Spatial Cluster Change of Schistosoma japonicum Transmission Foci in Indonesia During the Schistosomiasis Elimination Program.

PURPOSE: The Government of Indonesia committed to eliminating schistosomiasis by 2025. Collaboratively snail control became one of the crucial strategies to ensure that the prevalence of Schistosoma japonicum in Oncomelania hupensis lindoensis reaches zero by the end of the program. This research investigated the spatial cluster change of S. japonicum transmission foci in Indonesia between 2017 and 2021. METHODS: We mapped the snail foci, collected the snails, and calculated the snail density. We also conducted laboratory tests to detect the existence of cercariae in the snails. Identified infected snails were used to calculate the infection rate (IR) or snails' prevalence of schistosome cercariae among freshwater snails. We then analysed the spatial cluster using the Getis-Ord Gi* statistic to identify the hot and cold spots. RESULTS: The 5-year schistosomiasis elimination program successfully declined 18.84% of the snail foci and reduced 40.37% of the infected snail foci. Local spatial autocorrelation of snail density and infection rate identified that in 2017 and 2021, the number of cold spots decreased by 53.91% and 0%, while hot spots increased by 2.63% and 56.1%. The presence of more hot spots suggests a rise in the number of foci with high snail density and infection rates. The implementation of snail control was not optimal, and the parasite transmission through domestic animals still existed, causing the spatial cluster of hot spots to change during this period. Most hotspots have been observed near settlements, primarily in cocoa plantations, developed and deserted rice fields, grassland, and bush wetlands. CONCLUSION: During the schistosomiasis elimination program, the number of hot spots increased while cold spots decreased, and there were notable changes in the geographical distribution of hot spots, indicating a shift in the clustering pattern of schistosomiasis cases. The findings become essential for policymakers, particularly in selecting priority areas for intervention. In the Discussion section, we demonstrated the selection process based on the existence of hot and cold spots. Furthermore, we proposed that enhancing cross-sector integration is crucial, particularly in connection with the management of S. japonicum transmission through domestic animals.

Population genomic analyses of schistosome parasites highlight critical challenges facing endgame elimination efforts.

Schistosomiasis persists in Asian regions despite aggressive elimination measures. To identify factors enabling continued parasite transmission, we performed reduced representation genome sequencing on Schistosoma japonicum miracidia collected across multiple years from transmission hotspots in Sichuan, China. We discovered strong geographic structure, suggesting that local, rather than imported, reservoirs are key sources of persistent infections in the region. At the village level, parasites collected after referral for praziquantel treatment are closely related to local pre-treatment populations. Schistosomes within villages are also highly related, suggesting that only a few parasites from a limited number of hosts drive re-infection. The close familial relationships among miracidia from different human hosts also implicate short transmission routes among humans. At the individual host level, genetic evidence indicates that multiple humans retained infections following referral for treatment. Our findings suggest that end-game schistosomiasis control measures should focus on completely extirpating local parasite reservoirs and confirming successful treatment of infected human hosts.

Afforestation suppresses Oncomelania hupensis snail density through influencing algae in beaches of the Dongting Lake.

BACKGROUND: Oncomelania snails serve as the sole intermediate host for Schistosoma japonicum, one of the most important neglected tropical diseases in the world. Afforestation suppression of the Oncomelania hupensis snail has been a long-term effective national strategy to decrease snail density in China. Many previous studies have made clear that vegetation (biotic factors) and soil (abiotic factors) were the basic requirements for snail survival on beaches. Moreover, a lot of research on snail control has been focused on the specific influencing environmental factors for snail survival, such as the vegetation community structure, species composition, diversity index, and the physical and chemical properties of the soil. Most of the existing research has studied the influence of a single factor on snail population density. Conversely, there have been only a few studies focused on the food sources and food composition of the snails. The current research situation on snail control has indicated that the mechanisms underlying ecological snail control have not been systematically characterized. The question of whether biotic or abiotic factors were more important in influencing snail survival remains unclear. Afforestation on beaches has significantly suppressed snail density in China so far. In this study, we proposed that the reduction of snail density was not affected by a single factor but by the interactions of multiple related factors introduced by afforestation. Moreover, different biotic and abiotic factors have significantly different effects on snail control. Therefore the goal of this study was to evaluate the relative importance and interactions of related biotic and abiotic factors on snail density. Methods: Four major vegetation communities: Sedge, Reed, Artificial poplar (3 years of age) and Artificial poplar (5 years of age), on the beaches of the Yangtze River in China were selected for vegetation and snail surveys, as well as for soil sampling. Structural Equation Model (SEM) analysis was used to assess the interactions of biotic and abiotic factors in the context of snail ecology. The soil properties were considered as abiotic factors, while algae of Chlorophyta, Cyanophyta and Bacillariophyta phyla were considered to be biotic factors. In the path analysis, the total effect between the variables was the sum of the direct and indirect effects. RESULTS: The snail density had significant correlations with soil properties, such as water content, bulk density, capillary porosity and pH value, as well as with all three types of soil algae, Chlorophyta, Cyanophyta, and Bacillariophyta. Snail density had a direct negative relationship with capillary porosity and soil bulk density, an indirect negative relationship with soil pH value and an indirect positive relationship with soil water content via soil algae. Meanwhile, as an important food source for the snail, the Chlorophyta, Cyanophyta and Bacillariophyta algae had a significant positive correlation with snail density. High soil pH had a negative impact on Chlorophyta, Bacillariophyta, while soil water content had a positive impact on Chlorophyta, and soil bulk density had a negative impact on Cyanophyta. In addition, the soil pH value and soil bulk density both had negative correlations with soil water content. CONCLUSION: Afforestation of the beach environment can significantly reduce the snail population density by altering ecological factors. Soil algae (biological factors) might be the key element that drives ecological snail control. As important habitat determinants, the impact of the properties of the soil (non-biological factors) on the snail population was largely mediated through soil algae.

Patterns of relatedness and genetic diversity inferred from whole genome sequencing of archival blood fluke miracidia (Schistosoma japonicum).

Genomic approaches hold great promise for resolving unanswered questions about transmission patterns and responses to control efforts for schistosomiasis and other neglected tropical diseases. However, the cost of generating genomic data and the challenges associated with obtaining sufficient DNA from individual schistosome larvae (miracidia) from mammalian hosts have limited the application of genomic data for studying schistosomes and other complex macroparasites. Here, we demonstrate the feasibility of utilizing whole genome amplification and sequencing (WGS) to analyze individual archival miracidia. As an example, we sequenced whole genomes of 22 miracidia from 11 human hosts representing two villages in rural Sichuan, China, and used these data to evaluate patterns of relatedness and genetic diversity. We also down-sampled our dataset to test how lower coverage sequencing could increase the cost effectiveness of WGS while maintaining power to accurately infer relatedness. Collectively, our results illustrate that population-level WGS datasets are attainable for individual miracidia and represent a powerful tool for ultimately providing insight into overall genetic diversity, parasite relatedness, and transmission patterns for better design and evaluation of disease control efforts.

Current Status of Schistosomiasis Control and Prospects for Elimination in the Dongting Lake Region of the People's Republic of China.

Schistosomiasis japonica is an ancient parasitic disease that has severely impacted human health causing a substantial disease burden not only to the Chinese people but also residents of other countries such as the Philippines, Indonesia and, before the 1970s, Japan. Since the founding of the new People's Republic of China (P. R. China), effective control strategies have been implemented with the result that the prevalence of schistosomiasis japonica has decreased markedly in the past 70 years. Historically, the Dongting Lake region in Hunan province is recognised as one of the most highly endemic for schistosomiasis in the P.R. China. The area is characterized by vast marshlands outside the lake embankments and, until recently, the presence of large numbers of domestic animals such as bovines, goats and sheep that can act as reservoir hosts for Schistosoma japonicum. Considerable social, economic and environmental changes have expanded the Oncomelania hupensis hupensis intermediate snail host areas in the Dongting lake region increasing the potential for both the emergence of new hot spots for schistosomiasis transmission, and for its re-emergence in areas where infection is currently under control. In this paper, we review the history, the current endemic status of schistosomiasis and the control strategies in operation in the Dongting Lake region. We also explore epidemiological factors contributing to S. japonicum transmission and highlight key research findings from studies undertaken on schistosomiasis mainly in Hunan but also other endemic Chinese provinces over the past 10 years. We also consider the implications of these research findings on current and future approaches that can lead to the sustainable integrated control and final elimination of schistosomiasis from the P. R. China and other countries in the region where this unyielding disease persists.

[Impact of "Elaphurus davidianus return home project" on the transmission of schistosomiasis in Poyang Lake areas].

OBJECTIVE: To investigate the prevalence of Schistosoma japonicum infections in Elaphurus davidianus released to Poyang Lake areas and evaluate the impact of the project of "E. davidianus released to wild environments for natural reproduction and growth" "(E. davidianus return home project") on the transmission of schistosomiasis in Poyang Lake areas. METHODS: During the period from April 2018 to December 2019, the population distribution, inhabiting activity and natural reproduction of E. davidianus released to Poyang Lake areas were investigated by means of GPS and artificial observations. The S. japonicum infection was identified in animal feces in E. davidianus inhabitats using a hatching test, and snail distribution was surveyed in E. davidianus inhabiting grass islands using a systematic sampling method. RESULTS: A total of 51 E. davidianus were released to the Poyang Lake areas in 2018, which subsequently produced 5 E. davidianus habitats in Yinlong Lake, Longkou, Nanchi Lake, Lianzi Lake and Zhu Lake. E. davidianus was found to predominantly inhibit in grass islands, farmlands and forest lands in hilly regions around the Poyang Lake areas. The natural reproduction rate of E. davidianus was 25% in the habitats in 2019, and the mean density of snails was 0.009 to 0.039 snails/0.1 m2 in E. davidianus inhabitats; however, no S. japonicum infection was identified in snails. In addition, the mean densities of wild E. davidianus and bovine feces were 4.6 samples/hm2 and 2.1 samples/hm2, Conclusions The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on and the prevalence of S. japonicum infection was 4.35% and 13.16% (P = 0.236), respectively; however, the intensities of S. japonicum infections were "+++" and "+", respectively. CONCLUSIONS: The E. davidianus released to Poyang Lake areas may get infections with S. japonicum, and cause schistosomiasis transmission through fecal contamination in grass islands. The impact on local schistosomiasis transmission and the response strategy requires to be investigated following the release of E. davidianus to lake regions, to ensure the achievement of the goal of schistosomiasis elimination and the successful implementation of the "E. davidianus return home project" in Poyang Lake areas.

Schistosoma japonicum-infected sentinel mice: Surveillance and spatial point pattern analysis in Hubei province, China, 2010-2018.

OBJECTIVES: Progress in national schistosomiasis control in China has successfully reduced disease transmission in many districts. However, a low transmission rate hinders conventional snail surveys in identifying areas at risk. In this study, Schistosoma japonicum-infected sentinel mice surveillance was conducted to identify high-risk areas of schistosomiasis transmission in Hubei province, China. METHODS: The risk of schistosomiasis transmission was assessed using sentinel mice monitoring in Hubei province from 2010 to 2018. Field detections were undertaken in June and September, and the sentinel mice were kept for approximately 35 days in a laboratory. They were then dissected to determine whether schistosome infection was present. Ripley's K-function and kernel density estimation were applied to analyze the spatial distribution and positive point pattern of schistosomiasis transmission. RESULTS: In total, 190 sentinel mice surveillance sites were selected to detect areas of schistosomiasis infection from 2010 to 2018, with 29 (15.26%) sites showing infected mice. Of 4723 dissected mice, 256 adult worms were detected in 112 infected mice. The infection rate was 2.37%, with an average of 2.28 worms detected per infected mouse. Significantly more infected mice were detected in the June samples than in the September samples (χ2=12.11, p<0.01). Ripley's L(d) index analysis showed that, when the distance was ≤34.52km, the sentinel mice infection pattern showed aggregation, with the strongest aggregation occurring at 7.86km. Three hotspots were detected using kernel density estimation: at the junction of Jingzhou District, Gong'an County, and Shashi District in Jingzhou City; in Wuhan City at the border of the Huangpi and Dongxihu Districts, and in the Hannan and Caidian Districts. CONCLUSION: The results showed that sentinel mice surveillance is useful in identifying high-risk areas, and could provide valuable information for schistosomiasis prevention and control, especially concerning areas along the Yangtze River, such as the Fu-Lun, Dongjing-Tongshun, and Juzhang River basins.

The genetic variation of different developmental stages of Schistosoma japonicum: do the distribution in snails and pairing preference benefit the transmission?

BACKGROUND: Schistosoma japonicum is a waterborne parasite that causes schistosomiasis in humans and in more than 40 animal species. Schistosoma japonicum shows distinct genetic differentiation among geographical populations and multiple hosts, but the genetic diversity of different developmental stages of S. japonicum from is less studied. Such studies could elucidate ecological mechanisms in disease transmission by analysing feedbacks in individual physiology and population state. METHODS: After infection using cercariae from a pool of snails shedding together (Method I) and infection using mixed equal numbers of cercariae from individually shed snails (Method II), different developmental stages of S. japonicum were genotyped with microsatellite loci, including 346 cercariae, 701 adult worms and 393 miracidia. Genetic diversity and molecular variation were calculated at different population levels. Kinships (I') among cercariae at intra-snail and inter-snail levels were evaluated. Genetic distance (Dsw) was compared between paired and unpaired worms, and partner changing was investigated through paternity identification for miracidia. RESULTS: The cercaria clones in individual snails varied from 1 to 8 and the kinship of cercariae within individual snails was significant higher (P < 0.001) than that among different snails after deleting near-identical multi-locus genotypes (niMLGs). The allelic diversity of worms in Method I was lower (P < 0.001) than that in Method II, and allele frequency among mice in Method I was also less consistent. The parents of some miracidia were worms that were not paired when collected. The Dsw between each female of paired and unpaired males was much larger (P < 0.001) than that between the female and male in each pair. CONCLUSIONS: Most of the infected snails contained multiple miracidia clones. The aggregation of genetically similar S. japonicum miracidia in individual snails and the unbalanced distribution of miracidia among snails suggests a non-uniform genetic distribution of cercariae among snails in the field. This further influenced the genetic structure of adult worms from infections with different cercariae sampling methods. Schistosoma japonicum in mice can change paired partner, preferring to mate with genetically similar worms. These characteristics provide implications for understanding the balance in genetic diversity of S. japonicum related to the transmission of schistosomiasis.

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.

Metabolic profiles of Oncomelania hupensis after molluscicidal treatment: Carbohydrate metabolism targeted and energy deficiency.

Oncomelania hupensis is the intermediate host of Schistosoma japonicum, one of the Schistosoma species that can cause human schistosomiasis. Molluscicidal treatment remains the primary means to control snail. Niclosamide is the only molluscicide recommended by the World Health Organization, and it has been used throughout schistosomiasis-endemic areas in China for almost 30 years. In our previous studies on transcriptomics, morphology, and enzymology of snails after molluscicidal treatment, two effective molluscicides were used, 50% wettable powder of niclosamide ethanolamine salt (WPN) and a new molluscicide derived from niclosamide, the salt of quinoid-2', 5-dichloro-4'-nitro-salicylanilide (LDS, simplified for Liu Dai Shui Yang An). Genes involved in cell structure mintenance, inhibition of neurohumoral transmission, and energy metabolism showed significant differential expression after molluscicide treatments. Damages in the structure of liver and muscle cells were accompanied by inhibited activities of enzymes related to carbohydrate metabolism and energy supply. This study was designed to clarify the dynamic metabolic process by metabonomics, together with the previous transcriptomic and enzymological profiles, to identify potential metabolite markers and metabolism pathways that related to the toxic mechanism of the molluscicide. In total, 56 metabolites were identified for O. hupensis, and 75% of these metabolites consisted of amino acids and derivatives, organic acids, and nucleic acid components. The concentration of glucose, maltose, succinate, choline, and alanine changed significantly after molluscicide treatments. These changes in metabolites mainly occurred in the process of carbohydrate metabolism, energy metabolism, and amino acid metabolism, primarily related to glycolysis/gluconeogenesis, oxidative phosphorylation, and transamination by KEGG pathway identification. Most of the identified pathways were also related to those differentially expressed unigenes and observed enzymes from our previous studies. Inhibited aerobic respiration and oxidative phosphorylation, and energy deficiency were implied further to be the leading causes of the final death of snails after molluscicide treatments. The hypothesised mathematical model in this study identified the rational hysteresis to explain the inconsistency of responses of unigenes, enzymes, and metabolites to molluscicide treatments. This study contributes to the comprehensive understanding of the molluscicidal mechanism in the metabolic process and this could assist in improving existing molluscicide formulations or development of new molluscicides.

Oncomelania hupensis quadrasi: Snail intermediate host of Schistosoma japonicum in the Philippines.

Oncomelania hupensis quadrasi is the snail intermediate host of Schistosoma japonicum in the Philippines. It was discovered by Dr. Marcos Tubangui in 1932 more than two decades after the discovery of the disease in the country in 1906. This review, the first for O. h. quadrasi, presents past and present works on the taxonomy, biology, ecology, control, possible paleogeographic origin of the snail intermediate host and future in research, control and surveillance of the snail. Extensive references are made of other subspecies of O. hupensis such as the subspecies in China for which majority of the advances has been accomplished. Contrasting views on whether the snail is to be considered an independent species of Oncomelania or as one of several subspecies of Oncomelania hupensis are presented. Snail control methods such as chemical methods using synthetic and botanical molluscicides, environmental manipulation and biological control are reviewed. Use of technologies such as Remote Sensing, Geographical Information System and landscape genetics is stressed for snail surveillance. Control and prevention efforts in the Philippines have consistently focused on mass drug administration which has proved inadequate in elimination of the disease. An integrated approach that includes snail control, environmental sanitation and health education has been proposed. Population movement such as migration for employment and economic opportunities and ecotourism and global climate change resulting in heavy rains and flooding challenge the gains of control and elimination efforts. Concern for possible migration of snails to non-endemic areas is expressed given the various changes both natural and mostly man-made favoring habitat expansion.

[Endemic situation of schistosomiasis in Hunan Province in 2019].

OBJECTIVE: To analyze the endemic situation of schistosomiasis in Hunan Province in 2019, so as to provide insights into the achievement of transmission interruption of schistosomiasis in the province in 2020. METHODS: The data pertaining to Schistosoma japonicum infections in humans and livestock and snail status were captured from Hunan Province in 2019 and analyzed. RESULTS: Schistosomiasis was endemic in 281 townships (towns) from 41 counties (districts) of 6 cities in Hunan Province by the end of 2019. A total of 991 900 persons received blood testing in Hunan Province in 2019, and 22 773 were positive for the blood testing, with sero-prevalence of 2.30%. All stool examinations were negative in 22 933 individuals detected. The high sero-prevalence was seen in Nanxian County, Anxiang County and Ziyang District. Currently, there were 5 034 cases with advanced schistosomiasis detected in Hunan Province, and they were predominantly identified in Yuanjiang City, Heshan District and Yueyang County. There were 44 963 bovines fenced in schistosomiasis-endemic villages in Hunan Province in 2019, which were predominantly distributed in Yuanjiang City, Hanshou County and Ziyang District, and no positives were detected in 1 996 bovines receiving blood testing or 20 684 bovines receiving stool examinations. In 2019, there were snail habitats of 1.73 billion m2 found in Hunan Province, which were mainly found in Yuanjiang City, Hanshou County and Yueyang County. CONCLUSIONS: The endemic situation of schistosomiasis further decreases in Hunan Province in 2019; however, there is still a risk of schistosomiasis transmission in local areas of the province.

Oncomelania hupensis retains its ability to transmit Schistosoma japonicum 13 years after migration from permissive to non-permissive areas.

BACKGROUND: The East Route Project (ERP) of the South-to-North Water Diversion Project (SNWDP) stretches across schistosomiasis endemic and non-endemic areas in China, which may lead to the dispersal of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, from permissive areas along the Yangtze River Basin to non-permissive areas in northern China. A previous survey demonstrated that O. hupensis could survive and breed for 13 years (12 generations) after being transferred to a non-permissive area, and could be infected by S. japonicum. However, it is not clear if the migrated snails will change their ability to transmit S. japonicum. METHODS: We infected mice with the cercariae released from the infected transferred snails bred in Jining city of Shandong Province (non-permissive areas) for 13 years. The mice in the control group were infected with cercariae derived from the snails collected in their original habitat (Jiangdu county of Jiangsu Province, permissive areas). Then, we explored the pathogenicity to mice including worm burden, liver egg count and pathology. Additionally, the gene expression profiles of the adult male and female worms recovered from the infected mice were analyzed by RNA sequencing. RESULTS: The worm burden, liver egg count and pathology of the mice infected with cercariae released from transferred snails bred in non-permissive areas for 13 years showed no significant differences, when compared with the control cercariae. Slight changes occurred at the transcription level between adult male and female worms recovered from mice infected with cercariae derived from snails bred in permissive and non-permissive areas. Only fourteen genes were significantly differentially expressed in the comparison of adult female worms, and no significantly differentially expressed gene was found in the comparison of adult male worms. CONCLUSIONS: Our findings strongly suggest that transferred snails did not change their schistosomiasis transmission ability and the worms derived from them retained the original pathogenicity, even after migrating from permissive to non-permissive areas for 13 years. Therefore, a long-term surveillance system of snails along the SNWDP is urgently needed to prevent the diffusion of O. hupensis and reduce the risk of transmission of schistosomiasis.

Process Development of Sj-p80: A Low-Cost Transmission-Blocking Veterinary Vaccine for Asiatic Schistosomiasis.

Asiatic schistosomiasis caused by Schistosoma japonicum is a neglected tropical disease resulting in significant morbidity to both humans and animals - particularly bovines - in endemic areas. Infection with this parasite leads to less healthy herds, causing problems in communities which rely on bovines for farming, milk and meat production. Additionally, excretion of parasite eggs in feces perpetuates the life cycle and can lead to human infection. We endeavored to develop a minimally purified, inexpensive, and effective vaccine based on the 80 kDa large subunit of the calcium activated neutral protease (calpain) from S. japonicum (Sj-p80). Here we describe the production of veterinary vaccine-grade Sj-p80 at four levels of purity and demonstrate in a pilot study that minimally purified antigen provides protection against infection in mice when paired with a low-cost veterinary adjuvant, Montanide™ ISA61 VG. Preliminary data demonstrate that the vaccine is immunogenic with robust antibody titers following immunization, and vaccination resulted in a reduction of parasite eggs being deposited in the liver (23.4-51.4%) and intestines (1.9-55.1%) depending on antigen purity as well as reducing the ability of these eggs to hatch into miracidia by up to 31.6%. We therefore present Sj-p80 as a candidate vaccine antigen for Asiatic schistosomiasis which is now primed for continued development and testing in bovines in endemic areas. A successful bovine vaccine could play a major role in reducing pathogen transmission to humans by interrupting the parasitic life cycle and improving quality of life for people living in endemic countries.

Intestinal microbiome profiles in Oncomelania hupensis in mainland China.

Oncomelania hupensis plays a significant role in the transmission of schistosomiasis japonica, which remains a major public health concern in China. Understanding the biological characteristics of O. hupensis is a prerequisite for its control; however, there are currently no studies investigating the intestinal microbiota of the O. hupensis snail. This study aimed to profile the intestinal microbiome of O. hupensis across different ecological landscapes in mainland China. DNA was extracted from the intestines of the collected snails and the bacterial communities were detected using 454 pyrosequencing. A total of 3,799 operational taxonomic units (OTUs) were obtained, and Proteobacteria, Firmicutes, and Actinobacteria were identified as the dominant bacterial taxa at the phylum level. Bacillus and Lactococcus were the most common genera in samples obtained from the four ecological landscapes. Snail specimens were clustered into three clades according to microbial community diversity, and thirty-seven genera that contributed to differential microbiota distributions were identified. Co-occurrence network analysis indicated a symbiotic relationship for the intestinal microbiota of O. hupensis, and PICRUSt analysis predicted forty-one metabolic functions in all snail samples, including membrane transport, amino acid metabolism, carbohydrate metabolism, replication and repair, energy metabolism, as well as xenobiotics biodegradation and metabolism. These findings improve our understanding of bacterial ecology in the O. hupensis intestine; further studies will focus on the relationship between O. hupensis intestinal microbiota and the microbiota in their specific ecological environments.

Detection of Schistosoma japonicum and Oncomelania hupensis quadrasi environmental DNA and its potential utility to schistosomiasis japonica surveillance in the Philippines.

In recent years, the prevalence and infection intensity of Schistosoma japonicum in endemic areas of the Philippines have significantly decreased due to yearly population-based treatment strategies, yet transmission rates remain high and uninterrupted. An important indicator of active disease transmission is the presence of Schistosoma japonicum and its snail intermediate host Oncomelania hupensis quadrasi in freshwater habitats. In this study, we sought to apply a species-specific real-time PCR (qPCR) assay for the detection of S. japonicum and O. hupensis quadrasi in freshwater samples using environmental DNA approach that can complement the commonly utilized malacological survey in determining potential transmission foci in order to have a more effective snail surveillance strategy for schistosomiasis japonica in endemic areas. The newly developed assay was specific to S. japonicum and O. hupensis quadrasi with no amplification detected against non-target trematode Fasciola spp. and snails such as Lymnaea spp., Pomacea canaliculata, and Melanoides spp. that typically co-exist in the same environment. The assay effectiveness was determined using 19 environmental water samples collected from Northern Samar (N = 5 sites), Leyte (N = 11 sites) and Compostela Valley (N = 3 sites) and compared to malacological survey for determining O. hupensis quadrasi snail colonies and snail crushing to visualize S. japonicum cercariae. TaqMan qPCR targeting a short fragment of the cytochrome c oxidase subunit 1 (cox1) gene was positive for S. japonicum in 9 sites, for O. hupensis quadrasi in 9 sites, and for both S. japonicum and O. hupensis quadrasi in 5 sampling sites. Moreover, it was able to detect O. hupensis quadrasi in 3 out of 12 sites found negative and 6 out of 7 sites found positive through malacological survey, and in 4 of the 5 snail sites positive for snails with cercariae. Overall, this method can complement malacological surveys for monitoring of schistosomes in endemic areas of the Philippines, especially those with high risk of human infection.

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.

Distribution pattern of the snail intermediate host of schistosomiasis japonica in the Poyang Lake region of China.

BACKGROUND: With the closure of the Three Gorges Dam in 2003 the hydrology of Poyang Lake was altered dramatically leading to significant changes in the environment. In order to assess the impact on schistosomiasis this study assessed the spatial and temporal patterns of the snail intermediate host, Oncomelania hupensis in the Poyang Lake tributaries. The results of the study have important implications for future snail control strategies leading to disease elimination. METHODS: The marshland area surrounding Poyang Lake was divided randomly into 200 × 200 m vector grids using ArcGIS software, and the surveyed grids were randomly selected by the software. The snail survey was conducted in each selected grid using a survey frame of 50 × 50 m with one sideline of each grid serving as the starting line. No less than ten frames were used in each surveyed grid with Global Positioning System (GPS) recordings for each. All snails in each frame were collected to determine infection status by microscopy. Altitude data for all frames were extracted from a lake bottom topographic map in order to analyze the average altitude. All snail survey data were collected and statistically analyzed with SPSS 20.0 software in order to determine the difference of the percentage of frames with living snails and mean density of living snails in different regions of Poyang Lake. The altitude of the snail-infested marshlands and snail dens were subsequently identified. RESULTS: A total of 1159 potential snail sampling grids were surveyed, of which 15 231 frames (0.1 m2/frame) were investigated. 1241 frames had live Oncomelania snails corresponding to 8.15% of the total number of frames. The mean density of living snails was 0.463/0.1 m2 with a maximum of 57 snails per frame. The percent of frames with snails in the southern sector (8.13%) of Poyang Lake did not differ statistically from the north (8.21%). However, the mean density of live snails in the northern sector (0.164/0.1 m2) of the lake was statistically higher (F = 6.727; P = 0.010) than the south (0.141/0.1 m2). In the south of the lake, the elevation of snail-inhabited marshland ranged between 11 - 16 m, and could be further subdivided into two snail-concentrated belts at 12-13 m of elevation and 15-16 m of elevation respectively. In the north of the lake, the elevation of snail-inhabited marshland ranged between 9- 16 m with the elevation of 12-14 m being the snail-concentrated zone. CONCLUSIONS: The elevation of snail-infested marshlands in the Poyang Lake region ranged from 9 to 16 m. The snail distribution and habitat has moved north of the lake and to a lower altitude due to changes in the water level post dam closure. Based on the current geological features of the snail habitant focused mollusciciding should occur in snail dense northern regions with frequent bovine and human traffic. Targeting these identified 'hotspots' of transmission will assist in elimination efforts.

[Endemic situation of schistosomiasis in Wuhu City from 2009 to 2018].

OBJECTIVE: To analyze the endemic situation of schistosomiasis in Wuhu City from 2009 to 2018, so as to provide evidence for adjusting and developing the control strategy. METHODS: The data regarding the endemic situation were retrospectively collected and analyzed in Wuhu City from 2009 to 2018. RESULTS: The prevalence of human Schistosoma japonicum infections reduced from 0.450% in 2009 to 0.035% in 2018 in Wuhu City, and a reduction rate of 92.22% (χ2 = 1 6128.307, P < 0.01), and the prevalence of S. japonicum infections decreased from 0.483% in 2009 to 0 in 2018 (χ2 = 27.570, P < 0.01) in livestock. The area of snail habitats increased from 1 501.07 hm2 in 2009 to 4 408.62 hm2 in 2018, with an increase of 193.70%. No infected snails were found in Wuhu City since 2012, and no egg positives were detected in humans and livestock since 2016. CONCLUSIONS: Currently, the endemic situation of schistosomiasis is at a low level in Wuhu City; however, there are still factors affecting schistosomiasis transmission. In the future, the integrated strategy with emphasis on the control of infectious source and the surveillance-response system should be intensified to consolidate the achievements of schistosomiasis control.

Effectiveness of the new integrated strategy to control the transmission of Schistosoma japonicum in China: a systematic review and meta-analysis.

Since 2004, the national schistosomiasis control strategy in China has shifted from the morbidity control strategy (conventional strategy) to an integrated strategy (new strategy). We investigated the effectiveness of the new strategy and compared it against the conventional strategy. We retrieved from electronic databases the literature regarding the new strategy published from 2000 to 2017. The effect of the new or conventional strategy on infection by Schistosoma japonicum of humans and snails (Oncomelania hupensis) was evaluated with pooled log relative risk (logRR). A total of only eight eligible publications were included in the final meta-analysis. The results showed that implementation of the new strategy reduced the infection risk by 3-4 times relative to the conventional strategy. More specifically, the conventional strategy caused a reduction in both human (logRR = 0.56, 95% CI: 0.12-0.99) and snail infections (logRR = 0.34, 95% CI: -0.69-1.37), while the new strategy also significantly reduced both human (logRR = 1.89, 95% CI: 1.33-2.46) and snail infections (logRR = 1.61, 95% CI: 1.06-2.15). In contrast to the conventional strategy, the new strategy appeared more effective to control both human (logRR difference = 1.32, 95% CI: 0.78-1.86) and snail infections (logRR difference = 1.53, 95% CI: 0.76-2.31). Our data demonstrate that the new integrated strategy is highly effective to control the transmission of S. japonicum in China, and this strategy is recommended for schistosomiasis elimination in other affected regions across the world, with adaptation to local conditions.