-
Parasitology Apr 2020Only with the completion of the life cycles of Fasciola hepatica in 1883 and 30 years later those of Schistosoma japonicum (1913), Schistosoma haematobium and... (Review)
Review
Only with the completion of the life cycles of Fasciola hepatica in 1883 and 30 years later those of Schistosoma japonicum (1913), Schistosoma haematobium and Schistosoma mansoni (1915) did research on schistosomiasis really get underway. One of the first papers by Cawston in 1918, describing attempts to establish the means of transmission of S. haematobium in Natal, South Africa, forms the historical perspective against which to judge where we are now. Molecular biology techniques have produced a much better definition of the complexity of the schistosome species and their snail hosts, but also revealed the extent of hybridization between human and animal schistosomes that may impact on parasite adaptability. While diagnostics have greatly improved, the ability to detect single worm pair infections routinely, still falls short of its goal. The introduction of praziquantel ~1982 has revolutionized the treatment of infected individuals and led directly to the mass drug administration programmes. In turn, the severe pathological consequences of high worm burdens have been minimized, and for S. haematobium infections the incidence of associated squamous cell carcinoma has been reduced. In comparison, the development of effective vaccines has yet to come to fruition. The elimination of schistosomiasis japonica from Japan shows what is possible, using multiple lines of approach, but the clear and present danger is that the whole edifice of schistosome control is balanced on the monotherapy of praziquantel, and the development of drug resistance could topple that.
Topics: Animals; Carcinoma, Squamous Cell; Drug Resistance; History, 20th Century; History, 21st Century; Humans; Life Cycle Stages; Praziquantel; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Snails; Vaccines
PubMed: 31965953
DOI: 10.1017/S0031182020000049 -
Frontiers in Immunology 2021Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical... (Review)
Review
Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease - processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.
Topics: Animals; Disease Models, Animal; Host-Parasite Interactions; Humans; Immune Evasion; Lung; Lung Diseases, Parasitic; Mice; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 33953712
DOI: 10.3389/fimmu.2021.635513 -
PLoS Neglected Tropical Diseases Mar 2021We were tasked by the World Health Organization (WHO) to address the following question: What techniques should be used to diagnose Schistosoma infections in snails and...
BACKGROUND
We were tasked by the World Health Organization (WHO) to address the following question: What techniques should be used to diagnose Schistosoma infections in snails and in the water in potential transmission sites? Our goal was to review and evaluate the available literature and provide recommendations and insights for the development of WHO's Guidelines Development Group for schistosomiasis control and elimination.
METHODOLOGY
We searched several databases using strings of search terms, searched bibliographies of pertinent papers, and contacted investigators who have made contributions to this field. Our search covered from 1970 to Sept 2020. All papers were considered in a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, and retained papers were grouped by technique and subjected to our GRADE (Grading of Recommendations, Assessment, Development and Evaluations) evidence assessment profile determined in consultation with WHO. We also considered issues of sensitivity, specificity, coverage, cost, robustness, support needs, schistosome species discrimination, and relevant detection limits.
PRINCIPAL FINDINGS
Our PRISMA process began with the perusal of 949 articles, of which 158 were retained for data extraction and evaluation. We identified 25 different techniques and for each applied a GRADE assessment considering limitations, inconsistency, imprecision, indirectness, and publication bias. We also provide advantages and disadvantages for each category of techniques.
CONCLUSIONS
Our GRADE analysis returned an assessment of moderate quality of evidence for environmental DNA (eDNA), qPCR and LAMP (Loop-mediated isothermal amplification). No single ideal diagnostic approach has yet been developed, but considerable recent progress has been made. We note a growing trend to use eDNA techniques to permit more efficient and replicable sampling. qPCR-based protocols for follow-up detection offer a versatile, mature, sensitive, and specific platform for diagnosis though centralized facilities will be required to favor standardization. Droplet digital PCR (ddPCR) can play a complementary role if inhibitors are a concern, or more sensitivity or quantification is needed. Snail collection, followed by shedding, is encouraged to provide specimens for sequence verifications of snails or schistosomes. LAMP or other isothermal detection techniques offer the prospect of less expensive and more distributed network of analysis but may face standardization and verification challenges related to actual sequences amplified. Ability to detect schistosome infections in snails or in the water is needed if control and elimination programs hope to succeed. Any diagnostic techniques used need to be regularly verified by the acquisition of DNA sequences to confirm that the detected targets are of the expected species. Further improvements may be necessary to identify the ideal schistosome or snail sequences to target for amplification. More field testing and standardization will be essential for long-term success.
Topics: Animals; DNA, Environmental; DNA, Helminth; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Real-Time Polymerase Chain Reaction; Schistosoma; Schistosomiasis; Snails; Water
PubMed: 33760814
DOI: 10.1371/journal.pntd.0009175 -
Trends in Parasitology Nov 2018Linkage mapping - utilizing experimental genetic crosses to examine cosegregation of phenotypic traits with genetic markers - is now 100 years old. Schistosome parasites... (Review)
Review
Linkage mapping - utilizing experimental genetic crosses to examine cosegregation of phenotypic traits with genetic markers - is now 100 years old. Schistosome parasites are exquisitely well suited to linkage mapping approaches because genetic crosses can be conducted in the laboratory, thousands of progeny are produced, and elegant experimental work over the last 75 years has revealed heritable genetic variation in multiple biomedically important traits such as drug resistance, host specificity, and virulence. Application of this approach is timely because the improved genome assembly for Schistosoma mansoni and developing molecular toolkit for schistosomes increase our ability to link phenotype with genotype. We describe current progress and potential future directions of linkage mapping in schistosomes.
Topics: Animals; Chromosome Mapping; Crosses, Genetic; Genetic Markers; Genetic Variation; Genotype; Host Specificity; Phenotype; Schistosoma; Schistosoma mansoni; Schistosomiasis; Virulence
PubMed: 30150002
DOI: 10.1016/j.pt.2018.08.001 -
Frontiers in Cellular and Infection... 2016Schistosomes are metazoan parasites and can cause schistosomiasis. Epigenetic modifications include DNA methylation, histone modifications and non-coding RNAs. Some... (Review)
Review
Schistosomes are metazoan parasites and can cause schistosomiasis. Epigenetic modifications include DNA methylation, histone modifications and non-coding RNAs. Some enzymes involved in epigenetic modification and microRNA processes have been developed as drugs to treat the disease. Compared with humans and vertebrates, an in-depth understanding of epigenetic modifications in schistosomes is starting to be realized. DNA methylation, histone modifications and non-coding RNAs play important roles in the development and reproduction of schistosomes and in interactions between the host and schistosomes. Therefore, exploring and investigating the epigenetic modifications in schistosomes will facilitate drug development and therapy for schistosomiasis. Here, we review the role of epigenetic modifications in the development, growth and reproduction of schistosomes, and the interactions between the host and schistosome. We further discuss potential epigenetic targets for drug discovery for the treatment of schistosomiasis.
Topics: Animals; Epigenesis, Genetic; Host-Parasite Interactions; Reproductive Physiological Phenomena; Schistosoma
PubMed: 27891322
DOI: 10.3389/fcimb.2016.00149 -
Parasite Immunology Aug 2014There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas:... (Review)
Review
There is a wealth of immunologic studies that have been carried out in experimental and human schistosomiasis that can be classified into three main areas: immunopathogenesis, resistance to reinfection and diagnostics. It is clear that the bulk of, if not all, morbidity due to human schistosomiasis results from immune-response-based inflammation against eggs lodged in the body, either as regulated chronic inflammation or resulting in fibrotic lesions. However, the exact nature of these responses, the antigens to which they are mounted and the mechanisms of the critical regulatory responses are still being sorted out. It is also becoming apparent that protective immunity against schistosomula as they develop into adult worms develops slowly and is hastened by the dying of adult worms, either naturally or when they are killed by praziquantel. However, as with anti-egg responses, the responsible immune mechanisms and inducing antigens are not clearly established, nor are any potential regulatory responses known. Finally, a wide variety of immune markers, both cellular and humoral, can be used to demonstrate exposure to schistosomes, and immunologic measurement of schistosome antigens can be used to detect, and thus diagnose, active infections. All three areas contribute to the public health response to human schistosome infections.
Topics: Animals; Humans; Inflammation; Schistosoma; Schistosomiasis; Vaccines
PubMed: 25142505
DOI: 10.1111/pim.12087 -
Parasites & Vectors Nov 2019Many parasites migrate through different tissues during their life-cycle, possibly with the aim to enhance their fitness. This is true for species of three parasite... (Review)
Review
Many parasites migrate through different tissues during their life-cycle, possibly with the aim to enhance their fitness. This is true for species of three parasite genera of global importance, Ascaris, Schistosoma and Plasmodium, which cause significant global morbidity and mortality. Interestingly, these parasites all incorporate the liver in their life-cycle. The liver has a special immune status being able to preferentially induce tolerance over immunity. This function may be exploited by parasites to evade host immunity, with Plasmodium spp. in particular using this organ for its multiplication. However, hepatic larval attrition occurs in both ascariasis and schistosomiasis. A better understanding of the molecular mechanisms involved in hepatic infection could be useful in developing novel vaccines and therapies for these parasites.
Topics: Animals; Ascaris; Humans; Life Cycle Stages; Liver; Plasmodium; Schistosoma
PubMed: 31703729
DOI: 10.1186/s13071-019-3791-2 -
PLoS Pathogens Aug 2014Schistosomes are parasitic flatworms that infect >200 million people worldwide, causing the chronic, debilitating disease schistosomiasis. Unusual among parasitic... (Review)
Review
Schistosomes are parasitic flatworms that infect >200 million people worldwide, causing the chronic, debilitating disease schistosomiasis. Unusual among parasitic helminths, the long-lived adult worms, continuously bathed in blood, take up nutrients directly across the body surface and also by ingestion of blood into the gut. Recent proteomic analyses of the body surface revealed the presence of hydrolytic enzymes, solute, and ion transporters, thus emphasising its metabolic credentials. Furthermore, definition of the molecular mechanisms for the uptake of selected metabolites (glucose, certain amino acids, and water) establishes it as a vital site of nutrient acquisition. Nevertheless, the amount of blood ingested into the gut per day is considerable: for males ∼100 nl; for the more actively feeding females ∼900 nl, >4 times body volume. Ingested erythrocytes are lysed as they pass through the specialized esophagus, while leucocytes become tethered and disabled there. Proteomics and transcriptomics have revealed, in addition to gut proteases, an amino acid transporter in gut tissue and other hydrolases, ion, and lipid transporters in the lumen, implicating the gut as the site for acquisition of essential lipids and inorganic ions. The surface is the principal entry route for glucose, whereas the gut dominates amino acid acquisition, especially in females. Heme, a potentially toxic hemoglobin degradation product, accumulates in the gut and, since schistosomes lack an anus, must be expelled by the poorly understood process of regurgitation. Here we place the new observations on the proteome of body surface and gut, and the entry of different nutrient classes into schistosomes, into the context of older studies on worm composition and metabolism. We suggest that the balance between surface and gut in nutrition is determined by the constraints of solute diffusion imposed by differences in male and female worm morphology. Our conclusions have major implications for worm survival under immunological or pharmacological pressure.
Topics: Animals; Female; Host-Parasite Interactions; Humans; Male; Schistosoma; Schistosomiasis
PubMed: 25121497
DOI: 10.1371/journal.ppat.1004246 -
PLoS Neglected Tropical Diseases Apr 2022Schistosomiasis, a major cause of pulmonary arterial hypertension (PAH) worldwide, is most clearly described complicating infection by one species, Schistosoma mansoni....
BACKGROUND
Schistosomiasis, a major cause of pulmonary arterial hypertension (PAH) worldwide, is most clearly described complicating infection by one species, Schistosoma mansoni. Controlled exposure of mice can be used to induce Type 2 inflammation-dependent S. mansoni pulmonary hypertension (PH). We sought to determine if another common species, S. japonicum, can also cause experimental PH.
METHODS
Schistosome eggs were obtained from infected mice, and administered by intraperitoneal sensitization followed by intravenous challenge to experimental mice, which underwent right heart catheterization and tissue analysis.
RESULTS
S. japonicum sensitized and challenged mice developed PH, which was milder than that following S. mansoni sensitization and challenge. The degree of pulmonary vascular remodeling and Type 2 inflammation in the lungs was similarly proportionate. Cross-sensitization revealed that antigens from either species are sufficient to sensitize for intravenous challenge with either egg, and the degree of PH severity depended on primarily the species used for intravenous challenge. Compared to a relatively uniform distribution of S. mansoni eggs, S. japonicum eggs were observed in clusters in the lungs.
CONCLUSIONS
S. japonicum can induce experimental PH, which is milder than that resulting from comparable S. mansoni exposure. This difference may result from the distribution of eggs in the lungs, and is independent of which species is used for sensitization. This result is consistent with the clearer association between S. mansoni infection and the development of schistosomiasis-associated PAH in humans.
Topics: Animals; Hypertension, Pulmonary; Inflammation; Mice; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis
PubMed: 35417453
DOI: 10.1371/journal.pntd.0010343 -
Current Protocols in Immunology May 2001The trematode parasites in the family Schistosomatidae (phylum Platyhelminthes) infect a wide range of vertebrates. Three species of the genus Schistosoma are of major...
The trematode parasites in the family Schistosomatidae (phylum Platyhelminthes) infect a wide range of vertebrates. Three species of the genus Schistosoma are of major medical importance. This unit deals exclusively with the parasite Schistosoma mansoni, which is the species most frequently maintained in the laboratory. Among the far-ranging investigations in the immunology of schistosomiasis are studies in vaccine development, immunopathology of granulomatous inflammation and fibrosis, eosinophil function, and in vivo regulation of T(H)1 and T(H)2 responses. This unit describes maintenance and collection procedures for various stages of the schistosome that have immunologic interest, including infection of mice with cercariae, collection of cercariae, preparation of in vitro-derived schistosomules and in vivo-derived schistosomules, and collection of adult worms and eggs. Included also are techniques for preparing soluble egg antigen (SEA), one of the more commonly used schistosome antigenic preparations. A discussion is given of the basic steps that are important in maintaining the snail intermediate host, and infecting the snails with schistosome miracidia. The unit deals exclusively with the parasite Schistosoma mansoni, which is the species most frequently maintained in the laboratory. Since part of the life cycle of all schistosomes involves a snail host, a description of proper maintenance for the snails is provided. Often, problems in experiments can be traced back to improper snail and parasite maintenance, or lack of attention to detail during mammalian exposure to the infective stage (cercaria) of the parasite.
Topics: Animals; Antigens, Helminth; Humans; Life Cycle Stages; Mice; Schistosoma mansoni; Schistosomiasis; Snails; Solubility
PubMed: 18432750
DOI: 10.1002/0471142735.im1901s28