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      An economic evaluation of Wolbachia deployments for dengue control in Vietnam

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          Abstract

          Introduction

          Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the benefits of such an intervention at a large scale. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam–targeted at the highest burden urban areas.

          Methods

          Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). The effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases was assumed to be 75%. We assumed that the intervention would maintain this effectiveness for at least 20 years (but tested this assumption in the sensitivity analysis). A cost-utility analysis and cost-benefit analysis were conducted.

          Results

          From the health sector perspective, the Wolbachia intervention was projected to cost US$420 per disability-adjusted life year (DALY) averted. From the societal perspective, the overall cost-effectiveness ratio was negative, i.e. the economic benefits outweighed the costs. These results are contingent on the long-term effectiveness of Wolbachia releases being sustained for 20 years. However, the intervention was still classed as cost-effective across the majority of the settings when assuming only 10 years of benefits

          Conclusion

          Overall, we found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains.

          Author summary

          Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the health and economic benefits of such an intervention at a large scale, as well as its value for money. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam–targeted at the highest burden urban areas. Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). We assumed that the effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases would be 75%. We found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains. Overall, this work highlights the value of investment in the scaled implementation of Wolbachia deployments as an effective and cost-effective tool for dengue control in Vietnam, and more generally for addressing the global challenge of dengue control.

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          Most cited references32

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          The global distribution and burden of dengue

          Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes 1 . For some patients dengue is a life-threatening illness 2 . There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread 3 . The contemporary worldwide distribution of the risk of dengue virus infection 4 and its public health burden are poorly known 2,5 . Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanisation. Using cartographic approaches, we estimate there to be 390 million (95 percent credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of clinical or sub-clinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization 2 . Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help guide improvements in disease control strategies using vaccine, drug and vector control methods and in their economic evaluation. [285]
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            The current and future global distribution and population at risk of dengue

            Dengue is a mosquito-borne viral infection that has spread throughout the tropical world over the past 60 years and now affects over half the world’s population. The geographical range of dengue is expected to further expand due to ongoing global phenomena including climate change and urbanization. We applied statistical mapping techniques to the most extensive database of case locations to date to predict global environmental suitability for the virus as of 2015. We then made use of climate, population and socioeconomic projections for the years 2020, 2050 and 2080 to project future changes in virus suitability and human population at risk. This study is the first to consider the spread of Aedes mosquito vectors to project dengue suitability. Our projections provide a key missing piece of evidence for the changing global threat of vector-borne disease and will help decision-makers worldwide to better prepare for and respond to future changes in dengue risk.
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              Country-Level Cost-Effectiveness Thresholds: Initial Estimates and the Need for Further Research

              Background Cost-effectiveness analysis can guide policymakers in resource allocation decisions. It assesses whether the health gains offered by an intervention are large enough relative to any additional costs to warrant adoption. When there are constraints on the health care system’s budget or ability to increase expenditures, additional costs imposed by interventions have an “opportunity cost” in terms of the health foregone because other interventions cannot be provided. Cost-effectiveness thresholds (CETs) are typically used to assess whether an intervention is worthwhile and should reflect health opportunity cost. Nevertheless, CETs used by some decision makers—such as the World Health Organization that suggested CETs of 1 to 3 times the gross domestic product (GDP) per capita—do not. Objectives To estimate CETs based on opportunity cost for a wide range of countries. Methods We estimated CETs based on recent empirical estimates of opportunity cost (from the English National Health Service), estimates of the relationship between country GDP per capita and the value of a statistical life, and a series of explicit assumptions. Results CETs for Malawi (the country with the lowest income in the world), Cambodia (with borderline low/low-middle income), El Salvador (with borderline low-middle/upper-middle income), and Kazakhstan (with borderline high-middle/high income) were estimated to be $3 to $116 (1%–51% GDP per capita), $44 to $518 (4%–51%), $422 to $1967 (11%–51%), and $4485 to $8018 (32%–59%), respectively. Conclusions To date, opportunity-cost-based CETs for low-/middle-income countries have not been available. Although uncertainty exists in the underlying assumptions, these estimates can provide a useful input to inform resource allocation decisions and suggest that routinely used CETs have been too high.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Writing – original draft
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLOS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                30 May 2023
                May 2023
                : 17
                : 5
                : e0011356
                Affiliations
                [1 ] MRC Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, United Kingdom
                [2 ] World Mosquito Program, Ho Chi Minh City, Vietnam
                [3 ] World Mosquito Program, Monash University, Clayton, Australia
                [4 ] Department of Preventive Medicine, Ministry of Health, Hanoi, Vietnam
                Louisiana State University, UNITED STATES
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: HCT received funding from the World Mosquito Program to conduct this analysis. DLQ, RD, CPS and KLA are employees of the World Mosquito Program. PTH has declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-8428-3874
                Article
                PNTD-D-23-00238
                10.1371/journal.pntd.0011356
                10256143
                37253037
                0eef43c5-2bb9-4ac0-9a2d-a2c74984bd7e
                © 2023 Turner 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
                : 22 February 2023
                : 6 May 2023
                Page count
                Figures: 2, Tables: 3, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000265, Medical Research Council;
                Award ID: MR/R015600/1
                Award Recipient :
                HCT has received funding from the World Mosquito Program (WMP) to conduct this analysis. HCT acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. KLA, CPS, RD and DLQ acknowledge funding from the Wellcome Trust for this work (224459/Z/21/Z). 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
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Dengue Fever
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Dengue Fever
                Biology and Life Sciences
                Organisms
                Bacteria
                Wolbachia
                Social Sciences
                Economics
                Health Economics
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                Health Economics
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                Economic Analysis
                Cost-Effectiveness Analysis
                People and Places
                Geographical Locations
                Asia
                Vietnam
                Medicine and Health Sciences
                Epidemiology
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                Medical Conditions
                Infectious Diseases
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                Biology and Life Sciences
                Species Interactions
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                Biology and Life Sciences
                Zoology
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                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Arthropoda
                Insects
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                Biology and Life Sciences
                Zoology
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                Invertebrates
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                Biology and Life Sciences
                Physiology
                Physiological Parameters
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                Custom metadata
                vor-update-to-uncorrected-proof
                2023-06-09
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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