Field Testing Integrated Interventions for Schistosomiasis Elimination in the People's Republic of China: Outcomes of a Multifactorial Cluster-Randomized Controlled Trial.

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 Schistosoma japonicum 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 S. japonicum, 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 S. japonicum 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 S. japonicum 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 S. japonicum 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.

[Evaluation on effect of treatment and assistance to advanced schistosomiasis patients in Hunan Province from 2004 to 2013].

OBJECTIVE: To comprehensively evaluate the effect of the program of treatment and assistance to advanced schistosomiasis patients in Hunan Province from 2004 to 2013. METHODS: The fund investment of the program, the profits of hospitals and the improvement of the patients' health were investigated by data collection and questionnaire survey. The evaluation index system of treatment and assistance to advanced schistosomiasis in Hunan Province was constructed by the Delphi method and analytic hierarchy process, and the program was assessed comprehensively. RESULTS: The evaluation index system including 6 primary indices and 33 secondary indices was established. Among all the primary indices, the score of the treatment and assistance (22.25) was the highest, and that of the satisfaction assessment (8.15) was the lowest, and the score of the comprehensive assessment was 87.06. The average cure rate of the patients was 13.08% from 2004 to 2013. More than 60% of the patients' disease condition got better, and nearly 70% of the patients' psychological condition improved, and more than 70% of patients' self-help ability and social contact improved, as well as family happiness increased. In addition, the annual average cost for caretakers decreased by 2000 Yuan, and the profits of all the fixed-point hospitals for treatment and assistance increased. CONCLUSION: The effectiveness and efficiency of the treatment and assistance to advanced schistosomiasis patients in Hunan Province is obvious, and the government should continuously invest in the program.

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 50years, 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.

[Distribution of susceptible areas of schistosomiasis outside embankment in Hunan Province, 2011].

OBJECTIVE: To investigate the current distribution of susceptible areas of schistosomiasis outside embankment, so as to provide the evidence for making comprehensive measures in Hunan Province. METHODS: The outside embankment areas where Oncomelania snails possibly or historically distributed and people and animals had activities were surveyed. The schistosomiasis information of the susceptible areas was collected, a database was set up, the positions were marked with GPS, an E-map was drawn with Google Earth, and the distribution was analyzed. RESULT: The number of marshlands with schistosomiasis susceptible areas outside embankment was 787, the length was 1,429.64 km, and the area was 6,2017.17 hm(2). The average density of living snails was 0.37 snails/0.1 m(2), and the average density of infected snails was 0.0019 snails/0.1 m(2). The infected snails were found in 180 marshlands, and the area was 688.07 hm(2). Sixteen rivers had the susceptible areas, and the main vegetation was weeds. CONCLUSIONS: The susceptible area of schistosomiasis outside embankment is wide and complex. Therefore, the comprehensive control measures should be strengthened.

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.

[Role of socio-economy and management in sustainable transmission control of schistosomiasis in Taoyuan County, Hunan Province, China].

OBJECTIVE: To clarify the role of socio-economy and management in the sustainable schistosomiasis-control in Taoyuan County, an endemic area in hilly region, Hunan Province, China. METHODS: From 1996 to 2011, the data of socio-economy, the management of schistosomiasis control organizations, environment, and the changes in schistosomiasis prevalence were collected in Taoyuan County where schistosomiasis transmission had been controlled since 2008. A sampling survey of schistosomiasis prevalence of human and bovine was performed in 2011 to verify the current status of schistosomiasis transmission. All the data were analyzed statistically to evaluate the role of socio-economy and management in the sustainable schistosomiasis control. RESULTS: During the period from 1998 to 2012, the socio-economy including the residents' productive mode and daily life in Taoyuan County improved dramatically, but the recurrence risk of schistosomiasis endemic still existed due to the retuning of out-going workers and the migrating population. Moreover, the introduction of exotic species of plants and animals may increase the risk. The low running cost of schistosomiasis control organization as well as the efficient and adequate resource allocation in the county was in line with the national requirement to strengthen the rural grass-roots public health system. CONCLUSION: The harmonious development of socio-economy and the scientific and efficient health system in Taoyuan County are the key factors for the sustainable transmission control of schistosomiasis.

[Multi-disciplinary treatment for advanced schistosomiasis].

OBJECTIVE: To assess the efficiency of multi-disciplinary treatment (MDT) for advanced schistosomiasis. METHODS: A total of 173 advanced schistosomiasis patients who received MDT were selected from January 2010 to December 2011. These patients included 75 splenomegaly cases and 98 ascites cases. Other 193 advanced schistosomiasis patients who received single-discipline treatment (SDT) from January 2007 to December 2009 were also selected, and of them 84 cases were splenomegaly and 109 were ascites. The clinical efficiencies of the two different treatments were analyzed and assessed. RESULTS: Compared to the SDT group, the splenomegaly cases treated by MDT showed a shorter pre-operative preparation time and less days in hospitalization (both P < 0.01), less operation duration, decreased post-operative complications, lower hospitalization costs (all P < 0.05), and less patient complaints (P > 0.05). The ascites cases treated by MDT, compared to the SDT group, had less pre-treatment time, shorter ascites-disappearing time (both P <0.01), and less hospitalization duration, decreased post-treatment complications, lower hospitalization costs and less patient complaints (all P < 0.05). Conclusion MDT has a better efficiency in the treatment of advanced schistosomiasis, and it reduces the operation complications and improves the life quality of the patients.

TIAM2 enhances non-small cell lung cancer cell invasion and motility.

BACKGROUND: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. RESULTS: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down- regulate the expression of MMP-3, Twist and Snail. CONCLUSIONS: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.

[Surveillance of endemic situation of schistosomiasis in Wuyi Village of Dongting Lake region, Hunan Province from 2002 to 2010].

OBJECTIVE: To understand the epidemic trends of schistosomiasis in Wuyi Village of Muping Lake, so as to provide the references for making control strategy of schistosomiasis in embankment subtype in Dongting Lake region. METHODS: The data relating to the morbidity of schistosomiasis among human and domestic animals, the status of Oncomelania snails, the parameters of demographic and social economic development, and intervention measures were collected in Wuyi Village from 2002-2010. Based on this information, the changing trends of schistosomiasis were dynamically analyzed. RESULTS: The infection rate of schistosomiasis among human reduced from 11.44% in 2002 to 1.12% in 2010. The infection rate among male residents was higher than that of female ones. The fishermen had the highest infection rate among all the occupational groups. The positive rate of stool examination in cattle was stable at 10%. The density of snails outside embankment greatly decreased from 10.49 snails/0.1 m2 in Autumn of 2003 to 0.68 snails/0.1 m2 in Autumn of 2010. The mean density of infected snails outside embankment reached the peak of 0.026 snails/0.1 m2 in Spring of 2003, yet the figure reduced to zero from 2006 to now. CONCLUSION: The endemic situation of schistosomiasis in Wuyi Village has been greatly reduced, yet cattle and fishermen are still the targets of schistosomiasis control in the future.

[Longitudinal investigation on intestinal parasite infections among rural people in West Dongting Lake region].

The nylon pocket concentration method and modified Kato-Katz technique were used to detect the eggs of intestinal parasites and the iodine smear method was used for the detection of protozoa among the rural population in West Dongting Lake region. The infection rate of parasites in 2006 was 11.84%, and it declined by 86.63%, 81.34%, and 47.28%, respectively, compared to the rates in 1983, 1993, and 2003. Six major parasites were detected including Ascaris lumbricoides, Trichuris trichiura, Fasciolopsis buski, hookworm, Entamoeba histolytica and Giardia lamblia, and their infection rates were 8.60%, 6.41%, 1.75%, 0.14%, 2.50%, and 1.22%, respectively. The rate of multiple infections was 22.98%. The infection rates in the 5-9 years age group and 10-14 years age group were higher than those in other age groups.

[Selection of government instruments in schistosomiasis control services].

From the perspective of public administration and epidemiology, on the combination of the governance cases in the central and local government of China, the author explores ten modes of the provision of public goods and services in schistosomiasis control services, discusses seven main government instruments, and points out its pluralism, complexity and the slight changes of government' s preference. This paper also explores the approach to help the relevant government make schistosomiasis control work more practicable in field.

Risk factors for helminth infections in a rural and a peri-urban setting of the Dongting Lake area, People's Republic of China.

Schistosomiasis japonica and soil-transmitted helminthiasis are endemic parasitic diseases in the People's Republic of China (PR China). As very few studies have reported on the distribution and interaction of multiple species helminth infections, we carried out a comparative study of households in a rural village and a peri-urban setting in the Dongting Lake area of Hunan province in November and December 2006 to determine the extent of single and multiple species infections, the underlying risk factors for infection, and the relationships with clinical manifestations and self-reported morbidity. In each household, stool samples were collected and subjected to the Kato-Katz method for identifying Schistosoma japonicum, Ascaris lumbricoides, hookworm and Trichuris trichiura infections. Clinical examinations were performed and questionnaire surveys conducted at both household and individual subject levels. Complete parasitological, clinical and questionnaire data were obtained for 1,298 inhabitants of the two settings. The overall prevalences of single infections of S. japonicum, A. lumbricoides, hookworm and T. trichiura were 6.5%, 5.5%, 3.0% and 0.8%, respectively; the majority of the infections were of light intensity. We found significant negative associations between wealth and infections with S. japonicum and A. lumbricoides. Clinical manifestations of splenomegaly, hepatomegaly and anaemia were prevalent (9.0%, 3.7% and 10.9%, respectively), the latter two being significantly (P<0.05) associated with schistosomiasis. Self-reported symptoms were more common among females but there was considerable under-reporting in both sexes when relying only on spontaneous recall. Our findings may guide the design and targeting of a more equitable, comprehensive and integrated parasitic disease control programme in Hunan province and in other areas of PR China.

Comparison of two approaches for measuring household wealth via an asset-based index in rural and peri-urban settings of Hunan province, China.

BACKGROUND: There are growing concerns regarding inequities in health, with poverty being an important determinant of health as well as a product of health status. Within the People's Republic of China (P.R. China), disparities in socio-economic position are apparent, with the rural-urban gap of particular concern. Our aim was to compare direct and proxy methods of estimating household wealth in a rural and a peri-urban setting of Hunan province, P.R. China. METHODS: We collected data on ownership of household durable assets, housing characteristics, and utility and sanitation variables in two village-wide surveys in Hunan province. We employed principal components analysis (PCA) and principal axis factoring (PAF) to generate household asset-based proxy wealth indices. Households were grouped into quartiles, from 'most wealthy' to 'most poor'. We compared the estimated household wealth for each approach. Asset-based proxy wealth indices were compared to those based on self-reported average annual income and savings at the household level. RESULTS: Spearman's rank correlation analysis revealed that PCA and PAF yielded similar results, indicating that either approach may be used for estimating household wealth. In both settings investigated, the two indices were significantly associated with self-reported average annual income and combined income and savings, but not with savings alone. However, low correlation coefficients between the proxy and direct measures of wealth indicated that they are not complementary. We found wide disparities in ownership of household durable assets, and utility and sanitation variables, within and between settings. CONCLUSION: PCA and PAF yielded almost identical results and generated robust proxy wealth indices and categories. Pooled data from the rural and peri-urban settings highlighted structural differences in wealth, most likely a result of localized urbanization and modernization. Further research is needed to improve measurements of wealth in low-income and transitional country contexts.

Prevalence, intensity and associated morbidity of Schistosoma japonicum infection in the Dongting Lake region, China.

OBJECTIVE: To determine the prevalence and intensity of Schistosoma japonicum infection and associated morbidity, and to estimate the infected human and buffalo populations in the Dongting Lake region, Hunan province, China. METHODS: We used data from the third national schistosomiasis periodic epidemiological survey (PES) of 2004. These included 47 144 human serological and 7205 stool examinations, 3893 clinical examinations and questionnaire surveys, and 874 buffalo stool examinations, carried out in 47 villages in Hunan province. Serological examinations were performed using the enzyme linked immunosorbent assay technique and human stool samples were examined by the Kato-Katz method. Stools from buffaloes and other domestic animals were examined for schistosome infection by the miracidial hatching test. FINDINGS: Sero-prevalence was 11.9% (range: 1.3-34.9% at the village level), and the rate of egg-positive stools was estimated at 1.9% (0-10.9%) for the same population. The prevalence of infection among buffaloes was 9.5% (0-66.7%). Extrapolating to the entire population of the Dongting Lake region, an estimated 73 225 people and 13 973 buffaloes were infected. Most frequently reported symptoms were abdominal pain (6.2%) and bloody stools (2.7%). More than half of the clinically examined people reported having had at least one prior antischistosomal treatment. CONCLUSION: There was a significant reduction in the number of humans infected with S. japonicum since the previous national PES carried out in 1995, partially explained by large-scale chemotherapy campaigns. However, a near-stable number of buffalo infections suggest continuing human re-infection, which may lead to future increases in human prevalence.

Large water management projects and schistosomiasis control, Dongting Lake region, China.

Construction of the Three Gorges Dam across the Yangtze River will substantially change the ecology of the Dongting Lake in southern China. In addition, the Chinese Central and Hunan Provinces' governmental authorities have instigated a Return Land to Lake Program that will extend the Dongting Lake surface area from the current 2,681 km2 to 4,350 km2. The previous construction of embankments and the large silt deposits made by the Yangtze River and other connecting rivers have contributed to frequent disastrous flooding. As a consequence of the 2 water projects, > 2 million persons and their domestic animals are being resettled. This article provides an overview of the historical background of these 2 large water management projects, the associated population movement, and their impact on future transmission and control of schistosomiasis in the Dongting Lake area. The dam will likely substantially extend the range of the snail habitats and increase schistosome transmission and schistosomiasis cases.

Applications and outcomes of periodic epidemiological surveys for schistosomiasis and related economic evaluation in the People's Republic of China.

The great success in schistosomiasis control in China is attributable to a range of factors. Periodic epidemiological surveys (PES) used for monitoring and adapting control interventions over time are an integral feature of the national schistosomiasis control programme. PES have enabled the dynamic trends of schistosomiasis epidemics to be closely pursued and have assisted in analysing subtle changes in endemicity. The results can be summarised mathematically allowing the variation in efficacy of control measures to be readily determined and enabling control strategies to be adjusted and updated. PES have been used in both cross-sectional and longitudinal pilot studies selected by appropriate sampling methods. In the early 1990s, when the World Bank Loan Project for schistosomiasis control commenced, economic evaluations were initiated in parallel. Cost-effectiveness analysis became a necessary tool to identify the most financially feasible yet effective options among a range of alternative control strategies. There was, however, a lack of standardised approaches rendering study comparisons across sites difficult. The global burden of disease study established the disability adjusted life year (DALY) as a measure of population health, combining in a single indicator years lost from premature death and years of life lived with disability. However, a recent meta-analysis reveals that the burden of schistosomiasis is underestimated, and hence, needs to be revised. It is envisaged that after the revision of DALYs lost due to schistosomiasis japonica, they will become an essential measure in future schistosomiasis control assessments in China and in other schistosome-endemic areas of the world.

[Study on the strategy of interrupting schistosomiasis transmission in a hilly new endemic area of Taoyuan County].

OBJECTIVE: To develop a strategy for interrupting the transmission of schistosomiasis japonica in a hilly new endemic area. METHODS: Since 1996, chemotherapy with praziquantel (adult 40 mg/kg, child 50 mg/kg, cattle 30 mg/kg, once a year) on human beings in Taoyuan County who had ever contacted with infectious water and cattle which were herded in endemic situation was the major intervention, with focal control of Oncomelania snails in susceptible areas as supplementary one. RESULTS: The positive rate of stool examination for schistosomiasis in human and cattle reduced from 5.69% and 6.76% in 1996 to 0.04% and 0 in 2005 respectively. The positive rate of indirect hemagglutination test (IHA) in human dropped from 7.45% in 1996 to 1.61% in 2004. Though living snails were still found in most habitats, the density of infected snails decreased from 0.0036/0.11m2 in 1997 to 0 in 2005 and no infected snails were found since 2000. CONCLUSION: Due to less movement of human and cattle populations and the hilly area relatively isolated, chemotherapy combined with focal mollusciciding have been highly effective in eliminating the infection sources and interrupting transmission of schistosomiasis.