Schistosomal glomerulopathy and changes in the distribution of histological patterns of glomerular diseases in Bahia, Brazil

Distinct patterns of glomerular lesions, including membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis, are associated with infection by Schistosoma mansoni or Schistosoma japonicum. Evidence suggests that immune complex deposition is the main mechanism underlying the different forms of schistosomal glomerulonephritis and that immune complex deposition may be intensified by portal hypertension. The relationship between focal segmental glomerulosclerosis and schistosomiasis remains poorly understood. A clinicopathologic classification of schistosomal glomerulopathies was proposed in 1992 by the African Association of Nephrology. In Brazil, mass treatment with oral medications has led to a decrease in the occurrence of schistosomal glomerulopathy. In a survey of renal biopsies performed in Salvador, Brazil, from 2003-2009, only 24 (4 percent) patients were identified as positive for S. mansoni infection. Among these patients, only one had the hepatosplenic form of the disease. Focal segmental glomerulosclerosis was found in seven patients and membranoproliferative glomerulonephritis was found in four patients. Although retrospective studies on the prevalence of renal diseases based on kidney biopsies may be influenced by many patient selection biases, a change in the distribution of glomerulopathies associated with nephrotic syndrome was observed along with a decline in the occurrence of severe forms of schistosomiasis.

Distribution of mast cells in relation to Schistosoma japonicum induced lesions in pigs.

The pathogenesis of schistosomiasis japonica has been extensively studied, however only little attention has been paid to the presence and localization of mast cells in relation to Schistosoma japonicum induced lesions. The aim of the present pilot study was to assess the parasitological and pathological responses in S. japonicum infected pigs with emphasis on the description of the distribution of mast cells in relation to lesions in the liver and cecum. Six pigs were exposed to 2,000 cercariae and examined 9 weeks post-infection. Three unexposed pigs of the same age served as helminth free controls. All infected pigs developed granulomatous hepatitis and typhlitis. In the liver, the degree of mast cell infiltration was higher in the infected pigs compared to the unexposed control group. This distinction could not be shown in the cecum. In both the liver and cecum, a mild to moderate number of mast cells were present within the granulomas. A significant relation was found between infection with S. japonicum and the mast cell infiltration in the liver. Due to their possible association with hepatic fibrosis, it seems as if they have some function in the fibrogenic process and thereby play a dual role in the pathogenesis of S. japonicum. In conclusion, the results show that mast cells are recruited to egg induced lesions in both the liver and the cecum.

The protective immunity of a DNA vaccine encoding Schistosoma japonicum Chinese strain triose-phosphate isomerase in infected BALB/C mice.

The development of a DNA vaccine for schistosomiasis japonica and testing the protective efficacy after challenge in BALB/c mice were performed. Thirty-nine female BALB/c mice were divided into three groups. Each mouse of the control group was injected intramuscularly with 100 microg of pcDNA3.1 DNA. In the TPI group, each mouse was injected with 100 microg of pcDNA3.1-SjCTPI DNA. The TPI+IL-12 group was injected with 100 microg of pcDNA3.1-SjCTPI DNA and 100 microg of the mixture of pcDNA3.1-P35 and pcDNA3.1-P40 DNA. Each mouse was immunized three times at two-week intervals and challenged with 45 cercariae of Schistosoma japonicum Chinese strain four weeks post-immunization. Then the mice were sacrificed and perfused at 45 days after challenge; the recovered worms and hepatic eggs were counted. Cytotoxic T lymphocyte (CTL) activity mediated by SjCTPI was detected with the 51Cr release assay. ELISA was performed for the detection of anti-rTPI antibodies. Anti-rTPI antibody detection with ELISA after immunization showed ten serum samples from the control group were negative, five of ten serum samples from the TPI group were weakly positive, six of ten from the TPI+IL-12 group were also weakly positive. The CTL activity of the control group was 9.1%, while CTL activities of the TPI group and the TPI+IL-12 group were 27.6% and 54.4%, respectively. The worm and egg reduction rates of TPI group and the TPI+IL-12 group were 30.2%, 52.9%, 32.7%, and 47.0%, respectively in comparison with the control group. This study further proved the possibility of the SjCTPI DNA vaccine as a potential DNA vaccine for schistosomiasis.

Protective immunity induced with 23 kDa membrane protein dna vaccine of Schistosoma japonicum Chinese strain in infected C57BL/6 mice.

A 23 kDa membrane protein DNA vaccine for Schistosoma japonicum Chinese strain was developed and tested for its protective efficacy and immune responses in infected C57BL/6 mice. The cDNA encoding SjC23 amplified from pUC19-SjC23 were subcloned into an eukaryotic expression vector (pcDNA3.1). Forty-eight female C57BL/6 mice were divided into three groups. Each mouse of group A (control group) was immunized intramuscularly (i.m.) with 100 microg of pcDNA3.1; of group B (SjC23 group) was immunized (i.m.) with 100 microg of pcDNA3.1-SjC23; of group C (SjC23+IL-12) was immunized (i.m.) with a mixture of 100 microg of pcDNA3.1-SjC23, 100 microg of pcDNA3.1-p35 and 100 microg of pcDNA-p40. These were followed by two boosts of the same DNA once every two weeks. All mice were challenged with 45 cercariae of Schistosoma japonicum Chinese strain at week 8, and were killed and perfused at week 14. The numbers of recovered worms and hepatic eggs were counted. The expression of SjC23 and p35, p40 in muscle tissue was determined by immunohistochemical method. By culture of spleen cells, the production of IL-2, IL-4, IL-10 and IFN-gamma with the stimulation of specific antigen of the recombinant hydrophilic domain of SjC23 (rSjC23-HD) was determined after the last immunization (before challenge). Sera were collected from each group before immunization and two weeks before and after challenge. Anti-SjC23 antibodies were tested by Western blot. The results showed that SjC23 and p35, p40 of mouse IL-12 were expressed on the membrane and in the plasma of the muscle cells of immunized C57BL/6 mice. A rise of IL-2 and IFN-gamma in the SjC23 group and SjC23+IL-12 group was observed; No changes were found in IL-4 and IL-10. Detection of anti-SjC23 antibody with Western blot showed that after the third immunization (before challenge) all the serum samples from the control group were negative; 8 of 10 sera from the SjC23 group and 9 of 10 sera from the SjC23+IL-12 group were positive. The worm reduction rates in the SjC23 group and SjC23+IL-12 group were 26.9% and 35.4% respectively; the liver eggs reduction rates were 22.2% and 28.4%, respectively in comparison to the control group. This indicates that the pcDNA3.1-SjC23 DNA vaccine can induce partial protection against Schistosoma japonicum infection in C57BL/6 mice.

Anti-embryonation immunity in murine schistosomiasis japonica (Philippines)

The hypothesis that granuloma modulation and disease abatement in chronic infection with Schistosoma japonicum could be ascribed to antibody-mediated effects on egg maturation and egg viability, arose from studies performed with mice in the Philippines. This novel hypothesis has not yet been integrated into the schistosomiasis literature despite being formulated more than a decade ago. One reason for this is that the phenomenon might be confined to S. japonicum, even S. japonicum (Philippines).

Application of alcohol- or acetone-fixed Schistosoma eggs as an alternative to lyophilized eggs for the circumoval precipitin test.

Antigenicity of Schistosoma mansoni and S. japonicum eggs preserved in ethanol or acetone were assessed in a circumoval precipitin (COP) assay. The egg antigens were found to retain sufficiently their COP reactivity for the diagnosis of both schistosomiasis mansoni and japonica, although their reactivity became lower than that of lyophilized eggs. These alternative preparations for COP tests have advantages, such as keeping eggs directly in fixatives soon after the egg-purification process. Furthermore, evaporation-process may cause eggshell cleavages which facilitate the reaction. The possible usefulness of those eggs in COP assays in local endemic areas is discussed.

Detection of antibodies against Opisthorchis viverrini in patients before and after treatment with praziquantel.

Levels of antibody in sera of 78 patients with opisthorchiasis, 30 patients with other liver diseases, 10 patients with schistosomiasis and 30 healthy individuals were compared using three serodiagnostic tests, namely indirect haemagglutination (IHA), enzyme-linked immunosorbent assay (ELISA) and lectin immuno test (LIT). The geometric mean reciprocal titer in sera of opisthorchiasis patients was significantly higher than patients with other diseases, patients with schistosomiasis and healthy individuals (p less than 0.00001). After treatment with praziquantel, the antibody titers were decreased and became lowest 120 days after treatment. A statistically significant decrease from the pre-treatment sample was observed only at 120 days after infection and not earlier and only with ELISA (p = 0.03) and not with IHA and LIT (p greater than 0.05). Even with ELISA, significant decrease in antibody titer was apparent only when the pre-treatment sera had high enough antibody titer. ELISA was therefore better than the other two tests for the assessment of cure provided that the titer of pre-treatment sera was high.

Evidence of anti-embryonation immunity and egg destruction in mice sensitized with immature eggs of Schistosoma japonicum.

BALB/c mice sensitized by repeated injections of immature eggs of the trematode worm, Schistosoma japonicum, were challenged with low numbers of cercariae and evidence was sought for inhibition of embryonation by examination of eggs in livers and intestines at days 40 - 42 of infection. In contrast to the situation in unsensitized control mice, a greater proportion of dead eggs was noted in tissues of many of egg-sensitized mice. There was also a decrease in the proportion of mature eggs relative to control mice. A substantial number of egg - sensitized mice contained no eggs in the liver though eggs were readily detected in their intestinal walls. The data support the concept that immune effector mechanisms act on eggs in a manner that prevents their full development into a miracidium and thus a rich source of immunopathologic antigens.