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Extracellular vesicles are critical regulators of host-parasite interactions. We previously demonstrated that Schistosoma japonicum EVs contain a remarkably high abundance of host miR-148a. Here, we characterised the abundance of miR-148a in circulation, in peripheral immune cells, and in plasma EVs of S. japonicum-infected mice. The results suggested the high abundance of miR-148a in macrophages to be likely linked to S. japonicum EVs. Additionally, miR-148a was found to target PTEN through the PI3K/AKT pathway to regulate cytokine production in macrophages. Consequently, our findings suggest that high abundance of miR-148a in macrophages may be associated with S. japonicum EVs, and regulate the host immune response during schistosome infection.

Schistosoma japonicum infection is believed to be endemic in 28 of the 80 provinces of The Philippines and the most recent data on schistosomiasis prevalence have shown considerable variability between provinces. In order to increase the efficient allocation of parasitic disease control resources in the country, we aimed to describe the small-scale spatial variation in S. japonicum prevalence across The Philippines, quantify the role of the physical environment in driving the spatial variation of S. japonicum, and develop a predictive risk map of S. japonicum infection. Data on S. japonicum infection from 35,754 individuals across the country were geolocated at the barangay level and included in the analysis. The analysis was then stratified geographically for the regions of Luzon, the Visayas and Mindanao. Zero-inflated binomial Bayesian geostatistical models of S. japonicum prevalence were developed and diagnostic uncertainty was incorporated. Results of the analysis show that in the three regions, males and individuals aged ≥ 20 years had significantly higher prevalence of S. japonicum compared with females and children < 5 years. The role of the environmental variables differed between regions of The Philippines. Schistosoma japonicum infection was widespread in the Visayas whereas it was much more focal in Luzon and Mindanao. This analysis revealed significant spatial variation in the prevalence of S. japonicum infection in The Philippines. This suggests that a spatially targeted approach to schistosomiasis interventions, including mass drug administration, is warranted. When financially possible, additional schistosomiasis surveys should be prioritized for areas identified to be at high risk but which were under-represented in our dataset.

Schistosoma japonicum causes a chronic parasitic disease, which persists as a major public health concern in The Philippines, the People's Republic of China and Indonesia. This infection is unique among helminthic zoonoses because it can infect humans and more than 40 other mammals. The objective of this study was to estimate the sensitivity and specificity of the Danish Bilharziasis Laboratory technique in cats, dogs, pigs, water buffaloes and rats in the Philippines. Faecal samples from each animal were collected on up to five occasions on five consecutive days in four villages of Sorsogon and Western Samar Provinces between January and July 2003. The faecal samples were analysed with the filtration and sedimentation Danish Bilharziasis Laboratory technique. Sensitivity and specificity of one, two, three, four, and five faecal samples were estimated using a Bayesian latent class approach. A total of 59, 43, 74, and 80% of the censored cats, dogs, pigs, and water buffaloes in the four villages were sampled, respectively. For all species, the sensitivity estimates when using the results of only 1 day of sampling were less than 80%. However, the sensitivity improved to at least 96% in all species when three or more faecal samples were collected on three separate days. The specificity was estimated to be above 92% across all species, even if just a single sample is used. The prevalences and 95% credible intervals of S. japonicum, adjusted for imperfect sensitivity and specificity, in cats, dogs, pigs, rats, and water buffaloes were 11.9% (6.8-18.3%), 19.9% (15.1-25.2%), 2.9% (1.1-5.2%), 31.3% (18.3-45.6%) and 6.3% (2.1-12.6%), respectively. Our results suggest that the Danish Bilharziasis Laboratory technique is valid for the detection of infection with S. japonicum in animals, and that sensitivity estimates are excellent when faecal samples are collected on at least three different days. Monitoring S. japonicum infection in animal reservoirs with a valid test could contribute to more effective public health control programmes.

Spatio-temporal variations of Schistosoma japonicum infection risk in Jiangsu province, China, were examined and the relationships between key climatic factors and infection prevalence at the county level were determined. The parasitological data were collected annually by means of cross-sectional surveys carried out in 47 counties from 1990 to 1998. Climatic factors, namely land surface temperature (LST) and normalized difference vegetation index (NDVI), were obtained from remote sensing satellite sensors. Bayesian spatio-temporal models were employed to analyze the data. The best fitting model showed that spatial autocorrelation in Jiangsu province decreased dramatically from 1990 to 1992 and increased gradually thereafter. A likely explanation of this finding arises from the large-scale administration of praziquantel for morbidity control of schistosomiasis. Our analysis suggested a negative association between NDVI and risk of S. japonicum infection. On the other hand, an increase in LST contributed to a significant increase in S. japonicum infection prevalence. We conclude that combining geographic information system, remote sensing and Bayesian-based statistical approaches facilitate integrated risk modeling of S. japonicum, which in turn is of relevance for allocation of scarce resources for control of schistosomiasis japonica in Jiangsu province and elsewhere in China, where the disease remains of public health and economic significance.

To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRBI and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P = 0.012) and *1302 (P = 0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 (P = 0.012) and *0609 (P = 0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0609 found as: common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 (P = 0.025) and HLA-DQB 1*0601 (P = 0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection. (C) 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

A Bayesian approach to overcome the imperfections of an immunological test (an antibody-based ELISA) and a parasitological test (Kato-Katz) in the detection of Schistosoma japonicum infection, was used to estimate community prevalences of S. japonicum infection in China. At the same time, the similarity between the prevalence estimates based on data from ELISA alone and those using data from both ELISA and Kato-Katz tests was explored. The database from the third nationwide sampling survey of schistosomiasis in China, 2004, was used for analysis, in which a total of 239 endemic villages were sampled from seven endemic provinces through a stratified cluster sampling technique and 250,987 residents aged from 6 to 65 years, were examined by ELISA followed by a Kato-Katz test applied to the seropositives. Bayesian hierarchical models incorporating random effects to reflect the nested data structure and uncertainty about test properties were employed to analyse the data. Our analysis suggested that using data from ELISA alone or both ELISA and Kato-Katz tests resulted in similar prevalence estimates, probably owing to the lack of sensitivity of Kato-Katz and the fact that Kato-Katz was only applied to the seropositives. We conclude that it is feasible to employ only ELISA, instead of combined ELISA and Kato-Katz tests, to estimate prevalence of S. japonicum infection in large-scale epidemiological settings. This study confirmed heterogeneity in the prevalence of S. japonicum infection in space by the fact that the estimated prevalences of S. japonicum infection in the sampled villages ranged from 0.02% to about 56% (posterior median). It is indicated that the disease remains a threat in some areas along the Yangtze River, although great achievements have been made in the control programme of schistosomiasis in China.

The present study using a murine model heavily infected with Schistosoma japonicum aimed to elucidate the pathogenesis of adverse effects of praziquantel treatment of schistosome-infected subjects. Inbred BALB/c mice were infected with S. japonicum (Yamanashi strain) before being treated with a single dose of praziquantel at 4 or 8 weeks p.i. All the mice treated at 8 weeks p.i. exhibited signs typical of systemic anaphylaxis until half of them died shortly after praziquantel administration. At autopsy, these mice exhibited remarkable intestinal alterations characterised by increased mucosal permeability, mucosal oedema and petechial haemorrhage, which are changes typical of immediate intestinal anaphylaxis. In these mice treated at 8 weeks p.i., degranulation of intestinal mast cells was frequently observed, which was particularly remarkable around S. japonicum eggs hatched as an effect of praziquantel. Furthermore, the plasma histamine concentration just after praziquantel treatment was much higher in mice at 8 weeks p.i. than that in uninfected mice or in S. japonicum-infected mice without drug treatment. In contrast, none of these intestinal changes was observed in untreated or uninfected control mice, or in mice administered praziquantel at 4 weeks p.i., in which worm pairs had just reached sexual maturation and begun egg-laying. The finding by ELISA that serum IgM and IgA levels specific to S. japonicum eggs decreased immediately after praziquantel treatment, together with the results of immunohistochemistry, revealed the sudden release of parasite antigens from the eggs hatched by praziquantel treatment. The results of this study demonstrate that adverse effects of praziquantel treatment of schistosomiasis characterised by abdominal signs depend on anaphylactic reactions due to parasite antigens, especially antigens from eggs hatched as an effect of praziquantel.

Female mice of 12 inbred strains were exposed to 20–25 cercariae of Schistosoma japonicum and infection status determined at day 40 by counting numbers of adult worms, eggs in faeces and eggs in a segment of liver. Most mouse strains appeared to be ‘permissive’ hosts although at least one strain (129/J) was shown to be relatively resistant in terms of day 40 adult worm numbers. In a radioisotopic lung assay for sensitivity to eggs, and developed as a rapid means of assessing granuloma formation, CBA/H mice were shown to differ from C57BL/6 mice in being non-responders. Histological examination of lungs of sensitized CBA/H and C57BL/6 mice injected intravenously with eggs established that granuloma formation was much more intense in C57BL/6 than CBA/H mice. Preliminary indications are that infected CBA/H mice are also low anti egg circumoval precipitin (COP) responders. Analysis of immune responses to isolated egg antigens in these two strains, and identification of the antigens of eggs to which such responses are directed in C57BL/6 mice, should provide insights into immunological disease processes (such as granulomatous inflammation) in this model system of japonicum schistosomiasis.