@article{hollingsworth_cho_vella_roh_sass_lloyd_brown_2024, title={Economic optimization of <i>Wolbachia</i>-infected <i>Aedes aegypti</i> release to prevent dengue}, volume={4}, ISSN={["1526-4998"]}, DOI={10.1002/ps.8086}, abstractNote={Abstract BACKGROUND Dengue virus, primarily transmitted by the Aedes aegypti mosquito, is a major public health concern affecting ≈3.83 billion people worldwide. Recent releases of Wolbachia ‐transinfected Ae. aegypti in several cities worldwide have shown that it can reduce dengue transmission. However, these releases are costly, and, to date, no framework has been proposed for determining economically optimal release strategies that account for both costs associated with disease risk and releases. RESULTS We present a flexible stochastic dynamic programming framework for determining optimal release schedules for Wolbachia ‐transinfected mosquitoes that balances the cost of dengue infection with the costs of rearing and releasing transinfected mosquitoes. Using an ordinary differential equation model of Wolbachia and dengue in a hypothetical city loosely describing areas at risk of new dengue epidemics, we determined that an all‐or‐nothing release strategy that quickly brings Wolbachia to fixation is often the optimal solution. Based on this, we examined the optimal facility size, finding that it was inelastic with respect to the mosquito population size, with a 100% increase in population size resulting in a 50–67% increase in optimal facility size. Furthermore, we found that these results are robust to mosquito life‐history parameters and are mostly determined by the mosquito population size and the fitness costs associated with Wolbachia . CONCLUSIONS These results reinforce that Wolbachia ‐transinfected mosquitoes can reduce the cost of dengue epidemics. Furthermore, they emphasize the importance of determining the size of the target population and fitness costs associated with Wolbachia before releases occur. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.}, journal={PEST MANAGEMENT SCIENCE}, author={Hollingsworth, Brandon D. and Cho, Chanheung and Vella, Michael and Roh, Hyeongyul and Sass, Julian and Lloyd, Alun L. and Brown, Zachary S.}, year={2024}, month={Apr} }
 @article{vella_gould_lloyd_2021, title={Mathematical modeling of genetic pest management through female-specific lethality: Is one locus better than two?}, volume={14}, ISSN={["1752-4571"]}, url={https://doi.org/10.1111/eva.13228}, DOI={10.1111/eva.13228}, abstractNote={AbstractMany novel genetic approaches are under development to combat insect pests. One genetic strategy aims to suppress or locally eliminate a species through large, repeated releases of genetically engineered strains that render female offspring unviable under field conditions. Strains with this female‐killing characteristic have been developed either with all of the molecular components in a single construct or with the components in two constructs inserted at independently assorting loci. Strains with two constructs are typically considered to be only of value as research tools and for producing solely male offspring in rearing factories which are subsequently sterilized by radiation before release. A concern with the two‐construct strains is that once released, the two constructs would become separated and therefore non‐functional. The only female‐killing strains that have been released in the field without sterilization are single‐construct strains. Here, we use a population genetics model with density dependence to evaluate the relative effectiveness of female‐killing approaches based on single‐ and two‐construct arrangements. We find that, in general, the single‐construct arrangement results in slightly faster population suppression, but the two‐construct arrangement can eventually cause stronger suppression and cause local elimination with a smaller release size. Based on our results, there is no a priori reason that males carrying two independently segregating constructs need to be sterilized prior to release. In some cases, a fertile release would be more efficient for population suppression.}, number={6}, journal={EVOLUTIONARY APPLICATIONS}, publisher={Wiley}, author={Vella, Michael R. and Gould, Fred and Lloyd, Alun L.}, year={2021}, month={Jun}, pages={1612–1622} }
 @article{baltzegar_vella_gunning_vasquez_astete_stell_fisher_scott_lenhart_lloyd_et al._2021, title={Rapid evolution of knockdown resistance haplotypes in response to pyrethroid selection in Aedes aegypti}, volume={7}, ISSN={["1752-4571"]}, DOI={10.1111/eva.13269}, abstractNote={AbstractThis study describes the evolution of knockdown resistance (kdr) haplotypes in Aedes aegypti in response to pyrethroid insecticide use over the course of 18 years in Iquitos, Peru. Based on the duration and intensiveness of sampling (~10,000 samples), this is the most thorough study of kdr population genetics in Ae. aegypti to date within a city. We provide evidence for the direct connection between programmatic citywide pyrethroid spraying and the increase in frequency of specific kdr haplotypes by identifying two evolutionary events in the population. The relatively high selection coefficients, even under infrequent insecticide pressure, emphasize how quickly Ae. aegypti populations can evolve. In our examination of the literature on mosquitoes and other insect pests, we could find no cases where a pest evolved so quickly to so few exposures to low or nonresidual insecticide applications. The observed rapid increase in frequency of resistance alleles might have been aided by the incomplete dominance of resistance‐conferring alleles over corresponding susceptibility alleles. In addition to dramatic temporal shifts, spatial suppression experiments reveal that genetic heterogeneity existed not only at the citywide scale, but also on a very fine scale within the city.}, journal={EVOLUTIONARY APPLICATIONS}, author={Baltzegar, Jennifer and Vella, Michael and Gunning, Christian and Vasquez, Gissella and Astete, Helvio and Stell, Fred and Fisher, Michael and Scott, Thomas W. and Lenhart, Audrey and Lloyd, Alun L. and et al.}, year={2021}, month={Jul} }
 @article{sudweeks_hollingsworth_blondel_campbell_dhole_eisemann_edwards_godwin_howald_oh_et al._2019, title={Locally Fixed Alleles: A method to localize gene drive to island populations}, volume={9}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-019-51994-0}, abstractNote={AbstractInvasive species pose a major threat to biodiversity on islands. While successes have been achieved using traditional removal methods, such as toxicants aimed at rodents, these approaches have limitations and various off-target effects on island ecosystems. Gene drive technologies designed to eliminate a population provide an alternative approach, but the potential for drive-bearing individuals to escape from the target release area and impact populations elsewhere is a major concern. Here we propose the “Locally Fixed Alleles” approach as a novel means for localizing elimination by a drive to an island population that exhibits significant genetic isolation from neighboring populations. Our approach is based on the assumption that in small island populations of rodents, genetic drift will lead to alleles at multiple genomic loci becoming fixed. In contrast, multiple alleles are likely to be maintained in larger populations on mainlands. Utilizing the high degree of genetic specificity achievable using homing drives, for example based on the CRISPR/Cas9 system, our approach aims at employing one or more locally fixed alleles as the target for a gene drive on a particular island. Using mathematical modeling, we explore the feasibility of this approach and the degree of localization that can be achieved. We show that across a wide range of parameter values, escape of the drive to a neighboring population in which the target allele is not fixed will at most lead to modest transient suppression of the non-target population. While the main focus of this paper is on elimination of a rodent pest from an island, we also discuss the utility of the locally fixed allele approach for the goals of population suppression or population replacement. Our analysis also provides a threshold condition for the ability of a gene drive to invade a partially resistant population.}, journal={SCIENTIFIC REPORTS}, author={Sudweeks, Jaye and Hollingsworth, Brandon and Blondel, Dimitri V and Campbell, Karl J. and Dhole, Sumit and Eisemann, John D. and Edwards, Owain and Godwin, John and Howald, Gregg R. and Oh, Kevin P. and et al.}, year={2019}, month={Nov} }