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An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections

View ORCID ProfileT. Alex Perkins, Robert C. Reiner, Guido España, Quirine A. ten Bosch, Amit Verma, Kelly A. Liebman, Valerie A. Paz-Soldan, John P. Elder, Amy C. Morrison, Steven T. Stoddard, Uriel Kitron, Gonzalo M. Vazquez-Prokopec, Thomas W. Scott, David L. Smith
doi: https://doi.org/10.1101/082396
T. Alex Perkins
1Department of Biological Sciences and Eck Institute for Global Health, Universityof Notre Dame, Notre Dame, IN
2Fogarty International Center, National Institutes of Health, Bethesda, MD
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  • ORCID record for T. Alex Perkins
  • For correspondence: taperkins@nd.edu
Robert C. Reiner
2Fogarty International Center, National Institutes of Health, Bethesda, MD
3Department of Epidemiology and Biostatistics, Indiana University, Bloomington, IN
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Guido España
1Department of Biological Sciences and Eck Institute for Global Health, Universityof Notre Dame, Notre Dame, IN
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Quirine A. ten Bosch
1Department of Biological Sciences and Eck Institute for Global Health, Universityof Notre Dame, Notre Dame, IN
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Amit Verma
4Center for Disease Dynamics, Economics, and Policy, Washington, DC
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Kelly A. Liebman
5Department of Entomology and Nematology, University of California, Davis, CA
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Valerie A. Paz-Soldan
6Department of Global Community Health and Behavioral Sciences, Tulane UniversitySchool of Public Health and Tropical Medicine, New Orleans, LA
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John P. Elder
7Institute for Behavioral and Community Health, Graduate School of Public Health,San Diego State University, San Diego, CA
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Amy C. Morrison
5Department of Entomology and Nematology, University of California, Davis, CA
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Steven T. Stoddard
7Institute for Behavioral and Community Health, Graduate School of Public Health,San Diego State University, San Diego, CA
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Uriel Kitron
2Fogarty International Center, National Institutes of Health, Bethesda, MD
8Department of Environmental Sciences, Emory University, Atlanta, GA
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Gonzalo M. Vazquez-Prokopec
2Fogarty International Center, National Institutes of Health, Bethesda, MD
8Department of Environmental Sciences, Emory University, Atlanta, GA
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Thomas W. Scott
2Fogarty International Center, National Institutes of Health, Bethesda, MD
5Department of Entomology and Nematology, University of California, Davis, CA
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David L. Smith
2Fogarty International Center, National Institutes of Health, Bethesda, MD
9Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA
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ABSTRACT

Given the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia® from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) “statistical uncertainty” about the numerical value of the vaccine’s efficacy against disease, and (2) “biological uncertainty” about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia® took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccine’s public health impact.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 11, 2018.
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An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections
T. Alex Perkins, Robert C. Reiner, Guido España, Quirine A. ten Bosch, Amit Verma, Kelly A. Liebman, Valerie A. Paz-Soldan, John P. Elder, Amy C. Morrison, Steven T. Stoddard, Uriel Kitron, Gonzalo M. Vazquez-Prokopec, Thomas W. Scott, David L. Smith
bioRxiv 082396; doi: https://doi.org/10.1101/082396
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An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections
T. Alex Perkins, Robert C. Reiner, Guido España, Quirine A. ten Bosch, Amit Verma, Kelly A. Liebman, Valerie A. Paz-Soldan, John P. Elder, Amy C. Morrison, Steven T. Stoddard, Uriel Kitron, Gonzalo M. Vazquez-Prokopec, Thomas W. Scott, David L. Smith
bioRxiv 082396; doi: https://doi.org/10.1101/082396

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