Sonographic prediction of variceal bleeding in patients with liver fibrosis due to Schistosoma mansoni.

Several studies have shown that the characteristic hepatic abnormalities induced by Schistosoma mansoni detectable by ultrasound correlate with the degree of oesophageal varices. So far the value of ultrasound for predicting variceal haemorrhage has not been assessed. Fifty Brazilian patients with schistosomal periportal fibrosis from Alagoas State, 18 of whom had already bled from oesophageal varices, were enrolled in a combined cross-sectional and longitudinal study and investigated clinically, by endoscopy and by ultrasound. Twenty-seven of the patients were monitored until another bleeding episode, death or for a minimum of 28 months. Eight of these patients could be followed up for a further three years. A sonographic score, which accounts for the degree of echogenic periportal thickening and of portal vein dilatation, was calculated for all patients. A highly significant correlation (P < 0.0001) existed between the sonographic score and the occurrence of previous variceal haemorrhage, paralleled by a similar correlation between the sonographic score and the degree of oesophageal varices (P < 0.001). In the 27 patients monitored longitudinally, the sonographic score indicated the risk of future variceal bleeding (P < 0.0001). The sonographic score reliably predicts the risk of variceal bleeding in individual patients with periportal fibrosis. Hence, the application of endoscopy, if available at all in endemic areas, may be restricted to the patients at risk of future variceal bleeding, as determined by ultrasound. Since portable devices can be carried even to remote areas, the application of the proposed score in community surveys could provide a new means for the identification of high-risk patients in S. mansoni-infected populations.

Altered generation of interleukin 1 in chronic human schistosomiasis mansoni.

Chronic schistosomiasis mansoni is associated with impaired cell-mediated immune responsiveness (CMI). To assess co-stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL-1) concentration was determined in the sera and cell culture supernatants of Schistosoma mansoni-infected patients, and circulating monocytes were phenotyped, labelling membrane IL-1 and HLA-DP. In addition, adherent cell oxidative-burst capacity was investigated. Since involvement of IL-1 beta in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3-6 months after praziquantel therapy. Seventeen age- and sex-matched uninfected residents of the study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monocyte surface antigens and the capacity of adherent cells to generate H2O2, IL-1 beta release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL-1 beta were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL-1 beta was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL-1 release in vitro gradually increased in all patients and reached control values 6 months after therapy.

Tumour necrosis factor in hepatosplenic schistosomiasis.

Periportal fibroplasia is the dominating feature of hepatosplenic schistosomiasis. Since monokines play an important role in the regulation of fibroplasia, tumour necrosis factor (TNF) and interleukin 1 beta (IL-1 beta) were assessed in sera and cell culture supernatants from patients with intestinal and hepatosplenic schistosomiasis before and 3-6 months after treatment with praziquantel. Uninfected controls were from the study area in Alagoas, Brazil. TNF was measured using an L-M mouse fibroblast bioassay and radioimmunoassays specific for TNF-alpha. Whereas TNF-alpha was elevated threefold in the patients' sera, three- to five-fold reductions of TNF were observed by radioimmunoassay and bioassay, respectively, in cell culture supernatants of hepatosplenic schistosomiasis patients. Significant deviations, in opposite directions, from TNF levels in control sera and supernatants are most plausible in the event of a sequestration of TNF-alpha-producing cells from the circulation. This process may be disease stage-specific since a dichotomy between incipient and advanced cases of hepatosplenic schistosomiasis became apparent in the amplitude and kinetics of changes during the follow-up after treatment.

T cell phenotype alterations in hepatosplenic schistosomiasis mansoni normalize after chemotherapy.

Peripheral blood T cell phenotypes, CD3-induced mitogenesis and soluble IL 2 receptor and CD8 in sera were studied in intestinal and hepatosplenic Schistosomiasis mansoni before and three to six months after therapy with praziquantel. Fifteen pairs matched for intensity of infection were analyzed and compared with local, non-infected age-matched controls. CD3+ cell counts were lower in untreated hepatosplenic schistosomiasis (median 1040 cells/microliters; 95% confidence interval 608-1269) compared to controls (1534; 1264-1620). This difference was largely accounted for by immature CD1+/CD3-cells circulating in these patients (median 388/microliters, 252-474). The frequency of CD1+ T cells in circulation decreased drastically after chemotherapy. Similar, but less marked, alterations were seen in intestinal schistosomiasis. Lymphocyte proliferation initiated by agonistic anti-CD3 monoclonal antibody was severely impaired in hepatosplenic patients, who had suffered haemorrhagic complications, but not in the cases of incipient hepatomegaly. Soluble CD8 antigen circulated in increased amounts in hepatosplenic schistosomiasis. Remarkably, a negative correlation between CD3-induced mitogenesis and circulating levels of CD8 was noted in these patients. Whereas CD3-induced mitogenesis in hepatosplenic schistosomiasis normalized after therapy, circulating IL 2R and CD8 antigen in hepatosplenic patients still exceeded control levels. The results demonstrate disturbances of CD3 and CD8 expression and/or T cell maturation in hepatosplenic schistosomiasis. Imbalanced CD4/CD8 ratios and an increased IL 2R/CD8 turnover may reflect an inhibitory circuit within the T cell compartment.

Release of interleukin 2 and gamma interferon by peripheral mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy.

Interleukin 2 (IL-2) and gamma interferon (IFN-gamma) were determined in supernatants of mitogen- and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-gamma production was reduced more severely in hepatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-gamma activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.