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Background: Zoonotic schistosomiasis japonica is a major public health problem in China. Bovines, particularly water buffaloes, are thought to play a major role in the transmission of schistosomiasis to humans in China. Preliminary results (1998-2003) of a praziquantel (PZQ)-based pilot intervention study we undertook provided proof of principle that water buffaloes are major reservoir hosts for S. japonicum in the Poyang Lake region, Jiangxi Province. Methods and Findings: Here we present the results of a cluster-randomised intervention trial (2004-2007) undertaken in Hunan and Jiangxi Provinces, with increased power and more general applicability to the lake and marshlands regions of southern China. The trial involved four matched pairs of villages with one village within each pair randomly selected as a control (human PZQ treatment only), leaving the other as the intervention (human and bovine PZQ treatment). A sentinel cohort of people to be monitored for new infections for the duration of the study was selected from each village. Results showed that combined human and bovine chemotherapy with PZQ had a greater effect on human incidence than human PZQ treatment alone. Conclusions: The results from this study, supported by previous experimental evidence, confirms that bovines are the major reservoir host of human schistosomiasis in the lake and marshland regions of southern China, and reinforce the rationale for the development and deployment of a transmission blocking anti-S. japonicum vaccine targeting bovines.

Following the exciting announcement that Anhui Province, one of the historically most heavily Schistosoma japonicum endemic regions in China, has been officially declared to have achieved the goal of province-wide transmission interruption of schistosomiasis, we raise two concerns that merit further consideration. Firstly, S. japonicum is zoonotic, and in China it is known that humans, livestock, and wild animals such as rodents are major reservoirs of infection. While S. japonicum infections both in humans and bovines have recently been reduced to zero prevalence, infection persists at moderate to high levels within rodents with, for example, prevalence’s reported of up to 12.81% within Anhui Province over last 5 years. Therefore, surveillance of schistosome infections in wild animals, at least in rodents, must be included in the criteria of verifying transmission interruption or elimination in China. Secondly, regarding how the official procedure of verification of transmission of interruption was assessed, we propose that a more accurate survey design and foci selection would be based, at least in part, upon areas where schistosome infections in either humans, domestic/wild animals and/or snails have recently been documented. This is particularly urgent, not only in terms of the long-term sustainability of disease control in China, but because many other countries are now fully acknowledging the zoonotic potential of schistosomiasis and are/or will soon enter this final elimination phase as officially outlined in the WHO’s 2021–2030 Neglected Tropical Diseases Roadmap.

The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks' gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks' gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-γ. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. ClinicalTrials.gov (NCT00486863).

More than 80% of schistosomiasis patients in China live in the lake and marshland regions. The purpose of our study is to assess the effect of a comprehensive strategy to control transmission of Schistosoma japonicum in marshland regions. In a cluster randomized controlled trial, we implemented an integrated control strategy in twelve villages from 2009 through 2011 in Gong'an County, Hubei Province. The routine interventions included praziquantel chemotherapy and controlling snails, and were implemented in all villages. New interventions, mainly consisting of building fences to limit the grazing area for bovines, building safe pastures for grazing, improving the residents' health conditions and facilities, were only implemented in six intervention villages. Results showed that the rate of S. japonicum infection in humans, bovines, snails, cow dung and mice in the intervention group decreased from 3.41% in 2008 to 0.81% in 2011, 3.3% to none, 11 of 6,219 to none, 3.9% to none and 31.7% to 1.7%, respectively (P<0.001 for all comparisons). In contrast, there were no statistically significant reductions of S. japonicum infection in humans, bovines and snails from 2008 to 2011 in the control group (P>0.05 for all comparisons). Moreover, a generalized linear model showed that there was a higher infection risk in humans in the control group than in the intervention group (OR = 1.250, P = 0.001) and an overall significant downward trend in infection risk during the study period. The integrated control strategy, designed to reduce the role of bovines and humans as sources of S. japonicum infection, was highly effective in controlling the transmission of S. japonicum in marshland regions in China. Chinese Clinical Trial Registry ChiCTR-PRC-12002405.

Inhibiting the activation of hepatic stellate cells (HSCs) represents a key therapeutic strategy for alleviating liver fibrosis induced by schistosomiasis. Diverse cell populations secrete pro-inflammatory cytokines and chemokines, which induce HSC activation and thereby promote hepatic fibrosis progression. Tristetraprolin (TTP) exerts a pivotal role in the post-transcriptional regulation of pro-inflammatory cytokines by either accelerating mRNA degradation or suppressing translation, a regulatory mechanism closely associated with the pathogenesis of various hepatic disorders. However, the pathological roles of TTP in Schistosoma japonicum -induced liver fibrosis remain largely elusive. Here, we report that TTP is upregulated in the liver during S. japonicum -induced liver fibrosis, and its overexpression markedly ameliorates this fibrotic pathology in vivo . We further identify that TTP negatively regulates TGF-β1 mRNA stability by promoting N6-methyladenosine (m 6 A) RNA methylation, thereby inhibiting HSC activation. Mechanistically, TTP enhances transcription of the WT1-associated protein ( WTAP ) gene through its interaction with SMAD2/3. Furthermore, treatment with an m 6 A RNA methylation inhibitor confirms that TTP-mediated protection against S. japonicum -induced liver fibrosis, an effect associated with increased m⁶A RNA methylation in vivo . Thus, our findings uncover a novel and critical role of TTP in exerting its anti-fibrotic function via the WTAP/m 6 A epitranscriptomic machinery in the pathogenesis of S. japonicum -induced liver fibrosis. This finding provides a rationale for the therapeutic targeting of TTP-mediated m 6 A RNA methylation in S. japonicum -induced liver fibrosis.

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the , lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) our team developed showed encouraging efficacy against in Chinese water buffaloes. Here we report the results of a double-blind cluster randomized trial aimed at determining the impact of a combination of the SjCTPI bovine vaccine (given as a prime-boost regimen), human mass chemotherapy and snail control on the transmission of in 12 selected administrative villages around the Dongting Lake in Hunan province. The trial confirmed human praziquantel treatment is an effective intervention at the population level. Further, mollusciciding had an indirect ~50% efficacy in reducing human infection rates. Serology showed that the SjCTPI vaccine produced an effective antibody response in vaccinated bovines, resulting in a negative correlation with bovine egg counts observed at all post-vaccination time points. Despite these encouraging outcomes, the effect of the vaccine in preventing human infection was inconclusive. This was likely due to activities undertaken by the China National Schistosomiasis Control Program, notably the treatment, sacrifice or removal of bovines from trial villages, over which we had no control; as a result, the trial design was compromised, reducing power and contaminating outcome measures. This highlights the difficulties in undertaking field trials of this nature and magnitude, particularly over a long period, and emphasizes the importance of mathematical modeling in predicting the potential impact of control intervention measures. A transmission blocking vaccine targeting bovines for the prevention of with the required protective efficacy would be invaluable in tandem with other preventive intervention measures if the goal of eliminating schistosomiasis from China is to become a reality.

In recent years, the prevalence and infection intensity of Schistosoma japonicum in endemic areas of the Philippines have significantly decreased due to yearly population-based treatment strategies, yet transmission rates remain high and uninterrupted. An important indicator of active disease transmission is the presence of Schistosoma japonicum and its snail intermediate host Oncomelania hupensis quadrasi in freshwater habitats. In this study, we sought to apply a species-specific real-time PCR (qPCR) assay for the detection of S. japonicum and O. hupensis quadrasi in freshwater samples using environmental DNA approach that can complement the commonly utilized malacological survey in determining potential transmission foci in order to have a more effective snail surveillance strategy for schistosomiasis japonica in endemic areas. The newly developed assay was specific to S. japonicum and O. hupensis quadrasi with no amplification detected against non-target trematode Fasciola spp. and snails such as Lymnaea spp., Pomacea canaliculata, and Melanoides spp. that typically co-exist in the same environment. The assay effectiveness was determined using 19 environmental water samples collected from Northern Samar (N = 5 sites), Leyte (N = 11 sites) and Compostela Valley (N = 3 sites) and compared to malacological survey for determining O. hupensis quadrasi snail colonies and snail crushing to visualize S. japonicum cercariae. TaqMan qPCR targeting a short fragment of the cytochrome c oxidase subunit 1 (cox1) gene was positive for S. japonicum in 9 sites, for O. hupensis quadrasi in 9 sites, and for both S. japonicum and O. hupensis quadrasi in 5 sampling sites. Moreover, it was able to detect O. hupensis quadrasi in 3 out of 12 sites found negative and 6 out of 7 sites found positive through malacological survey, and in 4 of the 5 snail sites positive for snails with cercariae. Overall, this method can complement malacological surveys for monitoring of schistosomes in endemic areas of the Philippines, especially those with high risk of human infection.

Schistosoma japonicum has been successfully controlled in villages along Poyang Lake, the largest freshwater lake in China. In addition to synchronous chemotherapy for humans and cattle, successful interventions have included the removal of cattle from snail-infested grasslands, improvements in sanitation, and intensive health education. The use of such interventions has now been adopted as the national control strategy for China. Schistosoma japonicum has been successfully controlled in villages along Poyang Lake, the largest freshwater lake in China. In addition to synchronous chemotherapy for humans and cattle, successful interventions have included the removal of cattle from snail-infested grasslands, improvements in sanitation, and intensive health education. During the past five decades, the Chinese government has placed a high priority on the control of schistosomiasis and has carried out many control programs. 1 – 3 These efforts have resulted in a substantial reduction in the prevalence of infection with Schistosoma japonicum in humans, from approximately 11.6 million cases in the mid-1950s to 726,000 cases in 2004. 4 The number of provinces in which this disease is endemic has been reduced from 12 to 7. In spite of these achievements, progress in the control of this disease appeared to be stagnating. 5 , 6 National surveys of schistosomiasis in China showed that the . . .

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.

In China, schistosomiasis is targeted for elimination. As the country approaches elimination, it is critical to evaluate how the dynamics of transmission are changing in remaining pockets of disease. We have been studying areas of schistosomiasis reemergence and persistence in Sichuan, China since 2007. This study used gradient boosting machines to identify key predictors of infection across two periods, 2007–2010, a period when schistosomiasis had reemerged, and 2016–2019, a period when schistosomiasis was approaching elimination. We also evaluated how key predictors of infection have shifted over time and whether combinations of predictors amplified risk. We considered predictors describing agriculture, domestic animals, socio-economic status, water and sanitation infrastructure, and demographics at individual, household and village-level scales. Our re-emergence and elimination models demonstrated strong predictive performances (AUC-PR = 0.92 and AUC = 0.85, respectively). In both periods, a person’s age and village level agricultural practices including the average area of dry crops, rice planted, and night soil use, were among the most influential factors. Village-level factors dominated in 2007–2010, while household and individual predictors increased in predictive importance in 2016–2019. Between 2007–2010 and 2016–2019, there were increases in the importance of household agricultural practices such as the area of dry crops and rice cultivated, and household cat and dog ownership, while the importance of factors describing water and sanitation infrastructure decreased. In the elimination period, our models found the combination of high village dry crop cultivation and lack of improved sanitation amplified infection probability. Our findings suggest adding precision interventions targeting high-risk households on top of existing community-wide measures may accelerate schistosomiasis elimination. Practitioners should consider adding agricultural, sanitation and animal infection data to end-game surveillance programs, while researchers evaluate the consistency of these findings in other low-endemic settings and explore causal pathways to inform adaptive, locally tailored strategies.