Applying collocation and APRIORI analyses to chimpanzee diets: Methods for investigating nonrandom food combinations in primate self-medication.

Identifying novel medicinal resources in chimpanzee diets has historically presented challenges, requiring extensive behavioral data collection and health monitoring, accompanied by expensive pharmacological analyses. When putative therapeutic self-medicative behaviors are observed, these events are often considered isolated occurrences, with little attention paid to other resources ingested in combination. For chimpanzees, medicinal resource combinations could play an important role in maintaining well-being by tackling different symptoms of an illness, chemically strengthening efficacy of a treatment, or providing prophylactic compounds that prevent future ailments. We call this concept the self-medicative resource combination hypothesis. However, a dearth of methodological approaches for holistically investigating primate feeding ecology has limited our ability to identify nonrandom resource combinations and explore potential synergistic relationships between medicinal resource candidates. Here we present two analytical tools that test such a hypothesis and demonstrate these approaches on feeding data from the Sonso chimpanzee community in Budongo Forest, Uganda. Using 4 months of data, we establish that both collocation and APRIORI analyses are effective exploratory tools for identifying binary combinations, and that APRIORI is effective for multi-item rule associations. We then compare outputs from both methods, finding up to 60% agreement, and propose APRIORI as more effective for studies requiring control over confidence intervals and those investigating nonrandom associations between more than two resources. These analytical tools, which can be extrapolated across the animal kingdom, can provide a cost-effective and efficient method for targeting resources for further pharmacological investigation, potentially aiding in the discovery of novel medicines.

Folklore, Animal Self-Medication, and Phytotherapy-Something Old, Something New, Something Borrowed, Some Things True.

The use of medicines was long considered by Western schools of thought to be a a domain unique to humans; however, folklore/Traditional Ecological Knowledge (TEK) from around the world suggests that animals have also long provided inspiration for the discovery of some medicinal plants used to treat humans and their livestock. Searching for medicinal knowledge from animals depends on the recognition of their ability to select and effectively use medicinal plants to prevent or actively ameliorate disease and other homeostatic imbalances. The interdisciplinary field of animal self-medication is providing scientific evidence for this ability in species across the animal kingdom and lends support to animal-origin medicinal plant folklore and recent ethnomedicinal information. Here, 14 case studies of purported animal-inspired plant medicines used by cultures around the world are presented together with ethnomedicinal and pharmacological evidence. Based on this evidence, the diversity and potential mode of self-medicative behaviors are considered. Over 20 animal species, including llama, sloth and jaguar in South America, reindeer and yak in Eurasia, langur and macaque in Asia, and chimpanzee, wild boar, porcupine and elephant in Africa, are linked to these case studies, representing a variety of potential preventative or therapeutic self-medicative behaviors. These examples provide an important perspective on what is likely to have been a much wider practice in the development of human traditional medicine. A role for animal self-medication research in the rejuvenation of old therapies and possible new discoveries of phytotherapies for human and livestock health is encouraged.

Asian elephant self-medication as a source of ethnoveterinary knowledge among Karen mahouts in northern Thailand.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnoveterinary medicine is often assumed to be a subset of human medicinal knowledge. Here we investigate the possibility that some ethnoveterinary medicine rather originates from observations of animal self-medication. We document and analyze the ethnoveterinary medicine used by Karen mahouts for elephant care and attempt to determine whether this knowledge originated from humans or elephants. MATERIALS AND METHODS: Elephant camp owners and mahouts in four communities in northern Thailand were interviewed about their knowledge and use of plants for ethnoveterinary elephant care. For each ethnoveterinary plant, data were collected on Karen human medicinal uses and whether elephants independently consume them. Based on overlaps between ethnoveterinary use, human medicinal use and elephant dietary use, plants were classified into three categories: those that originated from Karen human medicine, those that originated from Asian elephant self-medication, and those which were present in both human and elephant knowledge traditions. RESULTS: The use of 34 plants (32 identified at least to genus) and two additional non-plant remedies (salt and human urine) were reported to be used in ethnoveterinary elephant medicine. A total of 44 treatments in 11 use categories were recorded: tonic, wounds, compress, eye problems, indigestion, broken bones, galactagogue, snakebite, fatigue, skin and musth regulation. Of the ethnoveterinary plants, 55% had the same use in human medicine, 43% had different uses and 2% had no use. Elephants consume 84% of the ethnoveterinary plants as part of their natural diet. DISCUSSION: Analysis indicates that 32% of plant uses likely originated from Karen human medicine, 60% of plant uses likely existed independently in both human and elephant knowledge systems, and 8% of plant uses likely originated from elephant self-medicating behavior. The tonic use category shows the strongest evidence of influence from observations of elephant self-medication. The use of tonic medicines appears to be increasing as a way to mitigate the unnaturally limited diet of elephants in tourist camps. CONCLUSION: Ethnoveterinary medicine for elephant care is influenced by both human medicinal knowledge and elephant knowledge of plants for self-medication. The ethnoveterinary knowledge domain appears to be the result of an interactive process linked to convergent evolution or co-evolution between humans and Asian elephants.

Antiprotozoal and antihelminthic properties of plants ingested by wild Japanese macaques (Macaca fuscata yakui) in Yakushima Island.

ETHNOPHARMACOLOGICAL RELEVANCE: Primates forage on a variety of plant parts to balance their dietary intake to meet requirements of energy, nutrition and maintenance, however the reason(s) leading them to ingest some plants which have no nutritional value and/or contain bioactive or even toxic secondary metabolites is recently gaining closer attention. The growing literature suggests that primates consume plants for medicinal purposes (self-medication) as well, particularly when infected with parasites and pathogens (bacteria, viruses, microbes). Interestingly, some of the plants they consume are also used by humans for similar purposes or may have potential uses for humans. MATERIALS AND METHODS: As part of a 16-month study of the parasite ecology of a sub-species of Japanese macaques (Macaca fuscata yakui) on the island of Yakushima, we surveyed their feeding habits and collected a subset of plants and plant parts observed being ingested by macaques. The ethnomedicinal value of these plants was surveyed and methanolic extracts of 45 plant parts were tested in vitro against important parasites of humans, including four protozoan parasites Plasmodium falciparum, Trypanosoma brucei rhodesiense, T. cruzi and Leishmania donovani, and the trematode flatworm Schistosoma mansoni. Potential toxicity of the extracts was also assessed on mammalian cells. RESULTS: A wide range of ethnomedicinal uses in Asia for these plants is noted, with 37% associated with the treatment of parasites, pathogens and related symptoms. Additionally, the 45 extracts tested showed broad and significant activity against our test organisms. All extracts were active against T. b. rhodesiense. The majority (over 80%) inhibited the growth of P. falciparum and L. donovani. Half of the extracts also displayed antiprotozoal potential against T. cruzi while only several extracts were active against both larval and adult stages of S. mansoni. Cytotoxicity was generally low, although several extracts lacked specific toxicity to test parasites. CONCLUSIONS: Our results indicated a number of plants and their parts to have antiparasitic activity not previously reported in the ethnopharmacological literature. Enhanced understanding of the primate diets, particularly during periods of intensified parasite infection risk may help to further narrow down plants of interest for lead compound development. The study of animal self-medication is a complementary approach, with precedence, to drug discovery of new lead drug compounds against human parasitic diseases.

Geophagy among nonhuman primates: A systematic review of current knowledge and suggestions for future directions.

OBJECTIVES: Geophagy, the intentional consumption of earth, is widely practiced among humans and other mammals, but its causes are not well understood. Given the growing number of reports of geophagy among nonhuman primates (NHP), we sought to (1) advance and codify our understanding of the patterns and functional and evolutionary significance of geophagy among NHP and (2) provide a research agenda for a more unified approach to its study. METHODS: We systematically reviewed all available literature on NHP geophagy, extracted available data on taxa, geography, climate, diet, sex, age-class, reproductive status, and the characteristics of the earth. We used these data to evaluate three major hypotheses about geophagy, that it is protective, provides mineral supplementation, and is nonadaptive. RESULTS: We identified 287 accounts of geophagy among 136 species, adding 79 new primate species to the list of those considered in prior reviews. Nineteen percent of species were in the suborder Strepsirrhini, while 81% were in the suborder Haplorrhini. There were reports of geophagy from 9 of the 17 families and 39 of the 76 genera currently recognized by the International Union for Conservation of Nature. DISCUSSION: The limited evidence suggests that geophagy is adaptive, and provides protection and mineral supplementation. We specify the behavioral, dietary, and soil data required to more rigorously investigate these hypotheses across representative species of all taxonomic groups, geographical regions, and dietary classification. Given the plausibility of geophagy for maintaining the health of both wild and captive populations, we urge further study and conservation of geophagy sites.

Medicinal plants in the diet of woolly spider monkeys (Brachyteles arachnoides, E. Geoffroy, 1806) – a bio-rational for the search of new medicines for human use?

ABSTRACT The present study aimed to compare the plant food diet of woolly spider monkeys (Brachyteles arachnoides) inhabiting Intervales State Park in São Paulo, Brazil, with medicinal plant species used by humans in the surrounding areas of the park. The diet of a group of woolly spider monkeys living in an Atlantic forest area was recorded during 43 months of fieldwork. Fifty-three species (87 food items) were recorded. Plant specimens were collected and identified at the University of São Paulo and the Botanical Institute of São Paulo State. Using semi-structured interviews, ethnomedicinal data were also collected from four preselected respondents regarding the human therapeutic value of these plants. The study showed that 24.5% (13/53) of these species are used by residents around the park for medicinal purposes. Of these thirteen, seven species also have validated pharmacological properties, and three are utilized by local residents for similar medicinal purposes. Overlap in the plant food/medicinal diet of woolly spider monkey populations elsewhere were also noted, suggesting potential overlap in their medicinal value for humans and primates. The similarities between the ingestion of plants by primates and their medicinal use by humans provide a bio-rational for the search of bioactive plants in the primate diet. Further detailed investigation of their pharmacological and phytochemical value is warranted.

Soil consumed by chacma baboons is low in bioavailable iron and high in clay.

Despite widespread consumption of soil among animals, the role of geophagy in health maintenance remains an enigma. It has been hypothesized that animals consume soil for supplementation of minerals and protection against toxins. Most studies determine only the total elemental composition of soil, which may not reflect the amount of minerals available to the consumer. Our aim was to test these hypotheses by evaluating the bioavailability of iron in soil consumed by chacma baboons, using a technique that simulates digestion and adsorption. Our results indicate that, despite variation in absolute iron concentration of soil samples, actual iron bioavailability was low while clay content was quite high. This suggests that iron supplementation is unlikely to be the primary motivation for geophagy in this population, and that detoxification is a plausible explanation. This study demonstrates that more research on bioavailability and clay composition is needed to determine the role geophagy plays in health maintenance.

Parasite transmission risk from geophagic and foraging behavior in chacma baboons.

Numerous behavioral and ecological factors are associated with parasite transmission. One factor explored in human research, but absent from nonhuman primate research, is parasite transmission from soil ingestion. Human studies suggest geophagy, the regular and deliberate consumption of soil, increases risk of soil-transmitted helminth (STH) infection. Geophagy, which is prevalent in nonhuman primates, has several positive associations: gastrointestinal distress alleviation, possible mineral supplementation, and bacterial infection prevention. Our objective was to determine whether STH transmission was possible from deliberate or accidental soil ingestion, in a troop of chacma baboons (Papio hamadryas ursinus) that engaged in geophagy, foraged on the terrestrial substrata, and had a Trichuris sp. sample prevalence of 100%. We collected and analyzed 80 soil samples from geophagy and ground foraging sites on and around Wildcliff Nature Reserve, South Africa. Forty soil samples were collected from sites where soil was consumed, and 40 were collected from sites where soil was not consumed. At geophagy sites, the number of Trichuris sp. eggs recovered varied significantly between areas used and unused by the baboons, suggesting behavior is an important factor. In contrast, at foraging sites, there was only a tendency to recover more eggs at used than unused areas, and we propose egg recovery was influenced by fecal contamination that occurred throughout foraging stands. The difference in egg recovery between used areas at geophagy sites and used areas at foraging sites was not significant. These preliminary findings suggest both geophagy and foraging sites are a potential source of STH infection for this troop. Whether geophagy benefits outweigh the potential cost of parasite reinfection for this baboon troop is unknown, so we encourage future research on the influence that host foraging behavior may have on parasite reinfection.

High frequency of leaf swallowing and its relationship to intestinal parasite expulsion in "village" chimpanzees at Bulindi, Uganda.

Self-medication by great apes to control intestinal parasite infections has been documented at sites across Africa. Chimpanzees (Pan troglodytes) swallow the leaves of certain plant species whole, without chewing. Previous studies demonstrated a relationship between chimpanzee leaf swallowing and expulsion of nematode worms (Oesophagostomum sp.) and tapeworms (Bertiella sp.) in dung. We investigated the relationship between leaf swallowing and parasite expulsion in chimpanzees inhabiting a fragmented forest-farm mosaic at Bulindi, Uganda. During 13 months whole undigested leaves occurred in chimpanzee dung at a considerably higher frequency (10.4% of dungs) than at other sites (0.4-4.0%). Leaf swallowing occurred year-round and showed no pronounced seasonality. Chimpanzees egested adults of multiple species of Oesophagostomum (including O. stephanostomum) and proglottids of two tapeworms-Bertiella sp. and probably Raillietina sp. The latter may not be a true infection, but the byproduct of predation on domestic fowl. Compared to previous studies, the co-occurrence of whole leaves and parasites in chimpanzee dung was low. Whereas the presence of leaves in dung increased the probability of adult nematode expulsion, no association between leaf swallowing and the shedding of tapeworm proglottids was apparent. Anthropogenic habitat changes have been linked to alterations in host-parasite interactions. At Bulindi, deforestation for agriculture has increased contact between apes and people. Elevated levels of leaf swallowing could indicate these chimpanzees are especially vulnerable to parasite infections, possibly due to environmental changes and/or increased stress levels arising from a high frequency of contact with humans. Frequent self-medication by chimpanzees in a high-risk environment could be a generalized adaptation to multiple parasite infections that respond differently to the behavior. Future parasitological surveys of apes and humans at Bulindi are needed for chimpanzee health monitoring and management, and to investigate the potential for disease transmission among apes, people, and domestic animals.

Geophagy in chacma baboons: patterns of soil consumption by age class, sex, and reproductive state.

Despite baboons' widespread distribution across Africa, geophagy among all subspecies has been poorly documented. We used video camera traps and soil analyses to investigate geophagy in chacma baboons (Papio cynocephalus ursinus) inhabiting the Western Cape of South Africa. During an 18-month study, from August 2009 to January 2011, we continually monitored the largest and most frequently visited geophagy sites with camera traps for 545 days and captured soil consumption at one or more sites on 266 of those days (49%). In 3,500 baboon visits to geophagy sites, video camera traps captured 58.6 hr of geophagy. From these data, we evaluated site preference based on time spent consuming soil among these four geophagy sites. One hundred and seventy days of soil consumption data from the most frequently visited geophagy site allowed us to look for demographic trends in geophagy. Selected consumed soils from geophagy sites were analyzed for mineral, physical, and chemical properties. The baboons spent more time consuming white alkaline soils with high percentages of clay and fine silt, which contained higher concentrations of sodium than non-white acidic soils that contained higher concentrations of iron. Our data indicate that pregnant chacma baboons spent more time consuming soil at monitored geophagy sites than baboons of any other age class, sex, or reproductive state. Based on analytical results, the soils consumed would be effective at alleviating gastrointestinal distress and possibly supplementing minerals for all age/sex classes, but potentially for different age/sex requirements.

Bioactive properties of plant species ingested by chimpanzees (Pan troglodytes schweinfurthii) in the Kibale National Park, Uganda.

We measured the biological activities of a selected sample (84 crude extracts) of 24 species eaten by wild chimpanzees (Pan troglodytes schweinfurthii) in the Kibale National Park, western Uganda, to assess their potential chemotherapeutic values. Antibacterial, antimalarial, and/or antileishmania activities were observed in some crude extracts, and five of these extracts showed a significant cytotoxicity against human tumor cells. Active compounds isolated from three plant parts occasionally ingested by chimpanzees (Diospyros abyssinica (Ebenaceae) bark, Uvariopsis congensis (Annonaceae) leaves, and Trichilia rubescens (Meliaceae) leaves) showed highly significant medicinal properties. Two novel antiparasitic limonoids were isolated from Trichilia rubescens and their molecular structures were determined. In addition to elucidating the natural equilibrium maintained between hosts and pathogens, our investigation of the diet of wild chimpanzees may serve as a guideline to discovering plants with bioactive properties that should be preserved from destruction because of their health maintenance value for great ape populations.

Animal self-medication and ethno-medicine: exploration and exploitation of the medicinal properties of plants.

Early in the co-evolution of plant-animal relationships, some arthropod species began to utilize the chemical defences of plants to protect themselves from their own predators and parasites. It is likely, therefore, that the origins of herbal medicine have their roots deep within the animal kingdom. From prehistoric times man has looked to wild and domestic animals for sources of herbal remedies. Both folklore and living examples provide accounts of how medicinal plants were obtained by observing the behaviour of animals. Animals too learn about the details of self-medication by watching each other. To date, perhaps the most striking scientific studies of animal self-medication have been made on the African great apes. The great ape diet is often rich in plants containing secondary compounds of non-nutritional, sometimes toxic, value that suggest medicinal benefit from their ingestion. Chimpanzees (Pan troglodytes), bonobos (Pan paniscus) and gorillas (Gorilla gorilla) are known to swallow whole and defecate intact leaves. The habit has been shown to be a physical means of purging intestinal parasites. Chimpanzees and man co-existing in sub-Saharan Africa are also known to ingest the bitter pith of Vernonia amygdalina for the control of intestinal nematode infections. Phytochemical studies have demonstrated a wide array of biologically-active properties in this medicinal plant species. In light of the growing resistance of parasites and pathogens to synthetic drugs, the study of animal self-medication and ethno-medicine offers a novel line of investigation to provide ecologically-sound methods for the treatment of parasites using plant-based medicines in populations and their livestock living in the tropics.