anti-S. mansoni antibodies, evidence of past or active infection. HCV-specific ELISPOT responses were examined using pools of 180 overlapping 9-mer peptides with offsets of one covering the core of HCV genotype 4a. Comparison of T-cell responses in blood units positive for both anti-HCV and anti-Schistosoma antibodies with blood units positive only for anti-HCV antibodies showed a significant decrease in core-specific T-cell IFN-gamma (505+/- 46 vs. 803 +/- 66 ISC/10(6) cells, P < 0.001), IL-4 (2 +/- 108 vs. 641 +/- 131 ISC/10(6) cells, P < 0.001), and IL-10 (159 +/- 105 vs. 466 +/- 407 ISC/10(6) cells, P < 0.002) responses. In contrast, there was no significant difference in cell-mediated immune response (CMI) to PHA mitogen between these two groups. Therefore, we concluded T cells from persons with anti-Schistosoma have reduced IFN-gamma, IL-4, and IL-10 secreting HCV-specific T-cell responses. This may explain why Schistosoma coinfection increases persistence and severity of HCV infection.

Epidemiology and immunodiagnosis of schistosomiasis haematobium in low endemic area in Egypt.

A survey was performed in Behbeet village in Giza governorate including 370 individuals (172 males and 198 females) representing 10% of the house holds. Clinical, stool, urine and serological tests accompanied by a questionnaire were applied to all participants to find out the prevalence, intensity of infection of S. haematobium, underlying sociodemographic factors, morbidity indicators and the awareness and treatment status among the infected population. It was revealed that the overall prevalence of S. haematobium based on the detection of eggs in urine was 18.1% while the prevalence of antibodies to S. haematobium species specific microsomal antigen was 57.6% detected by enzyme-linked immuno-transfer blot (EITB). The highest age specific prevalence and intensity of infection were detected among school children in the early teenage. Males were at a higher risk of contracting infection than females with a sex ratio of 2.5:1. Occupational and recreational water contact were significantly more frequent among the egg positives than the negative ones. Present history of haematuria and microhaematuria detected by reagent strips had the strongest association with S. haematobium infection followed by leucocyturia and dysuria. Microhaematuria had the strongest negative predictive value (85.7%) in discrimination between egg positive and negative groups while its positive predictive value was the highest (92.9%) when seropositives and negatives were discriminated. Less than half of the infected population were aware of having the disease (43.3% and 41.8% among the egg positives and seropositives, respectively) and lower percentages reported receiving previous treatment for schistosomiasis. No significant differences were detected between groups (P>0.05). Culturally appropriate and effective health education of the population, and training of the staff of rural health units to improve diagnostic and outreach skills are recommended.

T and B cell reactivity to a 42-kDa protein is associated with human resistance to both schistosomiasis mansoni and haematobium.

Egyptian subjects living in areas endemic for Schistosoma mansoni or Schistosoma haematobium were selected on the basis of their apparent extremes of resistance or susceptibility to schistosomiasis and examined for T and B cell responses against the major electrophoretically resolved protein species from soluble adult worm extracts. A 42-kDa band was specifically recognized by a significant majority of subjects resistant to schistosomiasis. The 42-kDa species (p-42) from S. mansoni and S. haematobium were immunologically cross-reactive and induced significant protection in mice and hamsters against infection with cercariae. Amino acid sequence analysis of S. mansoni p-42 showed that it consists predominantly of glyceraldehyde 3-P dehydrogenase (G3PDH), which has been shown to be preferentially recognized by the sera of Brazilian subjects resistant to schistosomiasis mansoni. The present data extend the previous findings and imply that S. mansoni-derived G3PDH represents a target of protective T and B cell-mediated antischistosomiasis immunity in humans.