Predation-driven spillover : Pathogen bioaccumulation in top predators

Title 1 2 Predation-driven spillover: Pathogen bioaccumulation in top predators. 3 4 Authors: 5 6 Jennifer Malmberg,1 Lauren White,2,3 and Sue VandeWoude4 7 1Department of Veterinary Sciences, University of Wyoming, Wyoming State Veterinary 8 Laboratory, Laramie, WY, USA, 82070, www.malmberglab.org 9 2National Socio-Environmental Synthesis Center, University of Maryland, Annapolis, MD, USA, 1

agents. Epizootics with high morbidity and mortality have been recorded following prey-to-23 predator spillover events with significant conservation implications, particularly for sensitive 24 species. However, relatively few virulent infections following prey consumption are reported, 25 given the very large number of exposures that presumably occur. Further, many transmitted 26 agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine 27 outcome of predator exposure to prey-based pathogens therefore represent an important, 28 understudied component of disease dynamics that should be considered in modeling approaches 29 and empirical research to better understand disease risk and emergence, particularly in 30 vulnerable or threatened species. 31

Main Text 32
Spillover (see Glossary) as a phenomenon has taken on urgent significance due to the emergence 33 of important diseases such as highly pathogenic avian influenza in North America, African swine 34 fever in Asia and Eastern Europe, Ebola in Western and Central Africa, Hendra in Australia, and 35 most recently the COVID-19 pandemic. Depending on the mode of transmission, host-switching 36 events are dependent on proximity and interaction between a reservoir host and a new 37 susceptible host species. Predation is one mechanism by which intraspecific contact occurs 38 naturally by exposing predators to potential pathogens of prey species as a consequence of 39 normal feeding behavior. While bioaccumulation of toxicants has been recognized as a 40 significant risk to species at the top of food chains, little research describes the potential for 41 predators to acquire or evade infectious diseases following exposure during hunting, capture, and 42 ingestion of prey. This opinion piece examines this omission and provides recommendations for 43 consideration of prey-to-predator spillover risk as an important but overlooked aspect of 44 conservation medicine and predator ecology. 45 46 Spillover risk during predator-prey interactions 47 Pathogen spillover, i.e., transmission of a pathogen from a reservoir host to a novel host, is a 48 widely understood concept, particularly as it relates to emerging zoonotic diseases.  transmission occurs in species besides humans, resulting in major threats to wildlife survival and 50 biodiversity (e.g., distemper in African lions [Panthera leo] [1], plague and distemper in black-51 footed ferrets [Mustela nigripes] [2, 3]), and disruption of agricultural industries (e.g., African 52 swine fever [4], avian influenza [5]). The ecological determinants of spillover have been 53 described as a series of permeable barriers that prevent infection of one host species by another 54 [6,7]. While there is much variability across host-pathogen systems, the initial mechanistic 55 barrier for all systems is sufficient contact for pathogen transmission. Predator-prey interactions 56 bring both closely and distantly related host species into close contact, creating opportunities to 57 surmount the initial barrier to spillover infection. 58

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The concept of predators bioaccumulating toxins has been considered extensively [8], so the 60 observation that predators "bioaccumulate" pathogens should not be surprising. However, there 61 is a paucity of literature that estimates the risk of predators as spillover recipients based upon 62 their prey-consumption behavior, and a surprising lack of scholarly work that has directly 63 evaluated this phenomenon. Table 1 lists fifteen examples of prey to predator spillover that have 64 been well characterized by experimental or observational studies, with a variety of outcomes for 65 the predator. Because the outcome of a predator-prey interaction would nearly always result in 66 survival of the predator versus the prey, spillover from these encounters would therefore be of 67 consequence only to the predator. 68 69

Outcomes of spillover transmission 70
The majority of well-publicized spillover events result in catastrophic consequences to the new 71 host, as these infections result in significant economic or conservation impacts. Recent studies 72 indicate, however, that cross-species transmission frequently occurs without substantial 73 population-level impacts to the recipient host. In the case of predation, a number of disease 74 outcomes may result following predator consumption of prey harboring a potential spillover 75 agent (i.e. consumption of a reservoir host), illustrated in Figure 1 and Table 1. These range 76 from no infection in the predator, to adaptation and replication of the pathogen in the predator 77 host, and transmission within the predator population, with either virulent or avirulent outcomes. 78 79 New advances in molecular technologies, including next generation sequencing and sensitive 80 serosurveillance, have afforded opportunities for detection of microparasites from free-ranging 81 wildlife [9-12]. Protocols permitting detection of pathogens in excreta have been perfected, 82 allowing noninvasive sampling techniques that augment sample collection protocols that would 83 otherwise be invasive, expensive, and potentially harmful to either animals or field personnel 84 Our analysis of disease transmission among domestic and nondomestic felids using highly 91 sensitive molecular methods has caused us to observe repeatedly that predator hosts are at risk 92 for pathogen spillover from prey species, and that both symptomatic and asymptomatic cross-93 species transmission events can be readily documented from subordinate to apex host (i.e., FFV, 94 interactions result in potential for successful spillover (Figure 1B, 2); however, in most cases 96 mechanisms driving predator-prey disease transmission outcomes have not been determined. opportunities for cross-species transmission, thereby increasing the potential for spillover 119 epidemics. Further, these changes also create opportunities for predator superinfection and 120 emergence of novel pathogen strains. 121

Conservation impact of prey-transmitted infections 123
Management of infectious disease in wildlife is a paramount modern conservation challenge.  Table 1 highlight the conservation implications of this topic, and 163 underscore a need for further assessment of the ecological and biological relationships between 164 predators and prey-harbored pathogens. 165

Mechanistic modeling of spillover risk to predators 166
Disease modeling is one possible avenue to evaluate and explore the risk of spillover from prey 167 to predators. However, mechanistic models of infectious diseases focusing on pathogen 168 spillover and emergence are still uncommon [7,46]. The majority of existing theory for 169 predator-prey systems stems from community ecology, and explores the potential of predation Another recent model suggests that generalist predators are better able to evade consequences 189 of infectious disease as compared to specialist predators, and that prey species may effectively 190 use pathogens to deter susceptible predators [56]. Future extensions of these types of 191 frameworks could explore feedbacks of predation-driven mortality and transmission, as well as 192 the degree of specialization of the predator, as illustrated in Figure 3. 193

Mechanisms underlying predator resistance 194
There are few studies that provide evidence of mechanisms that have evolved to limit predator 195 susceptibility to the large load of microparasites that are ingested every time a meal is taken. 196 As in the case of modeling prey to predator spillover, there is more scholarly activity invested 197 in examining how predation impacts the immune system, stress, and disease susceptibility in has not been well-studied, it is possible that such food hoarding behavior may result in 218 degradation of potential pathogens prior to ingestion. There is substantial evidence that 219 immune or resistance genes evolve to combat specific pathogens; coincidently, pathogens are 220 also under strong evolutionary pressure to adapt to hostile host environments-a circumstance 221   consumes an infectious donor, they also move into an exposed class (RE). Based on within-host 284 processes, exposed recipients have a probability, p, of becoming infectious from direct contact or 285 predation of the donor host. We assume that the latent period is comparatively short, such that 286 susceptible and infectious recipients drive predation events. We further assume that the donors 287 are not the only prey species for the recipient, and so we loosen the direct dependence of the 288 recipient population on donor density by assuming logistic growth for donor and recipient 289 populations. This logistic growth is governed by species-specific growth rates (e.g., rD and rR) 290 and carrying capacities (e.g., KD and KR). Infectious subclasses also have constant mortality rates 291 that are species-specific (e.g., mDI vs. mRI).