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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.

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 . . .

Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000–2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.

Purpose A comprehensive survey was conducted to assess the prevalence of Schistosoma japonicum infection in humans, water buffaloes, and snails in the two endemic municipalities of Talibon and Trinidad in Bohol, Philippines, which are nearing elimination. Methods and Results Human stool and blood samples were collected from barangays with snail breeding sites, and results showed higher positivity rates using the rSjTPx-1-ELISA compared to the Kato-Katz technique. Human stool examination for showed a 0.57% positivity rate for S. japonicum in San Vicente, Trinidad, while no cases were found in San Roque, Talibon. On the other hand, 3.43% of human serum samples from San Vicente, Trinidad, and 46.20% from San Roque, Talibon tested seropositive. Similarly, water buffalo samples revealed 16.95% seropositivity in Talibon and 10% in Trinidad. Additionally, snail infection was determined microscopically from collected Oncomelania hupensis quadrasi snails in Talibon, but no schistosome parasites were detected in the crushed snail tissues. Conclusion These findings highlight that despite progress towards elimination, schistosomiasis transmission persists in these areas, emphasizing the need for continued surveillance and targeted interventions.

Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained. Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK). Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.

Over the past decades China has made a great stride in controlling schistosomiasis, eliminating transmission of Schistosoma japonicum in 5 provinces and remarkably reducing transmission intensities in the rest of the seven endemic provinces. Recently, an integrated control strategy, which focuses on interventions on humans and bovines, has been implemented throughout endemic areas in China. This strategy assumes that a reduction in transmission of S. japonicum from humans and bovines to the intermediate Oncomelania snail host would eventually block the transmission of this parasite, and has yielded effective results in some endemic areas. Yet the transmission of S. japonicum is relatively complicated – in addition to humans and bovines, more than 40 species of mammalians can serve as potential zoonotic reservoirs. Here, we caution that some factors – potential roles of other mammalian reservoirs and human movement in sustaining the transmission, low sensitivity/specificity of current diagnostic tools for infections, praziquantel treatment failures, changes in environmental and socio-economic factors such as flooding in key endemic areas - may pose great obstacles towards transmission interruption of the parasite. Assessing potential roles of these factors in the transmission and implications for current control strategies aiming at transmission interruption is needed.

The cause of zoonotic schistosomiasis in the Philippines is Schistosoma japonicum, which infects up to 46 mammalian hosts, including humans and bovines. In China, water buffaloes have been identified as major reservoir hosts for schistosomiasis japonica, contributing up to 75% of human transmission. In the Philippines, water buffaloes (carabao; Bubalus bubalis carabanesis) have, historically, been considered unimportant reservoirs. We therefore revisited the possible role of bovines in schistosome transmission in the Philippines, using the recently described formalin-ethyl acetate sedimentation (FEA-SD) technique and a qPCR assay to examine fecal samples from 153 bovines (both carabao and cattle) from six barangays in Northern Samar. A high prevalence of S. japonicum was found using qPCR and FEA-SD in both cattle (87.50% and 77.08%, respectively) and carabao (80.00% and 55.24%, respectively). The average daily egg output for each bovine was calculated at 195,000. High prevalence and infection intensity of F. gigantica was also found in the bovines by qPCR and FEA-SD (95.33% and 96.00%, respectively). The identification of bovines as major reservoir hosts for S. japonicum transmission suggests that bovine treatment and/or vaccination, as one becomes available, should be included in any future control program that aims to reduce the disease burden due to schistosomiasis in the Philippines.