The expansion of human populations, coupled with natural habitat degradation, land-use change, and illegal hunting, have broken down the natural barriers between humans and non-human primates (hereafter, primates), forcing the latter to increasingly live in human-modified environments (1, 2). Even though humans have always shared habitats with primates in some regions, the dynamics of human–primate interactions are radically changing and intensifying. As a result, increasing contacts and conflicts occur, representing a growing risk for zoonotic transmission and wildlife conservation (3, 4). More specifically, the zoonotic risk increases with changes in the dynamics of interactions following (i) the loss and fragmentation of natural habitats for agricultural and industrialization purposes, (ii) the expansion of road networks, and (iii) the greater urban demands for bushmeat and exotic pets, which exacerbate wildlife exploitation (1, 5, 6). Zoonotic pathogens can be transmitted naturally from vertebrate animals to humans, as opposed to reverse zoonotic agents, which are transmitted from humans to animals (7). A large proportion of the major human infectious diseases like measles, plague, or yellow fever, originate in animals, notably in domestic animals within temperate regions, or in non-human primates, the closest evolutionary relatives to humans, found in tropical regions (8). Nowadays, pathogens can spread more rapidly to new regions through international travel and commerce, and be transmitted to new susceptible hosts (9). The alteration of historical distribution patterns of pathogens, associated with the increasing spatial proximity between species, has allowed novel species to come into contact with new specific infectious agents, thus increasing the risk of epidemics (10, 11).

Emerging infectious diseases (EIDs), of which ~75% are of animal origin and are caused by infectious organisms, are characterized by a very large increase of new infections in a host population over a given period of time. This surge in infections likely leads to epidemics or pandemics (12). Recent epidemics such as coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the Ebola virus disease, have stressed how knowledge about human–animal interactions and ecosystem health is essential to control the emergence and spread of zoonotic diseases (13). Thus, it is necessary to assess the factors influencing the risks for human and animal health (14). The process of disease emergence appears to be driven by recent changes in human demographics and behavior and by ecological disruption (15, 16). While habitat alteration typically leads to biodiversity loss (17, 18), the risk of pathogen transmission is strongly linked to the diversity of host species in an ecosystem (19). More specifically, the likelihood of the emergence of zoonotic pathogens depends on several factors, including the prevalence of zoonotic pathogens in wildlife reservoirs, the frequency and intensity of interspecies contacts, the effects of environmental changes on these reservoirs and vectors (e.g., modified geographic range of diseases following climate change), and the type of habitat (6, 20, 21). Currently, the influence of habitat degradation on the prevalence and diversity of infectious pathogens in wildlife is still debated, with conflicting findings reported (22, 23). Some studies have shown that habitat anthropization is negatively correlated with wildlife health, while other studies support that urban environments have no negative effect or even positive effects on animal health. Regarding primates, a study on parasite infection in toque macaques (Macaca sinica) and lion-tailed macaques (Macaca silenus) (24) living in (sub)urban habitats showed a higher parasite richness and prevalence compared with the populations living in undisturbed natural habitats. Conversely, in long-tailed macaques (Macaca fascicularis), it was found a lower prevalence and diversity of gastrointestinal (GI) parasites and protozoa in anthropogenic landscapes (25).

Two contrasting concepts in disease ecology describe the influence of biodiversity loss on the prevalence of pathogens in an ecosystem. The dilution effect implies that biodiversity may act as a barrier to the spread of infectious diseases. Indeed, in a diverse ecosystem, high species diversity may dilute the pool of host species that are competent for pathogens, including many poor reservoirs, thus reducing the persistence and transmission of some pathogens (26). Conversely, the amplification effect represents the scenario in which high biodiversity with diverse competent zoonotic reservoirs or vectors promotes the prevalence of more diverse pathogens and their transmission to humans (27). The predominance of those effects depends on many ecological factors, including the host community and the specific diseases. Nonetheless, it has been suggested that some synanthropic animal species that proliferate in human-dominated environments are more likely to be competent hosts for EIDs than others and, therefore, increase the risk of pathogen transmission to humans (28). Conversely, in less disturbed habitats, competent zoonotic reservoir hosts are less prevalent, and non-reservoir species predominate. Therefore, biodiversity loss in human-modified environments appears to increase the risk of human exposure to new or established zoonotic pathogens (26).

Humans tend to share a greater proportion of pathogens with primates compared with others animals, due to their genetic, physiological, and sometimes social similarities (29). Ebola virus and human immunodeficiency virus (HIV) are textbook examples of epidemic viruses that originated from primates (30–32). These epidemics illustrate how primates can be potential reservoirs of zoonotic infectious agents (33, 34). Zoonotic pathogens (viruses, bacteria, parasites, and fungi) can be transmitted between primates and humans via (in)direct contacts and several pathways (30). They may spread rapidly via direct host-to-host contacts (e.g., respiratory viruses) or by exchange of body fluids such as blood, urine, or saliva (e.g., herpesvirus B and simian foamy virus). GI parasites may enter hosts via exposure to shared contaminated environmental sources such as food, water, and soil. Pathogens can also be transmitted by vectors such as arthropods (e.g., Plasmodium knowlesi transmitted through the mosquitoes Anopheles latens and A. hackeri) (35).

The ongoing biodiversity crisis has taught us that primates are a particularly vulnerable group. Two thirds of primate species are threatened with extinction mostly due to anthropogenic pressures driving habitat loss, species exploitation, and emerging threats including zoonotic diseases (34, 36, 37). A recent interest has developed regarding the transmission mechanisms and the prevalence of zoonotic pathogens in primates that interact with humans (13, 38). The term “human–primate interface” encapsulates all aspects of the socio-ecological relationships linking humans and other primates together, that is, their dynamic interactions in shared environments (39). This interface is diverse. There are different degrees of habitat anthropization, such as urban settings, rural landscapes, and forest habitats, where multiple social and environmental factors may influence the likelihood of interspecies transmission of zoonotic pathogens (22, 40). Therefore, adopting a One Health transdisciplinary approach by recognizing the interconnected links between human, animal, and environmental health is particularly relevant in such interfaces (11, 41).

Asia represents a critical hotspot for zoonotic EIDs (42) given the high human population density combined with a large primate community and frequent human–primate contacts (28). Especially in South and Southeast Asia, humans and primates increasingly overlap spatially and ecologically in cities, temples, and recreational parks. Generalist primate species such as the rhesus macaque (Macaca mulatta) or the long-tailed macaque (M. fascicularis) are synanthropic species frequently encountered in anthropogenic habitats due to their ecological and behavioral flexibility (2, 43). Notwithstanding the critical significance of the cross-species transmission risk at the human–primate interface (44), lacunae persist in the comprehension of host–pathogen dynamics and the compilation of zoonotic pathogens across primate species, notably within specific regions such as Southeast Asia (45). Few studies have sought to review zoonotic pathogens detected in free-ranging Asian primates. Balasubramaniam et al. (40) focused on gastrointestinal parasites in Asian macaques. In another recent review, Liu et al. (46) surveyed viral infections among primates worldwide, encompassing studies involving both captive and wild individuals. Yet, a holistic review requires the inclusion of diverse types of pathogens and all Asian primate species. In addition, there is still a need to better understand how the risk of infections is influenced by environmental factors, such as the type of habitat.

Thus, the primary objective of this systematic review is to compile an inventory of the zoonotic pathogens reported from free-ranging Asian primates, exploring the diversity of pathogens found across diverse habitat types (i.e., forest vs. rural vs. urban habitat) and their routes of transmission. Through this updated overview, we aim to investigating potential disparities in the current knowledge about pathogen groups surveyed among primate species, Asian countries, and diagnostic methods employed.

The COVID-19 pandemic has been a reminder of the paramount importance of zoonotic diseases for global health (148). Many zoonoses originate from or have as reservoirs non-human primates (30, 149). Asia has been the origin of several suspected zoonotic transmission events over the past decades (e.g., previous SARS outbreaks in the 2000s, Nipah virus in 1998, and H5N1 avian influenza virus in the 2000s); underscoring the critical role of the region in the transmission dynamics and the emergence of zoonotic diseases (150). Surveillance of wildlife hosts and potential reservoirs is a crucial initial step to mitigate the risk of future pandemics (13). Given their genetic similarity to humans, non-human primates are important potential reservoirs of zoonotic infections (151). To limit the risk of transmission, it is essential to identify and document the zoonotic pathogens carried by free-ranging primates that often lead to interact with humans. In this review, we conducted the first comprehensive inventory of the various groups of zoonotic pathogens identified in non-captive Asian primates in urban, rural, and forest habitats. By doing so, we have highlighted current research gaps regarding zoonotic pathogens in wild Asian primates, focusing on coverage in primate taxonomic hosts, pathogen groups, and diagnostic methods. As an example, we could not draw a robust conclusion about the potential differences in pathogen-specific richness across habitat types due to insufficient research efforts.

Our review included 152 studies on zoonotic pathogens encompassing reports on 39 primate species from 15 Asian countries. This sampling represents only 33% of the extant primate species found in Asia (34). Hence, a small number of species, especially those of the Macaca genus, are oversampled in infectious disease studies, while many others are disregarded such as the doucs (Pygathrix sp.) or some gibbons (Hoolock sp. and Nomascus sp.). This result confirms a significant taxonomic bias of sampling in the scientific literature that has been raised previously. In their 2007 review, Hopkins and Nunn (45) examined research on infectious agents in primates throughout the world, and found that African primates were sampled twice as much as Asian primates. The disparities we found across Asian primate taxa could be explained by several factors. Sampling in infectious disease research is influenced by the geographic range and the locomotion mode of the primate species (152). Widespread and semi-terrestrial species are sampled more frequently than geographically restricted and strictly arboreal species. Consistently, the overrepresentation of M. fascicularis and M. mulatta may be ascribed to their extensive distribution range across Asia compared with other primate species (153). Moreover, M. fascicularis and M. mulatta are conspicuous and often found in anthropogenic habitats where they are more terrestrial, making their access and sample collection easier compared with elusive species in remote areas (154). Interestingly, while Semnopithecus entellus, a terrestrial species that often inhabits human-modified environments (2, 155) would represent an easy and relevant candidate for sampling and assessing zoonotic risks, it was underrepresented in our dataset, comprising only 2% (N = 5 studies) of the studies. Conversely, survey effort has been greater for emblematic and threatened species such as orangutans (Pongo sp.) (N = 10 studies, 5%). Furthermore, since this review primarily examined English-language publications, it could be advisable for future bibliographic searches to encompass literature published in Oriental languages, with careful consideration of potential publication biases.

The under-sampling of many primate taxa in surveillance studies may pose a public health risk as these primates are potential unknown reservoirs of zoonotic pathogens. This risk is exacerbated by the context of the growing demand for bushmeat and wildlife products, which is also observed in Asia (156, 157). The growing threat of illegal hunting has implications for primate conservation and human health as it intensifies the potential for the circulation of zoonotic pathogens (158, 159). As evidenced by several examples in Africa, the manipulation and consumption of primate meat facilitates the transmission of zoonotic diseases to humans, resulting in dire consequences, such as the emergence of HIV or Ebola virus outbreaks (30, 149). In Asia, although lorises (Loris sp. and Nycticebus sp.) and tarsiers (Tarsius sp., Cephalopachus sp., and Carlito sp.) are widely traded as pets, presenting risks of zoonotic transmission (160, 161), there are still very few infectious disease studies on these species, with the exception of a small fraction screening for GI parasites.

Another publication bias underscored by this review concerns the uneven allocation of sampling efforts regarding the types of screened pathogenic agents and studied transmission routes. Overall, we found that the focus of most empirical studies that examined zoonotic pathogens in free-ranging Asian primates was on protozoa and GI parasites, with most of the identified agents transmitted through the fecal-oral route. Concerning GI parasites, nematodes such as Strongyloides sp., Trichostrongylus sp., and Trichuris sp. were the most reported infectious agents. Viruses, bacteria, blood-borne parasites and fungi have been documented less frequently in the literature on Asian primates. These results are consistent with Hopkins and Nunn (45) and Cooper and Nunn (152) studies, who showed that helminths are the most commonly studied pathogens in primates, while bacteria, viruses, and fungi are the least investigated infectious agents. However, it is important to note that most GI parasites have frequent asymptomatic carriage in wildlife, which may not always reflect a significant health risk for animals or humans (162, 163). The oversampling of pathogens transmitted by the fecal-oral route, such as Strongyloides sp. and Entamoebas sp., could be explained by logistic and ethical constraints related to the sample matrix necessary for diagnosis. Indeed, fecal samples collected noninvasively from the ground are an easy and conventional tool for evaluating zoonotic pathogens in primates, in particular GI parasites (164). Given the vulnerable status of many primate species and ethical restrictions, it may be difficult to obtain authorizations to collect blood or other body fluid samples in the wild (165). Therefore, although molecular techniques with fecal samples can be used to identify diverse types of agents such as blood-borne pathogens (166), microscopy allowing researchers to identify macroparasites and protozoa are commonly used in the field. In future studies, it would be beneficial to expand surveillance strategies through other types of non-invasively collected sample matrices such as saliva, hairs or urine, which can also be gathered without harming the animals (167). These alternative samples could provide valuable insights into a broader range of pathogens, including viruses and bacteria or those difficult to detect through fecal sample analysis, thus enhancing our understanding and management of zoonotic diseases.

So far, PCR, microscopy, and serology have been the most prevalent methods used in studies on Asian primate infections. For all pathogens, except GI parasites and blood-borne parasites, more than half of the studies used pathogen-specific detection methods requiring an a priori selection of the pathogens potentially present in the population. Even though microscopy is a generic detection method (that is sometimes supplemented by more specific detection methods such as PCRs to allow the identification beyond the genus level), it is mainly used for the detection of GI parasites and protozoa. The predominance of those pathogen-specific methods likely skewed the true representation of the infectious agents. Indeed, while sensitive, specific, and efficient methods such as real-time polymerase chain reaction (qPCR) are routinely used for known pathogens, the identification of emerging or unknown pathogens is more challenging (168). In this regard, the de novo metagenomics approach has proved to be a powerful new tool with infinite fields of application (169). For example, many novel and divergent viruses can be detected simultaneously and genetically characterized for the first time (170). In addition, metagenomic analyses of the microbial community also provide important insights and tools to monitor the health and nutritional status of primates and thus contribute to primate conservation (171). Generic next-generation sequencing approaches, through a wide variety of samples (i.e., feces, blood, nasal swab, saliva, and biological tissues), are likely to shed light on little known or novel zoonotic pathogens in primates (169) such as the ChiSCVs virus detected in stool samples of wild chimpanzees (172) or the Primate Bocaparvovirus Species 3 discovered in wild rhesus macaques (173). However, the relatively limited use of generic methods can likely be attributed to the high cost associated with next-generation sequencing techniques. Primate conservation research in developing countries is often a low priority (174), given the growth needs of local populations and the lack of technical resources and funding (175). Despite improved efforts in recent years, there remains a lack of international collaboration, which reduces opportunities for local research, capacity building, and access to cutting-edge technologies needed to improve the detection of zoonotic EIDs and the underpinning mechanisms (175, 176).

Based on the existing literature, we were unable to confidently determine whether the type of habitat influences the diversity of zoonotic agents that infect wild Asian primates. With respect to protozoa, bacteria, viruses, and GI parasites, even though their specific richness did not show significant variations across forest, rural, and urban habitats, the inadequacy of sampling effort is apparent from the absence of asymptotes in the rarefaction curves. Yet, anthropogenic disturbances such as forest degradation and land-use conversion are suspected to deeply interact with infectious diseases in primates, notably through a multiplication of direct and indirect contacts with humans and domestic animals (30). In rhesus macaques, habitat attributes correlated with host density and appeared to be a significant determinant of GI parasite infections. Parasitic richness was higher in large macaque groups interacting with human communities and livestock in (peri-)urban habitats, although parasitic prevalence was higher in rural habitats (95). Consistently, the prevalence of Salmonella sp. and E. coli was higher in provisioned groups of rhesus macaques interacting with humans in anthropogenic habitats (38). Conversely, another study in Indonesia demonstrated that anthropogenic landscape components decreased the prevalence and intensity of GI parasites in long-tailed macaques, probably due to good nutritional conditions following heavy food provisioning near human settlements (25). The prevalence and risk of transmission of viruses transmitted through physical contact or aerosols are expected to be higher in urban habitats such as at touristic sites and temples in Asia (116, 118, 119), where close and frequent human–primate contacts are common (101). In rural landscapes, agricultural practices, such as the use of antibiotics, can also contribute to drug resistance of bacteria and therefore increase their prevalence in primates (135). Conversely, other several studies on African primates have shown a higher richness and prevalence of GI parasites in populations from disturbed forests compared with more preserved habitats (177, 178). Finally, the prevalence of vector-borne pathogens, such as protozoa responsible for malaria, may be increased by forest degradation and associated changes in vector (anopheline mosquitoes) and host (Macaca sp.) density (179, 180).

Nevertheless, it is important to acknowledge that the descriptive categorization of habitats based on site descriptions we used in this review to delineate three categories (i.e., urban, rural, and forest), may entail certain limitations in the results. A more empirical approach using satellite images of land cover could potentially provide a more accurate representation of the environmental complexity by considering finer variations in land use and thereby capturing a broader spectrum of anthropogenic influences on primate habitats. In sum, the influences of anthropogenic components on primate infections appear complex. Urgent additional comparative studies are needed to investigate changes in primate-pathogen dynamics in rapidly changing environments, particularly among primate populations inhabiting habitats with varying degrees of human disturbances (30, 40).

The different biases highlighted in this literature review warrant further investigation, particularly on the under-screened primate species and on a wider range of etiological agents by using generic diagnostic methods. Primates are good candidates as sentinels for the surveillance of zoonotic diseases, particularly in Asia, where their close spatial proximity to humans is rapidly increasing. This endeavor requires researchers to address knowledge gaps regarding the risks and mechanisms associated with zoonotic transmissions. For example, it would be promising to improve our understanding of the behavior and socio-ecology of synanthropic primates. So far, few studies have focused on the risk factors of disease transmission associated with primate social dynamics, personality traits, and risk-taking behaviors promoting contacts with humans, domestic animals, or shared resources (40). It is worth emphasizing that such knowledge into primate health and the mechanisms of disease transmission also has substantial implications for primate conservation (171).

A One Health conceptual approach grounded in multidisciplinary collaborations is crucial for conducting action research on the emergence and transmission of zoonoses (181, 182). Establishing effective preventive measures requires a targeted surveillance of potential zoonotic reservoirs to identify mechanisms and risk factors of EIDs, and to raise awareness among populations about zoonotic risks. Today, considering previous sanitary crises associated with wildlife reservoirs [e.g., Ebola, Middle East respiratory syndrome (MERS), and COVID-19], it is essential to draw on the lessons that have been learned to make informed decisions. Prioritizing preventive measures, such as identifying infection reservoirs, implementing surveillance, and communicating risks, is advised over reactive measures like implementing physical barriers and restricting human populations in response to zoonotic outbreaks.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

LP: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Software, Visualization, Writing – original draft. AH: Formal analysis, Methodology, Software, Supervision, Validation, Writing – review & editing. SA: Validation, Writing – review & editing. MG: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing – review & editing. FB: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Validation, Writing – review & editing.