Active Schistosomiasis Research Articles

Diagnosis of Human Schistosomiasis by Detection of Circulating Cathodic Antigen with a Monoclonal Antibody

Monoclonal antibody (MAb) 5H11 reacted with repeating epitopes on Schistosoma mansoni circulating cathodic antigen (CCA) and detected CCA in sera of Egyptian S. mansoni-infected patients. MAb 5H11 was both capture and biotinylated detection antibody in a sandwich ELISA of trichloroacetic acid-pretreated serum samples. Sera of patients with 7-500 eggs/g of stool were positive by MAb 5H11-CCA sandwich ELISA. Stool egg counts and CCA serum levels correlated (r = .52), and CCA levels decreased by 4 weeks after praziquantel treatment in patients with pretreatment egg counts of greater than or equal to 50/g of stool (P less than .05). Sera of Schistosoma haematobium-infected patients, uninfected individuals, and most patients with other helminths were negative in this assay. The MAb 5H11-CCA sandwich ELISA appears sensitive and specific for immunodetection of active schistosomiasis mansoni and useful for monitoring its chemotherapy.

Lymphokine Production by Blood or Spleen Mononuclear Cells from Patients with schistosomiasis mansoni

Peripheral blood mononuclear cells (PBMN) from individuals with active or former intestinal schistosomiasis mansoni or splenocytes from patients with the hepatosplenic form of the disease were evaluated for their ability to generate chemotactic factors for neutrophils in response to schistosomal antigenic preparations derived from adult worms (SWAP), eggs (SEA), or phytohemagglutinin (PHA). When supernatants from cultures of stimulated PBMN from normal donors were assayed, only those obtained from cells which had been cultured in presence of PHA displayed chemotactic activity for neutrophils. In contrast, supernatants from cultures of SWAP or SEA stimulated PBMN from patients with intestinal or hepatosplenic schistosomiasis were shown to contain chemotactic activity for neutrophils from normal individuals. PBMN from persons who previously had been infected with Schistosoma mansoni but had received chemotherapy years before presented a pattern of response to SWAP or SEA similar to those from patients with active infections. The response of splenocytes from patients with hepatosplenic schistosomiasis was considerably different from PBMN from individuals with active or with treated schistosomiasis. Splenocytes from most of those patients with hepatosplenic disease failed to produce chemotactic factors for neutrophils in response to stimulation with at least 1 of the schistosome antigens tested. These results indicate that the lymphocytes from schistosomiasis mansoni patients are able to recognize and are stimulated by adult worm and egg antigens to produce chemotactic substances for neutrophils, and that this ability persists for many years after chemotherapy with schistosomicidal drugs. At the hepatosplenic stage, immunoregulatory mechanisms, which may prevent the production of chemotactic factors by splenocytes and/or their activity upon neutrophils in vitro, seem to occur.

Renal Function in Urinary Schistosomiasis in the Natal Province of South Africa

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.

Schistosomal specific nephropathy leading to end–stage renal failure

In this study 17 patients, 11 with end-stage renal failure and six with nephrotic syndrome were selected. The selection criteria were presence of active intestinal schistosomiasis and absence of any surgical or other medical disease which could explain the renal disease. When examined by light microscopy, kidney biopsies showed membranoproliferative glomerulonephritis in nine, membranous in four, focal segmental glomerulosclerosis in two, sclerosing glomerulonephritis in one case, and no changes in another case. Direct immunofluorescence showed IgG deposits in 13 cases, IgM in 10 and different complement components (C3, C1q) in eight cases. Eluates from the kidney biopsies of the 17 schistosomal as well as six control cases were examined by ELISA against schistosoma mansoni adult worm antigen (AWA). This test showed the presence of antibodies against the AWA in 12 out of 17 of the schistosomal cases, and zero out of six of the controls. When examined by direct IFA using sheep anti-circulating anodic antigen/FITC and by indirect IFA using monoclonal antischistosomal CAA IgG3, kidney biopsies of the ELISA positive cases showed granular deposits of circulating anodic antigen (CAA). We conclude that schistosomal specific nephropathy does exist in the clinical settings and can lead to end-stage renal disease, with CAA probably being a major responsible antigen.

Immune responses during human Schistosomiasis mansoni. Evidence for antiidiotypic T lymphocyte responsiveness.

We present a method for the examination of antiidiotypic cell-mediated reactivity during chronic human infections. Pooled and individual sera from patients with schistosomiasis mansoni were purified on immunoaffinity columns of schistosomal egg antigens (SEA). The eluates contained anti-SEA antibodies, but not SEA. These antibody preparations, and their F(ab)2 fragments, stimulated dose-dependent proliferation of peripheral blood mononuclear cells (PBMN) and T lymphocytes from some, but not all active or former schistosomiasis mansoni patients, and could do so autologously. Stimulation required presentation by plastic-adherent cells. The eluates did not stimulate PBMN from persons who had never had schistosomiasis. Affinity-purified anti-SEA antibodies from former patients (cured for greater than 10 yr) did not stimulate PBMN from patients with active infections. Reabsorption on SEA columns removed stimulatory activity from the eluates. We propose that multiclonal, SEA-related idiotypes expressed by some anti-SEA antibodies stimulate proliferation of T lymphocytes that express antiidiotypic specificities.

Contraceptive steroid concentrations in women with early active schistosomiasis: Lack of effect of antischistosomal drugs

Plasma concentrations of the oral contraceptive steroids (OCS) ethinyloestradiol (EE 2) and levonorgestrel (LNG) have been determined in women with early active schistosomiasis and compared to those obtained in healthy volunteers. Steroid concentrations following a single dose of Ovral (500μg LNG, 50μg EE 2) or during a multiple dose regimen were unaffected by the disease. There was no significant effect of the antischistosomal drugs praziquantel (40 mg·kg −1) or metrifonate (10 mg·kg −1 × 3 at 2-week intervals) on plasma steroid concentrations. In regular users of OCS, significantly higher concentrations of LNG were observed than in women who received only a single dose. We conclude that there is no pharmacokinetic reason for witholding OCS from patients with early active schistosomiasis who are also receiving either praziquantel or metrifonate.

The pharmacokinetics of antipyrine in patients with graded severity of schistosomiasis.

The pharmacokinetics of antipyrine have been studied in patients with schistosomiasis. In comparison to a control group of subjects (n = 6), patients with early (active) schistosomiasis (passing live ova in urine or stools without clinical and laboratory evidence of liver involvement; n = 6) exhibited similar pharmacokinetic parameters. Of seven patients with hepatosplenic schistosomiasis (exhibiting hepatic fibrosis, splenomegaly, at least one episode of haematemesis, ascites), five showed markedly enhanced antipyrine half-life and reduced clearance. Compared to controls, the mean half-life of this group was increased from 10.9 +/- 2.4 to 19.9 +/- 9.5 h (mean +/- s.d.; P less than or equal to 0.05) and clearance reduced from 3.81 +/- 0.74 to 2.18 +/- 0.80 l h-1 (P less than or equal to 0.01). There was no change in the apparent volume of distribution. Liver biopsy was performed on all patients diagnosed as having hepatosplenic schistosomiasis in the 2 weeks prior to the antipyrine study. The results of this study indicate that hepatic microsomal metabolism is impaired in patients with advanced hepatosplenic schistosomiasis.

Immunoglobulin A, G and E levels in Egyptians with cancer: influence of schistosomiasis.

The main patient series consisted of 415 Egyptians attending the Cairo Cancer Institute and comprising 286 bladder cancer, 97 breast cancer, 14 head and neck cancer and 18 gastrointestinal cancer cases. Also included in the study were 36 patients with active schistosomiasis and 89 health controls. Serum IgA, IgG, IgG subclasses, IgE, Schistosoma and Ascaris-specific IgE (RAST) and the acute-phase protein CRP were measured in all, or sub-sets, of the main patient group. The well-established increase in IgE and IgG levels, and the more recently reported increase in the levels of IgG3 and IgG4 subclasses in patients with schistosomiasis, were also found in bilharzial bladder cancer, indicating that humoral immunity persists in cancer-bearing patients. However, the plasma protein profile in bilharzial bladder cancer is further modified by significant increases in the levels of IgA, IgG, IgG1, IgG2 and CRP when compared to levels in patients with Bilharzia in the absence of neoplastic change. Patients with cancers not associated with parasitic infestation also had significant increases in their serum levels of IgG1, IgG2, IgG, IgE and CRP when compared to healthy Egyptian controls, but 41% of these non-bladder cancer patients showed IgE responses to previous parasitic infestations suggesting that any immunological response to cancer would be on the background of a variable non-specific increase of IgE.

Effect of oral contraception on serum bile acid

Eighteen normal women, 20 with active urinary schistosomiasis, and 25 with past histories of viral hepatitis were given a contraceptive pill containing 0.05 mg ethinyl estradiol and 0.5 mg levonorgestrel for six consecutive cycles. Serum bile acid levels were measured by enzyme immunoassay method before and after 3 and 6 months of use. Simultaneously, conventional liver function tests (serum bilirubin, transaminases, alkaline phosphatase and albumin) were done. Serum bile acid concentration was not significantly changed by the contraceptive use in any group. The concentration of cholylglycine (the main bile acid measured) did not correlate with the values of any of the other tests. Pretreatment values of serum cholylglycine were significantly lower in the past-hepatitis group. The difference was maintained during treatment.

Immune responses during human schistosomiasis mansoni. X. Production and standardization of an antigen-induced mitogenic activity by peripheral blood mononuclear cells from treated, but not active cases of schistosomiasis.

Peripheral blood mononuclear cells (PBMN) from patients with active schistosomiasis mansoni are generally induced to proliferate upon exposure to a soluble worm antigenic preparation (SWAP). In contrast, only 25% of such patients responded to SWAP exposure by the production of detectable levels of a mitogenic factor (MF) activity capable of stimulating proliferation of resting cultures of allogeneic PBMN. When former schistosomal patients (chemotherapeutically cured 10 to 40 yr previously) were tested for these two responses to SWAP, all manifested blastogenesis; 80% also responded by the production of MF activity. Only 9% of control subjects with no history of schistosomiasis produced MF activity when exposed to SWAP. The production and assay of MF activity by former schistosomiasis patients was standardized. Reliable, optimal production was achieved by using 6 X 10(6) PBMN in 2-ml cultures upon exposure to 15 micrograms protein SWAP/ml. The cells were incubated for 20 hr in the presence or absence of SWAP, at which time they were washed and recultured in fresh medium for at least 28 more hours. Subject to subject variability occurred in the optimal time of detection of MF activity in culture supernatant fluids, but detection was assured between 24 and 48 hr after the wash. The assay system for MF detection required a 5 to 7-day culture. The consistent production of MF activity by former schistosomal patients emphasized the longevity of immunologic memory to SWAP, and may indicate a post-treatment decline of immunoregulatory mechanisms that are operative in patients with active schistosome infections.

Bilharzial portal hypertension.

Schistosomiasis is a major world health problem that is being encountered more frequently in North America as the immigration patterns from endemic areas change. At Henry Ford Hospital in Detroit, only two admissions for active schistosomiasis were recorded before 1970, but since then there have been 43 such cases. Of these 45 patients, six required seven portasystemic shunts, primarily to treat the complication of esophageal variceal hemorrhage, which is associated with portal hypertension secondary to presinusoidal hepatic fibrosis. No operative deaths occurred, and follow-up averaging 6.6 years revealed no late deaths and minimal encephalopathy. These excellent results are attributed to successful portal decompression and the well-preserved liver function that is typical of these patients. Bilharzial portal hypertension should be suspected in immigrants from endemic areas who have bleeding esophageal varices.

Serum IgE and IgG antibodies to tetanus toxoid and candidin in immunodeficient children with the hyper-IgE syndrome.

Serum IgG and IgE antibodies directed against tetanus toxoid and candidin were measured using a solid-phase radioimmunoassay in seven patients with the immunodeficiency syndrome with hyper-IgE. In parallel, six normal children, three normal adults, and eight patients with or without elevated serum IgE (including atopic diseases, Candida infections, and active schistosomiasis) were studied. Serum IgG antibodies to tetanus toxoid and candidin were present in the hyper-IgE patients in concordance with their immunization history. High concentrations of IgE antibodies against both antigens were found in the immune hyper-IgE patients but not in the controls. This suggests that elevated IgE antibody responses in the hyper-IgE syndrome results from a primary defect of IgE class regulation rather than an abnormal or deficient antibody response.

Effect of praziquantel on antigenemia in murine schistosomiasis.

Abstract. A substantial portion (63%) of circulating schistosomal antigen was cleared from the serum of hyperinfected mice within 72 hours after treatment with the helminthocide, praziquantel. This result suggests that circulating antigen may be a diagnostically useful marker for active schistosomiasis.

Effects of oral contraception on liver function tests and serum proteins in women with active schistcsomiasis

Thirty-eight women with urinary or intestinal schistosomiasis but without clinical or laboratory evidences of hepatic involvement and 30 healthy control women were treated with an oral contraceptive containing 0.05mg ethinyl estradiol and 0.5mg levonorgestrel for six consecutive months. Liver function tests (serum bilirubin, SGOT, SGPT, serum alkaline phosphatase) and serum proteins (total, albumin, globulins, ceruloplasmin, haptoglobin and alpha-1 antitrypsin) were measured before beginning the treatment and after three and six months of use. Both group experienced significant increases in SGOT, SGPT and serum alkaline phosphatase during the first three months of treatment with tendencies to decrease during the subsequent 3 month. No change occurred in serum bilirubin. There was significant decreases in serum albumin and haptoglobin and increases in alpha-1 globulin, ceruloplasmin and alpha-1 antitrypsin. With the exception of serum level of alpha-1 globulin, there were no significant differences between schistosomiasis patients and the controls in terms of changes in any laboratory test as a result of the treatment, thus suggesting that patients with active schistosomiasis do not incur a higher risk of hepatic dysfunction while using oral contraception.

Use of praziquantel in patients with schistosomiasis mansoni previously treated with oxamniquine and/or hycanthone: resistance of Schistosoma mansoni to schistosomicidal agents

Fourteen patients with active schistosomiasis mansoni in spite of previous treatment with oxamniquine and/or hycanthone were treated with praziquantel, single oral dose of 45 to 50 mg/kg body-weight. All underwent clinical, laboratory and electrocardiographic examination before and after treatment. Untoward effects (dizziness, drowziness, nausea and abdominal pain) were observed in ten. Laboratory findings disclosed no significant alteration and the electrocardiograms showed no abnormalities. Monthly follow-up examinations of 13 patients for six consecutive months showed parasitological cure in all. Before praziquantel treatment strains of Schistosoma mansoni were isolated from two patients, one treated three times with oxamniquine and the other with hycanthone once and oxamniquine twice. Progenies of these strains were maintained in Biomphalaria glabrata and mice. Groups of these infected mice were then treated with oxamniquine, hycanthone, niridazole and praziquantel and results compared with the BH strain maintained in our laboratory for many years. Schistosomicidal activity was assessed by the localization of worms in the portal vein system and oogram changes. Progenies from the strains isolated in this study were resistant to oxamniquine and hycanthone but sensitive to niridazole and praziquantel. The BH strain was sensitive to all four drugs. The serial runs of S. mansoni strains through intermediate and definitive hosts have not influenced their reactions to these schistosomicides.

Size and Shape Analysis of Schistosome Egg-Counts in Egyptian Autopsy Data

We study egg-counts from a series of Egyptian autopsy cases with active schistosomiasis at death (Kamel, Cheever, Elwi, Mosimann and Danner 1977). The data are unique, and enable us to study the proportional distribution of eggs among various organs in relation to infection intensity for two species of schistosome worms. We develop a model for the distribution of eggs in three organs of the mesenteric circulation. Under a lognormal distribution assumption, several exact statistical procedures are presented and used to examine model consistency as well as isometry with respect to geometric means. Mesenteric egg counts for both Schistosoma mansoni and S. haematobium behave consistently with the model, and show little or no departure from isometry in cases without Symmers' fibrosis of the liver. We show that cases with Symmers' fibrosis have relatively more S. mansoni eggs in the small, as opposed to large, intestine. In the genito-urinary organs we show that the proportion of S. haematobium eggs in the bladder is high for low-intensity infections. This is consistent with the conclusion of Smith, Elwi, Kamel and Lichtenberg (1975), based on egg/gram data, that such infections may be initiated in the bladder. The correspondingly high proportion of eggs in the ureters with high-intensity infections indicates that increased intensity may have a disproportionately large pathologic effect on the infected individual.

Intradermal test with histamine in Schistosomiasis mansoni.

Histamine diphosphate was injected intradermally, at dilutions of 10(-3), 10(-4), and 10(-5), into 25 boys (10--12 yr old), and 25 men (20--30 yr old) with active schistosomiasis mansoni. A linear relationship between the mean area of the wheals and the logarithm of histamine concentrations was determined. Both equations (men and boys) were significant (P less than 0.05) but showed no difference between their regression coefficients. These findings contrast with those obtained with the intradermal test performed with Schistosoma mansoni antigens, in which skin response in men is significantly greater than in boys.

Schistosomal polyposis of the urinary bladder.

Anatomic, clinical, and digestion analyses were done on 18 human urinary bladder polyps from patients with Schistosoma haematobium infections. Variations in histologic pattern conformed to stages in progression of the disease; most were from active cases with significant egg burdens. The data suggest that polypoid lesions of active schistosomiasis may persist as polyps in the inactive stage if antecedent active infection was heavy.

The relationship between serum carnitine levels and the nutritional status of patients with schistosomiasis

Serum carnitine levels were investigated in a group of normal adults and two groups of patients with active schistosomiasis who also showed signs of malnutrition and vitamin deficiency. The first group consisted of 16 patients with Schistosoma mansoni and/or Schistosoma haematobium infection. They received an adequate diet supplemented with vitamin and iron therapy and received no treatment for their parasitic infection till their hemoglobin levels were restored to normal. The second group consisted of 12 patients with schistosomiasis as well as intestinal polyposis. They received the same diet as the first group but because of their poor condition were immediately treated for parasitic infection. Results showed that both groups of patients had subnormal levels of serum carnitine with the polyps patients (Group II) having a significantly lower level than patients with simple schistosomiasis (Group I). After nutritional repletion a significant increase was observed in the carnitine levels of most patients in group I indicating a relationship between the nutritional status of the patients and their serum camitine levels. The patients with polyps also showed considerably increased camitine levels after treatment and dietary repletion. The usefulness of serum camitine measurement as an index of protein malnutrition in man is discussed.

Ensaio clínico com o Hycanthone no tratamento da esquistossome mansônica

Os A A. trataram 46 pacientes esquistossomóticos (40 com a forma hepatintestinal e seis com a forma hepatesplênica compensada) na Clínica de Dosnças Infecciosas e Parasitárias da F.M.U.F.Pe. com o Hycanthone na dose única de 2,5 mg por Kg. de peso e administrado por via intramuscular. O diagnóstico da helmintiase foi realizado através da técnica de Hoffman, Pons e Janer com sedimentação em água durante 24 horas e o controle de cura parasitológica foi também efetuado com o mesmo método em número de nove exames durante um período de um a seis meses. A tolerância foi considerada boa, apesar de um paciente ter desenvolvido subicterícia, e o índice de cura parasitológica obtido foi de 95,65% (44 doentes). Concluem os AA. que o Hycanthone é, no momento, a substância de escolha para o tratamento da bilharziose.