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      Forecasting the effectiveness of indoor residual spraying for reducing dengue burden

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          Abstract

          Background

          Historically, mosquito control programs successfully helped contain malaria and yellow fever, but recent efforts have been unable to halt the spread of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a dengue transmission model and results from indoor residual spraying (IRS) field experiments, we investigated how IRS-like campaign scenarios could effectively control dengue in an endemic setting.

          Methods and findings

          In our model, we found that high levels of household coverage (75% treated once per year), applied proactively before the typical dengue season could reduce symptomatic infections by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%]) in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five years of an annual program. Lower coverage had correspondingly lower effectiveness, as did reactive campaigns. Though less effective than preventative campaigns, reactive and even post-epidemic interventions retain some effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting an off-season control opportunity. Regardless, none of the campaign scenarios maintain their initial effectiveness beyond two seasons, instead stabilizing at much lower levels of benefit: in year 20, median effectiveness was only 27.3% (IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful program exposes a population with lowered herd immunity to the same historical threat, and we observed outbreaks more than four-fold larger than pre-intervention outbreaks. These results do not take into account evolving insecticide resistance, thus long-term effectiveness may be lower if new, efficacious insecticides are not developed.

          Conclusions

          Using a detailed agent-based dengue transmission model for Yucatán State, Mexico, we predict that high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied a few months before the typical seasonal epidemic peak. However, vector control succeeds by preventing infections, which precludes natural immunization. Thus, as a population benefits from mosquito control, it gradually loses naturally acquired herd immunity, and the control effectiveness declines; this occurs across all of our modeled scenarios, and is consistent with other empirical work. Long term control that maintains early effectiveness would require some combination of increasing investment, complementary interventions such as vaccination, and control programs across a broad region to diminish risk of importation.

          Author summary

          Using realistic simulation of dengue in the state of Yucatán, Mexico, we show high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied proactively. However, initial success relies on population-level immunity, which declines with reduced infection rates, so simulated IRS campaigns stabilize at much lower effectiveness than initially observed. Moreover, if a campaign then suddenly stops, the model predicts large outbreaks until population immunity recovers. These results suggest that mosquito control could enable elimination in endemic settings, but that natural infections must be replaced, e.g. with vaccination, to achieve that end. Regardless, early campaign years’ performance cannot be assumed representative of longterm benefit, and campaign cost estimates must account for increasing population susceptibility.

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          Most cited references33

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          Dengue, Urbanization and Globalization: The Unholy Trinity of the 21st Century

          Dengue is the most important arboviral disease of humans with over half of the world’s population living in areas of risk. The frequency and magnitude of epidemic dengue have increased dramatically in the past 40 years as the viruses and the mosquito vectors have both expanded geographically in the tropical regions of the world. There are many factors that have contributed to this emergence of epidemic dengue, but only three have been the principal drivers: 1) urbanization, 2) globalization and 3) lack of effective mosquito control. The dengue viruses have fully adapted to a human-Aedes aegypti-human transmission cycle, in the large urban centers of the tropics, where crowded human populations live in intimate association with equally large mosquito populations. This setting provides the ideal home for maintenance of the viruses and the periodic generation of epidemic strains. These cities all have modern airports through which 10s of millions of passengers pass each year, providing the ideal mechanism for transportation of viruses to new cities, regions and continents where there is little or no effective mosquito control. The result is epidemic dengue. This paper discusses this unholy trinity of drivers, along with disease burden, prevention and control and prospects for the future.
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            Epidemiology of dengue: past, present and future prospects

            Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265–420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012–2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective of this paper is to review historical and current epidemiology of dengue worldwide and, additionally, reflect on some potential reasons for expansion of dengue into the future.
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              Research on dengue during World War II.

              A SABIN (1952)
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                June 2018
                25 June 2018
                : 12
                : 6
                : e0006570
                Affiliations
                [1 ] Department of Biology, University of Florida, Gainesville, FL, USA
                [2 ] Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA
                [3 ] Very Good Research & Development, LLC, Gainesville, FL, USA
                [4 ] Department of Epidemiology, University of Florida, Gainesville, FL, USA
                [5 ] Health Systems Research Center, National Institute of Public Health, Cuernavaca, Mexico
                [6 ] Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [7 ] Center for Inference and Dynamics of Infectious Diseases, Seattle, WA, USA
                [8 ] Department of Biostatistics, University of Washington, Seattle, WA, USA
                [9 ] Department of Environmental Sciences, Emory University, Atlanta, GA, USA
                [10 ] Department of Biostatistics, University of Florida, Gainesville, FL, USA
                University of Texas Medical Branch, UNITED STATES
                Author notes

                CABP is the sole proprietor of VGR&D, LLC, a company which prides itself on providing quality, unbiased scientific consulting for hire; it sells no other product or service. All authors declare that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1819-6235
                http://orcid.org/0000-0003-0701-7860
                http://orcid.org/0000-0002-3127-1757
                Article
                PNTD-D-18-00398
                10.1371/journal.pntd.0006570
                6042783
                29939983
                f0e0fc7b-290e-4e94-ac4a-6a2bfb2c87fa
                © 2018 Hladish et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 March 2018
                : 30 May 2018
                Page count
                Figures: 2, Tables: 2, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;
                Award ID: U54 GM111274
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: DEB/EEID: 1640698
                Award Recipient :
                Funded by: Colombian Department of Science and Technology
                Award Recipient :
                This project was funded by a National Institutes of Health/National Institute of General Medical Sciences Grant ( https://www.nih.gov/; U54 GM111274) to MEH, a National Science Foundation Grant ( https://nsf.gov; DEB/EEID: 1640698) to GMVP, and a Fulbright - Colciencias doctoral scholarship ( http://www.fulbright.edu.co) to DPR from the Colombian Department of Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Biology and Life Sciences
                Immunology
                Immunity
                Medicine and Health Sciences
                Immunology
                Immunity
                Biology and Life Sciences
                Agriculture
                Agrochemicals
                Insecticides
                Medicine and Health Sciences
                Infectious Diseases
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Species Interactions
                Disease Vectors
                Insect Vectors
                Mosquitoes
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Arthropoda
                Insects
                Mosquitoes
                Medicine and Health Sciences
                Public and Occupational Health
                Medicine and Health Sciences
                Infectious Diseases
                Infectious Disease Control
                Vaccines
                Research and Analysis Methods
                Simulation and Modeling
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Custom metadata
                vor-update-to-uncorrected-proof
                2018-07-12
                All relevant data are within the paper and its Supporting Information file.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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