Can antibodies against flies alter malaria transmission in birds by changing vector behavior? Suma Ghosh a,b,c,n , Jessica L. Waite a,c , Dale H. Clayton a , Frederick R. Adler a,b a Department of Biology, University of Utah, UT, USA b Department of Mathematics, University of Utah, UT, USA c Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, PA, USA HIGHLIGHTS  Host immune defense against vector.  Change vector behavior.  Affect disease prevalence. article info Article history: Received 15 October 2013 Received in revised form 5 April 2014 Accepted 13 May 2014 Available online 29 May 2014 Keywords: Pairwise interaction Higher order interaction Anti-fly antibodies Avian malaria Vector movement abstract Transmission of insect-borne diseases is shaped by the interactions among parasites, vectors, and hosts. Any factor that alters movement of infected vectors from infected to uninfeced hosts will in turn alter pathogen spread. In this paper, we study one such pathogen–vector–host system, avian malaria in pigeons transmitted by fly ectoparasites, where both two-way and three-way interactions play a key role in shaping disease spread. Bird immune defenses against flies can decrease malaria prevalence by reducing fly residence time on infected birds or increase disease prevalence by enhancing fly movement and thus infection transmission. We develop a mathematical model that illustrates how these changes in vector behavior influence pathogen transmission and show that malaria prevalence is maximized at an intermediate level of defense avoidance by the flies. Understanding how host immune defenses indirectly alter disease transmission by influencing vector behavior has implications for reducing the transmission of human malaria and other vectored pathogens. Published by Elsevier Ltd. 1. Introduction Species interactions in ecological communities create the net- work of influences that different species have on one another (Abrams, 1987). The population dynamics and behavior of any one species can directly or indirectly affect the community as a whole. Most simply, we can think of a community as a set of two-way interactions between species that directly affect each other. How- ever, these direct pairwise interactions can be modified by the presence or density of other species (Adler and Morris, 1994), generating three-way or even higher-order interactions (Dungan, 1986; Billick and Case, 1994; Wootton, 1994). These interactions define the role that species play within communities and create the potentially complex chains by which they positively or negatively affect the species around them. Although pathogens are necessarily involved in a pairwise interaction with their hosts, those with multiple hosts can find themselves embedded in complex of higher-order interactions. Among the most widespread of these are pathogens transmitted by arthropod vectors in wildlife, agricultural, and human commu- nities. The full suite of interactions that regulate host–vector– pathogen dynamics shape vector-borne disease transmission, and thus pathogen prevalence, in the host community. This transmis- sion involves a triangle (Fig. 1) of pairwise interactions between parasites or pathogens, vectors, and vertebrate hosts. Movement of infected vectors from infected to uninfected hosts plays a central role in pathogen spread, and any factor that affects this movement has the potential to generate a higher-order interaction. In this paper, we study one such pathogen–vector–host system where complex three-way interactions play key roles in control- ling disease spread. Many species of haemosporidian parasites infect birds, including Plasmodium and related genera which are Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/yjtbi Journal of Theoretical Biology http://dx.doi.org/10.1016/j.jtbi.2014.05.020 0022-5193/Published by Elsevier Ltd. n Corresponding author at: Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, PA, USA. E-mail address: sug25@psu.edu (S. Ghosh). Journal of Theoretical Biology 358 (2014) 93–101