Schistosomiasis.

Schistosomiasis is a man-made disease related to water contact in the agricultural fields and affecting millions of people in developing countries in the tropical and subtropical parts of Africa, Asia and South America. It is a bisexual trematode living in the portal blood and perivesical venous plexus. Its life cycle necessitates the presence of an intermediate host - a fresh water mollusc - that differs according to place. The pathogenetic stage is the ova that initiate an immunologically delayed hypersensitivity cell-mediated reaction in the organs where they are deposited. The liver, colon, urinary bladder and ureter are the main organs affected; however, any organ can be affected, even the skin and the brain. The review discusses the pathogenesis, pathology, diagnosis: parasitological and immunological, the clinical picture, treatment and control. The present status of the research work on vaccination is also presented.

Immunoglobulin-A and the pathogenesis of schistosomal glomerulopathy.

Several observations suggest that the evolution of schistosomal glomerulopathy into clinically overt and progressive disease may involve pathogenetic mechanisms other than simple glomerular deposition of parasitic antigens. In a previous study, IgA was suggested to be a mediator of late glomerular lesions in this disease. This issue is further addressed in this work. The study includes 32 patients with hepatosplenic schistosomiasis, of whom 16 had overt glomerular involvement, along with four control groups: (a) 15 healthy volunteers; (b) 15 patients with simple intestinal mansoniasis; (c) 17 patients with non-schistosomal chronic liver disease; and (d) 21 subjects with primary nephrotic syndrome not associated with schistosomiasis. Routine assessment was done for all subjects including confirmatory tests for schistosomal infection, liver and renal function tests, hepatitis viral markers and abdominal ultrasonography. The total serum concentrations of IgG, IgM, IgA were measured, as well as their respective circulating immune complexes, rheumatoid factors, anti-gliadin- and anti-DNA-antibodies. Liver and renal biopsies were obtained from the relevant groups and studied by light microscopy. Renal biopsies were also examined by immunofluorescence. Patients with simple intestinal schistosomiasis had a significant increase in IgM antigliadin antibodies. Those complicated with hepatosplenic involvement also had a significant increase in the mean IgG anti-gliadin antibodies, IgG rheumatoid factor and IgM anti-DNA activity. Cases further complicated by overt glomerular disease showed a distinct IgA predominance, mainly expressed in the serum anti-gliadin antibody pool and anti-DNA activity. This profile was essentially similar to that observed in control cirrhotics. There was a significant increase in the frequency of IgA glomerular deposits in renal biopsies obtained from patients with overt schistosomal glomerulopathy, in contrast to control nephrotics. The deposits were mainly mesangial, but were also encountered in subendothelial, subepithelial and peritubular locations. Their frequency was significantly higher with more advanced lesions as seen by light microscopy. The relevance of these data is discussed, leading to the following conclusions: (a) serum IgA-anti-gliadin and -anti-DNA antibodies, and glomerular IgA deposits are markers of significant renal involvement in patients with hepatosplenic schistosomiasis. (b) IgA may be involved in the pathogenesis of advanced glomerular pathology when superimposed on parasite-induced lesions. (c) There is a significant increase in serum auto-reactivity in hepatosplenic schistosomiasis, which may also have pathogentic implications. (d) Increased production by the inflammatory bowel lesions, impaired clearance by the fibrotic livers and probable switching of immunoglobulin synthesis are suggested to explain the observed IgA predominance in those who develop renal complications.

Detection of circulating anodic antigen before and after specific chemotherapy in experimental murine Schistosomiasis mansoni.

In two groups of mice infected with 60 (group I) and 120 (group II) Schistosoma mansoni cercariae, respectively, the effects of intensity and duration of infection, and of praziquantel therapy (curative vs subcurative dose) on the levels of circulating anodic antigen (CAA), were studied. CAA was measured in trichloracetic acid-treated serum samples with an avidin-biotin enzyme-linked immunosorbent assay (AB-ELISA) using the monoclonal anti-CAA antibody. Total worm burdens, oogram patterns and ova counts/g liver and intestine were followed up. The lowest detectable level of CAA was about 1.0 ng/ml, and was positive with a worm load of 3-5/mouse. CAA levels became already detectable as early as 1-2 weeks post-infection (pi) before any parasitological parameter and showed a significant drop from the 11th-12th week pi onwards. A positive correlation was demonstrated between the CAA level and worm load. Following successful praziquantel therapy, CAA disappeared earlier than any of the other parameters studied.

Effect of specific chemotherapy on the immune response and resistance to reinfection in experimental Schistosomiasis mansoni.

Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with praziquantel in a dose of 500 mg/kg for two consecutive days had a significant lower resistance to reinfection when challenged two weeks after treatment (45% compared to 88% in infected challenged untreated mice). In praziquantel-treated mice, the reduction in the per cent resistance was accompanied by a diminution in the size of hepatic granulomata and its in vivo correlate the delayed foot pad swelling. Moreover, the granuloma proportionate T-cell subset enumeration revealed a significant reduction in the number of T-helper cells. The humoral immune response as measured by the immediate foot pad swelling was not affected by praziquantel. Results reveal besides the diminution of the state in resistance to reinfection after praziquantel, possible involvement of egg-related pathology as a T-cell mediated reaction and as a mechanical obstacle in maintenance of this resistance.

Levamisole restored the compromised state of immunity after specific chemotherapy in experimental schistosomiasis mansoni.

Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with levamisole (25 mg/kg subcutaneously) have more efficient acquired immunity when challenged with 240 Schistosoma mansoni cercariae the same day of treatment (97.7% # 87.7% in infected challenged controls). In praziquantel-treated mice (500 mg/kg for 2 days orally), the reduction in the percent resistance (45.5%) was accompanied by a significant diminution in the size of granuloma, delayed foot pad swelling and granuloma proportionate T-helper cells number. Levamisole when given two weeks post praziquantel treatment and with the challenge infection increased the percent resistance to 79.2%. The increase in percent resistance recorded in mice receiving both praziquantel and levamisole was accompanied by restoration of granuloma size, delayed foot pad swelling and granuloma proportionate T-helper cells number to infected challenged untreated control values. Results reveal-beside efficacy of levamisole as immunoregulant in schistosome immunity--a possible role for the granuloma as a T-cell mediated response in maintenance of immunity.