Assessing the role of Filopaludina martensi martensi as a biocontrol agent of Bithynia siamensis goniomphalos, the first intermediate host of Opisthorchis viverrini.

The freshwater snail Bithynia siamensis goniomphalos serves as the first intermediate host of liver fluke Opisthorchis viverrini, a foodborne parasite, of which human infection has persisted in Southeast Asia for decades. The snail Filopaludina martensi martensi has been proposed as a biological control agent against B.s. goniomphalos, but knowledge on the snail ecology and population dynamics between the two species remains rudimentary. This study investigated selected abiotic and biotic factors influencing the distribution and abundance of B.s. goniomphalos and F.m. martensi. Water quality, soils, and snails were collected from 34 localities in Northeast Thailand. Soil properties and snail soft tissue elemental concentrations were analyzed. Experiments were performed to examine interspecific competition. Statistical analysis was conducted to explore the associations between water and soil properties and soft tissue elemental concentrations. The results showed that B.s. goniomphalos had the highest mean dominance in streams and red-yellow podzolic soils, while F.m. martensi snails preferred ponds and latosol soils. Negative correlation in species abundances was found between the two species. Interspecific competition was detected, with B.s. goniomphalos growth rates hampered by the presence of F.m. martensi. Despite the possibility of using F.m. martensi to control B.s. goniomphalos, B.s. goniomphalos exhibited a greater adaptability to different water and soil properties, suggesting that the species could colonize a wide range of environmental conditions. This study provides further insights into the ecology of the two snail species, underscoring the importance of considering abiotic factors when assessing the possible biological control agent to control O. viverrini transmission.

Establishing the Production of Male Schistosoma mansoni Cercariae for a Controlled Human Infection Model.

To accelerate the development of novel vaccines for schistosomiasis, we set out to develop a human model for Schistosoma mansoni infection in healthy volunteers. During natural infections, female schistosomes produce eggs that give rise to morbidity. Therefore, we produced single-sex, male Schistosoma mansoni cercariae for human infection without egg production and associated pathology. Cercariae were produced in their intermediate snail hosts in accordance with the principles of good manufacturing practice (GMP). The application of GMP principles to an unconventional production process is a showcase for the controlled production of complex live challenge material in the European Union or under Food and Drug Administration guidance.

Lessons from a 15-year-old boy with advanced schistosomiasis japonica in China: a case report.

Schistosomiasis is a chronic, parasitic disease caused by flukes (trematodes) of the genus Schistosoma, which presents the most important global burden of the 17 neglected tropical diseases listed by the World Health Organization. China has made great achievements in schistosomiasis control, and now China is planning to move forward, to eliminate schistosomiasis within 2020, but the fact cannot be denied that the possibility of schistosome infection is still there in some endemic due to its zoonotic nature as well as wide distribution of its intermediate hosts (snails). Thus, how to interrupt the transmission in areas with distribution of schistosomes and intermediate snails becomes a very serious challenge that China is facing. In this paper, it is reported an advanced schistosomiasis japonica case of a 15-year-old boy which is extremely rare in the current schistosomiasis control in China. Thus, it is supposed to strengthen health education of school children and to train professional physicians of local hospitals.

Advances in the Diagnosis of Human Schistosomiasis.

Schistosomiasis is a major neglected tropical disease that afflicts more than 240 million people, including many children and young adults, in the tropics and subtropics. The disease is characterized by chronic infections with significant residual morbidity and is of considerable public health importance, with substantial socioeconomic impacts on impoverished communities. Morbidity reduction and eventual elimination through integrated intervention measures are the focuses of current schistosomiasis control programs. Precise diagnosis of schistosome infections, in both mammalian and snail intermediate hosts, will play a pivotal role in achieving these goals. Nevertheless, despite extensive efforts over several decades, the search for sensitive and specific diagnostics for schistosomiasis is ongoing. Here we review the area, paying attention to earlier approaches but emphasizing recent developments in the search for new diagnostics for schistosomiasis with practical applications in the research laboratory, the clinic, and the field. Careful and rigorous validation of these assays and their cost-effectiveness will be needed, however, prior to their adoption in support of policy decisions for national public health programs aimed at the control and elimination of schistosomiasis.

History of schistosomiasis epidemiology, current status, and challenges in China: on the road to schistosomiasis elimination.

Schistosomiasis is a snail-borne disease caused by worms of the genus Schistosoma. Worldwide, human schistosomiasis remains a serious public health problem, threatening ∼800 million people in 78 countries with a loss of 70 million disability-adjusted life years. Schistosoma japonicum is the only human blood fluke that occurs in China. As one of the countries suffering greatly from schistosomiasis, over the past 65 years, China has made great strides in controlling schistosomiasis, blocking the transmission of S. japonicum in five provinces, remarkably reducing transmission intensities in the other seven endemic provinces, and China is currently preparing to move toward the elimination of this disease before 2025. However, while on the road to schistosomiasis elimination, emerging challenges merit attention, including severe advanced cases, increased movements of population and livestock, large-area distribution of intermediate host snails, limitations of new drug developments and no vaccine available, as well as imported schistosomiasis and its potential risk.

Accelerating snail vector genomics.

The three most important genera of snails for the transmission of schistosomes are Bulinus, Biomphalaria and Oncomelania. Each of these genera, found in two distantly related families, includes species that act as the intermediate host for one of the three most widespread schistosome species infecting humans, Schistosoma haematobium, S. mansoni and S. japonicum, respectively. An important step in the fight against schistosomiasis in Asia has been taken with the publication of the article "Chromosome-level genome assembly of Oncomelania hupensis: the intermediate snail host of Schistosoma japonicum", which means that genomes for all three major genera, including species across three continents, are now available in the public domain. This includes the first genomes of African snail vectors, namely Biomphalaria sudanica, Bi. pfeifferi and Bulinus truncatus, as well as high-quality chromosome level assemblies for South American Bi. glabrata. Most importantly, the wealth of new genomic and transcriptomic data is helping to establish the specific molecular mechanisms that underly compatibility between snails and their schistosomes, which although diverse and complex, may help to identify potential targets dictating host parasite interactions that can be utilised in future transmission control strategies. This new work on Oncomelania hupensis and indeed studies on other snail vectors, which provide deep insights into the genome, will stimulate research that may well lead to new and much needed control interventions.

First bovine vaccine to prevent human schistosomiasis - a cluster randomised Phase 3 clinical trial.

OBJECTIVE: Schistosomiasis is a neglected tropical parasitic disease caused by blood flukes of the genus Schistosoma. Schistosoma japonicum is zoonotic in China, the Philippines, and Indonesia, with bovines acting as major reservoirs of human infection. The primary objective of the trial was to examine the impact of a combination of human mass chemotherapy, snail control through mollusciciding, and SjCTPI bovine vaccination on the rate of human infection. METHODS: A 5-year phase IIIa cluster randomized control trial was conducted among 18 schistosomiasis-endemic villages comprising 18,221 residents in Northern Samar, The Philippines. RESULTS: Overall, bovine vaccination resulted in a statistically significant decrease in human infection (relative risk [RR] = 0.75; 95% confidence interval [CI] = 0.69 to 0.82) across all trial follow-ups. The best outcome of the trial was when bovine vaccination was combined with snail mollusciciding. This combination resulted in a 31% reduction (RR = 0.69; 95% CI = 0.61 to 0.78) in human infection. CONCLUSION: This is the first trial to demonstrate the effectiveness of a bovine vaccine for schistosomiasis in reducing human schistosome infection. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12619001048178).

Workshop on research priorities for management and treatment of angiostrongyliasis(1).

In a concluding session of the workshop, the participants developed a list of 115 research and outreach needs, outlining the top 5-7 needs in each of 8 areas (Table). For complete information, including presenter details and abstracts, visit the workshop website at www.hawaii.edu/cowielab/Angio%20website%20home.htm.

A strategy to control transmission of Schistosoma japonicum in China.

BACKGROUND: Schistosoma japonicum causes an infection involving humans, livestock, and snails and is a significant cause of morbidity in China. METHODS: We evaluated a comprehensive control strategy in two intervention villages and two control villages along Poyang Lake in the southeastern province of Jiangxi, where annual synchronous chemotherapy is routinely used. New interventions, implemented from 2005 through 2007, included removing cattle from snail-infested grasslands, providing farmers with mechanized farm equipment, improving sanitation by supplying tap water and building lavatories and latrines, providing boats with fecal-matter containers, and implementing an intensive health-education program. During the intervention period, we observed changes in S. japonicum infection in humans, measured the rate of infection in snails, and tested the infectivity of lake water in mice. RESULTS: After three transmission seasons, the rate of infection in humans decreased to less than 1.0% in the intervention villages, from 11.3% to 0.7% in one village and from 4.0% to 0.9% in the other (P<0.001 for both comparisons). The rate of infection in humans in control villages fluctuated but remained at baseline levels. In intervention villages, the percentage of sampling sites with infected snails decreased from 2.2% to 0.1% in one grassland area and from 0.3% to no infection in the other (P<0.001 for both comparisons). The rate of infection in mice after exposure to lake water decreased from 79% to no infection (P<0.001). CONCLUSIONS: A comprehensive control strategy based on interventions to reduce the rate of transmission of S. japonicum infection from cattle and humans to snails was highly effective. These interventions have been adopted as the national strategy to control schistosomiasis in China.

What is the role of health education in the integrated strategy to control transmission of Schistosoma japonicum in China?

In 2009, Wang et al.'s field trial published in the New England Journal of Medicine, reported that a comprehensive strategy aiming to reduce the roles of humans and cattle as sources of Schistosoma japonicum infection in snails was implemented and proved effective and promising in dramatically reducing the percentage of infected humans and snails, which had been extended to other endemic provinces in China afterwards. This implies that the integrated schistosomiasis-control strategies of interventions including political will, financial support and residents' participation to control human and bovine sources of S. japonicum infection in snails may direct to successfully interrupt the parasitic transmission and to ultimately eliminate schistosomiasis. Confusingly, however, the role of health education, which is a critical part of the integrated strategy and should play an active role in schistosomiasis control, was not reflected. We wish the authors to provide the readers a better and clearer statement of the role of health education as part of the integrated control strategy and so we write this comment.

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.

[Progresses of research on patterns and monitoring approaches of Oncomelania hupensis spread].

Oncomelania snail is the only intermediate host of Schistosoma japonicum, and controlling snail breeding and spread is an important intervention for schistosomiasis control. This review summarizes factors affecting snail spread, characteristics of snail spread in various endemic areas, high-risk environments of snail spread and monitoring methods of snail spread, so as to provide insights into the prevention of snail spread.

[Progress of schistosomiasis control in Dongting Lake regions].

As an ancient parasitic disease, schistosomiasis has been endemic in Dongting Lake areas for more than 2 100 years. In the early 20th century, the first human case of schistosomiasis in China was reported in Dongting Lake areas, which was paid extensive attention. After the founding of the People's Republic of China, large-scale schistosomiasis control activities were launched promptly in Dongting Lake areas, and great successes have been achieved following the three stages of control efforts, including the snail control-based stage, synchronous chemotherapy for humans and livestock-based control stage and infectious source control-based control stage. In 2015, transmission control of schistosomiasis was achieved in Hunan Province. This paper comprehensively describes the discovery and control of schistosomiasis, analyzes the challenges for the current schistosomiasis control programs and proposes the emphasis for future control activities in Dongting Lake areas, so as to provide insights into the schistosomiasis control program in this area.

Public health concerns over gene-drive mosquitoes: will future use of gene-drive snails for schistosomiasis control gain increased level of community acceptance?

With the advent of CRISPR (clustered regularly interspaced short palindromic repeat)-based gene drive, present genetic research in schistosomiasis vector control envisages the breeding and release of transgenic schistosome-resistant (TSR) snail vectors to curb the spread of the disease. Although this approach is still in its infancy, studies focussing on production of genetically modified (GM) mosquitoes (including gene-drive mosquitoes) are well advanced and set the pace for other transgenic vector research. Unfortunately, as with other GM mosquitoes, open field release of gene-drive mosquitoes is currently challenged in part by some concerns such as gene drive failure and increased transmission potential for other mosquito-borne diseases among others, which might have adverse effects on human well-being. Therefore, not only should we learn from the GM mosquito protocols, frameworks and guidelines but also appraise the applicability of its current hurdles to other transgenic vector systems, such as the TSR snail approach. Placing these issues in a coherent comparative perspective, I argue that although the use of TSR snails may face similar technical, democratic and diplomatic challenges, some of the concerns over gene-drive mosquitoes may not apply to gene-drive snails, proposing a theory that community consent will be no harder and possibly easier to obtain for TSR snails than the experience with GM mosquitoes. In the future, these observations may help public health practitioners and policy makers in effective communication with communities on issues regarding the use of TSR snails to interrupt schistosomiasis transmission, especially in sub-Saharan Africa.

[Flood disasters and schistosomiasis control].

Currently, the endemic situation of schistosomiasis has dropped to the lowest level in China; however, there are still factors affecting the transmission of schistosomiasis. Flood disasters may pose a great impact on the transmission of schistosomiasis and even affect the progress of schistosomiasis control and the consolidation of schistosomiasis control achievements. In 2020, major flood disasters occur across China. This paper analyzes the current status of schistosomiasis and the impact of flood disasters on the transmission of schistosomiasis in China, and systematically describes the assessment of and response to schistosomiasis transmission risk before flood disasters, the prevention of Schistosoma japonicum infections during flood disasters and the assessment of the endemic situation of schistosomiasis and surveillance of schistosomiasis after flood disasters. It is considered that schistosomiasis control is an important part of conventional schistosomiasis control activities and an important part of anti-flood and schistosomiasis-preventive activities in flood disaster-affected areas. It is recommended that emergence response interventions are implemented in a scientific and well-organized manner to avoid or reduce the risk of schistosomiasis transmission caused by flood disasters. In addition, the research on early surveillance and forecast approaches for schistosomiasis should be emphasized and reinforced to provide the scientific and precise tools for achieving the goal of the 13th Five-year Plan for Schistosomiasis Control and elimination of schistosomiasis in China.

The Schistosomiasis Consortium for Operational Research and Evaluation Rapid Answers Project: Systematic Reviews and Meta-Analysis to Provide Policy Recommendations Based on Available Evidence.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research to inform global health practices related to the control and elimination of schistosomiasis. The greatest part of the SCORE investment has been in multiyear, long-term efforts, including cluster-randomized trials of gaining and sustaining control of schistosomiasis, trials on elimination of schistosomiasis, and diagnostic test development and evaluation. In the course of planning and conducting SCORE studies, critical questions were raised that could be answered relatively quickly by collecting, collating, and synthesizing existing data. Through its Rapid Answers Project (RAP), the SCORE conducted seven systematic reviews, including four associated meta-analyses, on issues related to screening for schistosomiasis, enhancing mass drug administration, treatment impacts, and the efficacy of snail control for prevention of human schistosomiasis. This article summarizes the findings of the seven RAP reports and provides links to the studies and their supporting information.

[Challenges of schistosomiasis control in China during the coronavirus disease 2019 (COVID-19) epidemic].

OBJECTIVE: To investigate the implementation of schistosomiasis control activities in China during the coronavirus disease 2019 (COVID-19) epidemic, so as to evaluate the impact of COVID-19 epidemic on the national schistosomiasis control program in China. METHODS: On April 2020, 3 counties (districts) were randomly selected from each of the 12 schistosomiasis-endemic provinces (municipality, autonomous region), and a questionnaire survey was conducted to investigate the implementation of schistosomiasis control activities in these counties (districts) from January to March 2020. Then, the impact of the COVID-19 epidemics on the national schistosomiasis control program of China was evaluated using a comparative analysis approach. RESULTS: Among the 36 counties (cities, districts) sampled from 12 provinces (municipality, autonomous region), 66.67% were at a high and medium risk of COVID-19 epidemics. The implementation of schistosomiasis control activities assignment, human schistosomiasis examination and treatment, snail control with chemical treatment and health education reduced by 44.26% to 91.56% as compared to 2019 during the same time period, and the schistosomiasis control program was more affected by COVID-19 in transmission-controlled provinces. The gross funds invested into the schistosomiasis control program reduced by 23.39% in relative to the expected, while the total expenditure increased by 41.22%. In addition, all 36 surveyed counties (districts) considered that the COVID-19 epidemic had a short-term impact on the schistosomiasis control program, with the most predominant impact on schistosomiasis control activities assignment, human resources and monitoring of endemic situation of schistosomiasis. CONCLUSIONS: The COVID-19 epidemics affect the routine schistosomiasis control program across the endemic-foci of China. Policy and financial support should be strengthened to ensure the completion of the schistosomiasis control program.

Core components, concepts and strategies for parasitic and vector-borne disease elimination with a focus on schistosomiasis: A landscape analysis.

Efforts to control and eliminate human schistosomiasis have accelerated over the past decade. In a number of endemic countries and settings, interruption of schistosome transmission has been achieved. In others, Schistosoma infections continue to challenge program managers at different levels, from the complexity of the transmission cycle, over limited treatment options and lack of field-friendly accurate diagnostics, to controversy around adequate intervention strategies. We conducted a landscape analysis on parasitic and vector-borne disease elimination approaches with the aim to identify evidence-based strategies, core components and key concepts for achieving and sustaining schistosomiasis control and for progressing elimination efforts towards interruption of transmission in sub-Saharan Africa. A total of 118 relevant publications were identified from Web of Science, Pubmed and the grey literature and reviewed for their content. In addition, we conducted in-depth interviews with 23 epidemiologists, program managers, policymakers, donors and field researchers. Available evidence emphasizes the need for comprehensive, multipronged and long-term strategies consisting of multiple complementary interventions that must be sustained over time by political commitment and adequate funding in order to reach interruption of transmission. Based on the findings of this landscape analysis, we propose a comprehensive set of intervention strategies for schistosomiasis control and elimination. Before deployment, the proposed interventions will require review, evaluation and validation in the frame of an expert consultation as a step towards adaptation to specific contexts, conditions and settings. Field testing to ensure local relevance and effectiveness is paramount given the diversity of socio-ecological and epidemiological contexts.

Essential oils as molluscicidal agents against schistosomiasis transmitting snails - a review.

This review aims to describe essential oils with bioactivity on adult snails of the genera Bulinus and Biomphalaria, which are intermediate hosts of schistosomes, and brings together information relating to the importance of molluscicides and the chemical composition and toxicity of such oils for other aquatic species. Analysis of the data of original articles revealed that 50 essential oils obtained from 46 plant species were evaluated for molluscicidal activity against the genera cited. More than 80% of the volatile oils studied were active, according to the criteria of the World Health Organization (LC90 or LC100 ≤100 µg/mL or LC50 <40 µg/mL), and most of the oils came from plants belonging to the Rutaceae, Lamiaceae and Pinaceae. Around 37% of the surveyed plant species were obtained in Brazil and 88% of these plants were collected in the northeast of the country, a region with a high prevalence of schistosomiasis mansoni. The essential oils with the highest toxicity against host snails had high levels of hydrocarbon monoterpenes and oxygenated monoterpenes, which may be responsible for the molluscicidal activity. Some volatile components were subjected to molluscicidal evaluation, and the monoterpene compounds exhibited a significant molluscicide effect. This review confirmed the importance of essential oils as a promising alternative for the development of natural molluscicide products. However, in order to be safe for use at sites where schistosome intermediate hosts are found, information on ecotoxicity is required and, to date, few oils have been tested against non-target aquatic species.

Schistosomiasis Consortium for Operational Research and Evaluation: Mission Accomplished.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), a program focusing on schistosomiasis control in sub-Saharan Africa between 2008 and 2019, investigated ways to improve coverage and efficacy of ongoing chemotherapy programs and concluded that because of continued transmission, mass distribution of praziquantel cannot eliminate the disease without complementary control activities. Schistosomiasis Consortium for Operational Research and Evaluation's activities comprised large-scale, multicountry field studies comparing various mass drug administration strategies and some specific research avenues, such as assessment of high-sensitivity diagnostics, identification of hotspots, quantification of the role of the snail host, predictive modeling, and changes in schistosome population genetics under drug pressure. The discoveries made and the insights gained regarding cost-effective strategies for delivering preventive chemotherapy should assist policy makers to develop guidelines for the control and ultimate elimination of schistosomiasis.