Elimination of schistosomiasis in China: Current status and future prospects

Elimination of schistosomiasis as a public health problem among all disease-endemic countries in 2030 is an ambitious goal. Recent achievements resulting from mass drug administration (MDA) with praziquantel is promising but may need to be complemented with also other means. Schistosomiasis was highly prevalent in China before the initiation of the national schistosomiasis control program in the mid-1950s, and, at that time, the country bore the world’s highest burden of schistosomiasis. The concerted control efforts, upheld without interruption for more than a half century, have resulted in elimination of the disease as a public health problem in China as of 2015. Here, we describe the current status of schistosomiasis in China, analyze the potential challenges affecting schistosomiasis elimination, and propose the future research needs and priorities for the country, aiming to provide more universal insights into the structures needed for a global schistosomiasis elimination encompassing also other endemic regions.     

Achievements of schistosomiasis control in China

The control of schistosomiasis has been spectacularly successful in terms of controlling endemicity and severity of the disease during the last 50 years. It can be categorized into two stages. From 1955 through 1980, the transmission-control strategy had been widely and successfully carried out. By the end of 1980, the epidemic of schistosomiasis was successfully circumscribed in certain core regions including areas at the middle and low reaches of the Yangtze River and some mountainous areas in Sichuan and Yunnan provinces, where control of schistosomiasis had been demonstrated to be very difficult to be sustained. Therefore, since 1980, schistosomiasis control in China has been modified to employ a stepwise strategy, based on which morbidity control has been given priorities and if possible transmission control has been pursued. However, since snail-ridden areas remain unchanged so far, reinfections occur frequently. This necessitates a maintenance phase to consolidate the achievements in the control of schistosomiasis. In the mean time, we are challenged with some environmental, social and economical changes in terms of controlling schistosomiasis. Successfully controlling schistosomiasis in China is still a long-term task but will be achieved without doubt along with the economic development and the promotion of living and cultural standard of people.     

Spatio-temporal Transmission and Environmental Determinants of Schistosomiasis Japonica in Anhui Province,China

Background

Schistosomiasis japonica still remains of public health and economic significance in China, especially in the lake and marshland areas along the Yangtze River Basin, where the control of transmission has proven difficult. In the study, we investigated spatio-temporal variations of S. japonicum infection risk in Anhui Province and assessed the associations of the disease with key environmental factors with the aim of understanding the mechanism of the disease and seeking clues to effective and sustainable schistosomiasis control.

Methodology/Principal Findings

Infection data of schistosomiasis from annual conventional surveys were obtained at the village level in Anhui Province, China, from 2000 to 2010 and used in combination with environmental data. The spatio-temporal kriging model was used to assess how these environmental factors affected the spatio-temporal pattern of schistosomiasis risk. Our results suggested that seasonal variation of the normalized difference vegetation index (NDVI), seasonal variation of land surface temperature at daytime (LSTD), and distance to the Yangtze River were negatively significantly associated with risk of schistosomiasis. Predictive maps showed that schistosomiasis prevalence remained at a low level and schistosomiasis risk mainly evolved along the Yangtze River. Schistosomiasis risk also followed a focal spatial pattern, fluctuating temporally with a peak (the largest spatial extent) in 2005 and then contracting gradually but with a scattered distribution until 2010.

Conclusion

The fitted spatio-temporal kriging model can capture variations of schistosomiasis risk over space and time. Combined with techniques of geographic information system (GIS) and remote sensing (RS), this approach facilitates and enriches risk modeling of schistosomiasis, which in turn helps to identify prior areas for effective and sustainable control of schistosomiasis in Anhui Province and perhaps elsewhere in China.     

Assessment of the national schistosomiasis control program in a typical region along the Yangtze River,China

Schistosomiasis remains a major public health problem in eastern China, particularly along the Yangtze River Basin. The latest national schistosomiasis control program (NSCP) was implemented in 2005 with the main goal of reducing the rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress, we applied a Bayesian spatio-temporal model to describe dynamics of schistosomiasis in Guichi, Anhui Province, China, using annual parasitological and environmental data collected within 41 sample villages for the period 2005–2011. Predictive maps of schistosomiasis showed that the disease prevalence remains constant and low. Results of uncertainty analysis, in the form of probability contour maps (PCMs), indicated that the first goal of “infection rate less than 5% by 2008” was fully achieved in the study area. More longitudinal data for schistosomiasis are needed for the assessment of the second goal of “infection rate less than 1% by 2015”. Compared with the traditional way of mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more realistic information for schistosomiasis control.     

Health Access Livelihood Framework Reveals Potential Barriers in the Control of Schistosomiasis in the Dongting Lake Area of Hunan Province,China

Background

Access to health care is a major requirement in improving health and fostering socioeconomic development. In the People''s Republic of China (P.R. China), considerable changes have occurred in the social, economic, and health systems with a shift from a centrally planned to a socialist market economy. This brought about great benefits and new challenges, particularly for vertical disease control programs, including schistosomiasis. We explored systemic barriers in access to equitable and effective control of schistosomiasis.

Methodology

Between August 2002 and February 2003, 66 interviews with staff from anti-schistosomiasis control stations and six focus group discussions with health personnel were conducted in the Dongting Lake area, Hunan Province. Additionally, 79 patients with advanced schistosomiasis japonica were interviewed. The health access livelihood framework was utilized to examine availability, accessibility, affordability, adequacy, and acceptability of schistosomiasis-related health care.

Principal Findings

We found sufficient availability of infrastructure and human resources at most control stations. Many patients with advanced schistosomiasis resided in non-endemic or moderately endemic areas, however, with poor accessibility to disease-specific knowledge and specialized health services. Moreover, none of the patients interviewed had any form of health insurance, resulting in high out-of-pocket expenditure or unaffordable care. Reports on the adequacy and acceptability of care were mixed.

Conclusions/Significance

There is a need to strengthen health awareness and schistosomiasis surveillance in post-transmission control settings, as well as to reduce diagnostic and treatment costs. Further studies are needed to gain a multi-layered, in-depth understanding of remaining barriers, so that the ultimate goal of schistosomiasis elimination in P.R. China can be reached.     

Schistosomiasis research in the dongting lake region and its impact on local and national treatment and control in China

Schistosomiasis is a chronic and debilitating parasitic disease that has often been neglected because it is a disease of poverty, affecting poor rural communities in the developing world. This is not the case in the People's Republic of China (PRC), where the disease, caused by Schistosoma japonicum, has long captured the attention of the Chinese authorities who have, over the past 50-60 years, undertaken remarkably successful control programs that have substantially reduced the schistosomiasis disease burden. The Dongting Lake region in Hunan province is one of the major schistosome-endemic areas in the PRC due to its vast marshland habitats for the Oncomelania snail intermediate hosts of S. japonicum. Along with social, demographic, and other environmental factors, the recent completion and closure of the Three Gorges dam will most likely increase the range of these snail habitats, with the potential for re-emergence of schistosomiasis and increased transmission in Hunan and other schistosome-endemic provinces being a particular concern. In this paper, we review the history and the current status of schistosomiasis control in the Dongting Lake region. We explore the epidemiological factors contributing to S. japonicum transmission there, and summarise some of the key research findings from studies undertaken on schistosomiasis in Hunan province over the past 10 years. The impact of this research on current and future approaches for sustainable integrated control of schistosomiasis in this and other endemic areas in the PRC is emphasised.     

A multi-component integrated approach for the elimination of schistosomiasis in the People’s Republic of China: design and baseline results of a 4-year cluster-randomised intervention trial

Despite major successes in its control over the past 50 years, schistosomiasis japonica continues to be a public health problem in the People’s Republic of China (P.R. China). Historically, the major endemic foci occur in the lakes and marshlands along the Yangtze River, areas where transmission interruption has proven difficult. The current endemic situation may alter due to the closure of the Three Gorges Dam. Considerable environmental and ecological changes are anticipated that may result in new habitats for the oncomelanid intermediate snail host of Schistosoma japonicum (Sj), thereby increasing the risk of transmission. The current national control program for P.R. China involves a multi-component integrated strategy but, despite targeting multiple transmission pathways, certain challenges remain. As the Chinese government pushes towards elimination, there is a requirement for additional tools, such as vaccination, for long-term prevention. Whereas the zoonotic nature of schistosomiasis japonica adds to the complexity of control, it provides a unique opportunity to develop a transmission blocking vaccine targeting bovines to assist in the prevention of human infection and disease. Mathematical modelling has shown that control options targeting the various transmission pathways of schistosomiasis japonica and incorporating bovine vaccination, mass human chemotherapy and mollusciciding could lead to its elimination from P.R. China. Here we present the study design and baseline results of a four-year cluster randomised intervention trial we are undertaking around the schistosomiasis-endemic Dongting Lake in Hunan Province aimed at determining the impact on schistosome transmission of the multi-component integrated control strategy, including bovine vaccination using a heterologous “prime-boost” delivery platform based on the previously tested SjCTPI vaccine.     

Dynamics of spatial clustering of schistosomiasis in the Yangtze River Valley at the end of and following the World Bank Loan Project

The 10-year (1992–2001) World Bank Loan Project (WBLP) contributed greatly to schistosomiasis control in China. However, the re-emergence of schistosomiasis in recent years challenged the long-term progress of the WBLP strategy. In order to gain insight in the long-term progress of the WBLP, the spatial pattern of the epidemic was investigated in the Yangtze River Valley between 1999–2001 and 2007–2008. Two spatial cluster methods were jointly used to identify spatial clusters of cases. The magnitude and number of clusters varied during 1999–2001. It was found that prevalence of schistosomiasis had been greatly reduced and maintained at a low level during 2007–2008, with little change. Besides, spatial clusters most frequently occurred within 16 counties in the Dongting Lake region and within 5 counties in the Poyang Lake region. These findings precisely pointed out the prior places for future public health planning and resource allocation of schistosomiasis.     

The Schistosoma japonicum self-cure phenomenon in water buffaloes: potential impact on the control and elimination of schistosomiasis in China

Schistosomiasis japonica, caused by Schistosoma japonicum, is an important zoonotic disease in China, the Philippines and small pockets of Indonesia. In addition to infecting people, S. japonicum can infect over 40 species of wild and domestic animals which have varying impacts on human infection. It is now generally accepted that bovines, particularly water buffaloes, are the major reservoir for human infection in China as they are naturally infected with schistosomes and deposit more eggs into the environment than humans or any other animal host. This complicates control efforts and the economic burden associated with schistosomiasis morbidity and mortality has taken its toll on both human and livestock populations. Over the last 50 years, the schistosomiasis control program in China has made great strides in reducing prevalence and morbidity, and the Chinese authorities now aim to eliminate the disease nationwide in the next decade. Current Chinese control strategies place particular importance on interventions targeting bovines including: praziquantel treatment, barrier farming to prevent grazing in transmission areas, their replacement with mechanized tractors and possible bovine vaccination. A number of studies have shown that in the period following S. japonicum infection, the worm burden drops sharply in water buffaloes and some other animal hosts such as pigs. This is due to a self-cure phenomenon whereby there is parasite clearance by both immune and non-immune factors. Here we review studies investigating the self-cure effect, paying particular attention to S. japonicum infection in water buffaloes, and discuss its potential impact on the future schistosomiasis control and elimination efforts in China. Further understanding of the mechanism of self-cure in water buffaloes could be important for future schistosome vaccine design and delivery.     

Reduction Patterns of Acute Schistosomiasis in the People's Republic of China

Background

Despite significant, steady progress in schistosomiasis control in the People''s Republic of China over the past 50 years, available data suggest that the disease has re-emerged with several outbreaks of acute infections in the early new century. In response, a new integrated strategy was introduced.

Methods

This retrospective study was conducted between Jan 2005 and Dec 2012, to explore the effectiveness of a new integrated control strategy that was implemented by the national control program since 2004.

Results

A total of 1,047 acute cases were recorded between 2005 and 2012, with an annual reduction in prevalence of 97.7%. The proportion of imported cases of schistosomiasis was higher in 2011 and 2012. Nine clusters of acute infections were detected by spatio-temporal analysis between June and November, indicating that the high risk areas located in the lake and marshland regions.

Conclusion

This study shows that the new integrated strategy has played a key role in reducing the morbidity of schistosomiasis in the People''s Republic of China.     

A vaccine against Asian schistosomiasis

There is continued transmission of schistosomiasis japonica in China and Philippines despite highly effective control programs that focus on the application of the highly effective drug praziquantel (PZQ). The massive Three Gorges Dam across the Yangtze River in Southern China, soon to be completed, is expected to significantly increase schistosomiasis transmission and introduce the disease into areas currently unaffected. After long-term experience it is generally accepted that PZQ chemotherapy, although the cornerstone of current control programs, does have significant limitations. Furthermore, efficient drug delivery requires a substantial infrastructure to regularly cover all parts of an endemic area. Although there is not yet clear-cut evidence for the existence of PZQ-resistant schistosome strains, decreased susceptibility to the drug has been observed in several countries. As a result, a protective vaccine represents an essential component for the long-term control of schistosomiasis. This article briefly reviews aspects of anti-schistosome protective immunity that are important in the context of vaccine development. The current status in the development of vaccines against Schistosoma japonicum will then be discussed as will new approaches that may improve on the efficacy of available vaccines, and aid in the identification of new targets for immune attack. With new and extensive data becoming available from the S. japonicum genome project, the prospects for developing an effective vaccine are encouraging. The challenges that remain are many but it is crucial that the momentum towards developing effective anti-schistosome vaccines is maintained.     

The effects of health education on schistosomiasis japonica prevalence and relevant knowledge in the People's Republic of China: A systematic review and meta-analysis

Schistosomiasis japonica continues to be an important zoonotic disease in the People's Republic of China (P.R. China), despite decades of dedicated control efforts. Different interventions for its control including chemotherapy of humans and animals, mollusciciding, environmental modification, and health education have been implemented at various stages of the control efforts and in different combinations, resulting in remarkable achievements. Here, we present a systematic review and meta-analysis of the documented effectiveness of health education to reduce schistosomiasis japonica transmission in P.R. China. A total of 10 relevant publications were identified and included in the meta-analysis. The reported results indicate that the prevalence of Schistosoma japonicum infection in humans and schistosomiasis-related knowledge are significantly influenced by health education. The implementation of health education over more than 2 years was associated with an overall schistosomiasis japonica prevalence decrease of 6% (95% CI: 2%, 11%) and an overall increase of 51% (95% CI: 41%, 61%) in schistosomiasis-related knowledge after controlling for confounding factors. Among control groups, the prevalence of schistosomiasis japonica and relevant knowledge levels were not significantly influenced. The relative risk (RR) of an infection with S. japonicum following health education lasting more than 2 years was 0.43 (95% CI: 0.24, 0.78). In summary, a considerable effectiveness of health education with regard to preventing S. japonicum infections in P.R. China and increasing relevant knowledge is documented in the extant literature. This suggests that the effectiveness of health education may be considerable, particularly after its long-term implementation.     

Spatio-temporal pattern of schistosomiasis in Anhui Province,East China: Potential effect of the Yangtze River - Huaihe River Water Transfer Project

Anhui Province has been one of typical epidemic areas of schistosomiasis in East China as a wide range of large lake and marshland regions provide an ideal environment for growth and reproduction of the intermediate snail host. With the completion of the Yangtze River-Huaihe River Water Transfer Project (YHWTP), launched by the end of 2016, the epidemic areas are expected to expand and controlling schistosomiasis remains a challenge. Based on annual surveillance data at the county level in Anhui for the period 2006–2015, spatial and temporal cluster analyses were conducted to assess the pattern of risk through spatial (Local Moran's I and flexible scan statistic) and space-time scan statistic (Kulldorff). It was found that schistosomiasis sero-prevalence was dramatically reduced and maintained at a low level. Cluster results showed that spatial extent of schistosomiasis contracted, but snail distribution remained geographically stable across the study area. Clusters, both for schistosomiasis and snail presence, were common along the Yangtze River. Considering the effect of the ongoing YHWTP on the potential spread of schistosomiasis, Zongyang County and Anqing, which will be transected by the new water-transfer route, should be given a priority for strengthened surveillance and control. Attention should also be paid to Guichi since it is close to one of the planned inlets of the YHWTP.     

Shifts in the Spatiotemporal Dynamics of Schistosomiasis: A Case Study in Anhui Province,China

Background

The Chinese national surveillance system showed that the risk of Schistosoma japonicum infection fluctuated temporally. This dynamical change might indicate periodicity of the disease, and its understanding could significantly improve targeted interventions to reduce the burden of schistosomiasis. The goal of this study was to investigate how the schistosomiasis risk varied temporally and spatially in recent years.

Methodology/Principal Findings

Parasitological data were obtained through repeated cross-sectional surveys that were carried out during 1997-2010 in Anhui Province, East China. A multivariate autoregressive model, combined with principal oscillation pattern (POP) analysis, was used to evaluate the spatio-temporal variation of schistosomiasis risk. Results showed that the temporal changes of schistosomiasis risk in the study area could be decomposed into two sustained damped oscillatory modes with estimated period of approximately 2.5 years. The POPs associated with these oscillatory components showed that the pattern near the Yangtze River varied markedly and that the disease risk appeared to evolve in a Southwest/Northeast orientation. The POP coefficients showed decreasing tendency until 2001, then increasing during 2002-2005 and decaying afterwards.

Conclusion

The POP analysis characterized the variations of schistosomiasis risk over space and time and demonstrated that the disease mainly varied temporally along the Yangtze River. The schistosomiasis risk declined periodically with a temporal fluctuation. Whether it resulted from previous national control strategies on schistosomiasis needs further investigations.     

Is there immunity to Schistosoma japonicum?

The Oriental schistosome, Schistosoma japonicum, unlike the other two major schistosomes that infect humans (S. mansoni and S. haematobium), is a zoonotic species. The transmission dynamics and the potential effects of host-related regulatory factors, including immunity, are likely to be distinct for this parasite. Here, Allen Ross and collaborators from Australia, China and the Philippines discuss recently published and established epidemiological and laboratory data bearing on anti-infection immunity to Asian schistosomiasis, and contrast these findings with the emerging picture of development of anti-infection immunity against the African schistosomes. Implications for vaccines and other control strategies for schistosomiasis japonica are also discussed.     

Spatially Explicit Modeling of Schistosomiasis Risk in Eastern China Based on a Synthesis of Epidemiological,Environmental and Intermediate Host Genetic Data

Schistosomiasis japonica is a major parasitic disease threatening millions of people in China. Though overall prevalence was greatly reduced during the second half of the past century, continued persistence in some areas and cases of re-emergence in others remain major concerns. As many regions in China are approaching disease elimination, obtaining quantitative data on Schistosoma japonicum parasites is increasingly difficult. This study examines the distribution of schistosomiasis in eastern China, taking advantage of the fact that the single intermediate host serves as a major transmission bottleneck. Epidemiological, population-genetic and high-resolution ecological data are combined to construct a predictive model capable of estimating the probability that schistosomiasis occurs in a target area (“spatially explicit schistosomiasis risk”). Results show that intermediate host genetic parameters are correlated with the distribution of endemic disease areas, and that five explanatory variables—altitude, minimum temperature, annual precipitation, genetic distance, and haplotype diversity—discriminate between endemic and non-endemic zones. Model predictions are correlated with human infection rates observed at the county level. Visualization of the model indicates that the highest risks of disease occur in the Dongting and Poyang lake regions, as expected, as well as in some floodplain areas of the Yangtze River. High risk areas are interconnected, suggesting the complex hydrological interplay of Dongting and Poyang lakes with the Yangtze River may be important for maintaining schistosomiasis in eastern China. Results demonstrate the value of genetic parameters for risk modeling, and particularly for reducing model prediction error. The findings have important consequences both for understanding the determinants of the current distribution of S. japonicum infections, and for designing future schistosomiasis surveillance and control strategies. The results also highlight how genetic information on taxa that constitute bottlenecks to disease transmission can be of value for risk modeling.     

Establishing and Applying a Schistosomiasis Early Warning Index (SEWI) in the Lower Yangtze River Region of Jiangsu Province,China

Background

China has made remarkable progress in schistosomiasis control over the past decades. Transmission control has replaced morbidity control as the country moves towards the goal of elimination and the current challenge is to find a sensitive measure capable of gauging transmission risk in low-prevalence areas. The study aims to develop a Schistosomiasis Early Warning Index (SEWI) and demonstrate its use in Jiangsu Province along the lower Yangtze River.

Methodology/Principal Findings

The Delphi approach, a structured communication technique, was used to develop the SEWI. Two rounds of interviews with 30 public health experts specialized in schistosomiasis control were conducted using 40 indicators that reflected different aspects of schistosomiasis transmission and control. The necessity, feasibility, and sensitivity of each indicator were assessed and the weight value of each indicator determined based on these experts'' judgment. The system included 3 first-order indicators, 7 second-order indicators, and 30 third-order indicators. The 3 first-order indicators were endemic status, control measures, social and environmental factors, with the weight values 0.366, 0.343 and 0.291, respectively. For the 7 second-order indicators, the highest weight value was for control measures for snails (0.175) and the lowest for transmission route (0.110). We estimated and mapped the SEWI for endemic areas at the county scale in Jiangsu Province finding that the majority of the endemic areas were characterized as medium transmission risk (SEWI risk values between 0.3 and 0.6), while areas where transmission interruption had been officially declared showed SEWI values <0.30. A few isolated areas (e.g. endemic islands in the Yangtze River) produced SEWI values >0.60. These estimates are largely in agreement with the endemicity levels based on recent epidemiological surveys.

Conclusions/Significance

The SEWI should be useful for estimation of schistosomiasis transmission surveillance, particularly with reference to the elimination of the disease in China.     

Quantifying quality of life and disability of patients with advanced schistosomiasis japonica

Background

The Chinese government lists advanced schistosomiasis as a leading healthcare priority due to its serious health and economic impacts, yet it has not been included in the estimates of schistosomiasis burden in the Global Burden of Disease (GBD) study. Therefore, the quality of life and disability weight (DW) for the advanced cases of schistosomiasis japonica have to be taken into account in the re-estimation of burden of disease due to schistosomiasis.

Methodology/Principal Findings

A patient-based quality-of-life evaluation was performed for advanced schistosomiasis japonica. Suspected or officially registered advanced cases in a Schistosoma japonicum-hyperendemic county of the People''s Republic of China (P.R. China) were screened using a short questionnaire and physical examination. Disability and morbidity were assessed in confirmed cases, using the European quality of life questionnaire with an additional cognitive dimension (known as the “EQ-5D plus”), ultrasonography, and laboratory testing. The age-specific DW of advanced schistosomiasis japonica was estimated based on patients'' self-rated health scores on the visual analogue scale of the questionnaire. The relationships between health status, morbidity and DW were explored using multivariate regression models. Of 506 candidates, 215 cases were confirmed as advanced schistosomiasis japonica and evaluated. Most of the patients reported impairments in at least one health dimension, such as pain or discomfort (90.7%), usual activities (87.9%), and anxiety or depression (80.9%). The overall DW was 0.447, and age-specific DWs ranged from 0.378 among individuals aged 30–44 years to 0.510 among the elderly aged ≥60 years. DWs are positively associated with loss of work capacity, psychological abnormality, ascites, and active hepatitis B virus, while splenectomy and high albumin were protective factors for quality of life.

Conclusions/Significance

These patient-preference disability estimates could provide updated data for a revision of the GBD, as well as for evidence-based decision-making in P.R. China''s national schistosomiasis control program.