BackgroundSchistosomiasis in the People’s Republic of China (PRC) can be traced back to antiquity. In the past 60 years, the Chinese government has made great efforts to control this persistent disease with elimination slated by 2020 through the implementation of a comprehensive control strategy. This strategy aims to reduce the role of bovines and humans as sources of infection as a pre-requisite for elimination through transmission interruption. The goal of elimination will be achievable only by the implementation of a sustainable surveillance and control system, with sensitive diagnosis a key feature so that the true disease burden is not underestimated. Currently used diagnostics lack the necessary sensitivity to accurately determine the prevalence of Schistosoma japonicum infection in areas with low infection intensities. It is of critical importance to find and treat people and to identify animals with low-level infections if the National Control Programme for China is to achieve schistosomiasis elimination.MethodsWe evaluated a real-time polymerase chain reaction (qPCR) assay using 633 human stool samples collected from five villages in Hunan, Anhui, Hubei, and Jiangxi provinces, and 182 bovine (70 cattle and 112 buffalo) stool samples obtained from four villages in Hunan, Anhui, and Jiangxi provinces in the PRC. All stool samples were subjected to the miracidium hatching test (MHT, a diagnostic procedure used in the National Schistosomiasis Control Programme) and the qPCR assay. Samples positive by MHT were subjected to either the Kato-Katz technique for humans, or the formalin-ethyl acetate sedimentation-digestion (FEA-SD) procedure for bovines, to determine infection intensities.ResultsThe qPCR assay exhibited a high level of sensitivity in the detection of S. japonicum infections. With both the human and bovine samples, a significantly higher prevalence was determined using the qPCR assay (11.06% humans, 24.73% bovines) than with the MHT (0.93% humans, 7.69% bovines). The animal contamination index (calculated using data obtained with the qPCR technique) for all positive bovines was 27 618 000 eggs per day, indicating a considerable amount of environmental egg contamination that would be underestimated using less sensitive diagnostic procedures.ConclusionsThe qPCR assay we have evaluated will be applicable as a future field diagnostic and surveillance tool in low-transmission zones where schistosomiasis elimination is targeted and for monitoring post-intervention areas to verify that elimination has been maintained.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0390-y) contains supplementary material, which is available to authorized users.
Schistosomiasis is among the major neglected tropical diseases and effective prevention by boosting the immune system is still not available. T cells are key cellular components governing adaptive immune response to various infections. While common laboratory mice, such as C57BL/6, are highly susceptible to schistosomiasis, the SD rats are extremely resistant. However, whether adaptive immunity is necessary for such natural resistance to schistosomiasis in rats remains to be determined. Therefore, it is necessary to establish genetic model deficient in T cells and adaptive immunity on the resistant SD background, and to characterize liver pathology during schistosomiasis. In this study we compared experimental schistosomiasis in highly susceptible C57BL/6 (B6) mice and in resistant SD rats, using cercariae of Schistosoma japonicum. We observed a marked T cell expansion in the spleen of infected B6 mice, but not resistant SD rats. Interestingly, CD3e−/− B6 mice in which T cells are completely absent, the infectious burden of adult worms was significantly higher than that in WT mice, suggesting an anti-parasitic role for T cells in B6 mice during schistosome infection. In further experiments, we established Lck deficient SD rats by using CRISPR/Cas9 in which T cell development was completely abolished. Strikingly, we found that such Lck deficiency in SD rats severely impaired their natural resistance to schistosome infection, and fostered parasite growth. Together with an additional genetic model deficient in T cells, the CD3e−/− SD rats, we confirmed the absence of T cell resulted in loss of natural resistance to schistosome infection, but also mitigated liver immunopathology. Our further experiments showed that regulatory T cell differentiation in infected SD rats was significantly decreased during schistosomiasis, in contrast to significant increase of regulatory T cells in infected B6 mice. These data suggest that T cell mediated immune tolerance facilitates persistent infection in mice but not in SD rats. The demonstration of an important role for T cells in natural resistance of SD rats to schistosomiasis provides experimental evidences supporting the rationale to boost T cell responses in humans to prevent and treat schistosomiasis.
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