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Schistosomiasis and the molecular biology of the male-female interaction of S. mansoni
Abstract
Parasitic helminths of the genus Schistosoma are the causative agents of schistosomiasis, an infectious disease affecting humans and animals. For humans, it is one of the most prevalent parasitemias in the world, second behind malaria. Estimates of the World Health Organisation (WHO) indicate that more than 200 million people live in endemic areas (WHO, Fact Sheet No 115). With respect to animals, a number of 530 million cattle is estimated to live in endemic territories of Africa and Asia. In the last two decades ambitious efforts have been made to develop an effective vaccine against schistosomes, but without resounding success. In addition, there is a pressing need to develop new anthelmintics due to the potential emerging resistance against the commonly used drug praziquantel. Therefore, the understanding of essential physiological or developmental processes of schistosome biology and attempts to intervene in these processes may open new ways to control the parasite. Towards this end, one possibility is to study the unusual biology of schistosomes. These digenean parasites differ from other parasitic flukes by living in the blood vessels. Furthermore, schistosomatids are the only bisexual family of the class trematoda. A nearly unique phenomenon in nature is that a continuous pairing-contact is essential for the development of the reproductive organs of the female, an aspect for the possible design of novel control strategies.
... As the only members of the trematodes, schistosomes have evolved to form separate sexes-dioecious (Platt and Brooks, 1997;Kunz, 2001). Furthermore, mating is required to induce sexual development and maturation of the female worms as a prerequisite for egg production (Kunz, 2001;Ross et al., 2002;Hu et al., 2004;Quack et al., 2006;Beckmann et al., 2010;Lu et al., 2016). The latter finally leads to inflammatory processes in the affected organs of their host (such as the gut and liver of the hosts infected with Schistosoma japonicum or Schistosoma mansoni parasites) due to egg deposition, culminating in the formation of granulomas and fibrosis (Ross et al., 2002). ...
Schistosomiasis, caused by the parasitic flatworms called schistosomes, remains one of the most prevailing parasitic diseases in the world. The prodigious oviposition of female worms after maturity is the main driver of pathology due to infection, yet our understanding about the regulation of development and reproduction of schistosomes is limited. Here, we comparatively profiled the transcriptome of Schistosoma japonicum recovered from SCID and BALB/c mice, which were collected 35 days post-infection, when prominent morphological abnormalities could be observed in schistosomes from SCID mice, by performing RNA-seq analysis. Of the 11,183 identified genes, 62 differentially expressed genes (DEGs) with 39 upregulated and 23 downregulated messenger RNAs (mRNAs) were found in male worms from SCID mice (S_M) vs. male worms from BALB/c mice (B_M), and 240 DEGs with 152 upregulated and 88 downregulated mRNAs were found in female worms from SCID mice (S_F) vs. female worms from BALB/c mice (B_F). We also tested nine DEGs with a relatively higher expression abundance in the gonads of the worms (ovary, vitellaria, or testis), suggesting their potential biological significance in the development and reproduction of the parasites. Gene ontology (GO) enrichment analysis revealed that GO terms such as “microtubule-based process,” “multicellular organismal development,” and “Rho protein signal transduction” were significantly enriched in the DEGs in S_F vs. B_F, whereas GO terms such as “oxidation–reduction process,” “response to stress,” and “response to DNA damage stimulus” were significantly enriched in the DEGs in S_M vs. B_M. These results revealed that the differential expression of some important genes might contribute to the morphological abnormalities of worms in SCID mice. Furthermore, we selected one DEG, the mitochondrial prohibitin complex protein 1 (Phb1), to perform double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) in vivo targeting the worms in BALB/c mice, and we found that it was essential for the growth and reproductive development of both male and female S. japonicum worms. Taken together, these results provided a wealth of information on the differential gene expression profiles of schistosomes from SCID mice when compared with those from BALB/c mice, which were potentially involved in regulating the growth and development of schistosomes. These findings contributed to an understanding of parasite biology and provided a rich resource for the exploitation of antischistosomal intervention targets.
... According to WHO, schistosomiasis is the second most socioeconomically devastating parasitic disease (malaria as the first), and schistosome is among the top ten most important agents causing more deaths [2] . An estimated 779 million individuals are at risk of schistosomiasis and more than 200 million are infected, yet schistosomiasis is often neglected [3] . In Egypt, the disease is well established and it is estimated that up to 70% of the rural population in endemic areas is affected by Schistosoma mansonai [4] . ...
... This indicates the female schistosome worms were affected more severely than the male worms in SCID mice, which was verified by the subsequent finding that more differential metabolites were acquired in IS-FEMALE vs. IB-FEMALE than IS-MALE vs. IB-MALE. This is expectable and reasonable as the growth and development of female worms were affected by male worms as well as the host's factors, i.e., the sexual maturation of female worms depends on pairing with male worms (Shaw et al., 1977;Popiel, 1986;Gupta and Basch, 1987;Boissier and Mone, 2001;Kunz, 2001;Osman et al., 2006; Quack et al., 2006;LoVerde et al., 2009;Wang et al., 2017). These differential metabolites common and distinct in male worms or female worms in SCID mice compared with BALB/c mice may be associated with the abnormal growth and development of worms in SCID mice, and the differential metabolites distinct in male worms or female worms should be associated with larger differences between IS-FEMALE and IB-FEMALE than those between IS-MALE and IB-MALE. ...
The growth and development of schistosome has been affected in the immunodeficient hosts. But it remains unresolved about the molecular mechanisms involved in the development and reproduction regulation of schistosomes. This study tested and compared the metabolic profiles of the male and female Schistosoma japonicum worms collected from SCID mice and BALB/c mice at 5 weeks post infection using liquid chromatography tandem mass spectrometry (LC-MS/MS) platform, in which the worms from SCID mice were the investigated organisms and the worms from BALB/c mice were used as the controls. There were 1015 ion features in ESI+ mode and 342 ion features in ESI- mode were identified after filtration by false discovery rate. Distinct metabolic profiles were found to clearly differentiate both male and female worms in SCID mice from those in BALB/c mice using multivariate modeling methods including the Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). There were more differential metabolites in female worms than in male worms between SCID mice and BALB/c mice. And common and uniquely perturbed metabolites and pathways were identified among male and female worms from SCID mice when compared with BALB/c mice. The enriched metabolite sets of the differential metabolites in male worms between SCID mice and BALB/c mice included bile acid biosynthesis, taurine and hypotaurine metabolism, sphingolipid metabolism, retinol metabolism, purine metabolism, etc. And the enriched metabolite sets of differential metabolites in female worms included retinol metabolism, alpha linolenic acid and linoleic acid metabolism, purine metabolism, sphingolipid metabolism, glutamate metabolism, etc. Further detection and comparison in transcript abundance of genes of the perturbed retinol metabolism and its associated meiosis process in worms identified clues suggesting accumulated retinyl ester and perturbed meiotic process. These findings suggested an association between the schistosome with retarded growth and development in SCID mice and their perturbed metabolites and metabolic pathways, and provided a new insight into the growth and development regulation of S. japonicum worms from the metabolic level, which indicated great clues for discovery of drugs or vaccines against the parasites and disease with more researches.
... For this reason, praziquantel (PZQ) remains the mainstay of the disease control. 6 PZQ has high cure and egg reduction rates with only mild side effects, but suffers from two serious drawbacks. Firstly, it is active only at the adult stage of the worm which means that it exerts its action after sexual maturation and oviposition. ...
The roots of Ozoroa pulcherrima Schweinf are used in traditional medicine to treat intestinal helminthiasis. The aim of this study was to assess the effect of Ozoroa pulcherrima roots methanolic extract (OPME) on liver injury induced by Schistosoma mansoni in mice. A preliminary phytochemical study of OPME was conducted. OPME was given daily and orally to S. mansoni-infected mice at 100, 200 or 400 mg/kg for 28 days, starting from the 36th day post-infection. Praziquantel was used as reference drug. Non-infected and infected-untreated mice served as controls. Worm burden and egg output, transaminases, total bilirubin, alkaline phosphatase and total protein; as well as malondialdehyde, catalase and reduced glutathione were evaluated. In OPME, total phenolic was 79.61 ± 0.25 mg gallic acid equivalent/g, while total flavonoid was 7.98 ± 0.04 mg rutin equivalent/g. Treatment of S. mansoni-infected mice with OPME produced significant reduction of worm burden and ova count in the faeces, liver and intestine. Significant reduction of alanine aminotransferase activity (p < 0.001) as well as significant increase of total protein content (p < 0.001) was recorded after OPME treatment at all doses. Total bilirubin level was also reduced (p < 0.01). Administration of OPME at all doses corrected the high malondialdehyde level (p < 0.001) induced by the infection. At 200 mg/kg, catalase activity and reduced glutathione concentration were significantly increased (p < 0.001). OPME at 200 mg/kg showed moderate schistosomicidal effect, but was effective as the standard drug praziquantel in restoring the liver function after S. mansoni infection. © 2017 Center for Food and Biomolecules, National Taiwan University
... Schistosoma are the causative agents of schistosomiasis, which is a neglected disease, so it remains a significant public health problem in tropical and subtropical regions (Quack et al., 2006;Steinmann et al., 2006). In Egypt, the disease is well established and it is estimated that up to 70% of the rural population in endemic areas is affected (Al Sherbiny et al., 2003). ...
Schistosomiasis is the second most predominant tropical disease in Africa after malaria. In the developing world, it has a great public health and socioeconomic importance. Here, we aimed to assess the antioxidant and anti-schistosomal activities of Morus alba leaves (MLE) methanolic extract (200, 400 and 800 mg/kg) on the noticed tissue damage caused by Schistosoma mansoni infection in mice. The infection resulted in marked histopathological abnormalities in the spleen and jejunum. Moreover, infection induced splenomegally and the spleen appeared with disorganized red and white pulps while the jejunum of the infected mice appeared with some inflammation, vacuolation of the epithelium, and destruction of some villi. Also, the number of goblet cells within the infected villi was significantly increased. In addition, schistosomiasis caused oxidative damage where the level of glutathione (GSH) was reduced significantly while the levels of malondialdehyde (MDA) and nitrite/nitrate were elevated significantly. On the other hand, oral gavage of MLE extract ameliorated the tissues damage and oxidative stress induced by Schistosomasis. The present study indicates that MLE extract possess a highly promising ameliorative effect against histopathological damages and oxidative stress induced by Schistosomasis.
... According to WHO, schistosomiasis is the second most socioeconomically devastating parasitic disease (malaria as the first), and schistosome is among the top ten most important agents causing more deaths [2] . An estimated 779 million individuals are at risk of schistosomiasis and more than 200 million are infected, yet schistosomiasis is often neglected [3] . In Egypt, the disease is well established and it is estimated that up to 70% of the rural population in endemic areas is affected by Schistosoma mansonai [4] . ...
Background: Hepatosplenomegaly is a characteristic feature of Schistosoma infestation. However, splenic injury had received little scientific researches than the well-known liver injury. Moreover, the role of bone marrow derived mesenchymal stem cells (BMMSCs) in treatment of splenic injury due to schistosomiasis has not yet been investigated. Aim of the work: To explore the structural changes which might occur to spleen during chronic infestation with schistosomiasis and the possible therapeutic role of (BMMSCs) in ameliorating these changes. Materials & Methods: Fifty female Swiss Albino mice, weighing about 25 gm were classified into group A (control group) and group B (experimental group). Animals in group A were equally subdivided into subgroup AI which served as donors for stem cells obtained from their bone marrow, and subgroup AII which were injected with phosphate buffer saline (PBS) and used to collect control spleen samples. Whereas, animals in group B, were all infected with S. mansoni cercariae (60/ mouse) by subcutaneous injection, then subdivided into three subgroups; subgroup BI sacrificed after eight weeks, subgroup BII treated intraperitoneally with 2x106 MSCs suspended in PBS per mouse at eighth week after infestation hen scarified four weeks later, and subgroup BIII allowed to survive for twelve weeks without treatment then sacrificed. Results: Histological examination of spleen sections of subgroup BI showed structural changes including deposition of eggs which were surrounded by inflammatory cells and collagen fibers. Subgroup BIII showed more extensive structural changes. This was associated with significant increase in collagen fibers and TNF-α immunological reaction compared to control. However, (BMMSCs) treated subgroup BII illustrated improvement of splenic structure. Conclusions: Chronic Schistosoma mansoni infestation has a deleterious effect on the structure of the spleen. Bone marrow derived mesenchymal stem cells have a relevant therapeutic potential on the spleen of an animal model of Schistosoma mansoni.
... Upon pairing, differentiation processes are induced, leading to the maturation of the ovary and vitellarium that characterizes a sexually mature female (bF). In contrast with females, pairing-inexperienced males (sM) possess testes with differentiated spermatocytes and exhibit no morphological differences from pairingexperienced males (bM) [28][29][30][31]. Nevertheless, pairing also induces changes in male gene expression [32][33][34]. ...
Schistosomes are blood-dwelling trematodes with global impact on human and animal health. Because medical treatment is currently based on a single drug, praziquantel, there is urgent need for the development of alternative control strategies. The Schistosoma mansoni genome project provides a platform to study and connect the genetic repertoire of schistosomes to specific biological functions essential for successful parasitism. G protein–coupled receptors (GPCRs) form the largest superfamily of transmembrane receptors throughout the Eumetazoan phyla, including platyhelminths. Due to their involvement in diverse biological processes, their pharmacological importance, and proven druggability, GPCRs are promising targets for new anthelmintics. However, to identify candidate receptors, a more detailed understanding of the roles of GPCR signalling in schistosome biology is essential. An updated phylogenetic analysis of the S. mansoni GPCR genome (GPCRome) is presented, facilitated by updated genome data that allowed a more precise annotation of GPCRs. Additionally, we review the current knowledge on GPCR signalling in this parasite and provide new insights into the potential roles of GPCRs in schistosome reproduction based on the findings of a recent tissue-specific transcriptomic study in paired and unpaired S. mansoni. According to the current analysis, GPCRs contribute to gonad-specific functions but also to nongonad, pairing-dependent processes. The latter may regulate gonad-unrelated functions during the multifaceted male–female interaction. Finally, we compare the schistosome GPCRome to that of another parasitic trematode, Fasciola, and discuss the importance of GPCRs to basic and applied research. Phylogenetic analyses display GPCR diversity in free-living and parasitic platyhelminths and suggest diverse functions in schistosomes. Although their roles need to be substantiated by functional studies in the future, the data support the selection of GPCR candidates for basic and applied studies, invigorating the exploitation of this important receptor class for drug discovery against schistosomes but also other trematodes.
The tegument of schistosomes is the interface between the worm and the host environment. Some molecules distributed on the tegument participate in host–parasite interactions. Aspartyl aminopeptidase (AAP), identified on the tegument of Schistosoma japonicum (S. japonicum), facilitate protein turnover by acting in concert with other aminopeptidases. In this study, the gene encoding S. japonicum aspartyl aminopeptidase (SjAAP) was cloned, expressed and characterized. Quantitative real-time PCR analysis showed that SjAAP was expressed in all studied developmental stages. The transcript level was higher in 8, 14, 21, and 28 days old worms than the other detected stages. Moreover, the level of expression in 42-day-old male worms was significantly higher than that in females. The recombinant SjAAP (rSjAAP) was expressed as both supernatant and inclusion bodies in Escherichia coli BL21 cells. The enzymatic activity of rSjAAP was 4.45 U/mg. The Km and Vmax values for H-Asp-pNA hydrolysis were discovered to be 5.93 mM and 0.018 mM•min–1. Immunofluorescence analysis revealed that SjAAP is primarily distributed on the tegument and parenchyma of schistosomes. Western blot showed that rSjAAP possessed good immunogenicity. Although specific antibodies were produced in BALB/c mice vaccinated with rSjAAP emulsified with ISA 206 adjuvant, no significant reduction of worm burden and number of eggs in the liver was observed. Therefore, rSjAAP may not be a suitable to act as a potential vaccine candidate against schistosomiasis japonica in mice. However, this study provides some foundation for further exploration of the biological function of this molecule.
The high price of new generations of vaccines relative to their predecessors has become an important consideration in debates over whether the benefits of the new vaccines justify their costs. An increasingly central line of inquiry in the literature on valuing vaccination surrounds accounting for the full social and economic benefits of vaccination. This paper applies this emerging perspective to the particular case of vaccination against serogroup B meningococcal disease (MenB). We explore key issues involved in health technology assessments of MenB vaccination, which have led to pronounced heterogeneity in evaluation methods and recommendation outcomes across countries such as France, Germany, the US, and the UK. Accounting for typically neglected sources of socioeconomic benefit could potentially impact recommendation and reimbursement decisions. We propose a taxonomy of such benefits built around four dimensions: (i) internalized health benefits, (ii) internalized non-health benefits, (iii) externalized health benefits, and (iv) externalized non-health benefits. This approach offers a systematic, comprehensive evaluation framework that can be used in future assessment of MenB vaccines as well as other health technologies.
Recent advances in systems biology have shifted vaccine development from a largely trial-and-error approach to an approach that promote rational design through the search for immune signatures and predictive correlates of protection. These advances will doubtlessly accelerate the development of a vaccine for schistosomiasis, a neglected tropical disease that currently affects over 250 million people. For over 15 years and with contributions of over 120 people, we have endeavored to test and optimize Sm-p80-based vaccines in the non-human primate model of schistosomiasis. Using RNA-sequencing on eight different Sm-p80-based vaccine strategies, we sought to elucidate immune signatures correlated with experimental protective efficacy. Furthermore, we aimed to explore the role of antibodies through in vivo passive transfer of IgG obtained from immunized baboons and in vitro killing of schistosomula using Sm-p80-specific antibodies. We report that passive transfer of IgG from Sm-p80-immunized baboons led to significant worm burden reduction, egg reduction in liver, and reduced egg hatching percentages from tissues in mice compared to controls. In addition, we observed that sera from Sm-p80-immunized baboons were able to kill a significant percent of schistosomula and that this effect was complement-dependent. While we did not find a universal signature of immunity, the large datasets generated by this study will serve as a substantial resource for further efforts to develop vaccine or therapeutics for schistosomiasis.
The biology of the helminth parasiteSchistosoma mansoni is closely integrated with that of its mammalian host. SmRK1, a divergent type I transforming growth factor-β (TGF-β) receptor
of unknown ligand specificity, was previously identified as a candidate for a receptor that allows schistosomes to respond
to host-derived growth factors. The TGF-β family includes activin, bone morphogenetic proteins (BMPs), and TGF-β, all of which
can play crucial roles in metazoan development. The downstream signaling protein of receptors that respond to TGF-β and activin
is Smad2, whereas the receptors that respond to BMPs signal via Smad1. When a constitutively active mutant of SmRK1 was overexpressed
with either schistosome Smad1 (SmSmad1) or SmSmad2, a receptor-dependent modulation of SmSmad phosphorylation and luciferase
reporter activity occurred only with SmSmad2. To evaluate potential ligand activators of SmRK1, a chimeric receptor containing
the extracellular domain of SmRK1 joined to the intracellular domain of the human type I TGF-β receptor was used. The chimeric
receptor bound radiolabeled TGF-β and could activate a luciferase reporter gene in response to both TGF-β1 and TGF-β3 but
not BMP7. Confirmatory results were obtained using full-length SmRK1. These experiments implicate TGF-β as a ligand for SmRK1
and as a potential host-derived regulator of parasite growth and development.
We have established an in vitro culture system for adult schistosomes that allows monitoring gene expression for up to more than ten days. Comparing female worms that are paired with those that have been separated, we find distinct differences, clearly documenting an influence of the male in female gene expression. In perfect coincidence with classical observations that were based on histological techniques, we find that the male particularly regulates gene expression in those tissues that are characterized by cell proliferation, e.g. the vitellaria. From these results, we hypothesize that the key target for the inductive signal that is transferred from the male to the female during pairing is the activation of a growth factor that stimulates mitotic proliferation.
Egg production by worm pairs is a major cause of pathogenesis in schistosomiasis. To further the understanding of female reproductive development, we have isolated and characterized a complete copy of an eggshell protein precursor gene, p48. Sequence analysis reveals that the gene has 3 open reading frames and does not contain an intron. One of the open reading frames, ORF1, encodes a polypeptide of 50 kDa which shows strong homology to insect chorion proteins. Determination of the position of the mRNA cap-site facilitated identification of putative regulatory elements in the 5' upstream region of the gene. Some of these elements (e.g., TCACGT) have been shown to play a role in the regulation of chorion gene expression in insects. p48 mRNA is detectable only in mature female worms and the ability to detect the mRNA coincides temporally with worm pairing. Quantitative comparisons, during female reproductive development, of p48 transcripts to those from another eggshell protein precursor gene, p14, show that the p48 mRNA is significantly less abundant than p14 mRNA. In mature female worms, p48 mRNA can only be detected in vitelline cells. Antibodies made against the polypeptide sequence deduced from ORF1 of the p48 gene recognize a 50-kDa molecule in extracts from mature female worms, but not in extracts from immature females or males.
Syk protein tyrosine kinase is essential for immune system development and function [1] and for the maintenance of vascular integrity [2, 3]. In leukocytes, Syk is activated by binding to diphosphorylated immune receptor tyrosine-based activation motifs (pITAMs) [1]. Syk can also be activated by integrin adhesion receptors [4, 5], but the mechanism of its activation is unknown. Here we report a novel mechanism for Syk's recruitment and activation, which requires that Syk bind to the integrin β3 cytoplasmic tail. We found that both Syk and the related kinase ZAP-70 bound the β3 cytoplasmic tail through their tandem SH2 domains. However, unlike Syk binding to pITAMs, this interaction was independent of tyrosine phosphorylation and of the phosphotyrosine binding function of Syk's tandem SH2 domains. Deletion of the four C-terminal residues of the β3 cytoplasmic tail [β3(759X)] decreased Syk binding and disrupted its physical association with integrin αIIbβ3. Furthermore, cells expressing αIIbβ3(759X) failed to exhibit Syk activation or lamellipodia formation upon cell adhesion to the αIIbβ3 ligand, fibrinogen. In contrast, FAK phosphorylation and focal adhesion formation were unimpaired by this mutation. Thus, the direct binding of Syk kinase to the integrin β3 cytoplasmic tail is a novel and functionally significant mechanism for the regulation of this important non-receptor tyrosine kinase.
We describe the cloning and functional characterization of Schistosoma mansoni retinoid-X-receptor (SmRXR; NR2B4-B), a novel member of the nuclear receptor superfamily from S. mansoni, a homologue of vertebrate retinoid-X-receptor. The DNA-binding C domain of SmRXR shows 80% sequence identity to both human RXR and Drosophila ultraspiracle (USP), but a much lower level of conservation of the ligand-binding E domain (22–25% identity). Phylogenetic analysis places SmRXR within the RXR group as an early offshoot of this clade. SmRXR mRNA is expressed at all life-cycle stages but at higher levels in the free-living larval stages. However, the SmRXR protein is expressed at markedly different levels, being almost absent from eggs while present at the highest concentration in schistosomula. Recombinant SmRXR fails to bind to the consensus direct repeat response elements, either alone, or as a heterodimer with mouse retinoic acid receptor or the Drosophila ecdysone receptor. However, the use of chimaeric constructions shows that the C domain of SmRXR will bind to conventional response elements as a heterodimer, and that its specificity is modified by the presence of the D and E domains. In accordance with these results, native SmRXR failed to transactivate the transcription of a reporter gene after cotransfection of mammalian cell lines.
The protein-tyrosine kinase Syk participates in signal transduction pathways downstream from multiple immune recognition receptors. Recent evidence indicates that Syk is also functionally coupled to cell surface integrins, which mediate interactions between the actin cytoskeleton and extracellular matrix proteins. The interactions of undifferentiated, promonocytic HL60 or U937 cells with fibronectin or anti-β1 integrin antibodies leads to an apparent activation and tyrosine phosphorylation of Syk that is independent of tight cellular adhesion and spreading. In response to fibronectin or anti-β1 integrin antibodies, β1 integrins become associated with a complex of proteins that include the Lyn protein tyrosine kinase and endogenous kinase substrates of 29 and 75 – 80 kDa. Lyn becomes transiently activated following integrin engagement and co-localizes with the actin cytoskeleton. These studies suggest a major role for Lyn in coupling β1 integrins to the activation of Syk.
Popiel I., Cioli D. and Erasmus D. A. 1984. The morphology and reproductive status of female Schistosoma mansoni following separation from male worms. International Journal for Parasitology14: 183–190. Sexually mature females of Schistosoma mansoni were separated from their male partners and surgically transferred to Nile rats (Arvicanthis niloticus). Over a period of 35 days there was a significant decrease in size of these worms and regression of the reproductive system took place. Electron microscope observations of the vitelline gland and ovary provided details of and a time scale for the regressive changes which took the form of a cessation of cell differentiation and turnover, together with extensive cell death. Survival of cells within these organs was restricted to the undifferentiated cells and by day 35 the worms resembled immature females. It is concluded that regression of the female reproductive system was the result of discontinued male stimulation.The nature and implications of the obligatory relationship between male and female S. mansoni are discussed.
The relationship between cell-mediated granulomatous inflammation and transmission of disease in schistosomiasis and tuberculosis has been explored. In 2 experiments involving Schistosoma mansoni-infected normal and T cell-deprived mice, and infected deprived mice that had been variously reconstituted with immune or normal lymphocytes or immune serum, there was a significant positive numerical correlation between mean liver granuloma diameters and faecal egg counts in individual animals. Lymphocytes from donors with recently patent infections were more active than cells from chronically infected or uninfected donors in reconstituting egg excretion rates in deprived recipients, and mesenteric lymph node (MLN) cells were more active than spleen cells. Modulation of granulomatous activity with increasing chronicity of infection in the donors, resulting in a decrease in granuloma size around freshly produced tissue-bound eggs, was paralleled by a waning of the capacity of transferred lymph node cells to reconstitute egg excretion in the recipients. Serum taken from chronically infected donor mice over the same period and transferred to infected deprived recipients became more active in enhancing egg excretion in the recipients as the cell-mediated activity declined. A recent study in Kenya has found that S. mansoni-infected patients with concurrent human immunodeficiency virus (HIV) infection excrete fewer eggs than patients exposed to the same levels of schistosome infection, but who are not HIV-infected, thus indicating that schistosome egg excretion in humans is also immune-dependent. Attention is drawn to an apparently parallel situation in human tuberculosis, another pathogen which induces a cell-mediated granulomatous immune response. Several studies have shown that patients with tuberculosis who are also HIV-seropositive tend to have fewer tubercle bacilli detectable in their saliva than those with tuberculosis, but who are HIV-negative. This discrepancy, associated with differences in lung pathology in HIV-positive patients, suggests that in tuberculosis immune cell-mediated granulomatous inflammation causes the destruction of host tissue in a manner which facilitates onward transmission of the bacterial pathogen.
The relative distribution of Schistosoma japonicum eggs in the intestine of man is inconsistent in the literature. Some scientists believe that the adult S. japonicum worms reside mainly in the superior mesenteric vein and their eggs are deposited predominately in the small intestine, whereas others have shown that the adult worms have a predilection for inhabiting the branches of the inferior mesenteric vein and superior haemorrhoidal vein and their eggs are deposited in much higher density in the large intestine, especially in the rectum, sigmoid and descending colon, than in the small intestine. A review of the literature was made which includes the results from animal experiments as well as from human clinical and pathological studies. The author is in favour of the latter view that in man, S. japonicum eggs are deposited predominately in the large intestine and small intestine involvement is usually slight.