Abstract. Health questionnaires and parasitologic examinations of urine and stool were evaluated from a stratified random sample of 89,180 individuals from 17,172 households in 251 rural communities in 9 governorates of Egypt to investigate the prevalence of, risk factors for, and changing pattern of infection with Schistosoma sp. in Egypt. A subset, every fifth household, or 18,600 subjects, had physical and ultrasound examinations to investigate the prevalence of and risk factors for morbidity. Prevalence of S. haematobium in 4 governorates in Upper Egypt in which it is endemic ranged from 4.8% to 13.7% and averaged 7.8%. The geometric mean egg count (GMEC) ranged from 7.0 to 10.0 ova/ 10 ml of urine and averaged 8.1. Age stratified prevalence of infection peaked at 15.7% in the 10-14-year-old age group and decreased to 3.5-5.5% in all groups more than 25 years of age. Age-stratified intensity of infection peaked at approximately 10.0 ova/10 ml of urine in the 5-14-year-old age groups and was about half that in all groups more than 25 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma mansoni was rare in Upper Egypt, being consequential in only Fayoum, which had a prevalence of 4.3% and an average intensity of infection of 44.0 ova/g of stool. Risk factors for S. haematobium infection were male gender, an age Ͻ21 years old, living in smaller communities, exposures to canal water; a history of, or treatment for, schistosomiasis, a history of burning micturition or blood in the urine, and reagent strip-detected hematuria or proteinuria. The more severe grades (II and III) of ultrasonography-detected periportal fibrosis (PPF) were rare (15 of 906) in these schistosomiasis haematobia-endemic governorates. Risk factors for morbidity (ultrasonography-detected urinary bladder wall lesions and/or obstructive uropathy) were similar to those for infection, with the exception that risk progressively increased with age. Subjects with active S. haematobium infections were 3 times as likely as those without active S. haematobium infections to have urinary tract morbidity. The prevalence of S. mansoni in 5 governorates in Lower Egypt, where it is endemic, ranged from 17.5% to 42.9% and averaged 36.4%. The GMEC ranged from 62.6 to 93.3 eggs/g of stool and averaged 81.3. Age-stratified prevalence of infection peaked at 48.3% in the 15-19-year-old age group, but averaged 35-45% in all groups more than 10 years of age. The intensity of infection was highest in the 10-14-year-old age group, and showed a range of 70-85 eggs/g of stool in those Ն5 years of age. Males had higher infection rates and ova counts than females in all age groups. Schistosoma haematobium was rare in these governorates; Ismailia (1.8%) had the highest infection rate. Risk factors for S. mansoni were male gender, an age Ͼ10 years old, living in smaller communities, exposures to canal water, a history of, or treatment for, schistosomiasis or blood in the stool, detection of splenomegaly by either physical...

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Abstract. This supplement is a report on the Epidemiology 1, 2, 3 (EPI 1, 2, 3) investigation, its origins, evolution, and findings that were carried out over a period beginning in 1990 and ending in 1994 in Egypt. The large scope and size of the study, the largest to date on schistosomiasis in Egypt, was a rationale for publishing a supplement to document EPI 1, 2, 3 methods and results collectively in sufficient detail to serve as a reference for planning, designing, and analyzing future epidemiologic studies and evaluation of schistosomiasis control in Egypt. The 3 objectives of EPI 1, 2, 3 were to 1) determine the changing patterns of Schistosoma haematobium and S. mansoni, 2) investigate factors contributing to differences between villages in the Nile Delta, Middle Egypt, and Upper Egypt, and 3) investigate risk factors for morbidity. The objectives were addressed using standardized techniques, stool and urine examinations, clinical examinations (including abdominal ultrasound), and questionnaires on a selected sample of the populations of selected villages in 9 governorates in Egypt.

An antigen-capture ELISA using monoclonal antibody (MAb) 128C3/3/21 was used to detect circulating parasite-derived antigens in the sera of patients actively infected with Schistosoma haematobium (31 males and four females, 5-25 years of age). The assay had a sensitivity of 100% (35 of 35 patients with antigen levels Ͼ 80 ng/ml) and a specificity Ͼ 99%. We used this ELISA to monitor antigenemia before treatment and one, three, and six months after treatment with a single oral dose of praziquantel (PZQ) (60 mg/kg in 20 patients or 40 mg/kg in 15 patients) and compared our findings with those indicated by other measures of disease progression. Circulating antigen levels decreased drastically after PZQ treatment (P Ͻ 0.001), with a significantly higher decrease occurring after treatment with 60 mg/kg than with 40 mg/kg. Although the mean antigen level was still significantly reduced (P Ͻ 0.001) at six months after treatment, 16 patients remained antigen-positive after six months, and nine had increased levels of antigenemia, reflecting reinfection in six patients and persistence of infection in another. We observed a correlation (r ϭ 0.6, P Ͻ 0.01) between the level of circulating antigen and the intensity of infection as measured by egg count. We also found a direct relationship (P Ͻ 0.001) between antigen level and the severity of the disease as monitored by ultrasonography. We conclude that our ELISA may be a useful adjunct to other methods, such as ultrasonography, for monitoring the course of S. haematobium infection and treatment.

These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. C57BL/6 mice were depleted in vivo of L3T4+, Lyt-1+, Lyt-2+, IL-2R+ cells, or IL-4 by administration of appropriate mAb. Resistance and various correlative parameters of the immune response were studied in normal, depleted, and congenitally athymic mice. Depletion of T lymphocytes by anti-L3T4 or anti-IL-2R mAb reduced the development and expression of resistance, IgG2a and IgE antibody formation, and delayed type hypersensitivity reactivity against schistosome Ag. Depletion with anti-IL-4 antibody led to profound suppression of IgE-eosinophil-mediated antibody-dependent cell-mediated cytotoxicity and passive cutaneous anaphylaxis responses against the parasite and no effect on IgG2a antibody, Ag-mediated blast transformation, or resistance. Depletion of Lyt-2+ cells produced augmented development and expression of resistance and an increase in the immunological parameters of anti-schistosome reactivity. These studies suggest that protective immunity to S. mansoni in mice, induced by irradiated cercariae, is dependent on L3T4+, IL-2R+ lymphocytes and negatively regulated by Lyt-2+ cells. IL-4 does not appear to be essential for the development of resistance but is essential for the IgE response to the parasite.

These studies assess the roles of subpopulations of T lymphocytes in resistance to Schistosoma mansoni. CDF rats were depleted of the T cell subpopulation bearing the high affinity IL-2R by in vivo treatment with ART18+ mAb or of soluble IL-4 by treatment with 11B11 mAb. The development of parasites, the expression of resistance after sensitization, and the intensity of delayed type hypersensitivity (DTH), Ag-mediated blast transformation (AMBT), IgG2a, passive cutaneous anaphylaxis, and IgE-mediated antibody-dependent cell-mediated cytotoxicity responses against S. mansoni or control Ag were ascertained. Isolated T cell subpopulations were assessed in vivo and in vitro for effects upon the protective Ir. Depletion with ART18 mAb suppressed the development of W3/25+ helper-inducer cells and resulted in the initial survival of more worms, decreased resistance to challenge after initial sensitization, decreased IgG2a and IgE antibody, AMBT, and DTH reactivity against schistosome Ag. Depletion with ART18 did not prevent the development of OX8+ (T suppressor) cells. Depletion with 11B11 mAb led to insignificant changes in initial parasite survival and resistance to challenge; had no effect on IgG2a antibody, AMBT, or DTH; but profoundly suppressed the IgE responses against the parasite. Protective immunity to S. mansoni in rats is dependent upon IL-2R-bearing T lymphocytes and regulated by OX8+ cells but not absolutely contingent upon IL-4 or the IgE response.

Auto-anti-idiotypic mechanisms can regulate the protective immune response against Schistosoma mansoni. Anti-idiotypic responses were stimulated by immunization of mice either with nonspecifically induced lymphoblasts, produced with Con A, or with Ag-induced lymphoblasts bearing specific idiotypic receptors. The effect of the induced anti-idiotypic response upon clonotypic cellular reactivity was assessed in vitro through the suppression of antigen-mediated blast transformation by cloned T cells and in vivo by suppression of resistance to S. mansoni and delayed-type hypersensitivity responses against specific Ag. Differential regulation of humoral immune responses was studied at the levels of specific epitopic recognition, the expression of specific Id, and the production of anti-idiotypic responses directed against mAb bearing specific Id. Anti-idiotypic sensitization resulted in variable (10 to 90%) suppression of the immune response to discrete antigenic epitopes, the expression of specific idiotypic phenotypes, and anti-idiotypic, antiparatopic responses against T cell clonotypes and antibody idiotypic phenotypes. In vitro admixture and in vivo challenge studies resulted in consonant differential suppression. Thus idiotypic regulation can mold the fine specificities of the protective immune response to S. mansoni at the clonal level and may provide an approach to optimize the expression and assessment of resistance.

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