Antigenic cross‐reactivity between Schistosoma mansoni and peanut: a role for cross‐reactive carbohydrate determinants (CCDs) and implications for the hygiene hypothesis

The antigenic reactivity of constituents of Schistosoma mansoni and peanut (Arachis hypogaea) was investigated to determine whether identical antigenic epitopes possessed by both organisms provided a possible explanation for the negative correlation between chronic schistosome infection and atopy to allergens. Aqueous extracts of peanuts were probed in Western immunoblots with rabbit IgG antibodies raised against the egg, cercarial and adult worm stages of S. mansoni. Several molecules in the peanut extract were antigenically reactive with antibodies from the various rabbit anti‐schistosome sera. A pair of cross‐reactive peanut molecules at ~30 000–33 000 molecular weight was purified and both proteins were identified by mass spectrometric analysis as the peanut allergen Ara h 1. Anti‐S. mansoni soluble egg antigen antibodies that were eluted off the peanut molecules reacted with two S. mansoni egg antigens identified by mass spectrometry as IPSE/α‐1 and κ‐5. Alignments of the amino acid sequences of Ara h 1 and either IPSE/α‐1 or κ‐5 revealed a low level of peptide sequence identity. Incubation of nitrocellulose paper carrying electrophoresed peanut molecules, six constituents of other allergic plants and S. mansoni egg antigens in a mild solution of sodium metaperiodate before probing with antibodies, inhibited most of the cross‐reactivities. The results are consistent with the antigenic cross‐reactive epitopes of S. mansoni egg antigens, peanut and other allergic plants being cross‐reactive carbohydrate determinants (CCDs). These findings are novel and an explanation based on ‘blocking antibodies’ could provide an insight for the inverse relationship observed between schistosome infection and allergies.     

Schistosoma japonicum migration through mouse skin compared histologically and immunologically with S. mansoni

The migration of Schistosoma japonicum and S. mansoni through mouse skin epidermis and dermis was compared by immunofluorescence techniques from 4 to 22 h after infection. At all times, the percentage of parasites detected in the dermis was significantly higher for S. japonicum than for S. mansoni. Thus, S. japonicum migrates more rapidly very early after infection. This agrees with the quicker migration observed previously by this species for later times. Both species expressed antigens related to the cercarial glycocalyx on the parasite body and antigenically detectable elastase in the acetabular glands, at least until 22 h after infection. Bot sets of antigens were also left as traces in cercarial migration channels in the skin as well as in skin tissue in the absence of detectable worms or migration channels. The data further substantiate differences between schistosome species in the speed of migration, and suggest that glycocalyx-related antigens and cercarial elastase continue to be expressed for at least 1 day after infection.     

Detection and quantification of circulating antigen in schistosomiasis by a monoclonal antibody. I. Specificity analysis of a monoclonal antibody with immunodiagnostic capacity.

Monoclonal antibodies were obtained after immunization of mice with Schistosoma mansoni excretory/secretory antigen, previously shown to contain the circulating cathodic (M) antigen. Among these, the 40:B1 monoclonal antibody proved to be specific for the schistosome genus and to detect only adult worm-derived antigens as shown both by immunoprecipitation and with a two-site immunoradiometric assay using the monoclonal as both the solid-phase and the labelled antibody. The two-site immunoradiometric assay allows a sensitive measurement (detection limit: 5 ng) of circulating schistosome antigen in blood and in urine from patients with schistosomiasis. The amount of circulating schistosome M antigen is correlated with schistosome egg excretion in stool.     

Serum levels of circulating anodic antigen and circulating cathodic antigen detected in mice infected withSchistosoma japonicum orS. mansoni

Serum concentrations of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) were studied in mice infected with eitherSchistosoma japonicum orS. mansoni cercariae. Sera from uninfected mice were negative for both antigens. CAA was detectable in theS. japonicum-infected mice as early as at 2 weeks post-infection (p.i.), and levels were higher in these animals than in theS. mansoni-infected group during the full study period. At the moment of perfusion, 10 weeks p.i., a median of 9 and 29 worms, respectively, were recovered from theS. japonicum-andS. mansoni-infected mice, and the median CAA levels were 326 and 27 ng/ml, respectively. In contrast, CCA levels were much lower in theS. japonicum-infected group (27 ng/ml) as compared with theS. mansoni-infected mice (282 ng/ml). These results suggest an important difference betweenS. japonicum andS. mansoni infections in CAA and CCA production and/or clearance and indicate a significant role for CAA in the diagnosis of human schistosomiasis japonicum.     

Characterization of the Glycoprotein Antigens Which Mediate the Schistosoma japonicum Circumoval Precipitin Reaction

The circumoval precipitin test is a serological test used for diagnosis of schistosomiasis japonica. Soluble egg antigens of Schistosoma japonicum block the formation of the circumoval precipitin by serum from infected humans. Consequently, circumoval precipitin inhibition was used to monitor purification of the soluble egg antigens of S. japonicum. Crude egg antigens were separated into protein and glycoprotein fractions by lectin chromatography on concanavalin A Sepharose. The glycoprotein fraction produced two intense precipitin lines upon immunodiffusion analysis with human chronic infection sera. The protein fraction produced two faint precipitin lines which did not cross-react with those of the glycoprotein fraction. The glycoprotein fraction contained 90% of the circumoval precipitin inhibitory activity. Isoelectric focusing of ¹²⁵I-labeled concanavalin A Sepharose fractions revealed at least four groups of potential S. japonicum antigens, termed JAG I, II, and III, and a JAG IV complex. These had isoelectric points ranging from 3.2 to 6.7. In these respects, the S. japonicum egg antigen glycoproteins are similar to those of Schistosoma mansoni. The glycoproteins were further separated by diethylaminoethyl ion-exchange chromatography. On immunodiffusion analysis it was found that one of the strong Ouchterlony precipitin lines was associated with glycoproteins that did not adsorb to diethyl-aminoethyl columns, whereas the second Ouchterlony precipitin was heterodisperse, being present in the first, second, and third of the four peaks eluted from the diethylaminoethyl column. Immunoelectrophoresis of the diethylaminoethyl fractions demonstrated that the antigen present in highest concentration in soluble egg antigen glycoproteins, JAG II, was extremely heterodisperse in its behavior on diethylaminoethyl columns. This is unlike the S. mansoni antigens which can be easily separated by diethylaminoethyl ion-exchange chromatography.     

Parthenogenesis in the genusSchistosoma: Electrophoretic evidence for this reproduction system inS. japonicum andS. mansoni

Mixed infections withSchistosoma japonicum andS. mansoni were carried out in mice.S. japonicum females paired withS. mansoni males developed normally and produced numerous viable eggs; very little sperm was found in the female genital tract. The eggs yielded many miracidia infective toOncomelania hupensis, the host ofS. japonicum. Cercariae arising from miracidia developed into male worms with an electrophoretic pattern of malate dehydrogenase (MDH) corresponding only to mae maternal speciesS. japonicum. S. mansoni females paired withS. japonicum produced few viable eggs; sperm was found in the female genital tract. Miracidia hatched from mime of these eggs were infective toBiomphalaria glabrata, the host ofS. mansoni. Cercariae arising from miracidia developed into female worms with an electrophoretic pattern of MDH typical of the maternal speciesS. mansoni. It was concluded thatS. japonicum females paired withS. mansoni males andS. mansoni females paired withS. japonicum males reproduce parthenogenetically. Parthenogenesis in schistosomes is discussed.     

Immunoblot analysis of membrane antigens of Schistosoma mansoni, Schistosoma intercalatum, and Schistosoma haematobium against Schistosoma-infected patient sera

Antigens present in aqueous n-butanolic extracts (BE) of Schistosoma mansoni (Venezuelan JL strain), Schistosoma intercalatum (Cameroon EDEA strain), and Schistosoma haematobium (Yemen strain) adult worm membranes were compared in immunoblot against sera of patients infected with S. mansoni, S. intercalatum, S. haematobium, Schistosoma japonicum, or Schistosoma mekongi looking for similarities (common antigens) and differences (species-specific antigens). About 17 S. mansoni BE polypeptides (M _r ∼8 to >80 kDa) were commonly recognized by S. mansoni-infected patient sera from Venezuela, Senegal, and Ethiopia. S. intercalatum-, S. haematobium-, or S. japonicum-infected sera were almost unreactive with S. mansoni BE. Nonetheless, S. mekongi-infected sera weakly cross-reacted with a ∼10–15-kDa subset of S. mansoni BE. About 72.7% of S. intercalatum-infected patient sera reacted with a ∼19–21-kDa complex in S. intercalatum BE and cross-reacted with a similar complex in S. haematobium BE. Conversely, all S. haematobium-infected patient sera reacted with a ∼19–21-kDa complex in S. haematobium BE and cross-reacted with the ∼19–21-kDa complex in S. intercalatum BE; S. mansoni- and S. japonicum-infected patient sera did not react with S. intercalatum or S. haematobium BE. Results showed the presence of a common membrane antigen between African schistosome species and species-specific antigens in S. mansoni BE that could be useful to discriminate between species and/or to detect Schistosoma infections.     

Circulating antigens in schistosomiasis: detection of 31/32-kDa proteins in sera from patients infected with Schistosoma japonicum,S. mansoni,S. haematobium,or S. intercalatum

A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect 31/32-kDa schistosome proteins as circulating antigens in sera from schistosomiasis patients. A monoclonal antibody was used as a capture antibody and rabbit antiserum raised against purified 31/32-kDa proteins was the detecting antibody. Positive results were obtained with patients infected with Schistosoma japonicum (88%; n=69), S. mansoni (80%; n=56), S. haematobium (100%; n=40), or S. intercalatum (94%; n=65). Sera from uninfected Chinese and African individuals and from Chinese patients with trichinosis, cysticercosis, or paragonimiasis did not react in the assay. This ELISA appears to be valuable in diagnosing infections by all major human schistosome species.     

Schistosoma mansoni: Analysis of monoclonal antibodies reactive with gut-associated antigens

The analysis of a series of monoclonal antibodies (mAbs) developed in our laboratory against gutassociated antigens ofSchistosoma mansoni is described. It was found that mAbs that recognized epitopes of antigens in the gut and on the eggshell were mainly of the IgM isotype; these epitopes are likely to be carbohydrate in composition. Of a number of mAbs that were reactive with antigens important to the human humoral immune response, 75% appeared to be reactive with the circulating cathodic antigen.     

Mechanisms of eosinophil accumulation around eggs ofSchistosoma japonicum: Role of two purified components,allergen and eosinophil chemotactic factor,from soluble egg antigens measured on sensitized guinea pig skin

Mechanisms of eosinophil response induced by soluble egg antigen (SEA) inSchistosoma japonicum-infected guinea pig tissues were analyzed using two purified components of SEA: major allergenic components (JEAL) and a major eosinophil chemotactic component (ECF-SjE). Eosinophil response to the crude SEA ofS. japonicum was detected at the injection site mainly at 2–8 h after the antigenic challenge; this response consisted of two different phases of eosinophil attraction. An early phase (2 h) was mediated by an immediate-type hypersensitivity reaction; JEAL played an important role in mediating this phase of eosinophil response. A late phase (8 h) was mediated by ECF-SjE. Therefore, this phase of eosinophil response was caused by direct eosinophilotactic activity of SEA. These two types of eosinophil response must be important processes in the formation ofS. japonicum egg-associated eosinophilic granuloma.     

Reactivity of IgE in humanSchistosoma mansoni sera toS. mansoni antigens

Sera fromSchistosoma mansoni-infected human patients were tested for total IgE levels and specific IgE and IgG antibodies toS. mansoni adult worm, cercaria, and egg antigen by ELISA. Of 50 sera, 28 were investigated by enzyme-linked crossed immunoelectrophoresis (ELCIE) to detect IgE reactivity to individual adult worm extract components. All sera showed increased total IgE levels. Specific IgE antibody levels to the different antigens varied; they were significantly correlated with each other but independent from total IgE. No correlation was found between specific IgG and any of the IgE antibody levels. Testing of the 28 individual sera by ELCIE revealed heterogeneous patterns. Seven sera were found to be non-reactive: three reacted with one precipitate, and the others reacted with between two and nine precipitates. However, in no case were identical patterns recognized, although four antigens reacted with about 80% of the sera. The number of bands detected by the individual sera depended neither on the levels of total IgE nor on those of specific IgE.Supported by the Bundesministerium für Forschung und Technologie der Bundesrepublik Deutschland (grant PTB 8324)     

Increased susceptibility of mice infected with Schistosoma mansoni to recombinant vaccinia virus: Association of viral persistence with egg granuloma formation

BALB/c mice infected 7 weeks previously with Schistosoma mansoni and challenged with a recombinant vaccinia virus vPE16 expressing the human immunodeficiency virus envelope protein gp160 show a marked delay in hepatic viral clearance as compared to mice infected with vPE16 alone. This increase in viral persistence is accompanied by reduced gp120-specific Th1-associated cytokine responses as well as by impaired cytotoxic T lymphocyte (CTL) activity against targets expressing epitopes of the same antigen. To investigate the contribution of these defects to the observed delay in clearance of recombinant vaccinia virus, animals were challenged with vPE16 at different times following S. mansoni infection, and virus titers in tissues and viral-specific immune responses were measured simultaneously in the same animals. While normal resolution of virus occurred in schistosome-infected mice prior to parasite egg deposition, persistence within the liver was observed in animals challenged during the onset and peak phase of granuloma formation (6 to 8 weeks after S. mansoni infection). At later times, when schistosomiasis is in its chronic phase, normal viral clearance returned. This time course of viral resolution correlated in part with the observed pattern of decreased Th1 cytokine production toward viral antigens but was clearly less temporally related to the defect in virus-specific CTL activity. Immunohistochemical staining of liver sections from vaccinia/S. mansoni co-infected mice with polyclonal anti-vaccinia antibodies revealed that viral epitopes are localized primarily within granulomas. These experiments suggest that egg granulomas, by providing a microenvironment for viral expansion, in combination with the cytokine imbalance present during schistosome infection, can promote the expansion of vaccinia virus and possibly other viral agents.     

Regulation of the human T-cell response toSchistosoma japonicum egg antigen by concomitant cellular and humoral mechanisms in vitro

Serum-mediated regulation of T-cell responses specific for soluble egg antigen (SEA) ofSchistosoma japonicum was tested in human hosts. When we added autologous serum to SEA-specific human T-cell lines (CD3+, 4+, 8–), we observed suppression of T-cell proliferation, and this suppressive activity was detected in the immunoglobulin-G2 (IgG₂) subclass. Suppression was dose-dependent and antigen-specific. T-cell proliferation induced by only one SEA fraction of >18 kDa was modulated in the presence of 100 g/ml autologous as well as allogeneic infected IgG₂. This SEA fractiondriven proliferation was also regulated by suppressor T-cells through distinct suppressive mechanisms. Our results suggest that T-cell responses to a particular component(s) of SEA are strictly regulated through both cellular and humoral mechanisms in human chronicS. japonicum infection.     

Schistosomal granuloma modulation. I. Schistosoma mansoni worm antigens CAA and CCA prime egg-antigen-induced hepatic granuloma formation

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. Received: 10 April 1998 / Accepted: 25 June 1998     

Schistosoma japonicum soluble egg antigens: Separation by con a chromatography and immunoaffinity purification

A crude soluble egg antigen (SEA) preparation from Schistosoma japonicum eggs was used for immunoabsorbent fractionation of anti-SEA antibody. Anti-SEA antibodies were isolated from serum pooled from mice infected with S. japonicum for 7 weeks and from mice infected for 12 weeks. These anti-SEA immunoglobulins were then used for immunoabsorbent fractionation of specific SEA antigens. Crude SEA was also partially purified by Con A chromatography. Crude SEA, the Con A fraction, an antigen isolated with 7 week infection serum, and antigens isolated with 12 week infection serum were analysed by immunoprecipitation and SDS polyacrylamide gel electrophoresis.     

Schistosoma mansoni infection of Syrian golden hamsters: The host humoral immune response in relation to the adult worm burdens after primary infection

Seven-week-old female Syrian golden hamsters (Mesocricetus auratus) showed different degrees of susceptibility toSchistosoma mansoni, as assessed by the percentage of cercariae recovered as adult worms 6 weeks after infection. Plasma of the low (A), medium (B) and high (C) susceptibility groups were tested immunochemically. No differences were observed in the concentrations of albumin, α₁-, α₂-, ;β- and γ-globulins as measured by cellulose acetate electrophoresis. However, a significantly higher percentage of animals in groups A and B than in group C had anS. mansoni specific “beforked” IgG precipitin band and specific antibodies against a worm tegumental antigen preparation (AWT). Conversely, more animals in group C made antibodies against a “denuded” worm-body antigen preparation (AWB) than in groups A and B. However, by using the enzyme-linked immunosorbent assay, no significant differences in antibody titres against AWT, AWB and a total worm antigen (AVA) were observed in the animals in groups A, B and C. Upon consideration of the immunochemical data in relation to the distribution pattern of susceptibility to infection, we propose that the intensity ofS. mansoni infection in the hamster is a polygene-controlled phenomenon and depends upon the presentation of differing parasite antigenic component(s) to the host.     

A monoclonal antibody against Schistosoma haematobium soluble egg antigen: efficacy for diagnosis and monitoring of cure of S. haematobium infection

A monoclonal antibody (mAb), 2F/11F, raised against Schistosoma haematobium soluble egg antigen (SEA) was found to be nonreactive with S. mansoni SEA or other parasite antigens (Fasciola hepatica, Echinococcus granulosus). This IgG₁ mAb recognized a repetitive epitope on S. haematobium SEA in the molecular-weight regions of 70, 42, and 35 kDa. It was employed as both an antigen-capture and a biotinylated detection antibody in a sandwich enzyme-linked immunosorbent assay (ELISA) for the detection of circulating schistosome antigen (CSA) and had a detection limit of <1 ng S. haematobium SEA/ml. CSA levels were measured in serum and urine samples from 116 S. haematobium-infected rural students before therapy and at 4, 8, and 12 weeks after praziquantel treatment. Serum and urine samples from 50 S. mansoni -infected patients, 15 patients harboring other parasites, and 30 noninfected individuals were also assessed. CSA was detected in 90.5% of serum samples and 94% of urine samples from S. haematobium-infected patients. CSA was undetectable in serum from the 15 patients harboring other parasites and in 94% of serum samples and 84% of urine samples from S. mansoni-infected patients. In the S. haematobium-infected group a positive correlation was detected between CSA levels in serum and urine samples and the egg load per 10 ml urine. A significant reduction in CSA levels was detected in serum and urine samples after praziquantel therapy. CSA was undetectable in 87% of serum samples and 81.5% of urine samples from schistosomiasis haematobium patients at 12 weeks post-treatment. These data demonstrate that the use of mAb 2F/11F for detection of CSA provides a sensitive method for the immunodiagnosis and monitoring of cure of schistosomiasis haematobium. Received: 5 December 1998 / Accepted: 26 June 1999     

A comparison of the susceptibility to praziquantel of Schistosoma haematobium,S. japonicum,S. mansoni,S. intercalatum and S. mattheei in hamsters

Summary Groups of six- to eight-week-old hamsters each experimentally infected with Sudanese and South African strains of S. haematobium, Puerto Rican and Liberian strains of S. mansoni, S. japonicum from mainland China, a Congo strain of S. intercalatum and a Nelspruit South African strain of S. mattheei, were treated with different dosage regimens of a new schistosomicide — praziquantel.The drug is more effective against S. haematobium when administered by the intramuscular route than per os, a complete parasitological cure being obtained following a single intramuscular injection of 200 mg/kg bwt. Per os the best results were obtained using the three highest regimens of 5×100 mg/kg, 5×50 mg/kg and 3×100 mg/kg bwt. It was observed that S. haematobium female worms are more susceptible to the compound than male worms.The results show that S. japonicum in the hamster is very susceptible to the compound, a dosage of 100 mg/kg administered orally for three days resulting in a complete parasitological cure. More than a 90% reduction in adult worms was obtained at all the dosage regimens used except 1×50 mg/kg (73.2%). Female worms were again found to be more susceptible to the drug than male worms. Hatching tests performed on ova in liver tissue of control and treated animals were positive up to four weeks after treatment, thus showing that praziquantel has no ovicidal properties.Immature S. japonicum worms were found to be markedly less susceptible to treatment than the mature schistosomes (5×100 mg/kg reduced mature adults by 99.7%, but immature forms were reduced by only 54.2%).A 100% cure rate was obtained in the hamster infected with the Liberian strain of S. mansoni following treatment with praziquantel at 3×100 mg/kg given on consecutive days, and at 3×50 mg/kg administered in one day. Treatment of the hamsters infected with the Puerto Rican strain of S. mansoni also resulted in substantial reductions of adult worms. Praziquantel was also found to be highly effective against S. intercalatum and S. mattheei.It is noted that the efficacy of the compound against S. haematobium, S. japonicum and S. mattheei in the hamster is significantly greater than that of metrifonate (Bilarcil). Following treatment with praziquantel most S. haematobium and S. japonicum worms undergo a classic hepatic shift and are trapped and killed in the liver tissue.It is considered that the present study shows that this new compound exhibits a high degree of activity against the three major schistosome species S. haematobium, S. japonicum and S. mansoni, against S. intercalatum, and against the cattle schistosome S. mattheei in the hamster, with no apparent significant differences in efficacy against the different geographical strains of the parasites used in the trials.

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Zusammenfassung Gruppen von 6–8 Wochen alten Goldhamstern wurden jeweils mit einem sudanesischen und südafrikanischen Stamm von S. haematobium, mit einem puertoricanischen und liberianischen Stamm von S. mansoni, mit S. japonicum aus Kontinentalchina, S. intercalatum vom Kongo und mit S. mattheei aus Nelspruit, Südafrika, infiziert und mit verschiedenen Dosierungen des neuen Schistosomenmittels Praziquantel behandelt.Praziquantel ist gegen S. haematobium bei intramuskulärer Gabe wirksamer als bei oraler Gabe. Eine parasitologische Heilung konnte durch eine einmalige intramuskuläre Injektion von 200 mg/kg erreicht werden. Bei oraler Gabe ergaben die drei höchsten Dosen 5×100, 5×50 und 3×100 mg/kg die besten Ergebnisse. Es wurde beobachtet, daß die Weibchen von S. haematobium empfindlicher gegen Praziquantel sind als die Männchen.Die Ergebnisse zeigen, daß S. japonicum im Goldhamster sehr empfindlich gegen Praziquantel ist. Eine parasitologische Heilung wird durch 3×100 mg/kg erreicht. Mit allen verabreichten Dosen wurde die Zahl der adulten Parasiten um mehr als 90% reduziert. Nur bei Gabe von 1×50 mg/kg betrug die Parasitenreduktion 73,2%. Wieder waren die Weibchen empfindlicher gegen Praziquantel als die Männchen. Der Miracidienschlüpfversuch wurde an Eiern aus der Leber behandelter und unbehandelter Kontrolltiere durchgeführt. Er war bis zu vier Wochen nach der Behandlung positiv; Praziquantel wirkt also nicht ovizid.Jugendliche S. japonicum waren gegen die Behandlung deutlich unempfindlicher als adulte Schistosomen (5×100 mg/kg bewirkten bei Adulten eine Reduktion um 99,7%, bei den Jugendlichen eine um 54,2%).Eine parasitologische Heilung wurde bei Goldhamstern, die mit einem liberianischen Stamm von S. mansoni infiziert waren, mit 100 mg/kg (verabreicht an drei aufeinanderfolgenden Tagen) und mit 3×50 mg/kg/die erreicht. Die Behandlung von Goldhamstern, die mit einem puertoricanischen S. mansoni-Stamm infiziert waren, ergab ebenfalls eine sehr starke Reduktion der Anzahl adulter Schistosomen. Gegen S. intercalatum und S. mattheei war Praziquantel ebenfalls sehr gut wirksam.Es wurde gefunden, daß die Wirksamkeit von Praziquantel gegen S. haematobium, S. japonicum und S. mattheei im Hamster deutlich besser ist als die von Metrifonat (Bilarcil). Nach Behandlung mit Praziquantel zeigen die meisten S. haematobium- und S. japonicum-Würmer eine klassische liver shift und werden im Lebergewebe festgehalten und abgetötet.Die Untersuchung zeigt, daß Praziquantel gegen alle drei wichtigen Schistosomenarten, S. haematobium, S. japonicum und S. mansoni, und auch gegen S. intercalatum sowie gegen den Rinderparasiten S. mattheei im Hamster hoch wirksam ist. Zwischen den in dieser Untersuchung verwendeten Parasitenstämmen unterschiedlicher geographischer Herkunft bestehen in der Wirksamkeit keine wesentlichen Unterschiede.

     

Heterologous immunity againstSchistosoma mansoni in mice by administration ofHeterobilharzia americana

Three groups of Swiss albino mice were exposed to cercariae ofHeterobilharzia americana a mammalian schistosome in Southern United States. They were challenged at different intervals with cercariae of a Puerto Rican strain ofSchistosoma mansoni, and a fourth group (control for the first two groups) was exposed only toS. mansoni. With a patent infection (two months) ofH. americana there was a noticeable reduction of the worm recovery rates ofS. mansoni and its eggs deposited in the tissues. In the two other groups exposed simultaneously or at a 3-week interval, there was no significant reduction in the recovery rates of adultS. mansoni and the number of eggs exceeded in some cases that noted for the control group. Thus a patent infection withH. americana is necessary to confer immunity against a challenge infection withS. mansoni.     

Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the serodiagnosis of Schistosoma mansoni

Schistosomiasis is traditionally diagnosed by microscopic detection of ova in stool samples, but this method is labour intensive and its sensitivity is limited by low and variable egg secretion in many patients. An alternative is an ELISA using Schistosoma mansoni soluble egg antigen (SEA) to detect anti-schistosome antibody in patient samples. SEA is a good diagnostic marker in non-endemic regions but is of limited value in endemic regions, mainly because of its high cost and limited specificity. Here we assess seven novel antigens for the detection of S. mansoni antibody in an endemic region (the Northern Nile Delta). Using recombinant S. mansoni calreticulin (CRT) and fragments thereof, anti-CRT antibodies were detected in the majority of 97 patients sera. The diagnostic value of some of these antigens was, however, limited by the presence of cross-reacting antibody in the healthy controls, even those recruited in non-endemic areas. Cercarial transformation fluid (CTF), a supernatant that contains soluble material released by the cercariae upon transformation to the schistosomula, is cheaper and easier to produce than SEA. An ELISA using CTF as the detection antigen had a sensitivity of 89.7% and an estimated specificity of 100% when used in non-endemic regions, matching the performance of the established SEA ELISA. CTF was substantially more specific than SEA for diagnosis in the endemic region, and less susceptible than SEA to cross-reacting antibody in the sera of controls with other protozoan and metazoan infections.