Modeling the efficacy of CRISPR gene drive for schistosomiasis control

CRISPR gene drives could revolutionize the control of infectious diseases by accelerating the spread of engineered traits that limit parasite transmission in wild populations. While much effort has been spent developing gene drives in mosquitoes, gene drive technology in molluscs has received little attention despite the role of freshwater snails as obligate, intermediate hosts of parasitic flukes causing schistosomiasis -- a disease of poverty affecting more than 200 million people worldwide. A successful drive in snails must overcome self-fertilization, which prevents a drive's spread. Simultaneous hermaphroditism is a feature of snails -- distinct from gene drive model organisms -- and is not yet incorporated in gene drive models of disease control. Here we developed a novel population genetic model accounting for snails' sexual and asexual reproduction, susceptibility to parasite infection regulated by multiple alleles, fitness differences between genotypes, and a range of drive characteristics. We then integrated this model with an epidemiological model of schistosomiasis transmission and snail population dynamics. Simulations showed that gene drive establishment can be hindered by a variety of biological and ecological factors, including selfing. However, our model suggests that, under a range of conditions, gene drive mediated immunity in snails could maintain rapid disease reduction achieved by annual chemotherapy treatment of the human population, leading to long-term elimination. These results indicate that gene drives, in coordination with existing public health measures, may become a useful tool to reduce schistosomiasis burden in selected transmission settings with effective CRISPR construct design and close evaluation of the genetic and ecological landscape.

The Use of Jayanti (Sesbania Sesban) Molluscicide in Overcoming Golden Snail, Pest Of Rice Plant in The Village of Bunut Baok, Central Lombok

As a result of the attack golden snails, rice production declined to 30 % in some places in the province of West Nusa Tenggara. Application of science and technology activities for the community ( IbM ) to address the problem of golden snail pest have been conducted in The Village of Bunut Baok, Central Lombok. IbM program conducted by subject matter covers characteristics of jayanti plant (Sesbania sesban ) and its cultivation method, characteristics of golden snail species that is pests of the rice plant, how to prepare and manufacture of jayanti molluscicide, and its application to control rice pest snails. The methods used include lecture, discussion, demonstration and practice. IbM activity followed by 12 members of Farmers Group Mohon Petunjuk Bunut Baok Village. The results of the practice is that the use of 1 ppm solution jayanti leaf can be lethal 48% to 84% of golden snail population. Other results achieved are covering the growing appreciation of farmers to plant jayanti, increasing farmers' knowledge and skills in identifying plants jayanti, skilled to make jayanti molluscicide, and its use to control rice pest golden snails.

Saponin Stabilization via Progressive Freeze Concentration and Sterilization Treatment

Saponin is a biopesticide used to suppress the growth of the golden apple snail population. This study aims to determine the stabilized conditions for saponin storage. The maceration process was used for saponin extraction, and for saponin concentration, progressive freeze concentration (PFC) was used. Afterwards, stability analysis was performed by storing the sample for 21 days in two conditions: Room temperature (26 °C) and cold room (10 °C). The samples kept in a cold room were sterilized samples that undergo thermal treatment by placing the sample in the water bath. The non-sterilized samples were kept in room temperature condition for 21 days. The results showed that saponin stored in the cold room (sterilized sample) has low degradation with higher concentration than those stored at room temperature in stability analysis with the highest saponin concentration (0.730 mg/mL) at a concentration temperature of −6 °C and concentration time of 15 min. The lowest saponin concentration obtained by saponin stored at room temperature (non-sterilized sample) is 0.025 mg/mL at a concentration temperature of −6 °C and concentration time of 10 min. Thus, the finding concluded that saponin is sensitive to temperature. Hence, the best storage condition to store saponin after thermal treatment is to keep it in a cold room at 10 °C.

Schistosomiasis Model Incorporating Snail Predator as Biological Control Agent

Schistosomiasis is a parasitic disease caused by the schistosoma worm. A snail can act as the intermediate host for the parasite. Snail-population control is considered to be an effective way to control schistosomiasis spread. In this paper, we discuss the schistosomiasis model incorporating a snail predator as a biological control agent. We prove that the solutions of the model are non-negative and bounded. The existence condition of equilibrium points is investigated. We determine the basic reproduction number when the predator goes to extinction and when the predator survives. The local stability condition of disease-free equilibrium point is proved using linearization, and the Lienard–Chipart and Routh–Hurwitz criteria. We use center-manifold theory to prove the local stability condition of the endemic equilibrium points. Furthermore, we constructed a Lyapunov function to investigate the global stability condition of the disease-free equilibrium points. To support the analytical results, we presented some numerical simulation results. Our findings suggest that a snail predator as a biological control agent can reduce schistosomiasis prevalence. Moreover, the snail-predator birth rate plays an essential role in controlling schistosomiasis spread.

Population Dynamics of Intermediate-Host Snails in the White Nile River, Sudan: A Year-Round Observational Descriptive Study

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were <i>Biomphalaria pfeifferi</i> and <i>Bulinus truncatus</i>. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated <i>S. mansoni</i> and <i>S. haematobium</i> cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.

Comprehensive Risk Assessment of Schistosomiasis Epidemic Based on Precise Identification of Oncomelania hupensis Breeding Grounds—A Case Study of Dongting Lake Area

Spatio-temporal epidemic simulation, assessment, and risk monitoring serve as the core to establishing and improving the national public health emergency management system. In this study, we investigated Oncomelania hupensis breeding grounds and analyzed the locational and environmental preferences of snail breeding in Dongting Lake (DTL), Hunan, China. Using geographic information systems and remote sensing technology, we identified schistosomiasis risk areas and explored the factors affecting the occurrence and transmission of the disease. Several key conclusions were drawn. (1) From 2006 to 2016, the spatial change of potential O. hupensis breeding risk showed a diminishing trend from the eastern and northern regions to southwest DTL. Environmental changes in the eastern DTL region resulted in the lakeside and hydrophilic agglomerations of the O. hupensis populations. The shift in snail breeding grounds from a fragmented to centralized distribution indicates the weakening mobility of the O. hupensis population, the increasing independence of solitary groups, and the growing dependence of the snail population to the local environment. (2) The spatial risk distribution showed a descending gradient from west Dongting area to the east and an overall pattern of high in the periphery of large lakes and low in other areas. The cold-spot areas had their cores in Huarong County and Anxiang County and were scattered throughout the peripheral areas. The hot-spot areas had their center at Jinshi City, Nanxian County, and the southern part of Huarong County. The areas with increased comprehensive risks changed from centralized and large-scale development to fragmented shrinkage with increased partialization in the core area. The risk distribution’s center shifted to the northwest. The spatial risk distribution exhibited enhanced concentricity along the major axis and increased dispersion along the minor axis.

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.

Modeling schistosomiasis transmission: the importance of snail population structure

Background Schistosomiasis is a neglected tropical disease endemic in 54 countries. A major Schistosoma species, Schistosoma mansoni, is sustained via a life cycle that includes both human and snail hosts. Mathematical models of S. mansoni transmission, used to elucidate the complexities of the transmission cycle and estimate the impact of intervention efforts, often focus primarily on the human host. However, S. mansoni incurs physiological costs in snails that vary with the age of the snail when first infected. Snail demography and the age of snail infection could thus affect the force of infection experienced by humans, which is frequently used to predict the impact of various control strategies. Methods To address how these snail host and parasite interactions influence model predictions, we developed deterministic models of schistosomiasis transmission that include varying complexity in the snail population age structure. Specifically, we examined how model outputs, such as schistosome prevalence in human and snail populations, respond to the inclusion of snail age structure. Results Our models suggest that snail population age structure modifies the force of infection experienced by humans and the relationship between snail infection prevalence and corresponding human infection prevalence. There are significant differences in estimated snail infection, cercarial density and mean worm burden between models without snail population dynamics and those with snail populations, and between models with a homogeneous snail population and those with age stratification. The variation between finely age-stratified snail populations and those grouped into only juvenile and adult life stages is, however, minimal. Conclusions These results indicate that including snails and snail age structure in a schistosomiasis transmission model alters the relationship between snail and human infection prevalence. This highlights the importance of accounting for a heterogeneous intermediate host population in models of schistosomiasis transmission where the impact of proposed control measures is being considered.

Schistosoma transmission in a dynamic seasonal environment and its impact on the effectiveness of disease control

Background A seasonal transmission environment including seasonal variation of snail population density and human-snail contact patterns can affect the dynamics of Schistosoma infection and the success of control interventions. In projecting control outcomes, conventional modeling approaches have often ignored seasonality by using simplified intermediate-host modeling, or by restricting seasonal effects through use of yearly averaging. Methods We used mathematical analysis and numerical simulation to estimate the impact of seasonality on disease dynamics and control outcomes, and to evaluate whether seasonal averaging or intermediate-host reduction can provide reliable predictions of control outcomes. We also examined whether seasonality could be used as leverage in creation of effective control strategies. Results We found models that used seasonal averaging could grossly overestimate infection burden and underestimate control outcomes in highly seasonal environments. We showed that proper intra-seasonal timing of control measures could make marked improvement on the long-term burden reduction for Schistosoma transmission control, and we identified the optimal timing for each intervention. Seasonal snail control, implemented alone, was less effective than mass drug administration, but could provide additive impact in reaching control and elimination targets. Conclusion Seasonal variation makes Schistosoma transmission less sustainable and easier to control than predicted by earlier modeling studies.