Bioaccumulation of Pathogen Exposure in Top Predators
Authors: Jennifer L. Malmberg, Lauren A. White, Sue VandeWoude
Journal: Trends in Ecology & Evolution (2021)

Advances in pathogen detection technologies have allowed more thorough characterization of infections in free-ranging wildlife.In well-studied predators like Puma concolor, multiple occurrences of spillover following consumption of reservoir hosts as prey have been observed.Outcomes of predator exposures to infectious agents harbored by prey vary, but rarely result in widespread disease.Models of disease transmission have largely considered predator behavior in the context of effects in the prey species, versus consequences to the predator.However, certain prey-transmitted infections can result in high mortality rates, sometimes with significant negative impacts on conservation of vulnerable/threatened species. Predator–prey interactions present heightened opportunities for pathogen spillover, as predators are at risk of exposure to infectious agents harbored by prey. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events, which have had significant conservation implications for sensitive species. Using felids as a detailed case study, we have documented both virulent and clinically silent infections in apex predators following transfer of microbes from prey. We draw on these examples and others to examine the mechanisms that determine frequency and outcome of predator exposure to prey-based pathogens. We propose that predator–prey dynamics should be more thoroughly considered in empirical research and disease dynamic modeling approaches in order to reveal answers to outstanding questions relating to pathogen bioaccumulation. Predator–prey interactions present heightened opportunities for pathogen spillover, as predators are at risk of exposure to infectious agents harbored by prey. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events, which have had significant conservation implications for sensitive species. Using felids as a detailed case study, we have documented both virulent and clinically silent infections in apex predators following transfer of microbes from prey. We draw on these examples and others to examine the mechanisms that determine frequency and outcome of predator exposure to prey-based pathogens. We propose that predator–prey dynamics should be more thoroughly considered in empirical research and disease dynamic modeling approaches in order to reveal answers to outstanding questions relating to pathogen bioaccumulation. Bioaccumulation (see Glossary) of toxicants is recognized as a significant risk to species at the top of food chains [1.Rattner B.A. History of wildlife toxicology.Ecotoxicology. 2009; 18: 773-783Crossref PubMed Scopus (72) Google Scholar]. By contrast, the cumulative or additive impacts of exposure to infectious agents resulting from predatory behavior has not been widely considered. Exposures to parasites during hunting, capture, and ingestion of prey accumulate over a predator's lifetime, posing a risk for the burden of infectious agents to exceed a clinically significant dose or pathogen load, potentially resulting in spillover infection. Furthermore, hunting and feeding behaviors expose predators to an increasing number and variety of infectious agents with time, presenting an opportunity for predator superinfection (i.e., infection with multiple pathogen strains), synergistic co-infection, and/or the emergence of new genetic variants that arise through recombination or other means [2.Wrangham R. et al.Chimpanzee predation and the ecology of microbial exchange.Microb. Ecol. 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Spillover may result in catastrophic consequences to the new host, resulting in significant economic [4.Hosono H. et al.Economic impact of Nipah virus infection outbreak in Malaysia.in: Proceedings of the 11th International Society for Veterinary Epidemiology and Economics. 2006Google Scholar,5.Zinsstag J. et al.Economics of bovine tuberculosis.in: Thoen C.O. Mycobacterium bovis Infection in Animals and Humans. 2nd edn. Wiley & Sons, 2006: 68-83Crossref Scopus (47) Google Scholar] or conservation [6.Chiu E.S. et al.Multiple introductions of domestic cat feline leukemia virus in endangered Florida panthers.Emerg. Infect. Dis. 2019; 25: 92Crossref PubMed Scopus (21) Google Scholar, 7.Meli M.L. et al.Feline leukemia virus infection: a threat for the survival of the critically endangered Iberian lynx (Lynx pardinus).Vet. Immunol. 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B. 2019; 37420180435Crossref PubMed Scopus (20) Google Scholar, 16.Plowright R.K. et al.Pathways to zoonotic spillover.Nat. Rev. Microbiol. 2017; 15: 502-510Crossref PubMed Scopus (355) Google Scholar, 17.Viana M. et al.Assembling evidence for identifying reservoirs of infection.Trends Ecol. Evol. 2014; 29: 270-279Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar], predation has not been directly implicated as a risk factor. A number of disease outcomes may result following predation on prey harboring a potential spillover agent (i.e., consumption of a reservoir host), illustrated in Figure 1. Table 1 highlights 15 well-characterized examples of predator exposure to prey-based infectious agents with a variety of outcomes. These range from no infection in the predator; for example, fecal shedding of infectious prions following carnivore ingestion of cervids with chronic wasting disease (CWD) [18.Nichols T.A. et al.CWD prions remain infectious after passage through the digestive system of coyotes (Canis latrans).Prion. 2015; 9: 367-375Crossref PubMed Scopus (24) Google Scholar], to adaptation and replication of the pathogen in the predator host, and transmission within the predator population, with either virulent or avirulent outcomes. Pathogen characteristics are diverse in these examples, which include both generalist (e.g., rabies) and specialist (e.g., feline leukemia) viruses, bacteria, protozoa, and prions. Predator characteristics, however, trend toward strictly carnivorous mammalian predators, many of which consume smaller mammals (e.g., parvoviruses in wild canids and felids [19.Behdenna A. et al.Transmission ecology of canine parvovirus in a multi-host, multi-pathogen system.Phil. Trans. R. Soc. Lon. B. 2019; 28620182772Google Scholar,20.Steinel A. et al.Parvovirus infections in wild carnivores.J. Wildl. Dis. 2001; 37: 594-607Crossref PubMed Scopus (150) Google Scholar]) or ungulates (e.g., bovine tuberculosis in coyotes [21.Atwood T.C. et al.Coyotes as sentinels for monitoring bovine tuberculosis prevalence in white-tailed deer.J. Wildl. Manag. 2007; 71: 1545-1554Crossref Scopus (12) Google Scholar] and anthrax in wolves [22.Blackburn J.K. et al.Dances with anthrax: Wolves (Canis lupus) kill anthrax bacteremic plains bison (Bison bison) in southwestern Montana.J. Wildl. Dis. 2014; 50: 393-396Crossref PubMed Scopus (19) Google Scholar]).Table 1Spillover of Pathogens from Prey to Predator Is a Common OccurrenceaEvidence for predation as the putative route of transmission is based upon observation, experimental studies, and/or phylogenetic analysis. Sections are organized to correspond to infection outcomes in the predator.AgentPredatorPreyOutcome of spillover in the predatorEvidence for transmission routeRefsNonproductive infectionPrion (PrPCWD/chronic wasting disease)Coyote (Canis latrans)Deer (Odocoileus virginianus and Odocoileus hemionus), elk (Cervus elaphus), and moose (Alces alces)Nonproductive infection, but with fecal shedding of infectious prionsExperimental[18.Nichols T.A. et al.CWD prions remain infectious after passage through the digestive system of coyotes (Canis latrans).Prion. 2015; 9: 367-375Crossref PubMed Scopus (24) Google Scholar]Productive subclinical infectionFIVPuma(Puma concolor)Bobcat(Lynx rufus)Productive subclinical infectionPhylogenetic[13.Lee J. et al.Feline immunodeficiency virus cross-species transmission: implications for emergence of new lentiviral infections.J. Virol. 2017; 91e02134-16Crossref PubMed Scopus (34) Google Scholar,34.Franklin S. et al.Frequent transmission of immunodeficiency viruses among bobcats and pumas.J. Virol. 2007; 81: 10961-10969Crossref PubMed Scopus (54) Google Scholar]FFVPuma(P. concolor)Domestic cat(Felis catus)Productive subclinical infectionPhylogenetic[14.Kraberger S. et al.Frequent cross-species transmissions of foamy virus between domestic and wild felids.Virus Evol. 2020; 6vez058Crossref PubMed Scopus (10) Google Scholar]SalmonellosisRed fox (Vulpes vulpes), other carnivoresNumerous mammalian prey speciesProductive subclinical infectionNatural and experimental[79.Chiari M. et al.Isolation and identification of Salmonella spp. from red foxes (Vulpes vulpes) and badgers (Meles meles) in northern Italy.Acta Vet. Scand. 2014; 56: 86Crossref PubMed Scopus (13) Google Scholar,80.Handeland K. et al.Natural and experimental Salmonella Typhimurium infections in foxes (Vulpes vulpes).Vet. 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Dis. 2014; 50: 393-396Crossref PubMed Scopus (19) Google Scholar]Haemoplasmosis (Candidatus Mycoplasma spp.)Bobcat (L. rufus) and puma (P. concolor)Domestic cat (F. catus)Productive infection, variable clinical outcomePhylogenetic[35.Kellner A. et al.Transmission pathways and spillover of an erythrocytic bacterial pathogen from domestic cats to wild felids.Ecol. Evol. 2018; 8: 9779-9792Crossref PubMed Scopus (16) Google Scholar]Productive virulent infectionFeLVPuma(P. concolor)Domestic cat(F. catus)Productive virulent infectionPhylogenetic[6.Chiu E.S. et al.Multiple introductions of domestic cat feline leukemia virus in endangered Florida panthers.Emerg. Infect. Dis. 2019; 25: 92Crossref PubMed Scopus (21) Google Scholar,36.Cunningham M.W. et al.Epizootiology and management of feline leukemia virus in the Florida puma.J. Wildl. Dis. 2008; 44: 537-552Crossref PubMed Scopus (52) Google Scholar]Toxoplasma gondiiSouthern sea otter(Enhydrea lutris nereis)Snails, filter-feeding marine bivalvesProductive virulent infectionNatural and experimental[81.Mazzillo F.F. et al.A new pathogen transmission mechanism in the ocean: the case of sea otter exposure to the land-parasite Toxoplasma gondii.PLoS One. 2013; 8e82477Crossref PubMed Scopus (25) Google Scholar,82.Miller M. et al.Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: new linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters.Int. J. 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Dis. 2006; 42: 646-650Crossref PubMed Scopus (22) Google Scholar,12.Matchett M.R. et al.Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in Montana.Vector Borne Zoonotic Dis. 2010; 10: 27-35Crossref PubMed Scopus (90) Google Scholar,83.Elbroch L.M. et al.Plague, pumas and potential zoonotic exposure in the Greater Yellowstone Ecosystem.Environ. Conserv. 2020; 47: 75-78Crossref Scopus (3) Google Scholar]Bovine tuberculosis (Mycobacterium bovis)Coyotes (C. latrans)White-tailed deer (O. virginianus)Productive virulent infectionNatural observation[21.Atwood T.C. et al.Coyotes as sentinels for monitoring bovine tuberculosis prevalence in white-tailed deer.J. Wildl. Manag. 2007; 71: 1545-1554Crossref Scopus (12) Google Scholar]Bluetongue virusAfrican carnivoresRuminants, shrews, some rodentsProductive virulent infectionNatural observation[84.Alexander K.A. et al.Evidence of natural bluetongue virus infection among African carnivores.Am. J. Trop. Med. 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Our analysis of disease transmission among domestic and nondomestic felids using highly sensitive molecular methods has led us to observe repeatedly that predator hosts are at risk for pathogen spillover from prey species, and that both symptomatic and asymptomatic cross-species transmission events can be readily documented from subordinate to apex hosts [6.Chiu E.S. et al.Multiple introductions of domestic cat feline leukemia virus in endangered Florida panthers.Emerg. Infect. Dis. 2019; 25: 92Crossref PubMed Scopus (21) Google Scholar,13.Lee J. et al.Feline immunodeficiency virus cross-species transmission: implications for emergence of new lentiviral infections.J. Virol. 2017; 91e02134-16Crossref PubMed Scopus (34) Google Scholar,14.Kraberger S. et al.Frequent cross-species transmissions of foamy virus between domestic and wild felids.Virus Evol. 2020; 6vez058Crossref PubMed Scopus (10) Google Scholar,34.Franklin S. et al.Frequent transmission of immunodeficiency viruses among bobcats and pumas.J. Virol. 2007; 81: 10961-10969Crossref PubMed Scopus (54) Google Scholar,35.Kellner A. et al.Transmission pathways and spillover of an erythrocytic bacterial pathogen from domestic cats to wild felids.Ecol. Evol. 2018; 8: 9779-9792Crossref PubMed Scopus (16) Google Scholar]. Specifically, we have documented both silent and fatal spillover infections in puma originating from close contact with, and putative predation on sympatric bobcats (Lynx rufus) and domestic cats (Felis catus) (Figure 2). Clinically inapparent cross-species transmissions recorded include: (i) feline immunodeficiency virus (FIV) from bobcat to puma [13.Lee J. et al.Feline immunodeficiency virus cross-species transmission: implications for emergence of new lentiviral infections.J. Virol. 2017; 91e02134-16Crossref PubMed Scopus (34) Google Scholar,34.Franklin S. et al.Frequent transmission of immunodeficiency viruses among bobcats and pumas.J. Virol. 2007; 81: 10961-10969Crossref PubMed Scopus (54) Google Scholar]; (ii) Mycoplasma haemominutum from domestic cats to bobcats and puma, and (iii) from bobcat to puma [35.Kellner A. et al.Transmission pathways and spillover of an erythrocytic bacterial pathogen from domestic cats to wild felids.Ecol. Evol. 2018; 8: 9779-9792Crossref PubMed Scopus (16) Google Scholar]; and (iv) feline foamy virus (FFV) from domestic cat to puma [14.Kraberger S. et al.Frequent cross-species transmissions of foamy virus between domestic and wild felids.Virus Evol. 2020; 6vez058Crossref PubMed Scopus (10) Google Scholar]. FIV infection is highly restricted following host switching in geographically limited sites [23.Malmberg J.L. et al.Altered lentiviral infection dynamics follow genetic rescue of the Florida panther.Phil. Trans. R. Soc. Lon. B. 2019; 28620191689Google Scholar], while FFV infection has rapidly disseminated to high prevalence in free-ranging puma populations [14.Kraberger S. et al.Frequent cross-species transmissions of foamy virus between domestic and wild felids.Virus Evol. 2020; 6vez058Crossref PubMed Scopus (10) Google Scholar]. While of no apparent impact to the host, such asymptomatic prey-transmitted infections result in population level changes in microflora, which may have consequences for host immunity or susceptibility to other pathogens. In contrast to these asymptomatic infections, spillover of feline leukemia virus (FeLV) from domestic cat to puma resulted in fatal outbreaks of disease in the endangered Florida panther (Puma concolor coryi) that significantly impacted the population and hindered the species recovery program [6.Chiu E.S. et al.Multiple introductions of domestic cat feline leukemia virus in endangered Florida panthers.Emerg. Infect. Dis. 2019; 25: 92Crossref PubMed Scopus (21) Google Scholar,36.Cunningham M.W. et al.Epizootiology and management of feline leukemia virus in the Florida puma.J. Wildl. Dis. 2008; 44: 537-552Crossref PubMed Scopus (52) Google Scholar]. Recent evidence suggests FeLV may be able to replicate more competently in puma than the native domestic cat host [37.Chiu E.S. VandeWoude S. Presence of endogenous viral elements negatively correlates with feline leukemia virus susceptibility in puma and domestic cat cells.J. Virol. 2020; 94Crossref Scopus (5) Google Scholar] due to differences in host genomic content. FeLV originating in domestic cats has also been recorded to cause high mortality in Iberian lynx (Lynx pardinus) [7.Meli M.L. et al.Feline leukemia virus infection: a threat for the survival of the critically endangered Iberian lynx (Lynx pardinus).Vet. Immunol. Immunopathol. 2010; 134: 61-67Crossref PubMed Scopus (34) Google Scholar]. Clinically silent cross-species transmissions are not apparent from casual observation, and in our felid studies, were elucidated by advanced detection protocols, improved genomic characterization methods, and innovative phylogenetic analyses. Our studies support both ecological and host–virus interactions as important risk factors for spillover (Figure 2); however, more research is needed to determine the mechanisms driving predator–prey disease transmission outcomes. Furthermore, the degree of pathogen adaptation and frequency of intraspecific transmission of spillover agents in feline predators varies from minimal (i.e., FIV of bobcat origin in puma [13.Lee J. et al.Feline immunodeficiency virus cross-species transmission: implications for emergence of new lentiviral infections.J. Virol. 2017; 91e02134-16Crossref PubMed Scopus (34) Google Scholar,23.Malmberg J.L. et al.Altered lentiviral infection dynamics follow genetic rescue of the Florida panther.Phil. Trans. R. Soc. Lon. B. 2019; 28620191689Google Scholar]) to extensive (i.e., FeLV in Florida panthers [6.Chiu E.S. et al.Multiple introductions of domestic cat feline leukemia virus in endangered Florida panthers.Emerg. Infect. Dis. 2019; 25: 92Crossref PubMed Scopus (21) Google Scholar,36.Cunningham M.W. et al.Epizootiology and management of feline leukemia virus in the Florida puma.J. Wildl. Dis. 2008; 44: 537-552Crossref PubMed Scopus (52) Google Scholar]), highlighting the varied outcomes in predatory species and the need for additional studies of this phenomenon. Spillover research has focused on categorizing risk based on species relatedness and geographic distribution via phylogenetic approaches [33.Albery G.F. et al.Predicting the global mammalian viral sharing network using phylogeography.Nat. Commun. 2020; 11: 1-9Crossref PubMed Scopus (36) Google Scholar,38.Carlson C.J. et al.Global estimates of mammalian viral diversity accounting for host sharing.Nat. Eco. 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Others have demonstrated that geographic overlap also explains disease links between host species, with numerous instances of spillover from a reservoir host to a distantly related recipient host (e.g., bats and rodents to humans, birds to mammals, etc.) [33.Albery G.F. et al.Predicting the global mammalian viral sharing network using phylogeography.Nat. Commun. 2020; 11: 1-9Crossref PubMed Scopus (36) Google Scholar,39.Olival K.J. et al.Host and viral traits predict zoonotic spillover from mammals.Nature. 2017; 546: 646-650Crossref PubMed Scopus (477) Google Scholar]. Beyond strictly trophically transmitted parasites, additional phylogenetic analysis should assess the risk of transmission between unrelated species [43.Stephens P.R. et al.Parasite sharing in wild ungulates and their predators: effects of phylogeny, range overlap, and trophic links.J. Anim. Ecol. 2019; 88: 1017-1028Crossref PubMed Scopus (13) Google Scholar]. Patterns of predator resource selection are also an important consideration for spillover and concurrent conservation efforts. There is evidence that with increasing urbanization, climate and land-use change, and other anthropogenic factors, prey base may shift in response to availability and sympatry [44.Rodewald A.D. et al.Anthropogenic resource subsidies decouple predator–prey relationships.Ecol. Appl. 2011; 21: 936-943Crossref PubMed Scopus (156) Google Scholar,45.Moss W.E. et al.Quantifying risk and resource use for a large carnivore in an expanding urban–wildland interface.J. Appl. Ecol. 2016; 53: 371-378Crossref Scopus (43) Google Scholar]. Studies have shown that urbanized habitat can provide sufficient food for predators; however, alterations in ecological and trophic relationships should be expected [44.Rodewald A.D. et al.Anthropogenic resource subsidies decouple predator–prey relationships.Ecol.