Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

https://dm5migu4zj3pb.cloudfront.net/manuscripts/34000/34261/JCI0834261.v1.pdf

Helminth infections: the great neglected tropical diseases

Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin
degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.

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The Schistosoma japonicum genome reveals features of host-parasite interplay

Schistosomiasis, caused by trematode blood flukes of the genus Schistosoma, is recognized as the most important human helminth infection in terms of morbidity and mortality Infection follows direct contact with freshwater harboring free-swimming larval (cercaria) forms of the parasite Despite the existence of the highly effective antischistosome drug praziquantel (PZQ), schistosomiasis is spreading into new areas, and although it is the cornerstone of current control programs, PZQ chemotherapy does have limitations In particular, mass treatment does not prevent reinfection Furthermore, there is increasing concern about the development of parasite resistance to PZQ Consequently, vaccine strategies represent an essential component for the future control of schistosomiasis as an adjunct to chemotherapy An improved understanding of the immune response to schistosome infection, both in animal models and in humans, suggests that development of a vaccine may be possible This review considers aspects of antischistosome protective immunity that are important in the context of vaccine development The current status in the development of vaccines against the African (Schistosoma mansoni and S haematobium) and Asian (S japonicum) schistosomes is then discussed, as are new approaches that may improve the efficacy of available vaccines and aid in the identification of new targets for immune attack

https://cmr.asm.org/content/cmr/21/1/225.full.pdf

Current Status of Vaccines for Schistosomiasis

Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4(+) Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Ralpha2, IFN-gamma and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.

Immunopathogenesis of human schistosomiasis

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200,000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties...

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control

Schistosoma japonicum causes schistosomiasis in humans and livestock in the Asia-Pacific region. Knowledge of the genome of this parasite should improve understanding of schistosome-host interactions, biomedical aspects of schistosomiasis and invertebrate evolution. We assigned 43,707 expressed sequence tags (ESTs) derived from adult S. japonicum and their eggs to 13,131 gene clusters. Of these, 35% shared no similarity with known genes and 75% had not been reported previously in schistosomes. Notably, S. japonicum encoded mammalian-like receptors for insulin, progesterone, cytokines and neuropeptides, suggesting that host hormones, or endogenous parasite homologs, could orchestrate schistosome development and maturation and that schistosomes modulate anti-parasite immune responses through inhibitors, molecular mimicry and other evasion strategies.

Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay.

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New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum

Objective To sub-clone and express the gene encoding Schistosoma japonicum calcium-binding protein (SJE16) and study its immunological response. Methods The specific primers were designed according to the expressed sequence tags(ESTs) sequence, which was used for amplification of the encoding sequence from the cDNA clone containing SJE16. The gene was subcloned into pGEX4T-l plasmid and expressed. The rSjE16 was tested for its immunological response by ELISA. Results The gene encoding Schistosoma japonicum SJE16 was cloned and expressed successfully. The immuno-genicity and diagnostic potential of rSjE16 were investigated. It was demonstrated by immunoassay in rabbits that the specificity and sensitivity of the test were 94.1% (16/17) and 88. 2% (15/17), respectively, and the level of antibody liter of the untreated group reached a peak at 9 - 11 wk post infection and maintained high at least for 21 wk post infection, while the antibody level in the treated group rapidly decreased to pre-infection level in 11 wk after treatment. In human, the specificity of the test was 98.3% (57/58); the sensitivity of acute and chronic patient serum assay was 85.5% (53/62) and 70.2% (40/57), respectively. Conclusion The recombinant protein of SjE16 (rSjE16) was acquired. It can be recognized by the sera from schistosomiasis patients, and the level of antibodies decreased quickly after treatment in experimental rabbits, which implicates the potential value for the evaluation of chemotherapy and detection of active infection.

Ju-Jun Wang

Papers

Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource

New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum

Prokaryotic expression of gene encoding Schistosoma japonicum SjE16 and its potential application in immunodiagnosis