Two-year impact of praziquantel treatment for Schistosoma japonicum infection in China: re-infection, subclinical disease and fibrosis marker measurements

We studied a community cohort of 193 individuals exposed to endemic Schistosoma japonicum infection in the Dongting Lake region of China to assess subclinical morbidity and the 2-year benefit of curative therapy (praziquantel) administered in 1996. Prevalence and intensity of S. japonicum infection before treatment were 28% and 192 eggs per gram faeces (epg), respectively. Two years after cure, 22% of the cohort were reinfected, but with a lighter intensity (67 epg). Sixty-four subjects (37%) showed significant improvement in ultrasound parenchyma images after treatment and 51 subjects (54%) showed significant improvement of periportal fibrosis. Left-lobe enlargement also reversed (P 0·05). The serum levels of laminin and collagen IV associated with reinfection and intensity and hyaluronic acid levels correlated with ultrasound findings (P < 0·01). Overall, treatment induced a marked decrease in subclinical hepatosplenic morbidity attributable to S. japonicum although low-intensity re-infection after treatment remained relatively frequent. Stratified analysis and logistic models evaluated potential confounding factors for assessment of treatment effects on hepatic fibrosis. S. japonicum infection and moderate-heavy alcohol intake interacted: improvement in parenchymal morbidity was impeded among drinkers (P < 0·05). Chemotherapy focused on at-risk residents controls prevalent subclinical hepatic fibrosis but re-infection indicates the need for complementary control strategie

Five-year impact of repeated praziquantel treatment on subclinical morbidity due to Schistosoma japonicum in China

We report the 5-year impact (1996-2001) of repeated praziquantel chemotherapy on subclinical morbidity related to Schistosoma japonicum infection. We repeated stool examinations and hepatosplenic ultrasonography in a cohort of 120 individuals living on an island with endemic infection in Dongting Lake, China. Prevalence of schistosome infection fell by 43% and intensity (geometric mean eggs per gram) declined by 80% over the 5 years. However, transmission persisted at a dangerously high rate of 13% per year for re-infection or new infection in the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell significantly (P 0.05). However, endpoint infection was even more strongly associated with left-lobe enlargement (57% versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and periportal fibrosis were much higher than the proportions of subjects that progressed (P < 0.05). Reduction of prevalence and intensity of infection, and improvement of subclinical morbidity, were benefits of repeated treatments. Further research is needed to understand why some patients developed fibrosis despite substantial reductions in egg counts and to evaluate the functional importance of residual subclinical morbidity after chemotherapy-based control in the lake and marshland area of Chin

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

Potent and selective inhibitors of the TASK-1 potassium channel through chemical optimization of a bis-amide scaffold

TASK-1 is a two-pore domain potassium channel that is important to modulating cell excitability, most notably in the context of neuronal pathways. In order to leverage TASK-1 for therapeutic benefit, its physiological role needs better characterization; however, designing selective inhibitors that avoid the closely related TASK-3 channel has been challenging. In this study, a series of bis-amide derived compounds were found to demonstrate improved TASK-1 selectivity over TASK-3 compared to reported inhibitors. Optimization of a marginally selective hit led to analog 35 which displays a TASK-1 IC 50 = 16 nM with 62-fold selectivity over TASK-3 in an orthogonal electrophysiology assay

Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

Background Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field.Methods We did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format.Findings From array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC](serum)=0.98 [95% CI 0.95-1.00]; AUC(urine)=0.96 [0.93-0.99]), and MS3_01370 (AUCserum=0.93 [0.89-0.97]; AUC(urine)=0.81 [0.72-0.89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0.79 [0.69-0.90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%.Interpretation We identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Host-parasite interactio

Whole genome analysis of a schistosomiasis-transmitting freshwater snail

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis

Molecular epidemiology of cystic echinococcosis

Echinococcus granulosus exhibits substantial genetic diversity that has important implications for the design and development of vaccines, diagnostic reagents and drugs effective against this parasite. DNA approaches that have been used for accurate identification of these genetic variants are presented here as is a description of their application in molecular epidemiological surveys of cystic echinococcosis in different geographical settings and host assemblages. The recent publication of the complete sequences of the mitochondrial (mt) genomes of the horse and sheep strains of E. granulosus and of E. multilocularis, and the availability of mt DNA sequences for a number of other E. granulosus genotypes, has provided additional genetic information that can be used for more in depth strain characterization and taxonomic studies of these parasites. This very rich sequence information has provided a solid molecular basis, along with a range of different biological, epidemiological, biochemical and other molecular-genetic criteria, for revising the taxonomy of the genus Echinococcus. This has been a controversial issue for some time. Furthermore, the accumulating genetic data may allow insight to several other unresolved questions such as confirming the occurrence and precise nature of the E. granulosus G9 genotype and its reservoir in Poland, whether it is present elsewhere, why the camel strain (G6 genotype) appears to affect humans in certain geographical areas but not others, more precise delineation of the host and geographic ranges of the genotypes characterised to date, and whether additional genotypes of E. granulosus remain to be identified

Towards a taxonomic revision of the genus Echinococcus

Echinococcus remains a significant public health problem worldwide and, in several regions, the aetiological agents of cystic hydatid disease/echinococcosis are extending their range. The taxonomy of Echinococcus has been a controversial issue for decades, but the outcome of recent molecular epidemiological studies has served to reinforce proposals made ten years ago to revise the taxonomy of Echinococcus. A formal nomenclature is essential for effective communication, and provides the stability that underpins epidemiological investigations. It will also serve to recognize the contribution of early taxonomists

The epidemiology of hydatid disease in the United Kingdom and Kenya

Unilocular hydatid disease, caused by larvae of the tapeworm, Echinococcus granulosus, is endemic in the U.K. and Kenya. In the U.K., there are foci of human infection notably in the sheep-rearing areas of South Wales and North-West Scotland, where there is a correspondingly high prevalence in sheep and farm dogs. Red foxes may play a significant role in the sheep/dog cycle in Wales. In the Turkana region of North West Kenya, the incidence for human hydatidosis is the highest anywhere in the world. This is related, in part, to large numbers of heavily infected feral and domestic dogs. Silver backed and golden jackals also harbour the parasite, but wild, infected, intermediate hosts have not been found. The disease has a low prevalence in cattle, sheep and goats and, uniquely, man is a potential biological participant in the cyclic transmission of E. granulosus. In contrast, in Masailand (Southern Kenya), there is a low incidence in man, a high prevalence in domestic animals and a sylvatic cycle perpetuated between lions, Cape hunting dogs, jackals and a range of wild ungulates. A sheep/dog strain and a horse/ dog strain of E. granulosus have been identified in the U.K. Whereas the former strain is known to be infective to man, the precise host-specificity of the latter remains undetermined although indirect epidemiological evidence suggests a low infectivity to man. The strain picture emerging from Kenya indicates an unusually complex strain situation with the sheep/dog, human/dog and majority of goat/dog parasites being similar and probably infective to one another. The cattle/dog and, particularly the camel/dog parasites have major differences from the human/dog form and their status remains undefined, especially with regard to their potential infectivity to man.L’hydatidose (échinococcose uniloculaire) causée par la larve d'E .granulosus est endémique en Grande-Bretagne et au Kenya. Il existe en Grande-Bretagne des foyers notables d’infection dans les secteurs d’élevage ovin au sud du pays de Galles et au nord-ouest de l’Ecosse où existe une forte prévalence concordante entre moutons et chiens de ferme. Les renards peuvent jouer un rôle significatif dans le cycle mouton/chien au pays de Galles. Dans la région du Turkana au nord-ouest du Kenya, l’incidence humaine d’hydatidose est la plus forte du monde. Ceci est en partie lié au grand nombre de chiens errants et domestiques lourdement infestés. Les deux espèces de chacals hébergent le parasite, mais les hôtes intermédiaires sauvages restent inconnus. La prévalence est assez faible chez les bovins, moutons et chèvres et fait unique, l’homme participe potentiellement, comme hôte intermédiaire, au cycle de E. granulosus. Au contraire en pays Masai (sud du Kenya) l’incidence est faible chez l’homme et la prévalence forte chez les espèces domestiques. Un cycle selvatique se perpétue entre les lions, lycaons, chacals et divers ongulés sauvages. Une souche chien/mouton et une autre chien/cheval de E. granulosus ont été reconnues en Grande-Bretagne. Alors que la première souche est connue pour contaminer l’homme, la spécificité d’hôte précise de la seconde reste indéterminée, quoique des éléments épidémiologiques indirects suggèrent un pouvoir infectieux faible chez l’homme. Au Kenya, la situation des souches est plus confuse car les parasites chien/mouton, chien/homme et la majorité des parasites chien/chèvre sont semblables, et probablement inter-infectieux. Les parasites chien/bétail et surtout chien/dromadaire présentent des différences majeures de la forme chien/homme et leur situation reste mal définie, particulièrement sous l’aspect de la contagion à l’homme.McManus D.P., Smyth J.D., Macpherson C.N.L. The epidemiology of hydatid disease in the United Kingdom and Kenya . In: Revue d'Écologie (La Terre et La Vie), tome 40, n°2, 1985. pp. 217-223

Genetic immunization of mice with DNA encoding the 23 kDa transmembrane surface protein of Schistosoma japonicum (Sj23) induces antigen-specific immunoglobulin G antibodies

The 23 kDa transmembrane surface protein of schistosomes is of recognized interest in studies of immune responsiveness in schistosomiasis. To examine the immunogenicity of the 23 kDa antigen of Schistosoma japonicum, Sj23, when delivered by genetic immunization, mice were immunized using a DNA construct containing the Sj23 cDNA under the control of a CMV promotor. Serological analysis of peripheral blood from immunized mice demonstrated that this construct was able to induce the production of antigen-specific IgG antibodies that recognized a schistosome antigen of 23 kDa in Western blots. Despite inducing antigen-specific antibodies, the Sj23 DNA vaccine was unable to confer protection in immunized mice subjected to challenge with S.japonicum cercariae. Appropriate engineering of the unique structure of the Sj23 kDa transmembrane protein of schistosomes may provide a novel vehicle for expressing foreign epitopes from other infectious agents or, possibly, cancer antigens, anchored to the surface of transfected cells