Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model

霊長類研究 Primate Res. 30：23 − 51, 2014（doi：10.2354 / psj.30.003）

特集霊長類を巡る種間関係（２）

総説

1） 2） Andrew James Jonathan MacIntosh ,

1） Kyoto University Wildlife Research Center, Kyoto, Japan 2） Center for International Collaboration and Advanced Studies in Primatology (CICASP), Kyoto University Primate Research Institute, Inuyama, Japan

INTRODUCTION (Moore 1995), including the induction of sickness behaviours (Hart 1988), interference in sexual 1.1 Ecology of Parasitism selection processes (i.e. the immunocompetence handicap hypothesis) (Hamilton & Zuk 1982), In its broadest sense, parasitism represents one evolution of life history traits (Michalakis & class of ecological interactions falling under the Hochberg 1994), population regulation (Anderson umbrella of symbiosis, alongside phoresis, & May 1978; May & Anderson 1978) and commensalism and mutualism, in which one structuring of community assemblages (Holt 1994). organism lives at some cost to another (Roberts & So although parasites and other disease-causing Janovy 2005). Because more or less all free-living organisms were traditionally the subjects of a organisms are infected with parasites, it can be said strictly biomedical research paradigm, parasitism is that parasitism is also one of the most successful fundamentally an ecological interaction, and the strategies in existence, with one estimate suggesting realization that like predation and competition ca. 40% of all life on the planet (Rohde 1982), parasites play important roles in ecosystem though this figure is likely much higher on account functioning has sparked great interest in their of under-sampling and the potentially large number evolutionary ecology, a fact which can be seen in of cryptic species - those that are morphologically the many recent volumes dedicated to this topic similar but genetically distinct - in existence (Grenfell & Dobson 1995; Hudson et al. 2002; (Dobson et al. 2008). The costs exacted by parasites Thomas et al. 2005; Thomas et al. 2007; Ostfeld et on their hosts vary across taxa, but known effects al. 2008; Hatcher & Dunn 2011; Schmid-Hempel include direct pathology and indirect 2011). But a clear overarching driver for the study immunopathology (e.g. through the inﬂammatory of parasitism, inclusive of their evolution and response), immunoregulation (Maizels & ecology, is its implication in human and wild and Yazdanbakhsh 2003), manipulation of behaviour domestic animal health and well-being.

2013 年 9 月 21 日受付，2014 年 3 月 16 日受理，2014 年 5 月 23日早期公開（ J-STAGE） e-mail: [email protected]

23 24 Andrew James Jonathan MacIntosh

1.2 Primate Disease in Perspective in addition to infection outcomes, is thus critical for assessing conservation issues surrounding Indeed, parasites are ubiquitous in nature and, endangered species. although they can often appear benign, typically An obvious additional concern regarding attributed to host-parasite coevolution (Price 1980), parasites and diseases of wildlife is the possible in many cases they can have profound impacts on spillover of pathogens into human and domestic their host populations (Gulland 1995; Wobeser animal populations. Emerging infectious diseases 2007). There is growing concern that decreasing (EIDs) pose a significant problem for global health numbers put wildlife populations at greater risk and economics, and the fact that most ( ～ 60%) are from the stochastic processes such as disease spread of zoonotic origin with ～ 72% of zoonotic diseases that can lead to local extinction (Deem et al. 2001; originating in wildlife (Jones et al. 2008) further Leendertz et al. 2006). In particular, many viral, underscores our need to better understand the bacterial and protistan microparasites are highly ecological processes underlying disease emergence, virulent and can lead to significant levels of host resurgence and spread. Although helminths mortality (Gulland 1995), which can be highlighted represent only a small fraction of the total number by a number of poignant examples: Phocine of EIDs, many of the more cosmopolitan species Distemper Virus (PDV) in harbour seals (Phoca infecting humans, or at least closely-related vitulina) (Heide-Jorgensen et al. 1992), rinderpest cosmopolitan species, are also commonly found in in wild ungulates (Plowright 1982), and the Zaire nonhuman primates. Because roughly half of the strain of the Ebola virus (ZEBOV) in chimpanzees world’s human population is infected by one or (Pan troglodytes) and gorillas (Gorilla gorilla) in more species of parasitic helminth, resulting in Gabon and the Republic of Congo (Leroy et al. large scale constraints to achieving normal 2004; Bermejo et al. 2006). Although fewer development and maintaining health and positive charismatic examples exist for direct effects of energy balance particularly among afﬂicted children macroparasites (e.g. parasitic helminths) on wildlife (Drake & Bundy 2001), the need to monitor host populations, these organisms result nonetheless infection dynamics in primate and other potential in chronic infection incurring widespread morbidity reservoirs for human infection is imperative. (Hudson & Dobson 1995) and are theoretically Because of their close phylogenetic relationships capable of inﬂuencing host population dynamics by with humans, nonhuman primates are perhaps one reducing host survival or fecundity in a density- of the most important sources of zoonotic diseases dependent manner (Anderson & May 1978; May & in humans, particularly in areas of continued human Anderson 1978). The latter has been demonstrated encroachment (Wolfe et al. 2007; Pedersen & empirically, however, in only a few study systems Davies 2009). This makes primates an important including red grouse (Lagopus lagopus scoticus), focal point for research into transmission of Soay sheep (Ovis aries) and Svalbard reindeer infectious organisms, particularly those that host (Rangifer tarandus platyrhynchus), all of which many common parasite species shared by other appear to be regulated by strongyle nematode nonhuman and human primates (Gómez et al. parasites (Grenfell et al. 1992; Gulland 1992; 2013). However, primates are also among the most Hudson et al. 1992; Hudson et al. 1998; Albon et threatened animals in the world with approximately al. 2002). The need to understand the dynamics of 50% of species currently under risk of extinction, disease transmission through wildlife populations, and rising (Mittermeier 2009). The potential Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 25

negative effects of parasitism can be exacerbated researched nonhuman primate species in existence by a destabilization of the ecological balance (in non-laboratory settings at least) (Nakagawa et between hosts and parasites, such as through al. 2010). In this review, therefore, I aim to anthropogenic disturbance of natural ecosystems establish a working model system through which (Chapman et al. 2005; Gillespie et al. 2008). various aspects of the primate host-parasite Unfortunately, our ability to predict specific disease relationship can be investigated and interpreted, outcomes of such changes remains poor (Gillespie focusing on one of the simplest and most accessible & Chapman 2006; Gillespie et al. 2008; Chapman models available: Japanese macaques and their et al. 2009b). The growing body of literature gastrointestinal nematode parasites as a single-host, addressing potential impacts of anthropogenic multi-parasite study system. The ultimate goal of disturbance on the relationship between primates this ongoing research is to develop a mechanistic and their parasites is clear indication that the understanding of the processes underlying parasite primatological community is taking this problem transmission dynamics and outcomes, which can seriously (Hahn et al. 2003; Chapman et al. 2005; then be used to inform future conservation and Gillespie et al. 2005; Chapman et al. 2006; management strategies for primates around the Gillespie & Chapman 2006; Weyher et al. 2006; world. Trejo-Macias et al. 2007; Gillespie & Chapman 2008; Mbora & McPeek 2009; Mbora et al. 2009; 1.3 Scope of this Review Lane et al. 2011). However, truly understanding the potential impacts of anthropogenic disturbance on The aims of this review are modest: to explore these relationships, or the impacts of specific what is currently known about epidemiological parasitic organisms on their primate hosts for that patterns of nematode infection (the model parasites) matter, requires investigation of baseline in Japanese macaques (a model host primate) and epidemiological factors that naturally contribute to re-frame current knowledge as well as future infection dynamics (Chapman et al. 2005). questions about primate-parasite interactions in the Longitudinal and comparative studies detailing the context of host and parasite population processes, dynamics and mechanisms of primate host-parasite with a focus on parasite aggregation. What this interactions are thus badly needed (Nunn & Altizer paper is not is a systematic or exhaustive review of 2006; Huffman & Chapman 2009). infection patterns across the primate order. For Fortunately, field-based studies in primatology reviews concerning variation in infection across have focused intensively on the socioecology and primate hosts, see for starters the excellent volume life histories of non-human primates (Sussman by Nunn & Altizer (2006) and the paper by 2006; Nakagawa et al. 2010; Kappeler & Watts Chapman et al. (2009a) in the volume edited by 2012), providing a robust data set with which to Huffman & Chapman (2009). In addition, while I test how these factors contribute to host-parasite focus solely on an empirical model system here, I processes (Stuart & Strier 1995; Nunn & Altizer echo the sentiments of Chapman et al. (2009b) and 2006; Gillespie et al. 2008; Chapman et al. 2009a; Nunn (2009) and call for better integration of Hernandez et al. 2009). A good illustration of such computational modeling and simulation into studies a concerted effort can be seen in the multitude of of infection processes and potential outcomes in socio-ecological studies on the Japanese macaque primate-parasite systems. (Macaca fuscata), arguably the most intensively 26 Andrew James Jonathan MacIntosh

AN EMPIRICAL MODEL SYSTEM some aspects in the ecology of their infectious diseases may not be representative. However, 2.1 A Model Host Japanese macaques do inhabit a broad range of forested ecosystems (Suzuki 1965), extending from The first question to ask is perhaps why Japanese cool-temperate forests with snow cover in winter - macaques provide a useful model system. Because including the northern-most geographic limit of the they inhabit a highly industrialized country with distribution of all extant nonhuman primate species less reliance on traditional forms of subsistence and - to the warm-temperate and subtropical forests at stronger policies concerning wildlife management lower latitudes which begin to approach conditions and protection (Sprague 2002; Sprague & Iwasaki faced by the majority of the world’s primates. The 2006), their threat status is much lower than that of potential exists, therefore, to investigate both in the average primate and they do not face many of detail and in extreme cases the importance of the same pressures faced by the majority living in environmental conditions in the transmission of developing nations; they are currently listed as parasites. Least Concern in the IUCN Red List of Threatened Oddly enough, however, few of the earlier Species (Watanabe & Tokita 2008). This can in part studies of parasitic infection in Japanese macaques be attributed to the long and distinguished history had addressed variation across individuals or the of primate research in Japan, which has now socio-ecological variables that might explain it produced an overwhelming amount of data (Horii et al. 1982; Gotoh 2000). Instead, the concerning the social structure, ecology and life majority had focused on clinical, veterinary or histories of Japanese macaques throughout the taxonomic aspects of infection (Tanaka & Nigi ranges of both subspecies, M. fuscata fuscata and 1967; Kagei & Hasegawa 1974; Nigi et al. 1975; M. f. yakui, the latter being endemic to the southern Machida et al. 1978; Itoh et al. 1988; Uni et al. island of Yakushima (Nakagawa et al. 2010). Such 1994; Arizono et al. 2012). The obvious benefit of detailed records allow us to ask specific questions this work is that the gastrointestinal parasite fauna about the impacts of, say, seasonal physiological infecting Japanese macaques has now been changes or social relationships on likely variation described in detail for a large number of in susceptibility and exposure to parasitic infection, populations across the Japanese archipelago - an and even ask whether divergent parasite-related extremely useful feature of this model system selection pressures exist in the two subspecies. The because the identities of many of the parasites process (habituation) behind accumulating these infecting tropical primates remain elusive - but they data also means that there are many accessible contributed little to our understanding of the populations of Japanese macaques on which to test ecological or epidemiological processes involved. our hypotheses, living under both free-ranging but Over the past 5 years, however, studies have begun provisioned (e.g. Koshima, Takasakiyama, to address the various processes that do regulate Jigokudani) and undisturbed, natural (e.g. parasite component communities, i.e. parasites of Yakushima, Kinkazan) conditions to further all species infecting a host population, in wild enhance the potential predictive value of our Japanese macaques (Hernandez et al. 2009; research. MacIntosh et al. 2010; MacIntosh et al. 2012). Also unlike most primate taxa, Japanese Though we are only scratching the surface of how macaques are temperate primates, meaning that these parasites might be impacting, or alternatively Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 27

tolerated by, their macaque hosts at either the Arizono et al. 2012) and a recently described individual or population levels, accumulated data “pinworm” Enterobius macaci (Oxyurida) are beginning to allow at least some of the scales to (Hasegawa et al. 2011). Another species of gullet fall from our eyes and are providing various worm (G. macrogubernaculum) has also been intriguing areas for future exploration into this and reported in Japanese macaques that had been other model systems. Before getting into these translocated to the Japan Monkey Center from the epidemiological processes, however, let us first get southern island of Yakushima (Uni et al. 1994). acquainted with the parasitic organisms in question. However, studies demonstrating the existence of this parasite in wild-born samples are necessary to 2.2 The Model Parasites confirm whether this species actually occurs under natural conditions (Gotoh 2000). In addition to The second component of this model system is these nematodes, Japanese macaques are infected comprised of the gastrointestinal nematode by a cestode (Bertiella studeri) (Ando et al. 1994), parasites infecting Japanese macaques. Parasitic at least four protistan parasites including helminths are an exceptionally diverse group, with Balantidium coli (H Hasegawa pers. comm.), estimates of somewhere between 75,000 and Entamoeba dispar (Rivera & Kanbara 1999), 300,000 species infecting vertebrate hosts alone Entamoeba nuttalli (Tachibana et al. 2009) and (Poulin & Morand 2000; Dobson et al. 2008). Giardia intestinalis (Itagaki et al. 2005), two Helminths are among the most frequently reported species of lice (Pedicinus obtusus and P. and diverse group of parasites infecting primate eurygaster) (Kaneko 1971 cited in Tanaka & hosts, and within this group nematodes seem to be Takefushi 1993), and various viral and bacterial the most species rich in mammalian hosts in parasites too numerous to cover here. An extensive general, with a mean of ca. 4 species per host list of parasites infecting Japanese macaques across (Dobson et al. 2008). Gastrointestinal nematodes the country has been compiled from some of the are also among the most accessible of primate above studies, and can be found at http:// parasites because infections tend to be chronic, mammalparasites.org/ (Nunn & Altizer 2005). though strong temporal variation does often exist, From this point forward, however, our focus will be and non-invasive sampling of host feces can nematology. provide useful information about current infections Three of the nematode parasites infecting and future transmission potential. Japanese macaques are directly-transmitted Japanese macaques are infected by six species of geohelminths commonly observed in other primate gastrointestinal nematode parasites across the taxa, including humans in some cases, and are Japanese archipelago: Streptopharagus pigmentatus characterized by cosmopolitan distributions (Sprirurida), the “gullet worm” Gongylonema (Anderson 2000; Acha & Szyfres 2003; Roberts & pulchrum (Spirurida), the “nodular worm” Janovy 2005). In general, O. aculeatum and S. Oesophagostomum aculeatum (Strongylida), the fuelleborni eggs are voided in host feces where “thread worm” Strongyloides fuelleborni juveniles rapidly hatch, typically within a few days,

(Rhabditida), the“ whipworm” Trichuris trichiura and develop into infective stage (L3) larvae. (Enoplida) (Tanaka & Nigi 1967; Kagei & Transmission occurs when these infective stages Hasegawa 1974; Nigi et al. 1975; Machida et al. are ingested by definitive hostsO. ( aculeatum) or 1978; Itoh et al. 1988; Uni et al. 1994; Gotoh 2000; through percutaneous transmission (S. fuelleborni). 28 Andrew James Jonathan MacIntosh

Species of the genus Strongyloides also exhibit both intermediate hosts. Although a vague reference to homogonic and heterogonic life cycles, beetles found in the gut of a macaque during facultatively alternating between parasitic and free- necropsy exists (Itoh et al. 1988), there was no living life cycles, with the parasitic life cycle mention of whether the beetles were of the consisting of parthenogenic females only (Streit coprophagous variety and therefore capable of 2008). Two additional possibilities are transmitting the worms to their definitive hosts. A transmammary transmission, which has been number of Asian and African cercopithecines are documented in S. fuelleborni in other host species infected by Streptopharagus spp. (Myers & Kuntz (Brown & Girardeau 1977; Anderson 2000), and 1965; Dewit et al. 1991; Muller-Graf et al. 1996; transplacental transmission, which can also occur Karere & Munene 2002; Hahn et al. 2003; Gillespie in this genus (Stone 1964). In contrast to the above et al. 2004), while G. pulchrum has been found in a species, T. trichiura eggs voided in host feces hatch wide range of mammalian hosts, including only when embryonated ova are ingested by nonhuman primates and, rarely, humans (Anderson appropriate definitive hosts. The prepatent periods, 2000; Acha & Szyfres 2003; Kudo et al. 2003; i.e. time between infection with the parasite and Haruki et al. 2005; Roberts & Janovy 2005). transmission stages being detected, range from 20- Gongylonema pulchrum is therefore the only 50 days for Oesophagostomum spp. (Talvik et al. species to infect Japanese macaques with the 1997), approximately 2 weeks for S. fuelleborni potential to be shared with other sympatric (Ashford et al. 1992), and 2-3 months for T. mammals, a possibility that to my knowledge has trichiura (Bundy & Cooper 1989). Both not yet been investigated. Once an intermediate O.aculeatum and T. trichiura typically live in the host has been ingested, it takes ca. 60 days for adult large intestine, while S. fuelleborni inhabits the S. pigmentatus worms to develop and begin small intestine of the host. Although these parasites reproducing (Machida et al. 1978), while G. do include developmental stages requiring some pulchrum adults have been found as early as 7 degree of environmental exposure, technically weeks post-infection in other Japanese mammals binding them to an indirect mode of transmission, (Kudo et al. 2003). Adult S. pigmentatus occur they are nonetheless commonly regarded as within the stomach and small intestine of their directly-transmitted nematodes which can easily be definitive hosts, while G. pulchrum are found in the distinguished from the indirectly- or trophically- esophageal and buccal mucosas. transmitted species discussed in the next section. The extents to which these five nematode The two Spiruroid nematodes, S. pigmentatus parasites impact the health of Japanese macaques in and G. pulchrum, each require an intermediate host the wild are currently unknown, though some to complete its life cycle (Anderson 2000; Roberts evidence for behavioral regulation exists that might & Janovy 2005). In Japan, these are most likely indicate fitness consequences for heavily and coprophagous beetles (Coleoptera) of the genera chronically infected individuals (MacIntosh et al. Aphodius, Onthophagus or Geotrupes (Machida et 2011). Nonetheless, each of the direct life cycle al. 1978; Kudo et al. 1996; Boze et al. 2012). parasites may indeed be an important pathogen Cockroaches may also be suitable hosts to spirurid infecting primate host populations. For example, nematodes (Anderson 2000; Acha & Szyfres 2003). Oesophagostomum spp. can be associated with Unfortunately, no data exist concerning the significant pathology because juvenile stages of frequency with which the macaques ingest known these parasites encyst during development and Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 29

cause nodules in the intestinal mucosa, which in the oral cavity as a result of adult worm motility, eventually burst open to release adult forms of the and in some cases may be associated with the parasite (Huffman et al. 1997; Anderson 2000; development of tumors (Acha & Szyfres 2003; Huffman & Caton 2001; Storey et al. 2001; Acha & Bleier et al. 2005; Roberts & Janovy 2005). To my Szyfres 2003; Ziem et al. 2005; Krief et al. 2008). knowledge, no data exist concerning the pathology Strongyloides spp. can potentially cause pathology of Streptopharagus spp., nor whether hosts are during three stages of infection, both directly capable of mounting an immune response against through worm activity and indirectly through the either of these parasites. A necropsy of an old (ca. occurrence of secondary bacterial infection: 1) 26 years) Japanese macaque female from skin-penetrating larva cause“ larva currens” as they Yakushima, which evidently died primarily of a migrate through the epidermis; 2) migrating larva pneumonial infection during winter of 2007, can damage host lungs and other tissues; and, 3) revealed large numbers of S. pigmentatus adults sexually mature worms burrow into the intestinal inhabiting the small intestine (N=1270) and a mucosa causing intestinal pathology (Anderson considerable number of G. pulchrum adults as well 2000; Marquardt et al. 2000; Acha & Szyfres 2003; in the buccal and esophageal mucosas (N=208) Roberts & Janovy 2005). Finally, T. trichiura is an (Hayakawa et al. 2011). While no clear evidence of important disease agent among human populations pathology was associated with these worms, it is where the parasite is endemic, causing dysentery easy to imagine that such large numbers of worms and rectal prolapse under intense infection may have at the very least caused discomfort (e.g. conditions, and in general can stunt both physical G. pulchrum activity in the mouth and throat) and and mental growth in children (Bundy et al. 1987; increased energy stress (e.g. S. pigmentatus Cooper & Bundy 1988; Bundy & de Silva 1998). competing for host nutritional resources) in this Because of the potentially deleterious effects of aged and already waning individual, particularly these parasite species, it is perhaps not surprising given each worms’ size, which can range up to ca. that host animals, including humans, are known to 7cm for the larger females. respond with a protective immune response to Moving beyond host individuals, we also know infection with each of Oesophagostomum (Pit et al. very little about how gastrointestinal helminth 2001), Strongyloides (Korenaga et al. 1991; Herbert parasites might contribute to Japanese macaque, or et al. 2000; Watanabe et al. 2003) and Trichuris indeed any other primate for that matter, population spp. (Else et al. 1993; Grencis 1993; Faulkner et al. regulation. A mass mortality in 1998 and 1999 on 2002). This further indicates their importance to Yakushima (Hanya et al. 2004), and a long-term host fitness, because such physiological responses study of macaques transplanted to the USA in 1972 are costly (e.g. immunopathology, altered nutrient (Fedigan & Zohar 1997), suggest that some use, energy expenditure) (Colditz 2008) and are infectious diseases, in combination with other only expected to occur when the benefits outweigh ecological factors like food availability, may play a the costs of infection, i.e. infections lead to greater strong regulatory role. Ultimately, the possibility reductions in host fitness (Boots & Bowers 2004). that parasites do present fitness costs to wild In contrast to these three directly transmitted primate populations can only be determined parasites, the potential health impacts of the two through experimental, systematic and longitudinal trophically-transmitted parasites are less clear. investigations. It is an admittedly difficult task to Gongylonema spp. can cause irritation and bleeding demonstrate population regulation unambiguously 30 Andrew James Jonathan MacIntosh

from field data (Tompkins et al. 2002), but a critical The reason for this interest is that there are first step is to gain a solid understanding ofthe numerous important implications of parasite processes generating infection patterns in wildlife aggregation. First, because macroparasites tend to populations. The next sections therefore discuss the affect their hosts in a density-dependent manner, a few clear epidemiological patterns observed for direct consequence of aggregation is the imposition Japanese macaques and their nematode parasites, of fitness constraints on specific hosts or sets of what inferences can be made from them and where hosts, ultimately mediating the potential outcomes future work should be directed. I discuss these of host population regulation by parasites patterns through the perspective of parasite (Anderson & May 1978; May & Anderson 1978). aggregation in host populations, which forms a But determining how aggregation should affect the practical framework within which to study parasite role of parasites in host population regulation is a infection dynamics. complex matter. For example, while it was traditionally thought that aggregation should reduce PARASITE AGGREGATION the overall negative effects of infection at the population level and even increase density- 3.1 The First General Law of Parasite Ecology dependent regulation of parasites (e.g. when intense infections cause host, and thus parasite, mortality A good starting point for improving our or more intense intraspecific competition among understanding of the relationship between primates parasites), aggregation may in fact increase host and their parasites is to examine the“ first general regulation and decrease parasite regulation under law of parasite ecology” (Poulin 2007), which is an certain conditions (Jaenike 1996). Another overstatement of the most commonly observed interesting implication of aggregation relates to pattern found in empirical studies of host-parasite parasite-mediated host sexual selection. The relationships; that parasites are aggregated within immunocompetence handicap hypothesis of their respective host populations (Crofton 1971; Hamilton & Zuk (1982) leads to the prediction that Hudson & Dobson 1995; Shaw & Dobson 1995; females can increase their fitness by choosing males Shaw et al. 1998; Wilson et al. 2002; Nunn & capable of investing in costly but attractive sexual Altizer 2006). The generality of parasite signals, i.e.“ bright males”, if the production of aggregation even led Crofton (1971) to state that such traits is afforded by heritable parasite this feature should be included in the definition of resistance or tolerance. However, given the parasitism! Parasite aggregation often conforms to observed range of signal variance across hosts, the 20/80 rule common to many statistical parasite distributions would have to be much less phenomena, because 20% of the host population is aggregated than they are known to be in order to infected with 80% of the parasites. While have significant effects on both female choosiness aggregation can generally be predicted before and male resistance (Poulin & Vickery 1993; 1996). sampling of a given wildlife population is even Finally, patterns of aggregation can also be used to begun (e.g. Hernandez et al. 2009), understanding determine whether certain key hosts, a.k.a. super- the mechanisms responsible for its generation spreaders, are likely to play disproportionate roles remains an active area of research in ecology in the future spread of parasites (Galvani & May (Wilson et al. 2002; Duerr et al. 2003; Cattadori et 2005; Lloyd-Smith et al. 2005). The study of al. 2005; Cornell et al. 2008; but see: Poulin 2013). parasite aggregation thus has implications for host Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 31

socioecology, with evolutionary, population and (k) of the negative binomial distribution (the community level consequences. From a practical theoretical distribution that best approximates perspective, understanding parasite aggregation macroparasite distributions across a wide range of means being able to make better informed choices hosts (Shaw et al. 1998)), using the estimator concerning management of parasite spread in wild provided in Wilson et al. (2002). Not only were all and domestic animals, including in the design of parasite distributions found to be aggregated, as large scale vaccination and treatment programs they were in each of the above-mentioned studies, (Carne et al. 2013; Rushmore et al. 2013), and Monteiro et al. (2007a) further demonstrate a sex conservation of endangered species. bias, such that the degree of aggregation was higher Short of this, however, investigating patterns of among females than among males, though they parasite aggregation in wild primates should could only speculate as to what might have caused highlight possible mechanisms underlying infection this pattern. dynamics. Yet, there are only a few studies that have examined parasitism among primates 3.2 Parasite Aggregation among Japanese specifically in the context of parasite aggregation - Macaques i.e. the parasite’s perspective - or attempted to empirically test existing predictions for such Unsurprisingly, and like the vast majority of distributional characteristics. Indeed, a Web of other studies, all nematode parasites infecting Science search (as of February 2014) using the Japanese macaques that have been examined to search terms primat*, parasit* and aggregat* finds date do indeed exhibit aggregated distributions, at only 14 results with 3 relevant primary articles least according to fecal egg count data (Figure 1; investigating parasite infection within the Hernandez et al. 2009; MacIntosh et al. 2010). aggregation framework (removal of the term Parasite aggregation reﬂects heterogeneity in primat*, in contrast, reveals over 2000 articles). infection across hosts, which results, of course, Perhaps the earliest was the work by Muller-Graf et from differential exposure to infective stages of al. (1996) which plotted the distribution of fecal parasites in the environment and susceptibility to egg counts across host baboons and presented the these organisms once exposed. The simplicity of variance-to-mean ratio for Trichuris sp., using the this statement is belied, however, by the fact that idea of aggregation to infer infection processes. observed infection patterns are mediated by a large Similarly, MacIntosh et al. (2010) also provide number of interacting factors, among them host variance-to-mean ratios for the 5 nematode species traits such as age, sex, reproduction, genetic infecting Japanese macaques on Yakushima island, composition and behaviour (Wilson et al. 2002). while framing their research in the context of Studies have shown that some of these host traits parasite population processes. Interestingly, this may be important to infection processes among appears to be the only study published in a journal primate hosts (Nunn & Altizer 2006; Chapman et dedicated to the study of primates focusing on such al. 2009a), but the lack of consistency across study parasite population processes. Finally, Monteiro et systems suggests that such relationships are far al. (2007a) provide the only study of parasite from simple. Furthermore, the importance of host aggregation in a primate host (golden lion tamarins, traits in determining patterns of parasite Leontopithecus rosalia) using relatively modern aggregation cannot be examined in isolation of the methods: they estimated the dispersion parameter environmental conditions that determine baseline 32 Andrew James Jonathan MacIntosh

Figure 1. A series of histograms illustrating the frequency distributions for fecal egg counts of five nematode parasites infecting Japanese macaques on Yakushima island, Japan, between October 2007 and August 2009. Data used represent seasonal fecal egg counts based on ca. 3-4 fecal samples per adult and 1-2 fecal samples per juvenile per season across 8 seasons. Note differences in the scales of the axes: the y-axis represents the number of individuals per fecal egg count bin listed on the x-axis. I also show the mean ± SD (rounded to the nearest integer) and both the variance- to-mean ratios (∂2:μ) and dispersion parameters (k) of the negative binomial distribution to illustrate aggregation (overdispersion) in the parasite distributions (see text for details). Note also that, despite associating parasite distributions with the negative binomial, data for b, c and e are zero-inﬂated and thus better approximated by the zero-inﬂated negative binomial distribution, which becomes important when modeling variation in these data (Zuur et al. 2009). The sample size for all histograms is 306.

levels of exposure. Independent measures of 1984; Huffman et al. 1997; Gotoh 2000; Nunn et exposure risk, e.g. environmental contamination, al. 2005; Huffman et al. 2009; MacIntosh et al. are surprisingly rare in primate-parasite systems 2010). The following paragraphs describe (Gillespie et al. 2005; Pebsworth et al. 2012), but heterogeneities in infection across Japanese studies of temporal and geographic variation in macaque hosts, in relation to both extrinsic (e.g. infection prevalence and intensity clearly environmental) and intrinsic (i.e. host-specific) demonstrate the importance of climate and variables. seasonality as key drivers of infection (Pettifer Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 33

3.3 Heterogeneity in the External Environment highly resistant to environmental conditions - they are able to produce patent infections after up to 11 One of the most commonly cited causes of years (Burden et al. 1987) - (Larsen & Roepstorff variation in disease dynamics relates to conditions 1999) (and references therein) demonstrate that in the external environment (e.g. climate, these eggs can degrade rather quickly after entering seasonality), which can both facilitate and constrain the external environment, and this is exacerbated as the spread of infection (Harvell et al. 2002; Altizer temperatures increase. Interestingly, these authors et al. 2006; Lass & Ebert 2006; Hernandez et al. showed that eggs deposited during the colder 2013). In addition to the studies noted above that months showed no signs of development until the show climate effects on infection in primates, clear subsequent summer, at which point they could indication in Japanese macaques comes from a develop rapidly (within 5 weeks). The large study demonstrating a strong latitudinal gradient in majority of eggs deposited during the summer helminth parasite species richness, which appears months tended to disappear within a few months to increase significantly with decreasing latitude (Larsen & Roepstorff 1999). This may explain why (Gotoh 2000). In a comparative analysis of parasite T. trichiura is most reproductively active in winter, richness across primate taxa, Nunn et al. (2005) to ensure an adequate supply of embryonated eggs showed that protozoan parasite diversity did indeed for the coming warmer months without wasting increase approaching the equator, whereas that of reproductive effort producing eggs that are likely to helminths did not. It is possible that the existing either degrade rapidly in the peak temperatures of literature is simply too coarse to detect the often summer or begin developing too late into the subtle changes in species diversity, compounded by season. Unlike O. aculeatum and S. fuelleborni, the fact that there are typically few populations which develop rapidly into infective stage larvae examined for parasites per host species. The that can actively seek out their hosts, or S. latitudinal gradient presented for helminth richness pigmentatus which is sheltered and transmitted by in Japanese macaques, in contrast, was based on an intermediate host, embryonated Trichuris sp. data from 14 study populations (Gotoh 2000), some eggs must be passively encountered and ingested, of which are blanketed in snow during the winter and this may explain these contrasting patterns in months (Izawa & Nishida 1963) and with external egg output. Despite the seasonal differences in peak conditions that may generally constrain parasite egg output, however, peak reinfection periods may transmission (MacIntosh & Huffman 2010). actually coincide. Even within populations of Japanese macaques, Regardless of the particulars, the patterns however, there is strong temporal variation in observed in Japanese macaques and other primates infection both intra- and inter-annually, with fecal clearly suggest the importance of climate in egg counts generally, but not always, covarying governing infection potential. This is particularly with external conditions that should facilitate relevant when considering the potential impacts transmission, e.g. warmer, wetter and with an that climate change may have on infection abundance of intermediate hosts (Horii et al. 1982; dynamics. For example, (Barrett et al. 2013) used a MacIntosh et al. 2010). In contrast, however, fecal climate modelling approach to estimate changes in egg counts of T. trichiura were highest during the patterns of lemur parasitism in relation to predicted winter months in both of these studies. Despite that patterns of climate change. They predicted that eggs of Trichuris sp. are widely thought to be while the geographic distributions of some parasites 34 Andrew James Jonathan MacIntosh

would contract, that of others, including some adults the patterns of infection begin to diverge, potentially pathogenic species, would expand their and they seem to diverge along lines of parasite ranges by as much as 60%, encompassing naïve transmission strategy, with directly-transmitted hosts that may be particularly susceptible to the species remaining more or less at low levels of negative effects of such infections. It is currently infection through adulthood and trophically- unknown how climate change might actually affect transmitted species, particularly S. pigmentatus, primate-parasite interactions, as good models are accumulating linearly with age (MacIntosh et al. lacking. However, primates inhabiting more 2010). seasonal climates and higher latitudes, like the These observed age-infection profiles can do lemurs mentioned above and the Japanese nothing to distinguish between competing macaques in our own model system, may hypotheses about their generation, but they can experience the greatest effects of shifting parasite narrow down the possibilities. For example, age- ranges (Harvell et al. 2002). This makes Japanese infection profiles have been used to determine macaques an important eco-indicator of the whether or not immune regulation of parasites can potential for climate change effects on primate explain field data (Woolhouse 1992; 1998; host-parasite dynamics, underscoring our need to Cattadori et al. 2005; MacIntosh et al. 2010). continue to develop this and other model systems. Convex age-infection associations, such as those observed for each of the 3 directly-transmitted 3.4 Heterogeneity in the Internal Environment worms infecting Japanese macaques on Yakushima island, have been suggested to indicate adaptive 3.4.1 Age- and sex-biased infection immunity to parasites (Anderson & May 1985; Woolhouse 1998; Cattadori et al. 2005; Cornell et Like most aspects of an organism’s biology, age al. 2008), although they can be explained by other and sex are predicted to inﬂuence patterns of mechanisms, e.g. parasite-mediated mortality or parasite infection. Although they perhaps represent age-related exposure to infective parasite stages the low-hanging fruit, variation as a function of age through variation in behaviour (Anderson and and sex can provide useful information about the Gordon 1982; Pacala and Dobson 1988), or perhaps mechanics of infection. Early reports concerning even the superposition of multiple processes (Duerr Japanese macaques hinted that infections with some et al. 2003). Concerning mortality, evidence of these parasite species may be host age- and sex- suggests that approximately 40% of macaques on dependent (Horii et al. 1982; Gotoh 2000), and Yakushima die before sexual maturity (Takahata et these patterns have since been confirmed in a more al. 1998), so it is at least plausible that infection rigorous fashion (MacIntosh et al. 2010). For intensity can mediate which individuals live to example, juvenile Yakushima macaques between successfully reproduce. So, while we can’t conclude the ages of 1 and 2 shed the largest numbers of immunoregulation of these parasites, we can be parasite eggs into the environment (Figure 2), fairly confident that adaptive immunity is unlikely which suggests either high intensity infections or at to play a key role in regulating S. pigmentatus the very least high reproductive output per female numbers in adult macaques. worm, both of which indicate little if any regulation The single necropsy of a wild Japanese macaque of parasite infrapopulations. This pattern holds for noted above presents a similar story to that of our most parasite species, but as juveniles mature into fecal egg count data: there were large numbers of S. Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 35

Figure 2. Observed age-infection profiles for (a) probability of infection and (b) fecal egg counts of five nematode parasites infecting Japanese macaques on Yakushima island, Japan, between October 2007 and August 2009. Data are fit by spline curves to geometrically represent the progression of parasitic infection over the course of a macaque’s life span. Note the similarity in the shape of the curves in juveniles and subsequent divergence in relation to parasite transmission strategy (i.e. direct versus trophic). No data exist for macaques at birth, but values of both indices of infection were taken to be 0. pigmentatus (N=1270) and G. pulchrum (N=208) regulate the latter three directly-transmitted species adults found in this old female, which corresponded (MacIntosh et al. 2010). to exceptionally high fecal egg counts at ca. 10x Other lines of evidence from Japanese macaques and 25x the seasonal average of that year, which support the hypothesis that directly- but not respectively (Hayakawa et al. 2011). Adult O. trophically-transmitted parasites are regulated by aculeatum (n=36) and T. trichiura (n=10) were also host immunity include the male bias in infection in found during the examination but at considerably the former but not the latter, and the apparent smaller numbers, while S. fuelleborni was absent relationship between reproduction and/or entirely. Though I do not wish to generalize from a reproductive hormones and O. aculeatum infection single observation, these results are consistent with (MacIntosh et al. 2010), although stress hormones, other results indicating a potential for immunity to despite what we might expect, do not seem to play 36 Andrew James Jonathan MacIntosh

a significant role (MacIntosh et al. 2012). Sex male and female Japanese macaques are strikingly differences in infection are one of the most different; females form life-long bonds with each commonly cited sources of parasite aggregation, other, particularly with kin, while males emigrate with males typically being reported to support from their natal groups and their future social larger numbers as well as even larger sizes of activities depend heavily on their “success” in worms than females (Poulin 1996a; b). Inequities in immigrating into and moving between new groups immune function between the sexes are thought to (Sprague 1992; Suzuki et al. 1998; Yamagiwa & cause this pattern, resulting proximately from the Hill 1998). If young or even for that matter old differential effects of reproductive hormones - males have fewer social contacts because they testosterone is immunosuppressive while estrogen spend significant amounts of time outside of may be immunoprotective (Grossman 1989; Zuk groups, they may be less exposed to directly- 1990; Folstad & Karter 1992; Klein 2000) - and transmitted parasite species (MacIntosh et al. ultimately from the divergent selection pressures 2010). favoring longevity in females and mating success Interestingly, some evidence does exist to in males, i.e. Bateman's principle (Rolff 2002; support this hypothesis in relation to nematode McKean & Nunney 2005). Among reproductive infection in Japanese macaques; females occupying females, on the other hand, relaxation of immunity high ranks, and therefore central positions within often occurs around the time of parturition, i.e. the the group’s social network, produced higher periparturient rise in parasite fecal egg output, prevalences and/or fecal egg counts of two of their leading to increased infection as well as an three directly-transmitted nematode species, both of increased force of infection for newly born naïve which have motile environmental stages hosts (Lloyd 1983a; Lloyd 1983b; Barger 1993; (MacIntosh et al. 2012). Patterns for males were Cattadori et al. 2005). These are all plausible much more variable in relation to grooming explanations for observed patterns of infection in networks, but one thing that is clear is that full Japanese macaques, but as direct tests of these adult males, which were clearly part of the study hypotheses are currently lacking, and alternative group and often interacted with females, had hypotheses can also explain these patterns, much significantly larger parasite prevalences and fecal work still needs to be done before any conclusions egg counts than did young adult males, which tend can be made. to form satellite groups with each other that are attached to, but rarely interact with (outside of the 3.4.2 Host behaviour and socially-mediated mating season at least), bisexual groups (MacIntosh infection unpublished data). If infection is socially-mediated, this could explain why young females appear to One alternative to the above hypotheses, which support larger parasite infrapopulations than young are all concerned with susceptibility to infection, is males, while the reverse is true among adults host behaviour, which does vary by age, sex and (MacIntosh et al. 2010). One of the main difficulties season in Japanese macaques. While the potential in assessing the role of social contact in male for age- or sex-related variation in behaviors infection patterns, however, is the fact that age and capable of mediating parasite exposure has yet to dominance rank, and thus patterns of social be examined in any detail, some speculation is interaction, are strongly correlated in male Japanese warranted here. For example, the life histories of macaques (Sprague 1992). Therefore, while rank Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 37

and networks do appear important in mediating studies of other social groups or populations should exposure to parasites among females, particularly be able to rule out whether or not shared inheritance since the relationship between dominance rank and can explain this link between social rank, networks physiological stress does not follow the same and infection, and these studies are currently pattern as rank and infection (i.e. middle ranking underway. females exhibited the highest fecal cortisol levels compared to high ranking females having the 3.3 Variation in Parasite Aggregation among greatest infection risk) (MacIntosh et al. 2012), it is Japanese Macaques impossible to separate the role that these variables might play in either exposure or susceptibility I conclude this section by exploring how among males. examination of the dispersion parameter k can add It may not be surprising to find that social insight into the processes underlying observed contact and networks relate to infection patterns. infection patterns in Japanese macaques. Poulin Networks are certainly predicted to dictate the (2013) reports that this may be unnecessary given spread of pathogens through host populations the low amounts of variance left to be explained - (Newman 2002), and this has been modelled in upwards of 80% can be explained via an inverse primate hosts (Griffin & Nunn 2011; Nunn 2012; relationship to the mean - but let’s not forget that Carne et al. 2013; Gómez et al. 2013; Rushmore et ecologists and evolutionary biologists are generally al. 2013). Empirical evidence that networks happy to explain small amounts of variance (i.e. modulate disease spread also exists for various <10%), as we are seldom capable of explaining study systems, albeit mainly in relation to more (Møller & Jennions 2002), at least at the ectoparasites and microparasites or other single factor effect level (Peek et al. 2003). In commensals, e.g. meerkats, possum, badgers, cattle keeping with the previous sections, I have separated and tuberculosis (Corner et al. 2003; Böhm et al. individuals by ages, sexes, dominance ranks and 2009; Drewe 2010), tuatara, skinks, ticks and finally by seasons, to estimate variation in k across protozoan blood parasites (Godfrey et al. 2009; these groups via maximum likelihood using the Godfrey et al. 2010), giraffe and intestinal bacteria VGAM package (Thomas 2013) in R statistical (VanderWaal et al. 2013), and mouse lemurs and software (R Core Team 2013). I focus here only on lice (Zohdy et al. 2012). Ours was the first study to the two most prevalent parasite species infecting relate social networks to nematode parasitism. But Japanese macaques, for which the epidemiological again, establishing the mechanism underlying this patterns presented in this review are clearest: observation may be difficult; the results may Oesophagostomum aculeatum and Streptopharagus indicate that the actual contact network structure pigmentatus. It should be noted, however, that the mediates exposure, but they may also reﬂect shared values presented should be interpreted with caution, inheritance in parasite susceptibility (adjacently- first because accurate estimation of k remains an ranked Japanese macaque females tend to be kin) area of active research (Zhang et al. 2007; or shared travel routes or co-feeding leading to Calabrese et al. 2011), second because I make no coincident parasite acquisition from the effort to control for pseudoreplication caused by environment (MacIntosh et al. 2012), though the repeated sampling of the same individuals and third latter possibility would not diminish the important because I am examining but a single group of role that networks may play. At the very least, animals; for estimates of dispersion to have any 38 Andrew James Jonathan MacIntosh

real biological significance one must have access to exposure and/or susceptibility in general among the multiple groups with which to test the significance latter. The same may be said of high-ranking of observed variation (i.e. current sample size, relative to low-ranking females. Finally, like fecal N=1). egg counts (MacIntosh et al. 2010), aggregation in As predicted by Poulin (2013), parasite O. aculeatum showed significant seasonal variation aggregation could be explained more or less by its while S. pigmentatus did not. negative relationship to mean fecal egg counts across most groups examined (dominance rank, sex FUTURE DIRECTIONS and across seasons) for both parasite species; ie. higher mean values correlated positively with 4.1 From Pattern to Process values of k (Table 1). The relationship was reversed among age groups (adults versus juveniles), but this Investigating patterns can lead to novel questions is likely due to the fact that, here, juveniles actually about mechanism, but they can take us only so far. represent two very distinct infection-phenotypic For example, age-infection profiles might hint at groups: young juveniles of 1 and 2 years of age processes regulating (or not) parasite abundance, experience rather large infections that drive the but field-data are generally too coarse to distinguish mean upwards, whereas infection is reduced in between competing mechanistic hypotheses. One older juveniles of 3 and 4 years (Figure 1; example in which field data have proven sufficient MacIntosh et al. 2010). These groups had to be to explain age-infection profiles is the peak shift, a combined due to small sample sizes, but it is likely phenomenon whereby infants born early in the that aggregation would be reduced if each group season experience low force trickle infections and were examined separately. As was reported for are thus slow to develop resistance and thereby tamarins (Monteiro et al. 2007a), female Japanese clear infections, whereas those born later in the macaques also showed higher aggregation levels season experience a high force of infection, reach than did males, possibly suggesting greater peak levels sooner and are thus quicker to develop

Table 1. Predictors of variation in aggregation in nematode parasite populations of the most prevalent species infecting Japanese macaques on Yakushima island, 57 Japan, between October 2007 and August 2009. Aggregation is estimated via 2185 Tables the dispersion parameter (k) of the negative binomial distribution. The mean 2186 (mu) is also provided. See text for details.

Predictors of k O. aculeatum S. pigmentatus Factor Levels mu k mu k Age Adult 229.327 0.316 1545.446 0.278 Juvenile 546.035 0.276 2019.688 0.164 Rank High 314.120 0.487 1487.467 0.309 Mid 157.492 0.343 2610.286 0.445 Low 206.963 0.193 780.366 0.181 Season Autumn 308.133 0.559 1744.262 0.246 Winter 20.111 0.089 914.875 0.238 Spring 515.047 1.042 1411.478 0.279 Summer 298.022 0.335 2131.032 0.305 Sex Female 243.973 0.260 1394.380 0.209 Male 426.520 0.365 2096.081 0.295 2187

2188 Table 1. Predictors of variation in aggregation in nematode parasite populations of the most prevalent 2189 species infecting Japanese macaques on Yakushima island, Japan, between October 2007 and August 2190 2009. Aggregation is estimated via the dispersion parameter (k) of the negative binomial distribution. 2191 The mean (mu) is also provided. See text for details.

2192 Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 39

immunity and clear infection (Woolhouse 1992; (Hawley & Altizer 2010). 1998; Cattadori et al. 2005; Cornell et al. 2008). And of course the ﬂip side of parasite resistance, Attaining such data from Japanese macaques the ability to limit infection, is parasite tolerance, should be feasible, given their strict breeding which instead reﬂects an organism’s ability to seasonality with all infants generally born over a reduce the harm caused by parasites, though the 3-month period during spring and summer (Fooden latter has received considerably less attention & Aimi 2003). Short of this, however, integration (Råberg et al. 2009; Little et al. 2010; Ayres & of field-based observation and laboratory analysis Schneider 2012). There are few empirical studies in of immunological parameters may shed further animals that have investigated variation in tolerance light on this situation. Investigating the presence of, (Leuciscus leuciscus: Blanchet et al. 2010; Bufo and variation in, parasite-specific immune americanus, Rana clamitans: Rohr et al. 2010; responses will allow us to begin to distinguish Danaus plexippus: Lefèvre et al. 2011), but the between mechanisms possibly underlying observed concept, at least, is relatively simple: tolerance age- and sex-biased infection patterns. represents a change in reactivity to some threat Determining whether parasites are such as a parasite or other invading organism, and immunomodulated is of course a fundamental can be examined in a dose-response framework. component of the ability to predict the outcomes of While complicating the issue somewhat, the idea of changing habitat conditions on infection dynamics tolerance does provide a useful framework for and parasite-related health risks in wild primates. addressing cases in which the observed For example, increased physiological stress, and relationships between infection, resistance and thus greater susceptibility to parasitism, is a fitness are not as predicted. For example, in the potential outcome of large-scale anthropogenic case of the network-mediated infection disturbance. Conversely, human-induced habitat demonstrated previously for Japanese macaques changes may grant primates access to agricultural (MacIntosh et al. 2012), high-ranking and central crops, which may improve the nutritional quality of individuals would appear to suffer greater costs of a primate’s diet and thereby reduce susceptibility to parasitism simply based on the presence of larger parasitic infection (Chapman et al. 2006), or parasite infrapopulations. However, it is generally perhaps promote tolerance (see below). Indeed, thought that dominance confers fitness advantages nutritional stress can dramatically reduce immune rather than constraints, and this has been function, leading to an increase in susceptibility to demonstrated by Tsuji & Takatsuki (2012) in wild infection (van Houtert & Sykes 1996; Ezenwa Japanese macaques inhabiting the northern island 2004; Petkevicius 2007; Hoste et al. 2008). These of Kinkazan, wherein high-ranking females can arguments, however, are based on the presumption meet their energy demands even in food-scarce that parasites are immune regulated. It is possible conditions whereas low-ranking females cannot, that habitat disturbance changes rates of exposure resulting in higher mortality rates in the latter. to infective stages of nematode parasites as well Perhaps well-fed dominant individuals can simply (Gillespie & Chapman 2008), but understanding the support larger infections, i.e. increase their internal mechanisms underlying the infection tolerance to infection, while lower-ranking dynamics of each parasite species is nonetheless individuals are forced to divert more energy into imperative to our understanding of the conservation costly parasite resistance. Examining the reaction and health risks facing wild primate populations norms for host fitness, or a proxy of fitness given 40 Andrew James Jonathan MacIntosh

varying parasite infrapopulation sizes (i.e. the actually divided into separate sub-populations tolerance statistical framework) (Råberg et al. which circulated within and not between each 2009) may shed further light on this possibility. respective host species. The conclusion was that nonhuman primates were not a reservoir for human 4.2 Putting the Ecology back into Primate Parasite infection and therefore did not represent an Ecology important risk factor for human oesophagostomiasis (van Lieshout et al. 2005). Nonetheless, studies To fully understand the role that parasites play in clearly demonstrating cases in which human and regulating primate populations, the model presented nonhuman primates do indeed pose an infection in this review can only take us so far, as it is one of risk for each other are beginning to surface (Ravasi the simplest primate models in existence. In tropical et al. 2012; Ghai et al. 2014), so models capable of ecosystems it is rare to find single primate taxa capturing transmission dynamics incorporating living in isolation of others, and so the importance human and multiple nonhuman primate hosts of community assemblages must be taken into remain necessary. account, exponentially increasing the complexity of Another unanswered question concerning our the system, particularly in cases with shared current model system arises from the fact that, parasitism. The work by Holt and colleagues (Holt despite the existence of multiple parasites in the et al. 2003; Holt & Dobson 2006) provides a robust system, nothing is yet known about the co-infective analytical framework through which community processes that might be regulating parasite level effects can be addressed in primate-parasite component communities. It is well-established that systems, though it will certainly be challenging to parasites can exert facilitative or antagonistic demonstrate such effects through empirical data. effects on one another within their hosts, usually But before we can even attempt to do so, much through immunomodulation (Behnke et al. 2001; work must be done to determine to what extent Cox 2001; Drake & Bundy 2001; Cattadori et al. parasites are actually shared between hosts. 2007; Pullan & Brooker 2008). Among primates, Numerous cautionary tales exist demonstrating that co-infection has been examined in detail in only a what we previously thought was a shared parasite pair of studies (Monteiro et al. 2007b; Monteiro et system turned out to in fact be multiple parasites al. 2010), and it was suggested that both facilitative co-existing in the same external environment but and antagonistic effects can occur among different remaining largely specific to separate hosts despite parasite species: while spirurid nematodes may having more or less the same morphotype. A classic increase the deleterious effects of infection by other example of this concerning primates comes from more pathogenic nematode parasites, infection by work on human oesophagostomiasis in Northern the protistan blood parasite Trypanosoma cruzi may Ghana and Togo (de Gruijter et al. 2004; van confer some resistance to such negative effects Lieshout et al. 2005; de Gruijter et al. 2006; Gasser (Monteiro et al. 2010). In Japanese macaques, et al. 2006). Early work suggested that nonhuman perhaps the most intriguing observation to date that primates might be a reservoir for human infection may suggest an interaction between parasite species because the parasite responsible for the disease, is the striking drop in S. pigmentatus infection in Oesophagostomum bifurcum, was also found to older juveniles (Figure 1; MacIntosh et al. 2010). infect monkeys around the villages. But these Since this parasite subsequently appears to increase studies showed that the parasite population was linearly with age, immunity is an unlikely Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model 41

explanation for this effect, but an immune response Japanese macaque and other primate definitive directed at other and potentially more pathogenic hosts remains an exciting, yet no doubt challenging, parasites remains a possibility. This could be a good problem for future research. example of an antagonistic interaction between A final consideration lies in overall parasite parasite species with serious population level biodiversity. While many authors have examined consequences for a parasite which may have parasitic infection in primates inhabiting otherwise evolved to avoid invoking a host immune anthropogenically-disturbed environments from the response altogether. perspective that poor quality habitat is a stress that Even going beyond host populations and can increase parasite infection, an equally likely or communities, it will also be important to address perhaps even more realistic expectation is that poor the cascading effects of regulation. To preserve quality habitats are associated with reduced parasite healthy ecosystem functioning, both primates and biodiversity (Lafferty & Kuris 2005; Altizer et al. parasites must fulfil their various functional roles. 2007). Indeed numerical simulation has shown that What has not yet been demonstrated or perhaps such environmental stressors are capable of even addressed in the primate literature, however, producing various disease outcomes (Lafferty & is the extent to which parasites might mediate the Holt 2003). This latter study suggests that parasites various functional roles that primates do play with high host-specificity living in closed systems within their respective ecosystems. For example, may be negatively impacted through environmental Chapman et al. (2013) explore the likelihood that disturbance, whereas other parasites in open primates are ecosystem engineers; organisms with systems may in fact ﬂourish. The latter approach the ability to modify the physical environment by would in fact lead to opposite predictions to the changing, maintaining, and/or creating new former and may explain the variable results found habitats. Numerous organisms fall into this in the literature. And indeed, a comparative analysis category, with a classic example being that of dam has shown that more threatened primates seem to construction by beavers and its cascading effects host a smaller number of parasite species than their (Jones et al. 1994). Because parasites can mediate less-threatened counterparts (Altizer et al. 2007). A host health, behaviour and large-scale population further possibility is that differential parasite- processes, they may be important regulators of the mediated mortality across host individuals might engineering capabilities of primates and other put certain individuals at greater risk, while at the hosts. For example, dung beetles are likely same time reducing the host population-level ecosystem engineers on the island of Yakushima parasite burden by restricting further spread where they transmit S. pigmentatus and G. (Lafferty & Kuris 2005). This is not to say that pulchrum to Japanese macaques. These beetles some parasite species would not enter dangerous sequester feces from the environment for growth disequilibrium with their primate hosts, leading to and reproduction, and in the process perform an long-term health and fitness costs, but from the important detritivorous ecosystem function, but it perspective of biodiversity it becomes difficult to has been demonstrated that nematode infection state that richer parasite infections equate to greater reduces their capacity to function maximally in this parasite stress, as has been suggested in various role (Boze et al. 2012). Whether the same parasite, publications. We should not forget that parasites or any other for that matter, can exact similar factor into many ecological interactions such as modifications of the engineering functions of food webs - up to 75% of food webs in fact 42 Andrew James Jonathan MacIntosh

(Dobson et al. 2008) - and it appears therefore that Iwanaka A 1994: The occurrence of Bertiella studeri a healthy system, irrespective of direct and indirect (Cestoda: Anoplocephalidae) in Japanese macaque, Macaca fuscata, from Mie Prefecture, Japan. Jpn J impacts on specific hosts, is indeed one that is rich Parasitol 43: 211-213. in parasites (Hudson et al. 2006). Arizono N, Yamada M, Tegoshi T, Onishi K 2012: Molecular Identification of Oesophagostomum and ACKNOWLEDGEMENTS Trichuris Eggs Isolated from Wild Japanese Macaques. Korean J Parasitol 50(3): 253-257. Ashford RW, Barnish G, Viney ME 1992: Strongyloides I thank the Kagoshima Prefectural Government, fuelleborni kellyi: Infection and disease in Papua New the Yakushima World Heritage Office, and the Guinea. Parasitol Today 8(9): 314-318. Ayres JS, Schneider DS 2012: Tolerance of Infections. Cooperative Research Program of the Kyoto Annu Rev Immunol 30(1): 271-294. University Wildlife Research Center for permission Barger IA 1993: Inﬂuence of sex and reproductive status to conduct the research presented in this review. I on susceptibility of ruminants to nematode parasitism. am grateful for the continued support of Dr. Int J Parasitol 23(4): 463-469. Barrett MA, Brown JL, Junge RE, Yoder AD 2013: Michael Huffman, Dr. Alexander Hernandez and Climate change, predictive modeling and lemur health: Dr. Hideo Hasegawa. I also thank Dr. Yamato Tsuji assessing impacts of changing climate on health and and Dr. Mieko Fuse for the invitation to submit my conservation in Madagascar. Biol Conserv 157(0): work to this special issue. This research has been 409-422. Behnke JM, Bajer A, Sinski E, Wakelin D 2001: funded by the Japan Ministry of Education, Culture, Interactions involving intestinal nematodes of rodents Sports, Science and Technology (MEXT) and the experimental and field studies. Parasitology 122: Japan Society for the Promotion of Science (JSPS). S39-S49. Bermejo M, Rodriguez-Teijeiro JD, Illera G, Barroso A,

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（要約）

Ecology and Epidemiology of Nematode Infection in Japanese Macaques: Building an Empirical Model

1 2 Andrew James Jonathan MacIntosh ), )

1) Kyoto University Wildlife Research Center, Kyoto, Japan 2) Center for International Collaboration and Advanced Studies in Primatology (CICASP), Kyoto University Primate Research Institute, Inuyama, Japan

Parasites are ubiquitous in nature and can have profound impacts on host populations. Primates are among the most threatened animals in the world, yet our understanding of the baseline epidemiological factors that naturally contribute to infection dynamics, and thus our ability to predict specific disease outcomes, remains poor. In this invited review, I argue for the necessity of good empirical model systems through which just such an understanding can be approached. I highlight the utility of one such model system that is both parsimonious and highly accessible: the Japanese macaque and its gastrointestinal nematode parasites as a single-host, multi-parasite study system. I explore epidemiological patterns of nematode infection in Japanese macaques and re-introduce the concept of parasite aggregation in an attempt to re-frame current understanding of, as well as re-direct future questions about, primate-parasite interactions as host and parasite population processes. Despite the fact that parasite aggregation has critical implications for understanding the processes involved in both host and parasite regulation, including the various cascading ecological effects regulation can have, this approach is seldom used in studies of primate parasite ecology. Ultimately, this review aims to remind us that parasitism is fundamentally an ecological interaction and that, like predation and competition, parasites play important roles in mediating ecosystem health, including the various functional roles that primates may fulfil.

Keywords: Wildlife Disease, Macaca fuscata, Ecological Immunology, Parasites, Ecosystem Health Andrew J. J. MacIntosh Center for International Collaboration and Advanced Studies in Primatology (CICASP) Kyoto University Primate Research Institute Inuyama, Aichi, Japan 484-8506 email: [email protected]