Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.

Efficacy of China-made praziquantel for treatment of Schistosomiasis haematobium in Africa: A randomized controlled trial.

BACKGROUND: In the roadmap on the neglected tropical diseases (NTD) the World Health Organization (WHO) aims at attaining at least 75% coverage of preventive chemotherapy in pre-school and school-age children by 2020. A randomized controlled trial was used to compare the effectiveness of praziquantel in treating Schistosoma haematobium in Africa using two different sources for the drug, Merck Limited Partnership (KgaA), Germany and Nanjing Pharmaceutical Factory (NPF), China. METHODS: More than 6,000 participants testing positive for S. haematobium infection were enrolled from three villages (shehias) situated in the northern, middle and southern part of Pemba Island, Zanzibar. Applying criteria of inclusion and exclusion, resulted in a study population of 152 people (84 males, 68 females). A randomized controlled trial was conducted assigning participants to either praziquantel from NPF or Merck KGaA. After one month, the cure rate of S. haematobium and adverse events were compared to evaluate effectiveness. The ratio of male to female, the ratio of light/high infection intensity, and the average value of age were calculated between the two drug manufacturers. Chi-squared test and T-test were used for consistency analysis. RESULTS: Out of the total of 73 cases receiving praziquantel from NPF, the cure rate achieved was 97.3% (73/75), while the 74 cases receiving the drug from Merck KgaA reached a similar cure rate (96.1% or 74/77). There was no significant difference between the two outcomes (χ2 = 0.003, P = 0.956). Among the 75 patients treat, only one (a 16-years old female student), who had received the drug made in China had slight adverse reactions manifested as dizziness, headache and abdominal pain. CONCLUSION: The efficacy of China-made praziquantel does not differ significantly from praziquantel made by Merck KGaA in Germany. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133832.

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.

Analysis of multiple pesticide residues in polyphenol-rich agricultural products by UPLC-MS/MS using a modified QuEChERS extraction and dilution method.

An efficient method for the rapid extraction and clean-up of 20 pesticide residues from polyphenol-rich agricultural samples (tea, apple, broccoli, and shallot) for analysis by UPLC-MS/MS was developed. Following extraction, PVPP was used to precipitate polyphenols, supernatant was diluted to minimize matrix effects. Homogenized samples were vortexed in acetonitrile prior to cleanup with a combination of PVPP (150 mg), PSA (50 mg) and GCB (10 mg). Supernatant (1 mL) was filtered and diluted 10-fold before analysis. In 4 agricultural products that usually produce high interference, the matrix effects were overcome for all pesticides expect in green and oolong tea for acephate, omethoate, dinotefuran and nitenpyram. Mean recoveries ranged from 73% to 106%, and RSD ≦ 13%. Limits of quantification ranged from 0.01 to 0.02 mg kg-1. PVPP as one of excellent QuEChERS material combined with dilution was verified as a promising method for multiple pesticide residues analysis in complex matrices.

Schistosomiasis in a migrating population in the lake region of China and its potential impact on control operation.

Coverage of migrating people in schistosomiasis control program is a growing concern in China. Schistosomiasis caused by Schistosoma japonicum is still one of the major infectious diseases of public health importance in China though tremendous efforts have been made to control the transmission over the past decades. Along with the rapid social-economic development, migrant population has been remarkably increasing across the country. The infected migrants may introduce a new souse of infection to endemic areas or the areas where the transmission had been controlled or interrupted but the intermediate host Oncomelania snail is still present. Preliminary studies for surveillance on schistosomiasis prevalence in migrants were reported, but there is little basic information provided. We carried out an investigation on the prevalence in immigrants, emigrants and permanent residents in three villages of Hunan province located in the main endemic area of lake region, and analyzed the potential impact of migration on control practice. In the study villages, the migrant population accounts for 53.6% of the total. Schistosoma infection was detected by modified Kato-Katz method and miracidium hatching test. Questionnaire survey was conducted comprising knowledge of disease and its transmission, water contact, personal protective measures, and whether examined and treated after water contact. The survey indicated that the migrants and permanent residents had similar life style, and the majority of them experienced water contact in agricultural work or routine life activities. However, the infection rate in immigrants was significantly higher than that in permanent residents. It was also found that the migrants had significantly less knowledge about the disease than the permanent residents, and took no personal protective measures. This is due to that the control program could not cover the migrants when they were absent at the time the program being implemented. The present study suggested that the surveillance and intervention for migrants, immigrants in particular, should be included and strengthened in schistosomiasis control program and a feasible scheme be developed.

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.

[Effect of niclosamide spreading oil on killing schistosome cercariae].

Dechlorinated water (100 ml, 30 degrees C) was put into a plate (diameter 15 cm), and 1% niclosamide spreading oil 5 microl was added, then a ring of Schistosoma japonicum cercariae were picked up to the plate. The time of killing all the cercariae was observed at three time points (immediately, 24, 48 h), and the dechlorinated water was used as control. The results showed that schistosome cercariae were all killed in three minutes by 1% niclosamide spreading oil at the three time points. The cercaria-killing effects of each time point were not significantly different (F = 0.062, P > 0.05). The cercariae were alive in the control in 48 h.

Five-year longitudinal assessment of the downstream impact on schistosomiasis transmission following closure of the Three Gorges Dam.

BACKGROUND: Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with about 800,000 people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that, long-term, the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes. METHODOLOGY/PRINCIPAL FINDINGS: We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages of the three transmission modes below the TGD across four provinces (Hunan, Jiangxi, Hubei and Anhui) to determine whether there was any immediate impact of the TGD on schistosomiasis transmission. Eight sentinel villages were selected to represent both province and transmission mode. The primary end point measured was human incidence. Here we present the results of this five-year longitudinal cohort study. Results showed that the incidence of human S. japonicum infection declined considerably within individual villages and overall mode over the course of the study. This is also reflected in the yearly odds ratios (adjusted) for infection risk that showed significant (P<0.01) downward trends in all modes over the follow-up period. CONCLUSIONS/SIGNIFICANCE: The decrease in human S. japonicum incidence observed across all transmission modes in this study can probably be attributed to the annual human and bovine PZQ chemotherapy. If an increase in schistosome transmission had occurred as a result of the TGD, it would be of negligible size compared to the treatment induced decline seen here. It appears therefore that there has been virtually no immediate impact of the TGD on schistosomiasis transmission downstream of the dam.

Performance of a dipstick dye immunoassay for rapid screening of Schistosoma japonicum infection in areas of low endemicity.

BACKGROUND: The dipstick dye immunoassay (DDIA), recently commercially available in the People's Republic of China (P.R. China), is a rapid and simple test to detect human antibodies against Schistosoma Japonicum. Its performance and utility for screening schistosome infection in low endemic areas is little known. We therefore carried out a cross-sectional survey in seven villages with low endemicity of schistosomiasis in P.R. China and assessed the performance and utility of DDIA for diagnosis of schistosomiasis. Stool samples were collected and examined by the Kato-Katz method and the miracidium hatching technique. Serum samples, separated from whole blood of participants, were tested by DDIA. RESULTS: 6285 individuals aged 6-65 years old participated in this study, with a prevalence of schistosomiasis of 4.20%. Using stool examination as a gold reference standard, DDIA performed with a high overall sensitivity of 91.29% (95% CI: 87.89-94.69%) and also a high negative predictive value, with a mean value of 99.29% (95% CI: 98.99-99.58%). The specificity of DDIA was only moderate (53.08%, 95% CI: 51.82-54.34%). Multivariate analysis indicated that age, occupation and history of schistosome infection were significantly associated with the false positive results of DDIA. CONCLUSIONS: DDIA is a sensitive, rapid, simple and portable diagnostic assay and can be used as a primary approach for screening schistosome infection in areas of low endemicity. However, more sensitive and specific confirmatory assays need to be developed and combined with DDIA for targeting chemotherapy accurately.

A 5-year longitudinal study of schistosomiasis transmission in Shian village, the Anning River Valley, Sichuan Province, the Peoples' Republic of China.

BACKGROUND: Schistosoma japonicum is a major public health concern in the Peoples' Republic of China (PRC), with over one million people infected and another 50 million living in areas at risk of infection. Based on ecological, environmental, population genetic and molecular factors, schistosomiasis transmission in PRC can be categorised into four discrete ecosystems or transmission modes. It is predicted that the Three Gorges Dam (TGD) will impact upon the transmission of schistosomiasis in the PRC, with varying degree across the four transmission modes. We undertook longitudinal surveillance from 2002 to 2006 in sentinel villages both above and below the TGD across five provinces (Hunan, Jiangxi, Hubei, Anhui and Sichuan) to determine whether there was any impact of the TGD on schistosomiasis transmission during its construction. Here we present the results from a schistosomiasis-endemic village located above the dam in Sichuan Province. RESULTS: Baseline results showed a human S. japonicum prevalence of 42.0% (95% CI: 36.6-47.5). At follow-up, results showed that the incidence of S. japonicum infection in the selected human cohort in Shian decreased by three quarters from 46% in 2003 to 11.3% in 2006. A significant (P < 0.01) downward trend was also evident in the yearly adjusted (for water contact) odds ratios. Over the four years of follow-up, the incidence of S. japonicum infection in bovines declined from 11.8% in the first year to zero in the final year of follow-up. CONCLUSIONS: The substantial decrease in human (75%) and bovine (100%) incidence observed in Shian village can probably be attributed to the annual human and bovine PZQ treatment of positives; as seen in drug (PZQ) intervention studies in other parts of PRC. If an increase in schistosome transmission had occurred as a result of the TGD, it would be of negligible size compared to the treatment induced decline seen here. It appears therefore that the construction of the TGD had virtually no impact on schistosomiasis transmission in Shian village over the period of study. Furthermore, contrary to previous reports from Sichuan downplaying the role of animals in human schistosome transmission, bovines may indeed play a role.

[Efficacy and adverse effects of film coated praziquantel for treatment of schistosomiasis japonica].

OBJECTIVE: To understand the adverse and curative effects of film coated praziquantel for treatment of schistosomiasis japonica. METHODS: A questionnaire survey was conducted among 6 to 65 years old inhabitants from epidemic areas of schistosomiasis japonica in Jiangxi, Anhui and Hubei provinces, while indirect haemagglutination assay (IHA) was also administrated. The Serological positives were tested by Kato-Katz technique. A total of 509 habitats of serological positives and healthy persons were given praziquantel. 460 targets with no relative symptoms were followed up for adverse effect of drugs in one month and efficacy evaluation of praziquantel was carried out in 104 parasitological positives 3 months post-treatment. RESULTS: The 84.7% (144/170) individuals thought film coated tablets were no smell or only with little smell while 92.9%(315/339) targets in control group fell that tablets smelled bad. The total side effect rates of film coated praziquantel group and control group in 1-2 hours post-treatment were 20.30% (27/133) and 83.18% (272/327) respectively. There was significantly different between two groups (chi(2) = 164.316, P < 0.05). The adverse effect rates of film coated praziquantel group in neuromuscular system, digestive system and cardiovascular system were 15.79% (21/133), 9.77% (13/133), 2.26% (3/133) individually which were significantly lower than those of control groups with 81.65% (267/327), 49.24% (161/327), 12.84% (42/327) in corresponding systems (chi(2)(neuromuscular system) = 175.188, chi(2)(digestive system) = 62.601, chi(2)(cardiovascular system) = 12.010, P < 0.05). And the adverse effect rate of allergic reaction of film coated group was no significant difference with control group (2.26%(3/133) versus 0.92% (3/327), chi(2) = 1.315, P = 0.235). One day after treatment, the adverse effect rate of film coated tablets of praziquantel decreased to 3.01% (4/133), significantly lower than that of control group (P < 0.05). There was no significant difference after 2 weeks treatment while the adverse effect rates decreased to 0.75%(1/133), 0.61% (2/327) in film coated praziquantel group and control group respectively (chi(2) = 0.029, P = 0.642). The curative rates 3 months post treatment were 84.91% (45/51) in film coated tablets of praziquantel group and 82.35% (42/53) in control group without significant difference (chi(2) = 1.536, P = 0.215). CONCLUSION: The smell and adverse effects of film coated tablets of praziquantel were decreased significantly and its efficacy for treatment of schistosomiasis japonica was equal to the control tablets. The film coated tablets of praziquantel might be applied in field widely after a further verification.

A cluster-randomized bovine intervention trial against Schistosoma japonicum in the People's Republic of China: design and baseline results.

We describe the design and report baseline results of a cluster-randomized intervention to determine the importance of bovines for Schistosoma japonicum transmission in southern China. The study involves four matched village pairs in Hunan and Jiangxi Provinces, with a village within each pair randomly selected as intervention (human and bovine praziquantel treatment) or control (human praziquantel treatment only). Total study population prevalences at baseline were 12.4% (n = 5,390) and 15.2% (n = 1,573) for humans and bovines, respectively; village prevalences were similar within pairs. Bovine contamination index calculations showed that bovines less than 24 months of age were responsible for 74% of daily bovine environmental contamination with S. japonicum eggs. The village characteristics and baseline results underpin a rigorous study, which has major implications for deployment of a transmission-blocking bovine vaccine against S. japonicum. The combination of such a vaccine with other control strategies could potentially eliminate S. japonicum from southern China.

A drug-based intervention study on the importance of buffaloes for human Schistosoma japonicum infection around Poyang Lake, People's Republic of China.

Schistosomiasis japonica is a zoonosis of major public health importance in southern China. We undertook a drug intervention to test the hypothesis that buffalo are major reservoirs for human infection in the marshlands/lake areas, where one million people are infected. We compared human and buffalo infection rates and intensity in an intervention village (Jishan), where humans and buffalo were treated with praziquantel, and a control village (Hexi), where only humans were treated, in the Poyang Lake region. Over the four-year study, human incidence in Jishan decreased but increased in Hexi. Adjustment of incidence by age, sex, water exposure, year, and village further confirmed the decreased human infection in Jishan. Chemotherapy for buffaloes resulted in a decrease in buffalo infection rates in Jishan, which coincided with the reduction in human infection rates there in the last two years of the study. Mathematical modeling predicted that buffalo are responsible for 75% of human transmission in Jishan.

The role of 'passive chemotherapy' plus health education for schistosomiasis control in China during maintenance and consolidation phase.

In order to explore the possibility of further optimising schistosomiasis control during the maintenance and consolidation phase in China, two highly endemic villages were selected to compare the strategy of 'passive chemotherapy' plus health education to that of mass chemotherapy singly. Emphasis was placed on treatment coverage with praziquantel among individuals infected with Schistosoma japonicum and costs incurred for treating an infected person. The results show that the former strategy was almost as good as the latter producing treatment coverage rates among egg-positives of 96.2-97.1% during 2 years, while corresponding rates of 100% were achieved in the village where mass chemotherapy was employed. Importantly, the cost of the former strategy was only about half that of mass chemotherapy, i.e. 49.0% in the first year and 54.6% in the following. Moreover, 'passive chemotherapy' together with health education can conveniently be integrated into the primary health care system making it an attractive strategy for schistosomiasis control during the maintenance and consolidation phase.

[The current status of schistosomiasis epidemics in China].

OBJECTIVE: To analyze the change of tendency on schistosomiasis epidemics in China in the last 5 years. METHODS: Data on schistosomiasis epidemics in the history and particularly in the last 5 years were collected. Tendency and the re-emerging status after 1998 were analyzed. RESULTS: Data in 2003 showed that in 42%, 40% and 53% of the provinces, counties and townships with epidemics, the transmission of the disease has been interrupted or controlled. The number of estimated patients of schistosomiasis and areas with snails were also reduced by 92.74% and 73.56%, in 2003. The annual estimated number of chronic cases was around 800 000 and 31 321.5 hectare of snail infested areas were newly identified in recent 5 years. Among 20 national villages under longitudinal surveillance, 30%, 70% and 35% of the villages were presented a tendency of increase in the rates of human infection, bovine infection and Oncomelania snails infection, respectively. A total of 38 counties from 7 provinces have re-emerged in schistosomiasis transmission after those counties having reached criteria of transmission under control or interrupted. In 6 non-endemic counties, snails were presented, and 16 marshlands in Xan river were found with appearance of acute cases of schistosomiasis. More snail infested areas were found in Shanghai, Zhejiang, and Fujian. Both snail infested areas and newly infected cases were occurred in urban areas along the Yangtze River. CONCLUSION: The tendency of increase was presented in focal areas along the Yangtze River, due to changes of environmental, ecological, societal and economic status, as well as on the forces of control.