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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.

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.

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.

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.

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.

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 . . .

Schistosomiasis is a snail-borne disease caused by worms of the genus Schistosoma. Worldwide, human schistosomiasis remains a serious public health problem, threatening ∼800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Schistosoma japonicum is the only human blood fluke that occurs in China. As one of the countries suffering greatly from schistosomiasis, over the past 65 years, China has made great strides in controlling schistosomiasis, blocking the transmission of S. japonicum in five provinces, remarkably reducing transmission intensities in the other seven endemic provinces, and China is currently preparing to move toward the elimination of this disease before 2025. However, while on the road to schistosomiasis elimination, emerging challenges merit attention, including severe advanced cases, increased movements of population and livestock, large-area distribution of intermediate host snails, limitations of new drug developments and no vaccine available, as well as imported schistosomiasis and its potential risk.

Schistosomiasis is a significant public health threat, and Oncomelania hupensis is the only intermediate host for schistosoma japonicum . We conducted 12-year monthly repeated surveys to explore the interactive and lag effects of environmental factors on snail density and to monitor their long-term and seasonal trends in a bottomland around the Dongting Lake region in China. Relevant environmental data were obtained from multiple sources. A Bayesian kernel machine regression model and a Bayesian temporal model combined with a distributed lag model were constructed to analyze interactive and lag effects of environmental factors on snail density. The results indicated the average annual snail density in the study site exhibited an increasing and then decreasing trend, peaking in 2013. Snail densities were the highest in October and the lowest in January in a year. Normalized Difference Vegetation Index (NDVI) and water level were the most effective predictors of snail density, with potential interactions among temperature, precipitation, and NDVI. The mean minimum temperature in January, water level, precipitation and NDVI were positively correlated with snail density at lags ranging from 1 to 4 months. These findings could serve as references for relevant authorities to monitor the changing trend of snail density and implement control measures, thereby reducing the occurrence of schistosomiasis.

Oncomelania hupensis ( O. hupensis ), the sole intermediate host of Schistosoma japonicum , greatly influence the prevalence and distribution of schistosomiasis japonica. The distribution area of O. hupensis has remained extensive for numerous years. This study aimed to establish a valid agent-based model of snail density and further explore the environmental conditions suitable for snail breeding. A marshland with O. hupensis was selected as a study site in Dongting Lake Region, and snail surveys were monthly conducted from 2007 to 2016. Combined with the data from historical literature, an agent-based model of snail density was constructed in NetLogo 6.2.0 and validated with the collected survey data. BehaviorSpace was used to identify the optimal ranges of soil temperature, pH, soil water content, and vegetation coverage for snail growth, development and reproduction. An agent-based model of snail density was constructed and showed a strong agreement with the monthly average snail density from the field surveys. As soil temperature increased, the snail density initially rose before declining, reaching its peak at around 21°C. There were similar variation patterns for other environmental factors. The findings from the model suggested that the optimum ranges of soil temperature, pH, soil water content and vegetation coverage were 19°C to 23 °C, 6.4 to 7.6, 42% to 75%, and 70% to 93%, respectively. A valid agent-based model of snail density was constructed, providing more objective information about the optimum ranges of environmental factors for snail growth, development and reproduction.