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Gene drives for schistosomiasis transmission control.

ABSTRACT: Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites' intermediate snail hosts are a crucial part of the integrated strategy required to move toward disease elimination. The recent revolution in gene drive technology naturally leads to questions about whether gene drives could be used to efficiently spread schistosome resistance traits in a population of snails and whether gene drives have the potential to contribute to reduced disease transmission in the long run. Responsible implementation of gene drives will require solutions to complex challenges spanning multiple disciplines, from biology to policy. This Review Article presents collected perspectives from practitioners of global health, genome engineering, epidemiology, and snail/schistosome biology and outlines strategies for responsible gene drive technology development, impact measurements of gene drives for schistosomiasis control, and gene drive governance. Success in this arena is a function of many factors, including gene-editing specificity and efficiency, the level of resistance conferred by the gene drive, how fast gene drives may spread in a metapopulation over a complex landscape, ecological sustainability, social equity, and, ultimately, the reduction of infection prevalence in humans. With combined efforts from across the broad global health community, gene drives for schistosomiasis control could fortify our defenses against this devastating disease in the future.

SUBMITTER: Maier T

PROVIDER: S-EPMC6922350 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Gene drives for schistosomiasis transmission control.

Maier Theresa T Wheeler Nicolas James NJ Namigai Erica K O EKO Tycko Josh J Grewelle Richard Ernest RE Woldeamanuel Yimtubezinash Y Klohe Katharina K Perez-Saez Javier J Sokolow Susanne H SH De Leo Giulio A GA Yoshino Timothy P TP Zamanian Mostafa M Reinhard-Rupp Jutta J

PLoS neglected tropical diseases 20191219 12

Schistosomiasis is one of the most important and widespread neglected tropical diseases (NTD), with over 200 million people infected in more than 70 countries; the disease has nearly 800 million people at risk in endemic areas. Although mass drug administration is a cost-effective approach to reduce occurrence, extent, and severity of the disease, it does not provide protection to subsequent reinfection. Interventions that target the parasites' intermediate snail hosts are a crucial part of the ...[more]

PMID: 31856157

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Project description:Schistosomiasis is a chronic but preventable disease that affects 260 million people worldwide. In the Philippines, 860,000 people are afflicted with Schistosoma japonicum annually, and another 6.7 million live in endemic areas. The disease's complex epidemiology as well as the influence of poverty in endemic areas demand an integrated, multi-sectoral approach to disease control. Results from behavioral or sociocultural studies on schistosomiasis could improve the content and impact of schistosomiasis control in rural villages in the Philippines. We investigated knowledge, attitudes and practices related to schistosomiasis transmission and control in an endemic village in Leyte Province, Philippines. We administered a questionnaire to 219 participants covering 1) knowledge and attitudes related to schistosomiasis, its symptoms, and its transmission; 2) attitudes and practices in relation to schistosomiasis prevention; 3) willingness to comply with public health control programs; and 4) whether the respondent had previously contracted schistosomiasis. Responses revealed fairly high measures of schistosomiasis knowledge (mean 17.0 out of 23 questions, range 6-23), but also inconsistent disease prevention behavior. A high proportion of participants (72.6%, n = 159) reported previous disease. Participant belief in the preventability of schistosomiasis was revealed to be a key attitude, as carabao owners who believed in prevention were over five times more likely to be willing to vaccinate their carabaos (OR = 5.24, 95% CI 1.20-27.68, P = 0.04). Additionally, participants who did not believe in prevention were about twice as likely to report previous disease (OR = 2.31, 95% CI 1.02-5.63, P = 0.05). Our results suggest that future public health interventions should address barriers to disease-preventing behavior, as well as maintaining community belief in disease prevention. Comprehensive disease control programs should be supplemented by sociocultural and behavioral context in order to improve their impact in endemic communities.

Project description:BackgroundSchistosomiasis 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.MethodsTo 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.ResultsOur 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.ConclusionsThese 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.

Project description:Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections.We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection.The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period.

Project description:BackgroundDespite twelve rounds of school-based preventive chemotherapy for schistosomiasis in endemic areas of Tanzania such as Mtama district, Lindi: the burden of Schistosoma haematobium infection has remained highly conceivable due to re-infections. The factors associated with continuity of S.haematobium transmission in Mtama district, Lindi have not been fully established. This study investigated the burden and factors contributing to the ongoing transmission of S.haematobium infection in the endemic district of Mtama, Lindi.MethodsA quantitative cross-sectional survey was carried out among 649 school-age children in the Mtama district to determine the burden and factors associated with continuity of S.haematobium infection transmission. A single urine specimen was obtained from each pupil and tested for macro- and microhaematuria, presence of S.haematobium ova, as well intensity of infection; this was complemented with a survey of Bulinus spp snail intermediate hosts and their infectivity. A structured questionnaire was employed to gather information on individual and environmental risk factors for S.haematobium transmission. Summary statistics were computed for individual variables; while a univariate and multivariate logistic regression analysis was performed to assess the association between risk factors with S.haematobium infection.ResultsPrevalence of S.haematobium infection by macro- and microhaematuria was 13.1% and 46.2% respectively. The prevalence of S.haematobium ova was 52.7%; intensity of infection was light in 53.1%, and heavy in 46.9%. Snail intermediate hosts were Bulinus globosus and B.nasutus, whose infectivity was 2.2% and 1.3%, respectively. Among the assessed risk factors, long residency (10-13 years) in the area was a significant risk factor for the continuity of S.haematobium transmission (AOR: 21.79, 95% CI: 1.37-346.4).ConclusionsThe observed 52.7% prevalence of S.haematobium infection represents unacceptably high prevalence after 12 rounds of preventive chemotherapy. Therefore, an urgent need for the implementation of integrated multiple control interventions in the Mtama district; is considered to be imperative.

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Gene drives for schistosomiasis transmission control.

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Gene drives for schistosomiasis transmission control.

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