title: Integrating Transgenic Vector Manipulation with Clinical Interventions to Manage Vector-Borne Diseases.
abstract: Many vector-borne diseases lack effective vaccines and medications, and the limitations of traditional vector control have inspired novel approaches based on using genetic engineering to manipulate vector populations and thereby reduce transmission. Yet both the short- and long-term epidemiological effects of these transgenic strategies are highly uncertain. If neither vaccines, medications, nor transgenic strategies can by themselves suffice for managing vector-borne diseases, integrating these approaches becomes key. Here we develop a framework to evaluate how clinical interventions (i.e., vaccination and medication) can be integrated with transgenic vector manipulation strategies to prevent disease invasion and reduce disease incidence. We show that the ability of clinical interventions to accelerate disease suppression can depend on the nature of the transgenic manipulation deployed (e.g., whether vector population reduction or replacement is attempted). We find that making a specific, individual strategy highly effective may not be necessary for attaining public-health objectives, provided suitable combinations can be adopted. However, we show how combining only partially effective antimicrobial drugs or vaccination with transgenic vector manipulations that merely temporarily lower vector competence can amplify disease resurgence following transient suppression. Thus, transgenic vector manipulation that cannot be sustained can have adverse consequences-consequences which ineffective clinical interventions can at best only mitigate, and at worst temporarily exacerbate. This result, which arises from differences between the time scale on which the interventions affect disease dynamics and the time scale of host population dynamics, highlights the importance of accounting for the potential delay in the effects of deploying public health strategies on long-term disease incidence. We find that for systems at the disease-endemic equilibrium, even modest perturbations induced by weak interventions can exhibit strong, albeit transient, epidemiological effects. This, together with our finding that under some conditions combining strategies could have transient adverse epidemiological effects suggests that a relatively long time horizon may be necessary to discern the efficacy of alternative intervention strategies.
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America.|Yale Institute for Biospheric Studies, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Kenichi W
authors.initials: KW
authors.lastname: Okamoto
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America.|Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Fred
authors.initials: F
authors.lastname: Gould
authors.affiliation: Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.|Department of Mathematics and Biomathematics, Graduate Program, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Alun L
authors.initials: AL
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy / Q000379:methods; D003141:Communicable Diseases / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D003198:Computer Simulation; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D007303:Insect Vectors / Q000235:genetics*; D008957:Models, Genetic; D016896:Treatment Outcome