Schistosoma mansoni was introduced in the Senegal basin around 1988, due to man-made ecological changes. Since 1991, we investigate a recent but very intense focus, Ndombo, a village near the city of Richard Toll where the outbreak was first described. Four cohorts, each a random sample (+/- 400 subjects each) from this community, were examined and followed up after treatment, starting at 8 month intervals over a 2-year period. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; followed up 6-10 weeks, one and two years after treatment; and monitored for water contact patterns and local snail densities. In the first cohort, the prevalence was 91%, with a mean egg count of 663 epg. Prevalences are near 100% in all age groups, but egg counts decline strongly in adults. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens, not e.g. of worm fecundity. This is surprising, as in this focus acquired immunity in adults should not have yet developed according to current hypothesis. The antigen detection assays (CAA/CCA) showed high sensitivity and quantitative power, and promising perspectives as a research tool and possibly as a method for non-invasive diagnosis and screening in urine. Epidemiological in subsequent cohorts were highly similar, although seasonal variations were observed possibly due to transmission fluctuations. Anti-AWA and anti-SEA IgE levels increased with age, while IgG4 peaked in the age-group 10 years and correlated well with egg counts.(ABSTRACT TRUNCATED AT 250 WORDS)
Ultrasonography (US) was applied in this community-based study in northern Madagascar to compare urogenital findings in Schistosoma haematobium-positive individuals (105 women and 116 men) from the high-endemic Sirama village, with urinary egg negative controls (100 women and 108 men) from the neighboring low-endemic Mataipako village. In addition to examination of the urinary tract, the female genitals were examined by transvaginal US, whereas the male genitals were examined by transrectal and transscrotal US. Pathology of the urinary tract was significantly more prevalent among women and men in Sirama. There were no differences in female genital tract between the two study populations, whereas significantly higher proportions of men in Sirama were detected with hyperechogenic and calcified lesions in the seminal vesicles and the prostate. Moreover, the mean size of the seminal vesicles was significantly larger in Sirama. There were no differences with respect to the external male genitals. Six months after anti-schistosome treatment, no changes were observed in the female genital tract in Sirama, whereas hyperechogenicity of the prostate and the seminal vesicles, in addition to size of the seminal vesicles, declined significantly. This study has provided new insight into genital pathology in S. haematobium-infected men and women. However, the clinical significance of these findings needs further exploration.
Parasitic worms of the genus Schistosoma excrete relatively large amounts of immunogenic glycoproteins (circulating cathodic antigen [CCA]) that contain polysaccharide side chains with the trisaccharide Lewis-x (L(ex)) as a repeating unit. These carbohydrates evoke high titers of specific IgM antibodies that cross-react with the repeating L(ex) units on the surface of granulocytes. Consequently this might lead, in the presence of complement, to lysis of the granulocytes. In the present study, this hypothesis was investigated using anti-CCA mouse monoclonal antibodies (MoAbs) and polyclonal antibodies purified from sera of infected humans. By flow cytometry, it was demonstrated that the mouse MoAbs directed against CCA strongly recognized the granulocytes. It could also be shown that these MoAbs, as well as anti- CCA IgM antibodies purified from infected human sera, caused lysis of granulocytes in a complement-dependent cytotoxicity assay. Sera from healthy controls or from patients with other helminth infections resulted in negligible granulocytotoxicity. These in vitro observed phenomena may explain the mild to moderate neutropenia that occurs in schistosomiasis patients.
The present work investigated the transplacental passage of circulating anodic schistosome antigens (CAA) and the production of foetal antibodies in response to antigenic stimulation in Schistosoma mattheei infected cows. Three groups were available: six calves born to non-infected cows received colostrum from a pool from non-infected cows (group 1), six calves born to non-infected cows (group 2) and six calves born to infected cows (group 3) received colostrum from a pool from infected cows. Schistosoma-specific IgG1 antibody and CAA levels were measured in the colostrum pools, the sera collected from the cows, and the sera collected from the calves at birth, after intake of colostrum and at day 30. The specific IgG1 antibody levels were significantly higher in the sera from cows of group 3. In four cows of group 3 high CAA levels were detected. The specific IgG1 antibody levels were 0.646 and 0.176 OD for the infected and non-infected colostrum pool, respectively, and the CAA levels were 5667 and 2557 pg CAA/mL, respectively. At birth high levels of specific IgG1 antibody and CAA were detected in 4 calves of group 3; levels in the other two calves were negligible. After intake of colostrum, specific IgG1 antibody levels of group 1 increased slightly at day 1 to become again insignificant at day 30. In group 2 specific IgG1 antibody levels increased significantly between days 0 and 1, to decrease, although not significantly, at day 30. Finally, in group 3 the delta OD values increased at day 1 and remained high until day 30. After intake of colostrum the CAA level increased very slightly for groups 1 and 2 to become again undetectable at day 30. In group 3 a nonsignificant decrease in CAA levels was observed at day 1 followed by a further significant decrease to reach low levels at day 30. The suggested intrauterine antigenic stimulation may be important not only for generating immune responses to natural early infections, but also for enhancing the immunogenicity and efficacy of vaccines administered to newborns.
Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S.mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.
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