Predictors of bovine Schistosoma japonicum infection in rural Sichuan,China

In China, bovines are believed to be the most common animal source of human schistosomiasis infections, though little is known about what factors promote bovine infections. The current body of literature features inconsistent, and sometimes contradictory results, and to date, few studies have looked beyond physical characteristics to identify the broader environmental conditions that predict bovine schistosomiasis. Because schistosomiasis is a sanitation-related, water-borne disease transmitted by many animals, we hypothesised that several environmental factors – such as the lack of improved sanitation systems, or participation in agricultural production that is water-intensive – could promote schistosomiasis infection in bovines. Using data collected as part of a repeat cross-sectional study conducted in rural villages in Sichuan, China from 2007 to 2016, we used a Random Forests, machine learning approach to identify the best physical and environmental predictors of bovine Schistosoma japonicum infection. Candidate predictors included: (i) physical/biological characteristics of bovines, (ii) human sources of environmental schistosomes, (iii) socio-economic indicators, (iv) animal reservoirs, and (v) agricultural practices. The density of bovines in a village and agricultural practices such as the area of rice and dry summer crops planted, and the use of night soil as an agricultural fertilizer, were among the top predictors of bovine S. japonicum infection in all collection years. Additionally, human infection prevalence, pig ownership and bovine age were found to be strong predictors of bovine infection in at least 1 year. Our findings highlight that presumptively treating bovines in villages with high bovine density or human infection prevalence may help to interrupt transmission. Furthermore, village-level predictors were stronger predictors of bovine infection than household-level predictors, suggesting future investigations may need to apply a broad ecological lens to identify potential underlying sources of persistent transmission.     

The challenge of effective surveillance in moving from low transmission to elimination of schistosomiasis in China

Until recently, intensified efforts in China to suppress the transmission of Schistosoma japonicum relied principally on routine praziquantel treatment, extensive use of molluscicides and health education programs. These efforts, now supplemented by a broader range of control measures, have been quite successful in reducing the prevalence and intensity of human infection to very low levels. However, re-emergent transmission has occurred in formerly endemic areas of several provinces, signalling the need for more locally effective, integrated control strategies. We argue that these low but persistent levels of transmission also require important changes in both the tactics and strategy of disease surveillance to move forward towards elimination. Here we present recent data exemplifying the low transmission environment which suggests that we are reaching limits of detection of current diagnostic techniques used for human infection surveillance in these communities. However, both epidemiological data and theoretical results indicate that (i) transmission in the human population can persist at very low infection intensities even in the presence of routine control activities; (ii) the parasite can be reintroduced into parasite-free environments by very modest external inputs; and (iii) transmission at these low infection intensities exhibits very slow inter-year dynamics. These observations motivate the need for new, sensitive tools to identify low-level infections in mammalian or snail hosts, or the presence of S. japonicum in environmental media. Environmental monitoring offers an alternative, and perhaps more efficient, approach to large-scale surveillance of human infections in low transmission regions.     

A potential impact of climate change and water resource development on the transmission of Schistosoma japonicum in China

There is growing consensus among climate modellers that the unusual global warming observed in the last decades of the 20th century is primarily forced by human activities, namely greenhouse gas increases in the atmosphere. Global warming will trigger alterations in physical and biological systems, including shifts in the spatio-temporal distribution of disease vectors, but the nature and extent of these changes are poorly understood. The purpose of the present study was to assess the potential impact of climate change and water resource development on the distribution of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. We employed two 30-year composite datasets comprising average monthly temperatures collected at 623 observing stations throughout China, spanning the periods 1961-1990 and 1971-2000. Temperature changes were assessed spatially between the 1960s and 1990s for January, as this is the critical month for survival of O. hupensis. Our database shows that January temperatures increased at 590 stations (94.7%), and that China's average January temperature in the 1990s was 0.96 degrees C higher than 30 years earlier. The historical 0-1 degrees C January isotherm, which was considered the approximate northern limit of S. japonicum transmission, has shifted from 33 degrees 15' N to 33 degrees 41' N, expanding the potential transmission area by 41,335 km2. This translates to an additional 20.7 million people at risk of schistosomiasis. Two lakes are located in this new transmission area that form part of the proposed South-North water transfer project. Climate change, coupled with water resource developments in China, may pose additional challenges for the control of schistosomiasis.     

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China. The total target population was 3148 from four separate administrative villages. Two thousand seven hundred and five of these comprised 400 families ranging in size from 3 to 188. After adjustments were made for gender, water contact and past history of having had schistosomiasis, the heritable component was estimated to account for as much as 58% of the phenotype variation under the polygenic model. Household was not shown to be an important environmental factor. Incorporating village effects indicated that the results were valid for the total population. We conclude that genetic heritability in this region is high and plays an important role in determining risk of infection with S. japonicum.     

The potential of artemether for the control of schistosomiasis

Schistosomiasis continues to rank – following malaria – at the second position of the world's parasitic diseases in terms of the extent of endemic areas and the number of infected people. There is yet no vaccine available and the current mainstay of control is chemotherapy with praziquantel used as the drug of choice. In view of concern about the development of tolerance and/or resistance to praziquantel, there is a need for research and development of novel drugs for the prevention and cure of schistosomiasis. Interestingly, derivatives of artemisinin, which are already effectively used in the treatment of malaria, also exhibit antischistosomal properties. Significant advances have been made with artemether, the methyl ether derivative of artemisinin. We review the discovery of the antischistosomal activity of artemether by Chinese scientists two decades ago; the detailed laboratory studies of the susceptibility of, and effect on, the different developmental stages of Schistosoma japonicum, Schistosoma mansoni and Schistosoma haematobium to artemether; the possible mechanism of action and the potential long-term toxicity. Finally, we look at the effect of combined treatment with artemether and praziquantel; and clinical findings thus far obtained from randomised controlled trials with oral artemether for the prevention of patent infections and morbidity. The review intends to create a forum for strategic discussion of how these laboratory and clinical findings could be translated into public health actions. We conclude that artemether – as part of integrated current control measures and adapted to specific socio-ecological and epidemiological settings – has considerable potential to significantly reduce the current burden of schistosomiasis in many parts of the world.     

Schistosoma mansoni: relationship between parasite age and time of spontaneous elimination from the rat

Laboratory rats infected with Schistosoma mansoni invariably reject the majority of parasites between the fourth and sixth week after infection (self-cure). This investigation was designed to determine whether the timing of rejection is dictated by the rat or by the parasite. Schistosomes were perfused from rats infected 2, 3, or 4 weeks previously and were transferred into the mesenteric veins of normal rats. Recipient animals were perfused at weekly intervals after transfer, and the timing of worm elimination was determined in recipients. It was found that 2-week-old worms were rejected 2 weeks after transfer, 3-week-old worms 1 week after transfer, and 4-week-old worms immediately after transfer. Schistosomes perfused from mice or hamsters and transferred into rats showed the same pattern of worm elimination. It is concluded that at the fourth week of normal schistosome development there is a critical event which makes virtually impossible any further survival of the parasite in laboratory rats.     

Treatment and reinfection of water buffaloes and cattle infected with Schistosoma japonicum in Yangtze River Valley, Anhui province, China

The aim of the present study was to evaluate the efficacy of praziquantel treatment of Schistosoma japonicum infections in cattle and water buffaloes and to assess the natural rate of reinfection after treatment. The studies were conducted on 2 islands in the Yangtze River, Anhui province, China, from March 2003 to January 2004. The efficacy of praziquantel was 97% when applied orally wrapped in tree leaves at the recommended doses. The efficacy was measured using a miracidium hatching technique on fecal samples collected 20 days after treatment. The treatment did not give rise to any major side effects. Reinfection after treatment was high and occurred throughout the year in both cattle and water buffaloes. Age-related resistance was only observed in water buffaloes. It is concluded that although praziquantel is highly effective against S. japonicum in cattle and water buffaloes, a single annual treatment strategy does not effectively control transmission. New strategies for integrated control of animal schistosomiasis are needed to control schistosomiasis transmission more effectively in farm areas of China.     

Cloning and partial nucleotide sequence of Schistosoma japonicum paramyosin: a potential vaccine candidate against schistosomiasis.

, , , and 1992. Cloning and partial nucleotide sequence of Schistosoma japonicum paramyosin: a potential vaccine candidate against schistosomiasis. International Journal for Parasitology 22: 1187–1191. Paramyosin from the blood fluke, Schistosoma mansoni, has shown promise as a vaccine candidate for schistosomiasis mansoni. Here we report the cloning and partial nucleotide sequence of a cDNA encoding paramyosin from the related human parasite, Schistosoma japonicum. Affinity purified antibodies to this clone recognized a S. japonicum antigen of molecular weight 97 kDa, equivalent to the reported size of S. mansoni paramyosin. Alignment of the cDNA sequence with that of S. mansoni paramyosin revealed 90% identity. Comparison of the predicted amino acid sequences revealed 95% identity. Although these two parasites differ in many characteristics, the substantial homology demonstrated here between S. mansoni and S. japonicum paramyosin could have important implications for the development of a S. japonicum vaccine.     

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.     

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.     

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.     

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control

Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we first applied the Bayesian formulation of the immigration-death model to the dataset from Egypt. We further analysed data obtained from a cross-sectional parasitological survey that determined the infection prevalence of S. mansoni among 447 individuals in a village in C?te d'Ivoire. Three consecutive stool samples were collected from each participant and analysed by the Kato-Katz technique. In the C?te d'Ivoire study, the observed S. mansoni infection prevalence was 41.6% and varied with age. The immigration-death model was able to correctly predict 50% of the observed age group-specific point prevalences. The model presented here can be utilized to estimate S. mansoni community infection prevalences, which in turn helps in the strategic planning of schistosomiasis control.     

Epidemiology of Schistosoma japonicum in China: morbidity and strategies for control in the Dongting Lake region

Dongting Lake, covering a very large surface water area of 2691km(2), is located in Hunan Province in the southern part of the People's Republic of China. It is the second-largest freshwater lake in China and plays an important role in regulating the amount of water in the Yangtze River, China's longest river. The annual water level of the lake changes by as much as 15m, rising in summer and falling in winter. Asian schistosomiasis has been endemic in the Dongting Lake region for centuries and it has had a devastating effect on the public health of the local people. After a difficult struggle for more than four decades, a concerted programme, supported by the World Bank Loan and instigated in 1992, has resulted in remarkable progress in the control of the disease in many endemic areas of the region. However, the great challenge remains to consolidate and maintain the achievements made to date. The Schistosoma japonicum intermediate host (Oncomelania hupensis hupensis) snail habitats are huge, estimated at 1768km(2) in 1996; these are increasing at a rate of 34.7km(2) annually due to high silt deposition from the Yangtze River itself and from the connecting rivers in Hunan province, and construction of embankments in the Dongting Lake region. It is anticipated that the construction of the Three Gorges Super Dam, the largest engineering project ever undertaken, will substantially extend the range of the snail habitats and increase the number of new schistosomiasis cases. In many areas, human re-infections with S. japonicum after drug (praziquantel) treatment remain unacceptably high (up to 20% of those treated are re-infected annually) due to occupational (mainly fishing) water contact. This paper reviews the history and the current status of schistosomiasis control in the lake region, it explores the epidemiological factors which influence the prevalence of the infection and the disease it causes, and it provides insight into future approaches to control which might finally eradicate the infection.     

Apoptosis phenomenon in the schistosomulum and adult worm life cycle stages of Schistosoma japonicum

Apoptosis is an important aspect of a number of biological processes, from embryogenesis to the stress–injury response. It plays a central role in balancing cell proliferation and tissue remodeling activity in many organisms. In the present study, apoptosis in 14 days post infection schistosomula was evaluated using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assays and DAPI staining. Additionally, flow cytometry using the Annexin V-FITC/propidium iodide (PI) (Annexin V/PI) assay confirmed the percentage of early apoptotic, late apoptotic, and necrotic cells in 14 and 23 days post infection worms. Conserved Domain Database (CDD) BLAST analysis and alignment analysis of known schistosome proteins demonstrated the feasibility of detecting the activity of caspase-3 and -7 using the caspase-3/7 Glo analysis assay. Analysis of caspase-3 and -7 activities in schistosome demonstrated that both caspases were active in each developmental stage of Schistosoma japonicum, but was highest in the 14 days post infection schistosomula. Additionally, the caspase peptide inhibitor (Z-VAD-FMK) inhibited the caspase-3/7 activity at all developmental stages examined. Therefore, we hypothesized that two main signaling pathways are involved in apoptosis in S. japonicum, the caspase cascade and the mitochondrial-initiated pathway. We have constructed a model of these two pathways, including how they may interact and their biological outcomes. qRT-PCR analyses of the gene expression profiles of apoptosis-related genes supported our hypothesis of the relationship between the apoptotic pathway and parasite development. The data presented here demonstrates that apoptosis is an important biological process for the survival and development of the schistosome, and identifies potential novel therapeutic targets.     

Provincial water use efficiency measurement and factor analysis in China: Based on SBM-DEA model

This paper estimates water use efficiency of 31 provinces in China during 2004–2013 using slack based measure-data envelopment analysis (SBM-DEA) model which takes consideration of sewage. By using panel data model, factors that influence water use efficiency are explored. The results show that: (1) water use efficiency is higher in economically developed provinces such as Beijing, Shanghai and Tianjin. (2) In general, inefficiencies of labor input and water input are larger than that of capital input. (3) After taking into account sewage as unexpected output, inefficiency of gross domestic product (GDP) for each province is quite low, but most provinces have inefficient sewage emission. (4) It is found in the analysis of influencing factors that the ratio of added value of agricultural sector, water usage per capita and sewage per unit of output have negative impact on water resources use efficiency, while the import dependence and export dependence have positive impact. The results are robust.     

Boron supplementation in peripartum Murrah buffaloes: The effect on calcium homeostasis,bone metabolism,endocrine and antioxidant status

BackgroundCalcium homeostasis and immuno-endocrine system undergoes drastic changes in peripartum dairy animals and failure to adapt these physiological changes causes major impact on animal health as well as productivity. Boron (B), a newer trace element, influences calcium (Ca), phosphorus (P) and magnesium (Mg) metabolism as well as immune system by manipulating several hormones or enzyme systems. Present study was conducted to determine the effect of dietary B supplementation on Ca homeostasis, bone metabolism, endocrine and antioxidant status in peripartum Murrah buffaloes.MethodsThirty advanced pregnant Murrah buffaloes (8th month pregnant) were allocated into three groups based on their most probable producing ability (MPPA) and parity (n = 10 in each group) viz. B0, B200 and B400 and supplemented with 0, 200 and 400 ppm of B in the form of boric acid. Blood samples were collected at periodic intervals (-45, -30, -21, -15, -7, 0, 7, 15, 30, 60, 90 and 120 day relative to expected date of calving) and analysed for minerals concentration, hormonal profile, bone health biomarkers and antioxidant enzymes.Results and conclusionBoron supplementation at 200 and 400 ppm increased (p < 0.05) plasma Ca, Mg and osteocalcin (OCN) concentration during postpartum stage. Higher (p < 0.05) levels of plasma 25-hydroxy vitamin D₃ were observed in both B supplemented groups as compared to B unsupplemented group irrespective of physiological stages. Plasma parathyroid hormone (PTH) and cortisol levels were lower (p < 0.05) in both B supplemented groups than B unsupplemented group, especially during postpartum stage. Whereas, plasma ferric reducing total antioxidant power (FRAP) activity was found to be higher (p < 0.05) in B supplemented groups as compared to B unsupplemented group. Furthermore, antioxidant enzymes (erythrocytic superoxide dismutase; SOD, catalase, glutathione peroxidase; GPx), plasma level of total immunoglobulins (TIg), bone specific alkaline phosphatase (BALP) and tartrate resistant acid phosphatase (TRAP) remained unaffected by dietary B supplementation. Overall, it can be concluded that supplementation of B at 200 ppm in the diet of peripartum Murrah buffaloes helped to induce metabolic adaptations for improving Ca homeostasis, bone metabolism and antioxidant status without much additional benefits at higher level used in the present study.     

An insight into the genetic variation of Schistosoma japonicum in mainland China using DNA microsatellite markers

This study presents the first microsatellite investigation into the level of genetic variation among Schistosoma japonicum from different geographical origins. S. japonicum isolates were obtained from seven endemic provinces across mainland China: Zhejiang (Jiashan County), Anhui (Guichi County), Jiangxi (Yongxiu County), Hubei (Wuhan County), Hunan (Yueyang area), Sichuan 1 (Maoshan County), Sichuan 2 (Tianquan County), Yunnan (Dali County), and also one province in the Philippines (Sorsogon). DNA from 20 individuals from each origin were screened against 11 recently isolated and characterized S. japonicum microsatellites, and a set of nine loci were selected based on their polymorphic information content. High levels of polymorphism were obtained between and within population samples, with Chinese and Philippine strains appearing to follow different lineages, and with distinct branching between provinces. Moreover, across mainland China, genotype clustering appeared to be related to habitat type and/or intermediate host morph. These results highlight the suitability of microsatellites for population genetic studies of S. japonicum and suggest that there may be different strains of S. japonicum circulating in mainland China.     

The host antigen phenomenon in experimental murine schistosomiasis: The transfer of 3-week old Schistosoma mansoni between two inbred strains of mice

A surgical technique for the transfer of 3-week old Schistosoma mansoni to the mesenteric veins of mice is described. Parasites grown in a donor C3H/StCrl strain survive on transfer to recipient C57BL/10J mice despite prior immunization with C3H/StCrl cells or skin grafts. The findings indicate that the ‘species-specific’ mouse host antigens associated with adult worms in xenogeneic transfers do not have an allogeneic basis in these two strains.