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Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drug—praziquantel—is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines.

Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause.

Taxonomic revision by molecular phylogeny is needed to categorize members of the genus Echinococcus (Cestoda: Taeniidae). We have reconstructed the phylogenetic relationships of E. oligarthrus, E. vogeli, E. multilocularis, E. shiquicus, E. equinus, E. ortleppi, E. granulosus sensu stricto and 3 genotypes of E. granulosus sensu lato (G6, G7 and G8) from their complete mitochondrial genomes. Maximum likelihood and partitioned Bayesian analyses using concatenated data sets of nucleotide and amino acid sequences depicted phylogenetic trees with the same topology. The 3 E. granulosus genotypes corresponding to the camel, pig, and cervid strains were monophyletic, and their high level of genetic similarity supported taxonomic species unification of these genotypes into E. canadensis. Sister species relationships were confirmed between E. ortleppi and E. canadensis, and between E. multilocularis and E. shiquicus, regardless of the analytical approach employed. The basal positions of the phylogenetic tree were occupied by the neotropical endemic species, E. oligarthrus and E. vogeli, whose definitive hosts are derived from carnivores that immigrated from North America after the formation of the Panamanian land bridge. Host-parasite co-evolution comparisons suggest that the ancestral homeland of Echinococcus was North America or Asia, depending on whether the ancestral definitive hosts were canids or felids.

Schistosomiasis is a common neglected tropical disease of impoverished people and livestock in many developing countries in tropical Africa, the Middle East, Asia, and Latin America. Substantial progress has been made in controlling schistosomiasis in some African countries, but the disease still prevails in most parts of sub-Saharan Africa with an estimated 800 million people at risk of infection. Current control strategies rely primarily on treatment with praziquantel, as no vaccine is available; however, treatment alone does not prevent reinfection. There has been emphasis on the use of integrated approaches in the control and elimination of the disease in recent years with the development of health infrastructure and health education. However, there is a need to evaluate the present status of African schistosomiasis, primarily caused by Schistosoma mansoni and S. haematobium, and the factors affecting the disease as the basis for developing more effective control and elimination strategies in the future. This review provides an historical perspective of schistosomiasis in Africa and discusses the current status of control efforts in those countries where the disease is endemic.

Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132. Quantitative proteomic analyses reveals crosstalk between substrates that control protein degradation, and highlights co-regulation of SUMOylation and ubiquitylation levels on deubiquitinase enzymes and the SUMOylation of proteasome subunits. The SUMOylation of the proteasome affects its recruitment to promyelocytic leukemia protein (PML) nuclear bodies, and PML lacking the SUMO interacting motif fails to colocalize with SUMOylated proteasome further demonstrating that this motif is required for PML catabolism. Ubiquitylation and SUMOylation are two important related post-translational modifications. Here the authors present an approach for the simultaneous identification and quantification of protein-wide SUMO and ubiquitin sites from a single sample, uncovering widespread crosstalk between the two modifications.

Zoonotic schistosomiasis in Asia, caused by Schistosoma japonicum, remains a major public health concern in China and the Philippines. The developing epidemiological and socio-economic picture of the disease in endemic areas necessitates the development of affordable and highly accurate field diagnostics as an important component in evaluating ongoing integrated control and elimination efforts. Three diagnostic methods, namely Kato-Katz (KK) stool microscopy, ELISA and droplet digital (dd) PCR assays, were compared by detecting infection in a total of 412 participants from an area moderately endemic for schistosomiasis in the Philippines. This comprehensive comparison further defined the diagnostic performance and features for each assay. Compared with the ddPCR assay analysing DNA from faeces (F_ddPCR), which exhibited the highest sensitivity, the SjSAP4 + Sj23-LHD-ELISA had the best accuracy (67.2%) among all five ELISA assays assessed. Schistosomiasis prevalence determined by the SjSAP4 + Sj23-LHD-ELISA and ddPCRs was similar and was at least 2.5 times higher than obtained with the KK method. However, the agreement between these assays was low. In terms of cost and logistical convenience, the SjSAP4 + Sj23-LHD-ELISA represents a cost-effective assay with considerable diagnostic merits. In contrast, although the ddPCR assays exhibited a high level of diagnostic performance, the high cost and the need for specialized equipment presents a major obstacle in their application in screening campaigns. The SjSAP4 + Sj23-LHD-ELISA represents a cost-effective tool for the diagnosis of schistosomiasis that could prove an important component in the monitoring of integrated control measures as elimination draws closer, whereas the ddPCR assays, in addition to their high sensitivity and specificity, are capable of quantifying infection intensity. However, the high cost of ddPCR hinders its wider application in screening programs, although it could be a valuable reference in the development and improvement of other diagnostic assays.

The protein inhibitor of activated STAT1 (PIAS1) is an E3 SUMO ligase that plays important roles in various cellular pathways. Increasing evidence shows that PIAS1 is overexpressed in various human malignancies, including prostate and lung cancers. Here we used quantitative SUMO proteomics to identify potential substrates of PIAS1 in a system-wide manner. We identified 983 SUMO sites on 544 proteins, of which 62 proteins were assigned as putative PIAS1 substrates. In particular, vimentin (VIM), a type III intermediate filament protein involved in cytoskeleton organization and cell motility, was SUMOylated by PIAS1 at Lys-439 and Lys-445 residues. VIM SUMOylation was necessary for its dynamic disassembly and cells expressing a non-SUMOylatable VIM mutant showed a reduced level of migration. Our approach not only enables the identification of E3 SUMO ligase substrates but also yields valuable biological insights into the unsuspected role of PIAS1 and VIM SUMOylation on cell motility. PIAS1 is an E3 SUMO ligase involved in various cellular processes. Here, the authors use quantitative proteomics to identify potential PIAS1 substrates in human cells and elucidate the biological consequences of PIAS1-mediated SUMOylation of vimentin.

Schistosomiasis remains a major public health issue, with an estimated 230 million people infected worldwide. Novel tools for early diagnosis and surveillance of schistosomiasis are currently needed. Elevated levels of circulating microRNAs (miRNAs) are commonly associated with the initiation and progression of human disease pathology. Hence, serum miRNAs are emerging as promising biomarkers for the diagnosis of a variety of human diseases. This study investigated circulating host miRNAs commonly associated with liver diseases and schistosome parasite-derived miRNAs during the progression of hepatic schistosomiasis japonica in two murine models. Two mouse strains (C57BL/6 and BALB/c) were infected with a low dosage of Schistosoma japonicum cercariae. The dynamic patterns of hepatopathology, the serum levels of liver injury-related enzymes and the serum circulating miRNAs (both host and parasite-derived) levels were then assessed in the progression of schistosomiasis japonica. For the first time, an inverse correlation between the severity of hepatocyte necrosis and the level of liver fibrosis was revealed during S. japonicum infection in BALB/c, but not in C57BL/6 mice. The inconsistent levels of the host circulating miRNAs, miR-122, miR-21 and miR-34a in serum were confirmed in the two murine models during infection, which limits their potential value as individual diagnostic biomarkers for schistosomiasis. However, their serum levels in combination may serve as a novel biomarker to mirror the hepatic immune responses induced in the mammalian host during schistosome infection and the degree of hepatopathology. Further, two circulating parasite-specific miRNAs, sja-miR-277 and sja-miR-3479-3p, were shown to have potential as diagnostic markers for schistosomiasis japonica. We provide the first evidence for the potential of utilizing circulating host miRNAs to indicate different immune responses and the severity of hepatopathology outcomes induced in two murine strains infected with S. japonicum. This study also establishes a basis for the early and cell-free diagnosis of schistosomiasis by targeting circulating schistosome parasite-derived miRNAs.

Background. There is evidence to support that nutritional deficiency can reduce the body's immune function, thereby decreasing resistance to disease and increasing susceptibility to intestinal parasites. Methods. A cross-sectional survey was carried out on 693 school-aged children from 5 schistosomiasis-endemic villages in Northern Samar, the Philippines. Data on dietary intake, nutritional status, and intestinal parasitic infection were collected. Results. The prevalence of stunting, thinness, and wasting was 49.2%, 27.8%, and 59.7% of all children. The proportion of children infected with Schistosoma japonicum (15.6%, P = .03) and hookworm (22.0%, P = .05) were significantly lower among children who met the recommended energy and nutrient intake (RENI) for total calories. The percentage of children infected with Trichuris trichiura was highest among children who did not meet the RENI for energy (74.1%, P = .04), iron (73.4%, P = .01), thiamine (74.0%, P = .00), and riboflavin (73.3%, P = .01). Susceptibility to having 1 or more parasitic infections was significantly associated with poor intake of energy (P = .04), thiamine (P = .02), and riboflavin (P = .01). The proportion of stunted children was significantly higher among children who did not meet the RENI for energy (68.9%, P = .002), protein (54.0%, P = .004), or niacin (30.8%, P = .02) and for those infected with hookworm (31.8%, P = .0002). After adjusting for potential confounders, protein intake less than the RENI (odds ratio [OR], 1.48; 95% confidence interval [CI], 1.03–2.14), and hookworm infection (OR, 1.77; 95% CI, 1.22–2.55) were the major predictors of stunting. Conclusions. The results support the hypothesis that poor nutrient intake may increase susceptibility to parasitic diseases and together they negatively affect childhood nutritional status.

SUMMARY POINTS Echinococcosis is a parasitic zoonosis caused by Echinococcus cestode worms The two major species of medical importance are Echinococcus granulosus and E multilocularis, which cause cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively CE and especially AE are life threatening chronic diseases with a high fatality rate and poor prognosis if careful clinical management is not carried out Human CE is cosmopolitan and the more common presentation, accounting for most of the estimated two to three million global echinococcosis cases. AE has an extensive geographical range in the northern hemisphere Diagnosis is based on clinical findings, imaging (radiology, ultrasonography, computed axial tomography, magnetic resonance imaging), and serology Treatment options for CE are: surgery, percutaneous sterilisation, drugs, and observation (watch and wait). Surgery is the basis of treatment for early AE, but patients not suitable for surgery and those who have had surgical resection of parasite lesions must be treated with benzimidazoles (albendazole, mebendazole) for several years