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      Alternative strategies for mosquito-borne arbovirus control

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          Abstract

          Background Mosquito-borne viruses—such as Zika, chikungunya, dengue fever, and yellow fever, among others—are of global importance. Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus, mitigation strategies continue to rely on vector control. However, vector control has failed to prevent recent epidemics and arrest expanding geographic distribution of key arboviruses, such as dengue. As a consequence, there has been increasing necessity to further optimize current strategies within integrated approaches and advance development of alternative, innovative strategies for the control of mosquito-borne arboviruses. Methods and findings This review, intended as a general overview, is one of a series being generated by the Worldwide Insecticide resistance Network (WIN). The alternative strategies discussed reflect those that are currently under evaluation for public health value by the World Health Organization (WHO) and represent strategies of focus by globally recognized public health stakeholders as potential insecticide resistance (IR)-mitigating strategies. Conditions where these alternative strategies could offer greatest public health value in consideration of mitigating IR will be dependent on the anticipated mechanism of action. Arguably, the most pressing need for endorsement of the strategies described here will be the epidemiological evidence of a public health impact. Conclusions As the burden of mosquito-borne arboviruses, predominately those transmitted by Aedes aegypti and A. albopictus, continues to grow at a global scale, new vector-control tools and integrated strategies will be required to meet public health demands. Decisions regarding implementation of alternative strategies will depend on key ecoepidemiological parameters that each is intended to optimally impact toward driving down arbovirus transmission.

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          Most cited references116

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          C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector

          The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, mutations of which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.
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            Pesticide Exposure, Safety Issues, and Risk Assessment Indicators

            Pesticides are widely used in agricultural production to prevent or control pests, diseases, weeds, and other plant pathogens in an effort to reduce or eliminate yield losses and maintain high product quality. Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water. Occupational exposure to pesticides often occurs in the case of agricultural workers in open fields and greenhouses, workers in the pesticide industry, and exterminators of house pests. Exposure of the general population to pesticides occurs primarily through eating food and drinking water contaminated with pesticide residues, whereas substantial exposure can also occur in or around the home. Regarding the adverse effects on the environment (water, soil and air contamination from leaching, runoff, and spray drift, as well as the detrimental effects on wildlife, fish, plants, and other non-target organisms), many of these effects depend on the toxicity of the pesticide, the measures taken during its application, the dosage applied, the adsorption on soil colloids, the weather conditions prevailing after application, and how long the pesticide persists in the environment. Therefore, the risk assessment of the impact of pesticides either on human health or on the environment is not an easy and particularly accurate process because of differences in the periods and levels of exposure, the types of pesticides used (regarding toxicity and persistence), and the environmental characteristics of the areas where pesticides are usually applied. Also, the number of the criteria used and the method of their implementation to assess the adverse effects of pesticides on human health could affect risk assessment and would possibly affect the characterization of the already approved pesticides and the approval of the new compounds in the near future. Thus, new tools or techniques with greater reliability than those already existing are needed to predict the potential hazards of pesticides and thus contribute to reduction of the adverse effects on human health and the environment. On the other hand, the implementation of alternative cropping systems that are less dependent on pesticides, the development of new pesticides with novel modes of action and improved safety profiles, and the improvement of the already used pesticide formulations towards safer formulations (e.g., microcapsule suspensions) could reduce the adverse effects of farming and particularly the toxic effects of pesticides. In addition, the use of appropriate and well-maintained spraying equipment along with taking all precautions that are required in all stages of pesticide handling could minimize human exposure to pesticides and their potential adverse effects on the environment.
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              Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

              Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                PLOS Neglected Tropical Diseases
                PLoS Negl Trop Dis
                Public Library of Science (PLoS)
                1935-2735
                January 3 2019
                January 3 2019
                : 13
                : 1
                : e0006822
                Article
                10.1371/journal.pntd.0006822
                583166e6-e53f-406f-be1b-ed7abc3ddebc
                © 2019

                http://creativecommons.org/licenses/by/4.0/

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